By Frances Bishopp

In a collaboration worth up to $78 million, Praecis Pharmaceuticals Inc. has entered into an agreement with French pharmaceutical company Synthelabo for the development and commercialization of PPI-149, Praecis' hormone antagonist drug used for the treatment of prostate cancer and other disorders treated by hormone modulation.

Praecis, employing a series of integrated technologies including gene-based and chemistry-based combinatorial chemistry and drug delivery methodology, works to develop drugs that target significant clinical needs.

Under terms of the agreement, Praecis retains responsibility for the development of PPI-149, with Synthelabo, of Paris, undertaking supplementary development activities to the extent required to obtain regulatory approvals in its licensed territory.

Synthelabo will be responsible for regulatory filings, and will receive development rights and exclusive marketing and distribution rights in that territory, which includes Europe, Latin America, the Middle East and certain African countries.

Praecis will retain manufacturing responsibility and will retain exclusive rights to PPI-149 for North America and the rest of the world.

The agreement calls for signing and milestone payments of up to $68 million. In addition, Praecis will receive royalties on product sales in the territory and a contribution to development costs.

In conjunction with signing the agreement, Sylamerica Inc., an affiliate of Synthelabo, located in New York, has purchased $10 million of Praecis common stock and warrants.

Joseph Limber, president and chief operating officer of Praecis, said his company filed an investigative new drug application with the FDA for PPI-149 in October 1996.

PPI-149, an LHRH (luteinizing hormone releasing hormone) antagonist, reduces the testosterone levels in males and estrogen levels in females, which is important in certain conditions where hormone modulation contributes to resolving diseases and indications such as prostate cancer, breast cancer, endometriosis and uterine fibroids, Limber explained.

These drugs as a class are known as LHRH analogues, which are separated into two categories: agonists or antagonists. "All of the drugs on the market today for hormone modulation, which constitute about $1.8 billion in worldwide sales, are agonists," Limber said. "This one [PPI-149] is the first one that is an antagonist."

Both agonists and antagonists accomplish the same goals, but by different mechanisms, Limber said. When a patient is given an agonist, it causes an initial surge in testosterone levels. Over a period of three to four weeks, the testosterone levels drop down to target levels.

When an antagonist is administered, there is a rapid and complete reduction in testosterone levels, which occurs in hours to days, Limber explained.

Praecis is completing Phase II clinical trials of an injectable formulation of PPI-149 and is preparing to initiate Phase I trials of a sustained-release formulation of PPI-149. Phase III studies of PPI-149 for prostate cancer and other indications will begin in the first quarter of 1998, using the sustained-release formulation, Limber said.

Praecis has two products in preclinical studies: an amyloid plaque inhibitor for Alzheimer's disease and a basic fibroblast growth factor for hormone-insensitive prostate cancer patients.

The collaboration is the Cambridge, Mass., company's second corporate partnership, the first signed in August 1996 with Boehringer Ingelheim International GmbH, of Ingelheim, Germany, which contracted Praecis to use its screening technology to test Boehringer Ingelheim's existing chemical library in the area of Alzheimer's disease.

Praecis scientists, Limber said, have been able to replicate their efficient drug discovery process to add to the company's pipeline in other areas.

The company's drug discovery method uses core technology to screen libraries to develop new pharmaceuticals with safety and efficacy characteristics.

Praecis uses a variety of proprietary screening and optimization techniques to rapidly identify compounds suitable for development in strategically important therapeutic areas, Limber said.

The company has developed a high-throughput screening technology that allows for a fast look at and analyzation of many possible compounds for the purpose of identifying lead compounds that are attractive development candidates.

"We want to build value for the shareholder," Limber said, "by developing and commercializing viable and value-added pharmaceutical products. This deal, I believe, illustrates that is exactly what we are doing."

Praecis was founded in 1993 and is backed by venture capital funds. Its burn rate is approximately $1 million per month and, Limber said, there is enough capital to carry the company for a number of years. *