Progenics Pharmaceuticals Inc. picked up a worldwide partner for methylnaltrexone (MNTX), its investigational treatment of opioid-induced side effects, signing a deal with Wyeth Pharmaceuticals for up to $416 million.

The Tarrytown, N.Y.-based company also bought back royalty rights to MNTX from UR Labs Inc., which acquired the drug from the University of Chicago before licensing it to Progenics in October 2001. Progenics agreed to pay UR Labs $2.6 million in cash plus 686,000 shares of its common stock in exchange for a "substantial portion" of the MNTX royalty rights, the company said.

"We've taken [MNTX] from a drug in academic clinical trials to one that is completing its first set of Phase III trials," said Richard Krawiec, vice president of investor relations and corporate communications at Progenics. "And now it's in a development and commercial deal with a major pharmaceutical company."

MNTX has "fit well with our business model to bring in drugs, do proof-of-concept and clinical trials and then, at late stage, license them under what we believe are favorable terms to the company," Krawiec added.

Wyeth Pharmaceuticals, a division of Madison, N.J.-based Wyeth, gets exclusive rights to MNTX, an opioid receptor antagonist in development for opioid-induced constipation and postoperative bowel dysfunction, in exchange for an up-front payment of $60 million plus milestone payments of up to $356.5 million.

Progenics retains co-promotion rights in the U.S., and is eligible for royalties on product sales outside the U.S.

Meanwhile, Wyeth is taking over all development and commercialization costs, and the companies will form a joint development committee to oversee further clinical work. Progenics' stock (NASDAQ:PGNX) gained $2.51 Friday, or 11 percent, to close at $25.60.

MNTX is being developed in three formulations and indications. The first, administered as a subcutaneous injection, is finishing up a second pivotal Phase III trial in intractable constipation in patients with advanced medical illness, such as cancer and AIDS.

Top-line data from the first Phase III study, reported in March, showed that the drug met its primary endpoint of inducing laxation within four hours at dosage levels of 0.15 mg/kg and 0.30 mg/kg. (See BioWorld Today, March 11, 2005.)

An intravenous formulation, aimed at treating patients with postoperative bowel dysfunction, recently completed a Phase II study, and Progenics will meet with Wyeth, as well as the FDA, to "determine the best way to go forward into Phase III," Krawiec said. "We will take the lead in conducting those trials in the U.S.," he told BioWorld Today, while Wyeth will be responsible for trials of the two injectable forms outside the U.S.

Wyeth also will handle all worldwide studies of the oral formulation of MNTX to treat opioid-induced constipation in patients with chronic pain. The oral version is preparing to enter Phase II development.

About 1.7 million patients in the U.S. suffer from advanced medical illness requiring opioid treatment, more than 2 million are at risk of developing postoperative bowel dysfunction following surgery, and about 5 million receive opioids on a chronic basis. While opioids, such as morphine, can relieve a patient's pain, they also can interact with opioid receptors in the central nervous system, resulting in severe side effects, such as constipation. MNTX is designed to work by blocking the peripheral opioid receptors without crossing the blood-brain barrier to interfere with brain-centered pain relief.

"There really are no adequate treatments for these disorders," Krawiec said. "We're targeting a major unmet need."

Elsewhere in Progenics' pipeline are drugs aimed at treating HIV infection and cancer. The company recently initiated a Phase Ib trial of PRO 140, a humanized monoclonal antibody designed to specifically bind CCR5, a receptor that serves as a point of entry for HIV into cells. It also has started research on ProVax, a prophylactic HIV vaccine candidate.

In cancer, Progenics' GMK cancer vaccine is in Phase III studies in patients with malignant melanoma, and is part of a collaboration with Princeton, N.J.-based Cytogen Corp. to develop immunotherapies against prostate cancer.

Progenics reported a net loss of $10.7 million for the third quarter. As of Sept. 30, it had cash, cash equivalents and marketable securities totaling $128 million.