UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
FORM 10-K
(MARK ONE)
[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
FOR THE TRANSITION PERIOD FROM ___________ TO _____________
Commission file number 000-0030755
Cepheid
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904 Caribbean Drive
Sunnyvale, California 94089-1189
(408) 541-4191
Securities registered pursuant to Section 12(b) of the Act: None
Securities registered pursuant to Section 12(g) of the Act:
COMMON STOCK, NO PAR VALUE AND THE ASSOCIATED STOCK PURCHASE RIGHTS
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 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
¨As of June 28, 2002, the last business day of the Registrant's most recently completed second fiscal quarter, the aggregate market value of the common stock held by non-affiliates of the registrant was approximately $136,583,819, based on the closing sale price for the registrant's common stock on the Nasdaq National Market on that date of $5.58. For purposes of determining this number, all executive officers and directors of the registrant are considered to be affiliates of the registrant, as well as individual shareholders holding more than 10% of the registrant's outstanding common stock. This number is provided only for the purpose of this report on Form 10-K and does not represent an admission by either the registrant or any such person as to the status of such person.
As of March 18, 2003, there were 32,374,028 shares of the registrant's common stock
outstanding.
DOCUMENTS INCORPORATED BY REFERENCE
Designated portions of Cepheid's definitive proxy statement for its 2003 annual meeting of shareholders are incorporated by reference into Part III hereof.

Cepheid
2002 ANNUAL REPORT ON FORM 10-K
TABLE OF CONTENTS
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Part I. |
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Item 1. |
Business | |
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Item 2. |
Properties | |
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Item 3. |
Legal Proceedings | |
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Item 4. |
Submission of Matters to a Vote of Security Holders | |
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Part II. |
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Item 5. |
Market for the Registrant's Common Equity and Related Stockholder Matters | |
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Item 6. |
Selected Consolidated Financial Data | |
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Item 7. |
Management's Discussion and Analysis of Financial Condition and Results of Operations | |
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Item 7a. |
Quantitative and Qualitative Disclosures About Market Risks | |
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Item 8. |
Consolidated Financial Statements and Supplementary Data | |
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Item 9. |
Changes in and Disagreements with Accountants on Accounting and Financial Disclosure | |
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Part III. |
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Item 10. |
Directors and Executive Officers of the Registrant | |
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Item 11. |
Executive Compensation | |
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Item 12. |
Security Ownership of Certain Beneficial Owners and Management | |
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Item 13. |
Certain Relationships and Related Transactions | |
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Item 14. |
Controls and Procedures | |
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Part IV. |
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Item 15. |
Exhibits, Consolidated Financial Statement Schedules and Reports on Form 8-K | |
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Signatures |
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Certifications |
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Cepheid®, I-CORE®, Smart Cycler®, and GeneXpert® are registered trademarks of
Cepheid.
FORWARD-LOOKING STATEMENTS
This report contains forward-looking statements within the meaning of the federal securities laws that relate to future events or our future financial performance. In some cases, you can identify forward-looking statements by terminology such as "may," "will," "should," "expect," "plan," "anticipate," "believe," "estimate," "predict," "intend," "potential" or "continue" or the negative of these terms or other comparable terminology. These statements are only predictions. Risks and uncertainties and the occurrence of other events could cause actual results to differ materially from these predictions. The risk factors set forth below should be considered carefully in evaluating us and our business.
Although we believe that the expectations reflected in the forward-looking statements are reasonable, we cannot guarantee future results, levels of activity, performance or achievements. Moreover, neither we nor any other person assumes responsibility for the accuracy and completeness of these forward-looking statements. We assume no obligation to update any of the forward-looking statements after the date of this report or to conform these forward-looking statements to actual results.
PART I
ITEM 1. BUSINESS
We develop, manufacture and market fully integrated systems that enable sophisticated genetic and DNA analysis of patients and organisms by automating complex manual laboratory procedures. Based on state-of-the-art microfluidic and microelectronic technologies, our easy-to-use systems analyze complex biological samples in disposable cartridges designed to perform rapidly and automatically all of the steps associated with sophisticated molecular biological procedures. We are focusing our efforts on those applications where rapid genetic and DNA testing is particularly important, such as the infectious disease, biothreat and cancer testing markets. In particular, we have designed our systems to be capable of use in genetic management of disease, performing a broad range of genetic tests that include identifying infectious organisms, evaluating at-risk populations for the early detection of disease such as cancer, determining the stage of the disease and assessing what might be the most effective therapy. We also have designed our systems to detect food, air and water contaminants rapidly through genetic identification of disease causing agents. We are collaborating with strategic partners to co-develop assays, or biological tests, and to provide marketing and sales support across a broad range of markets.
We commenced commercial sales of our first product, the Smart Cycler®, in May 2000. The Smart Cycler is a DNA amplification and detection system initially directed at the life sciences research market. We began shipping the Smart Cycler II, which features various enhancements to the Smart Cycler, in November 2002. We believe our Smart Cycler products allow users to analyze biological samples faster and more efficiently than any other product currently available.
Our GeneXpert® system, currently in the final stages of development, integrates automated sample preparation with our Smart Cycler amplification and detection technology. We expect to launch the GeneXpert system in unregulated markets in the second half of 2003. Following clinical trials and FDA approval, we anticipate commercial launch of the GeneXpert system to the clinical genetic assessment market in early 2005. We believe that the GeneXpert system is the only genetic analysis system that integrates automated sample preparation with genetic analysis, while also offering customers a complete testing system comprised of both instrumentation and disposable cartridges containing all necessary reagents for a particular test.
Our principal executive offices are located at 904 Caribbean Drive, Sunnyvale, California 94089-1189 and our telephone number is (408) 541- 4191.
Cepheid makes available free of charge on its web site its Annual Reports on Form 10-K, its Quarterly Reports on Form 10-Q, its Current Reports on Form 8-K and amendments to those Reports filed or furnished pursuant to Section 13(a) or 15(d) of the Securities Exchange Act of 1934, as amended, as soon as reasonably practicable after we electronically file them with or furnish them to the Securities and Exchange Commission, or the SEC. Information contained on our web site is not part of this Annual Report on Form 10-K or our other filings with the SEC.
INDUSTRY BACKGROUND
Overview
Nucleic acids are molecules found inside cells. Nucleic acids, such as deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), contain the unique blueprint, or genes, of each living creature. Advances in molecular biology have led to the development of techniques for reading the genome and for detecting the presence of a known nucleic acid sequence. The three key processing steps in genetic and DNA testing are:
The most widely used method for genetic analysis is first to amplify the nucleic acids isolated from the sample and subsequently to detect the resulting DNA with the use of fluorescent dyes. The most common amplification technique is polymerase chain reaction, or PCR.
The biochemicals that attach to the target DNA sequence generated in the amplification process and fluoresce are called DNA probes. Numerous probes have been developed for identifying organisms such as strep, human immunodeficiency virus ("HIV"), gonorrhea, syphilis, chlamydia, anthrax, E.coli and salmonella. In fact, probes can be designed for any unique genetic sequence and have been developed for many significant infectious disease organisms and many genetic mutations associated with human cancer and with inherited human characteristics.
These kinds of biological tests, or assays, are used extensively to detect and quantify nucleic acids and proteins in biological samples. With the recent advances in the field of genomics and the availability of vast DNA sequence libraries, there has been a shift towards biological tests that detect the presence of DNA sequences unique to a particular gene. Such gene-based testing offers a level of sensitivity and specificity unmatched by other technologies, but the growth of gene-based testing has been limited by technical complexity, labor intensity, cost and lack of automation.
Amplification and detection
For samples with low concentrations of target organisms, cell culturing is routinely used to grow naturally enough copies of the organism for detection and identification. However, cell culturing is a very slow amplification process, which may require several days to generate a detectable number of copies.
The discovery of PCR and other amplification techniques dramatically improved the turnaround and time sensitivity of DNA probe assays. PCR acts on a target molecule to generate a million or more copies of the target nucleic acid sequence through repeated cycles of heating and cooling. Originally, this thermal cycling was accomplished by manually moving the sample between hot and cold water baths. Detection is typically accomplished by tagging the DNA with fluorescent dyes and manually placing the amplified sample on a gel to read it. Later, thermal cyclers were developed to automate the heating and cooling functions, and fluorimeters were developed to read the fluorescent signal.
Sample preparation
Before a laboratory can perform PCR and other nucleic acid tests, a sequence of labor intensive, complex and time consuming sample preparation procedures must be performed to isolate the target cells and to separate and purify their nucleic acids. These sample preparation procedures include cell separation and washing, cell lysing (described below), and DNA or RNA purification. Each of the procedures involves many steps of reagent handling and mixing and assorted laboratory equipment such as balances, centrifuges, vortexers, pipettors, microplates, bead columns and plate readers. Kits containing reagents and consumables for DNA and RNA purification simplify these procedures, but they remain manually intensive and are subject to operator error and specimen cross-contamination.
Most samples require lysis, which is the rupturing of a cell membrane to release the DNA contained inside. Rapid, efficient, versatile lysis of cells and organisms to extract DNA, RNA or proteins is not an easy process. Today, this step can be one of the most time consuming and complex steps in bio- analysis. For example, red blood cells are extremely easy to lyse, but they do not contain any nucleic acids and are rarely of interest to genetic researchers. On the other hand, white blood cells do contain nucleic acids, including the complete human genome. White blood cells are more difficult to lyse and must be separated from the red blood cells, which contain PCR-inhibiting chemicals. Organisms such as spores, tuberculosis cells, chlamydia and other bacteria are even more difficult to lyse, and researchers today typically use harsh, PCR- inhibiting chemicals, at elevated temperatures for long periods of time in order to accomplish this task.
LIMITATIONS
Current technologies for determining the genetic or DNA composition of a call or organism generally have the following limitations:
Highly Skilled Technicians; Special Laboratory Required. Currently available methods require skilled scientists and technicians in a special laboratory setting, including, in many cases, separate rooms to prevent contamination of one sample by another.
Large and Inflexible Equipment. Most currently available equipment is large and inflexible and is typically configured to accommodate only one assay, or test, procedure.
Long Time to Result. Current sample preparation, amplification and detection technologies rely on manual or semi-automated processes that often require days to complete.
Sensitivity Constraints. Existing technologies accept and process only very small sample volumes, forcing laboratory technicians to spend significant effort in concentrating larger samples in order to obtain the required level of sensitivity.
Lack of Integration. We believe that current amplification and detection systems do not integrate sample preparation or the extraction, purification and concentration of DNA or RNA into their processes.
In summary, genetic and DNA testing is currently a complicated, time-consuming process that requires expensive, specialized, and inflexible equipment and highly trained staff. We believe that genetic and DNA testing will only achieve its full market potential upon the development of advanced instruments and integrated processes that are both rapid and automated
THE CEPHEID® SOLUTION
We have developed a complete testing system comprised of instrumentation and disposable cartridges that integrate automated sample preparation, amplification and detection technologies. The systems are designed to handle a variety of different biological samples in a variety of markets. Our two product platforms, the Smart Cycler system, which is in commercial production, and the GeneXpert system, currently in the final stages of development, offer the following key benefits:
Portability and ease of use. Our systems are easy to use, enabling non-scientific personnel to conduct sophisticated genetic and DNA analysis. Our systems are also designed to operate in a wide range of environments, such as a hospital, research laboratory, physician's office, public health clinic, and factory or combat zone.
Flexible modular platform. Our systems are highly flexible in two primary respects. First, they are able to run several different assays requiring different testing protocols, either simultaneously or asynchronously. For example, a disposable cartridge can be loaded with a sample for anthrax testing and, simultaneously or a few minutes later, another test can be conducted in a different disposable cartridge, on the same or a different sample, for streptococcus. Second, as many as four different genetic sequences in each sample can be simultaneously detected in the same cartridge.
Rapid results. Our systems are designed to substantially reduce the time to result. Our GeneXpert system is able to produce a result from a raw biological sample in as little as 30 minutes.
Enhanced sensitivity. Our GeneXpert cartridges are designed to handle a wide range of sample volumes, concentrating and purifying the target DNA in a sample and removing extraneous materials, thereby increasing the sensitivity of the resulting assay.
Integration of key steps. Our Smart Cycler integrates amplification and detection, while our GeneXpert system is designed to fully integrate sample preparation, amplification and detection into one system.
MARKETS
Our target markets include the life sciences research, clinical genetic assessment and biothreat markets. We believe that these markets still rely on tools such as test tubes, centrifuges and other equipment that require extensive manual manipulation. These methods are expensive and often imprecise and present significant productivity challenges. We believe that there is a significant need for simpler, faster and more accurate laboratory tests in these markets.
Life sciences research.
The life sciences research market includes biomedical, pharmaceutical, environmental, agricultural and clinical genetic assessment research. In recent years significant research efforts have focused on identifying genes and determining their function. This field, which is known as genomics, has accelerated the understanding of the molecular mechanisms of genetics, diseases and disease treatment. Sample preparation, amplification, and detection technologies are increasingly important and widely used procedures in the life sciences research field.Clinical genetic assessment. Numerous breakthroughs in molecular biology and genomics have provided new insights into the nature of human diseases and new therapies for treating them. As a result, DNA-based testing is being rapidly adopted in the field of clinical genetic assessment to detect, identify and characterize pathogens, to determine antibiotic resistance and to identify genetic abnormalities, such as cancer. DNA-based testing includes a variety of assay techniques, such as thermal cycling covered by patents held by Applied Biosystems (formerly PE Biosystems), as well as constant temperature, or isothermal, techniques. Diagnosis and prognosis of cancer currently depends on the pathological examination of tissue sections using special stains or specific antibody-based reagents to detect evidence of abnormal cell morphology or proliferation. Biopsies for staging cancer operations are obtained surgically, typically in the hospital or in specialized in-patient oncology clinics. The information obtained during these procedures and subsequent molecular analyses that determine the treatment may not be available in a timely manner. We believe integrated analysis systems that can rapidly and automatically process cells or tissues and detect cancerous genetic abnormalities will be required to meet the needs of the growing oncology field.
Biothreat detection. The world geopolitical climate in the wake of the September 11, 2001 terrorist attacks has created increased interest in biothreat detection systems. As a result, the US government has increased its allocation of funds to both homeland and military defense and in particular biothreat detection. The biothreat detection market encompasses environmental testing such as in United States Postal Service mail sorting facilities, water supply testing, and food testing as well as human clinical genetic assessment. Both the United States and foreign military have expressed an interest in on-site real time DNA detection.
THE CEPHEID STRATEGY
Our strategy is to become the leading supplier of integrated systems and tests for widely distributed genetic analysis when and where it is needed. Key elements of our strategy to achieve this objective include:
Provide a fully integrated genetic and DNA testing solution. We intend to provide a fully-integrated genetic and DNA testing solution, offering customers both the fully-automated laboratory instrumentation needed to run genetic and DNA analysis, including sample preparation, amplification and detection, and the necessary reagents incorporated in our disposable cartridges for a wide range of tests.
Apply core Technologies broadly, either directly or through strategic relationships. We intend to use our proprietary technologies to provide rapid biological analysis platforms with applicability across a number of markets. Our target markets include genetic management of disease, biothreat applications and life sciences research. We intend to enter other markets, such as the food, veterinary and industrial markets, through strategic partnering arrangements.
Leverage biothreat detection business. We intend to use the know-how, economies of scale and revenues generated from our existing business with government agencies, such as our development of tests for the detection of biothreats for the U.S. Army Medical Research Institute of Infectious Diseases and the U.S. Postal Service (USPS), to pursue the clinical genetic assessment market and to enhance our penetration of the life sciences research market.
Expand direct sales and distribution capabilities. We intend to increase our direct sales force in North America and pursue distribution agreements with key distributors in regions outside of North America.
Continue to pursue life sciences market. We intend to pursue additional opportunities in the life sciences market, as we believe that the speed, consistency, flexibility, and ease of use of our systems will enable broader use of DNA amplification and detection in clinical research.
Leverage installed systems base. We intend to develop, manufacture and sell an expanding menu of tests in the form of single- use cartridges pre-loaded with reagents that are optimized for use in our systems. Our installed systems base will enable our customers to more easily expand their test menu for modest incremental costs, making it more affordable for a customer to implement new tests and enabling accelerated market adoption of our products.
THE CEPHEID TECHNOLOGY
Automated sample preparation
Automated sample preparation remains the last major hurdle in creating fully integrated nucleic acid analysis systems. Most automated sample preparation instruments available today utilize robotics, with machines merely duplicating the steps technicians would perform in laboratories. These systems have been beneficial to high throughput, single assay applications, but require large capital investments and skilled personnel in a laboratory.
We believe that the proprietary automated sample preparation technology we are incorporating in the GeneXpert System will be the first to integrate the basic chemistry and physics required to prepare a raw sample for analysis. We have developed microfluidic technologies that perform these steps in a disposable cartridge. The key steps in sample preparation together with our corresponding technologies are as follows:
Adding reagents. We manufacture disposable sample preparation cartridges and lyophilize reagents into a bead format needed for the amplification process as well as probes for specific nucleic acid targets. Our low-cost, plastic molded cartridges also incorporate a proven fluid delivery system.
Measuring sample volume and mixing. We use pressure differences to flow liquids through our cartridges and use proprietary mechanical valving mechanisms to produce precise fluid flow control. Our flow- through technology allows the sample to be processed on a continuous basis and is critical to our ability to accommodate the larger sample sizes required for high sensitivity pathogen detection. Our cartridges mix fluids through a versatile, proprietary, plastic valve assembly that can accommodate a variety of sample preparation protocols.
Separating and capturing specific cells or targets. Our cartridges incorporate filters or nucleic acid capture assemblies that can perform functions ranging from basic sample clean up to specific cell or target capture.
Lysing cells. We have developed a very rapid proprietary lysis technology capable of releasing DNA from the cells of organisms that are difficult to lyse, such as spores. This versatile ultrasonic lysing technology is incorporated in our GeneXpert system and will allow lysis procedures, that now may take hours, to be performed in seconds. This technology does not require harsh chemicals, and therefore eliminates the difficult and time-consuming purification steps that are required by conventional technologies.
Preparing For Analysis. In the GeneXpert system, we will integrate the sample preparation cartridge with our proprietary reaction tube, the same tube design used in our I-CORE (Integrated, Cooling/Heating Optics Reaction) modules and Smart Cycler for amplification and detection. After capturing and concentrating the DNA from the sample, our cartridge automatically mixes the DNA with amplification reagents and moves the DNA to the reaction tube for amplification and detection.
Amplification and detection
In 1996, we licensed a technology from Lawrence Livermore National Laboratories that allows us to integrate amplification and detection. Our commercial version of the technology is called the I-CORE module, a single chamber module measuring approximately one inch by four inches by five inches. An I-CORE is a complete, independent, temperature- controlled fluorimeter for performing and continuously monitoring chemical reactions such as PCR, and is a key element of both our Smart Cycler and GeneXpert systems. The temperature of the sample can be controlled rapidly and accurately, allowing faster reactions and more accurate results. The I-CORE technology also allows the analysis of samples to be performed with much lower power than traditional methods. This permits our systems to be portable, giving our customers the capability to obtain bioanalytical results when and where they are needed. We use our I-CORE technology in both our Smart Cycler and GeneXpert platforms.
Independent control. One of the key distinguishing features of our I- CORE technology is that in a system composed of multiple I-COREs, each I-CORE can be operated and controlled independently. We believe that this is not possible with any other system currently on the market. In contrast to traditional thermal cycling systems, in which all the samples are subjected to the same time/temperature/optical protocol, each sample in an I-CORE-based instrument can be subjected to a different protocol. This allows the operator to perform many different assays or experiments at the same time on the same instrument.
Powerful optical analysis. Each I-CORE module includes a four-channel optical analysis system capable of complex chemical assays. This allows the detection and quantification of multiple fluorescent dyes and multiple target molecules in the same reaction tube. Continuous optical monitoring during amplification also allows the user to stop the reaction as soon as a target is detected, thereby shortening the time to result. For example, in a single reaction tube, the I-CORE module could simultaneously detect and quantify staphylococcus aureus, detect the presence or absence of the methicillin- resistance gene and measure the optical response of a separate internal control target. The internal control allows us to verify the performance of the system.
Patented reaction tube. Our disposable patented reaction tube is used in conjunction with the I-CORE module and has been optimized to provide rapid temperature cycling and long optical path lengths for optimum optical sensitivity. In addition, the tube is designed to eliminate entrapped air, which can interfere with the optical signal. This feature minimizes optical noise, makes assays more uniform and reproducible and minimizes the need for optical normalization.
Easy-to-use lyophilized PCR reagents. In order to attain our goal "of providing DNA test results, when and where they are needed," we must provide a total solution to the customer, which includes easy to use PCR reagents. Current liquid reagents are very inconvenient and must be stored at near freezing temperatures in order to maintain their performance. Cepheid has developed a PCR reagent technology in which all the liquid chemicals necessary to perform PCR are lyophilized, or freeze-dried, into small, stable pellets. These pellets are pre-mixed doses of PCR chemicals, they are stable over long periods of time at room temperature and are also very easy for the customer to use.
PRODUCTS
Our primary product platforms consist of our Smart Cycler and GeneXpert instrument systems. The following table sets forth the amplification and detection products we offer:
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Name |
Description |
Status |
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Smart Cycler |
Laboratory-based DNA analysis instrument containing 16 I-CORE modules |
In Production/ On the market |
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Smart Cycler TD |
Transportable DNA analysis instrument containing 16 I-CORE modules |
In Production/ On the market |
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Smart Cycler II |
Second version of Laboratory-based DNA analysis instrument containing 16 I-CORE Modules with enhanced optical features |
In Production/ On the market |
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Group B Streptococcus Assay |
Test which runs on Smart Cycler used to detect presence of Group B Streptococcus, developed in collaboration with Infectio Diagnostics, Inc |
Cleared by Food and Drug Administration |
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OmniMix |
General use PCR enzyme reagent for use on the Smart Cycler product, obtained through collaboration with Takara Bio, Inc |
In Production/ On the market |
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Smart Cycler Reaction Tubes (25 microliter and 100 microliter) |
Disposable I-CORE reaction tubes optimized for research and diagnostic applications |
In Production/ On the market |
The following table sets forth our family of products that integrate sample preparation, amplification and detection:
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Name |
Description |
Status |
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GeneXpert |
Automated system for sample preparation, amplification and detection from raw biological samples |
Pre-production prototype |
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GXPT-1 |
Disposable assay cartridge for spores and bacteria in aqueous- based solutions, including swab extractions in buffer |
Pre-production prototype |
I-Core module
Our I-CORE module is a low-cost, self-contained instrument for performing and continuously monitoring chemical reactions such as PCR. Each module can optically measure up to four separate reactions. The I-CORE module rapidly and accurately controls the heating and cooling of the sample, which allows for fast reactions and accurate results. I-CORE modules are also capable of being configured into a variety of other DNA analysis instruments. The I-CORE module is a key component in both our Smart Cycler and GeneXpert families of products.
Smart Cycler family
The Smart Cycler contains 16 I-CORE modules arranged into a rapid, flexible, multi-purpose instrument capable of performing DNA amplification and detection by means of a number of available fluorescent chemical techniques. Through December 2002, we had sold more than 1,000 Smart Cyclers. We have distribution agreements with Fisher Scientific in the United States and Canada; with various distributors in Europe, with Takara Bio, Inc in Japan, Taiwan, China, and South Korea, with Diagnostic Technology Party Limited in Australia and New Zealand, and with BioSynTech Sdn Bhd in Malaysia and Singapore.
We also offer Smart Cycler TD (Transportable Device), a transportable version of the Smart Cycler system which includes a field deployable case.
TheSmart Cycler II is the second version of the Smart Cycler product. It was released in November 2002 and incorporates enhanced optical and software features.
Reaction tubes
One of our patented reaction tubes is required for each assay run using our Smart Cycler family of products. We offer two types of patented reaction tubes for use with these systems. Both are designed to be disposed of after a single use and represent opportunities for recurring revenue from an installed base of instruments. We manufacture and sell a 25 microliter tube, typically preferred in the life sciences research market, and a 100 microliter tube, which is typical for applications that might require larger liquid reaction volumes. Through the end of December 2002, we had sold approximately 3.4 million reaction tubes.
OmniMix
Our OmniMix product is produced under a collaborative agreement with Takara Bio, Inc, ("Takara") under which we package and distribute a dry-formulated version of Takara's Taq HS polymerase product that has been optomized for use on the Smart Cycler and GeneXpert systems. The OmniMix product provides researchers with a general-use PCR enzyme reagent optimized for our products.
GeneXpert system
Our GeneXpert family of products combines sample preparation with the amplification and detection functions performed by our I- CORE module into an integrated, automated genetic analysis instrument. These products are designed to purify, concentrate, detect and identify targeted DNA sequences, from sample to result, generally in less than 30 minutes. Current techniques for accomplishing this same complex series of procedures require extensive manual labor by skilled technicians and can take anywhere from six hours to three days.
The GeneXpert system is designed to accept cartridges with several different internal configurations; each designed to perform a different class of assay or protocol. Each cartridge will be labeled with bar codes that, through the software, link to specific information on to how to direct the fluids through the cartridge and activate the various mixing, lysing, amplification, detection and other functions as required. The GeneXpert system is compact, uses low power and is suitable for applications requiring portability.
We expect to launch the GeneXpert system in unregulated markets by the second half of 2003. Following clinical trials and FDA approval, we anticipate commercial launch of the GeneXpert system to the clinical market in early 2005.
Disposable assay cartridges
We have one disposable assay cartridge, GXPT-1, in the final stage of development. The GXPT-1 cartridge will be a general-purpose assay cartridge optimized for rapidly extracting, concentrating and detecting spores and bacteria from aqueous-based samples. We have successfully demonstrated the usefulness of this cartridge for applications such as detecting infectious organisms in urine, bacteria from swabs and spores in environmental samples. More recently, our collaborators and us, including those we are joining in bids to develop biothreat detection systems for U.S. government facilities have demonstrated the utility of the pre-production prototype cartridge in the detection of anthrax spores from environmental samples. We anticipate this cartridge will also be used to detect bacteria in other medical specimens and to replace bacterial cultures. We are optimizing this cartridge to improve speed and sensitivity when targets are present in low concentration in a large volume.
RESEARCH AND DEVELOPMENT
Our research and development efforts are focused on refining and enhancing of our existing systems, significantly improving our basic technology and developing key future technologies and systems. As with our core technologies and products, we are concentrating our efforts in the areas of sample preparation, amplification and detection.
Sample preparation
Amplification
Detection
Reagents
We have devoted substantial financial and business resources to research and development efforts in the commercialization of the Smart Cycler and the GeneXpert families of products, and we expect such efforts to continue to demand substantial resources as we improve our technologies, develop and support our products, and explore and develop potential new products. Our research and development expenses for 2000, 2001, and 2002 were $15.0 million, $15.0 million, and $16.9million, respectively.
Development efforts
We are currently in the final stages of development for our GeneXpert system and our GXPT-1 cartridge. We are also engaged in early stage of development for the following additional disposal cartridges:
Genomic DNA in blood. Our GXPT-2 cartridge will be optimized for extracting and concentrating genomic DNA from blood or cell cultures. The ability to extract human genomic DNA from whole blood has been demonstrated using cartridge components. This cartridge will have broad applications in human leukocyte antigen, or HLA, analysis, genetic analysis and SNP detection and analysis. It will extract white blood cells from whole blood, automatically lyse these cells, extract and concentrate the genomic DNA, then selectively amplify and detect several genomic regions containing the SNPs of interest.
Viral pathogens in swabs. We intend to design our GXPT-3 cartridge to accept nasal swab extracts or other respiratory secretions, capture the viral pathogens, lyse the viruses and perform real time PCR. We believe that this cartridge could be widely adopted for rapid testing for respiratory viruses, such as flu and childhood viral pathogens, particularly as new antiviral treatments become available.
Pathogenic DNA or RNA in blood. We intend to design our GXPT-4 cartridge to accept up to ten milliliters of whole blood and extract and concentrate bacterial DNA. Relatively large volumes of blood are necessary to achieve the required diagnostic sensitivity to detect bacterial DNA, so the volume of this cartridge will enables tests to detect the presence of bacteria. In addition, this cartridge in the GeneXpert system will be designed to rapidly and simultaneously detect antibiotic resistance.
Viral pathogens (DNA and RNA) in blood
. We also intend to design our GXPT-5 cartridge to accept up to ten milliliters of whole blood, and to separate and concentrate viruses and their nucleic acids. This will enable the rapid screening of donor blood for transfusions and blood from organ donors. The cartridge could also be used to monitor therapeutic response to antiviral drugs.SALES
We sell our products into the life science research, clinical genetic assessment, and biothreat markets through both direct and various distribution channels. In the United States, we will sell through our non-exclusive distributor, Fisher Scientific as well as our ten-person direct sales force. We sell through direct channels in Germany and through distributors throughout the rest of Europe. In the Far East and and other non-U.S. markets, we sell solely through distribution channels.
Distribution and Collaboration Arrangements
We are collaborating with strategic partners to develop assays across a broad range of markets for both the Smart Cycler and GeneXpert. We plan to continue to partner with distributors to gain access to their marketing resources and their proprietary reagents and assays. For the year ended December 31, 2002, product sales through distributors represented 54% of our total product sales (including instruments, reagents, and disposables). We have entered into the following significant commercial collaborations and distribution arrangements:
Fisher Scientific Company L.L.C. In May 2000, we launched our first product, the Smart Cycler system, into the U.S. life sciences research market through the Life Sciences group of Fisher Scientific Company L.L.C. ("Fisher"). Under this agreement, Fisher has non-exclusive distribution rights to certain markets in the United States. Fisher sells under the Cepheid label and trade dress. In December 2000, we expanded this agreement to include non-exclusive distribution rights in Canada. On December 2002, we expanded our non-exclusive distribution agreement with Fisher for the Smart Cycler to include the following markets in the United States: life science research, environmental (excluding bio-threat), pharmaceutical quality control, in vitro fertilization, quality control and cosmetics quality control. This arrangement continues through May 31, 2004 and may be extended by mutual agreement.
Takara Bio, Inc (Formerly Takara Shuzo Co., Ltd.). In the fourth quarter of 2000, we launched the Smart Cycler system into the life science research markets in Japan, Taiwan, South Korea, and China through Takara Bio, Inc ("Takara"). Takara has exclusive distribution rights in these countries under the three-year agreement subject to Takara's ongoing fulfillment of minimum purchase requirements. In December 2002, we entered into a collaboration agreement with Takara under which we will package and distribute a dry-formulated version of Takara's Taq HS polymerase product that has been optimized for use on the Smart Cycler system.
Infectio Diagnostic, Inc. In February 2000, we formed Aridia Corp., a joint venture we own equally with Infectio Diagnostic Inc. (IDI), a Canadian diagnostic company. IDI is developing a line of proprietary molecular diagnostic tests for the rapid, time critical identification of bacterial and fungal infections, such as group B Strepococcos, antibiotic resistant bacteria, meningitis and sepsis. The first products from this venture, a line of assays adapted to our Smart Cycler system, will be directed primarily to hospital laboratories. Products incorporating our GeneXpert technology will follow and will enable diagnostic procedures to be performed closer to the patient. These products will require FDA approval or clearance, or other applicable regulatory approval or clearance. The first such approval was obtained for IDI's group B Strepococcos test in the fourth quarter of 2002. To date, Aridia has not been funded and does not conduct any independent operations, and no amounts were incurred by or recorded by the joint venture through December 31, 2002. In February 2003, we entered into an agreement with IDI to act as its exclusive distributor for the group B Strepococcos product in the United States.
Smiths Detection. In August 2001, we entered into a patent and technology licensing and supply agreement with Smiths Detection, formerly Environmental Technologies Group, Inc. The focus of this collaboration is to develop biological-agent detection systems for military and other domestic preparedness applications. Under this agreement we will provide sub-systems and sub-assemblies to Smiths for integration into, and manufacture of, fully automated bio-detection systems that will range from hand-held units to stationary monitoring systems for use in a variety of military and civilian settings. The agreement also provides for royalties to be paid by Smiths to Cepheid based on sales of the completed products to end-users on a quarterly basis with minimum royalty payments to be made for the life of this agreement on an annual basis.
In November 2001, we entered into a patent sublicense agreement with Smiths and granted them the worldwide non-exclusive rights to key patents for the development of rapid, handheld DNA analysis systems for bioagent detection. Under the agreement, we will receive royalties on Smiths' system sales and retain rights to commercialize the handheld system for other DNA- testing applications, including environmental testing and veterinary diagnostics.
In January 2002, we entered into a teaming agreement with Smiths in connection with our participation in bids to obtain contracts to develop biothreat detection systems for the USPS.
U.S. government. In May 2002, we announced that we were part of a Northrop-Grumman-led consortium selected by the USPS for a pilot program to evaluate the use of the team's integrated DNA-based biothreat detection system in mail sorting facilities. In December 2002, we announced that the Northrop Grumman consortium received a contract award from the USPS to expand and continue testing of the biothreat detection system being developed by the consortium. Under the pre-production contract, biothreat detection system units will be installed and tested at 14 USPS facilities. If a full production contract is awarded, the biothreat detection system may eventually be deployed at postal service mail sorting facilities throughout the country.
In addition to the USPS project, we have received grants and research contracts from the following U.S. government agencies that have contributed funding toward much of our fundamental technology development:
In addition, all of the agencies above as well as the following U.S. government agencies have purchased Smart Cycler and Smart Cycler TDs:
Applied BioSystems. In October 2002, we entered into a collaboration agreement with Applied Biosystems to develop reagents for use in the biothreat detection system under development for the USPS by the consortium led by Northrop Grumman Corporation. Under the agreement, reagents will be manufactured by Applied Biosystems for packaging by us into our GeneXpert test cartridges and sold by us for use in the biothreat detection system. This agreement calls for collaboration profits to be shared.
Ortho-Clinical Diagnostics. In December 2002, we entered into an agreement to collaborate with Ortho-Clinical Diagnostics, Inc in the development and sale of DNA-based tests to be run on our Smart Cycler instrument in the field of cancer. Under the agreement, Ortho-Clinical Diagnostics will develop and commercialize a line of molecular diagnostic assays in the field of oncology and will serve as the a manufacturer's representative for Cepheid in the sale of Smart Cycler II's for use with oncology assays on a worldwide basis.
MANUFACTURING
Our facilities and manufacturing processes are designed to comply with FDA's Quality Systems Requirements to enable us to market our systems in the future into the clinical genetic assessment and industrial testing markets. We perform final assembly, calibration and test of our instruments. We produce our patented disposable reaction tubes on a custom, automated assembly line. We believe that this line can be expanded to deliver up to 20 million tubes per year. In April 2002, we moved all our operations to new facilities in Sunnyvale, California. Our new manufacturing facility provides increased capacity for assembly, test and inventory of our products and is has been built to fully comply with International Organization for Standardization and Current Good Manufacturing Practice requirements. During 2003, we intend to complete the design and construction of an automated assembly line for our GeneXpert cartridges.
During 2002, we received ISO 9001 certification through Underwriters Laboratories Inc. ISO 9001 certification is a manufacturing quality standard set by the International Organization for Standardization quality standards. The ISO 9001 certification's scope includes the design, manufacture and service of our DNA detection systems and tests.
COMPETITION
Several companies provide instruments and reagents for DNA amplification or detection. Applied Biosystems, Hoffmann La Roche, BioRad and Stratagene sell systems integrating amplification and detection (sequence detection systems) to the commercial market. Idaho Technologies sells sequence detection systems to the military market. Hoffman LaRoche, Abbott, and GenProbe sell large batch sequence detection systems, some with separate robotic batch DNA purification systems and sell reagents to the clinical genetic assessment market. Organon Teknika, Promega and Qiagen are competitors in the area of sample preparation, selling both sample preparation kits and robotic systems.
We face intense competition from a number of companies that offer products in our targeted application areas. These competitors include:
In order to compete against vendors of conventional products, we will need to demonstrate the advantages of our products over alternative well-established technologies and products. We will also need to demonstrate the potential economic value of our products relative to these conventional technologies and products.
We also face competition from both established and development-stage companies that continually enter these markets. Several companies are currently making or developing products that may or will compete with our products. Our competitors may succeed in developing, obtaining FDA approval for, or marketing technologies or products that are more effective or commercially attractive than our potential products or that render our technologies and potential products obsolete. As these companies develop their technologies, they may develop proprietary positions that prevent us from successfully commercializing our products.
We will also need to compete effectively with companies developing their own microfluidics technologies and products, such as ACLARA Biosciences, Caliper, and Nanogen. Other companies we are aware of that are involved in microfluidic research include Affymetrix, Motorola, 3M and Applied Biosystems. Microfluidic technologies have undergone and are expected to continue to undergo rapid and significant change. Rapid technological development may result in our products or technologies becoming obsolete. Products we offer could be made obsolete either by less expensive or more effective products based on similar or other technologies. Our future success will depend on our ability to establish and maintain a competitive position in these and future technologies.
We also compete against universities and public and private research institutions. While these organizations primarily have educational or basic research objectives, they may develop proprietary technology and acquire patents that we need for the development of our products. Licenses to this proprietary technology may not be available to us on acceptable terms, if at all.
In many instances, particularly in the clinical genetics assessment area, our competitors have substantially greater financial, technical, research and other resources, and larger, more established marketing, sales, distribution and service organizations than we have. Moreover, these competitors may offer broader product lines and tactical discounts and have greater name recognition. If we fail to compete effectively against these and other competitors, we will lose sales and our business will be harmed.
We believe that the principal competitive factors affecting sales of genetic and DNA analysis systems include the speed, integrated functionality and portability of the equipment, the quality of the test results, price, market acceptance of the technology, regulatory approvals and possession of the necessary intellectual property licenses for specific markets, collaborations and distributor relationships for specific markets and assays, and the selection of assays available for the equipment. We believe our products more completely integrate the various processes associated with genetic and DNA analysis than other currently available equipment, and that the speed, portability, flexibility, and reliability of our products is very competitive. Our systems are competitively priced with other similar systems in the marketplace. The timely introduction and commercial launch of GeneXpert system will be an important part of establishing our leadership with respect to each of these factors. Our sales are relatively small compared to those of many of our competitors, but we believe that the introduction of GeneXpert, our growing distributor and collaborative base, and securing some high-profile contacts would build our public profile and market acceptance.
GOVERNMENT REGULATION
For the biomedical research market, we do not anticipate the need for FDA or other regulatory approval. We anticipate, however, the manufacturing, labeling, distribution and marketing of some or all of the diagnostic products under development or diagnostic products we may develop and commercialize in the future will be subject to regulation in the United States and in other countries. In addition to clinical genetic assessment markets, we also may pursue forensic, agricultural, environmental, laboratory and industrial applications for our products, which may be subject to different government regulation. Aspects of our manufacturing and marketing activities may also be subject to federal, state and local regulation by various governmental authorities.
In the United States, the FDA regulates, as medical devices, most diagnostic tests and in vitro reagents that are marketed as finished test kits and equipment. Pursuant to the Federal Food, Drug and Cosmetic Act, and the regulations promulgated thereunder, the FDA regulates the preclinical and clinical testing, design, manufacture, labeling, distribution and promotion of medical devices. We will not be able to commence marketing or commercial sales in the United States of new medical devices under development that fall within the FDA's jurisdiction until we receive clearance or approval from the FDA, which can be a lengthy, expensive, and uncertain process. Noncompliance with applicable requirements can result in, among other things, administrative or judicially imposed sanctions such as injunctions, civil penalties, recall or seizure of products, total or partial suspension of production, failure of the government to grant premarket clearance or premarket approval for devices, withdrawal of marketing clearances or approvals, or criminal prosecution. To date, we have only received FDA approval for use of the group B strep assay for Smart Cycler that we developed with IDI. We have not sought approval from the FDA or any other governmental body for other assays for the Smart Cycler, and we have not received any such approvals.
INTELLECTUAL PROPERTY
We rely upon a combination of patent, copyright, trade secret and trademark laws, and contractual restrictions, such as confidentiality agreements and licenses, to establish and protect our proprietary rights.
Patents and patents pending
We hold an exclusive license to key technologies from the Lawrence Livermore National Laboratory ("LLNL") in the fields of nucleic acid analysis and ligand binding assays with integrated optical detection. These technologies have resulted in two issued U.S. patents and include two pending U.S. patent applications and two pending international counterpart patent applications. The LLNL technologies are the basis of our I-CORE module and encompass the key I-CORE features.
We have an additional 11 issued or allowed U.S. patent on our disposable reaction tube, thermocycling with optics, and disposable sample preparation cartridges. We have an additional 31 pending U.S. patent applications plus corresponding international counterpart applications relating to our technologies. Our pending patent applications relate to our I-CORE module, reaction tubes, lysing technology, nucleic acid concentration chip and microfluidic devices, and methods and systems as applied to sample processing and automated DNA analysis.
Outside technologies required
We have obtained a thermal cycling license from Applied Biosystems for the sale of thermal cycling systems in the life sciences research, industrial testing and drug discovery and development markets. We may require a license from Applied Biosytems to sell thermal cycling systems in the field of clinical genetic assessment.
In the area of clinical genetic assessment for PCR-based applications, we will require licenses from various parties, including Hoffmann La Roche for application to this field. These licenses may include substantial up front payments as well as ongoing royalties on product sales. In most cases, these royalties on product sales will be based on the end user sales price. In some cases, we may obtain these licenses directly while in other cases we may obtain these rights through a partnership or collaboration.
Our competitive success will be affected in part by our continued ability to obtain and maintain patent protection for our inventions, technologies and discoveries, including intellectual property that we license. Our pending patent applications may lack priority over others' applications or may not result in the issuance of patents. Even if issued, our patents may not be sufficiently broad to provide protection against competitors with similar technologies and may be challenged, invalidated or circumvented.
In addition to patents, we rely on a combination of trade secrets, copyright and trademark laws, nondisclosure agreements, licenses and other contractual provisions and technical measures to maintain and develop our competitive position with respect to intellectual property. Nevertheless, these measures may not be adequate to safeguard the technology underlying our products. For example, employees, consultants and others who participate in the development of our products may breach their agreements with us regarding our intellectual property and we may not have adequate remedies for the breach. We also may not be able to effectively protect our intellectual property rights in some foreign countries. For a variety of reasons, we may decide not to file for patent, copyright or trademark protection outside of the United States. Our trade secrets could become known through other unforeseen means. Notwithstanding our efforts to protect our intellectual property, our competitors may independently develop similar or alternative technologies or products that are equal or superior to our technology. Our competitors may also develop similar products without infringing on any of our intellectual property rights or design around our proprietary technologies.
EMPLOYEES
As of December 31, 2002, we had 148 fulltime employees. Approximately 75 employees were engaged in research and product development, of which 56 are in engineering and 19 in biotechnology. None of our employees are represented by a labor union. We place a high value on our human capital and consider our employee relations to be good.
EXECUTIVE OFFICERS
Set forth below is the name, age, position and a brief account of the business experience of each of our executive officers and directors:
|
Name |
Age |
Position |
|
John L. Bishop |
58 |
Chief Executive Officer and Director |
|
Thomas L. Gutshall |
65 |
Chairman of the Board and Director |
|
Kurt Petersen, PhD |
55 |
President, Chief Operating Officer and Director |
|
John R. Sluis |
57 |
Vice President, Finance and Chief Financial Officer |
__________
John L. Bishop. Mr. Bishop joined us as chief executive officer and as a director in April 2002. Mr. Bishop served as president and a director of Vysis from 1993 to 2002 and as Chief Executive Officer from 1996 to 2002. From 1991 until November 1993, Mr. Bishop was Chairman and Chief Executive Officer of Microprobe Corporation and, from 1987 to 1991, of Source Scientific Systems. From 1984 to 1986, Mr. Bishop was President and Chief Operating Officer of Gen- Probe, Inc. From 1968-1984, Mr. Bishop held various management positions with American Hospital Supply Company and its affiliates, including a three year assignment in Japan as an Executive Vice President and Chief Executive Officer of International Reagents Corp., a joint venture between American Hospital Supply Company and Green Cross Corporation.
Thomas L. Gutshall. Mr. Gutshall is a co-founder of Cepheid and has served us as Chairman of the Board since August 1996. From August 1996 until April 2002, he also served as our Chief Executive Officer. From January 1995 to August 1996, he was President and Chief Operating Officer of CV Therapeutics. From 1989 to 1994, he was Executive Vice President at Syntex Corporation and a member of the Pharmaceutical Executive Committee. His responsibilities while at Syntex included managing Syva Company, Syntex Agribusiness, Pharmaceutical and Chemical Operations and Services, Syntex Pharmaceutical Intl. Ltd. and Environmental Health and Safety. He is also a member of the board of directors of CV Therapeutics and Metrika, Inc.
Kurt Petersen, Ph.D. Dr. Petersen is a co-founder of Cepheid and has served us as President and Chief Operating Officer since August 1996, and has served as our secretary since May 2002. From January 1996 through July 1996, Dr. Petersen worked as a private consultant. From 1985 to 1995, he served as Vice President, Technology for NovaSensor. While at NovaSensor, he was responsible for commercializing many innovative micromachined devices and fundamental fabrication processes. He holds over 20 patents and has authored over 80 technical papers and presentations. Dr. Petersen is a fellow of the IEEE and a member of the National Academy of Engineering. In 2001, he was awarded the Simon Ramo Medal by the IEEE.
John R. Sluis. Mr. Sluis joined us as Vice President, Finance and Chief Financial Officer in July 2002. Prior to joining the company, Mr. Sluis was Senior Vice President and Chief Financial Officer of Vysis from June 2000 through February 2002. Before joining Vysis, he held various positions at Sanofi Diagnostics, from 1989 through 1999 including serving as its President of North American Operations from 1997 to 1999.
RISK FACTORS
You should carefully consider the risks described below, together with all of the other information included in this report, in considering our business and prospects. The risks and uncertainties described below are not the only ones facing Cepheid. Additional risks and uncertainties not presently known to us or that we currently deem immaterial also may impair our business operations. The occurrence of any of the following risks could harm our business, financial condition or results of operations
.If we cannot successfully commercialize our GeneXpert system, we may never achieve profitability.
Although we plan to introduce it commercially in the second half of 2003, our GeneXpert system is still in the development stage. We anticipate that for the foreseeable future our ability to achieve profitability will depend in part on the successful commercialization of our GeneXpert system. Many factors may affect the market acceptance and commercial success of our GeneXpert system, including:
We have not established the accuracy, reliability or ease of operation of the GeneXpert system in commercial use. If the GeneXpert system does not gain market acceptance, we will be unable to generate significant sales, which may prevent us from achieving profitability. If the GeneXpert system is not accepted in the marketplace, this could have a negative effect on our ability to sell subsequent systems.
Our participation in the USPS biothreat detection program evaluation and other similar programs may not result in contracts or revenues.
We are part of a Northrop Grumman-led team being evaluated by the USPS to produce a DNA-based biothreat detection system for installation in USPS mail sorting facilities. We cannot state with certainty when this evaluation process will conclude, whether our team will be awarded a production contract, whether such a contract would be concluded on terms acceptable to all parties, or whether actual funding, deployment and operating parameters, or product purchases, will meet expected levels. The USPS biothreat detection system program, like many governmental contracting programs, involves significant uncertainties in the timing of decision-making and deployment and is highly sensitive to changes in national and international priorities and budgets. In addition, if components developed by us or our collaborators in the program fail to meet specifications, the entire proposal team could be rejected. In this and any similar future pilot programs, there may be no obligation on the part of the eventual customer to buy a minimum number of units, so, even if we are awarded a production contract, we may be subject to our customer's future spending patterns and budgetary cycles. Accordingly, our participation in the USPS biothreat detection system program and other similar programs are subject to a number of risks and uncertainties and may never yield significant revenues.
We may not achieve or maintain profitability and may be unable to continue our operations.
We have experienced significant operating losses each year since our inception and expect to have negative cash flow from operations through at least the end of 2003. We experienced net losses of approximately $14.8 million in 2000, $15.5 million in 2001 and $19.7 million in 2002. As of December 31, 2002, we had an accumulated deficit of approximately $62.6 million. Our ability to become profitable will depend on our revenue growth, which depends on a number of factors including market acceptance of our products, the success of any pilot programs in which we are participating, and our expense levels. Our expense levels are, in turn, influenced by a number of factors, including the resources we devote to developing and supporting our products, continued progress of our research and development of potential products and the need to acquire licenses to new technology or to use our technology in new markets. If we fail to grow our revenue and manage our expenses, we may never achieve profitability.
We may require licenses for new product features and products, and our strategic plans and growth could be impaired if we are unable to obtain such licenses.
We will need to introduce new products and product features in order to market our products to a broader customer base. Our products typically require licenses from third-party suppliers in order to be sold. Accordingly, our introduction of new products and product features could require us to obtain additional licenses. We may not be able to obtain such licenses on commercially reasonable terms, if at all. The failure to obtain necessary licenses or other rights could have a material adverse effect on our anticipated strategies and growth.
We will require licenses for certain reagents to produce a more complete solution, and our business will suffer if we are unable to obtain such licenses.
For certain markets, we intend to manufacture reagents for use with our Smart Cycler and GeneXpert systems to offer a more complete solution for the detection and analysis of DNA. We require licenses for many reagents. We believe that manufacturing reagents for use in our Smart Cycler and GeneXpert systems is important to our business and growth prospects. We may not be able to obtain licenses for certain reagents on commercially reasonable terms, if at all. Some of our competitors have rights to reagents that we have not yet obtained. Our failure to obtain similar rights would limit our ability to offer a system that includes reagents and would adversely affect our competitive position and our performance.
The regulatory approval process is expensive, time-consuming, uncertain and may prevent us from obtaining required approvals for the commercialization of some of our products.
Some of our products, depending upon their intended use, will be subject to approval or clearance by the FDA or foreign governmental entities prior to their marketing for commercial use. Products, such as the Smart Cycler and, when it is launched commercially, the GeneXpert system, when used for clinical diagnostic purposes will require such approval. To date, we have only received FDA approval for use of the group B strepococcos assay for Smart Cycler that was developed through our collaboration with IDI. We have not sought approval from the FDA or any other governmental body for other assays for the Smart Cycler, and we have not received any such approvals. The process of obtaining necessary FDA or foreign clearance or approvals can be lengthy, expensive and uncertain. We generally expect to rely on our collaborators to direct the regulatory approval process for our products. There are no assurances that such collaborators will timely and diligently pursue such process, or that they or we can obtain any required clearance or approval. Any such failure, or any material delay in obtaining the clearance or approval, could harm our business, financial condition and results of operations.
In addition, our failure or the failure of our collaborators to comply with regulatory requirements applicable to our products could result in significant sanctions, including:
If we fail to respond to changing technologies, demand for our products and our ability to enhance our revenues will suffer.
If we do not continue to improve our products and develop new products that keep pace with competitive product introductions and technological developments, satisfy diverse and rapidly evolving customer requirements and achieve market acceptance; we might be unable to attract new customers. The development of proprietary technology and necessary service enhancements entails significant technical and business risks and requires substantial expenditures and lead-time. We may also need to modify our manufacturing processes with respect to changes in product design or new product introductions. We might not be successful in developing and marketing product enhancements and new products that respond to technological advances and market changes, on a timely or cost- effective basis. In addition, even if these products are developed and released, they might not achieve market acceptance.
If our competitors and potential competitors develop superior products and technologies our competitive position and results of operations would suffer.
We face intense competition from a number of companies that offer products in our targeted application areas. These competitors include:
We also face competition from both established and development-stage companies that continually enter these markets. Several companies are currently making or developing products that may or will compete with our products. Our competitors may succeed in developing, obtaining FDA approval for, or marketing technologies or products that are more effective or commercially attractive than our potential products, or that render our technologies and potential products obsolete. As these companies develop their technologies, they may develop proprietary positions that prevent us from successfully commercializing our products.
We also need to compete effectively with companies developing their own microfluidics technologies and products. Microfluidic technologies have undergone and are expected to continue to undergo rapid and significant change. Rapid technological development may result in our products or technologies becoming obsolete. Products we offer could be made obsolete either by less expensive or more effective products based on similar or other technologies. Our future success will depend on our ability to establish and maintain a competitive position in these and future technologies.
We also compete against universities and public and private research institutions. While these organizations primarily have educational or basic research objectives, they may develop proprietary technology and acquire patents that we need for the development of our products. Licenses to this proprietary technology may not be available to us on acceptable terms, if at all.
In many instances, particularly in the clinical genetic assessment area, our competitors have substantially greater financial, technical, research and other resources, and larger, more established marketing, sales, distribution and service organizations than we have. Moreover, these competitors may offer broader product lines and tactical discounts and have greater name recognition. If we fail to compete effectively against these and other competitors, we will lose sales and our business will be harmed.
If our products do not perform as expected, or the reliability of the technology on which our products are based is questioned, we could experience lost revenue, delayed or reduced market acceptance of our products, increased costs and damage to our reputation.
Our success depends on the market's confidence that we can provide reliable, high quality genetic and DNA testing systems. We believe that customers in the life sciences research, biothreat applications and genetic management of disease markets are likely to be particularly sensitive to product defects and errors. Our reputation and the public image of our products or technologies may be impaired for any of the following reasons:
Even after any underlying concerns or problems are resolved, any widespread concerns regarding our technology or any manufacturing defects or performance errors in our products could result in lost revenue, delay in market acceptance, damage to our reputation, increased service and warranty costs, and claims against us.
If product liability lawsuits are successfully brought against us, we may face reduced demand for our products and incur significant liabilities.
We face an inherent business risk of exposure to product liability claims if our technologies or systems are alleged to have caused harm. We cannot be certain that we can successfully defend any product liability lawsuit brought against us. Regardless of merit or eventual outcome, product liability claims may result in:
If we are the subject of a successful product liability lawsuit which exceeds the limits of any insurance coverage we may have, we may incur substantial liabilities, which would adversely affect our earnings and financial condition.
The world geopolitical climate has created increased financial expectations that may not materialize.
The world geopolitical climate in the wake of the September 11, 2001 terrorist attacks has created increased interest in bio-threat detection systems. However, we are uncertain what the long-term impact will be on our product sales. Even if our products are chosen as a part of the solution for the biothreat detection system for the USPS, it is unclear what the level and how quickly funding may be made available. These factors may adversely impact us and create unpredictability in our revenues and operating results.
If we are unable to maintain our relationships with collaborative partners, we may have difficulty selling our products and services.
We believe that our success in penetrating our target markets and in bidding for certain kinds of contracts (such as the USPS pilot program) depends in part on our ability to develop and maintain collaborative relationships with key companies. However, our collaborative partners may not be able to perform their obligations as expected or devote sufficient resources to the development, supply or marketing of potential products developed under these collaborations. Also, if a key collaborative partner fails to perform its obligations as expected, including, for example, if it becomes insolvent or is acquired by another company with which we have no relationship, we may not be able to develop an adequate alternative in a timely manner.
Currently, our significant collaborative partners include:
Relying on these or other collaborative relationships is risky to our future success because, among other things:
If we are unable to manufacture the GeneXpert system and reagents in sufficient quantities and at acceptable costs, we may be unable to meet demand for our products and our ability to generate revenue will be diminished.
We are in the process of launching our manufacturing process for our GeneXpert system and reagents to support commercial sales. We have limited manufacturing experience, and we cannot assure you that manufacturing or quality control problems will not arise as we attempt to produce our GeneXpert systems or reagents, or that we can scale-up manufacture and quality control in a timely manner or at commercially reasonable costs. If we are unable to manufacture GeneXpert systems or reagents consistently on a timely basis because of these or other factors, our product sales will be negatively affected.
With the launch of a diagnostic product, our manufacturing facilities, where we produce the Smart Cycler system and the GeneXpert system, cartridges and reagents, will be subject to periodic regulatory inspections by the FDA and other federal and state regulatory agencies. These facilities are subject to Quality System Regulation, or QSR, requirements of the FDA. If we fail to maintain our facilities in accordance with the QSR requirements, international quality standards or other regulatory requirements, the manufacturing process could be suspended or terminated, which would impair our business.
If our direct selling efforts for our products fail, our business expansion plans could suffer and our ability to generate revenue will be diminished.
We are utilizing a direct sales force to market our products in some markets. We have relatively small sales force compared to our competitors. Failure to effectively promote and sell our products in these markets could have a negative impact on their market acceptance. If our systems fail to penetrate these expanding markets, this could have a negative effect on our ability to sell subsequent systems and hinder the planned expansion of our business.
If we fail to effectively manage our modifications and planned modifications to our distribution network, our sales could decline.
We are currently in the process of modifying our distribution network, phasing in new distributors, changing our relationships with our existing distributors and increasing our direct sales efforts. These relationships are new and we cannot predict whether they will be successful. Furthermore, we have limited experience and infrastructure for managing a larger network of distributors. If we cannot effectively manage this new broader network of distributors, our sales and marketing efforts in these geographic areas would be adversely affected and our operating results could suffer.
If our distributor relationships are not successful, our ability to market and sell our products in the life sciences research market would be harmed and our financial performance will be adversely affected.
We are dependent on relationships with distributors for the marketing and sales of our products in the life sciences research market in various geographic regions and we have a limited ability to influence their efforts. For example, Takara Bio, Inc. is the exclusive distributor of Smart Cycler in the life sciences research market in Japan, South Korea, China, and Taiwan and we also rely on various distributors for our sales of Smart Cycler in the European life sciences research market. Relying on distributors for our sales and marketing in these regions is risky to our future for various reasons, including:
We may be subject to third- party claims that we require additional licenses for our products, and such claims could interfere with our business.
Our industry is characterized by a large number of patents, claims of which appear to overlap in many cases. As a result, there is a significant amount of uncertainty regarding the extent of patent protection and infringement. Obtaining licenses to relevant patents could be costly and could materially harm our results of operations and future cash flows. Failing to obtain a license could result in litigation which may consume our resources and lead to significant damages, royalty payments or an injunction on the sale of our currently existing products.
If our products infringe on the intellectual property rights of others, we could face costly litigation, which could cause us to pay substantial damages and limit our ability to sell some or all of our products.
Our market success depends in part on us neither infringing valid, enforceable patents or proprietary rights of third parties, nor breaching any licenses that may relate to our technologies and products. We are aware of third-party patents that may relate to our technology. We plan to seek licenses, as we deem appropriate; however, it is possible that we may unintentionally infringe upon these patents or proprietary rights of third parties. In response, third parties may assert infringement or other intellectual property claims against us. We may consequently be subjected to substantial damages for past infringement or be required to modify our products if it is ultimately determined that our products infringe a third party's proprietary rights. Further, we may be prohibited from selling our products before we obtain a license, which, if available at all, may require us to pay substantial royalties. Even if these claims are without merit, defending a lawsuit takes significant time, may be expensive and may divert management attention from other business concerns. Any public announcements related to litigation or interference proceedings initiated or threatened against us could cause our stock price to decline.
We may need to initiate lawsuits to protect or enforce our patents, which would be expensive and, if we lose, may cause us to lose some, if not all, of our intellectual property rights, and thereby impair our ability to compete.
We rely on patents to protect a large part of our intellectual property. To protect or enforce our patent rights, we may initiate patent litigation against third parties, such as infringement suits or interference proceedings. These lawsuits could be expensive, take significant time and divert management's attention from other business concerns. They would also put our patents at risk of being invalidated or interpreted narrowly and our patent applications at risk of not issuing. We may also provoke these third parties to assert claims against us. Patent law relating to the scope of claims in the technology fields in which we operate is still evolving and, consequently, patent positions in our industry are generally uncertain. We cannot assure you that we would prevail in any of these suits or that the damages or other remedies awarded, if any, would be commercially valuable. During the course of these suits, there may be public announcements of the results of hearings, motions and other interim proceedings or developments in the litigation. If securities analysts or investors perceive any of these results to be negative, it could cause our stock to decline.
If we fail to maintain and protect our intellectual property rights, our competitors could use our technology to develop competing products and our business will suffer.
Our competitive success will be affected in part by our continued ability to obtain and maintain patent protection for our inventions, technologies and discoveries, including intellectual property that we license. Our pending patent applications may lack priority over others' applications or may not result in the issuance of patents. Even if issued, our patents may not be sufficiently broad to provide protection against competitors with similar technologies and may be challenged, invalidated or circumvented.
In addition to patents, we rely on a combination of trade secrets, copyright and trademark laws, nondisclosure agreements, licenses and other contractual provisions and technical measures to maintain and develop our competitive position with respect to intellectual property. Nevertheless, these measures may not be adequate to safeguard the technology underlying our products. For example, employees, consultants and others who participate in the development of our products may breach their agreements with us regarding our intellectual property and we may not have adequate remedies for the breach. We also may not be able to effectively protect our intellectual property rights in some foreign countries. For a variety of reasons, we may decide not to file for patent, copyright or trademark protection outside of the United States. Our trade secrets could become known through other unforeseen means. Notwithstanding our efforts to protect our intellectual property, our competitors may independently develop similar or alternative technologies or products that are equal or superior to our technology. Our competitors may also develop similar products without infringing on any of our intellectual property rights or design around our proprietary technologies.
Our international operations and proposed expansion subject us to additional risks and costs.
Our international operations are subject to a number of difficulties and special costs, including:
We intend to expand our international sales and marketing activities and enter into relationships with additional international distribution partners. We are in the early stages of developing our indirect distribution channels in markets outside the United States. We may not be able to attract distribution partners that will be able to market our products effectively.
Our international operations could also increase our exposure to international laws and regulations. If we cannot comply with foreign laws and regulations, which are often complex and subject to variation and unexpected changes, we could incur unexpected costs and potential litigation. For example, the governments of foreign countries might attempt to regulate our products and services or levy sales or other taxes relating to our activities. In addition, foreign countries may impose tariffs, duties, price controls or other restrictions on foreign currencies or trade barriers, any of which could make it more difficult for us to conduct our business.
The nature of our products may also subject us to export control regulation by the U.S. Department of State and the Department of Commerce. Violations of these regulations can result in monetary penalties and denial of export privileges.
If our single source suppliers fail to deliver key product components in a timely manner, our manufacturing ability would be impaired and our product sales could suffer.
We depend on long term delivery contracts with several single source suppliers that supply components used in the manufacture of our Smart Cycler andGeneXpert systems, disposable reaction tubes, and cartridges. If we need alternative sources for key component parts for any reason, such component parts may not be immediately available. If alternative suppliers are not immediately available, we will have to identify and qualify alternative suppliers, and production of such components may be delayed. We may not be able to find an adequate alternative supplier in a reasonable time period, or on commercially acceptable terms, if at all. Our inability to obtain a key source supplier for the manufacture of our potential products may force us to curtail or cease operations.
We expect that our operating results will fluctuate significantly, and any failure to meet financial expectations may disappoint securities analysts or investors and result in a decline in our stock price.
We expect that our quarterly operating results will fluctuate in the future as a result of many factors, some of which are outside of our control. Because our revenue and operating results are difficult to predict, we believe that period-to-period comparisons of our results of operations are not a good indication of our future performance. We expect our gross profit to fluctuate depending upon the timing of introduction and acceptance of our products. In addition, our operating results may be affected by the inability of some of our customers to consummate anticipated purchases of our products, whether due to changes in internal priorities or, in the case of governmental customers, problems with the appropriations process. It is possible that in some future quarter or quarters our operating results will be below the expectations of securities analysts or investors. In this event, the market price of our common stock may fall abruptly and significantly.
Broad market fluctuations in our stock price could result in the loss of market makers for our common stock, which could, in turn, result in a decline in the price of our common stock. To maintain our eligibility for listing on Nasdaq, we must maintain a minimum number of market makers and meet and maintain other eligibility requirements, including a minimum trading value of our common stock. A prolonged decline in the price of our common stock could effect the operation of our business by severely limiting our ability to raise capital or to use our common stock in connection with acquisitions. In addition because the price of our common stock is below $5.00 per share, broker dealers have to follow specific disclosure and suitability obligations requirements, which could limit the marketability of our common stock.
If revenue declines in a quarter, whether due to a delay in recognizing expected revenue or otherwise, our earnings will decline because many of our expenses are relatively fixed. In particular, research and development and selling, general and administrative expenses are not significantly affected by variations in revenue.
If we fail to obtain an adequate level of reimbursement for our products from third-party payers, our ability to sell products in some markets would be harmed.
Our ability to sell our products in the clinical genetic assessment market will depend in part on the extent to which reimbursement for our products and related treatments will be available from:
If appropriate reimbursement cannot be obtained, we could be prevented from successfully commercializing some of our potential products.
There are efforts by governmental and third-party payors to contain or reduce the costs of health care through various means. Additionally, third-party payors are increasingly challenging the price of medical products and services. If purchasers or users of our products are not able to obtain adequate reimbursement for the cost of using our products, they may forego or reduce their use. Significant uncertainty exists as to the reimbursement status of newly approved health care products and whether adequate third-party coverage will be available.
If we fail to retain key members of our staff, our ability to conduct and expand our business would be impaired.
We are highly dependent on the principal members of our management and scientific staff. The loss of services of any of these persons could seriously harm our product development and commercialization efforts. In addition, we will require additional skilled personnel in areas such as manufacturing, quality control, project management, microbiology, software engineering, mechanical engineering and electrical engineering. Retaining and training personnel with the requisite skills is challenging even in today's economy, and, when general economic conditions improve, is likely to become extremely competitive again, particularly in the Silicon Valley area of California where we are headquartered. If at any point we are unable to hire, train and retain a sufficient number of qualified employees to match our growth, our ability to conduct and expand our business could be seriously reduced. The inability to retain and hire qualified personnel could also hinder the planned expansion of our business.
If we fail to raise additional capital, our ability to fund our operations and advance our development programs would be impaired and our business would be adversely affected.
Including net proceeds received of $4.7 million from our common stock offering completed in March 2003, we anticipate that our existing capital resources will enable us to maintain currently planned operations through December 2003. This expectation is based on our current operating plan and may change as a result of many factors, including market acceptance of our products and future opportunities with collaborators. Consequently, we may need additional funding sooner than anticipated. We currently have no credit facility or committed sources of capital. To the extent operating and capital resources are insufficient to meet future requirements, we will have to raise additional funds. These funds may not be available on favorable terms, if at all. If adequate funds are not available on attractive terms, we may be required to curtail operations significantly or to obtain funds by entering into financing, supply or collaboration agreements on unattractive terms.
In addition, we may choose to raise additional capital due to market conditions or strategic considerations even if we believe we have sufficient funds for our current or future operating plans. To the extent that additional capital is raised through the sale of equity or convertible debt securities, the issuance of these securities could result in dilution to our shareholders. In addition, such securities may be sold at a discount from the market price of our common stock, and may include rights preferences or privileges senior to those of our common stock.
If we acquire companies, products or technologies, we may face risks associated with those acquisitions.
If we are presented with appropriate opportunities, we may make other investments in complementary companies, products or technologies. We may not realize the anticipated benefit of any acquisition or investment. If we acquire another company, we will likely face risks, uncertainties and disruptions associated with the integration process, including difficulties in the integration of this operations, and services of the acquired company, the diversion of our management's attention from other business concerns and the potential loss of key employees or customers of the acquired businesses. If we fail to successfully integrate other companies that we may acquire, our business could be harmed. Furthermore, we may have to incur debt or issue equity securities to pay for any additional future acquisitions or investments, the issuance of which could be dilutive to our existing shareholders or us. In addition, our operating results may suffer because of acquisition-related costs or amortization expenses or charges relating to acquired goodwill and other intangible assets.
If a catastrophe strikes our manufacturing facilities, we may be unable to manufacture our products for a substantial amount of time and we would experience lost revenue.
Our manufacturing facilities are located in Sunnyvale, California. Even though we have business interruption insurance, our facilities and some pieces of manufacturing equipment are difficult to replace and could require substantial replacement lead-time. Various types of disasters, including earthquakes, fires, floods and acts of terrorism, may affect our manufacturing facilities. Earthquakes are of particular significance since the manufacturing facilities are located in an earthquake-prone area. In the event our existing manufacturing facilities or equipment is affected by man-made or natural disasters, we may be unable to manufacture products for sale, meet customer demands or sales projections. If our manufacturing operations were curtailed or ceased, it would seriously harm our business.
If we become subject to claims relating to improper handling, storage or disposal of hazardous materials, we could incur significant cost and time to comply.
Our research and development processes involve the controlled storage, use and disposal of hazardous materials, including biological hazardous materials. We are subject to federal, state and local regulations governing the use, manufacture, storage, handling and disposal of materials and waste products. We may incur significant costs complying with both existing and future environmental laws and regulations. In particular, we are subject to regulation by the Occupational Safety and Health Administration, or OSHA, and the Environmental Protection Agency, or EPA, and to regulation under the Toxic Substances Control Act and the Resource Conservation and Recovery Act. OSHA or the EPA may adopt regulations that may affect our research and development programs. We are unable to predict whether any agency will adopt any regulations that would have a material adverse effect on our operations.
Although we believe that our safety procedures for handling and disposing of these hazardous materials comply with the standards prescribed by law and regulation, the risk of accidental contamination or injury from hazardous materials cannot be eliminated completely. In the event of an accident, we could be held liable for any damages that result, and any liability could exceed the limits or fall outside the coverage of our insurance. We may not be able to maintain insurance on acceptable terms, if at all. We could be required to incur significant costs to comply with current or future environmental laws and regulations.
ITEM 2. PROPERTIES
We currently lease approximately 76,000 square feet of office and laboratory space in Sunnyvale, California, which serves as the base for our manufacturing, product support and research and development efforts pursuant to a lease that expires in March 2012. We also own a 9,500 square feet building outside of Toulouse, France. We expect that this space will meet our currently anticipated facilities needs at least through 2007. If necessary, we believe we will be able to obtain additional facilities space on commercially- reasonable terms.
ITEM 3. LEGAL PROCEEDINGS
As previously reported in our quarterly report on Form 10Q for the quarter ended June 30, 2002, on July 17, 2002, Fisher Scientific Company L.L.C. ("Fisher") filed a lawsuit against Cepheid in the United States District Court. The parties entered into a settlement agreement with respect to the dispute in the fourth quarter of 2002, pursuant to which the parties dismissed all claims against each other.
We are currently not a party to any material pending legal proceedings.
ITEM 4. SUBMISSION OF MATTERS TO A VOTE OF SECURITY HOLDERS
No matters were submitted to a vote of security holders in the last quarter of 2002.
PART II
ITEM 5. REGISTRANT'S COMMON EQUITY AND RELATED SHAREHOLDER MATTERS
Our common stock has been traded on the Nasdaq National Market since our initial public offering on June 21, 2000 under the symbol CPHD. Prior to such time, there was no public market for our common stock. Through March 18, 2002, the high and low sale prices for our common stock, as reported on the Nasdaq National Market, were as follows:
|
|
High |
Low |
|
Fiscal 2001 First Quarter 2001 Fiscal 2002 First Quarter 2002 Fiscal 2003 First Quarter 2003 (through March 18, 2003) |
$9.97
5.75
6.15 |
$2.97
2.23
3.25 |
On March 18, 2003 the last reported sale price of our common stock on the Nasdaq National Market was $4.64 per share. On March 18, 2003, there were approximately 296 holders of record of our common stock.
We have never declared or paid any cash dividends on our capital stock. We currently intend to retain future earnings, if any, for development of our business and, therefore, do not anticipate that we will declare or pay cash dividends on our capital stock in the foreseeable future.
ITEM 6. SELECTED FINANCIAL DATA
The following tables contain selected consolidated financial data that were derived from our consolidated financial statements. The selected consolidated financial data set forth below should be read in conjunction with "Management's Discussion and Analysis of Financial Condition and Results of Operations," the consolidated financial statements and the related notes included elsewhere in this annual report on Form 10-K and in our prior annual and quarterly reports, and other information we have filed with the SEC. The historical results are not necessarily indicative of results to be expected for any future period. See "Management's Discussion and Analysis of Financial Condition and Results of Operations."
The pro forma net loss per share and shares used in computing pro forma net loss per share are calculated as if all of our convertible preferred stock was converted into shares of common stock on the date of their issuance. See Note 12 of Notes to Consolidated Financial Statements for information concerning the deemed dividend upon issuance of convertible preferred stock in the first quarter of 2000.
Year Ended December 31,
-----------------------------------------------------
2002 2001 2000 1999 1998
--------- --------- --------- --------- ---------
(in thousands, except per share data)
Consolidated Statements of Operations Data:
Revenues:
Product sales..................................... $ 12,413 $ 8,669 $ 4,397 $ 159 $ --
License and royalty revenue....................... 200 124 -- -- --
Grant and government sponsored
research revenue.................................. 1,838 2,554 2,249 2,249 2,870
Research and development
contract revenue.................................. 203 7 416 1,187 707
--------- --------- --------- --------- ---------
Total revenues....................................... 14,654 11,354 7,062 3,595 3,577
--------- --------- --------- --------- ---------
Operating costs and expenses:
Cost of product sales.............................. 8,766 6,330 3,851 97 --
Research and development (including
charges for stock-based compensation
of $351, $1,246 and $3,706 in 2002,
2001 and 2000, respectively)..................... 16,889 1