Washington Editor

In its first major partnership, Predix Pharmaceuticals Holdings Inc. could receive more than $307.5 million per terms of a new deal with Amgen Inc. on S1P1 modulators for autoimmune diseases.

Lexington, Mass.-based Predix largely will turn over the reins to a lead compound already in its preclinical portfolio to Amgen, and both companies will work jointly to create and develop new S1P1 modulators. The target is one of at least five different G protein-coupled receptors (GPCRs) that are activated by a phospholipid called Sphingosine-1-phosphate (S1P), and those GPCRs play a role in multiple biological processes such as immune system activation and cardiovascular function. Amgen would be responsible for the clinical development and commercialization of any resulting product candidates.

It's expected that S1P1 modulators "will provide a gentler but as effective immunosuppression" as widely used anti-inflammatory drugs such as methotrexate and cyclosporine, Predix President and CEO Michael Kauffman told BioWorld Today, "without some of the off-target effects."

That's what lured in Thousand Oaks, Calif.-based Amgen. Indeed, Kauffman pointed to hype around a Phase III multiple sclerosis trial testing an S1P1 modulator called FTY720, a product from Novartis AG, of Basel, Switzerland.

Like that late-stage compound, he said Predix's S1P1 agonist could induce peripheral lymphopenia, a reduction in circulating lymphocytes in the blood, in effect "asking the white blood cells to be a bit quieter but not shutting them off completely." That's critical, Kauffman said, "because you want your immune system to be able to fight off infection but you don't want it to cause autoimmunity."

That mechanism potentially could prove beneficial in autoimmune disorders such as multiple sclerosis, rheumatoid arthritis, inflammatory bowel disease and rejection of transplanted organs, indications on which the collaboration could focus.

For competitive reasons, he declined to elaborate on specific properties of Predix's lead S1P1 agonist. But notably, it and other S1P1 modulators are orally available small molecules, while newer biological products that largely avoid the immunosuppressive characteristics of methotrexate and cyclosporine are large molecules that require injections.

Payments to privately held Predix, which is in the midst of a definitive merger agreement with publicly held EPIX Pharmaceuticals Inc., include $20 million in up-front money and up to $287.5 million more for certain clinical, regulatory and sales milestones, followed eventually by double-digit royalties on sales. Kauffman, formerly a practicing rheumatologist, called Amgen "one of the foremost leaders" in the treatment of autoimmune disease. "We really couldn't have gotten a better partner."

Down the road, Predix has an option to co-promote a product from the collaboration in the U.S., fulfilling a longstanding goal of the company for full integration.

Predix's S1P1 program was born from its structure-guided drug design technology that models GPCRs, and Kauffman said the deal validates the in silico technology's broad potential. Already it has led to four clinical programs, all serotonin drugs, so Amgen's interest in the lipid-based S1P1 agonist points to its wider applicability.

The transaction with EPIX, of Cambridge, Mass., is valued as a $90 million buyout of Predix. Assuming a favorable shareholder vote scheduled for Aug. 15, the surviving entity will retain the EPIX name and Nasdaq trading symbol, and feature Predix's early stage discovery and design capabilities with EPIX's preclinical, clinical and regulatory capacity. (See BioWorld Today, April 4, 2006.)

"With four drugs in the clinic," Kauffman said, "we needed to round out our staff and bring to bear our critical mass."

Beyond the S1P1 drug class, Predix's four clinical-stage programs are led by PRX-00023, a product for generalized anxiety disorder. Later this year, the company expects to complete the first of at least two pivotal Phase III trials, and eventually plans to out-license it.

Its other clinical-stage drug candidates include PRX-03140 for Alzheimer's disease, which is expected to enter Phase IIa later this year; PRX-08066 for pulmonary hypertension, which recently entered Phase II; and PRX-07034, which recently entered Phase I and is expected to be developed for obesity, as well as cognitive impairment associated with Alzheimer's disease or schizophrenia. In addition, Predix has a partnership with the Cystic Fibrosis Foundation around two targets in that space.