Clinical and Pre-Clinical Studies of the VEGF Trap Show Potential for

Clinical and Pre-Clinical Studies of the VEGF Trap Show Potential for the Treatment of Neovascular Eye Diseases

    Pharmaceutical Writers/Business Editors/Health/Medical Writers
    2005 Association for Research in Vision and Ophthalmology (ARVO)

    TARRYTOWN, N.Y.--(BUSINESS WIRE)--May 3, 2005--Regeneron Pharmaceuticals, Inc. (Nasdaq: REGN) announced today that its phase 1 trial of the Vascular Endothelial Growth Factor (VEGF) Trap in the treatment of the neovascular form of age-related macular degeneration (wet AMD) successfully met its pre-specified efficacy endpoint in patients with advanced wet AMD. The data from this clinical trial and from several pre-clinical studies of the VEGF Trap in multiple neovascular eye diseases were presented at the 2005 Association for Research in Vision and Ophthalmology (ARVO) Annual Meeting.
    During a Special Interest Group (SIG) session on Tuesday, May 3, entitled "Blockade of VEGF: Lessons From Early Clinical Experiences", preliminary results from a phase 1 study of the VEGF Trap in 25 patients with advanced wet AMD were presented. Patients in this randomized, double-masked, ascending dose, placebo-controlled study received either placebo or systemic delivery of VEGF Trap at 1 of 3 doses (0.3 mg/kg, 1.0 mg/kg or 3.0 mg/kg). The results showed a statistically significant decrease in excess retinal thickness, which increased in both magnitude and duration with higher doses. The results also indicated that the VEGF Trap caused a dose-dependent increase in blood pressure. Increased blood pressure (hypertension) appears to be a "class-effect" of systemically administered anti-VEGF agents.
    This trial was conducted under Regeneron's collaboration with the sanofi-aventis Group for use of the VEGF Trap in eye diseases using systemic delivery. In January 2005, Regeneron and the sanofi-aventis Group announced that their collaboration would not pursue systemic VEGF Trap delivery for treatment of patients with eye diseases. While these phase 1 trial results establish the biological activity of the VEGF Trap at dosages presently under investigation in the oncology clinical development program, they also support further evaluation of the VEGF Trap in the treatment of neovascular eye diseases by local administration as a means to potentially reduce the risk of hypertension.
    Regeneron plans to initiate a phase 1 study for the VEGF Trap in mid-2005 in advanced wet AMD patients using direct injections into the eye. Pre-clinical studies have demonstrated that the VEGF Trap is a high potency blocker of VEGF and blocks both the long and short forms of VEGF, as well as placental growth factor (PlGF). Regeneron's future plan is to evaluate whether these distinguishing characteristics of the VEGF Trap will translate into better efficacy and/or a more convenient dosing schedule.
    Additional results presented (or scheduled to be presented) at ARVO, based on pre-clinical models, discuss the potential for the VEGF Trap in the treatment of a variety of neovascular eye diseases including AMD, corneal graft survival, corneal injury, diabetic retinopathy, and macular edema.
    The titles and presentation times of the pre-clinical posters accepted for ARVO are:

--	Systemic Administration of VEGF Trap Suppresses Vascular Leak and Leukostasis in the Retinas of Diabetic Rats (Sunday, May 1 2:30 PM - 4:15 PM)
--	VEGF Trap Both Prevents Experimental Choroidal Neovascularization and Causes Regression of Established Lesions in Non-Human Primates (Monday, May 2 11:15 AM - 1:00 PM)
--	Low Dose or Transient Administration of VEGF Trap Suppresses Corneal Neovascularization and Inflammation (Wednesday, May 4 3:00 PM - 4:45 PM)
--	Complete Inhibition of Neovascularization by VEGF Trap in a Matrigel CNV Model (Thursday, May 5 8:30 AM - 10:15 AM)
--	VEGF Trap Induces Significant Regression of Existing Choroidal Neovascularization (CNV) (Thursday, May 5 8:30 AM - 10:15 AM)
--	Inhibition of Angiogenesis and Lymphangiogenesis After High-Risk Keratoplasty by Neutralizing VEGF-A Improves Corneal Graft Survival (Thursday, May 5 2:15 PM - 2:30 PM)

    Role of VEGF in Abnormal Blood Vessel Growth

    Vascular Endothelial Growth Factor (VEGF) is a naturally occurring protein in the body whose normal role is to trigger formation of new blood vessels (angiogenesis) to support the growth of the body's tissues and organs. It has also been associated with the abnormal growth of new blood vessels surrounding tumors to support their expansion. Blocking tumor-associated angiogenesis has been shown to prevent tumor growth in a variety of pre-clinical models, with the most widely recognized and highly validated results achieved based on approaches that block VEGF.
    VEGF has also been associated with the abnormal growth and fragility of new blood vessels in the eye, important factors in the development of wet AMD. In addition, a number of pre-clinical studies have demonstrated that VEGF appears to generate abnormal blood vessel growth in several different eye indications.
    The VEGF Trap has been shown in pre-clinical studies to block the action of VEGF, thereby blocking the abnormal growth of blood vessels. Anti-VEGF molecules have demonstrated efficacy in advanced clinical programs. In a number of publications, Regeneron has reported a breakthrough in understanding how receptors work for an entire class of growth factors and cytokines in the human body (e.g., Davis et al., Science 260:1805 (1993); Stahl et al., Science 263:92 (1994)). Based on these findings, Regeneron developed the VEGF Trap to potently block VEGF.

    About Regeneron Pharmaceuticals

    Regeneron is a biopharmaceutical company that discovers, develops, and intends to commercialize therapeutic medicines for the treatment of serious medical conditions. Regeneron has therapeutic candidates in clinical trials for the potential treatment of cancer, eye diseases, inflammatory diseases, and asthma, and has pre-clinical programs in other diseases and disorders.

    This news release discusses historical information and includes forward-looking statements about Regeneron and its products, programs, finances, and business, all of which involve a number of risks and uncertainties, such as risks associated with pre-clinical and clinical development of drugs and biologics, determinations by regulatory and administrative governmental authorities, competitive factors, technological developments, the availability and cost of capital, the costs of developing, producing, and selling products, the potential for any collaboration agreement to be canceled or to terminate without any product success, and other material risks. A more complete description of these risks can be found in Regeneron's filings with the United States Securities and Exchange Commission (SEC), including its Form 10-K for the year ended December 31, 2004. 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.

    Additional Information about Regeneron and recent news releases are available on Regeneron's Worldwide Web Home Page at www.regeneron.com.

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CONTACT: Investors: Charles Poole, 914-345-7640 charles.poole@regeneron.com OR Media: Lauren Tortorete, 212-845-5609 ltortorete@biosector2.com

KEYWORD: NEW YORK INDUSTRY KEYWORD: PHARMACEUTICAL MEDICAL BIOTECHNOLOGY PRODUCT SOURCE: Regeneron Pharmaceuticals, Inc.

Copyright Business Wire 2005