[ X ] ANNUAL REPORT PURSUANT TO SECTION 13 OR 15(D)
OF THE SECURITIES EXCHANGE ACT OF 1934
FOR THE FISCAL YEAR ENDED DECEMBER 31, 2002
OR
[ ] TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(D)
OF THE SECURITIES EXCHANGE ACT OF 1934
COMMISSION FILE NUMBER 0-18311
NEUROGEN CORPORATION
(Exact name of registrant as specified in its charter)
|
DELAWARE |
22-2845714 |
35 NORTHEAST INDUSTRIAL ROAD
BRANFORD, CONNECTICUT 06405
(Address of principal executive offices) (Zip Code)
(203) 488-8201
(Registrant's telephone number, including area code)
Securities
registered pursuant to Section 12(b) of the Act:
None
Securities registered pursuant to Section 12(g) of the Act:
Common Stock, par value $.025 per share (the "Common Stock")
(Title of Class)
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 filing requirements for the past 90 days. YES [X] NO [ ]
Indicate by check mark if disclosure of delinquent filers pursuant to Item 405 of Regulation S-K 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. [X]
Indicate by check mark whether the registrant is an accelerated filer (as defined in Rule 12b-2 of the Act). Yes [X] No [ ]
The approximate aggregate market value of the registrant’s Common Stock held by non-affiliates was $158,297,000, based on the closing price of a share of Common Stock as reported on the NASDAQ National Market on June 28, 2002, which is the last business day of the registrant’s most recently completed second fiscal quarter. In determining the market value of non-affiliate voting stock, shares of Common Stock beneficially owned by officers and directors and one shareholder owning more than 20% of the Common Stock have been excluded from the computation. This number is provided only for purposes of this report and does not represent an admission by either the registrant or any person as to the status of such person.
As of February 28, 2003, the registrant had 17,955,859 shares of Common Stock outstanding.
DOCUMENTS INCORPORATED BY REFERENCE
(1) Portions of the Neurogen Corporation Proxy Statement for the Annual Meeting of Stockholders to be held on May 19, 2003 are incorporated by reference into Items 10, 11, 12 and 13 of Part III of this Form 10-K.
PART I
ITEM 1. BUSINESS
Overview
Neurogen Corporation (NASDAQ: NRGN) (“Neurogen” or “the Company”), incorporated under the laws of the State of Delaware in 1987, is a drug discovery and development company targeting new small molecule drugs to improve the lives of patients suffering from disorders with significant unmet medical needs including inflammation, pain, insomnia, depression, anxiety and obesity. Neurogen has generated a portfolio of compelling new drug programs through its fully integrated drug discovery and development processes. Neurogen’s Accelerated Intelligent Drug Discovery (“AIDD”)™ process and its expertise in cellular functional assays enhance the Company's ability to rapidly and cost effectively identify small molecule drug candidates. Small molecule drugs typically are suitable for oral administration as a pill, while large molecule drugs typically are administered by injection. The Company conducts its research and development independently and, when advantageous, collaborates with leading pharmaceutical companies during the drug research and development process to obtain additional resources and to access complementary expertise. Currently, Neurogen has active collaborations with Pfizer and Aventis.
Neurogen has diversified its drug discovery and development efforts across a broad number of disease-related targets and employs a strategy designed to efficiently discover multiple drug candidates for each target. In addition, several of the Company’s programs focus on medical targets which are implicated in numerous, related disease states. Throughout the pharmaceutical industry the majority of all drug candidates fail to overcome all of the obstacles on the way to commercialization. Because of this high attrition rate, the Company believes that the true value of a drug discovery and development company’s pipeline is most accurately measured by the company’s ability to rapidly discover multiple generations of improved candidates within each of several programs. Neurogen believes that this ability to rapidly and systematically produce multiple generations of drug candidates in multiple programs is the Company’s most valuable asset. Although much smaller than major pharmaceutical companies, Neurogen has discovered ten small molecule drug candidates that together with our pharmaceutical company partners have entered human clinical trials. During 2002, the Company completed Phase I human testing (see Government Regulation section below) of its lead drug candidate for the treatment of inflammatory disorders and is currently conducting two Phase II trials in rheumatoid arthritis and asthma. Neurogen owns all commercial rights to this program. Another candidate from the Company’s program for the treatment of insomnia is currently being tested in Phase I human trials by our partner, Pfizer Inc (“Pfizer”).
Background on the Drug Discovery Industry
The Traditional Drug Discovery Process
Most drugs work by binding to a particular protein, cell, or receptor, called a target, in the human body, thereby altering communication between cells or otherwise regulating cellular activity. Therefore, the traditional path to discovering small molecule drugs typically begins with the identification of a biological target that is believed to regulate cellular communication or activities which could be modulated to treat a given disorder. A test, or assay, is then developed in order to expose compounds to the target and determine whether biological activity occurs. Such an assay facilitates the screening of the target against a library of many compounds that have been synthesized in the laboratory. Compounds that bind to the target protein and alter its activity are referred to as "hits." Medicinal chemists then work to improve, or optimize these hits until they have sufficient potency to become lead candidates and then improve their “drug-like” properties, such as gastrointestinal absorption, stability, freedom from unwanted activities, etc., with the goal of producing a successful drug development candidate.
Some drug companies try to streamline the drug discovery process by copying chemical structures from known active compounds. Even taking this approach, however, the number of possible compounds that could be made is too vast to actually test against even a single target using any available technology. Generally, the search is further narrowed only by educated guessing. As a result of the uncertainty of this approach, traditional methods can take many years or may fail entirely.
If it were possible to predict in advance which compounds would result in a hit, and which chemical changes would help optimize hits into drug candidates, the drug discovery process would be vastly simplified. Unfortunately, the traditional drug discovery process has had to rely on a trial and error approach that has proven extremely expensive, inefficient and unreliable. Optimization of hits to achieve the extremely delicate balance of properties necessary for a successful drug is still a daunting task. Most hits are never optimized into successful drugs despite years of effort.
Neurogen’s Competitive Advantage
Neurogen’s drug discovery and development platform is designed to rapidly discover small molecule drug candidates for medical targets where other pharmaceutical or biotechnology companies have failed or for recently discovered targets. The Company’s proprietary platform enables the rapid and efficient discovery of compounds that hit potential drug targets, evaluate the utility of those targets, and optimize useful hits into new drug candidates. Neurogen’s C5a program for inflammatory diseases serves as a recent example of the Company’s capabilities. While many in the pharmaceutical industry searched for many years to discover small molecule C5a drug hits, Neurogen believes it is the first to discover small molecule C5a antagonists and, more importantly, the first to optimize these hits and advance a small molecule C5a antagonist drug candidate into human testing.
Neurogen discovers and develops orally available, or small molecule drugs which are orally available. Small molecule drugs are usually more stable and easily absorbed through cell layers than large molecule drugs, and so in most cases may be administered as a pill, a patch, or an ointment. In addition, small molecule drugs are generally much easier and less expensive to manufacture, distribute, and store. Protein-based large molecule drugs typically are administered by injection and require refrigeration, while most small molecule drugs do not. Small molecule drugs can also be safely shipped and stored at regular temperatures. Small molecule drugs that can be taken orally currently make up about three quarters of the sales of the top 100 prescription drugs. Where there is a choice, patients generally would rather take a pill than an injection.
Neurogen's Business Strategy
Neurogen's vision is to excel at the creation of small molecule drugs using a seamless, integrated discovery, development, clinical and regulatory paradigm. The following are the key elements of the business strategy the Company is employing to achieve the Neurogen vision:
Components of Neurogen's Discovery and Development Platform
The Company’s
AIDD™ system, as well as its focused compound library
and Virtual Library™, are key components of the drug discovery infrastructure.
AIDD™ is an integrated system of hardware, software, and processes that
allows scientists to improve on the trial and error approach traditionally
associated with drug discovery and development. This system incorporates automated
robotics guided by state-of-the-art computerization, including neural network-based
artificial intelligence, to aid the Company’s scientists in decision-making,
in the design, modeling, synthesis and screening of new chemical compounds.
Neurogen’s AIDD™ system works in tandem with the Company’s
focused compound library. Instead of randomly generating a compound library
for chemical diversity as many other pharmaceutical and drug discovery companies
have done, Neurogen has chosen to bias or "enrich" its compound library
in favor of selected families of compounds. Because the number of small organic
compounds
that can be synthesized is virtually infinite, the Company believes that
to be successful in the drug discovery process, it is not the biggest or
most diverse library that counts, but rather the richest and most intelligently
designed.
Also critical to Neurogen’s drug discovery and development capabilities
is the Company’s biological expertise. Neurogen believes it has one
of the leading receptor biology teams in the industry, and utilizes this
expertise in the design and construction of screening assays to capitalize
on medical targets. The Company focuses on discovering novel drugs, and all
of the drug candidates that have entered human testing in clinical trials
have worked by new or more selective target mechanisms which have the potential
to provide significant therapeutic advantages over existing drugs.
Neurogen Drug Programs
Neurogen designs and develops drugs that have the potential to offer enhanced therapeutic efficacy or reduced side effects over drugs currently available to treat a particular disease. Most of the Company’s programs address novel targets for which significant scientific evidence exists to suggest that the target mechanism plays a meaningful role in the disease or disorder. By designing drugs specifically targeting a new more selective mechanism, Neurogen compounds offer the potential for equivalent or improved efficacy with fewer side effects than drugs currently on the market, or may cause markets to grow in areas where few effective therapeutics currently exist. In addition, drugs active against new targets may offer the possibility of adding to or synergistically improving existing therapy.
The following table summarizes our most advanced programs in our current drug pipeline:
Disorder |
Target Mechanism |
Program Status |
Commercial
Rights |
| Inflammation and Autoimmune Disease: Rheumatoid arthritis Asthma |
C5a | Phase II (NGD 2000-1) Phase II (NGD 2000-1) |
Neurogen |
| Insomnia | GABA | Phase I (NGD 96-3) |
Pfizer Marketing/ Neurogen Royalty |
| Pain | VR-1 | Preclinical research and development | Neurogen |
| Depression and Stress | CRF-1 | Preclinical research | Aventis Pharmaceuticals Inc. Marketing/ Neurogen Royalty |
| Obesity | MCH-1 | Preclinical research | Neurogen |
Below, we describe our most significant active drug development programs in detail.
Inflammation Program: C5a receptor antagonist
Inflammatory and autoimmune conditions are debilitating diseases afflicting millions of Americans, causing substantial human suffering, and costing the United States economy billions of dollars in health care and lost productivity. These diseases include the many different forms of arthritis, autoimmune diseases, and pulmonary disorders. Most are chronic and many cause life-long pain, disability, or disfigurement. These diseases affect people of all ages, racial and ethnic populations, and economic strata. Industry estimates value sales of drugs to treat inflammation, autoimmune, and pulmonary disorder at over $23 billion annually.
Neurogen scientists believe that blocking the activation of the C5a receptor of the complement cascade may work to treat inflammation in rheumatoid arthritis, other autoimmune diseases and asthma. Complement component C5a is a protein in the body that is part of the innate immune system that protects the body against invading micro-organisms attracting and activating white blood cells, but when inappropriately stimulated may trigger the immune system to start attacking the body's own tissues, an inappropriate reaction central to autoimmune and inflammatory diseases.
Rheumatoid arthritis involves inflammation in the lining of the joints and/or other internal organs. It is a systemic disease affecting the entire body and is one of the most common forms of arthritis, characterized by the inflammation of the membrane lining the joint, resulting in pain, stiffness, warmth, redness and swelling. This disease affects 2.1 million Americans, mostly women--1.5 million women suffer from rheumatoid arthritis as compared to 600,000 men. Musculoskeletal conditions such as rheumatoid arthritis cost the U.S. economy nearly $65 billion in medical care and indirect expenses such as lost wages and production.
Currently, several types of drugs are used to treat rheumatoid arthritis. Recently, drugs which inhibit the tumor necrosis factor alpha (TNFa) protein, such as Enbrel® and Remicade®, have demonstrated the ability to not only treat the symptoms of rheumatoid arthritis but also slow the progression of the disease by inhibiting the destruction of healthy joint tissue. However, as large molecule proteins, these drugs must be taken by injection and are expensive to manufacture, distribute and administer. Anti-tumor necrosis factor drugs also have some side effects such as development of antinuclear antibodies (these are antibodies seen in various autoimmune diseases such as Lupus), Urticaria (reddish blotchy areas on the skin), infections, and rejection of these antibodies by the patients own immune system (similar to the body's rejection of an organ transplant).
Other drugs used to treat rheumatoid arthritis include the COX-2 inhibitors. Since the synthesis of aspirin in 1897, inhibitors of cyclooxygenase (an enzyme that controls inflammation) have been a source of relief from arthritis pain. These drugs are now collectively called non-steroidal anti-inflammatory drugs (NSAID’s). The newest generation of NSAID’s is called COX-2 selective inhibitors. Brand names of this type of medication include Celebrex® and Vioxx®. While COX-2 inhibitors are small molecule drugs and feature less risk of side effects such as blood thinning or stomach ulceration than earlier treatments, these drugs do not slow the tissue destruction associated with the progression of rheumatoid arthritis.
Neurogen believes that blocking the C5a receptor in patients with rheumatoid arthritis may inhibit the destruction of healthy tissue by blunting the immune system’s overreaction to the presence of the C5a protein. The Company believes that our small molecule drug candidate, taken as a pill for the treatment of rheumatoid arthritis, may offer many of the advantages of the COX-2 inhibitors with the potential to also slow the progression of the disease.
Asthma is an inflammatory condition suffered by more Americans than ever before. This chronic lung disease is characterized by inflammation of the air passages, which results in the temporary narrowing of the airways that transport air from the nose and mouth to the lungs. The prevalence of asthma has been increasing since the early 1980’s across all age, sex, and racial groups and affects more children than adults. It is the only chronic disease, besides AIDS and tuberculosis, with an increasing death rate; each day 14 Americans die from asthma.
The cost of asthma to the American economy is estimated to be over $11.3 billion; direct costs accounted for $7.5 billion with hospitalizations accounting for the single largest portion. Indirect costs were $3.8 billion of the total.
Currently, a number of medications are available to treat asthma. These treatments target different aspects of the disease: some focus on bronchospasm, or contraction of the muscles which line the airways, while others have their main effect on inflammation, swelling, and mucus production. Side effects can include jitteriness, palpitations, or abnormally fast heart rhythms. Steroids are the most powerful inflammation inhibitors currently available and are administered both orally and through inhalation. At this time, there is only limited information on adverse side effects from inhaled steroids, especially with higher doses. However, there is a concern for the potential of adverse effects and a recent clinical report raises concerns about the use of high dose inhaled steroids and an increased risk of developing ocular hypertension or glaucoma. Neurogen believes that blocking the C5a receptor in patients with asthma may represent an alternative to existing treatments.
The Company has identified several small molecule compounds that potently block the activation of C5a receptors. Neurogen's leading compound in this program, NGD 2000-1, is currently starting two Phase II clinical trials for rheumatoid arthritis and for asthma.
In the rheumatoid arthritis Phase II study, Neurogen will examine the ability of the compound to lower the levels of C-reactive protein (CRP is an important biomarker in rheumatoid arthritis patients) in patients with mild to moderate conditions. The study is multi-centered, double blinded and placebo controlled and will explore multiple doses of NGD 2000-1.
The asthma Phase II trial will study the safety and preliminary efficacy of NGD 2000-1 in patients with mild to moderate asthma. This trial is multi-centered, double-blinded, and placebo-controlled and will assess multiple doses of NGD 2000-1 using improvement in lung capacity (FEV1) as the primary endpoint.
Phase I study results indicated that NGD 2000-1 was safe and well-tolerated. These studies also indicated that NGD 2000-1 interacts with the 3A4 liver enzyme which metabolizes many drugs. This characteristic may limit the use of NGD 2000-1 by patients also taking other medications which are metabolized by the 3A4 enzyme. Further studies will be required to determine the extent of any such limitation.
To date, Neurogen has retained all rights to this C5a antagonist program.
Insomnia Program: unique GABA modulation profile
Recent studies indicate that as many as 20 million people in the United States experience chronic insomnia and an additional 20 to 30 million Americans experience intermittent sleep disorders. Industry analysts estimate that the annual market for drugs to treat insomnia is more than $1.5 billion worldwide and over $500 million in the United States. While currently marketed drugs to treat sleep disorders, known as hypnotics, are effective, they may cause numerous side effects, including "hangovers," rebound insomnia, short-term memory loss and addiction. Neurogen is developing drugs to treat sleep disorders, primarily insomnia, which selectively modulate certain receptor subtypes of the gamma-aminobutyric acid (GABA) neurotransmitter system.
The link between the GABA system and sleep is illustrated by the benzodiazepine class of drugs such as Valium(R), which cause sleepiness, and by drugs marketed to treat insomnia such as Ambien(R) and Sonata(R), which work through the same broad range of GABA receptors as the benzodiazepines. Neurogen has identified drug candidates to treat insomnia that have a more specific GABA receptor binding profile and limit the degree of receptor activation than currently marketed drugs. Animal studies, to date, suggest that these compounds are efficacious in inducing sleep with fewer side effects than existing therapies. Drugs to treat insomnia should not only induce sleep but they should have pharmacokinetic properties which cause the drug to work quickly and then be cleared from the patient's body before morning. Pfizer, our partner in this program, is currently evaluating our lead compound, NGD 96-3, in Phase I clinical studies.
Pain Management Program: VR-1 receptor antagonist
Industry sources estimate more than 60 million persons in the United States suffer from some type of persistent or recurrent acute pain sufficient to significantly impact their lives. Not only does such chronic pain adversely affect physical and psychological well-being, it also costs society billions of dollars in lost productivity, health care expenditures, and disability compensation. The health care costs incurred by patients with chronic pain range from $500 to more than $35,000 per year. Among cancer patients, available estimates suggest that chronic pain affects up to 95% of patients with advanced disease with less than 50% of these experiencing effective pain relief.
The Company believes that its approach to pain management offers the potential to relieve pain without the side effect profile of existing pain drugs such as opiates and non-steroidal anti-inflammatory drugs (NSAID’s). Opiates can result in respiratory depression, gastrointestinal tract motility, and are frequently abused by patients. NSAID’s side effect profile includes gastrointestinal tract toxicity and negative cardiovascular and renal effects.
Neurogen is currently advancing multiple, highly potent candidates for potential development in its vanilloid receptor-1 (VR-1) program, which targets a broad spectrum of pain indications including osteoarthritis, neuropathic pain, and bone cancer pain.
Studies in genetically altered mice lacking the VR-1 receptor provide strong evidence for a VR-1 role in the sensation of noxious heat as well as thermal hyperalgesia (heightened sensitivity to pain) in models of inflammatory pain. Neurogen researchers believe that a drug which blocks the VR-1 receptor could benefit patients suffering from various types of inflammatory pain states and specific types of nociceptive, or localized, pain.
Neurogen has established a broad intellectual property position on this new target for the relief of pain. In addition to establishing the first patent publications on small molecule VR-1 antagonists, the Company has been awarded a patent on a human VR-1 receptor gene sequence, has broad applications filed encompassing highly potent chemotypes, and has patent applications pending on the general use of VR-1 antagonists for the treatment of peripheral pain.
Neurogen is currently profiling and evaluating its most advanced compounds in consideration for human testing. To date, Neurogen retains all commercial rights to this program.
Depression/Anxiety Program: CRF-1 receptor antagonist
Depression is one of the most prevalent mental illnesses in the United States, affecting approximately 17 million people or 9% of the adult population annually according to the National Institute of Mental Health. While recent pharmaceutical research has led to improved drugs, such as Prozac(R), for the treatment of depression, these medications have limitations in their use, primarily because of their slow onset of therapeutic action (often greater than 10 days from the commencement of dosing), lack of efficacy in some patients, and side effects such as sexual dysfunction. Industry analysts estimate the current annual market for antidepressants to be over $17 billion worldwide.
Anxiety and stress are conditions commonly associated with depression. A number of neuropeptide receptors that appear to be involved in stress responses, including receptors for CRF-1, exhibit altered characteristics in depressed patients.
Neurogen believes that an orally available drug candidate that blocks the CRF-1 receptor may be efficacious in relieving depression, anxiety and/or stress related disorders without significant side effects. A number of companies are seeking to develop CRF-1 drug candidates. To date, many companies have experienced difficulties in identifying CRF-1 blockers which have drug properties appropriate for commercialization. Neurogen believes this is due to the fact that the scope of known chemical structures which block CRF-1 is relatively narrow.
Neurogen has discovered a number of compounds that block the CRF-1 receptor subtype and have demonstrated efficacy in animal models of depression and stress. Importantly, the chemical structure of these compounds is significantly outside of the scope of known CRF-1 blockers. We believe these novel chemical templates hold the potential of avoiding the development issues of known CRF-1 structures. In December of 2001, Neurogen entered into a collaborative agreement with Aventis Pharmacuticals Inc. (“Aventis”) (described below) to research and develop compounds to modulate CRF-1 receptors. Together Neurogen and Aventis are currently optimizing lead candidates in this program.
Obesity/Diabetes Program: MCH-1 receptor antagonist
Neurogen is optimizing lead compounds blocking the melanin concentrating hormone receptor-1 (MCH-1), which is an important mediator of food intake. These receptors are expressed in the hypothalamus, the feeding center of the brain. While obesity is caused by a complex process involving many hormones, neurotransmitters, nerve cells, and genes, the MCH neurotransmitter is now known to play a key role in controlling eating behavior. In industry preclinical studies, deleting the genes coding of the MCH peptide or MCH receptor gene has resulted in lean animals, while administering MCH peptide caused increased weight gain. The Company is currently optimizing lead drug candidates in this program. Neurogen owns all commercial rights to its MCH-1 receptor antagonist program.
Neurogen Collaborations
Neurogen conducts its research and development independently and, when advantageous, collaborates with world-class pharmaceutical companies during the drug development process to obtain additional resources and to access complementary expertise. The Company's collaboration agreements may provide funding for drug discovery and development programs as well as clinical, manufacturing, marketing, and sales expertise. At the same time, Neurogen has retained certain rights to future royalties or profit-sharing for successful drugs resulting from collaborative programs. These strategic alliances balance the Company's exposure to research and development risks inherent in the industry while retaining a share in the success of future products.
A summary of the material terms of agreements which relate to two currently partnered programs follows:
o The 1994 Pfizer Agreement - covers our GABA-based sleep disorder
program
- Pfizer purchased approximately 1.1 million shares of our common
stock for approximately $9.9 million.
- We received funding from 1994 through 2001 for research and
development under this program.
- Pfizer has the right to determine when to advance compounds in the
clinical process.
- We will receive milestone payments if specified development and
regulatory objectives are achieved.
- Pfizer received the exclusive worldwide license to manufacture,
use and sell GABA-based sleep disorder products developed in the
collaboration.
- Pfizer is required to pay us royalties based on net sales levels,
if any, for such products.
- In December 2001, our collaborative research program came to its
scheduled conclusion. Pfizer is currently developing our lead candidate from
this collaboration in Phase I studies and evaluating other candidates from
the program to determine whether further development is desirable.
o The 2001 Aventis Agreement – covers
our CRF1-based depression and anxiety program
- Aventis paid $10 million for the licensing of Neurogen's CRF1
drug candidates and technology.
- Neurogen receives committed research payments and is reimbursed for research
expenses for three years from the effective date.
- Neurogen will receive milestone payments if specified development
and regulatory objectives are achieved.
- Aventis received the exclusive worldwide license to manufacture,
use and sell CRF1 receptor modulatory products developed in the
collaboration.
- Aventis is required to pay Neurogen royalties based on net sales levels,
if any, for such products.
Neurogen incurred research and development costs (net of stock compensation) of $34,093,000, $34,494,000 and $28,048,000 for the years ending December 31, 2002, 2001 and 2000, respectively. During those same time periods, the Company recognized research and development revenue from its collaboration agreements (including the two agreements described above and other prior agreements), of $4,276,000, $3,056,000 and $9,205,000, respectively. Thus, during those time periods, overall research and development revenue as a percentage of total research and development costs (for both partnered and unpartnered programs) was 13%, 9% and 33%, respectively.
Patents and Proprietary Technology
Neurogen’s success depends, in part, on the Company’s
ability to obtain and enforce patents, maintain trade secrets and operate
without infringing
the intellectual property rights of third parties. Neurogen files patent applications
both in the United States and in foreign countries, as the Company deems appropriate,
for protection of both products and processes. At December 31, 2002, Neurogen
is the sole assignee of 204 issued United States patents and numerous foreign
patents.
Neurogen is not currently engaged in any research based on any technology transfer
that would obligate the Company to pay royalties to any third party.
The patent position of biotechnology and pharmaceutical firms is highly uncertain and involves many complex legal and technical issues. There is considerable uncertainty regarding the breadth of claims allowed in such cases and the degree of protection afforded under such patents. As a result, Neurogen cannot assure you that patent applications will be successful or that current or future patents will afford the Company protection against competitors. It is possible that Neurogen patents will be successfully challenged or that patents issued to others may preclude the Company from commercializing its products. Litigation to establish the validity of patents, to defend against infringement claims or to assert infringement claims against others can be lengthy and expensive, even if a favorable result is obtained. Moreover, much of the Company’s expertise and technology cannot be patented.
Neurogen also relies heavily on trade secrets and confidentiality agreements with collaborators, advisors, employees, consultants, vendors and other service providers. The Company cannot assure you that these agreements will not be breached or that trade secrets will not otherwise become known or be independently discovered by competitors. Neurogen’s business would be adversely affected if competitors were able to learn the Company’s secrets or if the Company were unable to protect its intellectual property.
Competition
The biopharmaceutical industry is highly competitive and subject to rapid and substantial technological change. Developments by others may render Neurogen’s drug candidates or technologies noncompetitive or obsolete, or we may be unable to keep pace with technological developments or other market factors. Technological competition in the industry from pharmaceutical and biotechnology companies, universities, governmental entities and others diversifying into the field is intense and is expected to increase. Many of these entities have significantly greater research and development capabilities than Neurogen, as well as substantially more marketing, manufacturing, financial and managerial resources. These entities represent significant competition. In addition, acquisitions of, or investments in, competing development-stage pharmaceutical or biotechnology companies by large corporations could increase such competitors' financial, marketing, manufacturing and other resources.
Competitors have developed or are in the process of developing products or technologies that are, or in the future may be, the basis for competitive products. The Company’s competitors may develop products that are safer, more effective or less costly than any Neurogen products or may be able to complete their development more quickly. Neurogen would be at a significant competitive disadvantage if a competitor developed and successfully commercialized a drug similar to a Neurogen drug candidate ahead of the Company’s efforts.
Manufacturing
Neurogen is currently relying, in part, on third-party manufacturers to produce large quantities of development candidate compounds for preclinical development and dosage forms of these candidates to support clinical trials.
Pfizer manufactures or will be responsible for manufacturing, drugs for clinical trials which are subject to the 1994 Pfizer Agreement and has the right to manufacture future products under this collaboration, if any, for commercialization.
Aventis will be responsible for manufacturing, or having manufactured, drugs for clinical trials which are subject to the Aventis Agreement, and has the right to manufacture future products under the collaboration, if any, for commercialization.
With respect to compounds not currently subject to collaborations, the Company currently utilizes third-party manufacturers for preclinical development and clinical trials.
Sales and Marketing
Neurogen's strategy is to market products either directly or through co-promotion arrangements or other licensing arrangements with large pharmaceutical or biotechnology companies. The Company does not expect to establish a direct sales capability for at least the next several years, though it may pursue such a capability in the future. Pfizer has the right to market worldwide future products, if any, resulting from the Pfizer Agreement. Aventis has the right to market worldwide future products, if any, resulting from the Aventis Agreement.
Government Regulation
The production and marketing of Neurogen’s products, as well as research and development activities are subject to regulation for safety, efficacy and quality by numerous governmental authorities in the United States and other countries. In the United States, drugs are subject to rigorous federal regulation (Food and Drug Administration or FDA) and, to a lesser extent, state regulation. The Federal Food, Drug and Cosmetic Act, as amended, and the regulations promulgated thereunder, and other federal and state statutes and regulations govern, among other things, the testing, manufacture, safety, efficacy, labeling, storage, record keeping, approval, advertising and promotion of our products. Product development and approval within this regulatory framework will take a number of years and involve the expenditure of substantial resources.
The steps required before a pharmaceutical agent may be marketed in the United States include:
1. Preclinical laboratory tests, in vivo preclinical studies and formulation studies,
2. The submission to the FDA of an Investigational New Drug Application (IND) for human clinical testing which must become effective before human clinical trials can commence,
3. Adequate and well-controlled human clinical trials to establish the safety and efficacy of the drug,
4. The submission of a New Drug Application (NDA) or Product License Application to the FDA, and
5. FDA approval of the NDA or Product License Application prior to any commercial sale or shipment of the drug.
In addition to obtaining FDA approval for each product, each domestic drug manufacturing establishment must be registered with, and approved by, the FDA. Domestic manufacturing establishments are subject to biennial inspections by the FDA and must comply with the FDA's Good Manufacturing Practices for both drugs and devices. To supply products for use in the United States, foreign manufacturing establishments must comply with Good Manufacturing Practices and are subject to periodic inspection by the FDA or by regulatory authorities in such countries under reciprocal agreements with the FDA.
Preclinical testing includes laboratory evaluation of product chemistry and formulation, as well as animal studies to assess the potential safety and efficacy of the product. Preclinical safety tests must be conducted by laboratories that comply with FDA regulations regarding Good Laboratory Practices. The results of the preclinical testing are submitted to the FDA as part of an IND and are reviewed by the FDA prior to the commencement of human clinical trials. Unless the FDA objects to an IND, the IND will become effective 30 days following its receipt by the FDA.
Clinical trials involve the administration of the new drug to healthy volunteers or to patients under the supervision of a qualified principal investigator. Clinical trials must be conducted in accordance with Good Clinical Practices under protocols that detail the objectives of the study, the parameters to be used to monitor safety and the efficacy criteria to be evaluated. Each protocol must be submitted to the FDA as part of the IND. Further, each clinical study must be conducted under the auspices of an independent Institutional Review Board. The Institutional Review Board will consider, among other things, ethical factors, the safety of human subjects and the possible liability of the institution. Compounds must be formulated according to Good Manufacturing Practices.
Clinical trials are typically conducted in three sequential phases, but the phases may overlap. In Phase I, the initial introduction of the drug into healthy human subjects, the drug is tested for safety, absorption, dosage tolerance, metabolism, bio-distribution, excretion and pharmacodynamics (clinical pharmacology). Phase II typically involves studies in a limited patient population:
1. to determine the efficacy of the drug for specific, targeted indications,
2. to determine dosage tolerance and optimal dosage, and
3. to identify possible adverse side effects and safety risks.
When a compound is found to be effective and to have an acceptable safety profile in Phase II evaluations, Phase III trials are undertaken to further evaluate clinical efficacy and to test for safety within an expanded patient population at geographically dispersed clinical study sites. Neurogen or the FDA may suspend clinical trials at any time if it is believed that the individuals participating in such trials are being exposed to unacceptable health risks.
The results of the pharmaceutical development, preclinical studies and clinical studies are submitted to the FDA in the form of a NDA for approval of the marketing and commercial shipment of the drug. The testing and approval process is likely to require substantial time and effort. The approval process is affected by a number of factors, including the severity of the disease, the availability of alternative treatments and the risks and benefits demonstrated in clinical trials. Consequently, there can be no assurance that any approval will be granted on a timely basis, if at all. The FDA may deny an NDA if applicable regulatory criteria are not satisfied, require additional testing or information or require post-marketing testing and surveillance to monitor the safety of a company's products if it does not believe the NDA contains adequate evidence of the safety and efficacy of the drug. Notwithstanding the submission of such data, the FDA may ultimately decide that an NDA does not satisfy its regulatory criteria for approval. Moreover, if regulatory approval of a drug is granted, such approval may entail limitations on the indicated uses for which it may be marketed. Finally, product approvals may be withdrawn if compliance with regulatory standards is not maintained or if problems occur following initial marketing.
Among the conditions for NDA approval is the requirement that any prospective manufacturer's quality control and manufacturing procedures conform to Good Manufacturing Practices. In complying with standards set forth in these regulations, manufacturers must continue to expend time, money and effort in the area of production and quality control to ensure full technical compliance. Manufacturing establishments, both foreign and domestic, also are subject to inspections by or under the authority of the FDA and by other federal, state or local agencies.
Whether or not FDA approval has been obtained, approval of a product by regulatory authorities in foreign countries must be obtained prior to the commencement of commercial sales of the product in such countries. The requirements governing the conduct of clinical trials and product approvals vary widely from country to country, and the time required for approval may be longer or shorter than that required for FDA approval. Although there are some procedures for unified filings for certain European countries, in general, each country at this time has its own procedures and requirements.
In addition to regulations enforced by the FDA, Neurogen is also subject to regulation under the Occupational Safety and Health Act, the Environmental Protection Act, the Toxic Substances Control Act, the Resource Conservation and Recovery Act and other present and potential future federal, state or local regulations. The Company’s research and development involves the controlled use of hazardous materials, chemicals, and various low-level radioactive compounds. Although the Company believes that safety procedures for handling and disposing of such materials comply with the standards prescribed by state and federal regulations, the risk of accidental contamination or injury from these materials cannot be completely eliminated. In the event of any accident, Neurogen could be held liable for any damages that result and any such liability could exceed our resources.
Employees
As of December 31, 2002, the Company had 163 full-time employees, of which 121 persons were scientists and, of these scientists, 56 had Ph.D. degrees. None of the employees are covered by collective bargaining agreements, and the Company considers relations with employees to be good. All current scientific personnel have entered into confidentiality and non-competition agreements with the Company.
Research and Development Expenses
The Company incurred research and development expenses of $34,093,000, $34,494,000 and $28,048,000 in 2002, 2001, and 2000, which exclude non-cash stock compensation charges of $51,000, $901,000 and $4,637,000, respectively.
Available Information
The Company’s website address is www.neurogen.com. Neurogen makes available free of charge through its website all of the Company’s filings with the Securities and Exchange Commission (“SEC”), including its Annual Report on Form 10-K, Quarterly Reports on Form 10-Q, Current Reports on Form 8-K and all amendments to these reports. The Company’s filings are made available as soon as reasonably practicable after such material is electronically filed with the SEC. Copies are also available, without charge, from Neurogen Corporation, 35 Northeast Industrial Road, Branford, CT 06405.
ITEM 2. PROPERTIES
The Company conducts its operations in laboratory and administrative facilities on a single site located in Branford, Connecticut. The total facilities under ownership comprise approximately 148,000 square feet, of which 106,000 square feet is in use. Approximately 27,000 square feet has not yet been adapted for the Company’s research and development efforts.
In 1995, the Company leased approximately 24,000 square feet of a 39,000 square foot building under a ten-year agreement, which provided an option to purchase the entire facility effective after the fifth year of the original term of the lease. In January 2001, Neurogen elected to purchase the entire facility for $2.4 million. The additional space acquired of approximately 15,000 square feet continues to be leased through Neurogen to the third-party tenants who occupied the facilities at the time of purchase.
ITEM 3. LEGAL PROCEEDINGS
The Company knows of no material litigation or proceeding pending or threatened to which Neurogen is, or may become, a party.
ITEM 4. SUBMISSION OF MATTERS TO A VOTE OF SECURITY HOLDERS
None.
CAUTIONARY STATEMENT FOR PURPOSES OF THE
"SAFE HARBOR" PROVISIONS OF THE PRIVATE SECURITIES
LITIGATION REFORM ACT OF 1995.
Except for historical matters, the matters discussed in this Form 10-K are" forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995 or any rules, regulations or releases of the Securities and Exchange Commission with respect thereto. Forward-looking statements in this Form 10K include, but are not limited to, statements in Item 1 under the caption "Business--Neurogen Drug Programs" with respect to the Company's various product development programs and statements in Item 7 under the caption "Management's Discussion and Analysis of Financial Condition and Results of Operations" with respect to the sufficiency of the Company's cash balance to fund planned operations. In addition, the Company may from time to time make forward-looking statements in the future.
Neurogen wishes to caution readers, and others to whom forward-looking statements are addressed, that any such forward-looking statements are not guarantees of future performance and that actual results may differ materially from estimates in the forward looking statements. In addition to the important factors described elsewhere in this Form 10-K and the Company's other filings with the Securities and Exchange Commission, the following important factors, among others, could affect Neurogen's actual future results and could cause such results to differ materially from estimates expressed in any forward-looking statements made by, or on behalf of, Neurogen:
PART II
ITEM 5. MARKET FOR REGISTRANT'S COMMON EQUITY AND RELATED STOCKHOLDER MATTERS
The common stock of Neurogen is traded on the NASDAQ Stock Market under the symbol NRGN. As of February 28, 2003, there were approximately 209 holders of record of the Company's common stock. No dividends have been paid on the common stock to date, and the Company currently intends to retain any earnings for further development of the Company's business.
The following table sets forth the high and low closing bid prices for the common stock as reported by NASDAQ.
HIGH |
LOW |
||
| FISCAL 2002: | |||
| First Quarter | $17.5100 |
$12.6700 |
|
| Second Quarter | 14.2500 |
8.3000 |
|
| Third Quarter | 12.1000 |
7.2500 |
|
| Fourth Quarter | 8.7300 |
3.6300 |
|
| FISCAL 2001: | |||
| First Quarter | $36.9375 |
$19.4688 |
|
| Second Quarter | 23.5938 |
18.3700 |
|
| Third Quarter | 23.4300 |
13.5500 |
|
| Fourth Quarter | 22.6000 |
15.6100 |
ITEM 6. SELECTED FINANCIAL DATA
For
the Year Ended December 31 (in thousands, except per share data) |
|||||||||
|
|
|||||||||
2002 |
2001 |
2000 |
1999 |
1998 |
|||||
|
|
|
|
|
||||||
| Total operating revenues | $
15,725 |
$
11,514 |
$
20,413 |
$
10,209 |
$
11,081 |
||||
| Total operating expenses | $
41,382 |
$
42,577 |
$
40,858 |
$
28,465 |
$
24,834 |
||||
| Net loss | $(23,692) |
$(25,362) |
$(15,471) |
$(14,618) |
$
(9,458) |
||||
| Net loss per share-basic and diluted | $
(1.35) |
$
(1.45) |
$
(0.94) |
$
(1.00) |
$
(.66) |
||||
| Total assets | $115,779 |
$145,956 |
$142,588 |
$
92,134 |
$101,810 |
||||
| Long-term debt | $
19,650 |
$
21,029 |
$
1,912 |
$
1,912 |
$
- |
||||
| Stockholders' equity | $
83,297 |
$105,383 |
$126,120 |
$
84,710 |
$
98,567 |
||||
| Weighted
average number of shares outstanding- basic and diluted |
17,614 |
17,441 |
16,490 |
14,576 |
14,419 |
||||
ITEM 7. MANAGEMENT'S DISCUSSION AND ANALYSIS OF FINANCIAL CONDITION AND
RESULTS OF OPERATIONS
OVERVIEW
Since its inception in September 1987, Neurogen has been engaged in the discovery and development of drugs. The Company has not derived any revenue from product sales and expects to incur significant losses in most years prior to deriving any such product revenues. Revenues to date have come from five collaborative research agreements, one license agreement and one technology transfer agreement.
The preparation of Neurogen's financial statements in conformity with generally accepted accounting principles requires management to make certain estimates and assumptions that affect the reported amounts of assets and liabilities and disclosure of contingent liabilities at the date of the financial statements and the reported amounts of revenues and expenses during the reporting period. Management makes estimates in the areas of revenue recognition, income taxes, stock-based compensation and marketable securities and investments. Estimates are based on historical experience and on various other assumptions that management believes to be reasonable under the circumstances. Actual amounts could differ from those estimates.
The Company believes the following critical accounting policies affect management's more significant judgments and estimates used in the preparation of Neurogen's financial statements:
Revenue Recognition
Each of Neurogen’s collaborative research, licensing and technology transfer agreements are significant since the terms of such arrangements may cause the Company’s operating results to vary considerably from period to period.
The Company has entered into collaborative research agreements which provide for the partial funding of specified projects in exchange for the grant of certain rights related to potential discoveries. Revenue under these arrangements typically includes upfront non-refundable fees, ongoing payments for specified levels of staffing for research and milestone payments upon occurrence of certain events. The upfront fees are recognized as revenue ratably over the period of performance under the research agreement. The research funding is recognized as revenue as the related research effort is performed. Revenue derived from the achievement of milestones is recognized when the milestone event occurs and such event represents the achievement of a specific, substantive goal measuring a substantive stage of development towards a long-term goal, such as the filing of a New Drug Application with the Food and Drug Administration.
Neurogen has also entered into, and now completed, a technology transfer agreement under which revenue has been recognized when a contractual arrangement exists, fees are fixed and determinable, delivery of the technology has occurred and collectibility is reasonably assured. When customer acceptance was required, revenue was deferred until acceptance occurred. Where there were on-going services or obligations after delivery, revenue has been recognized over the related term of the service on a percentage of completion basis, unless such service was maintenance, in which case revenue has been recognized on a straight line basis. For a contract with multiple elements, total contract fees are allocated to the different elements based on evidence of fair value.
Income Taxes
The liability method of Statement of Financial Accounting Standards (“SFAS”) No. 109, “Accounting for Income Taxes”, is used to account for income taxes. Deferred tax assets and liabilities are determined based on net operating loss carryforwards and differences between financial reporting and income tax bases of assets and liabilities. Deferred items are measured using the enacted tax rates and laws that are expected to be in effect when the differences reverse. Deferred tax assets may be reduced by a valuation allowance to reflect the uncertainty associated with their ultimate realization. Any subsequently recognized tax benefits relating to the valuation allowance for deferred tax assets would be recorded as an income tax benefit in the Statement of Operations or a charge to Additional Paid-In Capital.
Stock-Based Compensation
The Company primarily grants qualified stock options for a fixed number of shares to employees with an exercise price equal to the fair market value of the shares at the date of grant. The Company has also issued restricted stock to key executives which vest over specified service periods. The Company has adopted the disclosure-only provisions of SFAS No. 123, “Accounting for Stock-Based Compensation” and therefore accounts for grants of stock options and restricted stock in accordance with Accounting Principles Board (“APB”) Opinion No. 25, "Accounting for Stock Issued to Employees." Accordingly, Neurogen recognizes no compensation expense for the options when the option grants to employees have an exercise price equal to the fair market value at the date of grant and other relevant terms are fixed or determinable. If compensation cost for the Company's grant of stock awards was determined based on the fair value at the grant date consistent with the provisions of SFAS No. 123, the Company's net loss and loss per share would be materially effected.
The Company occasionally grants stock option awards to consultants. Such grants are accounted for pursuant to Emerging Issues Task Force (“EITF”) Issue No. 96-18, “Accounting for Equity Instruments That Are Issued to Other Than Employees for Acquiring, or in Conjunction with Selling, Goods or Services”, and accordingly recognizes compensation expense equal to the fair value of such awards. The fair value of each award is estimated using the Black-Scholes model with certain weighted average assumptions (described in Note 7 to the consolidated financial statements).
Marketable Securities
The Company invests in U.S. government and corporate debt securities. The fair value of these securities is subject to volatility and change. The Company considers its investment portfolio to be available-for-sale securities as defined in SFAS No. 115, "Accounting for Certain Investments in Debt and Equity Securities." Marketable securities at December 31, 2002 and 2001 consisted of debt securities with maturities of three months to six years. Available for sale securities are carried at fair value with the unrealized gains/losses reported as other comprehensive income. Realized gains and losses have been determined by the specific identification method and are included in investment income. Different classifications of the Company’s marketable securities pursuant to SFAS No. 115 would possibly result in material impacts to the valuation of the securities and investment income.
RESULTS OF OPERATIONS
Results of operations may vary from period to period depending on numerous factors, including the timing of income earned under existing or future collaborative research agreements, technology transfer agreements or joint ventures, the progress of the Company's partnered research and development projects, the size of the Company’s staff and the level of preclinical and clinical development spending on drug candidates in unpartnered programs. Neurogen believes its research and development costs may increase significantly over the next several years as its drug development programs progress. In addition, general and administrative expenses would be expected to increase to support any expanded research and development activities.
Years Ended December 31, 2002, 2001 and 2000
The Company's fiscal 2002 operating revenues increased 37 percent to $15.7 million from 2001 operating revenues of $11.5 million. The revenue increase consists of a $3.0 million increase in license fee revenues and a $1.2 million increase in research and development revenues. The $3.0 million increase in license fees is due to the recognition of a one-time $2.0 million payment from Pfizer to satisfy all obligations from Pfizer’s use of the AIDD™ technology as a part of the companies’ 1999 Technology Transfer Agreement (described below), a $1.8 million increase in license fees recognized from Aventis as part of the Aventis Agreement (described below) offset by a $0.8 million decrease in AIDD™ technology development and improvement services related to the Pfizer Technology Transfer Agreement. The increase in research revenues is due to a $4.1 million increase in research revenues from Aventis (to reflect a full year of research funding under the companies’ December 2001 collaboration agreement to develop drugs to treat depression and anxiety) offset in part by a $2.9 million decrease in revenues from Pfizer due to the scheduled conclusion in December 2001 of the companies’ joint research collaboration on GABA-based drugs.
Fiscal 2001 operating revenues decreased 44 percent from 2000 operating revenues of $20.4 million. This decrease was primarily due to a $5.9 million decrease in research and development revenues resulting from a scheduled reduction in the Company's staffing and related discovery research funding on GABA and neuropeptide Y (NPY) collaborative drug discovery programs with Pfizer which comprised $2.9 million of operating revenues in 2001 as compared to $8.8 million in 2000. The recognition of license fee revenues pursuant to the Pfizer Technology Transfer Agreement also decreased from $11.2 million in 2000 to $8.3 million in 2001.
Research and development expenses, excluding non-cash stock compensation charges, remained stable for fiscal 2002 at $34.1 million as compared to $34.5 million in 2001, and increased 23 percent in 2001 from $28.0 million in 2000. External development costs related to potential drug candidates decreased from $5.5 million in 2001 to $3.5 million in 2002 in part due to the assumption by Aventis commencing in December 2001 of the costs of developing potential drug candidates from the Company’s collaborative efforts. This decrease was offset by an overall increase in the Company’s ongoing investment in scientific personnel and research supplies. The increase in 2001 was primarily due to external development costs related to potential drug candidates which increased to $5.5 million from $1.4 million in 2000. The increase was also driven by the Company's continued expansion of its AIDD™ program for the discovery of new drug candidates. Research and development expenses represented 84 percent, 84 percent and 83 percent of total operating expenses (excluding non-cash stock compensation charges) for the years ended December 31, 2002, 2001 and 2000, respectively.
The Company expenses all research and development costs as incurred. While the Company maintains a system to record the level of staffing time spent on its research and development projects, it does not maintain a historical cost accounting system with sufficient accuracy to reliably estimate its research and development costs on a specific project-by-project basis. A significant portion of the Company’s research and development expenses (such as laboratory supplies, travel, information systems and services and facilities costs) benefit multiple projects and are not individually tracked to a specific project. Further, the Company’s staff timekeeping system does not account for differences in compensation costs between lower level technicians and more senior scientists.
General and administrative expenses, excluding non-cash stock compensation charges, remained stable at $6.7 million in 2002 as compared to $6.6 million in 2001, and increased 15 percent in 2001 from $5.7 million in 2000. The increase in 2001 was attributed to additional administrative and technical services and personnel to support the protection of Neurogen's growing intellectual property estate and to support Neurogen's expanding research pipeline.
Total stock compensation expenses were $0.6 million in 2002 compared to $1.5 million in 2001 and $7.1 million in 2000. The 2002 compensation expense is primarily composed of continuing non-cash charges for grants of certain stock awards in 1997, 2001 and 2002 to certain officers of the Company. The 2001 expense included non-cash charges to income for grants of certain stock awards in 1997 and 2001, as well as one-time non-cash charges totaling $1.0 million for the modification of certain stock options held by two executive officers. In 2000 the Company recorded $6.5 million in stock compensation expense for the vesting of restricted stock granted to certain employees in prior years. A portion of the stock compensation charges (those relating to the 1997 awards) are variable and as a result may fluctuate significantly in the future.
Other income was $1.7 million in 2002 compared to $4.5 million in 2001 and $5.5 million in 2000. The decrease in 2002 is primarily due to an increase in interest expense of $1.0 million associated with a $17.5 million first mortgage debt financing the Company entered into in December 2001. The remainder of the decrease in 2002, as well as the decrease in 2001, was due to a decrease in investment income due to lower overall returns on invested funds. This was a result of lower average cash and marketable securities balances as well as a reduction in prevailing market interest rates.
For the years ended December 31, 2002 and 2001, the Company recorded Connecticut income tax benefits of $0.3 million and $1.2 million, respectively, in the Statement of Operations. The Company recognized total income tax benefits of $0.6 million and $2.0 million for the years ended December 31, 2002 and 2001, respectively, a portion of which has been recorded to Additional Paid-In Capital. The benefits are the result of Connecticut legislation which allowed certain companies to obtain cash refunds from the State of Connecticut at an exchange rate of 65% of their research and development credits in exchange for foregoing the carryforward of these credits into future tax years.
The Company recognized a net loss of $23.7 million for the year ended December 31, 2002, $25.4 million for the year ended December 31, 2001, and $15.5 million for the year ended December 31, 2000. The decrease in the 2002 net loss is primarily due to the increase in operating revenues. The increase in the 2001 net loss is primarily due to the decrease in revenues and the increase in research and development and general and administrative expenses described above.
In December 1999, the staff of the Securities and Exchange Commission issued its Staff Accounting Bulletin ("SAB") No. 101, Revenue Recognition in Financial Statements. SAB No. 101, as amended by SAB No. 101A and 101B, provides guidance on the measurement and timing of revenue recognition in financial statements of public companies. SAB No. 101 permits application of its guidance to be treated as a change in accounting principle in accordance with Accounting Principles Board (“APB”) Opinion No. 20, Accounting Changes.
The Company adopted the guidance of SAB No. 101 in the fourth quarter of 2000, retroactive to January 1, 2000, and reflected a cumulative effect of change in accounting principle on prior years of $0.5 million, related to timing of revenue recognition on certain non-refundable up-front payments previously recognized on a technology transfer agreement.
LIQUIDITY AND CAPITAL RESOURCES
At December 31, 2002 and 2001, cash, cash equivalents (including restricted cash of $1.5 million in 2001) and marketable securities in the aggregate were $79.4 million and $106.8 million, respectively. A total amount of $44.8 million of the marketable securities at December 31, 2002 have maturities greater than one year. However, the Company can and may liquidate such investments prior to maturity to meet its strategic and/or investment objectives. The Company's cash and other short-term investment levels decreased ratably throughout 2002 due primarily to continued operating expenses, as well as purchases of property, plant and equipment of $2.1 million and scheduled payments on outstanding loans (described below) of $2.5 million. This decrease was partially offset by the receipt of $9.2 million in research funding and license fees and $2.6 million in income tax benefits from the State of Connecticut as described below. The levels of cash, cash equivalents and marketable securities have fluctuated significantly in the past and are expected to do so in the future as a result of the factors described below. The Company plans to use its cash, cash equivalents and marketable securities for its research and development activities, working capital and general corporate purposes.
Neurogen's cash requirements to date have been met by the proceeds of its equity financing activities, amounts received pursuant to collaborative research, licensing or technology transfer arrangements, certain debt arrangements and interest earned on invested funds. The Company's equity financing activities have included underwritten public offerings of common stock, private placement offerings of common stock and private sales of common stock in connection with collaborative research and licensing agreements. Total funding received from these financing activities was approximately $146.6 million. The Company's expenditures have been primarily to fund research and development and general and administrative expenses and to construct and equip its research and development facilities.
The Company is in the early stage of product development. It has not derived any product revenues from product sales and does not expect to derive any product revenues for at least the next several years, if at all. Prior to deriving any such product revenues, the Company expects to incur significant losses and negative cash flows which in the aggregate could exceed the Company’s existing cash resources. To provide cash to fund its operations until such time as it achieves sustainable revenues, the Company relies extensively on its ability to develop drug discovery programs of sufficient value to either partner the programs with pharmaceutical companies or raise capital through equity financings.
To the extent that drug candidates progress in the Company’s currently unpartnered programs, such as its program for the treatment of inflammatory disorders or earlier stage programs, such progress could lead to the opportunity to partner on terms which provide capital, revenues and cash flows to the Company or the opportunity to raise capital through equity offerings. If unpartnered programs do not progress or do not progress on schedule, such opportunities would be delayed or may not materialize at all.
To the extent that drug candidates progress in the Company’s partnered programs, such as the Company’s insomnia program partnered with Pfizer or its depression and anxiety program partnered with Aventis, such progress could result in milestone payments and additional research and development funding to the Company under the respective collaboration agreements. Such progress could also provide the opportunity to raise capital through equity offerings. If partnered programs do not progress or do not progress on schedule, such opportunities would be delayed or may not materialize at all.
Lack of progress, scheduling delays or failures in any of the Company’s major programs could significantly reduce the Company’s levels of revenues, cash flows and cash available to fund its business. It could also significantly increase the Company’s cost of capital and limit its ability to raise equity capital. All of the Company’s compounds in development, whether in human clinical trials or not, will require significant additional research, development and testing before they can be commercialized. Furthermore, the scope, magnitude and timing of future research and development expenses, as well as anticipated project completion dates, are a series of steps, ranging from preclinical testing to clinical studies in humans. Each step in the process is typically more expensive than the previous step, but actual timing and cost for completion depends on the specific progress of each product being tested.
While the Company cannot accurately predict the time required or the cost involved in commercializing any one of its candidates, new drug development typically takes many years and tens or hundreds of millions of dollars. In addition, developing new drugs is an extremely uncertain process where most candidates fail and uncertain developments such as clinical or regulatory delays, side effects, undesirable drug properties or ineffectiveness of a drug candidate would slow or prevent the development of a product. If we or our partners are unable to commercialize one or more of our drug products, we will never achieve product revenues and may eventually be unable to continue our operations. This result would cause our shareholders to lose all or a substantial portion of their investment.
The debt agreements entered into by the Company to date include the commercial term mortgage loan financing in December 2001 with Webster Bank, and a construction loan entered into in October 1999 with Connecticut Innovations, Inc. (“CII”). Total proceeds received under these agreements were $22.5 million, which are repayable through monthly installments over a maximum term of 15 years, bearing various interest rates which approximated 3.9%-7.5% from 1999 through 2002. Of these amounts received, $21.0 million remained outstanding as of December 31, 2002. An approximate aggregate amount of $1.4 million is due and payable in each of the next five years. Thereafter, approximately $14.0 million is payable in regular installments until the scheduled maturity dates, including a balloon payment of $5.9 million on the mortgage loan upon maturity in December 2011. The loan with CII contains certain subjective acceleration clauses, which upon occurrence of certain events, may cause amounts due under the agreement to become immediately due and payable. The Company has no indication that it is in default of any such clauses and therefore has classified its debt based on the dates regular payments are due. As of December 31, 2002, Neurogen is not engaged in any significant lease or capital expenditure commitments.
In October 2002, as a part of its Operational Excellence program, Neurogen reorganized certain departments and eliminated 24 employee positions, representing approximately 10% of its total workforce. The Company recorded a charge of approximately $0.3 million in the fourth quarter of 2002 for employee termination costs, such as severance pay, continuation of benefits and personal outplacement support. Restructuring payments of a minimal amount are expected to end in the first quarter of 2003.
Neurogen anticipates that under the restructured operating program, its current cash balance, as supplemented by research funding pursuant to its collaborative research agreement with Aventis, will be sufficient to fund its current and planned operations into at least early 2005. However, Neurogen's funding requirements may change and will depend upon numerous factors, including but not limited to: the progress of the Company's research and development programs; the timing and results of preclinical testing and clinical studies; the timing of regulatory approvals; technological advances; determinations as to the commercial potential of its proposed products; the status of competitive products and the ability of the Company to establish and maintain collaborative arrangements with others for the purpose of funding certain research and development programs; conducting clinical studies; obtaining regulatory approvals and, if such approvals are obtained, manufacturing and marketing products. Many of these factors could significantly increase the Company's expenses and use of cash. The Company anticipates that it may augment its cash balance through financing transactions, including the issuance of debt or equity securities and further corporate alliances. The Company has filed an S-3 registration statement which became effective in February 2003, under which the Company may issue debt, common or preferred stock or warrants of up to $75 million in total financing within two years of the effective date. No assurances can be given that adequate levels of additional funding can be obtained on favorable terms, if at all.
As of December 31, 2002, the Company had approximately $112.5 million and $7.1 million of net operating loss and research and development credit carryforwards, respectively, available for federal income tax purposes, which expire in the years 2004 through 2022. The Company also had approximately $99.0 million and $4.5 million of Connecticut state tax net operating loss and research and development credit carryforwards, respectively, which expire in the years 2003 through 2022. In September 2002, the Company applied to exchange 2001 Connecticut research and development credits for cash proceeds under Connecticut tax law provisions effective at that time (as mentioned above), resulting in the receipt of a $0.4 million payment from the State of Connecticut in November 2002. Neurogen also received a payment of $2.2 million in April 2002 for the exchange of 2000 research and development credits. Because of "change in ownership" provisions of the Tax Reform Act of 1986, the Company's utilization of its net operating loss and research and development credit carryforwards may be subject to an annual limitation in future periods.
COLLABORATIVE RESEARCH AGREEMENTS
In December 2001, Neurogen entered into a collaboration and license agreement with Aventis pursuant to which Aventis made an initial payment of $10 million and agreed, among other things, to fund a specified level of resources for three years for Neurogen's program for the discovery and research of CRF-1 receptor-based drugs for a broad range of applications, including the therapeutic treatment of depression and anxiety disorders. Aventis has the option to extend the discovery and research effort for up to an additional two years or terminate the collaboration prior to its scheduled conclusion and transfer all rights to the collaborative program to Neurogen. As of December 31, 2002, the Company has received $3.6 million of research funding from Aventis. Neurogen is also eligible to receive milestone payments if certain compound discovery, product development or regulatory objectives are achieved subject to the collaboration. In return, Aventis received the exclusive worldwide rights to develop, manufacture and market collaboration drugs that act through the CRF-1 receptor, for all therapeutic indications for which the drugs may be used. Aventis will pay Neurogen royalties based upon net sales levels, if any, for collaboration products. Also under the agreement, Aventis is responsible for funding the cost of development, including clinical trials, manufacturing and marketing of collaboration products, if any.
In June 1999, Neurogen and Pfizer entered into the Pfizer Technology Transfer Agreement. Under the terms of this agreement, Pfizer agreed to pay Neurogen up to a total of $27.0 million over a three year period for the licensing and transfer to Pfizer of certain of Neurogen's AIDD™ technologies for the discovery of new drugs, along with the installation of an AIDD™ system. Additional payments were also possible upon Pfizer's successful utilization of this technology. Pfizer received a non-exclusive license to certain AIDD™ intellectual property and the right to employ this technology in its own drug discovery programs. As of December 31, 2002, Pfizer had provided $29.0 million pursuant to the Pfizer Technology Transfer Agreement, which terminated on schedule in June 2002. Total fees include a $2.0 million one-time payment in December 2002 to satisfy all obligations from Pfizer’s use of the AIDD™ technology.
RECENTLY ISSUED ACCOUNTING PRONOUNCEMENTS
In August 2001, the Financial Accounting Standards Board (“FASB”) issued SFAS No. 144, "Accounting for the Impairment or Disposal of Long-Lived Assets." SFAS No. 144 supercedes SFAS No. 121, "Accounting for the Impairment of Long-Lived Assets and for Long-Lived Assets to be Disposed Of," in that it excludes goodwill from its impairment scope and allows for different approaches in cash flow estimation. However, SFAS No. 144 retains the fundamental provisions of SFAS No. 121 for recognition and measurement of the impairment of (a) long-lived assets to be held and used and (b) long-lived assets to be disposed of other than by sale. Neurogen adopted the provisions of SFAS No. 144 as of January 1, 2002. The implementation of this standard did not have any impact on the Company’s results of operations and financial position.
In July 2002, the Financial Accounting Standards Board issued SFAS No. 146, "Accounting for Costs Associated with Exit or Disposal Activities". SFAS No. 146 addresses financial accounting and reporting for costs associated with exit or disposal activities and nullifies EITF Issue No. 94-3, "Liability Recognition for Certain Employee Termination Benefits and Other Costs to Exit an Activity (including Certain Costs Incurred in a Restructuring)." The provisions of SFAS No. 146 are effective for exit or disposal activities initiated after December 31, 2002. However, as encouraged in the statement, the Company has early adopted SFAS No. 146 and has applied its respective provisions to the exit activity undertaken in 2002 (described in Note 12 to the consolidated financial statements).
In December 2002, the Financial Accounting Standards Board issued SFAS No. 148, "Accounting for Stock-Based Compensation – Transition and Disclosure". SFAS No. 148 amends SFAS No. 123 to address alternative methods of transition for a voluntary change from the intrinsic to the fair value method of accounting for stock-based employee compensation. The statement also amends certain disclosure provisions in SFAS No. 123. Neurogen continues to utilize the intrinsic value method to account for stock-based employee compensation. However, the disclosure provisions of SFAS No. 148 have been implemented in the 2002 consolidated financial statements.
In November 2002, the Financial Accounting Standards Board issued FIN No. 45, "Guarantor's Accounting and Disclosure Requirements for Guarantees, Including Indirect Guarantees of Indebtedness of Others”, which elaborates on the disclosures to be made by a guarantor in its interim and annual financial statements about its obligations under certain guarantees that it has issued. The Company has indemnification agreements with three employees as of December 31,2002 for contingent payments which may be required under provisions that exist in such employees' employment agreements with prior employers. The maximum amount of this potential obligation is approximately $3.0 million, however the Company believes the likelihood of payment of any amounts under such indemnifications is remote.
In January 2003, the Financial Accounting Standards Board issued EITF Issue No. 00-21, “Revenue Arrangements with Multiple Deliverables”. EITF 00-21 addresses, for arrangements with multiple deliverables, how the arrangement consideration should be measured, whether the arrangement should be divided into separate units of accounting and how the arrangement consideration should be allocated among the separate units of accounting. The guidance in EITF 00-21 is effective for revenue arrangements entered into in fiscal periods beginning after June 15, 2003, and therefore does not have any impact on the 2002 consolidated financial statements. The consensus in this EITF pronouncement may affect how the Company recognizes revenue under future collaboration and technology transfer arrangements since these often include multiple elements such as non-refundable upfront fees, ongoing payments for specified levels of staffing for research and milestone payments.
ITEM 7A. QUANTITATIVE AND QUALITATIVE DISCLOSURES ABOUT MARKET RISK
Interest rate risk. The Company's investment portfolio includes investment grade debt instruments. These securities are subject to interest rate risk, and could decline in value if interest rates fluctuate. Due to the short duration and conservative nature of these instruments, the Company does not believe that it has a material exposure to interest rate risk. Additionally, funds available from investment activities are dependent upon available investment rates. These funds may be higher or lower than anticipated due to interest rate volatility.
Capital market risk. The Company currently has no product revenues and is dependent on funds raised through other sources. One source of funding is through further equity offerings. The ability of the Company to raise funds in this manner is dependent upon capital market forces affecting the stock price of the Company.
ITEM 8. CONSOLIDATED FINANCIAL STATEMENTS AND SUPPLEMENTARY DATA
INDEX TO CONSOLIDATED FINANCIAL STATEMENTS
Consolidated Balance Sheets at December 31, 2002 and 2001
Consolidated Statements of Operations for the years ended December 31, 2002, 2001 and 2000
Consolidated Statements of Stockholders' Equity for the years ended December 31, 2002, 2001 and 2000
Consolidated Statements of Cash Flows for the years ended December 31, 2002, 2001 and 2000
Notes to Consolidated Financial Statements
Report of Independent Accountants
CONSOLIDATED BALANCE SHEETS |
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(In thousands, except per share data) |
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December 31 |
December 31 |
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2002 |
2001 |
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Assets |
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| Current assets: | ||||
| Cash and cash equivalents | $12,248 |
$51,062 |
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| Restricted cash | - |
1,500 |
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| Marketable securities | 67,164 |
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