Regeneron Updates AXOKINE Development.

TARRYTOWN, N.Y.--(BUSINESS WIRE)--Sept. 1, 1999--

Regeneron Pharmaceuticals, Inc. (NASDAQ:REGN) updated the status of the development of AXOKINE(R) second generation ciliary neurotrophic factor that is being developed for the treatment of obesity and diabetes. The Company summarized preliminary, interim results of the Phase I safety study of AXOKINE in a small number of mildly to moderately obese healthy volunteers. In that study, the nine patients who received daily administration of low doses of AXOKINE for 14 days lost weight and had decreased food intake. In the single dose phase of the study, patients who received higher doses of AXOKINE reported nausea and vomiting, and some patients who had previously contracted herpes simplex virus (HSV-positive) experienced "cold sores" related to reactivation of their HSV infection. Regeneron also announced that it plans to commence a Phase II clinical study of AXOKINE for the treatment of obesity in the first quarter of next year. Regeneron announced that The Procter & Gamble Company has returned to Regeneron product rights to AXOKINE, which P&G and Regeneron had been developing in collaboration.

Interim Data From AXOKINE Phase I Study

The Phase I study is still underway and will be completed by P&G. In this double-blind safety study, mildly to moderately obese patients are receiving increasing doses of AXOKINE (or placebo) administered subcutaneously in both single and multiple dose regimens. The single dose study demonstrated that AXOKINE is well tolerated at low doses. At higher single doses nausea, vomiting, and herpes cold sores were observed. Increased cold sores caused by HSV were also reported in previous clinical studies of ciliary neurotrophic factor, AXOKINE's parent molecule.

The multiple dose study (daily administration for 14 days) was conducted at doses that were well tolerated in the single dose part of the study. Nine patients and four placebo patients have been completed to date with no reports of nausea, vomiting, cough, or herpes cold sores. The treated patients lost weight and had decreased food (caloric) intake compared with those on placebo. "The initial efficacy results are encouraging but need to be confirmed in our planned Phase II study, which will include more patients who will receive AXOKINE for a significantly longer period of time," said P. Roy Vagelos, M.D., Regeneron's Chairman of the Board.

One patient in a multiple low dose group, who was HSV-positive prior to treatment and had been previously diagnosed with Bell's palsy, had a recurrence of Bell's palsy approximately two weeks after the patient's last administration of AXOKINE. It is not known whether AXOKINE had any role in this patient's recurrence of Bell's palsy, and the patient recovered. Bell's palsy is a potentially permanently disfiguring condition but most often resolves spontaneously within weeks. Many researchers believe that Bell's palsy may be caused by HSV.

Further details about the AXOKINE Phase I study will be reported when it is completed.

Regeneron Plans Phase II Clinical Trial 

Following completion of the Phase I trial, Regeneron plans to initiate in the first quarter of 2000 a Phase II dose-ranging trial to study the safety and efficacy of AXOKINE in obese patients who have not previously contracted HSV. "We believe that AXOKINE is an exciting product candidate," said Leonard S. Schleifer, M.D., Ph.D., President and Chief Executive Officer of Regeneron. "Preclinical data in a variety of animal species indicate that AXOKINE causes weight loss and acts by stimulating pathways that suppress food intake. The early Phase I results appear to confirm these findings. Given the observation that at high single doses AXOKINE appears to induce herpes cold sores in HSV-positive patients, and the single patient with Bell's palsy, Regeneron has decided to conduct a Phase II dose ranging study in obese HSV-negative patients. This will allow us to move ahead without delay to conduct a study to determine the lowest effective, well tolerated dose of AXOKINE, while continuing to collect data and conduct experiments on the relationship of AXOKINE and reactivation of HSV."

Dr. Schleifer added, "We think that the HSV-negative population is still very attractive from a business standpoint for Regeneron. There are many HSV-negative patients who need an effective treatment for obesity and diabetes."

Regeneron Reacquires Rights to AXOKINE

Under the long-term collaboration agreement between P&G and Regeneron, either party may opt out of continuing to participate in the development or commercialization of a product. Gordon S. Hassing, Ph.D., Vice President, Research & Development, of Procter & Gamble Pharmaceuticals stated that, "P&G decided to return AXOKINE to Regeneron after examining the interim data from the initial safety study of AXOKINE as part of P&G's internal review of its drug development programs and budgets. AXOKINE has shown promise as a potential treatment for diabetes and obesity. However, if the target population were ultimately limited to HSV-negative patients, we concluded that the total market size would not be large enough to be attractive to P&G. We are, therefore, returning the rights to AXOKINE to Regeneron so that they can continue to develop this product in a manner that makes sense for a company of their size." Under certain circumstances, P&G will receive a small royalty on sales of AXOKINE.

Dr. Hassing continued, "This decision has no impact on the broader P&G-Regeneron relationship. In 1997, P&G and Regeneron entered into a ten-year agreement to discover, develop, and commercialize pharmaceutical products, and we are pleased with the progress of that collaboration. Our research groups are working closely in a variety of research programs and we are enthusiastic about moving them forward together."

Added Dr. Schleifer, "We are delighted to continue to collaborate with P&G on other approaches to obesity and diabetes, as well as other joint research and preclinical programs in fields such as angiogenesis, bone growth, and muscle atrophy."

Regeneron is a leader in the application of molecular and cell biology to the search for novel human therapeutics. Regeneron uses its expertise in growth factors and their mechanisms of action to discover and develop protein-based and small molecule drugs. Regeneron is currently conducting a clinical program for AXOKINE second generation ciliary neurotrophic factor for the treatment of obesity and Type II diabetes in obese patients and uncomplicated obesity. Regeneron is also conducting clinical trials, in partnership with Amgen Inc., of brain-derived neurotrophic factor for the treatment of amyotrophic lateral sclerosis and of neurotrophin-3 for the treatment of constipation associated with spinal cord injury and other medical conditions. The Company has a number of research collaborations, including a broad-based, long-term agreement with The Procter & Gamble Company.

This news release discusses historical information and includes forward looking statements about Regeneron's products, programs, finances, and business, all of which involve a number of risks and uncertainties, such as risks associated with preclinical 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. Any additional clinical trials of AXOKINE in the U.S. will be subject to the authority of the United States Food and Drug Administration. A more complete description of factors that may affect future operating results can be found in Regeneron's Form 10-K for the year ended December 31, 1998, and current Form 10-Q, copies of which should be read before making any investment decision regarding Regeneron common stock.

Additional information about Regeneron and recent news releases are available on Regeneron's Worldwide Web Home Page at www.regeneron.com. Fax copies of news releases can be obtained from Regeneron's News-on-Demand Service by dialing [phone].