Regeneron and P&G Initiate Clinical Study to Treat Obesity Associated With Diabetes.

TARRYTOWN, New York--(BUSINESS WIRE)--March 30, 1999--Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) announced that Regeneron and The Procter & Gamble Company (NYSE: PG) have initiated a Phase I clinical study of Regeneron's AXOKINE(R) second generation ciliary neurotrophic factor under an Investigational New Drug application (IND) filed with the United States Food and Drug Administration.

AXOKINE is being developed for the treatment of obesity associated with Type II diabetes and possibly for uncomplicated obesity. The Phase I trial will be a randomized, placebo-controlled safety and tolerability study in mildly to moderately obese healthy volunteers. The study is the first clinical trial conducted jointly by P&G and Regeneron under their long-term collaboration agreement.

A 1998 National Institutes of Health report confirmed that obesity significantly increases a number of health risks, including non-insulin dependent Type II diabetes. Weight reduction leads to improved glycemic control in patients with Type II diabetes. Type II diabetes (also known as adult onset diabetes) is estimated to affect more than 15 million people in the United States, with 80-90% of these people having obesity as a contributing factor to their diabetes.

In May 1997, Regeneron and P&G entered into a 10-year agreement to discover, develop, and commercialize pharmaceutical products. In September 1997, that agreement was expanded to include AXOKINE and related molecules. P&G is funding the development of AXOKINE through initial clinical studies in humans to establish proof of concept. After this initial work, P&G and Regeneron will share clinical research and other development costs. P&G and Regeneron will jointly develop and market products resulting from the AXOKINE collaboration and will share equally in profits.

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 for the treatment of obesity and neurological, inflammatory, and muscle diseases, as well as angiogenesis, cancer, and abnormal bone growth. Amgen-Regeneron Partners is conducting human clinical studies of Regeneron's brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3).

Background information:

Potential use of AXOKINE for obesity and related conditions

- Body weight is determined by the competing balance of food intake

and energy expenditure. A major advance in understanding the

complex biological processes that regulate body weight was the

identification of leptin, a protein hormone that is secreted by

fat cells. Leptin plays a role in signaling the brain to regulate

food intake.

- Initially it was hoped that obesity in humans could be attributed

to a deficiency of leptin that could be treated with leptin

replacement therapy. However, studies have shown that the

majority of obese individuals have high circulating leptin

levels, suggesting that it is resistance to leptin's action that

is an important factor in their obesity.

- An alternative to using leptin to treat obesity might be to use a

different molecule, such as ciliary neurotrophic factor (CNTF) or

AXOKINE (Regeneron's patented second generation CNTF) to activate

the same intracellular signaling pathways as leptin does, thereby

circumventing leptin resistance.

- Recent experiments in mice with diet-induced obesity, which are

leptin resistant, revealed that administration of AXOKINE was

more effective than leptin in causing the animals to lose weight.

AXOKINE, but not leptin, suppressed appetite, and the mice did

not overeat after treatment was stopped. The weight loss was

predominantly accounted for by a reduction in body fat with

relative sparing of lean body mass, and the weight loss was

maintained for a period of time following cessation of treatment.

- In animals, AXOKINE causes weight loss in the face of leptin

resistance by binding to the AXOKINE/CNTF receptor in the

hypothalamus and stimulating the signaling pathways that suppress

appetite and reduce body weight. This provides a rationale

explaining the clinical observation that human patients injected

with CNTF lose weight.

This news release discusses historical information and includes forward looking statements about Regeneron's products, programs, finances, and business, including statements about the potential therapeutic uses of AXOKINE, other Regeneron product candidates, and future events relating to the Regeneron-Procter & Gamble collaboration, among other statements, all of which involve a number of risks and uncertainties. These include risks and uncertainties 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 the Procter & Gamble 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 Securities and Exchange Commission, including Regeneron's Form 10-K for the year ending December 31, 1998, 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].