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EX-21 - EXHIBIT 21 - Sucampo Pharmaceuticals, Inc.exh_21.htm
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EX-10.41 - EXHIBIT 10.41 - Sucampo Pharmaceuticals, Inc.exh_1041.htm
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UNITED STATES SECURITIES AND EXCHANGE COMMISSION

Washington, D.C. 20549

 

Form 10-K

(Mark One)

 

þANNUAL REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934

 

For the fiscal year ended December 31, 2015

 

   
oTRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934

 

For the transition period from __________ to __________.

 

Commission File Number: 001-33609

 

SUCAMPO PHARMACEUTICALS, INC.

(Exact name of registrant as specified in its charter)

 

Delaware 30-0520478
(State or other jurisdiction of (I.R.S. Employer
incorporation or organization) Identification No.)
   
805 King Farm Boulevard, Ste 550 20850
Rockville, MD (Zip Code)
(Address of principal executive offices,  
including zip code)  

 

(301) 961-3400

(Registrant’s telephone number)

 

Securities registered pursuant to Section 12(b) of the Act:

 

Title of each class   Name of each exchange on which registered
Class A common stock, par value $0.01   The NASDAQ Global Market

  

Securities registered pursuant to Section 12(g) of the Exchange Act: None

 

Indicate by check mark if the registrant is a well-known seasoned issuer, as defined in Rule 405 of the Securities Act. Yes ☐ No ☒

 

Indicate by check mark if the registrant is not required to file reports pursuant to Section 13 or Section 15(d) of the Act. Yes ☐ No ☒

 

Indicate by check mark whether the registrant (1) has filed all reports required to be filed by Section 13 or 15(d) of the Securities Exchange Act of 1934 during the preceding 12 months (or for such shorter period that the registrant was required to file such reports), and (2) has been subject to such filing requirements for the past 90 days. Yes ☐ No ☒

 

Indicate by checkmark whether the registrant has submitted electronically and posted on its corporate Web site, if any, every Interactive Data File required to be submitted and posted pursuant to Rule 405 of Regulation S-T (§ 232.405 of this chapter) during the preceding 12 months (or for such shorter period that the registrant was required to submit and post such files). Yes ☒ No ☐

 

Indicate by a check mark if disclosure of delinquent filers pursuant to Item 405 of Regulation S-K (§ 229.405 of this chapter) is not contained herein, and will not be contained, to the best of registrant’s knowledge, in definitive proxy or information statements incorporated by reference in Part III of this Form 10-K or any amendment to this Form 10-K. ☐

 

Indicate by check mark whether the registrant is a large accelerated filer, an accelerated filer, a non-accelerated filer, or a smaller reporting company. See the definitions of “large accelerated filer,” “accelerated filer” and “smaller reporting company” in Rule 12b-2 of the Exchange Act.

 

  Large accelerated filer ☐ Accelerated filer ☒ Non-accelerated filer ☐ Smaller reporting company ☐
      (Do not check if a smaller reporting company)

 

Indicate by check mark whether the registrant is a shell company (as defined in Rule 12b-2 of the Act). Yes ☐ No ☒

 

The aggregate market value of the 21,616,843 shares of class A common stock held by non-affiliates of the registrant (based on the closing price of the registrant’s class A common stock on the last business day of the registrant’s most recently completed second fiscal quarter) was $355.2 million.

 

As of March 1, 2016, there were 45,539,384 shares of the registrant’s class A common stock outstanding, par value $0.01 per share.

 

DOCUMENTS INCORPORATED BY REFERENCE:

 

Portions of the registrant’s Proxy Statement for its 2016 Annual Meeting of Stockholders to be held on June 2, 2016, which Proxy Statement is to be filed within 120 days after the end of the registrant’s fiscal year ended December 31, 2015, are incorporated by reference in Part III of this Annual Report on Form 10-K.

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Sucampo Pharmaceuticals, Inc.

 

Form 10-K

Table of Contents

 

    Page
Part I
Item 1. Business  3
Item 1A. Risk Factors  22
Item 1B. Unresolved Staff Comments  39
Item 2. Properties 39
Item 3. Legal Proceedings 39
Item 4. Mine Safety Disclosures  39
     
Part II
Item 5. Market for Registrant’s Common Equity, Related Stockholder Matters and Issuer Purchases of Equity Securities 40
Item 6. Selected Financial Data 42
Item 7. Management’s Discussion and Analysis of Financial Condition and Results of Operations 43
Item 7A. Quantitative and Qualitative Disclosures About Market Risk 58
Item 8. Financial Statements and Supplementary Data 59
Item 9. Changes in and Disagreements With Accountants on Accounting and Financial Disclosure 59
Item 9A. Controls and Procedures 59
Item 9B. Other Information 59
   
Part III
Item 10. Directors, Executive Officers and Corporate Governance 59
Item 11. Executive Compensation 60
Item 12. Security Ownership of Certain Beneficial Owners and Management and Related Stockholder Matters 60
Item 13. Certain Relationships and Related Transactions and Director Independence 60
Item 14. Principal Accounting Fees and Services 60
   
Part IV
Item 15. Exhibits, Financial Statement Schedules  60
Signatures 65
Index to Consolidated Financial Statements  F-1

 

 

 

 

 

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PART I

 

This Annual Report on Form 10-K, including the section entitled “Management’s Discussion and Analysis of Financial Condition and Results of Operations,” contains forward-looking statements regarding us and our business, financial condition, results of operations and prospects within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements may be identified by the words “project,” “believe,” “anticipate,” “plan,” “expect,” “estimate,” “intend,” “should,” “would,” “could,” “will,” “may” or other similar expressions. In addition, any statements that refer to projections of our future financial performance, our anticipated growth and trends in our business and other characterizations of future events or circumstances are forward-looking statements. We cannot guarantee that we will achieve the plans, intentions or expectations expressed or implied in our forward-looking statements. There are a number of important factors that could cause actual results, levels of activity, performance or events to differ materially from those expressed or implied in the forward-looking statements we make. These important factors are described under “Risk Factors” set forth below. In addition, any forward-looking statements we make in this document speak only as of the date of this document, and we do not intend to update any such forward-looking statements to reflect events or circumstances that occur after that date.

 

ITEM 1. BUSINESS

 

Overview

 

We are a global biopharmaceutical company focused on innovative research and development of proprietary drugs to treat gastrointestinal, ophthalmic, autoimmune, and oncology-based inflammatory disorders.

 

We currently generate revenue mainly from product royalties, upfront and milestone payments, product sales and reimbursements for development activities. We expect to continue to incur significant expenses for the next several years as we continue our research and development activities, seek additional regulatory approvals and additional indications for our approved products and other compounds and seek strategic opportunities for in-licensing new products.

 

Our operations are conducted through subsidiaries based in the United States (U.S.), Japan and Switzerland. We operate as one segment, which focuses on the development and commercialization of pharmaceutical products.

 

Our Strategy

 

Our strategy is focused on becoming a leading biopharmaceutical company. We are built on the ongoing pursuit of scientific innovation and an unwavering passion for improving the lives of patients, their family members and their caregivers. We are committed to harnessing our past successes to maximize in-market revenues, focus our clinical development efforts, and enhance our scientific capabilities.

 

In 2015, we advanced our corporate strategy by further solidifying our base business, executing on business development transactions and diversifying our pipeline portfolio through the acquisition of new product candidates. We executed and accomplished the following key milestones:

 

·Entered into an exclusive license, development, commercialization and supply agreement (China Gloria Agreement) with Harbin Gloria Pharmaceuticals Co., Ltd. (Gloria) for AMITIZA® (lubiprostone), through which Gloria has the rights to develop and commercialize AMITIZA in China, subject to the regulatory approval of the product by the China Food and Drug Administration (CFDA);
·Successfully completed the European mutual recognition procedure for AMITIZA for the treatment of chronic idiopathic constipation (CIC) in Austria, Belgium, Germany, Italy, Ireland, Luxembourg, Netherlands and Spain, resulting in a recommendation for marketing authorization in these markets, and received approval for AMITIZA in CIC from Health Canada;
·Received Fast Track Designation from the U.S. Food and Drug Administration (FDA) for cobiprostone for the prevention of oral mucositis (OM) and initiated a phase 2a clinical trial of cobiprostone oral spray for the prevention of OM in patients suffering from head and neck cancer (HNC). Also initiated a phase 2 clinical trial of cobiprostone for non-erosive reflux disease (NERD)/symptomatic gastroesophageal reflux disease (sGERD) in proton pump inhibitor-refractory patients; and
·Completed our acquisition of R-Tech Ueno, Ltd. (R-Tech), a global biopharmaceutical company focused on the research and development of drugs for inflammatory conditions, oncology and ophthalmology. The acquisition was immediately accretive, strengthening the global economics of AMITIZA and bringing in a diverse pipeline. In the fourth quarter of 2015, we closed a $250 million credit facility in connection with the financing of the acquisition.

 

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In 2016, we announced an option and collaboration agreement under which Cancer Prevention Pharmaceuticals, Inc. (CPP) has granted us the sole option to acquire an exclusive license to commercialize CPP-1X/sulindac combination product in North America. This product is currently in a phase 3 clinical trial for the treatment of familial adenomatous polyposis (FAP).

 

Through the continued advancement of our AMITIZA lifecycle management programs, a sustainable pipeline and the acquisition and licensing of additional drug candidates with near-term launch opportunities, we will seek transformative growth by launching additional products for new therapeutic areas, strengthening an already sizable revenue base, and creating a sustainable company that is built to last.

 

Additionally, we continue to seek opportunities for strategic partnerships to strengthen the development of our existing pipeline and to diversify our revenue base. It is our vision to develop into a fully integrated, biopharmaceutical company centered on science and innovation and driven by the passionate and relentless efforts of our employees.

 

Our Competitive Strengths

 

Product Pipeline

 

The table below summarizes the development status of our marketed products and key product candidates as of March 10, 2016. The commercialization rights to lubiprostone have been licensed to Takeda Pharmaceutical Company Limited (Takeda) on a global basis other than Japan and the People’s Republic of China, to Mylan for Japan, and to Gloria for the People’s Republic of China. For cobiprostone, we hold all of the commercialization rights globally. Commercialization of each product candidate may occur after successful completion of clinical trials and approval from appropriate governmental agencies. For CPP-1X, we have an option to acquire an exclusive license to commercialize in North America  .

 

Product/Product Candidate   Country   Program Type   Target Indication   Development Phase   Next Milestone
 Lubiprostone (AMITIZA ®)   U.S.   Commercial   Chronic idiopathic constipation (CIC) (adults of all ages)   Marketed    ___ ___
                     
    Canada   Clinical   Chronic idiopathic constipation (CIC) (adults of all ages)   Received approval from Health Canada   Market in Canada
                     
    U.S.   Commercial   Irritable bowel syndrome with constipation (adult women) (IBS-C)   Marketed    Initiate phase 4 study on higher dosage and with additional male subjects
                     
    U.S.   Commercial   Opioid-induced constipation (OIC) in patients with chronic non-cancer pain   Marketed    ___ ___
                     
    China   Clinical   Chronic idiopathic constipation (CIC) (adults of all ages)   IND accepted   Initiate CIC study
                     
    Japan   Commercial   Chronic constipation   Marketed    ___ ___
                     
    Switzerland   Commercial   Chronic idiopathic constipation (CIC) (adults of all ages)   Marketed    ___ ___
                     
    U.K.   Commercial   Chronic idiopathic constipation (CIC) (adults of all ages)   Marketed    ___ ___
                     
    European Union   Clinical   Chronic idiopathic constipation (CIC) (adults of all ages)   Received national marketing approvals in Ireland, Germany, Austria, Belgium, the Netherlands, Luxembourg, Italy and Spain (where product is not yet launched)    Develop pricing and reimbursement assessments and based on outcome determine launch feasibility and plans for Ireland, Germany, Austria, Belgium, the Netherlands, Luxembourg, Italy and Spain

 

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Product/Product Candidate   Country   Program Type   Target Indication   Development Phase   Next Milestone
    Switzerland   Commercial   Opioid-induced constipation (OIC) in patients with chronic non-cancer pain   Marketed    ___ ___
                     
    Russia   Clinical   Chronic idiopathic constipation (CIC) (adults of all ages)   CTA Approved   Initiate phase 3 trial
                     
    Russia   Clinical   Irritable bowel syndrome with constipation (adult women) (IBS-C)   CTA Approved   Initiate phase 3 trial
                     
    Mexico   Clinical   Chronic idiopathic constipation (CIC) (adults of all ages)   Submitted CTA   Initiate phase 3 trial
                     
    Mexico   Clinical   Irritable bowel syndrome with constipation (adult women) (IBS-C)   Submitted CTA   Initiate phase 3 trial
                     
    Mexico   Clinical   Opioid-induced constipation (OIC) in patients with chronic non-cancer pain   Submitted CTA   Initiate phase 3 trial
    South Korea   Clinical   Chronic idiopathic constipation (CIC) (adults of all ages)   Submitted CTA   Initiate phase 3 trial
                     
    South Korea   Clinical   Irritable bowel syndrome with constipation (adult women) (IBS-C)   Submitted CTA   Initiate phase 3 trial
                     
    South Korea   Clinical   Opioid-induced constipation (OIC) in patients with chronic non-cancer pain   Submitted CTA   Initiate phase 3 trial
        Clinical   Alternate formulation    In non-clinical development   Initiate phase 3 trial 
                     
        Clinical   Pediatric functional constipation
(6 years - 17 years)
  Pivotal and open label phase 3 trials ongoing   Complete pivotal and open label phase 3 trials 
                     
        Clinical   Pediatric functional constipation
(6 months - 6 years)
  Alternate formulation in development   Initiate phase 3 program
                     
Unoprostone isopropyl (RESCULA®)   Japan       Glaucoma and ocular hypertension   Marketed   ___ ___
    South Korea                
    Taiwan                
Cobiprostone        Clinical   Oral mucositis   Phase 2a initiated   Complete phase 2a trial
                     
        Clinical   PPI refractory-Non-erosive reflux disease (NERD)/symptomatic Gastroesophageal Reflux Disease (sGERD)   Phase 2a initiated   Complete phase 2a trial
                     
RTU-1096   Japan   Clinical   Inflammation/immune-related disorder   Phase 1 completed    Initiate phase 2a trial
                     
RTU-009   Japan   Preclinical   Inflammation/immune-related disorder   Development on-going   Initiate IND-enabling studies
                     
CPP-1X/sulindac combination product   U.S.   Option   Familial adenomatous polyposis (FAP)   Phase 3   Complete phase 3 trial

 

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AMITIZA (lubiprostone)

 

AMITIZA is a ClC-2 chloride channel activator developed for the treatment of constipation. AMITIZA acts with a dual mechanism of action, increasing intestinal fluid secretion while also stimulating recovery of mucosal barrier function. AMITIZA has been approved for three indications that cover distinct patient types: CIC, irritable bowel syndrome with constipation (IBS-C), and opioid-induced constipation (OIC). Since 2006, AMITIZA has been dispensed over 10 million times.

 

North America

AMITIZA was the first chloride channel activator approved by the FDA for the chronic treatment of CIC in adults of both genders and for IBS-C in women aged 18 years and older with demonstrated safety and efficacy for use beyond 12 weeks. In the U.S. and Canada, we and Takeda jointly develop and Takeda commercializes AMITIZA under the North America Takeda Agreement. More information on our collaboration with Takeda in North America is found under the heading “North America Takeda Agreement.”

 

In April 2013, we received approval for a supplemental new drug application (sNDA) for AMITIZA at dosage strength of 24 micrograms twice daily as the first and only oral medication for the treatment of OIC in adult patients with chronic, non-cancer pain. In October 2014, we signed an amendment to the North America Takeda Agreement which, among other things, extended the term beyond December 2020; during the extended term, we will share with Takeda the net sales revenue on branded AMITIZA sales. We have also partnered with Par Pharmaceuticals, Inc. (Par) in connection with the settlement of our patent litigation with Par in the U.S. related to our AMITIZA (lubiprostone) 8 mcg and 24 mcg soft gelatin capsule products. Under our agreement with Par, we granted Par a non-exclusive license to market Par’s generic version of lubiprostone 8 mcg soft gelatin capsule and 24 mcg soft gelatin capsule in the U.S. for the indications approved for AMITIZA beginning January 1, 2021, or earlier under certain circumstances. Beginning on January 1, 2021, Par will split with us the gross profits of the licensed products sold during the term of the agreement, which continues until each of our related patents has expired. In the event Par elects to launch an authorized generic form of lubiprostone, we agree to supply Par under the terms of a manufacturing and supply agreement at a negotiated price.

 

In October 2015, Health Canada approved AMITIZA for CIC in adults. AMITIZA will be marketed by Takeda Canada Inc. under the North America Takeda Agreement. Takeda Canada is currently assessing launch feasibility and timing.

 

Chronic Idiopathic Constipation (CIC)

Constipation is characterized by infrequent and difficult passage of stool and becomes chronic when a patient suffers specified symptoms for over 12 non-consecutive weeks within a 12-month period. Chronic constipation (CC) is idiopathic if it is not caused by other diseases or by use of medications. Symptoms of CIC include straining, hard stools, bloating and abdominal pain or discomfort. Some patients suffering from occasional constipation may be treated with lifestyle modification, dietary changes and increased fluid and fiber intake, although there is very limited well-controlled clinical trial data in support of these alternatives in CIC or IBS-C patients. For patients who fail to respond to these approaches, physicians may recommend laxatives, most of which are available over-the-counter (OTC), i.e., without a prescription, for acute use. These agents are generally not approved for long-term use by CIC or IBS-C patients nor is such use supported by long-term, well-controlled clinical trial data.

 

A study published in The American Journal of Gastroenterology in September 2011 estimates that approximately 14% of adults over 15 years of age, or over 30 million people, in the U.S., suffer from CIC. By the time most CIC patients seek care from a physician they have typically tried dietary and lifestyle changes, as well as a number of available OTC remedies, and remain unsatisfied. Commonly used OTC medications include laxatives, stool softeners and fiber supplements.

 

Irritable Bowel Syndrome with Constipation (IBS-C)

IBS is a disorder of the intestines with symptoms that include severe cramping, pain, bloating and changes of bowel habits, such as diarrhea or constipation. Patients diagnosed with IBS are commonly classified as having one of four forms: IBS-C, IBS with diarrhea, mixed-pattern IBS alternating between constipation and diarrhea, and unspecified irritable bowel syndrome. Currently, IBS in all its forms is considered to be one of the most common gastrointestinal disorders. Like CIC, some patients suffering from IBS-C may be treated with dietary measures, such as increasing fiber and fluid intake; if these measures prove ineffective, laxatives are frequently used for the management of this condition, though they are not approved for IBS-C.

 

Opioid-Induced Constipation (OIC)

OIC is a common adverse effect of chronic opioid use. Binding of opioids to peripheral opioid receptors in the gastrointestinal tract results in reduction of secretion of electrolytes, such as chloride, and subsequent reduction in small intestinal fluid. In addition, activation of enteric opioid receptors results in abnormal gastrointestinal motility. Together, these processes result in OIC, which is characterized by infrequent and incomplete evacuation of stool, hard stool consistency, and straining associated with bowel movements.

 

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Current treatment options for OIC include the use of stool softeners, enemas, suppositories and peristaltic stimulants such as senna, which stimulate muscle contractions in the bowel. Additionally, the standard prescription option for OIC is osmotic laxatives. The effectiveness of these products for the treatment of OIC is limited due to the severity of the constipation caused by opioids. In addition, physicians often cannot prescribe peristaltic stimulants for the duration of narcotic treatment because of the potential for dependence upon these stimulants. Opioid drugs are known to suppress firing of secretomotor neurons in the gut which reduces intestinal fluid secretion resulting in drier, harder stools. Lubiprostone works locally in the gut to reestablish fluid secretion thus alleviating OIC. As a result, we believe that AMITIZA holds a competitive advantage over drugs that do not work through this mechanism of action.

 

There are more than 200 million prescriptions for opioid use in the U.S. annually, and a substantial number of these prescriptions are for non-cancer chronic pain. Market research indicates that there are approximately 2.5-4.5 million moderate to severe sufferers of OIC, and 40-80% of patients taking opioids chronically for non-cancer pain report constipation in the U.S. 

 

Asia

In Japan, AMITIZA was approved in June 2012 for the treatment of CC excluding constipation caused by organic diseases, by the Ministry of Health, Labour and Welfare (MHLW). AMITIZA is Japan’s only prescription medicine for CC.

 

In Japan, Abbott Laboratories, Inc. and Mylan, Inc. (Mylan) closed Mylan’s purchase of Abbott’s non-U.S. developed markets specialty and branded generics business in February 2015, which included the license, commercialization and supply agreement (Japan Mylan Agreement) with us, dated February 2009. We did not experience any significant changes in the commercialization of AMITIZA in Japan as a result of the transfer of the Japan Mylan Agreement from Abbott to Mylan. AMITIZA is currently marketed under the Japan Mylan Agreement. More information on our collaboration with Mylan is found under the heading “Japan Mylan Agreement”.

 

In China, we signed the China Gloria Agreement to license, develop, commercialize and supply AMITIZA in the People’s Republic of China in May 2015. More information on our collaboration with Gloria is found under the heading “China Gloria Agreement.”

 

Chronic Constipation (CC)

According to MHLW epidemiology data, millions of people in Japan may live daily with the pain and discomfort of CC, yet not seek physician care. Medical attention could mean early diagnosis and effective, long-term treatment.

 

It is estimated that approximately 14.3% of the Japanese population, or over 18 million people, suffer from CC.

 

Other Global Markets

 

In October 2014, we signed an exclusive license, development, commercialization and supply agreement (Global Takeda Agreement) with Takeda to develop and commercialize AMITIZA in all global markets except in the U.S., Canada, Japan and the People’s Republic of China. More information on our collaboration with Takeda in global markets is found under the heading “Global Takeda Agreement.”

 

In the United Kingdom (U.K.), we received approval from the Medicines and Healthcare Products Regulatory Agency (MHRA) in September 2012 for the use of AMITIZA to treat CIC, and we made AMITIZA available in the U.K. in the fourth quarter of 2013. In 2014, we resubmitted an application to the MHRA for approval of AMITIZA for OIC following the MHRA’s initial decision to not approve AMITIZA for OIC in March 2014. In January 2016, we received notification from the MHRA that the appeal for the OIC indication was not approved. We will not pursue additional filings in the U.K. at this time. In July 2014, the National Institute of Health and Care Excellence (NICE) published the technology appraisal guidance recommending the use of AMITIZA in the treatment of CIC and associated symptoms in adults who have failed laxatives. In January 2015, we successfully completed the European mutual recognition procedure for AMITIZA for the treatment of CIC in Austria, Belgium, Germany, Italy, Ireland, Luxembourg, Netherlands and Spain, resulting in a recommendation for marketing authorization in these markets.

 

In Switzerland, AMITIZA was approved to treat CIC in 2009. In 2012, we reached an agreement with the Bundesamt fur Gesundheit (BAG), the Federal Office of Public Health in Switzerland, on a reimbursement price and limitations for AMITIZA in Switzerland, and began active marketing in the first quarter of 2013. In February 2014, we announced that the BAG revised several reimbursement limitations with which AMITIZA was first approved for reimbursement and inclusion in the SL to allow all Swiss physicians to prescribe AMITIZA to patients who have failed previous treatments with at least two laxatives over a nine month period.

 

In Switzerland, AMITIZA was approved for the treatment of OIC in chronic, non-cancer adult patients in July 2014 by the Swissmedic, the Swiss Agency for Therapeutic Products.

 

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Takeda became the marketing authorization holder in Switzerland in April 2015 and is expected to become the marketing authorization holder in the U.K., Austria, Belgium, Germany, Italy, Ireland, Luxembourg, the Netherlands and Spain in the first half of 2016.

 

Chronic Idiopathic Constipation (CIC)

 

A study published in The American Journal of Gastroenterology in September 2011 estimates that approximately 16% of adults over 15 years of age, or over 42 million people, in Northern Europe suffer from CIC.

 

In a study conducted in ten European countries, including Switzerland, the results of which were published in Alimentary Pharmacology and Therapeutics in 2012, approximately 28% of the participants suffering from constipation for at least 6 months were dissatisfied with their current treatment options using laxatives. Of that group, approximately 83% were interested in seeking alternative methods to relieve their constipation.

 

In October 2015, we and Takeda obtained approval of the clinical trial application (CTA) for AMITIZA for the treatment of CIC and IBS-C in Russia that was submitted in June 2015. In December 2015, a CTA was filed for AMITIZA for the treatment of CIC, IBS-C and OIC in Mexico and South Korea. We expect to initiate phase 3 registration trials in Russia, Mexico, and Korea in the first half of 2016. A new drug application (NDA) for the treatment of CIC, IBS-C, and OIC was submitted in Kazakhstan in December 2015.

 

RESCULA (unoprostone isopropyl)

 

RESCULA is a Big Potassium (BK) channel activator, which is different from other intraocular pressure (IOP) lowering agents. As part of the acquisition of R-Tech in October 2015, we acquired global rights to RESCULA.

 

United States

In the fourth quarter of 2014 we ceased marketing RESCULA and no product was made available after the March 2015 expiration date. In May 2015, we returned all licenses for unoprostone isopropyl to R-Tech.

 

Asia

In Japan, RESCULA was approved by the MHLW in 1994 for the treatment of glaucoma and ocular hypertension. In Japan, RESCULA is no longer protected by regulatory or intellectual property exclusivity. In March 2012, R-Tech signed a distribution agreement (Japan Santen Agreement) with Santen Pharmaceutical Co., Ltd. (Santen) to commercialize RESCULA in Japan. As part of the acquisition of R-Tech in 2015, we acquired R-Tech’s rights and obligations under the Japan Santen Agreement. For more information on R-Tech’s collaboration with Santen, see “Other Agreements - Japan Santen Agreement” below.

 

In South Korea, we signed the distribution agreement with Dong-A Pharm, Co., Ltd in April, 2010.

 

In Taiwan, we signed a manufacturing and supply agreement with Sinphar Pharmaceutical, Co., Ltd and also executed the distribution agreement with Zuelliq Pharma, Ltd in April, 2013.

 

Our Clinical Development Programs

 

Lubiprostone Lifecycle Management

 

Alternate Formulation

It is estimated that approximately 40% of American adults have difficulty swallowing pills. Of those who have experienced difficulty swallowing pills, approximately 14% have delayed taking doses of their medication, 8% have skipped a dose and 4% have discontinued using their medication. In addition, the current formulation of pills is not amenable for administration to young children (6 months and older). We are developing an alternate formulation of lubiprostone both for adult and pediatric patients who are unable to tolerate capsules, or for naso-gastric tube fed patients. Takeda has agreed to fund 100% of the costs, up to a specified amount, of the development of this alternate formulation and we expect to initiate a phase 3 trial of the alternate formulation of lubiprostone in adults in the second half of 2016.

 

Pediatric Functional Constipation

Constipation in children has similar characteristics to those of constipation in adults; symptoms include infrequent bowel movements, hard stools, large diameter stools and painful passage of stools. Children may also experience fecal retention due to withholding, since there is a tendency to avoid defecation and withhold bowel movements as a result of the pain experienced from the passage of large stools. This withholding of bowel movements can result in episodes of fecal incontinence. The Rome III diagnostic criteria for childhood functional constipation dictate that such symptoms occur at least once per week for at least 2 months prior to diagnosis. Furthermore, ninety percent of pediatric constipation is functional constipation and it occurs in all age groups.

 

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An analysis of longitudinal data in the U.S. showed that over the last decade there has been a nearly 4-fold increase in rates of constipation. Nevertheless, the estimates of the prevalence rate of functional constipation in the pediatric population worldwide have varied greatly, from 4% to 37%. Regardless of this wide range of estimated prevalence, only 50-70% of children with functional constipation achieve long-term improvement with the current treatments, indicating a need for better treatments.

 

The phase 3 program required to support an application for marketing approval of lubiprostone for pediatric functional constipation comprises four clinical trials, two of which are currently ongoing and are both testing the soft gelatin capsule formulation of lubiprostone in patients 6 to 17 years of age. The first of the two trials is a pivotal 12-week, randomized, placebo-controlled trial that was initiated in December 2013. The second trial is a follow-on, long-term safety extension trial that was initiated in March 2014. Following the successful completion of the phase 3 trial for the alternative formulation of lubiprostone, as described above, we are also planning to initiate two additional trials in our phase 3 program for pediatric functional constipation, which will be in children aged 6 months to less than 6 years testing the alternative formulation. Takeda has agreed to fund 70% of the costs, up to a specified amount, of this pediatric functional constipation program.

 

Cobiprostone

 

Cobiprostone, like AMITIZA, is an activator of the chloride ion channel, ClC-2, which is known to be present in gastrointestinal, liver and lung cells.

 

Oral Mucositis (OM)

A potential indication for cobiprostone is the prevention and/or treatment of OM.

 

OM refers to the serious inflammation of oral mucosa that results in patients that are undergoing chemotherapy (CT) and or radiation therapy (RT) and is the primary dose limiting adverse effect, accounting for greater than 60% of the treatment interruptions OM, symptoms include mouth pain, sores, infection, and bleeding. The condition is typically manifested as erythema or ulcerations, and may be exacerbated by local factors. Erythematous mucositis typically appears 7-10 days after initiation of radiation or high-dose cancer therapy. Additional consequences of OM include weight loss, use of feeding tube, hospitalization and dysphagia. We are initially focusing on treating patients for HNC that undergo RT. Most (89-100%) of these patients are at high risk of developing OM depending on whether the RT is in combination with CT or altered fractionation RT. Subsequently we may look at other patients who by virtue of their treatments, are at risk for developing OM which may be induced by CT of solid tumors or occur in patients being treated for hematopoietic stem cell transplant.

 

There is a large unmet medical need in OM. Currently treatment is largely palliative and includes basic oral care, cryotherapy, topical rinses, such as lidocaine, and carbomer. In the United States, there is currently no approved pharmaceutical treatment available to address OM. Palifermin, a growth factor, has been approved to treat OM in stem cell transplant patients who have undergone myelotoxic therapy.

 

It is estimated that 3-5% of all cancers are HNC and annually, in the United States, approximately 60,000 patients develop HNC and approximately 12,000 patients die from HNC. Half of the diagnosed patient have advanced stage disease and are treated with radiation. Worldwide, there are approximately 550,000 HNC cases annually.

 

In May 2015, the U.S. FDA granted Fast Track Designation for cobiprostone for the prevention of OM. In September 2015, we initiated a phase 2a clinical trial in the United States of cobiprostone oral spray for the prevention of OM in patients suffering from HNC receiving concurrent RT and CT.

 

Proton Pump Inhibitor-Refractory Non-Erosive Reflux Disease (NERD)/symptomatic Gastroesophageal Reflux Disease (sGERD)

We are developing cobiprostone to treat patients with non-erosive reflux disease (NERD) who have not had responded adequately to treatment with proton pump inhibitors (PPI) and continue to have troublesome gastroesophageal reflux symptoms despite PPI treatment.

 

About 20% of the U.S. adult population experiences GERD symptoms at least weekly. Furthermore, 50-70% of patients with typical symptoms have no endoscopic (macroscopic) evidence of erosive esophagitis. These patients are considered to have NERD.

 

NERD is a major subtype of GERD disease that is characterized macroscopically by the normal appearance of mucosa, but nevertheless patients have persistent symptoms of reflux disease. Microscopically NERD appears to be characterized by dilated intercellular spaces which may allow access of acid to the receptors in the nerves that signal to the brain.

 

GERD affects 25% to 40% of the adult population of the United States to some degree at some point.

 

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To date the medical treatment of GERD patients is primarily focused on the inhibition of gastric acid secretion with drugs such as PPIs. However, approximately 10-40% of patients with GERD fail to respond adequately to a standard-dose PPI treatment. NERD is one of the major areas of unmet need in the treatment of GERD and is related to less than optimal response to PPI therapy. NERD patients have a significantly lower response rate to PPI therapy as compared with other GERD groups and consequently constitute the majority of patients with refractory heartburn.

 

In December 2014, we initiated a phase 2a clinical trial in Japan for cobiprostone in NERD/sGERD patients who have had a non-satisfactory response to proton pump inhibitors. We expect to announce top-line data from this trial in the first half of 2016.

 

Unoprostone Isopropyl

 

Following our cessation of U.S. commercialization activities for RESCULA in 2014 and an analysis of preliminary top-line data from R-Tech’s phase 3 trial of unoprostone isopropyl in retinitis pigmentosa, we decided to discontinue development of the compound.

 

VAP-1 Inhibitors

 

Vascular adhesion protein (VAP-1) inhibitors are both an enzyme and an adhesion protein that has been implicated in the pathogenesis of inflammatory diseases. It mediates the interaction of leukocytes with the vasculature and plays an important role in immune cell trafficking. There are multiple opportunities for VAP-1 inhibitors in disease areas with great unmet medical needs and commercial opportunity. These include both autoimmune and inflammatory diseases. Additionally there is a growing understanding of the potential of VAP-1 inhibitors in regulating immune responses in cancer.

 

RTU-1096

RTU-1096 is an oral compound under development for the treatment of nonalcoholic steatohepatitis (NASH), chronic obstructive pulmonary disease (COPD), diabetic macular edema (DME) and diabetic retinopathy (DR) and immuno-oncology. In the first quarter of 2016, we completed a phase 1 trial in healthy individuals to evaluate the safety and pharmacokinetics of RTU-1096 and intend to assess the results in the first half of 2016. We will also look to generate additional preclinical data in the emerging area of immuno-oncology, to support the potential use of our molecules as a combination therapy with check-point pathway inhibitors.

 

RTU-009

RTU-009 is a pre-clinical stage, injectable VAP-1 inhibitor that is being studied in animal models of acute cerebral infarction. VAP-1 is found to cause increases in vascular cell damage, which lead to stroke. RTU-009 may inhibit VAP-1 and control the underlying cause of disease. We intend to complete IND-enabling studies, and thereafter initiate clinical development.

 

CPP 1-X/Sulindac Combination Product

 

This product is currently in a Phase 3 clinical trial, conducted by CPP for the treatment of familial adenomatous polyposis (FAP). Under our agreement with CPP, we have the exclusive option to license this product for North America. There are currently no approved treatments for FAP and no other products in late-stage development.  A genetic disease, FAP typically develops into colon cancer if left untreated.  Current treatment paradigms require patients to undergo the progressive removal of colon and rectum, ongoing endoscopies of the GI tract, and additional surgery throughout life.  As a result, patients with FAP experience poor quality of life, inconvenience and significant cost.  FAP has been designated an orphan indication in the U.S. and Europe, with a prevalence of about 1 in 10,000, and approximately 30,000 cases currently in the United States.

 

CPP-1X/sulindac oral combination product has demonstrated robust Phase 2 data in sporadic colon adenoma, additional evidence of efficacy in FAP with CPP-1X combinations, and has shown to be well-tolerated.  The ongoing Phase 3 study is a 150-patient, three-arm, double-blind, randomized trial of the combination agent and the single agent comparators.  Enrollment in the study is expected to be complete in the first half of 2016 and the trial is expected to conclude in 2018.

 

AMITIZA Collaboration Agreements

We have the following collaboration agreements with our partners to supply, develop and commercialize AMITIZA. The collaboration agreements entered into are covered by geographic location. The acquisition of R-Tech in October 2015 enabled us to secure a larger portion of the global economics of AMITIZA, as R-Tech is the exclusive manufacturer and supplier of AMITIZA.

 

North America Takeda Agreement

In October 2004, we entered into an agreement with Takeda to supply, develop and commercialize AMITIZA for gastrointestinal indications in the U.S. and Canada. The original agreement was amended on February 1, 2006 through a supplemental agreement, and in October 2014 we and Takeda and certain Takeda affiliates executed amendments to the agreement. Collectively, these are referred to as the North America Takeda Agreement. Payments to us under these agreements include a non-refundable upfront payment, non-refundable development and commercial milestone payments, reimbursement of certain development and co-promotion costs, product royalties and product sales.

 

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Under the North America Takeda Agreement, which has an initial contract term through 2020, and thereafter continues until terminated by Takeda in its sole discretion:

 

·We recognize product sales revenue from the supply of AMITIZA to Takeda at a negotiated supply price.
·We recognize royalty income from Takeda’s net sales of AMITIZA in the U.S. and Canada. The royalty rates consists of several tiers ranging from 18%-26% with the royalty rate resetting every year:
·We recognize research and development revenue for the reimbursement of research and development costs as Takeda has agreed to fund all development costs, including regulatory-required studies, to a maximum of $50.0 million for each additional indication and $20.0 million for each additional formulation. Takeda and we have agreed to equally share all costs in excess of those amounts. With respect to any studies required to modify or expand the label for AMITIZA for the treatment of CIC, IBS-C or OIC, Takeda has agreed to fund 70% of the costs of such studies, and we have agreed to fund the remainder. Additionally, Takeda has agreed to fund 100% of the development costs for the new formulation of AMITIZA, and 70% of the development costs for the treatment of pediatric functional constipation.
·Takeda is required to provide a minimum annual commercial investment during the current term of the North America Takeda Agreement and may reduce it when a generic equivalent enters the market.
·We retain the right to co-promote AMITIZA for gastrointestinal indications. In December 2014, as part of the amendments to the North America Takeda Agreement, we ceased our co-promoting activity.
·We are eligible for additional commercial milestone payments contingent on the achievement of certain net sales revenue targets.
·Our collaboration with Takeda is administered in part by four committees consisting of an equal number of representatives from both companies. In the case of a deadlock within the joint steering committee, our chief executive officer has the determining vote on matter arising from the joint development and manufacturing committees, while the chief operating officer of Takeda has the determining vote on matters arising from the joint commercialization committee.
·During the extended term, beginning on January 1, 2021, we will share equally with Takeda in the net annual sales revenue from branded AMITIZA sales.

 

Global Takeda Agreement

In October 2014, we entered into the Global Takeda Agreement to develop and commercialize AMITIZA for gastrointestinal indications. The territories excluded from the Global Takeda Agreement are Canada, the U.S., Japan and the People’s Republic of China. Canada and the U.S. are covered by the North America Takeda Agreement, Japan is covered by the Japan Mylan Agreement, and China is covered by the China Gloria Agreement. The agreement is effective until it expires on a country-by-country basis on the fourteenth anniversary of the date of first commercial sale in that country. Under the terms of the agreement:

 

·We received an upfront payment of $14.0 million from Takeda during October 2014.
·We will recognize revenues from the product sales of AMITIZA to Takeda at a negotiated supply price.
·We are eligible for up to $35.0 million in commercial milestone payments contingent on the achievement of certain net sales revenue targets.
·We are responsible for the first $6.0 million in development costs, and Takeda is responsible for all subsequent development activities and related costs.
·Takeda is the marketing authorization holder for Switzerland.
·Takeda will request the regulatory authorities to transfer the market authorization for the U.K. and will become the marketing authorization holder for other countries upon regulatory approval and will be responsible for all commercialization and regulatory activities.

 

Japan Mylan Agreement

In February 2009, we entered into a license, commercialization and supply agreement (the Japan Mylan Agreement) for AMITIZA in Japan with Mylan. Under the terms of the Japan Mylan Agreement (which continues until 2027):

 

·We recognize revenues from the product sales of AMITIZA to Mylan at a negotiated supply price.
·Mylan has a right of first exclusive negotiation to obtain a license to develop and commercialize AMITIZA in Japan for any new indications that we may develop, such as OIC. We retain the rights to AMITIZA for all other therapeutic uses. We are required to fund and complete all the development work including any additional clinical studies required to maintain regulatory approval in Japan. We own all the rights covered under the regulatory filings.

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·Mylan is required to fund and undertake all commercialization efforts including pre-launch and post-launch marketing, promotion and distribution. Mylan is required to maintain the number of sales staff and the estimated level of annual net sales based on the commercialization plan approved by the committees described below.
·We have retained the right to co-promote the product in Japan under certain conditions and all other development and commercialization rights to all other therapeutic areas and are responsible for the cost of co-promotion.
·Our collaboration efforts under the Japan Mylan Agreement are administered by two committees consisting of an equal number of representatives from both parties.

 

China Gloria Agreement

In May 2015, we entered into an exclusive license, development, commercialization and supply agreement (China Gloria Agreement), for AMITIZA in the People’s Republic of China. The China Gloria Agreement is effective until the thirteenth anniversary of the effective date and will automatically renew for successive three year periods unless terminated upon one year’s prior written notice by one of the parties. Under the terms of the China Gloria Agreement:

 

·We received an upfront payment of $1.0 million from Gloria during May 2015 and an upfront payment of $500,000 in June 2015 after the CFDA accepted the IND application for a pivotal trial of AMITIZA in patients with CIC.

·We are eligible to receive an additional payment in the amount of $1.5 million upon the occurrence of a specified regulatory or commercial milestone event.

·Gloria is responsible for all development activities and costs, as well as commercialization and regulatory activities, for AMITIZA in the People’s Republic of China.

·We will be the exclusive supplier of AMITIZA to Gloria at an agreed upon supply price.

 

RESCULA Agreement

 

Japan Santen Agreement

In March 2012, R-Tech entered into an exclusive transaction agreement (Japan Santen Agreement) with Santen Pharmaceutical Co. Ltd (Santen) to commercialize RESCULA in Japan. The initial term of the Japan Santen Agreement ends on March 31, 2016; thereafter, the agreement automatically extends for successive one-year renewal terms unless either party gives the other party an 11-month prior notice. Under the terms of the Japan Santen Agreement we recognize revenues from the product sales of RESCULA to Santen at a negotiated price.

 

Pipeline Agreement

 

CPP Agreement

In January 2016, we entered into an option and collaboration agreement (CPP Agreement) under which Cancer Prevention Pharmaceuticals, Inc. (CPP) has granted us the sole option to acquire an exclusive license to commercialize CPP-1X/sulindac combination product in North America. Under the terms of the CPP Agreement:

·We have invested $5.0 million in CPP in the form of a convertible note, with a planned additional $5.0 million equity investment in CPP’s next qualified financing, which will be either an IPO or a private financing as defined by the agreement;
·We will pay CPP an option fee of up to $7.5 million, payable in two tranches; the first tranche of $3.0 million was paid as signing;
·CPP will complete the ongoing phase 3 trial off CPP-1x/sulindac for the treatment of FAP under the oversight of a joint steering committee;
·Upon exercise of our exclusive option, we would acquire an exclusive license to the product, for all indications, and would be obligated to pay CPP up to an aggregate of $190.0 million in license fees and milestone payments upon the achievement of specified clinical development and sales milestones; and
·We and CPP would share equally in profits from the sale of licensed products.

 

Intellectual Property

 

Our success depends in part on our ability to obtain and maintain proprietary protection for the technology and know-how upon which our products are based, to operate without infringing on the proprietary rights of others and to prevent others from infringing on our proprietary rights.

 

We hold the ownership rights to develop and commercialize Prostones and VAP-1 inhibitors covered by patents and patent applications. Our portfolio of patents includes patents or patent applications with claims directed to compositions of matter, including both compounds and pharmaceutical formulations, methods of use, or a combination of these claims, and methods of manufacturing the compounds. Depending upon the timing, duration and specifics of FDA approval of the use of a compound for a specific indication, some of our U.S. patents may be eligible for a limited patent term extension under the Drug Price Competition and Patent Term Restoration Act of 1984, referred to as the Hatch-Waxman Act.

 

As of December 31, 2015, the patent rights relating to lubiprostone include compositions of matter, methods of use and methods of manufacturing, including 16 patents listed in the U.S. FDA Orange Book. These patent rights also include various U.S., European and Japanese patent applications relating to dosing regimens, pharmaceutical formulations and other claims. The U.S. patents expire between 2020 and 2027. Other foreign patents expire between 2020 and 2028.

 

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As of December 31, 2015, the patent rights relating to unoprostone isopropyl include compositions of matter, methods of use and methods of manufacturing, including two patents listed in the U.S. FDA Orange Book. The U.S. patents relating to compositions of matter expire between 2018; those relating to method of use expire in 2031. The other foreign patents and patent applications expire between 2029 and 2035.

 

The patent rights relating to cobiprostone include compositions of matter, methods of use and methods of manufacturing. These patent rights also include various U.S., European and Japanese patent applications relating to dosing regimens, pharmaceutical formulations and other claims. The U.S. patents relating to compositions of matter expire between 2020 and 2027. The other U.S. and foreign patents/patent applications expire between 2020 and 2035.

 

The patent rights relating to VAP-1 Inhibitors (RTU-1096 and RTU-009) include compositions of matter. The U.S. patents relating to compositions of matter expire between 2029 and 2031. The other U.S. and foreign patents/patent applications expire between 2029 and 2036.

 

We are actively seeking to augment our portfolio of compounds by focusing on the development of new chemical entities, or NCEs, which have not previously received FDA approval. Upon approval by the FDA, NCEs are entitled to market exclusivity in the U.S. with respect to generic drug products for a period of five years from the date of FDA approval, even if the related patents have expired. We are also engaged in lifecycle management strategies for our marketed products.

 

Manufacturing

 

We acquired R-Tech in October 2015. The acquisition transferred direct control and management to us for the production and supply chain of commercial quantities of AMITIZA or preclinical or clinical supplies of the other prostone compounds that we are testing in our development programs. This also includes the manufacture of RESCULA, cobiprostone and ion channel activators and any of our future prostone compounds.

 

Our manufacturing network is a combination of owned assets and external suppliers. There are existing supply agreements between R-Tech and the external suppliers to ensure continued supply of our products.

 

Competition

 

AMITIZA (lubiprostone)

 

In the U.S., an estimated 40-50 million patients who suffer from constipation that is idiopathic in nature or a consequence of other conditions such as IBS or chronic opioid use. Many patients are currently treated for CIC, IBS-C or OIC with a variety of medications. Over-the-counter (OTC) medications are available and are generally intended to provide relief for occasional constipation. Prescription products are also available and are generally intended to provide relief for chronic constipation. As such, the U.S. constipation market is expansive and diverse with a multitude of products intended to treat a large heterogeneous patient population.

 

The prescription chronic constipation market can generally be bifurcated into two categories: 1) generic laxatives and 2) branded products. Generic laxatives make up roughly 70%-80% of the total prescription volume while branded prescriptions have grown to represent 20%-30% of the prescription market. The branded prescription products are briefly described below:

 

·AMITIZA (lubiprostone): AMITIZA, is approved by the FDA for the treatment of CIC (from an unknown cause; not constipation due to another condition or treatment), IBS-C and CIC. AMITIZA softens the stool by increasing its water content, so the stool can pass easily. AMITIZA is taken twice daily.
·Linzess (linaclotide): Linzess is approved of CIC and IBS-C. This drug is a capsule taken once daily and helps relieve constipation by helping bowel movements occur more often. It is not approved for use in those age 17 years and younger.
·Lactulose: Lactulose, a prescription laxative for chronic constipation, draws water into the bowel to soften and loosen the stool.
·Polyethylene glycol (PEG): PEG is an osmotic laxative for chronic constipation and causes water to remain in the stool, which results in softer stools.
·Movantik (naloxegol): Movantik is approved for OIC. This drug works by binding to mu-receptors in the brain and other parts of the central nervous system to block pains signals as well as bind to mu-receptors in the bowel which may cause OIC.

 

At this time AMITIZA is the only branded product that has a unique mechanism of action. AMITIZA is also the only branded product on the market today to be indicated in three separate indications for CIC, IBS-C and OIC.

 

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AMITIZA Competitors

The key branded and generic products currently on the U.S. market include:

 

Product Company Approved Indications

AMITIZA
(lubiprostone)

Sucampo/Takeda CIC, IBS-C, OIC

Linzess
(linaclotide)

Allergan/Ironwood CIC, IBS-C

Movantik
(naloxegol)

AstraZeneca OIC
Relistor (SQ)
(methylnaltrexone bromide)
Valeant/Progenics Chronic Constipation
Lactulose Several CIC, IBIS-C
Generic PEG Several Chronic Constipation

 

Key pipeline competitors include:

 

Product Company Status
Plecanatide Synergy Pharmaceuticals Inc.

CIC filed January 2016
IBS-C filing expected Q4 2016

Naldemedine Shionogi OIC Phase III; positive Phase III topline, expected filing H1 2016

 

Other agents in various stages of development include:

 

Product Company Status
Tenapanor Ardelyx IBS-C, Phase III
Linaclotide Allergan/Ironwood Linaclotide Colonic Release, Phase II
RM-131/relamorelin Ipsen/Rhythm CIC, Phase II
TD-1211/axelopran Theravance OIC, Phase II
SP-333/dolcanatide Synergy OIC, IBD Phase II

 

Additionally, there are several 5-HT Receptor agonists in various stages of development as well (Resolor/Shire Phase III in CIC, YKP-10811/SK Biopharma in CIC Phase II)

 

RESCULA (unoprostone isopropyl)

 

RESCULA (unoprostone isopropyl) is approved for Ocular Hypertension and Open-Angle Glaucoma and is currently marketed in several global regions including Japan, South Korea and Taiwan.  RESCULA was originally launched in Japan in 1994 and is no longer covered by patent or regulatory exclusivity in Japan.  RESCULA is no longer commercialized in the U.S. (it was approved by the FDA in 2000).

 

According to recent market data in Japan, the glaucoma treatment market grew 0.9% to ¥105.7 billion.  Treatments for glaucoma represent the largest segment of Japan’s prescription ophthalmic pharmaceutical market, accounting for approximately 33% of the total.  Increased intraocular pressure is a significant risk factor resulting in damage to the optic nerve.  This can lead to visual field loss and in some cases, blindness.  Glaucoma is the most common cause of blindness in people with ophthalmic disease in Japan. The glaucoma market is expected to expand in the future, mainly due to the increase in patient numbers owing to population aging.

 

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RESCULA faces many competitors which promote products for primary-angle glaucoma (PAOG), and ocular hypertension.  There are several products in the regions where RESCULA is marketed that have become generic and have therefore had an impact on the usage of prostaglandins as first line therapy.  Other competitive products include latanaprost and travoprost, ophthalmic solutions and suspensions and generic beta blockers.  Prostaglandin analogues continue to have strong first line market share followed by generic beta blockers.  Our competitors are also developing additional pipeline products for PAOG and ocular hypertension. 

 

Product Candidates

We face similar competition from approved therapies and potential pipeline products for the diseases and conditions potentially addressed by lubiprostone, unoprostone isopropyl, cobiprostone, and VAP-1 inhibitors, and are likely to face competition for any other product candidates we may elect to develop in the future.

 

Government Regulation

 

Government authorities in the U.S., at the federal, state and local level, and in other countries extensively regulate the research, development, testing, approval, manufacturing, labeling, post-approval monitoring and reporting, packaging, promotion, storage, advertising, distribution, marketing and export and import of pharmaceutical products such as those we are developing. The process of obtaining regulatory approvals and the subsequent compliance with appropriate federal, state, local and foreign statutes and regulations require the expenditure of substantial time and financial resources.

 

United States Government Regulation

In the U.S., the FDA regulates drugs under the Federal Food, Drug, and Cosmetic Act, as amended, and implements regulations. The FDA has jurisdiction over all of our products and administers requirements covering the safety, effectiveness, manufacturing, quality control, distribution, labeling, marketing, advertising, dissemination of information, post-marketing study, and pharmacovigilance of our pharmaceutical products. Information that must be submitted to the FDA in order to obtain approval to market a drug varies depending upon whether the drug is a new product whose safety and efficacy have not previously been demonstrated in humans or a drug whose active ingredients and certain other properties are the same as those of a previously approved drug. The results of product development, preclinical studies and clinical trials must be submitted to the FDA as part of the approval process. The FDA may deny approval if the applicable regulatory criteria are not satisfied, or it may require additional clinical data or analyses or even an additional clinical trial. Even if such data are submitted, the FDA may ultimately decide that the application does not satisfy the criteria for approval.

 

Obtaining FDA approval for new products and manufacturing processes can take a number of years and involve the expenditure of substantial resources. To obtain FDA approval for the commercial sale of a therapeutic agent, the potential product must undergo testing programs on animals, the data from which is used to file an investigational NDA with the FDA. In addition, there are three phases of human testing following Good Clinical Practices (GCP) guidelines:

 

·Phase 1 consists of safety tests with human clinical evaluations, generally in normal, healthy volunteers;

·Phase 2 programs expand safety tests and measure efficacy along with dose finding evaluations and are conducted in volunteers with a particular disease condition that the drug is designed to treat; and

·Phase 3 programs are greatly expanded clinical trials to determine the effectiveness of the drug at a particular dosage level in the affected patient population.

 

The data from these clinical tests are combined with data regarding chemistry, manufacturing and animal pharmacology and toxicology, and are then submitted to the FDA in the form of an NDA. The preparation of an NDA requires the expenditure of substantial funds and the commitment of substantial resources.

 

Failure to comply with the applicable FDA requirements at any time during the product development process, approval process or following approval may result in administrative or judicial sanctions. These sanctions could include the FDA’s imposition of a hold on clinical trials, refusal to approve pending applications, withdrawal of an approval, warning letters, product recalls, product seizures, total or partial suspension of production or distribution, injunctions, fines, civil penalties or criminal prosecution. Any agency or judicial enforcement action could have a material adverse effect on our business.

 

The FDA extensively regulates all aspects of manufacturing quality under its current good manufacturing practice (cGMP) regulations. The FDA inspects the facility or the facilities at which drug products are manufactured. The FDA will not approve the product unless cGMP compliance is satisfactory. If the FDA determines the application, manufacturing process or manufacturing facilities are not acceptable, it will outline the deficiencies in the application and often will request corrective actions including additional validation or information.

 

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The pharmaceutical testing and approval process requires substantial time, effort and financial resources. Data obtained from clinical activities are not always conclusive and may be susceptible to varying interpretations, which could delay, limit or prevent regulatory approval. The FDA may not grant approval on a timely basis, or at all. We may encounter difficulties or unanticipated costs in our efforts to secure necessary governmental approvals, which could delay or preclude us from marketing our products. The FDA may limit the indications for use or place other conditions on any approvals that could restrict the commercial application of the products. After approval, some types of changes to the approved product, such as manufacturing changes and additional labeling claims, are subject to further FDA review and approval.

 

Post-Approval Requirement

After regulatory approval of a product is obtained, we are obligated to comply with a number of post-approval requirements. For example, the FDA may require post marketing, or phase 4 clinical trials to assess additional elements of the product’s safety or efficacy. In addition, holders of an approved NDA are required to report certain adverse drug reactions and production problems to the FDA, to provide updated safety information and to comply with requirements concerning advertising and promotional labeling for their products. The FDA periodically inspects manufacturing facilities to assess compliance with cGMP, which imposes certain fiscal, procedural, substantive and record-keeping requirements.

 

We rely substantially on third parties for the performance of certain activities related to the production, packaging and distribution of our drug products for clinical and commercial use. Future FDA inspections may identify compliance issues at our facilities or at the facilities of our manufacturers that may disrupt production or distribution, or require substantial resources to correct. In addition, discovery of problems with a product or the failure to comply with applicable requirements may result in restrictions on a product, manufacturer or holder of an approved NDA, including withdrawal or recall of the product from the market or other voluntary, FDA-initiated or judicial action that could delay or prohibit further marketing. Newly discovered or developed safety or effectiveness data may require changes to a product’s approved labeling, including the addition of new warnings, precautions and contraindications. Also, new government requirements, including those resulting from new legislation, may be established that could delay or prevent regulatory approval of our products under development.

 

Regulation Outside of the United States

In addition to regulations in the U.S., we are subject to a variety of regulations in other jurisdictions most notably by the Health Canada in Canada, European Medicines Agency (EMA) in the E.U., Swissmedic in Switzerland and the MHLW in Japan. Whether or not we obtain FDA approval for a product, we must obtain approval by the comparable regulatory authorities of countries outside the U.S. before we can commence clinical trials or marketing of the product in those countries. The requirements governing the conduct of clinical trials, product licensing, pricing and reimbursement vary greatly from country to country, and the time for approval is country dependent and may be longer or shorter than that required by the FDA.

 

Canada

In Canada the new drug approval process is similar to that in the U.S. The process is divided into four phases: preclinical studies, clinical trials, new drug submission and marketing. Health Canada regulates the clinical trials and grants market authorization based on an assessment of the safety, efficacy and quality of drug products. In addition to approval of new drugs, the federal government also regulates drug pricing through the Patented Medicines Prices Review Board (PMPRB).

 

Europe

In Europe medicinal products are governed by a framework of E.U. directives which apply across all E.U. member states. To obtain regulatory approval of a drug under the E.U. regulatory system, we may submit an MAA, either under a centralized, decentralized, or mutual recognition procedure (MRP). The centralized procedure, which is compulsory for medicines produced by certain biotechnological processes and optional for those which are innovative, provides for the grant of a single marketing authorization that is valid for all E.U. member states. The decentralized procedure provides for a member state, known as the reference member state, to assess an application, with one or more concerned, member states subsequently approving that assessment. The MRP provides approval in one country and then allows for a request from subsequent countries to mutually recognize the original country’s approval. The E.U. also governs among other areas, the authorization and conduct of clinical trials, the marketing authorization process for medical products, manufacturing and import activities, and post-authorization activities including pharmacovigilance. The E.U. has established regulations on pediatric medicines which impose certain obligations on pharmaceutical companies with respect to the investigation of their products in children.

 

Japan

In Japan, pre-marketing approval and clinical studies are required for all pharmaceutical products. The regulatory requirements for pharmaceuticals in Japan have in the past been so lengthy and costly that it has been cost-prohibitive for many pharmaceutical companies. Historically, Japan has required that pivotal clinical data submitted in support of a NDA be performed on Japanese patients. Recently, however, as a part of the global drug harmonization process, Japan has signaled a willingness to accept U.S. or E.U. patient data when submitted along with a bridging study, which demonstrates that Japanese and non-Japanese subjects react comparably to the product. This approach, which is executed on a case-by-case basis, may reduce the time required for approval and introduction of new products into the Japanese market. To obtain manufacturing/marketing approval, we must submit an application for approval to the MHLW with results of nonclinical and clinical studies to show the quality, efficacy and safety of a new drug. A data compliance review, GCP on-site inspection, cGMP audit and detailed data review are undertaken by the PMDA. The application is then discussed by the committees of the Pharmaceutical Affairs and Food Sanitation Council (PAFSC). Based on the results of these reviews, the final decision on approval is made by MHLW. After the approval, negotiations regarding the reimbursement price with MHLW will begin. The price will be determined within 60 to 90 days unless the applicant disagrees, which may result in extended pricing negotiations.

 

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Regulation of the Health Care Industry

In addition to the regulatory approval requirements described above, we are or will be directly or indirectly through our customers, subject to extensive regulation of the health care industry by the federal and state government and foreign countries in which we may conduct our business. The laws that directly or indirectly affect our ability to operate our business include the following:

 

  · The federal Medicare and Medicaid Anti-Kickback laws, which prohibit persons from knowingly and willfully soliciting, offering, receiving or providing remuneration, directly or indirectly, in cash or in kind, to induce either the referral of an individual, or furnishing or arranging for a good or service, for which payment may be made under federal healthcare programs such as the Medicare and Medicaid programs;
  · Other Medicare laws, regulations, rules, manual provisions and policies that prescribe the requirements for coverage and payment for services performed by our customers, including the amount of such payment;

 

  · The federal False Claims Act which imposes civil and criminal liability on individuals and entities who submit, or cause to be submitted, false or fraudulent claims for payment to the government;
  · The False Claims Act which prohibits knowingly and willfully falsifying, concealing or covering up a material fact or making any materially false statement in connection with the delivery of or payment for healthcare benefits, items or services;
  · The Foreign Corrupt Practices Act (FCPA), which prohibits certain payments made to foreign government officials;
  · State and foreign law equivalents of the foregoing and state laws regarding pharmaceutical company marketing compliance, reporting and disclosure obligations; and
  · The Patient Protection and Affordable Care Act (ACA), which among other things changes access to healthcare products and services; creates new fees for the pharmaceutical and medical device industries; changes rebates and prices for health care products and services; and requires additional reporting and disclosure.

 

If our operations are found to be in violation of any of these laws, regulations, rules or policies or any other law or governmental regulation, or if interpretations of the foregoing change, we may be subject to civil and criminal penalties, damages, fines, exclusion from the Medicare and Medicaid programs and the curtailment or restructuring of our operations.

 

Pharmaceutical Pricing and Reimbursement

 

In the U.S. and other countries, sales of any products for which we receive regulatory approval for commercial sale will depend in part on the availability of reimbursement from third-party payers. Third-party payers include government health administrative authorities, managed care providers, pharmacy benefit managers, private health insurers and other organizations. These third-party payers are increasingly challenging the price and examining the cost-effectiveness of medical products and services. In addition, significant uncertainty exists as to the reimbursement status of newly approved healthcare product candidates. We may need to conduct expensive pharmacoeconomic studies in order to demonstrate the cost-effectiveness of our products. Our products may not be considered cost-effective. Adequate third-party reimbursement may not be available to enable us to maintain price levels sufficient to realize an appropriate return on our investment in product development.

 

United States

Federal, state and local governments in the U.S. continue to work towards significant legislation aimed to limit the growth of healthcare costs, including the cost of prescription drugs. Following the U.S. Supreme Court decision in June 2012 upholding the Patient Protection and Affordable Care Act there has been an increase in the pace of regulatory issuances by those U.S. government agencies designated to carry out the extensive requirements of the ACA. These regulatory actions are expected to have both positive and negative impacts on the U.S. healthcare industry, although uncertainty remains regarding the ACA’s ultimate effects. This legislation has both current and long term impacts on us. The provisions of the U.S. Healthcare Reform Act are effective on various dates over the next several years.

 

Medicaid is a joint federal and state program that is administered by the states for low income and disabled beneficiaries. Under the Medicaid Drug Rebate Program, we are required to pay a rebate for each unit of product reimbursed by the state Medicaid programs. The amount of the rebate for each product is set by law as the greater of 23.1% of the average manufacturer price (AMP) or the difference between AMP and the best price available from us to any customer (with limited exceptions). The rebate amount must be adjusted upward if AMP increases more than inflation (measured by the Consumer Price Index - Urban). The adjustment can cause the rebate amount to exceed the minimum 23.1% rebate amount. The rebate amount is calculated each quarter based on our report of current AMP and best price for each of our products to the Centers for Medicare & Medicaid Services. The requirements for calculating AMP and best price are complex. We are required to report any revisions to AMP or best price previously reported within a certain period, which revisions could affect our rebate liability for prior quarters. In addition, if we fail to provide information timely or we are found to have knowingly submitted false information to the government, the statute governing the Medicaid Drug Rebate Program provides for civil monetary penalties.

 

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Medicare is a federal program that is administered by the federal government that covers individuals age 65 and over as well as those with certain disabilities. Medicare Part D provides coverage to enrolled Medicare patients for self-administered drugs (i.e., drugs that do not need to be injected or otherwise administered by a physician). Medicare Part D is administered by private prescription drug plans approved by the U.S. government and each drug plan establishes its own Medicare Part D formulary for prescription drug coverage and pricing, which the drug plan may modify from time-to-time. The prescription drug plans negotiate pricing with manufacturers and may condition formulary placement on the availability of manufacturer discounts. Manufacturers, including us, are required to provide a 50% discount on brand name prescription drugs utilized by Medicare Part D beneficiaries when those beneficiaries reach the coverage gap in their drug benefits.

 

Our products are subject to discounted pricing when purchased by federal agencies via the Federal Supply Schedule (FSS). FSS participation is required for our products to be covered and reimbursed by the Veterans Administration (VA) Department of Defense, (DoD), Coast Guard, and Public Health Service (PHS). Coverage under Medicaid, the Medicare Part B program and the PHS pharmaceutical pricing program is also conditioned upon FSS participation. FSS pricing is negotiated periodically with the Department of Veterans Affairs. FSS pricing is intended not to exceed the price that we charge our most-favored non-federal customer for a product. In addition, prices for drugs purchased by the VA, DoD (including drugs purchased by military personnel and dependents through the TriCare retail pharmacy program), Coast Guard, and PHS are subject to a cap on pricing equal to 76.0% of the non-federal average manufacturer price, or non-FAMP. An additional discount applies if non-FAMP increases more than inflation (measured by the Consumer Price Index - Urban). In addition, if we fail to provide information timely or we are found to have knowingly submitted false information to the government, the governing statute provides for civil monetary penalties in addition to other penalties available to the government.

 

To maintain coverage of our products under the Medicaid Drug Rebate Program, we are required to extend discounts to certain purchasers under the PHS pharmaceutical pricing program. Purchasers eligible for discounts include hospitals that serve a disproportionate share of financially needy patients, community health clinics and other entities that receive health services grants from the PHS.

 

Canada

The purpose of the PMPRB is to ensure that prices of patented and non-patented medicines are not excessive. Accordingly, the PMPRB monitors and reports prices of non-patented drugs and publishes annual reports on the prices using international median prices as a benchmark. The PMPRB does not set drug prices, analyze relative cost effectiveness or value of new drugs or take an active role in formulary listing and reimbursement pricing as these responsibilities are assumed either by the provinces and territories. In order to determine whether the price for a given drug is “excessive”, new drugs are labelled in one of three categories: Category 1 refers to line extensions of existing medicines. The price of a Category 1 drug is presumed excessive if it does not bear a reasonable relationship to the price of other medicines of the same strength sold by the patentee; Category 2 refers to breakthrough or substantial improvements over existing drugs. The price of a Category 2 drug is presumed excessive if it exceeds the prices of all the medicines in the same therapeutic class or the median of the prices in seven countries (France, Germany, Italy, Sweden, Switzerland, the U.K. and the U.S.). Category 3 refers to new chemical entities offering moderate, little or no therapeutic improvement. The price of a Category 3 drug is presumed excessive if it exceeds the prices of all the medicines in the same therapeutic class. The PMPRB also monitors the price of existing drugs, which is considered excessive if it exceeds the increase in the general Canadian Consumer Price Index. When manufacturers set the price of a patented medicine too high, the PMPRB first attempts to have the manufacturer reduce the price voluntarily. Barring this, it can hold a public hearing into the price following which it can order the manufacturer to reduce the price, withdraw the manufacturer’s market authorization, or impose a fine equal to or double the amount of the excessive increase in price.

 

Europe

Different pricing and reimbursement schemes exist in other countries. In Europe, governments influence the price of pharmaceutical products through their pricing and reimbursement rules and control of national health care systems that fund a large part of the cost of such products to consumers. The approach taken varies from state to state. Some jurisdictions permit products to be marketed only after a reimbursement price has been agreed. Other states allow companies to fix their own prices for medicines, but monitor company profits. In some cases, pharmacoeconomic analyses from clinical studies and other available resources are used to establish pricing using risk-benefit comparisons with currently available products.

 

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In the U.K., pharmaceutical companies set their own price, and then national bodies (e.g., NICE and Scottish Medicines Consortium), sub-national bodies (e.g., Greater Manchester Medicines Management Group and London Procurement Partnership), or local bodies (e.g., Clinical Commissioning Groups and Health Boards) will determine if a medicine is cost-effective. The national and sub-national bodies advise local bodies, which are greatly influenced by a NICE endorsement; however, ultimately the decision to pay for a medicine is made at a local level in the U.K.

 

In Switzerland, the Swiss health care system is a compulsory private system where patients pay a monthly variable fee to a registered health insurance fund. All insurers reimburse against a common national formulary, the SL. The BAG makes the decisions on reimbursement and pricing of all prescription drugs in the market with their review taking three to four months. For new drugs it is not uncommon for there to be several rounds of review. It also conducts regular price reviews of the drugs on the formulary. The Federal Commission on drugs or Arzneimittelkommission (EAK) is a body assisting the BAG with expert advice. Once a product is approved the BAG, in consultation with EAK, decides whether or not the drug will appear on the SL. After EAK’s evaluation of a drug, BAG and EAK decide on the maximum price in the market. The criteria used are:

 

·Internal comparison with reimbursed and non-reimbursed therapeutic equivalents,
· External cross country comparison (reference countries: Denmark, Germany, the U.K. and the Netherlands), and
· Cost benefit analysis

 

Japan

In Japan, pricing is established utilizing various information including reference prices from other international markets. However, the MHLW biannually reviews the pharmaceutical prices of individual products. In the past, these reviews have resulted in price reductions. We expect similar price reviews in the future, in line with the government’s previously announced plan for controlling health care costs. It is not possible to predict the outcome of these reviews, and it is possible that Japanese authorities will again reduce drug reimbursement rates, which could adversely affect the reimbursement levels for our products or product candidates.

 

Regulation Pertaining to Sales and Marketing

We are subject to various federal and state laws pertaining to health care “fraud and abuse,” including anti-kickback laws and false claims laws. Anti-kickback laws generally prohibit a prescription drug manufacturer from soliciting, offering, receiving, or paying any remuneration to generate business, including the purchase or prescription of a particular drug. Although the specific provisions of these laws vary, their scope is generally broad and there may be no regulations, guidance or court decisions that clarify how the laws apply to particular industry practices. There is therefore a possibility that our practices might be challenged under the anti-kickback or similar laws. False claims laws prohibit anyone from knowingly and willingly presenting, or causing to be presented for payment to third party payers (including Medicare and Medicaid), claims for reimbursed drugs or services that are false or fraudulent, claims for items or services not provided as claimed, or claims for medically unnecessary items or services. Our activities relating to the sale and marketing of our products may be subject to scrutiny under these laws. Violations of fraud and abuse laws may be punishable by criminal or civil sanctions, including fines and civil monetary penalties, and exclusion from federal health care programs (including Medicare and Medicaid). Federal and state authorities are paying increased attention to enforcement of these laws within the pharmaceutical industry and private individuals have been active in alleging violations of the laws and bringing suits on behalf of the government under the federal False Claims Act. If we were subject to allegations concerning, or were convicted of violating, these laws, our business could be harmed.

 

Laws and regulations have been enacted by the federal government and various states to regulate the sales and marketing practices of pharmaceutical manufacturers. The laws and regulations generally limit financial interactions between manufacturers and health care providers or require disclosure to the government and public of such interactions. The laws include federal “sunshine” provisions enacted in 2010 as part of the comprehensive federal health care reform legislation. The sunshine provisions apply to pharmaceutical manufacturers with products reimbursed under certain government programs and require those manufacturers to disclose annually to the federal government (for re-disclosure to the public) certain payments made to physicians and certain other healthcare practitioners or to teaching hospitals. State laws may also require disclosure of pharmaceutical pricing information and marketing expenditures. Many of these laws and regulations contain ambiguous requirements. Given the lack of clarity in laws and their implementation, our reporting actions could be subject to the penalty provisions of the pertinent federal and state laws and regulations. Outside the U.S., other countries have implemented requirements for disclosure of financial interactions with healthcare providers and additional countries may consider or implement such laws.

 

Other Regulations

 

Foreign Anti-Corruption

We are subject to various federal and foreign laws that govern our international business practices with respect to payments to government officials. Those laws include the U.S. Foreign Corrupt Practices Act which prohibits U.S. companies and their representatives from paying, offering to pay, promising, or authorizing the payment of anything of value to any foreign government official, government staff member, political party, or political candidate for the purpose of obtaining or retaining business or to otherwise obtain favorable treatment or influence a person working in an official capacity. In many countries, the health care professionals we regularly interact with may meet the Foreign Corrupt Practices Act (FCPA) definition of a foreign government official. The FCPA also requires public companies to make and keep books and records that accurately and fairly reflect their transactions and to devise and maintain an adequate system of internal accounting controls.

 

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The laws to which we are subject also include the U.K. Bribery Act 2010 (Bribery Act) which proscribes giving and receiving bribes in the public and private sectors, bribing a foreign public official, and failing to have adequate procedures to prevent employees and other agents from giving bribes. U.S. companies that conduct business in the U.K. generally will be subject to the Bribery Act. Penalties under the Bribery Act include potentially unlimited fines for companies and criminal sanctions for corporate officers under certain circumstances.

 

Other Laws

Our present and future business has been and will continue to be subject to various other laws and regulations. Various laws, regulations and recommendations relating to safe working conditions, laboratory practices, the experimental use of animals, and the purchase, storage, movement, import and export and use and disposal of hazardous or potentially hazardous substances used in connection with our research work are or may be applicable to our activities. Certain agreements entered into by us involving exclusive license rights may be subject to national or international antitrust regulatory control, the effect of which cannot be predicted. The extent of government regulation, which might result from future legislation or administrative action, cannot accurately be predicted.

 

Employees

As of March 1, 2016, we had 159 full-time employees, including 65 with doctoral or other advanced degrees. Of our workforce, 105 employees are engaged in research, development and manufacturing, and 54 are engaged in business development, legal, finance, administration and sales and marketing. None of our employees are represented by a labor union or covered by collective bargaining agreements. We have never experienced a work stoppage and believe our relationship with our employees is good.

 

Research and Development

For information regarding research and development expenses incurred during 2015, 2014 and 2013, see Item 7, “Management Discussion and Analysis of Financial Condition and Results of Operations—Research and Development Expenses”.

 

Financial Information About Geographic Areas

Consolidated revenues by geographic area where derived are as follows:

 

   Years Ended December 31,
(In thousands)  2015  2014  2013
United States  $95,769   $74,688   $73,637 
Japan   55,371    32,128    15,849 
Rest of the world   2,040    8,634    108 
Total  $153,180   $115,450   $89,594 

 

Total revenues generated outside the U.S. were $57.4 million, $40.8 million and $16.0 million in the years ended December 31, 2015, 2014 and 2013, respectively.

 

Property and equipment, net by geographic area where located is as follows:

 

   December 31,
(In thousands)  2015  2014  2013
United States  $3,105   $566   $869 
Japan   3,232    114    175 
Rest of the world   56    83    112 
Total  $6,393   $763   $1,156 

 

Our Class Capital Structure

We have two classes of common stock authorized; class A common stock and class B common stock. In 2012, our majority stockholder and only holder of our class B common stock converted all of its outstanding shares of our class B common stock into shares of our class A common stock. We are not authorized to issue additional shares of class B common stock except in limited circumstances. As a result of the conversion, there is now only a single class of outstanding common stock, class A common stock, which is entitled to one vote per share.

 

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Our Corporate Information

We were incorporated under the laws of Delaware in December 1996.

 

The following is a list of our direct and indirect subsidiaries as of December 31, 2015:

 

Subsidiary   State or other jurisdiction of incorporation or organization
Sucampo Pharma Americas, LLC   Delaware
Sucampo LLC   Delaware
Sucampo AG   Switzerland
Sucampo Pharma, LLC   Japan
Sucampo Pharma Europe Ltd.   United Kingdom
R-Tech Ueno, Ltd.   Japan
Sucampo Acquisitions GmbH   Switzerland

 

Our principal executive offices are located at 805 King Farm Boulevard, Suite 550, Rockville, Maryland 20850, and our telephone number is (301) 961-3400.

 

Website Access to United States Securities and Exchange Commission Reports

Our Internet address is http://www.sucampo.com. Through our website, we make available, free of charge, access to all reports filed with the U.S. Securities and Exchange Commission (SEC) including our Annual Reports on Form 10-K, our Quarterly Reports on Form 10-Q, our Current Reports on Form 8-K and amendments to these reports, as filed with or furnished to the SEC pursuant to Section 13(a) or 15(d) of the Securities Exchange Act of 1934, as amended (Exchange Act), as soon as reasonably practicable after we electronically file such material with, or furnish it to, the SEC. Copies of any materials we file with, or furnish to, the SEC can also be obtained free of charge through the SEC’s website at http://www.sec.gov or at the SEC’s Public Reference Room at 100 F Street, N.E., Room 1580, Washington, DC 20549. You may obtain information on the operation of the Public Reference Room by calling the SEC at 1-800-SEC-0330.

 

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ITEM 1A.  RISK FACTORS

 

Before deciding to purchase, hold or sell our common stock, you should carefully consider the risks described below in addition to the other cautionary statements and risks described elsewhere and the other information contained in this report and in our other filings with the SEC, including subsequent Quarterly Reports on Forms 10-Q and Current Reports on Form 8-K. We operate in a rapidly changing environment that involves a number of risks. The risks and uncertainties described below are not the only ones we face. Additional risks and uncertainties not presently known to us or that we currently deem immaterial may also affect our business. These known and unknown risks could materially and adversely affect our business, financial condition, prospects, operating results or cash flows.

 

Risks Related to Our Business and Industry

 

If we are unable to continue successful commercialization of AMITIZA for the approved indications and other indications or dosage forms for which we are developing this drug, or experience significant delays in doing so, our ability to generate royalty and product-based revenues and achieve profitability will be jeopardized.

 

Our business currently depends entirely on the successful commercialization of our first product, lubiprostone. Lubiprostone was launched in the U.S. in 2006 under the brand name AMITIZA. AMITIZA is currently marketed in the U.S., U.K., Switzerland and Japan for various indications. We have a limited history of generating global revenues from the sale of lubiprostone. Prior to the acquisition of R-Tech (the Acquisition), R-Tech was responsible for the manufacture and supply of all of our drug products for commercial use and clinical development. Through the Acquisition, we obtained control over the manufacturing and supply chain of AMITIZA. This increased responsibility could detract attention from operating the day-to-day components of our business prior to the Acquisition.

 

Our ability to meet expectations with respect to global sales of lubiprostone and revenues from such sales, and to attain profitability and maintain positive cash flow from the lubiprostone business, in the time periods we anticipate, or at all, will depend on a number of factors, including the following:

 

·our and our partners’ ability to continue to build, and to maintain, market acceptance for lubiprostone among healthcare professionals and patients in the U.S., and to gain such market acceptance in the countries where lubiprostone is approved, or may in the future receive approval;
·the efforts of Takeda and Mylan to commercialize and maximize net sales revenue of AMITIZA;
·the degree to which both physicians and patients determine that the safety and side effect profiles of lubiprostone are manageable, and that the benefits of lubiprostone outweigh the risks;
·the current and future prevalence of CIC, IBS-C, OIC, or chronic constipation;
·the willingness of insurance companies, managed care organizations, other private payers, and government entities that provide reimbursement for medical costs in the U.S. to continue to provide reimbursement for lubiprostone at the prices at which we offer lubiprostone without imposing any additional major hurdles to access or other significant restrictions or limitations, and the ability and willingness of patients to commit to any co-pay amounts for lubiprostone applicable under their insurance coverage;
·our commercial partners’ ability to obtain pricing approval and/or reimbursement required for selling lubiprostone in the major countries of the E.U., Japan and in other countries in which we may receive approval to market lubiprostone on a timely basis and at price levels that are acceptable to us without the applicable government agencies or other payers in such countries imposing onerous caps, rebate, risk sharing or other requirements which effectively and significantly lower the reimbursement rates for lubiprostone;
·the extent of the likely negative impact of the introduction of new competitive products on sales of lubiprostone;
·our ability to gain regulatory approval of lubiprostone outside the countries in which we have already received approval without restrictions that are substantially more onerous or manufacturing specifications that are more difficult to consistently achieve than those imposed in the U.S. and E.U.;
·our ability to accurately forecast revenues from sales of lubiprostone and the metrics that impact revenues, such as prescription rate, short-term and long-term drop-out rate, conversion rate, reimbursement and pricing; the timing and availability of named patient sales and the impact of future competition;
·our ability to successfully gain approval of a dosage form of lubiprostone for pediatric functional constipation, and to generate revenues from sales of the dosage form for pediatric functional constipation, if approved;
·successful completion of clinical trials of AMITIZA for the treatment of other constipation-related gastrointestinal indications beyond CIC, IBS-C and OIC as well as other dosage forms other than the 24 mcg and 8 mcg soft gelatin capsule, and successful commercialization of these indications and dosage forms within and outside the U.S.;
·our ability to manufacture sufficient bulk quantities of active pharmaceutical ingredient and sufficient quantities of each dosage strength and dosage form of lubiprostone to meet demand;
·our ability to hire and retain key personnel necessary to optimize the lubiprostone business; and

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·our and our partners’ ability to continue to execute effectively on key activities related to lubiprostone in the U.S. and to launch lubiprostone successfully in those key markets outside the U.S. in which we receive pricing and reimbursement approval, and the level of cost required to conduct such activities.

 

AMITIZA faces significant competition from competitors’ products like linaclotide and naloxegol, which, in addition to other factors, could in certain circumstances lead to a significant reduction in royalty revenues and product sales.

 

As a general matter, the pharmaceutical industry is highly competitive. To be successful, we must be able to, among other things, effectively discover, develop, test and obtain regulatory approvals for products. We or our partners must be able to effectively commercialize, market and promote approved products, including communicating the effectiveness, safety and value of products to actual and prospective customers and medical professionals. Many of our competitors have greater resources than we have. This enables them, among other things, to make greater investments in research and development, marketing and promotion.

 

Our product, AMITIZA, faces competition from competitors’ products. Specifically, AMITIZA faces competition from linaclotide which is approved for two of the three indications that AMITIZA has been approved in the U.S. and for IBS-C in certain European countries. Its manufacturer is seeking approval in other markets for IBS-C that we currently or intend to market AMITIZA. We also face competition from naloxegol which is approved for OIC in the U.S. and E.U. Competitor products such as linaclotide and naloxegol may be more effective or more effectively marketed and sold than AMITIZA is by our partners or by us. Alternatively, in the case of generic competition, including the generic availability of competitors’ branded products, they may be equally safe and effective products that are sold at a substantially lower price than our products. As a result, if we fail to maintain its competitive position, this could have a material adverse effect on its business, cash flow, results of operations, financial position and prospects.

 

Developments by our competitors, the entry of new competitors into the markets in which we compete, or consolidation in the pharmaceutical industry could make our products or technologies less competitive or obsolete. Our future growth depends, in part, on our ability to develop and introduce products which are more effective than those developed by our competitors. Royalties or sales from our existing products may decline rapidly if a new product is introduced that represents a substantial improvement over our existing products.

 

Our future success depends upon our ability to develop new products, and new indications for existing products, that achieve regulatory approval for commercialization.

 

For our business model to be successful, we must continually develop, manufacture and commercialize new products or achieve approval for new indications or label extensions for the use of our existing products. Prior to commercialization, these new products and product indications must satisfy stringent regulatory standards and receive requisite approvals or clearances from regulatory authorities in the U.S. and other countries. The development, regulatory review and approval, and commercialization processes are time consuming, costly and subject to numerous factors that may delay or prevent the development, approval or clearance, and commercialization of new products, including legal actions brought by our competitors. To obtain approval or clearance of new indications or products, we must submit, among other information, the results of preclinical and clinical studies on the new indication or product candidate to the applicable regulatory authorities. The number of preclinical and clinical studies that will be required for regulatory approval varies depending on the regulatory authority, the new indication or product candidate, the disease or condition for which the new indication or product candidate is in development and the regulations applicable to that new indication or product candidate. Even if we believe that the data collected from clinical trials of new indications for our existing products or for our product candidates are promising, applicable regulatory authorities may find such data to be insufficient to support approval of the new indication or product. The regulatory authority can delay, limit or deny approval or clearance of a new indication or product candidate for many reasons, including:

 

   · the product is not safe or effective either generally or for a new indication;
   · our preclinical and clinical data is interpreted in different ways than we interpret that data;
   · we may be required to perform post-marketing clinical studies; or
   ·  there may be changes in the approval policies or adoption of new regulations.

 

Products that we are currently developing, other future product candidates or new indications or label extensions for our existing products, may or may not receive the regulatory approvals or clearances necessary for marketing or may receive such approvals or clearances only after delays or unanticipated costs.

 

We continue to rely on third parties for the successful commercialization of some of our drug products. The success of these third parties will affect our ability to continue to develop new drug candidates.

 

For most of our operating history, we have been a research and development company. As we continue to expand our management, organizational and operational capabilities, expand our global partnerships, develop our diversified product pipeline, acquire non-prostone clinical candidates, and enhance our capital structure, our operations will focus on organizing and staffing our company, building the necessary infrastructure to support these capabilities, developing the pipeline and non-prostone technologies which we may acquire, undertaking preclinical and clinical trials of our product candidates, and pursuing the regulatory approval processes for additional indications for AMITIZA. Though we will continue to rely upon Takeda and Mylan to commercialize AMITIZA in most of the world, we may not be able to cause these third parties to effectively market and sell AMITIZA. In addition, we may encounter unforeseen expenses, difficulties, complications and delays as Takeda obtains regulatory approvals and establishes the commercial markets for AMITIZA outside of North America, Japan and China. As we continue to develop and seek regulatory approval of our product candidates, both within and outside the U.S., it could be difficult for us to access capital, to build the necessary infrastructure, to obtain and devote the resources necessary to obtain and develop product candidates, to effectively sell our products, and to provide resources to support commercialization of our products.

 

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We are subject to on-going obligations to monitor the safety of our products and product candidates. Any failure to meet these obligations could adversely affect our ability to generate revenue.

 

Safety problems or signals can arise as our products are marketed and our product candidates are evaluated in clinical trials. With our collaborators, we are required to continuously collect and assess adverse events reported to us and to communicate to regulatory agencies these adverse events and safety signals regarding our products. Regulatory agencies periodically perform inspections of our pharmacovigilance processes, including our adverse event reporting. If regulatory agencies determine that we or our collaborators have not complied with the applicable reporting or other pharmacovigilance requirements, we may become subject to additional inspections, warning letters or other enforcement actions, including monetary fines, marketing authorization withdrawal and other penalties.

 

We face potential product liability exposure, and, if claims are brought against us, we may incur substantial liability.

 

The use of lubiprostone or any other product candidate in clinical trials and the sale of AMITIZA or any other product candidate for which we obtain marketing approval expose us to the risk of product liability claims. Product liability claims might be brought against us by consumers, healthcare providers or others selling or otherwise coming into contact with our product and product candidates. If we cannot successfully defend ourselves against product liability claims, we could incur substantial liabilities. In addition, regardless of merit or eventual outcome, product liability claims may result in:

 

·decreased demand for lubiprostone or any other product candidate for which we obtain marketing approval;
·impairment of our business reputation and exposure to adverse publicity;
·increased warnings on product labels;
·withdrawal of clinical trial participants;
·costs as a result of related litigation;
·distraction of management’s attention from our primary business;
·substantial monetary awards to patients or other claimants;
·loss of revenue; and
·the inability to successfully commercialize lubiprostone or any other product candidate for which we obtain marketing approval.

 

We have obtained product liability insurance coverage for both our clinical trials and our commercial exposures. However, our insurance coverage may not be sufficient to reimburse us for any expenses or losses we may suffer. Moreover, insurance coverage is becoming increasingly expensive, and, in the future, we may not be able to maintain insurance coverage at a reasonable cost or in sufficient amounts to protect us against losses due to liability. On occasion, large judgments have been awarded in class action lawsuits based on drugs that had unanticipated side effects or warnings found to be inadequate. The cost of any product liability litigation or other proceedings, even if resolved in our favor, could be substantial. A product liability claim or series of claims brought against us could cause our stock price to decline and, if the claim is successful and judgments exceed our insurance coverage, could decrease our cash and adversely affect our business.

 

Recent federal legislation, including potentially unfavorable pricing regulations or other healthcare reform initiatives, and other negative pricing trends could limit our ability to generate revenues.

 

In March 2010, the Patient Protection and Affordable Care Act (ACA) was enacted in the U.S. In 2012, the U.S. Supreme Court upheld the ACA. This legislation may have both immediate and long-term impacts on us. A number of the provisions of legislation require rulemaking action by governmental agencies to implement, many of which have not yet occurred. The laws change access to health care products and services and create new fees for the pharmaceutical and medical device industries. Future rulemaking could increase rebates, reduce prices or the rate of price increases for health care products and services, or require additional reporting and disclosure. We cannot predict the timing or impact of any future rulemaking.

 

The regulations that govern, among other things, regulatory approvals, coverage, pricing and reimbursement for new drug products vary widely from country to country. In the United States and some foreign jurisdictions, there have been a number of legislative and regulatory changes and proposed changes regarding the healthcare system that could prevent or delay regulatory approval of our product candidates, restrict or regulate post-approval activities and affect our ability to successfully sell any product candidates for which we obtain regulatory approval.

 

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In the U.S., the E.U., and other potentially significant markets for our product candidates, government authorities and third-party payers are increasingly attempting to limit or regulate the price of medical products and services, particularly for new and innovative products and therapies, which has resulted in lower average selling prices. Furthermore, the increased emphasis on managed healthcare in the U.S. and on country and regional pricing and reimbursement controls in the E.U. will put additional pressure on product pricing, reimbursement and usage, which may adversely affect our future product sales and results of operations. These pressures can arise from rules and practices of managed care groups, judicial decisions and governmental laws and regulations related to Medicare, Medicaid and healthcare reform, pharmaceutical reimbursement policies and pricing in general.

 

We may generate growth through acquisitions and in-licensing and such strategy may not be successful if we are not able to identify suitable acquisition or licensing candidates, to negotiate appropriate terms of any such transaction or to successfully manage the integration of any acquisition.

 

As part of our business strategy, we intend to continue pursuing strategic acquisitions and in-licensing opportunities with third parties for our existing products and to complement our existing product pipeline. We have limited experience in completing acquisitions with third parties as well as performing under in-licensing agreements and we may not be able to identify appropriate acquisition or licensing candidates or to successfully negotiate the terms of any such transaction. The licensing and acquisition of pharmaceutical and biological products is a competitive area. A number of more established companies are also pursuing strategies to license or acquire products in the pharmaceutical field, and they may have a competitive advantage over us due to their size, cash resources and greater clinical development and commercialization capabilities. If we are unable to successfully complete acquisitions or in-licensing transactions for suitable products and product candidates, our prospects for growth could suffer.

 

Even if we are successful in completing one or more acquisitions, the failure to adequately address the financial, operational or legal risks of these transactions could harm our business. To finance an acquisition, we could be required to use our cash resources, issue potentially dilutive equity securities or incur or assume debt or contingent liabilities. Accounting for acquisitions can require impairment losses or restructuring charges, large write-offs of in-process research and development expense and ongoing amortization expenses related to other intangible assets. In addition, integrating acquisitions can be difficult, and could disrupt our business and divert management resources. If we are unable to manage the integration of any acquisitions successfully, our ability to develop new products and continue to expand our product pipeline may be impaired.

 

The acquisition of Sucampo AG (SAG), in December 2010 resulted in the issuance of two subordinated unsecured promissory notes in the aggregate amount of approximately $51.9 million to Ueno Trust and Kuno Trust. As of December 31, 2015, the outstanding balance on the notes was $17.7 million. However, on February 1, 2016, we repaid the entire outstanding balance of these notes.

 

In connection with the acquisition of R-Tech in October 2015, we entered into the Credit Facility and, under such facility, issued secured promissory notes in the aggregate amount of approximately $250.0 million to various lenders (the Term Notes). As of December 31, 2015, the outstanding balance on the Term Notes was $250.0 million. If we do not generate sufficient cash flows from our operations, we may not be able to pay the obligations of these notes on a timely basis, which may adversely affect our operating results. Our failure to comply with the covenants and/or obligations related to the Term Notes could result in an event of default, which could result in an immediate acceleration of the outstanding balance of the Term Notes and, if they are not repaid, foreclosure upon the assets securing our obligations under the Term Notes. These outcomes would materially and adversely affect our operating results and our financial condition. As of December 31, 2015, we were compliant with our covenants and conditions under the Term Notes.

 

Risks Related to Our Commercial Operations

 

We have a relatively short history of profitability. We may not maintain operating profitability in the future, and this could force us to delay, reduce or abandon our commercialization efforts or product development programs.

 

We have recorded net income since 2012. However, we expect to continue to incur significant and increasing expenses for at least the next several years as we continue our research activities, conduct development of the prostone technology, seek and develop non-prostone products and compounds, seek regulatory approvals for additional indications and additional territories for AMITIZA and for other drug candidates, and protect the patents of our products from generic challenges. Regulatory changes and changes in market conditions, including the generic competition, may require us to incur more expenses or change the timing of expenses such that we may incur unexpected losses. We may not be able to sustain or increase profitability on a quarterly or annual basis. If we are unable to maintain profitability, the market value of our class A common stock may decline.

 

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We may need substantial additional funding and be unable to raise capital when needed, which could force us to delay, reduce or abandon our commercialization efforts or product development programs.

 

We expect our research and development expenses and selling, general and administrative expenses to increase in connection with our ongoing activities. We may need substantial additional funding and be unable to raise capital when needed or on attractive terms, which would force us to delay, reduce or abandon our development programs.

 

We have continued to finance much of our operations by payments received under our collaboration agreements with Takeda and Mylan. We believe that our existing cash and cash equivalents and internally generated funds that we anticipate from AMITIZA royalty revenues and product sales will be sufficient to enable us to fund our current operating expenses but not for all of our future research and development programs. Our future funding requirements, however, will depend on many factors, including:

 

·actual levels of product royalty and product sales from AMITIZA;

·the cost of commercialization activities, including product marketing, sales and distribution;
·the scope and results of our research, preclinical and clinical development activities;
·the timing of, and the costs involved in, obtaining regulatory approvals;
·the costs involved in obtaining and maintaining proprietary protection for our products, technology and know-how, including litigation costs and the results of such litigation;
·our ability to recruit and retain internal qualified human resources to conduct these activities;
·the extent to which we acquire or invest in businesses, products and technologies;
·the success of our collaboration with Takeda and Mylan;
·the success of the commercialization efforts of AMITIZA; and
·our ability to establish and maintain additional collaborations.

 

If we are required to raise additional funds from external sources, we might accomplish this through at-the-market sales, public or private equity offerings, debt financings or corporate collaboration and licensing arrangements. If we raise additional funds by at-the-market sales or issuing equity securities, current stockholders may experience dilution. Debt financing, if available, may involve agreements that include covenants limiting or restricting our ability to take specific actions, such as incurring additional debt, making capital expenditures or declaring dividends. If we raise additional funds through collaboration and licensing arrangements with third parties, it may be necessary to relinquish valuable rights and related intellectual property to our technologies, research programs, products or product candidates.

 

We are developing internationally and licensing our products globally; therefore, we have an increased exposure to foreign political conditions and regulatory requirements and fluctuations in foreign currency exchange rates.

 

We expect that we will continue to seek global opportunities for our products and to develop candidates internationally in the future. Such opportunities and development will inherently subject us to a number of risks and uncertainties, including:

 

·changes in international regulatory and compliance requirements that could restrict our ability to develop, market and sell our products;
·political and economic instability;
·diminished protection of intellectual property in some countries outside of the U.S.;
·trade protection measures and import or export licensing requirements;
·difficulty in staffing and managing international operations;
·differing labor regulations and business practices;
·potentially negative consequences from changes in or interpretations of tax laws;
·changes in international medical reimbursement policies and programs;
·financial risks such as longer payment cycles, difficulty collecting accounts receivable and exposure to fluctuations in foreign currency exchange rates; and
·regulatory and compliance risks that relate to maintaining accurate information and control over sales and distributors’ and service providers’ activities that may fall within the purview of the FCPA or similar foreign laws such as the U.K. Bribery Act.

 

Any of these factors may, individually or as a group, have a material adverse effect on our business and results of operations. These or other similar risks could adversely affect our revenue and profitability. As we develop internationally, our exposure to these factors will increase.

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Risks Related to Product Pipeline

 

If our preclinical studies do not produce successful results or if our clinical trials do not demonstrate safety and efficacy in humans, our ability to develop and commercialize our pipeline will be impaired, which may jeopardize our business.

 

Before obtaining regulatory approval for the sale of our product candidates from our pipeline and from non-prostone acquisitions, we must conduct extensive preclinical tests and clinical trials to demonstrate the safety and efficacy in humans of our product candidates. Preclinical and clinical testing is expensive, is difficult to design and implement, can take many years to complete, is subject to varying regulatory requirements and is uncertain as to outcome. Success in preclinical testing and early clinical trials does not ensure that later clinical trials will be successful, and interim results of a clinical trial do not necessarily predict final results. A failure of one or more of our clinical trials can occur at any stage of testing. We may experience numerous unforeseen events during, or as a result of, preclinical testing and the clinical trial process that could delay or prevent our ability to receive regulatory approval or commercialize our product candidates, including:

 

·regulators or institutional review boards may not authorize us to commence a clinical trial or conduct a clinical trial at a prospective trial site;
·clinical research organizations we retain to conduct clinical trials may not perform according to the terms of the contract, causing delays or negative results in the clinical trials;
·our preclinical tests or clinical trials may produce negative or inconclusive results, and as a result we may decide, or regulators may require us, to conduct additional preclinical testing or clinical trials or we may abandon projects that we consider to be promising;
·design of or enrollment in our clinical trials may be slower than we currently anticipate, resulting in significant delays, or participants may drop out of our clinical trials at rates that are higher than we had anticipated;
·we might have to suspend or terminate our clinical trials, or perform additional trials, if we discover that the participating patients are being exposed to unacceptable health risks;
·regulators or institutional review boards may require that we hold, suspend or terminate clinical research for various reasons, including noncompliance with regulatory requirements;
·the cost of our clinical trials may be greater than we currently anticipate;
·we might have difficulty obtaining sufficient quantities of the product candidate being tested to complete our clinical trials;
·any regulatory approval we ultimately obtain may be limited or subject to restrictions or post-approval commitments that render the product not commercially viable;
·many of our competitors have significantly greater financial resources and expertise in research and development, manufacturing, preclinical testing, site selection, conducting clinical trials, obtaining regulatory approvals, and marketing approved products than we do and smaller or early stage companies may also prove to be significant competitors, particularly through collaborative arrangements with large and established companies;
·the effects of our product candidates may not be the desired or anticipated effects or may include undesirable side effects, or the product candidates may have other unexpected characteristics; and
·if we are required to conduct additional clinical trials or other testing of our product candidates beyond those that we currently contemplate, if we are unable to successfully complete our clinical trials or other testing or if the results of these trials or tests are not positive or are only modestly positive, we may be delayed in obtaining marketing approval for our product candidates, not be able to obtain marketing approval, or obtain approval for indications that are not as broad as those for which we apply.

 

Our product development costs will also increase if we experience delays in testing or approvals. We do not know whether our clinical trials will begin as planned, will need to be restructured or will be completed on schedule, if at all. Significant clinical trial delays also could allow our competitors to bring products to market before we do and impair our ability to commercialize our products or product candidates.

 

We may fail to select or capitalize on the most scientifically, clinically or commercially promising or profitable product candidates.

 

We continue to evaluate our business strategy and, as a result, may modify our strategy in the future. In this regard, we may, from time to time, focus our product development efforts on different product candidates or may delay or halt the development of various product candidates. As a result of changes in our strategy, we may change or refocus our existing product development, commercialization and manufacturing activities. This could require changes in our facilities and our personnel. Any product development changes that we implement may not be successful. In particular, we may fail to select or capitalize on the most scientifically, clinically or commercially promising or profitable product candidates. Our decisions to allocate our research and development, management and financial resources toward particular product candidates or therapeutic areas may not lead to the development of viable commercial products and may divert resources from better opportunities. Similarly, our decisions to delay or terminate product development programs may also prove to be incorrect and could cause us to miss valuable opportunities.

 

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We may perform additional clinical trials for other indications or in support of applications for regulatory marketing approval in jurisdictions outside the U.S. for our products. These supplemental trials could be costly and could result in findings inconsistent with or contrary to our historic U.S. clinical trials.

 

In the future, we may be required, or we may elect, to conduct additional clinical trials of AMITIZA to improve the current label or address regulatory authorities concerns about AMITIZA. In addition, if we seek marketing approval from regulatory authorities in jurisdictions outside the U.S., they may require us to perform additional clinical trials that would be costly and difficult to know if there will be successful outcomes and to submit data from supplemental clinical trials in addition to data from the clinical trials that supported our U.S. filings with the FDA. Any requirements to conduct supplemental trials would add to the cost of developing our product candidates. Additional or supplemental trials could also produce findings that are inconsistent with the trial results we have previously submitted to the FDA, in which case we would be obligated to report those findings to the FDA. This could result in new restrictions on the existing marketing approval for AMITIZA or could force us to stop selling AMITIZA. Inconsistent trial results could also lead to delays in obtaining marketing approval in the U.S. for other indications for AMITIZA or for other product candidates and could cause regulators to impose restrictive conditions on marketing approvals and could even make it impossible for us to obtain marketing approval. Any of these results could materially impair our ability to generate revenues and to achieve or maintain profitability.

 

Our agreements with makers of generic AMITIZA products are subject to government scrutiny in the U.S.

 

We are and have been involved in patent litigations that have resulted or may result in settlement agreements. We have filed our settlement and license agreements with Par and will file any future settlement agreements with the Federal Trade Commission (FTC) and the Antitrust Division of the Department of Justice for review. The FTC has, in the past, brought actions against some brand and generic companies that have entered into such agreements alleging violations of antitrust laws in connection therewith.

 

We may receive civil investigative demands from the FTC that requires us to provide the FTC information and documents relating to various settlement and other agreements with makers of generic AMITIZA products following patent infringement claims and litigation, and other efforts principally regarding AMITIZA. If the FTC believes that these or other agreements or efforts violates antitrust laws, it could challenge us through an administrative or judicial proceeding, which could result in the imposition of monetary and/or injunctive relief, including the invalidation of agreements, any of which could have a material adverse effect on our results of operations and financial condition. In addition, any such litigation could be protracted, requiring a substantial commitment of our management’s time and cash expenditures over multiple years.

 

Risks Related to Manufacturing

 

Following our acquisition of R-Tech, we now manufacture and supply the active ingredient for our product and product candidates. However, we have limited experience in the management of pharmaceutical manufacturing operations and still rely on third parties for encapsulation, packaging and other manufacturing activities. If we or our third party manufacturers are unable to manufacture AMITIZA or our other product candidates in sufficient quantities, at acceptable quality levels and at acceptable cost and if we are unable to identify a suitable replacement manufacturer, our sales of AMITIZA and our further clinical development and commercialization of other products could be delayed, prevented or impaired.

 

Although we now control the manufacture and supply of AMITIZA and our other product candidates, following our acquisition of R-Tech, we have little experience in manufacturing pharmaceutical products. In addition, we currently rely, and expect to continue to rely, on various third party suppliers to create the finished, packaged forms of AMITIZA, unoprostone, cobiprostone, and any future compounds that we may determine to develop or commercialize. We do not currently have an alternative source of supply for AMITIZA, unoprostone, or cobiprostone. If we are not able to supply AMITIZA or these other compounds on a timely basis, in sufficient quantities and at acceptable levels of quality and price, and if we are unable to identify an alternate manufacturer to perform these functions on acceptable terms, sales of AMITIZA would be significantly impaired, and our development programs could be seriously jeopardized.

 

The risks relating to the manufacture of our products include:

 

·we rely solely on our personnel, and that of our third party vendors, for quality assurance and their continued compliance with regulations relating to the manufacture of pharmaceuticals;
·our manufacturing capacity may not be sufficient to produce commercial quantities of our product, or to keep up with subsequent increases in the quantities necessary to meet potentially growing demand;
·we may not have access to the capital necessary to expand our manufacturing facilities in response to our needs;
·if our operations were to be interrupted, or were we to elect to contract with another manufacturer to supply us, it would be difficult and time consuming for us to find an alternate supplier and the change would need to be submitted to and approved by the FDA and/or foreign regulatory agencies;

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·we rely on numerous sub-contractors to fulfill its manufacturing obligations, and any difficulty or disruption at one of these sub-contractors could jeopardize our ability to produce AMITIZA or our other products;
·we may experience events, such as a fire or natural disaster, that force us to stop or curtail production for an extended period; and
·we could encounter significant increases in labor, capital or other costs that would make it difficult to produce our products cost-effectively.

 

In addition, we currently use one supplier for a key ingredient used in the manufacture of prostones. We could experience delays in production should it become necessary to switch its source of supply for such ingredient to another supplier or to manufacture such ingredient itself. We have subcontracted with a single contract manufacturer to encapsulate the bulk form AMITIZA we supply into soft gelatin capsules and another manufacturer to package the final product for distribution in the U.S. If these subcontractors experience difficulties or delays in performing these services for any reason, our ability to deliver adequate supplies of finished product to physicians and patients will be impaired, which could cause us to lose revenues. In addition, any change in the party providing encapsulation of AMITIZA would need to be approved by the FDA and/or foreign regulatory agencies, and any change in the party packaging the product would need to be submitted to and reviewed by the FDA and/or foreign regulatory agencies, which could increase the time required to replace these subcontractors should that become necessary.

 

Our current and anticipated future dependence upon these third parties for the manufacture of our products and product candidates may adversely affect our future revenues, our cost structure, our ability to expand globally and our ability to develop product candidates and commercialize any approved products on a timely and competitive basis. In addition, if our ability to manufacture prostones for our clinical trials is impaired for any reason, we likely would experience delays in advancing these trials while we seek to identify and qualify replacement suppliers. We may be unable to obtain replacement supplies on a timely basis, on terms that are favorable to us, or at all.

 

We and the other third-party manufacturers of our products and product candidates are subject to significant regulations governing manufacturing facilities and procedures.

 

We, our subcontractors and suppliers and any other potential manufacturer of our products or product candidates may fail to comply with the FDA’s cGMP regulations or other governmental regulations. These regulations govern manufacturing processes and procedures and the implementation and operation of systems to control and assure the quality of products approved for sale. In addition, the FDA or other regulatory agencies outside the U.S. may at any time audit or inspect a manufacturing facility to ensure compliance with cGMP or similar regulations. Our failure, or the failure of our subcontractors and suppliers or any other third-party manufacturer we use, to comply with applicable manufacturing regulations could result in sanctions being imposed on us, including fines, injunctions, civil penalties, failure of regulatory authorities to grant marketing approval of our product candidates, delays, suspension or withdrawal of approvals, license revocation, seizures or recalls of product candidates or products, operating restrictions and criminal prosecutions, any of which could significantly and adversely affect supplies of our products and product candidates.

 

If it were to become necessary for us to activate a second source of supply, we would compete with other companies for access to appropriate manufacturing facilities. Any such change would need to be submitted to and approved by the FDA and/or foreign regulatory agencies before commercial activities of AMITIZA or any other product could resume. Among manufacturers that operate under cGMP regulations, there are a limited number that would be both capable of manufacturing for us and willing to do so.

 

Risks Related to Our Dependence on Third Parties

 

We depend significantly on our collaborations with Takeda, Mylan Gloria, and Santen and may depend in the future on collaborations with other third parties, to develop and commercialize our product candidates.

 

A key element of our business strategy is to collaborate where appropriate with third parties, particularly leading pharmaceutical companies, to co-develop, commercialize and market our products and product candidates. We are currently party to the North America Takeda Agreement for the co-development and commercialization of AMITIZA for gastrointestinal indications in the U.S. and Canada, as well as to the Global License Agreement for AMITIZA whereby Takeda is responsible for all development, commercialization and regulatory activities other than in Canada, the U.S., Japan and the People’s Republic of China.

 

We are also party to the Japan Mylan Agreement for the development and commercialization of AMITIZA in Japan. On May 5, 2015, we entered into a license agreement with Harbin Gloria Pharmaceuticals Co., Ltd under which Gloria is responsible for all development, commercialization and regulatory activities for AMITIZA in the People’s Republic of China. We have no commercial experience collaborating with Gloria, and consequently the compatibility of our two companies is unknown.

 

We are a party to the Santen Agreement for the distribution and commercialization of RESCULA in Japan.

 

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The success of our collaboration arrangements will depend heavily on the efforts and activities of Takeda, Mylan, Gloria and Santen. The risks that we face in connection with these collaborations and that we anticipate being subject to in any future collaborations, include the following:

 

·our existing agreements are, and any future collaboration agreements that we may enter into are likely to be, subject to termination under various circumstances;
·our present and future collaborators may develop and commercialize, either alone or with others, products and services that are similar to or competitive with the products that are the subject of their collaboration with us;
·our present and future collaborators may underfund or not commit sufficient resources to the testing, marketing, distribution or other development of our products or may use committed resources inefficiently;
·we may become involved in disputes with our collaborators regarding operations, strategies, intellectual property or financial matters;
·our present and future collaborators may not properly maintain or defend our intellectual property rights or may utilize our proprietary information in such a way as to invite litigation that could jeopardize or invalidate our proprietary information or expose us to potential liability; and
·our present and future collaborators may change the focus of their development and commercialization efforts.

 

The ability of our products and product candidates to reach their potential could be limited if Takeda, Mylan, Gloria, Santen or any other future collaborators decrease or fail to increase spending relating to such products, fail to dedicate sufficient resources to developing or promoting our products or change their business focus.

 

We rely on third parties to conduct our clinical trials and those third parties may not perform satisfactorily or may fail to meet established deadlines for the completion of these trials.

 

We generally do not have the independent ability to conduct global clinical trials for our product candidates. We rely on third parties, such as contract research organizations (CROs), clinical data management organizations, medical institutions, and clinical investigators, to perform this function. We use multiple CROs to coordinate the efforts of our clinical investigators and to accumulate the results of our trials. Our reliance on these third parties for clinical development activities reduces our control over these activities. Furthermore, these third parties may also have relationships with other entities, some of which may be our competitors.

 

In addition, we are responsible for ensuring that each of our clinical trials is conducted in accordance with the general investigational plan and protocols for the trial. The FDA and foreign regulatory agencies require us to comply with standards, commonly referred to as cGCP, for conducting and recording and reporting the results of clinical trials to assure that data and reported results are credible and accurate and that the rights, integrity and confidentiality of trial participants are protected. Our reliance on third parties that we do not control does not relieve us of these responsibilities and requirements.

 

If tax authorities disagree with our transfer pricing policies or other tax positions, we could become subject to significant tax liabilities.

 

We are a member of an affiliated group of entities, and have had and will continue to have significant commercial transactions with these entities. Furthermore, we operate a number of foreign subsidiaries. We expect to operate through a consolidated organizational structure and we expect to enter into commercial transactions with some of these entities or future subsidiaries on an ongoing basis. As a result of these transactions, we will be subject to complex transfer pricing and other tax regulations in both the U.S. and the other countries in which we and our affiliates operate. Transfer pricing regulations generally require that, for tax purposes, transactions between our subsidiaries and affiliates and us be priced on a basis that would be comparable to an arm’s length transaction and that contemporaneous documentation be maintained to support the related party agreements. To the extent that U.S. or any foreign tax authorities disagree with our transfer pricing or other policies, we could become subject to significant tax liabilities and penalties related to prior, existing and future related party agreements. As of December 31, 2015, we performed updated tax analyses wherein liabilities for uncertain tax positions were recorded for certain state jurisdictions based on nexus related to the sourcing of revenues. Should the tax authorities in one or more of these states have different interpretations than us, we may be subject to additional tax liabilities.

 

Risks Related to Our Intellectual Property

 

We have received notifications from generic companies that they have filed Abbreviated New Drug Applications (ANDA) with the FDA against our products. In response, we initiated patent infringement lawsuits against those generic companies which are ongoing as to certain of these companies and settled as to others. If we are unable to obtain and maintain proprietary protection for the intellectual property relating to our technology and products, the value of our technology and products will be adversely affected and our ability to derive revenue from our products would be adversely affected.

 

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Our success depends in part on our ability to obtain and maintain proprietary protection for the technology and know-how upon which our products are based, to operate without infringing on the proprietary rights of others and to prevent others from infringing on our proprietary rights. The patent positions of companies like ours are generally uncertain and involve complex legal and factual questions. Our ability to maintain and solidify our proprietary position for our intellectual property will depend on our success, in obtaining effective claims and enforcing those claims once granted. The scope of protection afforded by a set of patent claims is subject to inherent uncertainty unless the patent has already been litigated and a court has ruled on the meaning of the claim language and other issues affecting how broadly a patent claim can be enforced. In some cases, we license patent applications from R-Tech instead of issued patents, and we do not know whether these patent applications will result in the issuance of any patents.

 

Our licensed patents have recently been challenged in the U.S. for AMITIZA (lubiprostone) by Par and Dr. Reddy’s Laboratories, Inc. (Dr. Reddy’s) and for RESCULA (unoprostone isopropyl) by Par Pharmaceutical and Apotex through the filing of ANDAs by those generic companies with the FDA. Other licensed patents may be challenged, invalidated or circumvented, which could limit the term of patent protection for lubiprostone, unoprostone isopropyl or our other products, diminish our ability to stop competitors from marketing related products, and materially adversely affect our business and results of operations. In response to the filed ANDAs, we filed patent infringement lawsuits regarding AMITIZA against Par and Dr. Reddy’s. In October 2014, we resolved our patent litigation with Par in the U.S. related to our AMITIZA (lubiprostone) 8 mcg and 24 mcg soft gelatin capsule products in which we and R-Tech granted Par a non-exclusive license to market Par’s generic version of lubiprostone 8 mcg soft gelatin capsule and 24 mcg soft gelatin capsule in the U.S. for the indications approved for AMITIZA beginning January 1, 2021, or earlier under certain circumstances. Beginning on January 1, 2021, Par will split with us the gross profits of the licensed products sold during the term of the agreement, which continues until each of our related patents has expired. In the event Par elects to launch an authorized generic form of lubiprostone, we agree to supply Par under the terms of a manufacturing and supply agreement at a negotiated price.

 

In November 2014, we, R-Tech, Takeda, and certain affiliates of Takeda filed a patent infringement lawsuit in the U.S. District Court for the District of New Jersey against Dr. Reddy's. The lawsuit claims infringement of the same 7 patents listed in the FDA's Orange Book involved in the Par lawsuit, with the latest expiring in 2027. Under the Hatch-Waxman Act, as a result of the patent infringement lawsuit, final FDA approval of Dr. Reddy's ANDA will be stayed up to 30 months from the date of receipt of the notice letter.

 

In February 2015, we and R-Tech executed a stipulation and license agreement (Stipulation Agreement) with Par Pharmaceutical for RESCULA (unoprostone isopropyl) ophthalmic solution 0.15% indicated for the lowering of intraocular pressure in patients with open-angle glaucoma or ocular hypertension. Subject to the terms of the Stipulation Agreement, we and R-Tech are obligated to grant Par Pharmaceutical, prior to the expiration of the latest expiring patent relating to RESCULA, a non-exclusive license to market Par Pharmaceutical’s generic version or authorized generic of unoprostone isopropyl ophthalmic solution 0.15% indicated for the lowering of intraocular pressure in patients with open-angle glaucoma or ocular hypertension product in the U.S. Under such license, Par Pharmaceutical will split with us the gross profits of the generic or authorized generic version sold during the term of the Stipulation Agreement, which continues until the last of our patents relating to RESCULA have expired. In the event Par Pharmaceutical elects to so launch an authorized generic form of unoprostone isopropyl, we will supply Par Pharmaceutical under the terms of a manufacturing and supply agreement at a negotiated price.

 

On July 10, 2015, R-Tech filed a patent infringement lawsuit in the U.S. District Court for the District of Delaware against Apotex related to the ANDA previously filed by Apotex and described in further detail under the heading “Legal Proceedings”. The lawsuit claims infringement of two patents that are listed in the FDA’s Orange Book, with the latest expiring in 2021. Under the Hatch-Waxman Act, as a result of the patent infringement lawsuit, final FDA approval of Apotex’s ANDA will be stayed up to 30 months from the date of receipt of the notice letter.

 

We have certain patents on our products that expire in the near future. We may not be able to use other existing patents or patent applications to successfully protect our products from generic competition. In addition, changes in either patent laws or in interpretations of patent laws in the U.S. and other countries may diminish the value of our patents and other intellectual property or narrow the scope of the protection provided by these patents. Accordingly, we cannot determine the degree of future protection for our proprietary rights in the patents and patent applications. Furthermore, because of the extensive time required for development, testing and regulatory review of a potential product, it is possible that, before any of our product candidates can be commercialized, a related patent may expire or may remain in force for only a short period following commercialization, thereby reducing any advantage of the patent.

 

Patents may not afford us protection against competitors with similar technology. Because patent applications in the U.S. and many foreign jurisdictions are typically not published until 18 months after filing, or in some cases not at all, and because publications of discoveries in the scientific literature often lag behind actual discoveries, we cannot be certain whether a judicial court will uphold the validity of a patent.

 

If our patent position does not adequately protect our product and product candidates, others could compete against us more directly, which would harm our business, possibly materially.

 

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The patent rights relating to lubiprostone consist of 16 issued U.S. patents, and various issued European and Japanese patents. Our patent rights also include various U.S., European and Japanese patent applications relating to dosing regimens, pharmaceutical formulations and other claims. The U.S. patents relating to compositions of matter expire between 2020 and 2027. The other U.S. and foreign patents expire between 2020 and 2035.

 

Our commercial success with respect to lubiprostone will depend significantly on our ability to protect our existing patent position with respect to lubiprostone as well as our ability to obtain and maintain adequate protection of other intellectual property for our technologies, product candidates and any future products in the U.S. and other countries.

 

The patent positions of biotechnology and pharmaceutical companies, including our patent position, involve complex legal and factual questions, and, therefore, validity and enforceability cannot be predicted with certainty.

 

The degree of future protection for our proprietary rights is uncertain, and we cannot ensure that:

 

·we or our licensors were the first to make the inventions covered by each of our pending patent applications;
·we or our licensors were the first to file patent applications for these inventions;
·others will not independently develop similar or alternative technologies or duplicate any of our technologies;
·any of our pending patent applications or those we have licensed will result in issued patents;
·any of our patents or those we have licensed will be valid or enforceable;
·any patents issued to us or our licensors and collaborators will provide a basis for any additional commercially viable products, will provide us with any competitive advantages or will not be challenged by third parties;
·we will develop additional proprietary technologies or product candidates that are patentable; or
·the patents of others will not have an adverse effect on our business.

 

We may infringe the intellectual property rights of others, which may prevent or delay our product development efforts and stop us from commercializing or increase the costs of commercializing our product and any product candidates.

 

Our success will depend in part on our ability to operate without infringing the proprietary rights of third parties. There could be issued patents of which we are not aware that our products or product candidates infringe. There also could be patents that we believe we do not infringe, but that we may ultimately be found to infringe.

 

The pharmaceutical industry is characterized by extensive litigation regarding patents and other intellectual property rights. Other parties may obtain patents in the future and allege that our products or product candidates or the use of our technologies infringes these patent claims or that we are employing their proprietary technology without authorization. Likewise, third parties may challenge or infringe upon our existing or future patents.

 

Proceedings involving our patents or patent applications or those of others could result in adverse decisions regarding:

 

·the patentability of our inventions relating to our product or any product candidates; and
·the enforceability, validity or scope of protection offered by our patents relating to our product or any product candidates.

 

Even if we are successful in these proceedings, we may incur substantial costs and divert management’s time and attention in pursuing these proceedings, which could have a material adverse effect on us. If we are unable to avoid infringing the patent rights of others, we may be required to seek a license, defend an infringement action or challenge the validity of the patents in court. Patent litigation is costly and time consuming. We may not have sufficient resources to bring these actions to a successful conclusion.

 

In addition, if we do not obtain a license, develop or obtain non-infringing technology, fail to defend an infringement action successfully or have infringed patents declared invalid, we may:

 

·incur substantial monetary damages;
·encounter significant delays in bringing our product candidates to market; and
·be precluded from manufacturing or selling our product candidates.

 

In such event, our business could be adversely affected, possibly materially.

 

Risks Related to Regulatory Approval and Oversight

 

If we are not able to obtain required regulatory approvals, we will not be able to commercialize our product candidates and our ability to generate revenue will be materially impaired.

 

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Our product candidates and the activities associated with their development and commercialization, including testing, manufacture, safety, efficacy, recordkeeping, labeling, storage, approval, advertising, promotion, sale and distribution, are subject to comprehensive regulation by the FDA and other regulatory agencies in and outside the U.S. Failure to obtain regulatory approval or appropriate pricing for a product candidate will prevent us from commercializing the product candidates.

 

As we increase our foreign license arrangements, we or our partner are seeking and will continue to seek approval in different territories. Different regulatory agencies may reach different decisions in assessing the approval and pricing of our product candidates. Securing regulatory approval requires the submission of extensive preclinical and clinical data, information about product manufacturing processes and inspection of facilities and supporting information to the regulatory agencies for each therapeutic indication to establish the product candidate’s safety and efficacy. Our future products may not be effective, may be only moderately effective or may prove to have undesirable side effects, toxicities or other characteristics that may preclude our obtaining regulatory approval or prevent or limit commercial use.

 

The process of obtaining regulatory approvals is expensive, often takes many years, if approval is obtained at all, and can vary substantially based upon the type, complexity and novelty of the product candidates involved. Changes in the regulatory approval policy during the development period, changes in or the enactment of additional statutes or regulations, or changes in regulatory review for each submitted product application, may cause delays in the approval or rejection of an application. The FDA and foreign regulatory agencies have substantial discretion in the approval process and may refuse to accept any application or may decide that our data are insufficient for approval and require additional preclinical, clinical or other studies. In addition, varying interpretations of the data obtained from preclinical and clinical testing could delay, limit or prevent regulatory approval of a product candidate. Any regulatory approval we ultimately obtain may be limited in scope or subject to restrictions or post-approval commitments that render the product not commercially viable. If any regulatory approval that we obtain is delayed or is limited, we may decide not to commercialize the product candidate after receiving the approval.

 

We may not be able to obtain orphan drug exclusivity for our product candidates. If our competitors are able to obtain orphan drug exclusivity for a product that is competitive with one or more of our product candidates and we cannot show that our product candidate is clinically superior, we may not be able to have competing products approved by the applicable regulatory authority for a significant period of time.

 

Regulatory authorities in some jurisdictions, including Europe and the U.S., may designate drugs that target relatively small patient populations as orphan drugs. Generally, if a product with an orphan drug designation subsequently receives the first marketing approval for the indication for which it has such designation, the product is entitled to a period of marketing exclusivity. The exclusivity applies only to the indication for which the drug has been designated and approved. The applicable exclusivity period is seven years in the U.S., but this period may be interrupted if a sponsor of a competitive product that is otherwise the same drug for the same use can show that its drug is clinically superior to our orphan drug candidate. The European exclusivity period is ten years, but may be reduced to six years if a drug no longer meets the criteria for orphan drug designation, including where it is shown that the drug is sufficiently profitable so that market exclusivity is no longer justified. We unsuccessfully sought orphan drug designation from EMA for cobiprostone for the treatment of oral mucositis and we may seek such status with additional product candidates. Even if we obtain orphan drug exclusivity for specified indications, we may not be able to maintain it if a competitor with a product that is otherwise the same drug can establish that its product is clinically superior.

 

We must comply with federal, state and foreign laws, regulations, and other rules relating to the health care business, and, if we are unable to fully comply with such laws, regulations and other rules, we could face substantial penalties.

 

We are or will be directly or indirectly through our collaborators, subject to extensive regulation by the federal government, the states and foreign countries in which we may conduct our business. The laws that directly or indirectly affect our ability to operate our business include the following:

 

·the federal Medicare and Medicaid Anti-Kickback law, which prohibits persons from knowingly and willfully soliciting, offering, receiving or providing remuneration, directly or indirectly, in cash or in kind, to induce either the referral of an individual, or furnishing or arranging for a good or service, for which payment may be made under federal healthcare programs such as the Medicare and Medicaid Programs;
·other Medicare laws, regulations, rules, manual provisions and policies that prescribe the requirements for coverage and payment for services performed by our customers, including the amount of such payment;
·the federal False Claims Act, which imposes civil and criminal liability on individuals and entities who submit, or cause to be submitted, false or fraudulent claims for payment to the government;
·the federal False Statements Act, which prohibits knowingly and willfully falsifying, concealing or covering up a material fact or making any materially false statement in connection with the delivery of or payment for healthcare benefits, items or services;
·the Foreign Corrupt Practices Act, which prohibits certain payments made to foreign government officials;

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·state and foreign law equivalents of the foregoing and state laws regarding pharmaceutical company marketing compliance, reporting and disclosure obligations; and
·the Patient Protection and Affordable Care Act, which changes access to healthcare products and services; creates new fees for the pharmaceutical and medical device industries; changes rebates and prices for health care products and services; and requires additional reporting and disclosure.

 

If our operations are found to be in violation of any of the laws, regulations, rules or policies described above or any other law or governmental regulation to which we or our collaborators are or will be subject, or if the interpretation of the foregoing changes, we may be subject to civil and criminal penalties, damages, fines, exclusion from the Medicare and Medicaid programs and the curtailment or restructuring of our operations. Similarly, we do not control our collaborators, including their compliance activities and if our collaborators are found non-compliant with applicable laws, they may be subject to sanctions, which could also have a negative impact on us. Any penalties, damages, fines, curtailment or restructuring of our operations would harm our ability to operate our business and our financial results. The risk of our being found in violation of these laws is increased by the fact that many of them have not been fully interpreted by the regulatory authorities or the courts, and their provisions may be open to a variety of interpretations. Any action against us for violation of these laws, even if we successfully defend against it, could cause us to incur significant legal expenses, divert management resources from the operation of our business and damage our reputation.

 

We only have regulatory approval for commercial distribution and reimbursement of lubiprostone and unoprostone isopropyl in a limited number of countries, and may not receive regulatory approval in other countries.

 

We are currently permitted to market our approved products in only a limited number of countries on a commercial basis. To obtain marketing approval in other countries, we must establish and comply with numerous and varying regulatory requirements of other countries regarding safety and efficacy and governing, among other things, clinical trials, pricing, promotion and distribution of the product. Approval procedures vary among countries, and can involve additional product testing and additional administrative review periods. For example, we and Takeda are currently exploring the commercialization of AMITIZA in a number of countries. We may not be successful in obtaining such approval.

 

In addition, regulatory authorities in countries outside the U.S. and E.U. are increasingly requiring risk management plans and post-marketing commitments which may be more onerous than those required in the U.S. and E.U. The time required to obtain approval in other countries may differ from that required to obtain FDA approval or marketing authorization from the E.U. In particular, in many countries outside the U.S., including most E.U. countries and Canada, a product must receive pricing and reimbursement approval before it can be commercialized broadly. This can result in substantial delays in such countries, and the price that is ultimately approved may be lower than the price for which we expect to offer, or would be willing to offer, lubiprostone in such countries, and may impact pricing in other countries. Marketing and pricing and reimbursement approval in one country does not ensure such approvals in another. Failure to obtain the approvals necessary to commercialize lubiprostone in other countries at reimbursement levels that are acceptable to us or any delay or setback in obtaining such approvals would impair our partners’ ability to develop foreign markets for lubiprostone.

 

Risks Related to Our Class A Common Stock

 

Our majority stockholders and their affiliates maintain the ability to have significant control over matters submitted to stockholders for approval, which could result in actions of which you or other stockholders do not approve.

 

As of March 1, 2016, our founders, Dr. Ryuji Ueno and Dr. Sachiko Kuno, together through their direct or indirect interest in S&R Technology Holding, LLC, held 21,075,255 shares of class A common stock, representing approximately 46.3% of our outstanding class A common stock. Therefore, until such time that such stockholders further dispose of additional shares of class A common stock, this concentration of ownership and voting power could influence all matters requiring stockholder approval and have the effect of delaying or preventing a change in control of our company and could prevent stockholders from receiving a premium over the market price if a change in control is proposed.

 

Provisions in our corporate charter documents and under Delaware law may prevent or frustrate attempts by our stockholders to change our management and hinder efforts to acquire a controlling interest in us, and the market price of our class A common stock may be lower as a result.

 

There are provisions in our certificate of incorporation and by-laws that may make it difficult for a third party to acquire, or attempt to acquire, control of our company, even if a change in control was considered favorable by our stockholders. For example, our Board of Directors has the authority to issue up to 5,000,000 shares of preferred stock. The Board of Directors can fix the price, rights, preferences, privileges, and restrictions of the preferred stock without any further vote or action by our stockholders. The issuance of shares of preferred stock may delay or prevent a change in control transaction. As a result, the market price of our class A common stock and the voting and other rights of our stockholders may be adversely affected. An issuance of shares of preferred stock may result in the loss of voting control to other stockholders.

 

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Our charter documents contain other provisions that could have an anti-takeover effect, including:

 

·only one of our three classes of directors will be elected each year;

·stockholders are not entitled to remove directors other than by a 75.0% vote and for cause;

·stockholders are not permitted to take actions by written consent;

·stockholders cannot call a special meeting of stockholders; and

·stockholders must give advance notice to nominate directors or submit proposals for consideration at stockholder meetings.

 

In addition, we are subject to the anti-takeover provisions of Section 203 of the Delaware General Corporation Law, which regulates corporate acquisitions. These provisions could discourage potential acquisition proposals and could delay or prevent a change in control transaction. They could also have the effect of discouraging others from making tender offers for our class A common stock. These provisions may also prevent changes in our management.

 

The price of our class A common stock is volatile; investors in our class A common stock could incur substantial losses.

 

The public trading market for our class A common stock is characterized by a highly volatile stock price. The stock market in general and the market for pharmaceutical and biotechnology companies in particular have experienced extreme volatility that has often been unrelated to the operating performance of particular companies. These broad market and industry factors might seriously harm the market price of our class A common stock, regardless of our operating performance. As a result of this volatility, investors may not be able to sell their class A common stock at or above the price they paid, and may have difficulty selling their shares at any price. The market price for our class A common stock may be influenced by many factors, including:

 

·failure of AMITIZA (lubiprostone) or other approved products, if any, to achieve commercial success;
·results of clinical trials of our product candidates or those of our competitors;
·the regulatory status of our product candidates;
·the success of competitive products or technologies;
·regulatory developments in the U.S. and foreign countries;
·developments or disputes concerning patents or other proprietary rights;
·the ability of our third party suppliers and manufacturers to perform;
·actual or anticipated fluctuations in our quarterly financial results;
·variations in the financial results of companies that are perceived to be similar to us;
·changes in the structure of healthcare payment systems and other regulatory developments;
·market conditions in the pharmaceutical and biotechnology sectors, including those relating to the pricing of pharmaceutical products, and issuance of new or changed securities analysts’ reports or recommendations; and
·general economic, industry and market conditions.

 

We will not be able to control many of these factors, and we believe that period-to-period comparisons of our financial results will not necessarily be indicative of our future performance.

 

We do not anticipate paying dividends on our capital stock.

 

We do not intend to pay dividends on our capital stock in the foreseeable future. We currently intend to retain all cash we generate to fund the growth of our business and the Credit Facility restricts the payment of dividends. The declaration of dividends is subject to the discretion of our board of directors and will depend on various factors, including our operating results, financial condition, future prospects and any other factors deemed relevant by our board of directors. You should not rely on an investment in our company if you require dividend income from your investment in our company. The success of your investment will likely depend entirely upon any future appreciation of the market price of our capital stock, which is uncertain and unpredictable. There is no guarantee that our capital stock will appreciate in value or even maintain the price at which you purchased your shares.

 

Substantial future sales of our class A common stock in the public market may depress our stock price and make it difficult for you to recover the full value of your investment in our class A common stock.

 

As of March 1, 2016, we had 45,539,384 shares of class A common stock outstanding. Substantially all of these shares are available for public sale, subject in some cases to volume and other limitations or delivery of a prospectus. The market price of our class A common stock may decline if our class A common stockholders sell a large number of shares of our class A common stock in the public market, or the market perceives that such sales may occur. In addition, as of March 1, 2016, we had 4,358,535 outstanding options to purchase an aggregate of 4,358,535 shares of our class A common stock. If these options are exercised and the shares issued upon exercise are sold, the market price of our securities may also decline. These factors also could impair our ability to raise needed capital by depressing the price at which we could sell our securities.

 

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Risks Related to Strategic Acquisitions

 

Our strategy of generating growth through acquisitions may not be successful.

 

Our business strategy includes growing our business through acquisition and in-licensing transactions. We may not be successful in identifying, effectively evaluating, acquiring or in-licensing, and developing and commercializing additional products on favorable terms, or at all. Competition for attractive product opportunities is intense and may require us to devote substantial resources, both managerial and financial, to an acquisition opportunity. A number of more established companies are also pursuing strategies to acquire or in-license products. These companies may have a competitive advantage over us due to their size, cash resources and greater development and commercialization capabilities.

 

Acquisition efforts can consume significant management attention and require substantial expenditures, which could detract from our other programs. In addition, we may devote significant resources to potential acquisitions that are never completed. Even if we are successful in acquiring a product or company, it may not result in a successfully developed or commercialized product or, even if an acquired product is commercialized, competing products or technologies could render a product noncompetitive, uneconomical or obsolete. Moreover, the cost of acquiring other companies or in-licensing products could be substantial, and in order to acquire companies or new products, we may need to incur substantial debt or issue dilutive securities. If we are unsuccessful in our efforts to acquire other companies or in-license and develop additional products, or if we acquire or in-license unproductive assets, it could have a material adverse effect on the growth of our business.

 

Our failure to successfully integrate acquired assets into our operations, including our recent acquisition of R-Tech Ueno could adversely affect our ability to grow our business.

 

We may not be able to integrate any acquired business successfully, including our recent acquisition of R-Tech, or operate any acquired business profitably. In addition, cost synergies, if achieved at all, may be less than we expect, or may take greater time to achieve than we anticipate.

 

Issues that could delay or prevent successful integration or cost synergies of an acquired business include, among others:

·retaining existing customers and attracting new customers;
·retaining key employees;
·diversion of management attention and resources;
·conforming internal controls, policies and procedures, business cultures and compensation programs;
·consolidating corporate and administrative infrastructures;
·consolidating sales and marketing operations;
·identifying and eliminating redundant and underperforming operations and assets;
·assumption of known and unknown liabilities;
·coordinating geographically dispersed organizations; and
·managing tax costs or inefficiencies associated with integrating operations.

 

If we are unable to successfully integrate the R-Tech Ueno acquisition or future acquisitions with our existing businesses, or operate any acquired business profitably, we may not obtain the advantages that the acquisitions were intended to create, which may materially adversely affect the growth of our business.

 

We may be unable to realize the benefits we anticipate from the acquisition of R-Tech, including an improved financial position, or it may take longer than anticipated for us to achieve those benefits.

 

Our realization of the benefits anticipated as a result of the acquisition of R-Tech (the Acquisition)—including an improved financial position, manufacturing and supply chain control and the expansion and diversification of our pipeline for development or outsourcing—will depend in part on the integration of R-Tech’s business with ours. However, there can be no assurance that we will be able to operate R-Tech’s business profitably or integrate it successfully into our operations in a timely fashion, or at all. Following the Acquisition, the size of the combined company’s business is significantly larger than our business prior to the Acquisition. Our future success as a combined company depends, in part, upon our ability to manage this expanded business, which will pose substantial challenges for our management, including challenges related to the management and monitoring of new operations and associated increased costs and complexity. The dedication of management resources to this integration could detract attention from our current day-to-day business, and we cannot assure stockholders that there will not be substantial costs associated with the transition process or other negative consequences as a result of these integration efforts. These effects, including incurring unexpected costs or delays in connection with integration of the two businesses, or the failure of the combined company to perform as expected, could negatively affect our stock price or could harm our financial condition, results of operations or business prospects.

 

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The loss of key personnel could hurt our business and our prospects.

 

The success of the Acquisition will depend, in part, on our ability to retain key employees who continue employment with the combined company after the Acquisition is completed. If any of these key employees terminate their employment, our manufacturing, supply or development activities might be negatively affected and our management’s attention might be diverted from successfully integrating R-Tech’s operations. In addition, we might not be able to locate suitable replacements on reasonable terms for any such key employees who leave the combined company.

 

Financial Related Risks

 

If we fail to comply with the covenants and other obligations under our Credit Facility, the Lenders may be able to accelerate amounts owed under the facility and may foreclose upon the assets securing our obligations.

 

Our Credit Facility, which we entered into in October 2015, consists of a total of $250 million in term loans and allows for the incurrence of incremental loans in an amount up to $25 million. The term loans are payable in quarterly installments starting in March 2016 through September 2021, with the balance due in a final installment in October 2021. The Credit Facility includes an annual mandatory prepayment of the term loans of 75% of excess cash flow minus specified voluntary prepayments with step downs as our leverage ratio decreases. Additionally, the Credit Facility requires mandatory prepayment of the term loans from a portion of net cash proceeds of specified asset dispositions, certain casualties and condemnations events, and certain debt. The obligations under the Credit Facility are secured, subject to customary permitted liens and other agreed upon exceptions, by a perfected security interest in (i) all of our tangible and intangible assets, except for specified customary excluded assets, and (ii) all of the capital stock we own, subject to specified exceptions.

 

The Credit Facility contains specified affirmative covenants, including the provision of annual and quarterly financial statements and compliance certificates, maintenance of property, insurance, compliance with laws and environmental matters. The Credit Facility also contains negative covenants, including restrictions on the incurrence of indebtedness, granting of liens, making investments and acquisitions, paying dividends, repurchases of equity interests, entering into affiliate transactions and asset sales. In addition, the Credit Facility contains a financial covenant that requires us to not exceed a maximum total leverage ratio. The Credit Facility also provides for a number of events of default, including failure to make a payment of principal or any premium when due, or failure to make an interest or other payment within three business days of the due date, bankruptcy or other specified insolvency event, failure to comply covenants, breach of representations or warranties, our default of specified other obligations relating to indebtedness, impairment of specified liens, a change of control of our company and judgment defaults. We are currently in compliance with all covenants under this Credit Facility. However, if we fail to comply with the covenants and our other obligations under the Credit Facility, the Lenders would be able to accelerate the required repayment of amounts due under the loan agreement and, if they are not repaid, could foreclose upon our assets securing our obligations under the Credit Facility.

 

The Credit Facility restricts the manner in which we may operate our business, which may prevent us from successfully implementing our business plan.

 

The Credit Facility contains restrictions on the operation of our business, including limits on our ability to: 

·make specified capital expenditures;
·merge, consolidate or liquidate;
·incur indebtedness;
·dispose of, or grant liens on, our assets;
·engage in business activities other than our current business activities;
·amend specified agreements;
·enter into transactions with our affiliates;
·change our fiscal year or accounting policies;
·pay dividends or make distributions to our stockholders;
·prepay indebtedness; and
·make specified loans, guarantees or indemnities.

 

Complying with these restrictions may cause us to take actions that are not favorable to our stockholders and may make it more difficult for us to successfully execute our business plan and compete against companies who are not subject to such restrictions.

 

Servicing our debt requires a significant amount of cash, and we may not have sufficient cash flow from our operations to pay our substantial debt.

 

As of December 31, 2015, our total consolidated indebtedness was $252.4 million. Our ability to make scheduled payments of the principal of, to pay interest on, or to refinance our indebtedness, depends on our future performance, which is subject to economic, financial, competitive and other factors beyond our control. Our business may not continue to generate cash flow from operations in the future sufficient to service our debt and make necessary capital expenditures. If we are unable to generate such cash flow, we may be required to adopt one or more alternatives, such as selling assets, restructuring debt or obtaining additional equity capital on terms that may be onerous or highly dilutive. Our ability to refinance our indebtedness will depend on the capital markets and our financial condition at such time. We may not be able to engage in any of these activities or engage in these activities on desirable terms, which could result in a default on our debt obligations.

 

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Our current indebtedness and any additional debt financing may restrict the operation of our business and limit the cash available for investment in our   business operations.

 

In addition to our current debt, we may seek additional debt financing to support our ongoing activities or to provide additional financial flexibility. Debt financing could have significant adverse consequences for our business, including:

·requiring us to dedicate a substantial portion of any cash flow from operations to payment on our debt, which would reduce the amounts available to fund other corporate initiatives;
·increasing the amount of interest that we have to pay on debt with variable interest rates, if market rates of interest increase;
·subjecting us to restrictive covenants that may reduce our ability to take certain corporate actions, acquire companies, products or technology, or obtain further debt financing;
·requiring us to pledge our assets as collateral, which could limit our ability to obtain additional debt financing;
·limiting our flexibility in planning for, or reacting to, general adverse economic and industry conditions; and
·placing us at a competitive disadvantage compared to our competitors that have less debt, better debt servicing options or stronger debt servicing capacity.

 

We may not have sufficient funds or be able to obtain additional financing to pay the amounts due under our indebtedness. In addition, failure to comply with the covenants under our debt instruments could result in an event of default under those instruments. An event of default could result in the acceleration of amounts due under a particular debt instrument and a cross default and acceleration under other debt instruments, and we may not have sufficient funds or be able to obtain additional financing to make any accelerated payments. Under these circumstances, our lenders could seek to enforce security interests, if any, in our assets securing our indebtedness.

 

We may require significant additional funding and may be unable to raise capital when needed or on acceptable terms, which would harm our ability to grow our business, results of operations and financial condition.

 

We may require significant additional funding to grow our business, including to acquire other companies or products, in-license and develop additional products, enhance our manufacturing capacity, support commercial marketing activities or otherwise provide additional financial flexibility. We may also require additional funding to support our ongoing operations in the event that our ability to sell Amitiza to Takeda, Mylan and Gloria or sell RESCULA to Santen is interrupted for an extended period of time, reducing our revenues and decreasing our cash balances.

 

As of December 31, 2015, we had approximately $131.0 million of cash, cash equivalents and accounts receivable. Our future capital requirements will depend on many factors, including, among others:

·the level, timing and cost of product sales;
·the extent to which we acquire or invest in companies, products or technologies;
·the payment obligations under our indebtedness;
·the scope, progress, results and costs of our development activities;
·our ability to obtain funding from collaborative partners, government entities and non-governmental organizations for our development programs; and
·the costs of commercialization activities, including product marketing, sales and distribution.

 

If our capital resources are insufficient to meet our future capital requirements, we will need to finance our cash needs through public or private equity or debt offerings, bank loans or collaboration and licensing arrangements. If we raise funds by issuing equity securities, our stockholders may experience dilution. Public or bank debt financing, if available, may involve agreements that include covenants, like those contained in our term loans, limiting or restricting our ability to take specific actions, such as incurring additional debt, making capital expenditures, pursuing acquisition opportunities or declaring dividends. If we raise funds through collaboration and licensing arrangements with third parties, it may be necessary to relinquish valuable rights to our technologies or product candidates or grant licenses on terms that may not be favorable to us.

 

Current economic conditions may make it difficult to obtain financing on attractive terms, or at all. If financing is unavailable or lost, our business, results of operations and financial condition would be adversely affected and we could be forced to delay, reduce the scope of or eliminate many of our planned activities.

 

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ITEM 1B. UNRESOLVED STAFF COMMENTS

 

None.

 

ITEM 2. PROPERTIES

 

Our corporate headquarters, including our principal executive office and some of our administrative and research and development activities, are now located in Rockville, Maryland. The lease for this facility, which comprises approximately 27,000 square feet of office space, has an initial term expiring in April 2027. We retain the lease to our former headquarters in Bethesda, Maryland which expires in February 2017. There are no continuing business activities at the Bethesda location.

 

Following our acquisition of R-Tech, we now maintain a manufacturing facility in Sanda, Japan. We own the structure at the Sanda facility and lease the land on which it is located. The current term of the land lease expires in 2031.

 

Our international subsidiaries lease offices in Tokyo, Osaka, and Kobe, Japan, as well as Zug, Switzerland to support our administrative, storage, and research and development activities. These facilities are under short-term leases.

 

ITEM 3. LEGAL PROCEEDINGS

 

On October 3, 2014, we received a Paragraph IV certification notice letter regarding an ANDA submitted to FDA by Dr. Reddy’s, requesting approval to market, sell, and use a generic version of the 8 mcg and 24 mcg soft gelatin capsule products. In its notice letter, Dr. Reddy’s alleges that U.S. Patent Nos. 6,414,016; 6,583,174; 7,064,148; 7,417,067; 8,026,393; 8,071,613; 8,088,934; 8,097,649; 8,114,890; 8,338,639; 8,748,481; 8,779,187; 7,795,312; 8,097,653; and 8,389,542, which cover compositions, formulations and methods of using AMITIZA, are invalid, unenforceable and/or will not be infringed by Dr. Reddy’s manufacture, use or sale of the product described in its ANDA. The latest of such patents expires in 2027. On November 12, 2014, we, Takeda, and certain affiliates of Takeda filed a patent infringement lawsuit in the U.S. District Court for the District of New Jersey against Dr. Reddy’s related to the ANDA previously filed by Dr. Reddy’s and described above. The lawsuit claims infringement of 7 patents that are listed in the FDA’s Orange Book, with the latest expiring in 2027. Under the Hatch-Waxman Act, as a result of the patent infringement lawsuit, final FDA approval of Dr. Reddy’s ANDA will be stayed up to 30 months from the date of receipt of the notice letter. As of the date of this filing, the lawsuit remains ongoing.

 

On December 22, 2014, we received a Paragraph IV certification notice letter regarding an ANDA submitted to the FDA by Par Pharmaceutical requesting approval to market, sell, and use a generic version of the RESCULA (unoprostone isopropyl ophthalmic solution) 0.15% product approved for the lowering of intraocular pressure in patients with open-angle glaucoma or ocular hypertension. In its notice letter, Par Pharmaceutical alleges that U.S. Patent Nos. 6,458,836 and 6,770,675, which cover compositions, formulations and methods of using RESCULA, are invalid and/or will not be infringed by Par Pharmaceutical's manufacture, use or sale of the product described in its ANDA. The latest of such patents expires in 2021. On February 5, 2015, the day on which the Hatch-Waxman lawsuit was to be filed, we and R-Tech executed the Stipulation Agreement with Par Pharmaceutical for RESCULA (unoprostone isopropyl) ophthalmic solution 0.15% indicated for the lowering of intraocular pressure in patients with open-angle glaucoma or ocular hypertension. Under this agreement, we granted a license to Par for a generic or authorized generic version of RESCULA, effective only upon the occurrence of certain events that would allow a generic version of RESCULA to enter the market prior to 2021. In the event that such events occur and we do grant Par the license, we will split product profits with Par; furthermore, if Par chooses to distribute an authorized generic product, we will supply the product at a negotiated supply price. The term of the agreement expires in 2021.

 

On May 27, 2015, R-Tech received a Paragraph IV certification notice letter regarding an ANDA submitted to the FDA by Apotex, Inc. requesting approval to market, sell, and use a generic version of the RESCULA (unoprostone isopropyl ophthalmic solution) 0.15% product approved for the lowering of intraocular pressure in patients with open-angle glaucoma or ocular hypertension. In its notice letter, Par Pharmaceutical alleges that U.S. Patent Nos. 6,458,836 and 6,770,675, which cover compositions, formulations and methods of using RESCULA, are invalid and/or will not be infringed by Apotex’s manufacture, use or sale of the product described in its ANDA. The latest of such patents expires in 2020 . On July 10, 2015, R-Tech filed a patent infringement lawsuit in the U.S. District Court for the District of Delaware against Apotex related to the ANDA previously filed by Apotex and described above. The lawsuit claims infringement of two patents that are listed in the FDA’s Orange Book, with the latest expiring in 2020. Under the Hatch-Waxman Act, as a result of the patent infringement lawsuit, final FDA approval of Apotex’s ANDA will be stayed up to 30 months from the date of receipt of the notice letter. On September 10, 2015, Apotex filed an answer and counterclaim to our complaint. As of the date of this filing, the lawsuit remains ongoing.

 

On December 28, 2015, in connection with our acquisition of R-Tech, three non-tendering stockholders of R-Tech submitted complaints to the Tokyo District Court alleging that the purchase price of R-Tech’s shares was unfair, and demanding an appraisal of the fair value of the shares. The number of shares subject to these proceedings is minimal. As of the date of this filing, these proceedings remain ongoing.

 

ITEM 4. MINE SAFETY DISCLOSURES

 

Not applicable.

 39 
 

PART II

 

ITEM 5. MARKET FOR REGISTRANT’S COMMON EQUITY, RELATED STOCKHOLDER MATTERS AND ISSUER PURCHASES OF EQUITY SECURITIES

 

Our class A common stock has been traded on The NASDAQ Global Market under the symbol “SCMP” since our initial public offering on August 2, 2007. The following table sets forth, for the periods indicated, the range of high and low sale prices of our class A common stock as reported on The NASDAQ Global Market.

 

2014  High  Low
First quarter  $10.81   $6.60 
Second quarter   7.44    6.65 
Third quarter   7.29    5.90 
Fourth quarter   14.28    6.36 
           
2015   High    Low 
First quarter  $18.56   $13.12 
Second quarter   21.75    14.50 
Third quarter   28.96    16.34 
Fourth quarter   21.48    15.56 

 

As of March 1, 2016, we had 45,539,384 shares of class A common stock outstanding held by 10 stockholders of record. The number of holders of record of our class A common stock is not representative of the number of beneficial holders because many shares are held by depositories, brokers or nominees. As of March 1, 2016, the closing price of our class A common stock was $13.09.

 

We have never declared or paid any cash dividends on our common stock. We currently intend to retain earnings, if any, to support our growth strategy and do not anticipate paying cash dividends in the foreseeable future.

 

The information regarding the securities authorized for issuance under our equity compensation plan is incorporated into this section by reference from the section captioned “Equity Compensation Plan Information” in our Proxy Statement for our 2016 Annual Meeting of Shareholders.

 

Purchases of Equity Securities

The table below presents information regarding shares of our common stock that were purchased during the three months ended December 31, 2015.

 

  Total Number of Shares Purchased  Average Price Paid per Share  Total Number of Shares Purchased as Part of Publicly Announced Plans or Programs  Maximum Approximate Dollar Value of Shares that May Yet Be Purchased Under the Plans or Programs
Period            
October 1 through December 31, 2015   2,485,150   $17.68    -    - 

 

The purchase of the 2,485,150 shares noted above was the result of acquiring R-Tech on October 20, 2015 (see note 5). On the acquisition date, R-Tech held 2,485,150 shares of our class A common stock as a long-term investment.

 

Stock Performance Graph

The information included under this heading “Stock Performance Graph” is “furnished” and not “filed” and shall not be deemed to be “soliciting material” or subject to Regulation 14A, shall not be deemed “filed” for purposes of Section 18 of the Exchange Act, or otherwise subject to the liabilities of that section, nor shall it be deemed incorporated by reference in any filing under the Securities Act, or the Exchange Act.

 

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The following graph compares the cumulative total return, assuming the investment of $100 on December 31, 2010, in each of (1) our class A common stock, (2) The NASDAQ Composite Index (U.S. and Foreign) and (3) the NASDAQ Biotechnology Index, assuming reinvestment of any dividends. These comparisons are required by the SEC and are not intended to forecast or be indicative of possible future performance of our class A common stock.

 

 

 

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ITEM 6. SELECTED FINANCIAL DATA

 

The following derived consolidated financial data as of December 31, 2015 and 2014 and for the years ended December 31, 2015, 2014 and 2013 are from our audited Consolidated Financial Statements appearing elsewhere in this Annual Report. The following consolidated financial data as of December 31, 2013, 2012 and 2011 and for the years ended December 31, 2012 and 2011 are derived from audited Consolidated Financial Statements not included in this Annual Report. The information set forth below is not necessarily indicative of the results of future operations and should be read in conjunction with Item 7, “Management’s Discussion and Analysis of Financial Condition and Results of Operations” and the Consolidated Financial Statements and related footnotes appearing elsewhere in this Annual Report on Form 10-K.

 

   Year Ended December 31,
(In thousands, except per share data)  2015  2014  2013  2012  2011
Statement of operations data               
Revenues:  $153,180   $115,450   $89,594   $81,487   $54,761 
Costs and expenses:                         
Costs of goods sold   36,731    16,269    12,402    3,030    - 
Intangible assets impairment   -    5,631    -    -    - 
Settlement of legal dispute   -    -    -    -    (11,100)
Research and development   33,631    20,566    21,524    21,292    33,497 
General and administrative   35,517    31,230    25,413    30,157    41,270 
Selling and marketing   2,842    14,523    21,059    18,691    8,783 
Total costs and expenses   108,721    88,219    80,398    73,170    72,450 
Income (loss) from operations   44,459    27,231    9,196    8,317    (17,689)
Total non-operating income (expense), net   (784)   (98)   1,747    (340)   (4,225)
Income (loss) before income taxes   43,675    27,133    10,943    7,977    (21,914)
Income tax benefit (provision)   (10,304)   (14,005)   (3,928)   (2,916)   4,608 
Net income (loss)  $33,371   $13,128   $7,015   $5,061   $(17,306)
                          
Basic net income (loss) per share  $0.76   $0.30   $0.17   $0.12   $(0.41)
Diluted net income (loss) per share  $0.73   $0.29   $0.16   $0.12   $(0.41)
Weighted average common shares outstanding - basic   44,150    43,691    41,716    41,660    41,839 
Weighted average common shares outstanding - diluted   45,680    44,506    42,544    41,785    41,839 

 

  December 31,
(In thousands)  2015  2014  2013  2012  2011
Balance sheet data:                         
Cash and cash equivalents  $108,284   $71,622   $44,102   $52,022   $50,662 
Investments, current   -    22,393    16,003    6,035    24,452 
Working capital   163,233    88,514    70,741    52,843    67,835 
Total assets   457,181    141,574    136,877    127,796    157,569 
Notes payable, current   39,083    8,240    26,892    19,129    20,400 
Notes payable, non-current   213,277    17,578    25,828    33,722    39,227 
Total liabilities   370,732    59,262    77,908    84,541    118,975 
Retained earnings (Accumulated deficit)   19,639    (13,732)   (26,860)   (33,875)   (38,936)
Total stockholders' equity   86,449    82,312    58,969    43,255    38,594 

 

 

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ITEM 7. MANAGEMENT’S DISCUSSION AND ANALYSIS OF FINANCIAL CONDITION AND RESULTS OF OPERATIONS

 

You should read the following discussion and analysis together with our Consolidated Financial Statements and the related notes included elsewhere in this Annual Report on Form 10-K. This discussion contains forward-looking statements that are based on our current expectations, estimates and projections about our business and operations. Our actual results may differ materially from those currently anticipated and expressed in such forward-looking statements as a result of a number of factors, including those we discuss under Item 1A - “Risk Factors” and elsewhere in this Annual Report.

 

Overview

We are a global biopharmaceutical company focused on innovative research and development of proprietary drugs to meet major unmet medical needs. In 2015, we advanced our corporate strategy by solidifying our base business, executing on business development transactions and diversifying our pipeline portfolio through the acquisition of new products.

 

First, we solidified our base business by executing an agreement to expand access of our flagship product, AMITIZA® (lubiprostone) to more patients. We entered into the Gloria China Agreement for AMITIZA, under which Gloria has the rights to develop and commercialize AMITIZA in the People’s Republic of China, subject to the regulatory approval of the product by the CFDA. China was the last un-partnered market for the brand, and this new agreement assists our growth of AMITIZA and facilitates our global expansion plans. Our partnership with Takeda remains strong as solid progress in planning for expansion of AMITIZA to new markets has continued. Together, we successfully completed the European mutual recognition procedure for AMITIZA for the treatment of CIC which resulted in a recommendation for marketing authorization: Austria, Belgium, Germany, Italy, Ireland, Luxembourg, Netherlands and Spain. Additionally, we received approval for AMITIZA in CIC from Health Canada. Takeda is also developing AMITIZA in Russia, S. Korea and Mexico and has submitted an application for approval Kazakhstan.

 

Second, we executed a business development transaction by completing our acquisition of R-Tech. The acquisition was immediately accretive, improved our share of the economics of AMITIZA and included a diverse pipeline. R-Tech’s pipeline offered development alternatives and/or partnership opportunities in ophthalmology, autoimmune and inflammatory diseases and oncology. We also closed on a $250 million credit facility in connection with the financing of the acquisition. This acquisition created value for our shareholders by positioning Sucampo for revenue growth in the near-term and laying the groundwork for continued financial performance in the future. We have now secured a larger portion of the global economics of AMITIZA and greater control over the manufacturing and supply chain for our flagship product.

 

Third, we diversified our pipeline portfolio through the acquisition of new products and continued to advance our current pipeline. Through the acquisition of R-Tech, we acquired two VAP-1 inhibitors. These programs could address both patients and disease areas where there is significant unmet clinical need. We have continued to work with Takeda to accelerate our new formulation work and our pediatric functional constipation program for AMITIZA. In 2015, we furthered our clinical development of cobiprostone for two indications: oral mucositis, including U.S. FDA Fast Track Designation, and NERD/sGERD.

 

Another important priority for us was the diversification of our shareholder base and the opportunity to address our capital structure. In 2015, we undertook a secondary offering of our class A common stock offered by S&R Technology Holdings, LLC, S&R Foundation, and our founders, Dr. Sachiko Kuno and Dr. Ryuji Ueno. This offering reduced the founders’ ownership to below 50% and, due to the accounting rules applicable to related party transactions, resulted in a lowering of our corporate tax rate.

 

We recently entered into an option and collaboration agreement under which CPP has granted us the sole option to acquire an exclusive license to commercialize CPP-1X/sulindac combination product in North America. We believe that this product represents a substantial market opportunity and, given clinical results to date, could be a valuable asset for us to leverage our gastrointestinal expertise and strategic focus.

 

We currently generate revenue mainly from product royalties, development, upfront and milestone payments, product sales and reimbursements for clinical development activities. We expect to continue to incur significant expenses for the next several years as we continue our research and development activities, seek additional regulatory approvals and additional indications for our approved products and other compounds and seek strategic opportunities for in-licensing new products.

 

Our operations are conducted through subsidiaries based in the United States (U.S.), Japan and Switzerland. We operate as one segment, which focuses on the development and commercialization of pharmaceutical products.

 

Our Products (Approved and in Clinical Development)

 

Our commercial-stage products are AMITIZA and RESCULA. Overviews of these products are:

 

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AMITIZA (lubiprostone)

 

North America

In October 2014, we signed the Takeda Amendment which, among other things, extended the term beyond December 2020 and during the extended term we will split the annual net sales revenue with Takeda on branded AMITIZA sales. Beginning April 2015, Takeda no longer reimburses us for the product detailing of healthcare professionals or for promotional materials used by us. In addition, we have granted Par a license to distribute either a generic or authorized generic version of AMITIZA beginning in 2021; we will split with Par the gross profits for the sales of such products. Further, if Par decides to distribute an authorized generic, we will supply the product at a negotiated supply price.

 

In October 2015, Health Canada approved AMITIZA for CIC in adults.

 

Asia

In Japan, AMITIZA was approved in November 2012 for chronic constipation (CC) excluding constipation caused by organic diseases. AMITIZA is Japan’s only prescription medicine for CC. In Japan, AMITIZA is marketed under a license, commercialization and supply agreement (the Japan Mylan Agreement) that was transferred to Mylan, Inc. (Mylan) from Abbott Laboratories, Inc. (Abbott), as of February 2015, as part of Mylan’s acquisition of a product portfolio from Abbott. We did not experience any significant changes in the commercialization of AMITIZA in Japan as a result of the transfer of the Japan Mylan Agreement from Abbott to Mylan.

 

In May 2015, we and Gloria entered into the China Gloria Agreement to license, develop, commercialize and supply AMITIZA in the People’s Republic of China. Upon entering into the China Gloria Agreement, we received an upfront payment of $1.0 million. In June 2015, the China Food and Drug Administration accepted an Investigational New Drug (IND) application for a pivotal trial of AMITIZA in patients with CIC; as a result we received an additional payment of $500,000 from Gloria. In addition to the $1.5 million in payments received to date, we are eligible to receive an additional payment in the amount of $1.5 million upon the occurrence of a specified regulatory or commercial milestone event.

 

Other Global Markets

In October 2014, we and Takeda entered into the Global Takeda Agreement to develop and commercialize AMITIZA. The territories excluded from the Global Takeda Agreement are Canada, the U.S., Japan and the People’s Republic of China. Under the terms of the Global Takeda Agreement, we will supply Takeda the clinical and commercial product at a negotiated price. In addition, under the Global Takeda Agreement, Takeda became the marketing authorization holder in Switzerland in April 2015 and will become the marketing authorization holder in the U.K. in the first half of 2016 and in other countries upon regulatory approval.

 

In the U.K., AMITIZA was approved for CIC in September 2012. We made AMITIZA available in the U.K. in the fourth quarter of 2013. In 2014, we resubmitted an application to the MHRA for approval of the OIC indication following its initial decision to not approve in March 2014. In January 2016, we received notification from the MHRA that the appeal for the OIC indication was not approved. We will not pursue additional filings in the U.K. at this time. In July 2014, NICE published the technology appraisal guidance recommending the use of AMITIZA in the treatment of CIC and associated symptoms in adults who have failed laxatives. In January 2015, we successfully completed the European mutual recognition procedure for AMITIZA for the treatment of CIC in Austria, Belgium, Germany, Italy, Ireland, Luxembourg, Netherlands and Spain, resulting in a recommendation for marketing authorization in these markets.

 

In Switzerland, AMITIZA was approved to treat CIC in adults in 2009 and OIC in chronic, non-cancer adult patients in July 2014. In February 2014, we announced that the BAG revised several limitations with which AMITIZA was first approved for reimbursement and inclusion in the SL to make it easier for all Swiss physicians to prescribe AMITIZA to patients who have failed previous treatments with at least two laxatives over a nine month period.

 

In December 2015, a CTA was filed for AMITIZA for the treatment of CIC, IBS-C and OIC in Mexico and South Korea. We expect to initiate phase 3 registration trials in Russia, Mexico, and South Korea in the first half of 2016. An NDA for the treatment of CIC, IBS-C, and OIC was submitted in Kazakhstan in December 2015.

 

RESCULA (unoprostone isopropyl)

 

In the U.S., we ceased marketing RESCULA in the fourth quarter of 2014 and no product was made available after the March 2015 expiration date. In May 2015, following an analysis of preliminary top-line data from R-Tech’s phase 3 trial of unoprostone isopropyl in retinitis pigmentosa, we decided to discontinue development of the compound and returned all licenses for unoprostone isopropyl to R-Tech.

 

As part of the acquisition of R-Tech in October 2015, we acquired all rights to RESCULA. RESCULA is being commercialized by Santen Pharmaceutical Co., Ltd in Japan, Dong-A Pharma Co., Ltd in South Korea and Zuelliq Pharma Co., Ltd in Taiwan.

 

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Our Clinical Development Programs

 

Lubiprostone

 

Lubiprostone Alternate Formulation

 

We are developing an alternate formulation of lubiprostone for both adult and pediatric patients who are unable to tolerate capsules and for naso-gastric tube fed patients. Takeda has agreed to fund 100% of the costs, up to a cap, of this alternate formulation work and we expect to initiate a phase 3 trial of the alternate formulation of lubiprostone in the second half of 2016.

 

Pediatric Functional Constipation

 

The phase 3 program required to support an application for marketing approval of lubiprostone for pediatric functional constipation comprises four clinical trials, two of which are currently ongoing and are both testing the soft gelatin capsule formulation of lubiprostone in patients 6 to 17 years of age. The first of the two trials is a pivotal 12-week, randomized, placebo-controlled trial which was initiated in December 2013. The second trial is a follow-on, long-term safety extension trial that was initiated in March 2014. Following the successful completion of the phase 3 trial for the alternative formulation of lubiprostone, as described above, we are also planning to initiate two additional trials in its phase 3 program for pediatric functional constipation, which will be in children aged 6 months to less than 6 years testing the alternative formulation. Takeda has agreed to fund 70% of the costs, up to a cap, of this pediatric functional constipation program.

 

Cobiprostone

 

Oral Mucositis

In May 2015, the U.S. FDA granted Fast Track Designation for cobiprostone for the prevention of OM. In September 2015, we initiated a phase 2a clinical trial in the U.S. of cobiprostone oral spray for the prevention of OM in patients suffering from HNC receiving concurrent RT and CT.

 

Proton Pump Inhibitor-Refractory Non-Erosive Reflux Disease (NERD)/symptomatic Gastroesophageal Reflux Disease (sGERD

In December 2014, we initiated a phase 2a clinical trial in Japan for cobiprostone in NERD/sGERD patients who have had a non-satisfactory response to proton pump inhibitors. We expect to announce top-line data from this study in the first half of 2016.

 

VAP-1 Inhibitors

 

VAP-1 (vascular adhesion protein-1) is also known as semicarbazide sensitive amine oxidase (SSAO). There are two forms of this protein: one exists in the lining of blood vessels as a membrane-bound molecule (VAP-1) and the other exists in serum as a free molecule (SSAO), sometimes described as VAP-1/SSAO. VAP-1/SSAO is a glycoprotein. VAP-1/SSAO activity becomes increased in various tissues and in the serum of patients with diabetes, atopic dermatitis, obesity, arterial sclerosis, heart diseases, etc. Therefore, the inhibitor is expected to control such excess VAP-1/SSAO and normalize its functions.

 

RTU-1096

 

In the first quarter of 2016, the phase 1 trial has been completed in healthy individuals that evaluated the safety and pharmacokinetics and the results will be assessed in the first half of 2016. We will also look to generate additional preclinical data in the emerging area of immune-oncology, to support partnership opportunities of combination therapy in cancer patients of our molecules with check-point pathway inhibitors.

 

RTU-009

 

Our next step is to complete IND-enabling studies, and thereafter initiate clinical-stage development.

 

AMITIZA Agreements

 

We have the following collaboration agreements with our partners to develop and commercialize AMITIZA. The collaboration agreements entered into are covered by geographic location. The acquisition of R-Tech enabled us to secure a larger portion of the global economics of AMITIZA as R-Tech is the exclusive manufacturer and supplier of AMITIZA.

 

North America Takeda Agreements

·Under the terms of the North America Takeda Agreement, we supply Takeda with AMITIZA at a negotiated supply price. We have recognized product sales revenue of approximately $10.3 million for the year ended December 31, 2015.
·Takeda is obligated to pay us a sliding royalty rate based on a percentage of the net sales revenue from their sale of AMITIZA in the U.S. and Canada. The actual percentage depends on the level of net sales revenue attained each calendar year. The gross to net is capped at 20% which protects us from deep discounting. AMITIZA is currently marketed only in the U.S. and during the years ended December 31, 2015, 2014 and 2013 we recognized a total of $74.1 million, $62.8 million and $52.1 million respectively, as product royalty revenue. We believe the year-over-year growth is primarily due to an increase in total market growth and continued performance of the AMITIZA brand in volume growth.

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·We received a nonrefundable payment from Takeda of $10.0 million upon the commercial sale of AMITIZA for OIC in the second quarter of 2013.
·Takeda has agreed to fund all development costs, including regulatory-required studies, to a maximum of $50.0 million for each additional indication and $20.0 million for each additional formulation. Takeda and we have agreed to equally share all costs in excess of those amounts. With respect to any studies required to modify or expand the label for AMITIZA for the treatment of CIC, IBS-C or OIC, Takeda has agreed to fund 70% of the costs of such studies, and we have agreed to fund the remainder. Additionally, Takeda has agreed to fund 100% of the development costs for the alternate formulation of AMITIZA, and 70% of the development costs for the treatment of pediatric functional constipation.
·Takeda agreed to reimburse a portion of our expenses related to our specialty sales force. We recognized zero, $3.4 million and $61,000 of co-promotion revenue reflecting these reimbursements for the years ended December 31, 2015, 2014 and 2013, respectively. In 2013, our sales force shifted away from selling AMITIZA, which was partially reimbursed by Takeda, to selling RESCULA. In November, 2013, we announced that we would be exercising our co-promotion option and again began co-promoting AMITIZA for OIC in adults with chronic, non-cancer pain in the first quarter of 2014. In December 2014, as a result of the amendment to the North America Takeda Agreement, we ceased co-promoting AMITIZA.
·Our agreements also require Takeda to pay us up to an additional aggregate of $50.0 million upon the achievement of specified targets for annual net sales revenue from AMITIZA in the U.S. and Canada. Sales of AMITIZA have not met these targets as of December 31, 2015, 2014 and 2013.

 

Global Takeda Agreement

·Upon signing the Global Takeda Agreement in October 2014, we received a nonrefundable upfront payment of $14.0 million, of which $8.0 million was allocated to collaboration revenue and $6.0 million was considered a collaboration obligation to reimburse Takeda for the first $6.0 million in developmental expenses incurred by Takeda.
·Takeda will be responsible for any additional development activities and costs incurred (including the supply price for any licensed product that is supplied by us to Takeda for development purposes).
·Under the terms of the Global Takeda Agreement, we will supply Takeda with AMITIZA at a negotiated supply price.
·Our agreement also requires Takeda to pay us up to an additional aggregate of $35.0 million upon the achievement of specified targets for annual net sales revenue from AMITIZA in global territories covered under the Global Takeda Agreement. We have not recognized any product sales revenue under the Global Takeda Agreement for the years ended December 31, 2015 and 2014.

 

Japan Mylan Agreement

·We have recognized product sales revenue of approximately $48.9 million, $29.6 million and $15.8 million for the years ended December 31, 2015, 2014 and 2013, respectively. We believe the year-over-year growth is due to strong physician patient awareness and that AMITIZA is still the only prescription medication approved in Japan for chronic constipation.
·We could receive additional milestone payments based on achieving other specified development and commercialization goals although there can be no assurance that we will receive any such payments.

 

China Gloria Agreement

·Upon signing the China Gloria Agreement in May 2015, we received an upfront payment of $1.0 million and an upfront payment of $500,000 in June 2015 after the CFDA accepted the IND application for a pivotal trial of AMITIZA in patients with CIC.

 

·Once AMITIZA is developed in China, we will supply AMITIZA to Gloria at a negotiated supply price.

 

RESCULA Agreement

 

Japan Santen Agreement

·We have recorded product sales revenue of approximately $1.4 million, for the year ended December 31, 2015.

 

Pipeline Agreement

 

CPP Agreement

In January 2016, we entered into an option and collaboration agreement (CPP Agreement) under which Cancer Prevention Pharmaceuticals, Inc. (CPP) has granted us the sole option to acquire an exclusive license to commercialize CPP-1X/sulindac combination product in North America. Under the terms of the CPP Agreement:

·We will invest $5.0 million in CPP in the form of a convertible note, with a planned additional $5.0 million equity investment in CPP’s next qualified financing, which will be either an IPO or a private financing as defined by the agreement;
·We will pay CPP an option fee of up to $7.5 million, payable in two tranches;

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·CPP will complete the ongoing phase 3 trial under the oversight of a joint steering committee;
·Upon exercise of its exclusive option, we would acquire an exclusive license to the product and would be obligated to pay CPP up to an aggregate of $190.0 million in license fees and milestone payments upon the achievement of specified clinical development and sales milestones; and
·We and CPP would share equally in profits from the sale of approved products.

 

R-Tech Supply Agreement

The acquisition of R-Tech enabled us to secure a larger portion of the global economics of AMITIZA as R-Tech is the exclusive manufacturer and supplier of AMITIZA.

 

Under the exclusive global manufacturing and supply agreement with R-Tech prior to the acquisition, R-Tech had the exclusive right to manufacture and supply lubiprostone in most global markets. During the years ended December 31, 2015, 2014 and 2013, we recorded the following expenses under all of our agreements with R-Tech:

 

  January 1
through
October 20,
  Year Ended December 31,
(In thousands)  2015  2014  2013
Clinical supplies  $155   $396   $827 
Other research and development services   347    171    194 
Commercial supplies   21,415    15,776    14,902 
   $21,917   $16,343   $15,923 

 

Critical Accounting Policies and Estimates

This discussion and analysis of our financial condition and results of operations is based upon our Consolidated Financial Statements, which have been prepared in accordance with Generally Accepted Accounting Principles (GAAP) in the United States. The preparation of our Consolidated Financial Statements requires us to make estimates and judgments that affect our reported assets, liabilities, revenues and expenses. Actual results may differ significantly from those estimates under different assumptions and conditions.

 

We regard an accounting estimate or assumptions underlying our financial statements as a critical accounting estimate if:

·the nature of the estimate or assumption is material due to the level of subjectivity and judgment necessary to account for highly uncertain matters or the susceptibility of such matters to change; and
·the impact of the estimates and assumptions on financial condition or operating performance is material.

 

Our significant accounting policies are described in more detail in note 2 of our Consolidated Financial Statements included elsewhere in this Annual Report on Form 10-K.

 

Revenue Recognition

Our revenues are derived primarily from collaboration and license agreements which include product royalties, product sales, upfront payments, development milestone payments, reimbursements of development and co-promotion costs.

 

We recognize revenue when four basic criteria are met: (1) persuasive evidence of an arrangement exists; (2) delivery has occurred or services have been rendered; (3) the fee is fixed and determinable; (4) collectability is reasonably assured. Determination of criteria (3) and (4) could require management’s judgments regarding the fixed nature of the fee charged for services rendered and products delivered and the collectability of those fees. While the majority of our sales agreements contain standard terms and conditions, we do enter into agreements that contain multiple-element or non-standard terms and conditions. Sometimes interpretation of the sales agreement or contract for multiple-element is complex in determining whether there is more than one unit of accounting and if so, how and when revenue should be recognized for each element is subject to certain estimates or assumptions. We record revenue as the separate elements are delivered to the customer if the delivered item has value on a stand-alone basis and delivery or performance of the undelivered items is probable and substantially in our control. Revenue is allocated according to the relative selling price method. Should changes in conditions cause management to determine that these criteria are not met for certain future transactions, revenue recognized for any reporting period could be adversely affected.

 

Since 2011, we have entered into the following multiple-element arrangements: (1) research and development studies which are being reimbursed by Takeda and are treated as separate elements within the North America Takeda Agreement, and (2) the Global Takeda Agreement. We evaluated the multiple deliverables under these arrangements to determine whether the delivered elements that are our obligation have value to other parties to the agreement on a stand-alone basis and whether objective, reliable evidence of fair value of the undelivered items exists. Deliverables that meet these criteria are considered a separate unit of accounting. Deliverables that do not meet these criteria are combined and accounted for as a single unit of accounting. The appropriate recognition of revenue is then applied to each separate unit of accounting.

 

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Where agreements include contingent milestones we evaluate whether each milestone is substantive. Milestones are considered substantive if all of the following conditions are met: (1) it is commensurate with either our performance to meet the milestone or the enhancement of the value of the delivered item or items as a result of a specific outcome resulting from the our performance to achieve the milestone, (2) it relates solely to past performance, and (3) the value of the milestone is reasonable relative to all the deliverables and payment terms (including other potential milestone consideration) within the arrangement. Where milestones are not considered substantive their treatment is based on either a time-based or proportional performance model.

 

We apply a time-based model of revenue recognition for cash flows associated with research and development deliverables entered into prior to January 1, 2011 under the North America Takeda Agreement. Under this model, cash flow streams related to each unit of accounting are recognized as revenue over the estimated performance period. Upon receipt of cash payments, such as development milestones, revenue is recognized to the extent the accumulated service time has occurred. The remainder is deferred and recognized as revenue ratably over the remaining estimated performance period. A change in the period of time expected to complete the deliverable is accounted for as a change in estimate on a prospective basis. In cases where milestone payments are received after the completion of the associated development period, we recognize revenue upon completion of the performance obligation. Revenue is limited to amounts that are nonrefundable and that the other party to the agreement is contractually obligated to pay to us. The research and development revenue for these obligations is limited to the lesser of the actual reimbursable costs incurred or the straight-line amount of revenue recognized over the estimated performance period. Revenues are recognized for reimbursable costs only if those costs can be reasonably determined.

 

For research and development deliverables agreed upon subsequent to January 1, 2011, which are reimbursable under the North America Takeda Agreement at contractually predetermined percentages, we recognize revenue when the underlying research and development expenses are incurred, assuming all other revenue recognition criteria are met.

 

Under the North America Takeda Agreement, royalties are based on net sales of licensed products and are recorded on the accrual basis when earned in accordance with contractual terms when third-party results are reliably measurable, collectability is reasonably assured and all other revenue recognition criteria are met.

 

Product sales consist of AMITIZA sales to Takeda under the North America Takeda Agreement and under the Global Takeda Agreement. Product sales also consist of Amitiza sales to Mylan in Japan under the Mylan Agreement and by us directly in Europe (prior to entering into the Global Takeda Agreement). In addition, product sales of RESCULA occur in Japan under the Santen Agreement and directly by us in the U.S. We ceased marketing RESCULA in the U.S. in the fourth quarter of 2014. Revenue from product sales is recognized when persuasive evidence of an arrangement exists, delivery has occurred and title to product and associated risk of loss have passed to the customer, the price is fixed or determinable, and collection from the customer is reasonably assured. We do not record sales deductions and returns for sales of AMITIZA to Mylan and Takeda due to the absence of discounts and rebates and no right of return under the contracts with Mylan and Takeda.

 

We recognize contract revenue related to development and commercialization activities under the time-based method over the applicable period.

 

We consider our participation in the joint committees under the North America Takeda Agreement and the Mylan Agreement as separate deliverables under the contracts and recognize the fair value of such participation as revenue over the period of the participation per the terms of the contracts.

 

Inventories 

Inventories are stated at the lower of cost or net realizable value, using the first-in, first-out convention. Inventories consist of raw material, work-in-process and finished goods. Our inventories include the direct purchase cost of materials and supplies and manufacturing overhead costs.

 

Accrued Research and Development Expenses

As part of our process of preparing our Consolidated Financial Statements, we are required to estimate an accrual for research and development expenses. This process involves reviewing and identifying services which have been performed by third parties on our behalf and determining the value of these services. Examples of these services are payments to clinical investigators and CROs. In addition, we make estimates of costs incurred to date but not yet invoiced to us in relation to external CROs and clinical site costs. We analyze the progress of clinical trials, including levels of patient enrollment; invoices received and contracted costs, when evaluating the adequacy of the accrued liabilities for research and development. We must make significant judgments and estimates in determining the accrued balance in any accounting period. No material adjustments have been required for this accrual during the years ended December 31, 2015 and 2014.

 

Stock-Based Compensation

We estimate the fair value of share-based payment awards on the date of the grant using an option-pricing model and recognize the expense over the required service periods.

 

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For recording our stock-based compensation expense, for service based and market condition options we have chosen to use:

·the straight-line method of allocating compensation cost for service based options and graded vesting for market condition options;
·the Black-Scholes-Merton option pricing formula for time based options and the Monte Carlo simulation model for the market condition options as our chosen option-pricing models;
·the simplified method to calculate the expected term for options as discussed under the SEC’s guidance for share-based payments for service based options;
·an estimate of expected volatility based on the historical volatility of our share price; and
·an estimate for expected forfeitures.

 

The three factors which most affect stock-based compensation are the fair value of the common stock underlying the stock options, the vesting term of the options, and the volatility of such fair value of the underlying common stock. If our estimates are too high or too low, we may overstate or understate our stock-based compensation expense.

 

Mergers and Acquisitions

In a business combination, the acquisition method of accounting requires that the assets acquired and liabilities assumed be recorded as of the date of the merger or acquisition at their respective fair values. Fair value is defined as the exchange price that would be received for an asset or paid to transfer a liability (an exit price) in the principal or most advantageous market for the asset or liability in an orderly transaction between market participants on the measurement date. Accordingly, we may be required to value assets at fair value measures that do not reflect our intended use of those assets. Any excess of the purchase price (consideration transferred) over the estimated fair values of net assets acquired is recorded as goodwill. Transaction costs and costs to restructure the acquired company are expensed as incurred. The operating results of the acquired business are reflected in our consolidated financial statements after the date of the merger or acquisition. If we determine the assets acquired do not meet the definition of a business under the acquisition method of accounting, the transaction will be accounted for as an acquisition of assets rather than a business combination and, therefore, no goodwill will be recorded. The fair values of intangible assets, including acquired in-process research and development (IPR&D) are determined utilizing information available near the merger or acquisition date based on expectations and assumptions of a market participant that are deemed reasonable by management. Given the considerable judgment involved in determining fair values, we typically obtain assistance from third-party valuation specialists for significant items. Amounts allocated to acquire IPR&D are capitalized and accounted for as indefinite-lived intangible assets. Upon successful completion of each project, we will make a separate determination as to the then useful life of the asset and begin amortization. The judgments made in determining estimated fair values assigned to assets acquired and liabilities assumed in a business combination, as well as asset lives, can materially affect results of operations.

 

The fair values of identifiable intangible assets related to currently marketed products and product rights are primarily determined by using an "income approach" through which fair value is estimated based on each asset's discounted projected net cash flows. Our estimates of market participant net cash flows consider historical and projected pricing, margins and expense levels; the performance of competing products where applicable; relevant industry and therapeutic area growth drivers and factors; current and expected trends in technology and product life cycles; the time and investment that will be required to develop products and technologies; the ability to obtain marketing and regulatory approvals; the ability to manufacture and commercialize the products; the extent and timing of potential new product introductions by competitors; and the life of each asset's underlying patent, if any. The net cash flows are then probability-adjusted where appropriate to consider the uncertainties associated with the underlying assumptions, as well as the risk profile of the net cash flows utilized in the valuation. The probability-adjusted future net cash flows of each product are then discounted to present value utilizing an appropriate discount rate.

 

The fair values of identifiable intangible assets related to IPR&D are determined using an income or cost approach. Under the income approach, fair value is estimated based on each asset's probability-adjusted future net cash flows, which reflect the different stages of development of each product and the associated probability of successful completion. The net cash flows are then discounted to present value using appropriate discounts. Under the replacement cost approach, historical research and development spending is analyzed to derive the costs incurred to date related to the asset. An expected return of 20% is applied to the cumulative research and development costs incurred to date, as this estimates the required rate of a return a prudent investor would require on a similarly situated asset. No tax amortization benefit is applied given the asset is valued under the replacement cost approach, which is representative of buying the asset in the market at fair value.

 

Income Taxes

As part of the process of preparing our Consolidated Financial Statements, we are required to estimate our income taxes in each of the jurisdictions in which we operate. We follow the FASB’s guidance for accounting for income taxes which requires us to estimate our actual current tax exposure while assessing our temporary differences resulting from the differing treatment of items for tax and accounting purposes. These differences have resulted in deferred tax assets and liabilities, which are included in our Consolidated Balance Sheets. We record a valuation allowance to reduce our deferred tax assets to the amount that is more likely than not to be realized. We consider forecasted earnings, future taxable income, the mix of earnings in the jurisdictions in which we operate, expiration dates of net operating loss carry-forwards, and prudent and feasible tax planning strategies in determining the need for a valuation allowance. Considerable judgment is involved in developing such estimates. In the event we were to determine that we would not be able to realize all or part of our net deferred tax assets in the future, we would recognize a valuation allowance in the period in which we make that determination. Likewise, if we later determine that it is more likely than not that the net deferred tax assets would be realized, we would reverse the applicable portion of the previously provided valuation allowance. In order for us to realize our deferred tax assets we must be able to generate sufficient taxable income in the tax jurisdictions in which our deferred tax assets are located.

 

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Significant judgment is required in determining the provision for income taxes and, in particular, any valuation allowance recorded against our net deferred tax assets in certain jurisdictions. Significant future events, not under our control, including continued success in commercialization of products in U.S. markets or regulatory approvals for products in international markets, could affect our future earnings potential and consequently the amount of deferred tax assets that will be utilized. We followed the FASB’s guidance for uncertainty in income taxes that requires the application of a “more likely than not” threshold to the recognition and de-recognition of uncertain tax positions. If the recognition threshold is met, this guidance permits us to recognize a tax benefit measured at the largest amount of the tax benefit that, in our judgment, is more than 50.0% likely to be realized upon settlement.

 

We recognize interest and penalties accrued related to uncertain tax positions as a component of the income tax provision.

 

Results of Operations

 

Comparison of years ended December 31, 2015 and December 31, 2014

 

Revenues

The following table summarizes our revenues for the years ended December 31, 2015 and 2014:

 

  Year Ended
December 31,
(In thousands)  2015  2014
Product royalty revenue  $74,138   $62,775 
Product sales revenue   66,276    33,252 
Research and development revenue   10,199    7,246 
Contract and collaboration revenue   2,567    8,817 
Co-promotion revenue   -    3,360 
Total  $153,180   $115,450 

 

Total revenues were $153.2 million in 2015 compared to $115.5 million in 2014, an increase of $37.7 million or 32.7%.

 

Product royalty revenue

Product royalty revenue represents royalty revenue earned on Takeda net sales of AMITIZA in North America and was $74.1 million in 2015 compared to $62.8 million in 2014, an increase of $11.4 million or 18.1%. The increase was primarily due to higher net sales of AMITIZA as reported by Takeda for royalty calculation purposes resulting from higher sales volume.

 

Product sales revenue

Product sales revenue represents drug product sales of AMITIZA in North America,  Japan and Europe, and drug product sales of RESCULA in Japan and the U.S. Product sales revenue was $66.3 million in 2015 compared to $33.3 million in 2014, an increase of $33.0 million or 99.3%. The increase was primarily due to a $19.2 million increase in AMITIZA sales in Japan, an increase of $9.4 million in R-Tech AMITIZA sales to Takeda, a $5.0 million milestone payment and $1.5 million of RESCULA sales in Japan due to the acquisition of R-Tech in October 2015.

 

Research and development revenue

Research and development revenue was $10.2 million in 2015 compared to $7.2 million in 2014, an increase of $2.9 million or 40.8%. The increase was primarily due to an increase in expenses reimbursed by Takeda in relation to the ongoing AMITIZA pediatric trial.

 

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Contract and collaboration revenue

Contract and collaboration revenue was $2.6 million in 2015 compared to $8.8 million in 2014, a decrease of $6.3 million or 70.9%. The decrease was primarily due to the recognition of $8.0 million in upfront payment from Takeda under the Global Takeda Agreement in 2014, partially offset by the recognition of $1.5 million in upfront payments from Gloria under the China Gloria Agreement in May and June 2015.

 

Co-promotion revenue

Co-promotion revenue represents reimbursements by Takeda of a portion of our co-promotion costs for our specialty sales force and was $3.4 million in 2014. Beginning in 2015, we no longer engage in co-promotion activities and, as a result, we no longer receive any co-promotion reimbursements from Takeda.

 

Costs of Goods Sold

The following table summarizes our costs of goods sold for the years ended December 31, 2015 and 2014:

 

  Year Ended
December 31,
(In thousands)  2015  2014
Product purchases  $27,288  $16,036 
Distribution   66    233 
Amortization of inventory step-up adjustment   5,645    - 
Amortization of intangibles   3,732    - 
Total  $36,731   $16,269 

 

Costs of goods sold were $36.7 million in 2015 compared to $16.3 million in 2014, an increase of $20.5 million or 125.8%. The increase in costs of goods sold was primarily due to the increased volume of AMITIZA sales in Japan, the addition of RESCULA sales in Japan due to the acquisition of R-Tech in October 2015 and the resulting amortization of the acquired intangible assets and inventory step-up adjustment.

 

Research and Development Expenses

The following table summarizes our research and development expenses for the years ended December 31, 2015 and 2014:

 

   Year Ended
   December 31,
(In thousands)  2015  2014
Direct costs:          
Lubiprostone  $16,306   $11,002 
Cobiprostone   8,740    1,887 
Ion Channel Activator   6    1,664 
Unoprostone isopropyl   478    846 
RTU-1096   1,131    - 
RTU-009   139    - 
Other   433    1,554 
Total   27,233    16,953 
           
Indirect costs   6,398    3,613 
Total  $33,631   $20,566 

 

Total research and development expenses were $33.6 million in 2015 compared to $20.6 million in 2014, an increase of $13.1 million or 63.5%. The increase was primarily due to costs associated with the initiation of phase 2 clinical trials for cobiprostone, an increase in expenses related to the ongoing AMITIZA pediatric trials, the acquisition of R-Tech in October 2015 and the inclusion of the respective share of R-Tech’s research and development costs during the post-acquisition period.

 

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General and Administrative Expenses

 

The following summarizes our general and administrative expenses for years ended December 31, 2015 and 2014:

 

   Year Ended
   December 31,
(In thousands)  2015  2014
Salaries, benefits and related costs  $10,963   $9,322 
Legal, consulting and other professional expenses   6,946    12,951 
Stock-based compensation expense   4,936    1,802 
Pharmacovigilance   1,406    1,289 
R-Tech transaction costs   5,115    - 
Restructuring costs   286    - 
Other expenses   5,865    5,866 
Total  $35,517   $31,230 

 

General and administrative expenses were $35.5 million in 2015 compared to $31.2 million in 2014, an increase of $4.3 million or 13.7%. The increase was primarily due to a $1.6 million increase in salaries, benefits and related costs, a $3.1 million increase in stock-based compensation expense, and $5.2 million of R-Tech transaction costs incurred in connection with the acquisition of R-Tech, partially offset by a $6.0 million decrease in legal fees due to settlement of our patent infringement lawsuit against Par Pharmaceutical, et al.

 

Selling and Marketing Expenses

The following summarizes our selling and marketing expenses for years ended December 31, 2015 and 2014:

 

   Year Ended
   December 31,
(In thousands)  2015  2014
Salaries, benefits and related costs  $830   $2,724 
Consulting and other professional expenses   188    5,732 
Samples expense   4    276 
Contract fees   66    1,816 
Data purchases   201    913 
Promotional materials & programs   71    982 
Restructuring costs   473    - 
Other expenses   1,009    2,080 
Total  $2,842   $14,523 

 

Selling and marketing expenses were $2.8 million in 2015 compared to $14.5 million in 2014, a decrease of $11.7 million or 80.4%. The decrease was the result of eliminating our contract sales force related to AMITIZA in the fourth quarter of 2014.

 

Non-Operating Income and Expense

The following table summarizes our non-operating income and expense for the years ended December 31, 2015 and 2014:

 

   Year Ended
   December 31,
(In thousands)  2015  2014
Interest income  $181   $172 
Interest expense   (6,854)   (1,520)
Other income, net   5,889    1,250 
Total  $(784)  $(98)

 

Interest expense was $6.9 million in 2015 compared to $1.5 million in 2014, an increase of $5.3 million or 350.9%. The increase was the result of additional debt incurred in conjunction with the acquisition of R-Tech.

 

Other income, net was $5.9 million in 2015 compared to $1.3 million in 2014, an increase of $4.6 million or 371.1%. The increase was primarily due to a $3.9 million settlement of a pre-existing relationship related to the R-Tech supply agreements and a $2.0 million payment received from R-Tech in May 2015 for the transfer and assignment of RESCULA licensing rights, partially offset by a $1.0 million decrease in unrealized and noncash foreign exchange gains.

 

Income Taxes

For the years ended December 31, 2015 and 2014, our consolidated effective income tax rate was 23.6% and 51.6%, respectively. For the years ended December 31, 2015 and 2014, we recorded a tax expense of $10.3 and $14.0 million, respectively. The change in our effective tax rate in 2015 compared to 2014 was attributable primarily to the change in the mix of earnings of our foreign subsidiaries.

 

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Comparison of years ended December 31, 2014 and December 31, 2013

 

Revenues

The following table summarizes our revenues for the years ended December 31, 2014 and 2013:

 

   Year Ended
   December 31,
(In thousands)  2014  2013
Product royalty revenue  $62,775   $52,100 
Product sales revenue   33,252    16,425 
Contract and collaboration revenue   8,817    654 
Research and development revenue   7,246    20,354 
Co-promotion revenue   3,360    61 
Total  $115,450   $89,594 

 

Total revenues were $115.5 million in 2014 compared to $89.6 million in 2013, an increase of $25.9 million or 28.9%.

 

Product royalty revenue

Product royalty revenue represents royalty revenue earned on net sales of AMITIZA in North America and was $62.8 million in 2014 compared to $52.1 million in 2013, an increase of $10.7 million or 20.5%. The increase was primarily due to higher net sales of AMITIZA as reported by Takeda for royalty calculation purposes resulting from higher sales volume.

 

Product sales revenue

Product sales revenue represents drug product net sales of AMITIZA in Japan and Europe and drug product net sales of RESCULA in the U.S. Product sales revenue was $33.3 million in 2014 compared to $16.4 million in 2013, an increase of $16.9 million or 102.4%. The increase was primarily due to a $13.8 million increase in AMITIZA sales in Japan and a $2.5 million milestone payment earned in Japan as a result of the first occurrence of annual net sales of lubiprostone in Japan exceeding ¥5.0 billion.

 

Contract and collaboration revenue

Contract and collaboration revenue was $8.8 million in 2014 compared to $654,000 in 2013, an increase of $8.2 million or 1248.2%. The increase was due to the recognition of $8.0 million of the upfront payment from Takeda under the Global Takeda Agreement.

 

Research and development revenue

Research and development revenue was $7.2 million in 2014 compared to $20.4 million in 2013, a decrease of $13.1 million or 64.4%. The decrease was primarily due to the 2013 receipt of the $10.0 million milestone payment from Takeda upon the first commercial sale of AMITIZA for OIC.

 

Co-promotion revenue

Co-promotion revenue represents reimbursements by Takeda of a portion of our co-promotion costs for our specialty sales force. Co-promotion revenue was $3.4 million in 2014 compared to $61,000 in 2013, an increase of $3.3 million or 5408.2%. The increase resulted from our specialty sales force shifting back to co-promoting AMITIZA in 2014 after having shifted away from selling AMITIZA in 2013.

 

Costs of Goods Sold

The following table summarizes our costs of goods sold for the years ended December 31, 2014 and 2013:

 

   Year Ended
   December 31,
(In thousands)  2014  2013
Product purchases  $16,036   $9,241 
Inventory write-off   -    3,003 
Distribution   233    158 
Total  $16,269   $12,402 

 

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Costs of goods sold were $16.3 million in 2014 compared to $12.4 million in 2013, an increase of $3.9 million or 31.2%. The increase in cost of goods sold was primarily due to the increased volume of AMITIZA sales in Japan, partially offset by a $3.0 million non-cash write-off of RESCULA inventory in 2013 which did not reoccur in 2014.

 

Research and Development Expenses

The following summarizes our research and development expenses for the years ended December 31, 2014 and 2013:

 

   Year Ended
   December 31,
(In thousands)  2014  2013
Direct costs:          
Lubiprostone  $11,002   $10,644 
Cobiprostone   1,887    1,269 
Ion Channel Activator   1,664    2,738 
Unoprostone isopropyl   846    1,060 
Other   1,554    2,912 
Total   16,953    18,623 
           
Indirect costs   3,613    2,901 
Total  $20,566   $21,524 

 

Total research and development expenses were $20.6 million in 2014 compared to $21.5 million in 2013, a decrease of $958,000 or 4.5%. The decrease in research and development expenses was primarily due to the discontinuation of our clinical studies for LSS, which were ongoing in 2013, but finished in the first half of 2014. This was partially offset by increased costs for lubiprostone and cobiprostone development and additional personnel.

 

General and Administrative Expenses

The following summarizes our general and administrative expenses for years ended December 31, 2014 and 2013:

 

   Year Ended
   December 31,
(In thousands)  2014  2013
Salaries, benefits and related costs  $9,322   $8,307 
Legal, consulting and other professional expenses   12,951    7,377 
Stock-based compensation expense   1,802    1,260 
Pharmacovigilance   1,289    2,474 
Other expenses   5,866    5,995 
Total  $31,230   $25,413 

 

General and administrative expenses were $31.2 million in 2014 compared to $25.4 million in 2013, an increase of $5.8 million, or 22.9%. The increase was primarily due to a significant increase in legal fees incurred in prosecuting a patent infringement lawsuit filed by us in February 2013, partially offset by a reduction in pharmacovigilance costs that were associated with launching AMITIZA in Japan in 2013.

 

Selling and Marketing Expenses

The following summarizes our selling and marketing expenses for years ended December 31, 2014 and 2013:

 

   Year Ended
   December 31,
(In thousands)  2014  2013
Salaries, benefits and related costs  $2,724   $6,735 
Consulting and other professional expenses   5,732    4,599 
Samples expense   276    2,563 
Contract fees   1,816    213 
Data purchases   913    829 
Promotional materials & programs   982    2,208 
Other expenses   2,080    3,912 
Total  $14,523   $21,059 

 

Selling and marketing expenses were $14.5 million in 2014 compared to $21.1 million in 2013, a decrease of $6.5 million or 31.0%. The decrease was primarily due to the replacement of our in-house sales force with a lower-cost contract sales force in 2014, and a $1.5 million non-cash write-off of RESCULA samples in 2013 that did not reoccur in 2014, partially offset by increased commercialization costs in 2014 for AMITIZA in Europe.

 

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Non-Operating Income and Expense

The following table summarizes our non-operating income and expense for the years ended December 31, 2013 and 2012:

 

   Year Ended
   December 31,
(In thousands)  2014  2013
Interest income  $172   $124 
Interest expense   (1,520)   (1,894)
Other income, net   1,250    3,517 
Total  $(98)  $1,747 

 

Interest income was $172,000 in 2014 compared to $124,000 in 2013, an increase of $48,000 or 38.7%. The increase was primarily due to higher cash balances earning interest in 2014.

 

Interest expense was $1.5 million in 2014 compared to $1.9 million in 2013, a decrease of $374,000 or 19.7%. The decrease was primarily the result of lower debt balances.

 

Other income was $1.3 million in 2014 compared to $3.5 million in 2013, a decrease of $2.3 million or 64.5%. The decrease was primarily due to a $1.7 million or 58.7%, decrease in unrealized and non-cash foreign exchange gains.

 

Income Taxes

For the years ended December 31, 2014 and 2013, our consolidated effective income tax rate was 51.6% and 35.9%, respectively. For the years ended December 31, 2014 and 2013, we recorded a tax expense of $14.0 and $3.9 million, respectively. The tax expense for the year ended December 31, 2014 includes the impact of intangible impairments, resulting in approximately $818,000 of additional expense. Without the intangible impairment, the effective income tax rate would be approximately 48.6%. The change in our effective tax rate in 2014 compared to 2013 was attributable primarily to the changes in the effective foreign and state tax rates, impact of the intellectual property transfer, Subpart F income in the US (partially offset by the lower tax rate in the local jurisdiction), the mix of earnings by jurisdiction and the continuation of foreign losses that are not benefited due to full valuation allowances. As of December 31, 2014, the remaining valuation allowance against our deferred tax assets was $2.1 million and related to foreign jurisdictions where it is not more likely than not that these deferred tax assets would be realized.

 

Liquidity and Capital Resources

 

Sources of Liquidity

We finance our operations principally from cash generated from revenues, cash and cash equivalents on hand, debt and to a lesser extent, from the issuance and sale of our class A common stock and through the exercise of employee stock options. Revenues generated from operations principally consist of a combination of product sales, royalty payments, upfront and milestone payments, and research and development expense reimbursements received from Takeda, Mylan and other parties.

 

Our cash, cash equivalents, restricted cash and investments consist of the following:

 

   Year Ended
   December 31,
(In thousands)  2015  2014
Cash and cash equivalents  $108,284   $71,622 
Restricted cash, current   55,218    213 
Restricted cash, non-current   -    2,224 
Investments, current   -    22,393 
Investments, non-current   -    13,540 
Total  $163,502   $109,992 

 

Our cash and cash equivalents are deposits in operating accounts and highly liquid investments with an original maturity at time of purchase of 90 days or less.

 

As of December 31, 2015, our restricted cash consisted primarily of $25.0 million related to the Credit Facility that requires us to maintain $25.0 million in a restricted cash account until at least $35 million of the Term Loans have been repaid or prepaid (see note 18 in the Notes to Consolidated Financial Statements included elsewhere in this Annual Report on Form 10-K), and as part of the R-Tech acquisition, $17.7 million is held in a restricted cash account for payment of the Ueno and Kuno Trust Notes (see note 17 in the Notes to Consolidated Financial Statements included elsewhere in this Annual Report on Form 10-K), and $8.2 million is held in restricted cash related to the squeeze out of non-tendering R-Tech shareholders (see note 5 in the Notes to Consolidated Financial Statements included elsewhere in this Annual Report on Form 10-K). As of December 31, 2014, our restricted cash consisted primarily of collateral pledged to support Numab’s loan with Zurcher Kantonalbank and operating leases with certain financial institutions.

 

55 

 

As of December 31, 2014, our current investments consisted of U.S. corporate commercial paper, municipal securities, certificates of deposit and variable rate demand notes which have maturities of one year or less. Our non-current investments consisted of U.S. government securities, certificates of deposit and corporate bonds.

 

Cash Flows

The following table summarizes our cash flows for the years ended December 31, 2015, 2014 and 2013:

 

   Year Ended December 31,
(In thousands)  2015  2014  2013
Cash provided by (used in):               
Operating activities  $18,585   $30,878   $(4,209)
Investing activities   (131,151)   12,959    (12,616)
Financing activities   149,341    (15,413)   10,581 
Effect of exchange rates   (113)   (904)   (1,676)
Net increase (decrease) in cash and cash equivalents  $36,662   $27,520   $(7,920)

 

Year ended December 31, 2015

Net cash provided by operating activities of $18.6 million for the year ended December 31, 2015 was primarily due to a net income of $33.4 million offset by net changes in operating assets and liabilities totaling $15.0 million. Net changes in operating assets and liabilities of $15.0 million consisted primarily of an increase in receivables of $8.5 million, a decrease in deferred revenue of $5.4 million, an increase in product royalties receivable of $4.2 million and a decrease in accounts payable of $1.7 million, offset by cash provided by other assets and liabilities, net of $5.7 million. Major offsetting components of the non-cash expenses were: depreciation and amortization of $10.6 million, stock-based compensation of $7.3 million offset by a deferred tax benefit of $9.8 million, unrealized currency translation gains of $3.7 million.

 

Net cash used in investing activities of $131.2 million for the year ended December 31, 2015 was primarily the result of acquisition, net of acquired cash of $161.2 million and investment purchases of $39.8 million, offset by cash from matured investments of $30.6 million and proceeds from investment sales of $45.1 million.

 

Net cash provided by financing activities of $149.3 million for the year ended December 31, 2015 was primarily due to proceeds of notes payable of $235.9 million net of debt issuance costs offset by purchase of treasury stock of $44.0 million and payment of notes payable of $8.2 million.

 

The effect of exchange rates on the cash balances of currencies held in foreign denominations for year ended December 31, 2015 was a decrease of $113,000.

 

Year ended December 31, 2014

Net cash provided by operating activities of $30.9 million for the year ended December 31, 2014 was primarily due to a net income of $13.1 million, non-cash expenses totaling $11.7 million (which includes an intangible assets impairment of $5.6 million, an increase in deferred charges of $3.2 million, stock-based compensation expense of $2.3 million, and depreciation and amortization of $1.1 million), cash provided by an increase in collaboration obligation of $6.0 million, and net changes in other assets and liabilities of $3.7 million, offset by cash used in net changes in receivables and payables of $3.7 million.

 

Net cash provided by investing activities of $13.0 million for the year ended December 31, 2014 was primarily the result of a decrease in restricted cash of $25.8 million, cash from matured investments of $14.7 million, and proceeds from investment sales of $1.7 million, offset by investment purchases of $29.2 million.

 

Net cash used in financing activities of $15.4 million for the year ended December 31, 2014 was primarily due to the payment of notes payable of $24.9 million, offset by proceeds of $5.3 million from our “at-the-market” stock offering and proceeds of $3.8 million from the exercise of employee stock options.

 

The effect of exchange rates on the cash balances of currencies held in foreign denominations for year ended December 31, 2014 was a decrease of $904,000.

 

Year ended December 31, 2013

Net cash used in operating activities was $4.2 million for the year ended December 31, 2013. This reflected cash provided by net income of $7.0 million, non-cash stock based compensation of $1.7 million, depreciation and amortization of $1.5 million, offset by non-cash unrealized currency translation gains of $2.0 million, an increase in accounts receivable of $4.0 million, and a decrease in both accrued expenses and deferred revenue of $4.7 million and $3.1 million, respectively.

 

56 

 

Net cash used in investing activities of $12.6 million for the year ended December 31, 2013 primarily reflected a $9.6 million increase in restricted cash and a $2.9 million increase in purchases of investments net of maturities and proceeds.

 

Net cash provided by financing activities of $10.6 million for the year ended December 31, 2013 primarily reflected proceeds of $5.3 million from our “at-the-market” stock offering, and proceeds of $2.3 million from the exercise of employee stock options.

 

The effect of exchange rates on the cash balances of currencies held in foreign denominations for year ended December 31, 2013 was a decrease of $1.7 million.

 

Commitments and Contractual Obligations

The following table summarizes our significant contractual obligations as of December 31, 2015:

 

(In thousands of U.S. dollars)   Total    Less than
1 year
    1 - 3
years
    3 - 5
years
    More than
5 years
 
Loans  $267,582   $42,582   $50,000   $50,000   $125,000 
Interest on loans   86,995    20,050    33,859    25,609    7,477 
Operating lease commitments   7,341    1,781    1,598    1,912    2,050 
Uncertain tax positions (1)   3,061    -    -    -    - 
   $364,979   $64,413   $85,457   $77,521   $134,527 

 

(1) The Company presently does not expect to settle any of this amount within the next twelve months in cash. It is reasonably possible that $1.3 million of the liability for unrecognized tax benefits will decrease within the next 12 months and the remaining $1.8 million in an unknown future period.

 

The table above does not include any contingent liability under the agreement with Numab in the event that Numab defaults under its loan with Zurcher Kantonalbank up to a maximum potential amount of $2.2 million. As of December 31, 2015, the potential amount of payments in the event of Numab’s default was $1.5 million (see note 17 in the Notes to Consolidated Financial Statements included elsewhere in this Annual Report on Form 10-K).

 

Off-Balance Sheet Arrangements

As of December 31, 2015, we did not have any off-balance sheet arrangements, as such term is defined in Item 303(a)(4) of Regulation S-K under the Securities Act of 1934, as amended.

 

Funding Requirements

We may need substantial amounts of capital to continue growing our business. We may require this capital, among other things, to fund:

·our share of the on-going development program of AMITIZA;
·research, development, manufacturing, regulatory and marketing efforts for our other products and product candidates, including the RTU-009 VAP-1 inhibitor compound;
·the costs involved in obtaining and maintaining proprietary protection for our products, technology and know-how, including litigation costs and the results of such litigation;
·activities to resolve our on-going legal matters;
·any option and milestone payments under general option and licensing ventures, including our exclusive option and collaboration agreement with CPP;
·other business development activities, including partnerships, alliances and investments in or acquisitions of other businesses, products and technologies;
·the expansion of our commercialization activities including the purchase of inventory; and
·the payment of principal and interest under our loan obligations.

 

The timing of these funding requirements is difficult to predict due to many factors, including the outcomes of our preclinical and clinical research and development programs and when those outcomes are determined, the timing of obtaining regulatory approvals and the presence and status of competing products. Our capital needs may exceed the capital available from our future operations, collaborative and licensing arrangements and existing liquid assets. Our future capital requirements and liquidity will depend on many factors, including, but not limited to:

 

·the cost and time involved to pursue our research and development programs;
·our ability to establish collaborative arrangements and to enter into licensing agreements and contractual arrangements with others; and
·any future change in our business strategy.

 

57 

 

To the extent that our capital resources may be insufficient to meet our future capital requirements, we may need to finance our future cash needs through at-the-market sales, public or private equity offerings, further debt financings or corporate collaboration and licensing arrangements.

 

At December 31, 2015, based upon our current business plan, we believe we have sufficient liquidity for the next 12 months.

 

Effects of Foreign Currency

We currently receive a portion of our revenue, incur a portion of our operating expenses, and have assets and liabilities in currencies other than the U.S. Dollar, the reporting currency for our Consolidated Financial Statements. As such, the results of our operations could be adversely affected by changes in exchange rates either due to transaction losses, which are recognized in the statement of operations, or translation losses, which are recognized in comprehensive income. We currently do not hedge foreign exchange rate exposure via derivative instruments.

 

Accounting Pronouncements

Refer to note 2 in the Notes to Consolidated Financial Statements included elsewhere in this Annual Report on Form 10-K.

 

ITEM 7A. Quantitative and Qualitative Disclosures about Market Risk

 

Foreign Currency Exchange Rate Risk

We are subject to foreign exchange risk for revenues and expenses denominated in foreign currencies. Foreign currency risk arises from the fluctuation of foreign exchange rates and the degree of volatility of these rates relative to the U.S. Dollar. We do not currently hedge our foreign currency transactions via derivative instruments.

 

Interest Rate Risk

Our exposure to market risks associated with changes in interest rates relates to both (i) the amount of interest income earned on our investment portfolio, and (ii) the amount of interest payable by us under the Credit Facility. These risks offset each other somewhat; for example, rising interest rates would increase both the amounts earned on our investments and amounts due under the Term Loans.

 

With respect to our investments, our goal is to ensure the safety and preservation of invested funds by limiting default risk, market risk and reinvestment risk. We attempt to mitigate default risk by investing in investment grade securities. A hypothetical one percentage point decline in interest rates would not have materially affected the fair value of our interest-sensitive financial instruments as of December 31, 2015.

 

In connection with our acquisition of R-Tech, we incurred the Term Loans in the aggregate principal amount of $250.0 million. As described in further detail in note 18, the Term Loans bear interest at a variable rate calculated by reference to the Federal Funds Rate or LIBOR, at our option. Accordingly, increases in these published rates would increase our interest payments under the Term Loans. Because no interest payments were due under the Term Loans in 2015, a hypothetical one percentage point increase in interest rates would not have materially affected our financial condition as of December 31, 2015

 

We do not use derivative financial instruments for trading or speculative purposes. However, we regularly invest excess cash in overnight repurchase agreements that are subject to changes in short-term interest rates. We believe that the market risk arising from holding these financial instruments is minimal.

 

Credit Risk

Our exposure to credit risk generally consists of cash and cash equivalents, restricted cash, investments and receivables. We place our cash, cash equivalents and restricted cash with what we believe to be highly rated financial institutions and invest the excess cash in highly rated investments. Our investment policy limits investments to certain types of debt and money market instruments issued by institutions primarily with investment grade credit ratings and places restriction on maturities and concentrations by asset class and issuer.

 

Our exposure to credit risk also extends to strategic investments made as part of our ongoing business development activities, such as the investment of $5.0 million in CPP in the form of a convertible note made in January 2016. A more detailed discussion of this arrangement is set forth under the heading “CPP Agreement”.

 

As of December 31, 2015 and December 31, 2014, approximately 3.6% and 33.6%, respectively, of our cash, cash equivalents, restricted cash and investments is issued or insured by the federal government or government agencies. We have not experienced any losses on these accounts related to amounts in excess of insured limits.

 

58 

 

ITEM 8. FINANCIAL STATEMENTS AND SUPPLEMENTARY DATA

 

The Consolidated Financial Statements and related financial statement schedules required by this item are included beginning on page F-1 of this report.

 

ITEM 9. CHANGES IN AND DISAGREEMENTS WITH ACCOUNTANTS ON ACCOUNTING AND FINANCIAL DISCLOSURE

 

None.

 

ITEM 9A. CONTROLS AND PROCEDURES

 

Evaluation of Disclosure Controls and Procedures

Our management, under the supervision and with the participation of our Chief Executive Officer and Chief Financial Officer, performed an evaluation of the effectiveness of the design and operation of our disclosure controls and procedures (as defined in Rules 13a-15(e) and 15d-15(e) under the Exchange Act) as of December 31, 2015. In designing and evaluating such controls, management recognizes that any controls and procedures, no matter how well designed and operated, can provide only reasonable assurance of achieving their objectives and management necessarily applies its judgment in evaluating the benefits of possible controls and procedures relative to their costs. Based upon the evaluation we carried out, our Chief Executive Officer and Chief Financial Officer have concluded that, as of December 31, 2015, our disclosure controls and procedures were effective to provide reasonable assurance that the information required to be disclosed by us in the reports that we file or submit under the Exchange Act is recorded, processed, summarized and reported within the time periods specified under the applicable rules and forms of the SEC, and that such information is accumulated and communicated to management, including our Chief Executive Officer and Chief Financial Officer, as appropriate, to allow timely decisions regarding required disclosures.

 

Changes in Internal Controls Over Financial Reporting

There were no changes in our internal control over financial reporting during the year ended December 31, 2015 that have materially affected, or are reasonably likely to materially affect, our internal control over financial reporting.

 

Management’s Annual Report on Internal Control Over Financial Reporting

Our management is responsible for establishing and maintaining adequate internal control over financial reporting (defined in Rules 13a-15(f) or 15d-15(f) under the Exchange Act) for our company. Our management assessed the effectiveness of our internal control over financial reporting as of December 31, 2015. In making this assessment, our management used the criteria set forth by the Committee of Sponsoring Organizations of the Treadway Commission, or COSO, in Internal Control-Integrated Framework (2013). Based on this evaluation, management concluded that our internal control over financial reporting was effective as of December 31, 2015.

 

Management’s assessment of and conclusion on the effectiveness of (1) disclosure controls and procedures and (2) internal controls over financial reporting did not include the internal controls related to the operations acquired in the acquisition of R-Tech, which is included in our 2015 consolidated financial statements and constituted total and net assets of $301.4 million and $217.6 million, respectively, as of December 31, 2015, and revenues and net loss of $11.8 million and $4.7 million, respectively, for the year then ended.

 

The effectiveness of our internal control over financial reporting as of December 31, 2015 has been audited by Ernst & Young LLP, an independent registered public accounting firm, as stated in their report which appears herein.

 

ITEM 9B. OTHER INFORMATION

 

On March 2, 2015, Ms. Barbara Munder advised the Board that she would not stand for election at the 2016 annual meeting of stockholders and will resign effective May 31, 2016 from the Board of Directors. The Board has decided to reduce the size of the Board from seven to six members effective upon such resignation and will determine if there is a need to increase the size of the Board in the future.

 

PART III

 

ITEM 10. DIRECTORS, EXECUTIVE OFFICERS AND CORPORATE GOVERNANCE

 

The following information will be included in our proxy statement, or Proxy Statement, for our 2016 Annual Meeting of Stockholders to be filed within 120 days after the fiscal year end of December 31, 2015, and is incorporated herein by reference:

·Information regarding our directors required by this item will be set forth under the heading “Election of Directors”;
·Information regarding our executive officers required by this item will be set forth under the heading “Executive Officers”;

59 

 
·Information regarding our Audit Committee and designated “audit committee financial expert” will be set forth under the heading “Corporate Governance Principles and Board Matters, Board Structure and Committee Composition — Audit Committee;” and
·Information regarding Section 16(a) beneficial ownership reporting compliance will be set forth under the heading “Section 16(a) Beneficial Ownership Reporting Compliance.”

 

Code of Ethics

We have adopted codes of ethics and business conduct that applies to our employees, including our principal executive officer, principal financial and accounting officer and persons performing similar functions. Our codes of ethics and business conduct can be found posted in the investors section on our website at http://www.sucampo.com.

 

ITEM 11. EXECUTIVE COMPENSATION

 

The information required by this item is incorporated by reference to the information provided under the heading “Executive Compensation” of our Proxy Statement for our 2016 Annual Meeting of Stockholders.

 

ITEM 12. SECURITY OWNERSHIP OF CERTAIN BENEFICIAL OWNERS AND MANAGEMENT AND RELATED STOCKHOLDER MATTERS

 

The information regarding security ownership of our beneficial owners, management and related stockholder matters is incorporated into this section by reference from the section captioned “Stock Ownership Information” in our Proxy Statement for our 2016 Annual Meeting of Stockholders. The information regarding the securities authorized for issuance under our equity compensation plan is incorporated into this section by reference from the section captioned “Equity Compensation Plan Information” in our Proxy Statement for our 2016 Annual Meeting of Stockholders.

 

ITEM 13. CERTAIN RELATIONSHIPS AND RELATED TRANSACTIONS AND DIRECTOR INDEPENDENCE

 

The information regarding certain relationships and related transactions is incorporated by reference to the information provided under the heading “Related Party Transactions” in our Proxy Statement for our 2016 Annual Meeting of Stockholders. The information regarding director independence is incorporated by reference to the information provided under the heading “Corporate Governance Principles and Board Matters, Board Structure and Committee Composition – Board Determination of Independence” in our proxy statement for our 2016 Annual Meeting of Stockholders.

 

ITEM 14. PRINCIPAL ACCOUNTING FEES AND SERVICES

 

The information required by this item is incorporated by reference to the information provided under the heading “Independent Registered Public Accounting Firm’s Fees” and “Pre-Approval Policy and Procedures” in our Proxy Statement for our 2016 Annual Meeting of Stockholders.

 

PART IV

 

 

ITEM 15. EXHIBITS, FINANCIAL STATEMENT SCHEDULES

 

(a)The following financial statements, financial statement schedule and exhibits are filed as part of this report or incorporated herein by reference:
(1)Consolidated Financial Statements. See Index to Consolidated Financial Statements on page F-1.
(2)Financial Statement Schedule: Schedule II – Valuation and Qualifying Accounts on page F-41. All other schedules are omitted because they are not applicable, not required or the information required is shown in the financial statements or notes thereto.
(3)Exhibits. See subsection (b) below.
(b)Exhibits. The following exhibits are filed or incorporated by reference as part of this report.

 

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Exhibit                    
Number   Description   Form   File No.   Exhibit   Filing Date
2.1   Agreement and Plan of Reorganization, dated as of December 29, 2008, among the Company, Sucampo Pharma Holdings, Inc. and Sucampo MS, Inc.   8-K   001-33609   2.1   12/29/2008
                     
2.2   Stock Purchase Agreement, dated December 23, 2010, among Dr. Ryuji Ueno, as trustee of the Ryuji Ueno Revocable Trust under Trust Agreement dated December 20, 2002, Dr. Sachiko Kuno as trustee of the Sachiko Kuno Revocable Trust under Trust Agreement dated December 20, 2002, Dr. Ryuji Ueno, Dr. Sachiko Kuno, Ambrent Investments S.à.r.l., and Sucampo Pharmaceuticals, Inc.   8-K   001-33609   2.1   12/29/2010
                     
2.3#   Strategic Alliance Agreement, dated as of August 26, 2015, among Sucampo Pharmaceuticals, Inc., Sucampo Pharma, LLC and R-Tech Ueno, Ltd.    10-Q   001-33609   10.2   11/4/2015
                     
2.4#   Share Purchase Agreement, dated August 26, 2015,  among Dr. Ryuji Ueno, Dr. Sachiko Kuno, S&R Technology Holdings, LLC, and Sucampo Pharmaceuticals, Inc.   10-Q   001-33609   10.3   11/4/2015
                     
3.1   Certificate of Incorporation   8-K   001-33609   3.1   12/29/2008
                     
3.2   Certificate of Amendment   8-K   001-33609   3.2   12/29/2008
                     
3.3   Amended and Restated Bylaws   8-K   001-33609   3.3   8/2/2013
                     
4.1   Specimen Stock Certificate evidencing the shares of class A common stock   S-1/A   333-135133   4.1   2/1/2007
                     
10.1^   Amended and Restated 2001 Stock Incentive Plan   S-1   333-135133   10.1   6/19/2006
                     
10.2^   Amended and Restated 2006 Stock Incentive Plan   10-Q   001-33609   10.2   11/14/2007
                     
10.3^   2006 Employee Stock Purchase Plan   S-1/A    333-135133   10.3   10/20/2006
                     
10.4^   Form of Investor Rights Agreement   S-1    333-135133   10.16   6/19/2006
                     
10.5*   Collaboration and License Agreement, dated October 29, 2004, between the Company and Takeda Pharmaceutical Company Limited    S-1    333-135133   10.21   6/19/2006
                     
10.6*   Agreement, dated October 29, 2004, among the Company, Takeda Pharmaceutical Company Limited and Sucampo AG   S-1    333-135133   10.22   6/19/2006
                     
10.7*   Supply Agreement, dated October 29, 2004, among the Company, Takeda Pharmaceutical Company Limited and R-Tech Ueno, Ltd.   S-1    333-135133   10.23   6/19/2006
                     
10.8*   Supply and Purchase Agreement, dated January 25, 2006, among the Company, Takeda Pharmaceutical Company Limited and R-Tech Ueno, Ltd.   S-1    333-135133   10.24   6/19/2006

 

 61 
 

10.9*   Supplemental Agreement, dated February 1, 2006, between the Company and Takeda Pharmaceutical Company Limited    S-1    333-135133   10.25   6/19/2006
                     
10.10   Letter agreement, dated January 29, 2007, between the Company and Takeda Pharmaceutical Company Limited   S-1/A    333-135133   10.36   5/14/2007
                     
10.11*   Supply Agreement, dated February 19, 2009, between Sucampo Pharma Ltd. and Abbott Japan Co. Ltd.   10-K   001-33609   10.43   3/16/2009
                     
10.12   Subordinated Unsecured Promissory Note, dated December 23, 2010, between Ambrent Investments S.à.r.l., as borrower, and Ryuji Ueno Revocable Trust Under Trust Agreement dated December 20, 2002, as lender   8-K   001-33609   10.1   12/29/2010
                     
10.13   Subordinated Unsecured Promissory Note, dated December 23, 2010, between Ambrent Investments S.à.r.l., as borrower, and Sachiko Kuno Revocable Trust Under Trust Agreement dated December 20, 2002, as lender   8-K   001-33609   10.2   12/29/2010
                     
10.14*   Loan Guarantee and Development Agreement, dated September 8, 2011, between Numab AG and Sucampo AG   10-K   001-33609   10.58   3/15/2012
                     
10.15   Master Lease Agreement, effective as of January 31, 2012, between Sucampo AG and Numab AG   10-Q   001-33609   10.1   5/10/2012
                     
10.16   Lease Agreement, dated December 18, 2006, between the Company and EW Bethesda Office Investors, LLC   10-K   001-33609   10.29   3/27/2008
                     
10.17^   Form of Indemnification Agreement, dated December 31, 2012, between the Company and an indemnitee   8-K   001-33609   99.6   1/7/2013
                     
10.18^   Employment Agreement, dated February 10, 2014, between the Company and Peter Greenleaf   10-K   001-33609   10.70   3/12/2014
                     
10.19*   Settlement and License Agreement, dated September 30, 2014, among the Company, Sucampo AG, R-Tech Ueno, Ltd., Takeda Pharmaceutical Company Limited, Takeda Pharmaceuticals USA, Inc., Takeda Pharmaceuticals America, Inc., Anchen Pharmaceuticals, Inc., Par Pharmaceutical, Inc. and Par Pharmaceutical Companies, Inc.   10-Q   001-33609   10.2   11/7/2014
                     
10.20*   Manufacturing and Supply Agreement, dated September 30, 2014, between Sucampo AG and Par Pharmaceutical, Inc.   10-Q   001-33609   10.3   11/7/2014
                     
10.21*   Amendment No. 1, dated September 30, 2014, to Collaboration and License Agreement dated October 29, 2004 and Supplemental Agreement, dated February 1, 2006, between Sucampo Pharma Americas, LLC and Takeda Pharmaceutical Company Limited   10-Q   001-33609   10.4   11/7/2014
                     
10.22   Amendment No. 1, dated September 30, 2014, to the Agreement dated October 29, 2004, between Sucampo Pharma Americas, LLC, Takeda Pharmaceutical Company Limited and Sucampo AG   10-Q   001-33609   10.5   11/7/2014
                     
10.23*   Amendment No. 1, dated September 30, 2014, to Supply Agreement dated October 29, 2004, Supply and Purchase Agreement dated January 25, 2006 and the Addendum to the Supply and Purchase Agreement dated November 6, 2013, among Sucampo Pharma Americas, LLC, Takeda Pharmaceutical Company Limited and R-Tech Ueno, Ltd.   10-Q   001-33609   10.6   11/7/2014

 

 62 
 

10.24*   License, Development, Commercialization and Supply Agreement For Lubiprostone, dated October 27, 2014, between Sucampo AG and Takeda Pharmaceuticals International GmbH Limited   10-K   001-33609   10.79   3/9/2015
                     
10.25^   Employment Agreement, dated as of October 27, 2014, between the Company and Dr. Peter Kiener   10-K   001-33609   10.80   3/9/2015
                     
10.26^   Employment Agreement, dated as of October 27, 2014, between the Company and Matthias Alder   10-K   001-33609   10.81   3/9/2015
                     
10.27^   Employment Agreement, dated as of October 27, 2014, between the Company and Dr. Steven Caffé   10-K   001-33609   10.82   3/9/2015
                     
10.28^   Employment Agreement, dated as of October 27, 2014, between Sucampo AG and Peter Lichtlen   10-K   001-33609   10.84   3/9/2015
                     
10.29^   Registration Rights Agreement, dated January 15, 2015, among the Company, S&R Technology Holdings, LLC, S&R Foundation, Dr. Ryuji Ueno and Dr. Sachiko Kuno   S-3    333-135133   10.1   1/16/2015
                     
10.30*   Stipulation and License Agreement, dated February 5, 2015, among the Company, Sucampo AG,  R-Tech Ueno, Ltd. and Par Pharmaceutical, Inc.   10-K   001-33609   10.88   3/9/2015
                     
10.31*   Manufacturing and Supply Agreement, dated as of February 5, 2015, between Sucampo AG and Par Pharmaceutical, Inc.   10-K   001-33609   10.89   3/9/2015
                     
10.32*   Office Lease Agreement, dated May 5, 2015, between Four Irvington Centre Associations, LLC and Sucampo Pharmaceuticals, Inc.   10-Q   001-33609   10.1   8/5/2015
                     
10.33*   License, Development, Commercialization And Supply Agreement For Lubiprostone for People's Republic of China, dated May 5, 2015, between Harbin Gloria Pharmaceuticals Co., Ltd. and Sucampo AG   10-Q   001-33609   10.2   8/5/2015
                     
10.34*   First Amendment to office Lease Agreement, dated September 14, 2015, between  Four Irvington Centre Associations, LLC and Sucampo Pharmaceuticals, Inc.   10-Q   001-33609   10.1   11/4/2015
                     
10.35^   Non-employee Director Compensation Summary   Included herewith            
                     
10.36^   Form Sucampo Pharmaceuticals, Inc. Duration-Based Stock Option Incentive Award Stock Option Agreement Terms and Conditions   Included herewith            
                     
10.37**   Amendment No. 1, dated November 18,  2015 to the License, Development, Commercialization and Supply Agreement for Lubiprostone dated October 17, 2014, between Sucampo AG and Takeda Pharmaceuticals International AG   Included herewith            

 

 63 
 

10.38**   Credit Agreement, dated October 16, 2015, among the Company as borrower, the financial institutions listed therein as Lenders and Jefferies Finance LLC, as administrative agent and collateral agent for the Lenders   Included herewith            
                     
10.39**   Lease Agreement, dated April 1, 2001, between Ueno Fine Chemicals and R-Tech Ueno Ltd.    Included herewith            
                     
10.40&   New Technology Development Consignment Agreement, dated April 1, 2015, between the Japan Agency for Medical Research and Development and R-Tech Ueno, Ltd.   Included herewith            
                     
10.41**   Manufacturing Agreement, dated May 22, 2004,  between R-Tech Ueno, Ltd. and Nissan Chemical Industries, Ltd.   Included herewith            
                     
101.[SCH]†   XBRL Taxonomy Extension Schema Document   Included herewith            
                     
101.[CAL]†    XBRL Taxonomy Extension Calculation Linkbase Document   Included herewith            
                     
101.[LAB]†    XBRL Taxonomy Extension Label Linkbase Document   Included herewith            
                     
101.[PRE]†    XBRL Taxonomy Extension Presentation Linkbase Document   Included herewith            
                     
21   Subsidiaries of the Company   Included herewith            
                     
23.1   Consent of Ernst & Young LLP, Independent Registered Public Accounting Firm   Included herewith            
                     
23.2   Consent of PricewaterhouseCoopers LLP, Independent Registered Public Accounting Firm   Included herewith            
                     
31.1   Certification of the Principal Executive Officer, as required by Section 302 of the Sarbanes-Oxley Act of 2002   Included herewith            
                     
31.2   Certification of the Principal Financial Officer, as required by Section 302 of the Sarbanes-Oxley Act of 2002   Included herewith            
                     
32.1   Certification of the Principal Executive Officer pursuant to 18 U.S.C. Section 1350, as adopted pursuant to Section 906 of the Sarbanes-Oxley Act of 2002   Included herewith            
                     
32.2   Certification of the Principal Financial Officer pursuant to 18 U.S.C. Section 1350, as adopted pursuant to Section 906 of the Sarbanes-Oxley Act of 2002   Included herewith            

 

^ Compensatory plan, contract or arrangement.

* Confidential treatment has been granted for portions of this exhibit.

** Confidential treatment has been requested for certain portions of this exhibit. The confidential portions of this exhibit have been omitted and filed separately with the Securities and Exchange Commission.

& English summary of a foreign language document.

# Pursuant to Item 601(b)(2) of Regulation S-K promulgated by the SEC, certain schedules to this agreement have been omitted. The registrant hereby agrees to furnish supplementally to the SEC, upon its request, any or all of such omitted schedules.

† Attached as Exhibit 101 to this report are documents formatted in XBRL (Extensible Business Reporting Language).  Users of this data are advised that, pursuant to Rule 406T of Regulation S-T, the interactive data file is deemed not filed or part of a registration statement or prospectus for purposes of Sections 11 or 12 of the Securities Act of 1933, as amended, is deemed not filed for purposes of Section 18 of the Securities Exchange Act of 1934, as amended, and is otherwise not subject to liability under these sections.

 

64 

 

Signatures

 

Pursuant to the requirements of Section 13 or 15(d) of the Securities Exchange Act of 1934, as amended, the registrant has duly caused this report to be signed on its behalf by the undersigned, thereunto duly authorized.

 

    Sucampo Pharmaceuticals, Inc.
     
     
March 10, 2016 By: /s/  PETER GREENLEAF
    Peter Greenleaf
    Chief Executive Officer
    (Principal Executive Officer)

  

Pursuant to the requirements of the Securities Exchange Act of 1934, as amended, this report has been signed below by the following persons on behalf of the registrant and in the capacities and on the dates indicated.

 

Signature   Title   Date
         
/s/  PETER GREENLEAF   Chief Executive Officer, Chairman of the Board   March 10, 2016
Peter Greenleaf   (Principal Executive Officer)    
         
         
/s/  ANDREW P. SMITH   Chief Financial Officer   March 10, 2016
Andrew P. Smith   (Principal Financial Officer)    
         
         
/s/  DANIEL P. GETMAN       March 10, 2016
Daniel P. Getman   Director    
         
         
/s/  JOHN JOHNSON       March 10, 2016
John Johnson   Lead Independent Director    
         
         
/s/  BARBARA A. MUNDER       March 10, 2016
Barbara A. Munder   Director    
         
         
/s/  MAUREEN E. O'CONNELL       March 10, 2016
Maureen E. O'Connell   Director    
         
         
/s/  ROBERT SPIEGEL       March 10, 2016
Robert Spiegel   Director    
         
         
/s/ TIMOTHY WALBERT       March 10, 2016
Timothy Walbert   Director    

 

65 

 

SUCAMPO PHARMACEUTICALS, INC.

INDEX TO CONSOLIDATED FINANCIAL STATEMENTS

 

 

 

Reports of Independent Registered Public Accounting Firms F-2
Consolidated Balance Sheets as of December 31, 2015 and 2014 F-5
Consolidated Statements of Operations and Comprehensive Income for the Years Ended December 31, 2015, 2014 and 2013 F-6
Consolidated Statements of Changes in Stockholders’ Equity for the Years Ended December 31, 2015, 2014 and 2013 F-7
Consolidated Statements of Cash Flows for the Years Ended December 31, 2015, 2014 and 2013 F-8
Notes to Consolidated Financial Statements F-9

 

 

 

F-1 

 

Report of Ernst & Young LLP,

Independent Registered Public Accounting Firm,

on the Audited Consolidated Financial Statements

 

The Board of Directors and Stockholders of Sucampo Pharmaceuticals, Inc.

 

We have audited the accompanying consolidated balance sheet of Sucampo Pharmaceuticals, Inc. as of December 31, 2015, and the related consolidated statements of operations and comprehensive income, changes in stockholders’ equity and cash flows for the year then ended. Our audit also included the financial statement schedule listed in the Index at Item 15(a)(2). These financial statements and schedule are the responsibility of the Company's management. Our responsibility is to express an opinion on these financial statements and schedule based on our audit.

 

We conducted our audit in accordance with the standards of the Public Company Accounting Oversight Board (United States). Those standards require that we plan and perform the audit to obtain reasonable assurance about whether the financial statements are free of material misstatement. An audit includes examining, on a test basis, evidence supporting the amounts and disclosures in the financial statements. An audit also includes assessing the accounting principles used and significant estimates made by management, as well as evaluating the overall financial statement presentation. We believe that our audit provides a reasonable basis for our opinion.

 

In our opinion, the financial statements referred to above present fairly, in all material respects, the consolidated financial position of Sucampo Pharmaceuticals, Inc. at December 31, 2015, and the consolidated results of its operations and its cash flows for the year then ended, in conformity with U.S. generally accepted accounting principles. Also, in our opinion, the related financial statement schedule, when considered in relation to the basic financial statements taken as a whole, presents fairly in all material respects the information set forth therein.

 

We also have audited, in accordance with the standards of the Public Company Accounting Oversight Board (United States), Sucampo Pharmaceuticals, Inc.’s internal control over financial reporting as of December 31, 2015, based on criteria established in Internal Control-Integrated Framework issued by the Committee of Sponsoring Organizations of the Treadway Commission (2013 framework), and our report dated March 10, 2016 expressed an unqualified opinion thereon.

 

/s/ Ernst & Young LLP

 

McLean, Virginia

March 10, 2016

 

 F- 2 
 

Report of Ernst & Young LLP,

Report of Independent Registered Public Accounting Firm,

Regarding Internal Control Over Financial Reporting

 

The Board of Directors and Stockholders of Sucampo Pharmaceuticals, Inc.

 

We have audited Sucampo Pharmaceuticals, Inc.’s internal control over financial reporting as of December 31, 2015, based on criteria established in Internal Control—Integrated Framework issued by the Committee of Sponsoring Organizations of the Treadway Commission (2013 framework), (the COSO criteria). Sucampo Pharmaceuticals, Inc.’s management is responsible for maintaining effective internal control over financial reporting, and for its assessment of the effectiveness of internal control over financial reporting included in the accompanying Managements Report on Internal Control over Financial Reporting. Our responsibility is to express an opinion on the company’s internal control over financial reporting based on our audit.

 

We conducted our audit in accordance with the standards of the Public Company Accounting Oversight Board (United States). Those standards require that we plan and perform the audit to obtain reasonable assurance about whether effective internal control over financial reporting was maintained in all material respects. Our audit included obtaining an understanding of internal control over financial reporting, assessing the risk that a material weakness exists, testing and evaluating the design and operating effectiveness of internal control based on the assessed risk, and performing such other procedures as we considered necessary in the circumstances. We believe that our audit provides a reasonable basis for our opinion.

 

A company’s internal control over financial reporting is a process designed to provide reasonable assurance regarding the reliability of financial reporting and the preparation of financial statements for external purposes in accordance with generally accepted accounting principles. A company’s internal control over financial reporting includes those policies and procedures that (1) pertain to the maintenance of records that, in reasonable detail, accurately and fairly reflect the transactions and dispositions of the assets of the company; (2) provide reasonable assurance that transactions are recorded as necessary to permit preparation of financial statements in accordance with generally accepted accounting principles, and that receipts and expenditures of the company are being made only in accordance with authorizations of management and directors of the company; and (3) provide reasonable assurance regarding prevention or timely detection of unauthorized acquisition, use, or disposition of the company’s assets that could have a material effect on the financial statements.

 

Because of its inherent limitations, internal control over financial reporting may not prevent or detect misstatements. Also, projections of any evaluation of effectiveness to future periods are subject to the risk that controls may become inadequate because of changes in conditions, or that the degree of compliance with the policies or procedures may deteriorate.

 

As indicated in the accompanying Management’s Annual Report on Internal Control Over Financial Reporting, management’s assessment of and conclusion on the effectiveness of internal control over financial reporting did not include the internal controls of R-Tech Ueno, Ltd., which is included in the 2015 consolidated financial statements of Sucampo Pharmaceuticals, Inc. and constituted $301.4 million and $217.6 million of total and net assets, respectively, as of December 31, 2015 and $11.8 million and $4.7 million of revenues and net loss, respectively, for the year then ended. Our audit of internal control over financial reporting of Sucampo Pharmaceuticals, Inc. and subsidiaries also did not include an evaluation of the internal control over financial reporting of R-Tech Ueno, Ltd.

 

In our opinion, Sucampo Pharmaceuticals, Inc. maintained, in all material respects, effective internal control over financial reporting as of December 31, 2015, based on the COSO criteria.

 

We also have audited, in accordance with the standards of the Public Company Accounting Oversight Board (United States), the consolidated balance sheet of Sucampo Pharmaceuticals, Inc. as of December 31, 2015, and the related consolidated statements of operations, comprehensive income, changes in stockholders’ equity and cash flows for the period ended December 31, 2015 of Sucampo Pharmaceuticals, Inc. and our report dated March 10, 2016 expressed an unqualified opinion thereon.

 

/s/ Ernst & Young LLP

 

McLean, Virginia

March 10, 2016

 

F-3

 

Report of Independent Registered Public Accounting Firm

 

To the Board of Directors and Stockholders of Sucampo Pharmaceuticals, Inc.:

 

In our opinion, the consolidated balance sheet as of December 31, 2014 and the related consolidated statements of operations and comprehensive income, of changes in stockholders’ equity and of cash flows for each of the two years in the period ended December 31, 2014 present fairly, in all material respects, the financial position of Sucampo Pharmaceuticals, Inc. and its subsidiaries at December 31, 2014, and the results of their operations and their cash flows for each of the two years in the period ended December 31, 2014, in conformity with accounting principles generally accepted in the United States of America. In addition, in our opinion, the financial statement schedule for each of the two years in the period ended December 31, 2014 presents fairly, in all material respects, the information set forth therein when read in conjunction with the related consolidated financial statements. These financial statements and financial statement schedule are the responsibility of the Company's management. Our responsibility is to express an opinion on these financial statements and financial statement schedule based on our audits. We conducted our audits of these statements in accordance with the standards of the Public Company Accounting Oversight Board (United States). Those standards require that we plan and perform the audit to obtain reasonable assurance about whether the financial statements are free of material misstatement. An audit includes examining, on a test basis, evidence supporting the amounts and disclosures in the financial statements, assessing the accounting principles used and significant estimates made by management, and evaluating the overall financial statement presentation. We believe that our audits provide a reasonable basis for our opinion.

 

 

 

/s/ PricewaterhouseCoopers LLP

 

Baltimore, Maryland

March 9, 2016, except for the change in the composition of reportable segments discussed in Note 4 to the consolidated financial statements, as to which the date is May 6, 2015.

 

 

 

 

F-4 

 

SUCAMPO PHARMACEUTICALS, INC.

Consolidated Balance Sheets

(In thousands, except share and per share data)

 

  

December 31,

2015

 

December 31,

2014

ASSETS:          
Current assets:          
Cash and cash equivalents  $108,284   $71,622 
Investments, current   -    22,393 
Product royalties receivable   22,792    18,576 
Accounts receivable, net   22,759    5,338 
Deferred charge, current   295    295 
Restricted cash, current   55,218    213 
Inventories, net   33,121    - 
Prepaid expenses and other current assets   8,891    3,411 
Total current assets   251,360    121,848 
Investments, non-current   -    13,540 
Property and equipment, net   6,393    763 
Intangible assets   130,315    151 
Goodwill   60,937    - 
In-process research & development   6,171    - 
Deferred tax assets, non-current   -    1,047 
Deferred charge, non-current   1,400    1,695 
Restricted cash, non-current   -    2,224 
Other assets   605    306 
Total assets  $457,181   $141,574 
LIABILITIES AND STOCKHOLDERS' EQUITY:          
Current liabilities:          
Accounts payable  $11,213   $4,143 
Accrued expenses   10,886    8,467 
Deferred revenue, current   676    2,051 
Collaboration obligation   5,623    6,000 
Income tax payable   6,507    1,291 
Notes payable, current   39,083    8,240 
Other current liabilities   14,139    3,618 
Total current liabilities   88,127    33,810 
Notes payable, non-current   213,277    17,578 
Deferred revenue, non-current   1,088    5,118 
Deferred tax liability net, non-current   52,497    820 
Other liabilities   15,743    1,936 
Total liabilities   370,732    59,262 
           
Commitments and contingencies (note 16)          
           
Stockholders' equity:          
Preferred stock, $0.01 par value; 5,000,000 shares authorized at December 31, 2015 and 2014; no shares issued and outstanding at December 31, 2015 and 2014, respectively   -    - 
Class A common stock, $0.01 par value; 270,000,000 shares authorized at December 31, 2015 and 2014; 45,509,150 and 44,602,988 shares issued and outstanding at December 31, 2015 and 2014, respectively   455    446 
Class B common stock, $0.01 par value; 75,000,000 shares authorized at December 31, 2015 and 2014;  no shares issued and outstanding at December 31, 2015 and 2014, respectively   -    - 
Additional paid-in capital   99,212    83,646 
Accumulated other comprehensive income   13,412    14,265 
Treasury stock, at cost; 3,009,942 and 524,792 shares at December 31, 2015 and 2014, respectively   (46,269)   (2,313)
Retained earnings (Accumulated deficit)   19,639    (13,732)
Total stockholders' equity   86,449    82,312 
Total liabilities and stockholders' equity  $457,181   $141,574 

 

The accompanying notes are an integral part of these Consolidated Financial Statements.

F-5 

 

SUCAMPO PHARMACEUTICALS, INC.

Consolidated Statements of Operations and Comprehensive Income

(In thousands, except per share data)

 

   Year Ended December 31,
   2015  2014  2013
Revenues:               
Product royalty revenue  $74,138   $62,775   $52,100 
Product sales revenue   66,276    33,252    16,425 
Research and development revenue   10,199    7,246    20,354 
Contract and collaboration revenue   2,567    8,817    654 
Co-promotion revenue   -    3,360    61 
Total revenues   153,180    115,450    89,594 
                
Costs and expenses:               
Costs of goods sold   36,731    16,269    12,402 
Intangible assets impairment   -    5,631    - 
Research and development   33,631    20,566    21,524 
General and administrative   35,517    31,230    25,413 
Selling and marketing   2,842    14,523    21,059 
Total costs and expenses   108,721    88,219    80,398 
                
Income from operations   44,459    27,231    9,196 
Non-operating income (expense):               
Interest income   181    172    124 
Interest expense   (6,854)   (1,520)   (1,894)
Other income, net   5,889    1,250    3,517 
Total non-operating income (expense), net   (784)   (98)   1,747 
                
Income before income taxes   43,675    27,133    10,943 
Income tax provision   (10,304)   (14,005)   (3,928)
Net income  $33,371   $13,128   $7,015 
                
Net income per share:               
Basic  $0.76   $0.30   $0.17 
Diluted  $0.73   $0.29   $0.16 
Weighted average common shares outstanding:               
Basic   44,150    43,691    41,716 
Diluted   45,680    44,506    42,544 
                
Comprehensive income:               
Net income  $33,371   $13,128   $7,015 
Other comprehensive income (loss):               
Unrealized gain (loss) on pension benefit obligation   105    (978)   - 
Unrealized gain (loss) on investments, net of tax effect   7    (7)   2 
Foreign currency translation   (965)   (351)   (567)
Total comprehensive income  $32,518   $11,792   $6,450 

 

The accompanying notes are an integral part of these Consolidated Financial Statements.

F-6 

 

SUCAMPO PHARMACEUTICALS, INC.

Consolidated Statements of Changes in Stockholders’ Equity

(In thousands, except share data)

 

            Accumulated        Retained   
   Class A  Additional  Other        Earnings  Total
   Common Stock  Paid-In  Comprehensive  Treasury Stock  (Accumulated  Stockholders'
   Shares  Amount  Capital  Income (Loss)  Shares  Amount  Deficit)  Equity
Balance at December 31, 2012   41,964,905    420    62,521    16,166    457,030    (1,977)   (33,875)   43,255 
Employee stock option expense   -    -    1,744    -    -    -    -    1,744 
Stock issued upon exercise of stock options   597,836    5    2,332    -    -    -    -    2,337 
Stock issued under employee stock purchase plan   3,625    -    25    -    -    -    -    25 
Stock issued under "at-the-market" offering   749,383    7    5,274    -    -    -    -    5,281 
Foreign currency translation   -    -    -    (567)   -    -    -    (567)
Unrealized loss on investments, net of tax effect   -    -    -    2    -    -    -    2 
Windfall tax benefit from stock-based compensation   -    -    213    -    -    -    -    213 
Treasury stock, at cost   -    -    -    -    67,762    (336)   -    (336)
Net income   -    -    -    -    -    -    7,015    7,015 
Balance at December 31, 2013   43,315,749    432    72,109    15,601    524,792    (2,313)   (26,860)   58,969 
Employee stock option expense   -    -    2,287    -    -    -    -    2,287 
Stock issued upon exercise of stock options   742,865    9    3,780    -    -    -    -    3,789 
Stock issued under employee stock purchase plan   5,853    -    36    -    -    -    -    36 
Stock issued under "at-the-market" offering   538,521    5    5,321    -    -    -    -    5,326 
Windfall tax benefit from stock-based compensation   -    -    113    -    -    -    -    113 
Unrealized loss on pension benefit obligation   -    -    -    (978)   -    -    -    (978)
Unrealized loss on investments, net of tax effect   -    -    -    (7)   -    -    -    (7)
Foreign currency translation   -    -    -    (351)   -    -    -    (351)
Net income   -    -    -    -    -    -    13,128    13,128 
Balance at December 31, 2014   44,602,988    446    83,646    14,265    524,792    (2,313)   (13,732)   82,312 
Employee stock option expense   -    -    7,349    -    -    -    -    7,349 
Stock issued upon exercise of stock options   897,077    9    5,614    -    -    -    -    5,623 
Stock issued under employee stock purchase plan   9,085    -    128    -    -    -    -    128 
Windfall tax benefit from stock-based compensation   -    -    2,475    -    -    -    -    2,475 
Unrealized gain on pension benefit obligation   -    -    -    105    -    -    -    105 
Unrealized gain on investments, net of tax effect   -    -    -    7    -    -    -    7 
Foreign currency translation   -    -    -    (965)   -    -    -    (965)
Treasury stock, at cost   -    -    -    -    2,485,150    (43,956)   -    (43,956)
Net income   -    -    -    -    -    -    33,371    33,371 
Balance at December 31, 2015   45,509,150   $455   $99,212   $13,412    3,009,942   $(46,269)  $19,639   $86,449 

 

The accompanying notes are an integral part of these Consolidated Financial Statements.

F-7 

 

SUCAMPO PHARMACEUTICALS, INC.

Consolidated Statements of Cash Flows

(In thousands)

 

   Year Ended December 31,
   2015  2014  2013
Cash flows from operating activities:               
Net income  $33,371   $13,128   $7,015 
Adjustments to reconcile net income to net cash provided by (used in) operating activities:               
Depreciation and amortization   10,580    1,090    1,488 
Intangible assets impairment   -    5,631    - 
Deferred tax provision (benefit)   (9,779)   770    (1,678)
Deferred charge   295    3,223    673 
Stock-based compensation   7,349    2,287    1,744 
Amortization of premiums on investments   121    82    110 
Foreign currency remeasurement gain   (3,687)   (1,146)   (2,023)
Shortfall from stock-based compensation   (70)   (227)   - 
Windfall benefit from stock-based compensation   (2,547)   -    - 
Transfer and assignment of licensing rights   (2,000)   -    - 
Changes in operating assets and liabilities:               
Accounts receivable   (8,481)   67    (4,047)
Unbilled accounts receivable   (668)   -    732 
Product royalties receivable   (4,216)   (3,747)   (654)
Inventory   (1,436)   206    (163)
Income taxes receivable and payable, net   1,110    592    560 
Accounts payable   (1,723)   (3,437)   2,242 
Accrued expenses   395    2,868    (4,685)
Deferred revenue   (5,351)   (191)   (3,126)
Collaboration obligation   (377)   6,000    - 
Accrued interest payable   (25)   (32)   (32)
Other assets and liabilities, net   5,724    3,714    (2,365)
Net cash provided by (used in) operating activities   18,585    30,878    (4,209)
Cash flows from investing activities:               
Purchases of investments   (39,775)   (29,153)   (10,127)
Proceeds from the sales of investments   45,062    1,700    755 
Maturities of investments   30,554    14,650    6,485 
Tenant improvement allowance   (1,880)   -    - 
Purchases of property and equipment   (3,557)   (66)   (168)
Transfer and assignment of licensing rights   2,000    -    - 
Changes in restricted cash   (2,368)   25,828    (9,561)
Acquisition, net of acquired cash   (161,187)   -    - 
Net cash provided by (used in) investing activities   (131,151)   12,959    (12,616)
Cash flows from financing activities:               
Proceeds from notes payable, net of debt issuance costs   235,911    -    10,600 
Repayment of notes payable   (8,236)   (24,904)   (7,539)
Changes in restricted cash   (42,676)          
Proceeds from exercise of stock options   5,623    3,789    2,337 
Proceeds from employee stock purchase plan   128    36    25 
Proceeds from "at-the market" stock issuance   -    5,326    5,281 
Purchase of treasury stock   (43,956)   -    (336)
Windfall benefit from stock-based compensation   2,547    340    213 
Net cash provided by (used in) financing activities   149,341    (15,413)   10,581 
Effect of exchange rates on cash and cash equivalents   (113)   (904)   (1,676)
Net increase (decrease) in cash and cash equivalents   36,662    27,520    (7,920)
Cash and cash equivalents at beginning of period   71,622    44,102    52,022 
Cash and cash equivalents at end of period  $108,284   $71,622   $44,102 
Supplemental cash flow disclosures:               
Cash paid for interest  $5,983   $129   $156 
Tax refunds received  $423   $76   $103 
Tax payments made  $17,621   $9,166   $4,939 

 

The accompanying notes are an integral part of these Consolidated Financial Statements.

F-8 

 

1. Business Organization and Basis of Presentation

 

Description of the Business

Sucampo Pharmaceuticals, Inc., (Company) is a global biopharmaceutical company focused on innovative research and development of proprietary drugs to treat gastrointestinal, ophthalmic, autoimmune, and oncology-based inflammatory disorders.

 

The Company currently generates revenue mainly from product royalties, upfront and milestone payments, product sales and reimbursements for development activities. The Company expects to continue to incur significant expenses for the next several years as the Company continues its research and development activities, seeks additional regulatory approvals and additional indications for approved products and other compounds and seeks strategic opportunities for in-licensing new products.

 

AMITIZA is being marketed for three gastrointestinal indications under the collaboration and license agreement (as amended in October 2014, the North America Takeda Agreement) with Takeda Pharmaceutical Company Limited (Takeda). These indications are chronic idiopathic constipation (CIC) in adults, irritable bowel syndrome with constipation (IBS-C) in adult women and opioid-induced constipation (OIC) in adults suffering from chronic non-cancer related pain. Under the North America Takeda Agreement, the Company is primarily responsible for clinical development activities, while Takeda is responsible for commercialization of AMITIZA in the U.S. and Canada. The Company and Takeda initiated commercial sales of AMITIZA in the U.S. for the treatment of CIC in April 2006, for the treatment of IBS-C in May 2008 and for the treatment of OIC in May 2013. Takeda is required to provide a minimum annual commercial investment during the current term of the North America Takeda Agreement and may reduce the minimum annual commercial investment when a generic equivalent enters the market. In October 2015, Health Canada approved AMITIZA for CIC in adults. In October 2014, the Company and Takeda executed amendments (Takeda Amendment) to the North America Takeda Agreement which, among other things, extended the term of the North America Takeda Agreement beyond December 2020. During the extended term, Takeda and the Company will split the annual net sales revenue of the branded AMITIZA products. In addition, beginning April 2015, the North America Takeda Agreement was amended to terminate the Company’s right to perform commercialization activities with respect to AMITIZA and Takeda’s obligation to reimburse the Company for such commercialization activities.

 

In Japan, AMITIZA is marketed under a license, commercialization and supply agreement (the Japan Mylan Agreement) that was transferred to Mylan, Inc. (Mylan) from Abbott Laboratories, Inc. (Abbott), as of February 2015, as part of Mylan’s acquisition of a product portfolio from Abbott. The Company received approval of its new drug application (NDA) for AMITIZA for the treatment of chronic constipation (CC), excluding constipation caused by organic diseases, from the Ministry of Health, Labour and Welfare in June 2012 and pricing approval in November 2012. AMITIZA is Japan’s only prescription medicine for CC. The Company did not experience any significant changes in the commercialization of AMITIZA in Japan as a result of the transfer of the Japan Mylan Agreement from Abbott to Mylan.

 

In the People’s Republic of China, the Company entered into an exclusive license, development, commercialization and supply agreement (the China Gloria Agreement) with Harbin Gloria Pharmaceuticals Co., Ltd. (Gloria), for AMITIZA in May 2015. Under the China Gloria Agreement, Gloria is responsible for all development activities and costs, as well as commercialization and regulatory activities, for AMITIZA in the People’s Republic of China. The Company will be the exclusive supplier of AMITIZA to Gloria at an agreed upon supply price. Upon entering into the China Gloria Agreement, the Company received an upfront payment of $1.0 million. In June 2015, the China Food and Drug Administration accepted an Investigational New Drug (IND) application for a pivotal trial of AMITIZA in patients with CIC; as a result the Company received an additional payment of $500,000 from Gloria. In addition to the $1.5 million in payments received and recognized as revenue through June 2015, the Company is eligible to receive an additional payment in the amount of $1.5 million upon the occurrence of a specified regulatory or commercial milestone event.

 

In October 2014, the Company entered into an exclusive license, development, commercialization and supply agreement (the Global Takeda Agreement) for lubiprostone with Takeda, through which Takeda has the exclusive rights to further develop and commercialize AMITIZA in all global markets, except the U.S., Canada, Japan and the People’s Republic of China. Takeda became the marketing authorization holder in Switzerland in April 2015 and is expected to become the marketing authorization holder in the United Kingdom (U.K.), Austria, Belgium, Germany, Italy, Ireland, Luxembourg, the Netherlands and Spain in the first half of 2016.

  

Before the execution of the Global Takeda Agreement, the Company retained full rights to develop and commercialize AMITIZA for the rest of the world’s markets outside of the U.S., Canada and Japan. In the U.K., the Company received approval in September 2012 from the Medicines and Healthcare Products Regulatory Agency (MHRA) for the use of AMITIZA to treat CIC. The Company made AMITIZA available in the U.K. in the fourth quarter of 2013. In 2014, the Company resubmitted an application to the MHRA for approval of the OIC indication following its initial decision to not approve in March 2014. In January 2016, the Company received notification from the MHRA that the appeal for the OIC indication was not approved. The Company will not pursue additional filings in the U.K. at this time. In July 2014, National Institute of Health and Care Excellence (NICE) published the technology appraisal guidance recommending the use of AMITIZA in the treatment of CIC and associated symptoms in adults who have failed laxatives. In January 2015, the Company successfully completed the European mutual recognition procedure (MRP) for AMITIZA for the treatment of CIC in select European countries, resulting in a recommendation for marketing authorization.

 

F-9 

 

In Switzerland, AMITIZA was approved to treat CIC in 2009. In 2012, the Company reached an agreement with the Bundesamt fur Gesundheit, (BAG), the Federal Office of Public Health in Switzerland, on a reimbursement price for AMITIZA in Switzerland, and began active marketing in the first quarter of 2013. Since February 2012, AMITIZA has also been available through a Named Patient Program throughout the European Union, Iceland and Norway. In February 2014, the Company announced that the BAG revised several reimbursement limitations with which AMITIZA was first approved for reimbursement and inclusion in the Spezialitätenliste (SL) to allow all Swiss physicians to prescribe AMITIZA to patients who have failed previous treatments with at least two laxatives over a nine month period. In July 2014, AMITIZA was approved for the treatment of OIC in chronic, non-cancer adult patients by the Swissmedic, the Swiss Agency for Therapeutic Products.

 

In October 2015, the Company and Takeda obtained approval of the clinical trial application (CTA) for AMITIZA for the treatment of CIC and IBS-C in Russia that was submitted in June 2015. In December 2015, a CTA was filed for AMITIZA for the treatment of CIC, IBS-C and OIC in Mexico and South Korea. The Company expects to initiate phase 3 registration trials in Russia, Mexico, and South Korea in the first half of 2016. An NDA for the treatment of CIC, IBS-C, and OIC was submitted in Kazakhstan in December 2015.

 

In the U.S., the Company ceased marketing RESCULA in the fourth quarter of 2014 and no product was made available after the March 2015 expiration date. In May 2015, the Company returned all licenses for unoprostone isopropyl to R-Tech. As part of the acquisition of R-Tech in October 2015, the Company acquired all rights to RESCULA. RESCULA is being commercialized by Santen Pharmaceutical Co., Ltd in Japan, Dong-A Pharmaceutical, Co., Ltd in South Korea and Zuelliq Pharma Co., Ltd in Taiwan.

 

The Company’s other clinical development programs include the following:

 

Lubiprostone Alternate Formulation

The Company has been developing an alternate formulation of lubiprostone for both adult and pediatric patients who are unable to tolerate capsules and for naso-gastric tube fed patients. Takeda has agreed to fund 100% of the costs, up to a cap, of this alternate formulation work and the Company expects to initiate a phase 3 trial of the alternate formulation of lubiprostone in the second half of 2016.

 

Lubiprostone for Pediatric Functional Constipation 

The phase 3 program required to support an application for marketing approval of lubiprostone for pediatric functional constipation comprises four clinical trials, two of which are currently ongoing and are both testing the soft gelatin capsule formulation of lubiprostone in patients 6 to 17 years of age. The first of the two trials is a pivotal 12-week, randomized, placebo-controlled trial which was initiated in December 2013. The second trial is a follow-on, long-term safety extension trial that was initiated in March 2014. Following the successful completion of the phase 3 trial for the alternative formulation of lubiprostone, as described above, the Company is also planning to initiate two additional trials in its phase 3 program for pediatric functional constipation, which will be in children aged 6 months to less than 6 years testing the alternative formulation. Takeda has agreed to fund 70% of the costs, up to a cap, of this pediatric functional constipation program.

 

Cobiprostone for Oral Mucositis

In May 2015, the U.S. FDA granted Fast Track Designation for cobiprostone for the prevention of OM. In September 2015, the Company initiated a phase 2a clinical trial in the U.S. of cobiprostone oral spray for the prevention of OM in patients suffering from HNC receiving concurrent RT and CT.

 

Cobiprostone for Proton Pump Inhibitor-Refractory Non-Erosive Reflux Disease (NERD)/symptomatic Gastroesophageal Reflux Disease (sGERD)

In December 2014, the Company initiated a phase 2a clinical trial in Japan for cobiprostone in NERD/sGERD patients who have had a non-satisfactory response to proton pump inhibitors. The Company expects to announce top-line data from this study in the first half of 2016.

 

F-10 

 

VAP-1 Inhibitor for RTU-1096

RTU-1096 is an oral compound under development for the treatment of nonalcoholic steatohepatitis (NASH), chronic obstructive pulmonary disease (COPD), diabetic macular edema (DME) and diabetic retinopathy (DR) and immune-oncology. In the first quarter of 2016, the phase 1 trial has been completed in healthy individuals that evaluated the safety and pharmacokinetics and the results will be accessed in the first half of 2016. The Company will also look to generate additional preclinical data in the emerging area of immune-oncology, to support partnership opportunities of combination therapy in cancer patients of our molecules with check-point pathway inhibitors.

 

VAP-1 Inhibitor for RTU-009 

RTU-009 is a pre-clinical stage, injectable VAP-1 inhibitor that is being studied in acute cerebral infarction as well as ophthalmic diseases. Our next step would be to complete IND-enabling studies, and thereafter initiate clinical-stage development.

 

Basis of Presentation

The accompanying Consolidated Financial Statements of the Company have been prepared in accordance with generally accepted accounting principles in the United States of America, (GAAP) and the rules and regulations of the Securities and Exchange Commission, (SEC). The Consolidated Financial Statements include the accounts of the Company and its wholly owned subsidiaries: Sucampo AG, based in Zug, Switzerland, through which the Company conducts certain worldwide and European operations; Sucampo Pharma, LLC, based in Tokyo and Osaka, Japan and R-Tech Ueno, Ltd. (acquired October 20, 2015), based in Kobe, Japan through which the Company conducts its Asian operations; Sucampo Pharma Americas LLC, based in Rockville, Maryland, through which the Company conducts operations in North and South America and Sucampo Pharma Europe, Ltd., based in Oxford, U.K.. All inter-company balances and transactions have been eliminated.

 

The preparation of financial statements in conformity with GAAP requires management to make estimates that affect the reported amounts of assets and liabilities at the date of the financial statements, disclosure of contingent assets and liabilities, and the reported amounts of revenue and expenses during the reporting period. Actual results could differ from those estimates.

 

2. Summary of Significant Accounting Policies

 

Principles of Consolidation

The consolidated financial statements include the accounts of Sucampo Pharmaceuticals, Inc. and its wholly owned subsidiaries. All intercompany accounts and transactions have been eliminated.

 

Use of Estimates

The preparation of financial statements in conformity with accounting principles generally accepted in the United States requires management to make estimates and assumptions that affect the reported amounts of assets, liabilities and disclosure of contingencies at the date of the financial statements as well as the reported amounts of revenues and expense during the reporting period. Actual results could differ from those estimates.

 

Cash and Cash Equivalents

For the purpose of the Consolidated Balance Sheets and Consolidated Statements of Cash Flows, cash equivalents include all highly liquid investments with a maturity of 90 days or less at the time of purchase.

 

Current and Non-Current Investments

Current and non-current investments consist primarily of U.S. government agency securities, certificates of deposit, corporate bonds, municipal securities and variable rate demand notes, and are classified as current or non-current based on their maturity dates. The Company classifies all investments as available-for-sale securities and reports unrealized gains or losses, net of related tax effects, in other comprehensive income.

 

Accounts Receivable

Accounts receivable primarily represents amounts due under the North America Takeda Agreement and Japan Mylan Agreement. The Company recorded an immaterial allowance for doubtful accounts at December 31, 2015 and 2014. Accounts receivable of zero and $779,000 were charged off against the allowance for doubtful accounts during the years ended December 31, 2015 and 2014, respectively.