Resources Connection Inc.
Annual Report 2007

Plain-text annual report

WORKING Regeneron Pharmaceuticals, Inc. 777 Old Saw Mill River Road Tarrytown, NY 10591 regeneron.com Regeneron Annual Report 2007 Regeneron was founded on the principle that strong science and innovative tech- nology could accelerate the development of new medicines. From the beginning, we assembled teams of talented scientists and challenged them to thoroughly understand the biology of diseases, develop new technology platforms, and discover and develop potential therapeutic candidates. Forward-looking Statements and Risk Factors: This news release discusses historical information and in- cludes forward-looking statements about Regeneron and its products, development programs, finances, and business, all of which involve a number of risks and uncertainties, such as risks associated with preclinical and clinical development of Regeneron’s drug candidates, determinations by regulatory and administrative governmental authorities which may delay or restrict Regeneron’s ability to continue to develop or commer- cialize its product and drug candidates, competing drugs that are superior to Regeneron’s product and drug candidates, uncertainty of market acceptance of Regeneron’s product and drug candidates, unanticipated expenses, the availability and cost of capital, the costs of developing, producing, and selling products, the potential for any collaboration agreement, including Regeneron’s agreements with the sanofi-aventis Group and Bayer HealthCare, to be canceled or to terminate without any product success, risks associated with third party intellectual property, and other material risks. A more complete description of these and other material risks can be found in Regeneron’s filings with the United States Securities and Exchange Commis- sion (SEC), including its Form 10-K for the year ended December 31, 2007. Regeneron does not undertake any obligation to update publicly any forward-looking statement, whether as a result of new information, future events, or otherwise unless required by law. Corporate Directory Directors P. Roy Vagelos, M.D. Chairman of the Board Senior Management Team Leonard S. Schleifer, M.D., Ph.D. President and Chief Executive Officer Leonard S. Schleifer, M.D., Ph.D. George D. Yancopoulos, M.D., Ph.D. President and Chief Executive Officer Executive Vice President, Charles A. Baker Retired Chairman of the Board, President and Chief Executive Officer of The Liposome Company, Inc. Michael S. Brown, M.D. Regental Professor, Department of Molecular Genetics, The University of Texas Chief Scientific Officer and President, Regeneron Research Laboratories Murray A. Goldberg Senior Vice President, Finance and Administration, Chief Financial Officer, Treasurer and Assistant Secretary Stuart Kolinski Southwestern Medical Center at Dallas Senior Vice President, General Counsel and Secretary Peter Powchik, M.D. Senior Vice President, Clinical Development Neil Stahl, Ph.D. Senior Vice President, Research and Developmental Sciences Robert J. Terifay Senior Vice President, Commercial Daniel Van Plew Senior Vice President and General Manager, Industrial Operations and Product Supply Alfred G. Gilman, M.D., Ph.D. Provost and Executive Vice President for Academic Affairs, The University of Texas Dean, Southwestern Medical School Joseph L. Goldstein, M.D. Regental Professor and Chairman, Department of Molecular Genetics, The University of Texas Southwestern Medical Center at Dallas Arthur F. Ryan Chairman of the Board and Retired Chief Executive Officer, Prudential Financial, Inc. Eric M. Shooter, Ph.D. Professor Emeritus, Department of Neurobiology, Stanford University School of Medicine George L. Sing Chief Executive Officer, Stemnion, Inc. Managing Director, Lancet Capital George D. Yancopoulos, M.D., Ph.D. Executive Vice President, Chief Scientific Officer and President, Regeneron Research Laboratories y t i C k r o Y w e N / l i e d n e r B s i t n a S e D : i n g s e D WORKING Targeting serious medical conditions, we built a fully integrated biopharmaceutical company, with capabilities spanning all key competencies – research, development, manufacturing, and commercialization. During the last 12 months, Regeneron’s vision resulted in exciting breakthroughs on several fronts: The FDA approved our fi rst drug, ARCALYST™ (rilonacept) Injection for Subcutaneous Use for the treatment of Cryopyrin-Associated Periodic Syndromes (CAPS), including Familial Cold Auto-infl ammatory Syndrome (FCAS) and Muckle-Wells Syndrome (MWS) in adults and children 12 and older. ARCALYST was designed, via our pro- prietary Trap platform, to be a specifi c blocker of an endogenous pro-infl ammatory agent known as interleukin-1. We entered into an unprecedented new global collaboration with sanofi -aventis that will enable us to more fully exploit the potential of our research capabilities and the VelociSuite of technologies – VelociGene, ® VelociMouse,™ VelocImmune® and VelociMab™ – to discover, develop, manufacture, and commercialize fully human therapeutic antibodies. The fi rst antibody from this collaboration, REGN88, a fully human monoclonal antibody to the interleukin-6 receptor, generated via VelocImmune technology, entered clinical development in patients with rheumatoid arthritis. Afl ibercept, our VEGF Trap product candidate for oncology (designed to potently block VEGF via the Trap technology platform also used to generate ARCALYST), moved into Phase 3 trials in four different types of cancer. Our VEGF Trap-Eye ophthalmology product candidate advanced into Phase 3 studies in the neovascular form of Age-related Macular Degeneration (wet AMD). These major milestones are not the result of happenstance. Instead, they represent the ongoing realization of a corporate vision to focus on innovative medical research that has guided our company since its inception and will continue to guide us as we strive to discover, develop, and commercialize new medicines. REGENERON AR 2007 1 We could use our Trap technology platform to create an effective inhibitor of interleukin -1 (IL-1) to treat specifi c infl ammatory diseases. Pioneering new technologies could streamline target discovery and validation, and create a robust pipeline of fully human therapeutic antibodies. 4 2 WORKING Targeting serious medical conditions, we built a fully integrated biopharmaceutical company, with capabilities spanning all key competencies – research, development, manufacturing, and commercialization. During the last 12 months, Regeneron’s vision resulted in exciting breakthroughs on several fronts: The FDA approved our fi rst drug, ARCALYST™ (rilonacept) Injection for Subcutaneous Use for the treatment of Cryopyrin-Associated Periodic Syndromes (CAPS), including Familial Cold Auto-infl ammatory Syndrome (FCAS) and Muckle-Wells Syndrome (MWS) in adults and children 12 and older. ARCALYST was designed, via our pro- prietary Trap platform, to be a specifi c blocker of an endogenous pro-infl ammatory agent known as interleukin-1. We entered into an unprecedented new global collaboration with sanofi -aventis that will enable us to more fully exploit the potential of our research capabilities and the VelociSuite of technologies – VelociGene, ® VelociMouse,™ VelocImmune® and VelociMab™ – to discover, develop, manufacture, and commercialize fully human therapeutic antibodies. The fi rst antibody from this collaboration, REGN88, a fully human monoclonal antibody to the interleukin-6 receptor, generated via VelocImmune technology, entered clinical development in patients with rheumatoid arthritis. Afl ibercept, our VEGF Trap product candidate for oncology (designed to potently block VEGF via the Trap technology platform also used to generate ARCALYST), moved into Phase 3 trials in four different types of cancer. Our VEGF Trap-Eye ophthalmology product candidate advanced into Phase 3 studies in the neovascular form of Age-related Macular Degeneration (wet AMD). These major milestones are not the result of happenstance. Instead, they represent the ongoing realization of a corporate vision to focus on innovative medical research that has guided our company since its inception and will continue to guide us as we strive to discover, develop, and commercialize new medicines. REGENERON AR 2007 1 We could use our Trap technology platform to create an effective inhibitor of interleukin -1 (IL-1) to treat specifi c infl ammatory diseases. Pioneering new technologies could streamline target discovery and validation, and create a robust pipeline of fully human therapeutic antibodies. 4 2 ARCALYST ™ (rilonacept): A Breakthrough Medication Steven Weinstein M.D., Ph.D. Clinical Development Mierette Stocker Regulatory Affairs Claudia Howard Program Management “Following the initiation of our “I was the regulatory liaison to “As program manager for ARCALYST clinical program in the FDA for the CAPS program. ARCALYST, I coordinated CAPS by our Translational Medi- I’ve been working on this program Regeneron’s cross-functional cine group, I served as medical since its inception in 2000, and effort to support the Biologics lead for late-stage ARCALYST when news of its approval came License Application. Although clinical development. It was inspir- through I literally jumped for joy. the CAPS patient population is ing to see so many groups and in- This is why we’re here – to develop very small, the process of fi ling dividuals working together to bring and commercialize medicines for a BLA is just as complex as for this new drug to market. But the patients who need them. Now a much larger indication. I’m so most exciting aspect for me has we’ve demonstrated that we have proud of what we accomplished. been hearing patient responses the resources, technology, and With ARCALYST, we proved we to the drug. It is gratifying to see capabilities to do it.” could bring a product from our the impact that our drug can have on the health and quality of life of patients suffering from this rare disease.” research laboratories all the way through clinical development and to market.” “CAPS is my body’s response to changes in temperature. My fl are-ups include hives that cover my entire body, headaches, tiredness, joint pain, and disabling eye pain.” – Patient from pivotal CAPS study of ARCALYST™ (rilonacept) Marina, White Plains, NY Targeting a How ARCALYST works. Working with patients. heartbreaking disease. CAPS are generally caused by Regeneron is committed to helping Cryopyrin-Associated Periodic mutations in the NLRP-3 gene patients suffering from CAPS gain Syndromes, or CAPS, is a group that controls the production of access to ARCALYST treatment. of rare, inherited, auto-infl amma- interleukin-1 (IL-1), a soluble We have developed a variety of tory diseases, including Familial protein secreted by certain cells assistance programs called the Cold Auto-infl ammatory Syndrome in the body. In excess, IL-1 can be Regeneron ARC (ARCALYST (FCAS) and Muckle-Wells Syn- harmful and has been linked to a Resource Center). As part of the drome (MWS). variety of infl ammatory diseases. ARC program, we help patients Patients with CAPS experience chronic, life-long symptoms (including rash, fever and chills, joint pain, eye redness and pain, and fatigue), punctuated by inter- mittent, disruptive exacerbations or fl ares which can be triggered at any time by exposure to cooling temperatures, stress, exercise, or other unknown stimuli. To avoid triggers that cause fl ares, patients often resort to a compromised lifestyle with limitations on everyday activities. ARCALYST is an IL-1 inhibitor gen- fi nd appropriate medical care from erated via our Trap technology and healthcare providers and work with therefore initially called the IL-1 physicians to help them diag- Trap. It attaches to and neutralizes nose and treat this rare disease. IL-1 before it can attach to cell- Through the ARC Program, we surface receptors and generate also provide assistance to CAPS signals that can trigger infl amma- patients in working with insurers tion in body tissue. Once attached and various patient assistance to ARCALYST, IL-1 cannot bind programs to facilitate access to the cell surface receptors and to therapy. is eventually eliminated from the body. ARCALYST is delivered by weekly injection. “Sometimes I have to just close my eyes and lie down, unable to continue with my day.” REGENERON AR 2007 ARCALYST™ A BREAKTHROUGH MEDICATION REGENERON AR 2007 ARCALYST™ A BREAKTHROUGH MEDICATION WORKING On February 27, 2008, the FDA approved ARCALYST ™ (rilonacept) Injection for Subcutaneous Use for the treatment of Cryopyrin-Associated Periodic Syndromes (CAPS), a group of rare, but serious, life-long diseases. CAPS may be just the beginning for ARCALYST. milestone for the company: we invented the Trap Regeneron is evaluating the potential use of technology in our laboratories, applied it to IL-1 ARCALYST in other conditions in which interleukin -1 inhibition, and developed and commercialized our may play a major role. In 2007, we initiated a Phase fi rst drug product. It also provides validation that 2 safety and effi cacy study of ARCALYST for the our novel Trap technology, also used to generate prevention of gout fl ares. the VEGF Trap and the VEGF Trap-Eye, can pro- With the approval of ARCALYST for CAPS, Regeneron duce effective biologic therapies. has become a fully integrated biopharmaceutical Pictured: company. The approval represents a signifi cant Patient from pivotal CAPS study of ARCALYST Marina, White Plains, NY 3 ARCALYST ™ (rilonacept): A Breakthrough Medication Steven Weinstein M.D., Ph.D. Clinical Development Mierette Stocker Regulatory Affairs Claudia Howard Program Management “Following the initiation of our “I was the regulatory liaison to “As program manager for ARCALYST clinical program in the FDA for the CAPS program. ARCALYST, I coordinated CAPS by our Translational Medi- I’ve been working on this program Regeneron’s cross-functional cine group, I served as medical since its inception in 2000, and effort to support the Biologics lead for late-stage ARCALYST when news of its approval came License Application. Although clinical development. It was inspir- through I literally jumped for joy. the CAPS patient population is ing to see so many groups and in- This is why we’re here – to develop very small, the process of fi ling dividuals working together to bring and commercialize medicines for a BLA is just as complex as for this new drug to market. But the patients who need them. Now a much larger indication. I’m so most exciting aspect for me has we’ve demonstrated that we have proud of what we accomplished. been hearing patient responses the resources, technology, and With ARCALYST, we proved we to the drug. It is gratifying to see capabilities to do it.” could bring a product from our the impact that our drug can have on the health and quality of life of patients suffering from this rare disease.” research laboratories all the way through clinical development and to market.” “CAPS is my body’s response to changes in temperature. My fl are-ups include hives that cover my entire body, headaches, tiredness, joint pain, and disabling eye pain.” – Patient from pivotal CAPS study of ARCALYST™ (rilonacept) Marina, White Plains, NY Targeting a How ARCALYST works. Working with patients. heartbreaking disease. CAPS are generally caused by Regeneron is committed to helping Cryopyrin-Associated Periodic mutations in the NLRP-3 gene patients suffering from CAPS gain Syndromes, or CAPS, is a group that controls the production of access to ARCALYST treatment. of rare, inherited, auto-infl amma- interleukin-1 (IL-1), a soluble We have developed a variety of tory diseases, including Familial protein secreted by certain cells assistance programs called the Cold Auto-infl ammatory Syndrome in the body. In excess, IL-1 can be Regeneron ARC (ARCALYST (FCAS) and Muckle-Wells Syn- harmful and has been linked to a Resource Center). As part of the drome (MWS). variety of infl ammatory diseases. ARC program, we help patients Patients with CAPS experience chronic, life-long symptoms (including rash, fever and chills, joint pain, eye redness and pain, and fatigue), punctuated by inter- mittent, disruptive exacerbations or fl ares which can be triggered at any time by exposure to cooling temperatures, stress, exercise, or other unknown stimuli. To avoid triggers that cause fl ares, patients often resort to a compromised lifestyle with limitations on everyday activities. ARCALYST is an IL-1 inhibitor gen- fi nd appropriate medical care from erated via our Trap technology and healthcare providers and work with therefore initially called the IL-1 physicians to help them diag- Trap. It attaches to and neutralizes nose and treat this rare disease. IL-1 before it can attach to cell- Through the ARC Program, we surface receptors and generate also provide assistance to CAPS signals that can trigger infl amma- patients in working with insurers tion in body tissue. Once attached and various patient assistance to ARCALYST, IL-1 cannot bind programs to facilitate access to the cell surface receptors and to therapy. is eventually eliminated from the body. ARCALYST is delivered by weekly injection. “Sometimes I have to just close my eyes and lie down, unable to continue with my day.” REGENERON AR 2007 ARCALYST™ A BREAKTHROUGH MEDICATION REGENERON AR 2007 ARCALYST™ A BREAKTHROUGH MEDICATION WORKING On February 27, 2008, the FDA approved ARCALYST ™ (rilonacept) Injection for Subcutaneous Use for the treatment of Cryopyrin-Associated Periodic Syndromes (CAPS), a group of rare, but serious, life-long diseases. CAPS may be just the beginning for ARCALYST. milestone for the company: we invented the Trap Regeneron is evaluating the potential use of technology in our laboratories, applied it to IL-1 ARCALYST in other conditions in which interleukin -1 inhibition, and developed and commercialized our may play a major role. In 2007, we initiated a Phase fi rst drug product. It also provides validation that 2 safety and effi cacy study of ARCALYST for the our novel Trap technology, also used to generate prevention of gout fl ares. the VEGF Trap and the VEGF Trap-Eye, can pro- With the approval of ARCALYST for CAPS, Regeneron duce effective biologic therapies. has become a fully integrated biopharmaceutical Pictured: company. The approval represents a signifi cant Patient from pivotal CAPS study of ARCALYST Marina, White Plains, NY 3 WORKING On February 27, 2008, the FDA approved ARCALYST ™ (rilonacept) Injection for Subcutaneous Use for the treatment of Cryopyrin-Associated Periodic Syndromes (CAPS), a group of rare, but serious, life-long diseases. CAPS may be just the beginning for ARCALYST. milestone for the company: we invented the Trap Regeneron is evaluating the potential use of technology in our laboratories, applied it to IL-1 ARCALYST in other conditions in which interleukin -1 inhibition, and developed and commercialized our may play a major role. In 2007, we initiated a Phase fi rst drug product. It also provides validation that 2 safety and effi cacy study of ARCALYST for the our novel Trap technology, also used to generate prevention of gout fl ares. the VEGF Trap and the VEGF Trap-Eye, can pro- With the approval of ARCALYST for CAPS, Regeneron duce effective biologic therapies. has become a fully integrated biopharmaceutical Pictured: company. The approval represents a signifi cant Patient from pivotal CAPS study of ARCALYST Marina, White Plains, NY 3 Pioneering new technologies could streamline target discovery and validation, and create a robust pipeline of fully human therapeutic antibodies. 4 WORKING The fi rst fully human antibody generated by the VelociSuite of technologies (including VelociGene®, VelociMouse™, VelocImmune® and VelociMab™) entered clinical trials in 2007. Our VelociSuite of technologies improves our ability the most desirable characteristics and generate high- to determine the best targets for therapeutic inter- producing cell lines to manufacture these antibodies. vention, and then rapidly generates high-quality fully human antibodies as drug candidates addressing these targets. VelociGene® and VelociMouse™ are new high-throughput approaches for generating thousands of knockout and transgenic mouse models, which can be used to evaluate each gene of interest as a potential drug target. Once a gene has been vali- dated for therapeutic intervention, our scientists use In 2007, vision became reality with the initiation of clinical trials in rheumatoid arthritis of an antibody to the interleukin-6 receptor (IL-6R). A second antibody against a novel angiogenesis target (Dll4) is slated to enter clinical development in mid-2008. These anti- bodies are being developed with sanofi -aventis as part of our global collaboration. VelocImmune® and VelociMab™ to rapidly generate Our goal is to bring two to three new antibodies high-quality, fully human antibody candidates. Using into clinical development each year. VelociMab, scientists screen for the antibodies with 5 Blocking angiogenesis through VEGF inhibition could starve tumors of the blood supply needed for them to grow, and provide a mechanism for treating cancer. 6 WORKING Four Phase 3 trials are underway evaluating afl ibercept (VEGF Trap) in multiple cancer indications. Tumor growth requires the development of new Together with sanofi -aventis, we are conducting piv- blood vessels, or angiogenesis, to provide oxygen otal Phase 3 trials that combine afl ibercept with stan- and nutrients. Blocking Vascular Endothelial Growth dard chemotherapy regimens in second-line metastat- Factor (VEGF) is the best validated anti-angiogen- ic colorectal cancer, fi rst-line metastatic pancreatic esis approach in cancer, and was recognized at an cancer, fi rst-line metastatic androgen independent early stage by the Regeneron oncology team as an prostate cancer, and second-line metastatic non-small important target for therapeutic intervention in solid cell lung cancer. A Phase 2 trial is studying afl ibercept tumors. Using our proprietary Trap technology (which for the treatment of symptomatic malignant ascites in we also used to develop ARCALYST™ (rilonacept), women with ovarian cancer. In addition, the National initially termed IL-1 Trap), Regeneron developed Cancer Institute is sponsoring more than 15 studies afl ibercept (VEGF Trap), an anti-angiogenesis agent evaluating afl ibercept as a single agent or in combi- that is designed to bind and neutralize VEGF, thereby nation with chemotherapy regimens in a variety of inhibiting the growth of blood vessels in tumors in cancer indications. numerous types of cancers. 7 Inhibiting blood vessel growth and abnormal vessel leakage in the eye could help restore vision in patients with certain serious eye disorders. 8 WORKING The large Phase 3 program of VEGF Trap-Eye is enrolling patients with the neovascular form of Age-related Macular Degeneration (wet AMD). Blocking the activity of Vascular Endothelial Growth Regeneron is conducting a 1,200 patient Phase 3 Factor (VEGF) in the eye can prevent abnormal blood clinical trial of VEGF Trap-Eye in wet AMD in North vessel growth and vascular leakage associated with America. Bayer HealthCare is initiating a Phase 3 eye diseases such as wet AMD, the leading cause of wet AMD trial that will enroll 1,200 patients outside blindness for people over the age of 65 in the U.S. North America. Both trials are comparing treatment and Europe. The VEGF Trap-Eye is a form of afl iber- with VEGF Trap-Eye at various dose regimens to cept that has been formulated for use by direct injec- treatment with ranibizumab, the current standard tion into the eye. We are developing VEGF Trap-Eye of care. in collaboration with Bayer HealthCare. 9 Envisioning the Future Over the past twelve months, we received FDA approval to market our fi rst product, advanced our lead product candidates into late-stage development, and initiated a sweeping new antibody collaboration. Yet what excites us most is the future: > > > Full commercialization of ARCALYST™ (rilon- acept) for patients who suffer from CAPS Expanding the global Phase 3 VEGF Trap-Eye > ophthalmology program to patients in North America, Europe, Asia, and Latin America Continued clinical evaluation of rilonacept in infl ammatory diseases, including gout Discovering and validating genes as drug > targets, and then using VelocImmune® to generate antibodies to these targets Enrollment of thousands of new patients in our late-stage afl ibercept oncology trials > Advancing 2 to 3 new fully human monoclonal antibodies into clinical development each year With an innovative new product on the market and a robust pipeline that includes two late-stage product candidates addressing large markets, we are looking forward to continued progress that will help us meet our goal of commercializing important new medicines for patients suffering from serious diseases. REGENERON AR 2007 10 REGENERON CLINICAL DEVELOPMENT Phase 1 Phase 2 Phase 3 Marketed ARCALYST ™ (rilonacept) CAPS Gout VEGF Trap-Eye Wet age-related macular degeneration Afl ibercept (VEGF Trap) Metastatic prostate cancer Metastatic non- small cell lung cancer Metastatic colorectal cancer Metastatic pancreatic cancer Other indications REGN88 (IL-6R antibody) Rheumatoid arthritis REGENERON AR 2007 11 Research Since its inception, Regeneron has been committed to the principle that strong science coupled with empowering new technology platforms could accelerate the effort to develop a large, diverse, and risk-balanced, development pipeline. Our VelociSuite of technologies (including VelociGene®, VelociMouse™, VelocImmune,® and VelociMab™) greatly increases the effi ciency of progressing from early discovery through drug candidate generation. Our scientists use these technologies to evaluate hundreds of new targets each year, and generate fully human therapeutic antibody candidates, resulting in a robust antibody pipeline. Development Regeneron has put in place an organizational structure to manage our growing pipeline. A translational medicine group was established to rapidly assess the potential of new product candidates and design and initiate fi rst-in- human clinical trials. Other groups in our clinical development department oversee the next stages of drug development through registration. These groups have additional support from our regulatory group, responsible for coordinating inter- actions with the U.S. Food and Drug Administration and other regulatory agencies. Our Medical Affairs group acts as a liaison between Regeneron and external constituencies of physicians, clinicians, and patients. REGENERON AR 2007 12 Manufacturing Our large-scale biologics manufacturing operations are located in Rensselaer, New York. With over 300,000 square feet of space, the Rensselaer site houses our Industrial Operations and Product Supply (IOPS) function and our clinical and commercial scale bioreactors (up to 10,000 liters). Operating under current Good Manufacturing Practice (cGMP) conditions, IOPS manufactures ARCALYST™ (rilonacept), our fi rst FDA approved drug, and product for our growing clinical development program. To date, this facility has manufactured investigational drugs used by several thousand patients in clinical trials. Commercialization With the FDA approval of ARCALYST, Regeneron has moved into an exciting new chapter in our corporate his- tory. We are now focused on bringing ARCALYST to CAPS patients who suffer from this debilitating disease. Our expanded commercial group is implementing our commer- cialization strategy, including disease awareness, marketing, patient advocacy, and customer service activities. The commercial group also provides input into the decision- making process on target and disease selection for our clinical development programs. REGENERON AR 2007 13 Leonard S. Schleifer, M.D., Ph.D. President and Chief Executive Offi cer P. Roy Vagelos, M.D. Chairman of the Board George Yancopoulos, M.D., Ph.D. Executive Vice President, Chief Scientifi c Offi cer and President, Regeneron Research Laboratories REGENERON AR 2007 14 Dear Shareholders, For Regeneron, the past twelve months have been among the most eventful, exciting, and productive in our history. Recently, we received FDA approval for ARCALYST™ ingenuity that went into discovering and developing (rilonacept), our fi rst marketed product, which was this unique medicine. Joy, because of the relief our designed using our proprietary Trap technology medicine can bring to CAPS patients who have platform to specifi cally block interleukin-1 (IL-1), and suffered life-long, debilitating symptoms that inter- was thus initially called the IL-1 Trap. We established fere with their ability to participate in everyday work, a groundbreaking collaboration with sanofi -aventis family, and social activities. that will help us exploit the immense potential of our drug discovery and therapeutic antibody develop- ment capabilities, which include our proprietary new technology platform for generating fully human antibodies, termed VelocImmune.® Jump-starting this important new collaboration, we recently initiated our fi rst clinical program testing a fully human antibody generated via VelocImmune technology. In our oncol- ogy collaboration with sanofi -aventis, we advanced afl ibercept (VEGF Trap) into four Phase 3 clinical trials, and in our ophthalmology collaboration with Bayer HealthCare, we advanced VEGF Trap-Eye into Phase 3 clinical trials. Any one of these events on its own would have made this an outstanding year for our company. Together, they represent a signifi cant leap forward, establishing a stronger and higher founda- tion on which to build a successful and sustainable biopharmaceutical company. For patients, the approval of ARCALYST is particularly welcome because it is the only therapy approved for CAPS, a group of rare, inherited, auto-infl amma- tory diseases characterized by life-long, recurrent symptoms of rash, fever and chills, joint pain, eye redness and pain, and fatigue. Intermittent, disruptive exacerbations or fl ares can be triggered at any time by exposure to cooling temperatures, stress, exercise, or other stimuli. We have had the opportunity to meet patients diagnosed with CAPS, and their stories paint a clear picture of how this disease can affect their lives – and how ARCALYST can provide relief. During clinical trials, patients treated with ARCALYST experienced a signifi cant improvement in their overall disease symptom scores. These improvements were sustained over time with continued ARCALYST treat- ment. The most commonly reported adverse react- ions reported with ARCALYST were injection site Let’s begin with ARCALYST. On February 27th of reaction and upper respiratory tract infection. Full this year, the FDA granted marketing approval for product and safety information is available at ARCALYST™ (rilonacept) Injection for Subcutaneous www.ARCALYST.com. Use for the treatment of Cyropyrin-Associated Peri- odic Syndromes (CAPS), including Familial Cold Auto- infl ammatory Syndrome (FCAS) and Muckle-Wells Syndrome (MWS) in adults and children 12 and older. This was very exciting news for us and for patients suffering from CAPS. We wish each of our sharehold- ers could have been at our offi ces that afternoon. Pride and joy were evident on the face of every one of our colleagues: Pride, because of the hard work and The launch of ARCALYST represents validation of our ability to discover, develop, manufacture, and commercialize novel therapeutics that meet unmet medical needs. What’s more, although CAPS is a very rare orphan disease that is estimated to affect only several hundred people in the United States, Regeneron continues to evaluate the potential use of rilonacept in other indications in which interleukin-1 is believed to play a key role, such as gout. REGENERON AR 2007 15 A groundbreaking collaboration We began reaping the benefi ts of this collaboration involving VelocImmune.® right out of the gate. At the end of last year, we initi- Another exciting event for our company was the ated our fi rst clinical trial of a therapeutic antibody: November 2007 global collaboration with sanofi - REGN88, a fully human antibody to the interleukin-6 aventis to discover, develop, and commercialize fully receptor (IL-6R) that is being evaluated in patients human monoclonal antibodies. This groundbreaking with rheumatoid arthritis. The second antibody sched- collaboration validates the potential of our research uled to enter clinical trials under the collaboration is capabilities and innovative technologies to add sig- a fully human antibody to Delta-like ligand-4 (Dll4), a nifi cantly to the future development pipelines of both novel anti-angiogenesis agent that currently is slated companies. Sanofi -aventis’ funding and expertise will to start clinical development in mid-2008. We and help us translate our research efforts into antibody sanofi -aventis plan to advance two to three antibody product candidates on a much broader scale than product candidates into clinical trials each year we could ever do alone. We’ve long believed that our beginning this year. strong research capabilities and VelociSuite of tech- nologies (which include VelociGene,® VelociMouse,™ and VelociMab™ in addition to VelocImmune®) had the potential to transform Regeneron – and, potentially, the health and healthcare of millions of people world- wide. Now we have the resources to begin to make this happen. Thus, the collaboration with sanofi -aventis will en- able us to bring promising new candidates into and through our pipeline at an accelerated pace. It also relieves us of much of the fi nancial obligations in- curred by biopharmaceutical companies with multiple drug candidates in development. As with our fi rst drug approval, we wish each of our shareholders could visit To understand the sweeping signifi cance of this col- our facilities and sense the spirit of enthusiasm and laboration for Regeneron, it’s important to understand commitment that pervades our labs, manufacturing its key components. As part of the collaboration, plant, and offi ces as we begin this important collabo- sanofi -aventis made an $85 million upfront payment ration. Our people are excited by the opportunity to to Regeneron and agreed to fund up to $475 million apply their creative talents and collaborate with their of research and preclinical development over the next counterparts at sanofi -aventis to build a new pipeline fi ve years. Sanofi -aventis has the exclusive option to of drug candidates for important diseases and disor- co-develop with Regeneron each antibody candidate ders with unmet medical needs. that emerges from the collaboration. If sanofi -aventis chooses to co-develop the antibody with us, they will fund all development costs up front through the fi rst successful Phase 3 trial. Following commercialization, Regeneron and sanofi -aventis will share future profi ts from sales of collaboration antibodies. At that time, we will reimburse sanofi -aventis for half of the devel- opment costs that they funded from our share of the profi ts. If sanofi -aventis elects not to co-devel- op an antibody with us, we retain exclusive rights to develop and commercialize the antibody and will pay sanofi -aventis a single digit royalty on sales of such an VelocImmune® Licenses. In 2007, Regeneron entered into non-exclusive license agreements with AstraZeneca and Astellas to allow those companies to utilize the VelocImmune technology in their internal research programs to discover human monoclonal antibody products. The licensing agreements highlight the acceptance of the VelocImmune technology as an emerging new standard for the development of fully human antibod- ies. Regeneron is also considering exploring additional license agreements. antibody. Oncology and ophthalmology. Clearly, this is a very important strategic collaboration for both companies. It is particularly important today because antibodies are playing a growing and increas- ingly important role in pharmaceutical development. The 23 antibody-based therapies currently on the market generated an estimated $32 billion of sales in the U.S. in 2007. The excitement surrounding ARCALYST™ (rilonacept) and the sanofi -aventis antibody collaboration should not obscure the great progress we made in 2007 with our two lead development candidates. In 2007, we achieved our goal of accelerating the progress of our oncology program. We now have more than 20 clinical trials underway of afl ibercept, our VEGF (Vascular Endothelial Growth Factor) inhibitor, including four REGENERON AR 2007 16 Phase 3 clinical trials in patients with metastatic Looking ahead. hormone-resistant prostate cancer, metastatic We fully expect 2008 to be another important year non-small cell lung cancer, metastatic colorectal for Regeneron as we record progress in all areas of cancer, and metastatic pancreatic cancer. These four the company. With the initiation of research under the trials are expected to enroll a total of almost 4,000 sanofi -aventis antibody collaboration, the progress patients, and additional trials are being planned. We in enrolling patients in each of our ongoing late stage and sanofi -aventis also have on-going Phase 1 and clinical programs, and the commercial launch of Phase 2 trials in a variety of solid tumors plus a trial in ARCALYST™ (rilonacept), Regeneron has already symptomatic malignant ascites in women with ovarian made great headway in the fi rst half of 2008. We cancer. In addition, the National Cancer Institute (NCI) expect this momentum to continue as our colleagues is sponsoring more than fi fteen studies with afl iber- here at Regeneron apply their collective talents and cept. In total, more than 1,000 patients have already enthusiasm to build upon this strong foundation and participated in clinical trials with afl ibercept, and remain focused on bringing important new therapeu- many more will soon join them. tics to patients. Our VEGF Trap-Eye ophthalmology program, which is being conducted in collaboration with Bayer HealthCare, also made signifi cant progress over the past year. Our pre-clinical and Phase 2 clinical data suggest that our VEGF Trap-Eye may offer an effi cacy advantage or require less frequent dosing compared with the current standard of care for the treatment of the neovascular form of Age-related Macular Degeneration (wet AMD). The VEGF Trap-Eye currently is in Phase 3 clinical development for wet AMD. The fi rst Phase 3 study, which we are conduct- ing, is enrolling 1,200 patients in more than 200 sites in North America. Bayer HealthCare is initiating a second Phase 3 wet AMD trial. This study will enroll approximately 1,200 patients in up to 200 centers in Europe, Asia, and Latin America. Regeneron retains exclusive rights to the VEGF Trap-Eye in the United States and will share profi ts with Bayer HealthCare from the commercialization of VEGF Trap-Eye outside the United States. Financial strength. We move forward from a very strong fi nancial posi- tion. At year-end 2007, we had nearly $850 million in cash and securities. Moreover, with almost 100 per- cent of our oncology and antibody programs funded by sanofi -aventis, almost 50 percent of our ophthal- mology program funded by Bayer HealthCare, and annual fees from our VelocImmune® licenses, we will be able to signifi cantly leverage our own investment in our research and development programs without a corresponding increase in our net cash usage. REGENERON AR 2007 17 Corporate Information Common Stock and Related Matters SEC Form 10-K Our Common Stock is quoted on The Nasdaq Stock A copy of our annual report to the Securities and Market under the symbol “REGN.” Our Class A Stock, Exchange Commission on Form 10-K is available par value $.001 per share, is not publicly quoted without charge from the Regeneron Investor or traded. Relations Department. The following table sets forth, for the periods Annual Meeting indicated, the range of high and low sales prices The Annual Meeting will be held on Friday, June 13, for the Common Stock as reported by The Nasdaq 2008 at 10:30 a.m. at the Westchester Marriott Stock Market. Hotel, 670 White Plains Road, Tarrytown, NY 10591. 2006 First Quarter Second Quarter Third Quarter Fourth Quarter 2007 First Quarter Second Quarter Third Quarter Fourth Quarter High $18.00 16.69 17.00 24.85 $22.84 28.74 21.78 24.90 Low $14.35 10.97 10.88 15.27 $17.87 17.55 13.55 16.77 Shareholders’ Inquiries Inquiries relating to stock transfer or lost certifi cates and notices of changes of address should be directed to our Transfer Agent, American Stock Transfer & Trust Co., 59 Maiden Lane, Plaza Level, New York, NY 10038, (800) 937-5449. General information regarding the Company, recent press releases, and SEC fi lings are available on our Worldwide Web Home Page at www.regn.com, or can be obtained by con- tacting our Investor Relations Department at (914) 345-7741. Transfer Agent and Registrar American Stock Transfer & Trust Co. As of April 15, 2008, there were 511 shareholders of record of our Common Stock and 42 shareholders of record of our Class A Stock. The closing bid price 59 Maiden Lane Plaza Level New York, NY 10038 for the Common Stock on that date was $18.23. Independent Registered Public Accounting Firm We have never paid cash dividends and do not PricewaterhouseCoopers LLP anticipate paying any in the foreseeable future. REGENERON® is a registered trademark Corporate Offi ce 777 Old Saw Mill River Road Tarrytown, NY 10591-6707 (914) 345-7400 of Regeneron Pharmaceuticals, Inc. REGENERON AR 2007 18 FINANCIAL REVIEW Regeneron was founded on the principle that strong science and innovative tech- nology could accelerate the development of new medicines. From the beginning, we assembled teams of talented scientists and challenged them to thoroughly understand the biology of diseases, develop new technology platforms, and discover and develop potential therapeutic candidates. Forward-looking Statements and Risk Factors: This news release discusses historical information and in- cludes forward-looking statements about Regeneron and its products, development programs, finances, and business, all of which involve a number of risks and uncertainties, such as risks associated with preclinical and clinical development of Regeneron’s drug candidates, determinations by regulatory and administrative governmental authorities which may delay or restrict Regeneron’s ability to continue to develop or commer- cialize its product and drug candidates, competing drugs that are superior to Regeneron’s product and drug candidates, uncertainty of market acceptance of Regeneron’s product and drug candidates, unanticipated expenses, the availability and cost of capital, the costs of developing, producing, and selling products, the potential for any collaboration agreement, including Regeneron’s agreements with the sanofi-aventis Group and Bayer HealthCare, to be canceled or to terminate without any product success, risks associated with third party intellectual property, and other material risks. A more complete description of these and other material risks can be found in Regeneron’s filings with the United States Securities and Exchange Commis- sion (SEC), including its Form 10-K for the year ended December 31, 2007. Regeneron does not undertake any obligation to update publicly any forward-looking statement, whether as a result of new information, future events, or otherwise unless required by law. Corporate Directory Directors P. Roy Vagelos, M.D. Chairman of the Board Senior Management Team Leonard S. Schleifer, M.D., Ph.D. President and Chief Executive Officer Leonard S. Schleifer, M.D., Ph.D. George D. Yancopoulos, M.D., Ph.D. President and Chief Executive Officer Executive Vice President, Charles A. Baker Retired Chairman of the Board, President and Chief Executive Officer of The Liposome Company, Inc. Michael S. Brown, M.D. Regental Professor, Department of Molecular Genetics, The University of Texas Chief Scientific Officer and President, Regeneron Research Laboratories Murray A. Goldberg Senior Vice President, Finance and Administration, Chief Financial Officer, Treasurer and Assistant Secretary Stuart Kolinski Southwestern Medical Center at Dallas Senior Vice President, General Counsel and Secretary Peter Powchik, M.D. Senior Vice President, Clinical Development Neil Stahl, Ph.D. Senior Vice President, Research and Developmental Sciences Robert J. Terifay Senior Vice President, Commercial Daniel Van Plew Senior Vice President and General Manager, Industrial Operations and Product Supply Alfred G. Gilman, M.D., Ph.D. Provost and Executive Vice President for Academic Affairs, The University of Texas Dean, Southwestern Medical School Joseph L. Goldstein, M.D. Regental Professor and Chairman, Department of Molecular Genetics, The University of Texas Southwestern Medical Center at Dallas Arthur F. Ryan Chairman of the Board and Retired Chief Executive Officer, Prudential Financial, Inc. Eric M. Shooter, Ph.D. Professor Emeritus, Department of Neurobiology, Stanford University School of Medicine George L. Sing Chief Executive Officer, Stemnion, Inc. Managing Director, Lancet Capital George D. Yancopoulos, M.D., Ph.D. Executive Vice President, Chief Scientific Officer and President, Regeneron Research Laboratories y t i C k r o Y w e N / l i e d n e r B s i t n a S e D : i n g s e D WORKING Regeneron Pharmaceuticals, Inc. 777 Old Saw Mill River Road Tarrytown, NY 10591 regeneron.com Regeneron Annual Report 2007 

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