Plexxikon has formed a multi-product collaboration with Wyeth Pharmaceuticals, a division of Wyeth. The collaboration is focused on the development of Plexxikon's clinical lead, PLX204, as well as several other novel small molecule drugs targeting the PPAR family of nuclear receptors, for the treatment of type 2 diabetes and other metabolic disorders, the company said here.

Under the terms of the agreement, Plexxikon will receive payments of over $22 million, including an upfront license fee and multi-year research funding. Additionally, Plexxikon may earn further milestone payments totaling nearly $350 million related to the successful development and commercialization of potential products emerging from the collaboration. Plexxikon also will receive royalties on future product sales. Wyeth also will provide a loan to fund Plexxikon's share of clinical development under a co-development and co-funding option for any collaboration product, according to the company release.

"Wyeth has the discovery, development and commercialization capabilities to leverage our PPAR product opportunities and discovery assets. Wyeth's extensive pharmaceutical development experience, as well as the company's desire to build a strong presence in metabolic disease, makes them the perfect partner for Plexxikon," said K. Peter Hirth, chief executive officer of Plexxikon. "Plexxikon's Scaffold-Based Drug Discovery platform is particularly well-suited to the development of multiple, distinct PPAR drugs addressing the medical need in the treatment of diabetes and metabolic syndrome," Hirth added.

The collaboration is focused on Plexxikon's PPAR (Peroxisome Proliferator-Activated Receptor) compounds and discovery programme. Plexxikon's PPAR modulators represent an entirely novel chemical class of orally-active compounds that could be used to treat a variety of metabolic conditions, including diabetes, insulin resistance, dyslipidemia and obesity.

The focus of Plexxikon's PPAR programme is to discover and develop modulators that demonstrate improved safety as well as additional therapeutic benefits compared to currently marketed therapies. Moreover, Plexxikon's discovery platform enables the design of novel drug candidates that target one or more of the key PPAR receptors, and in varying degrees, allowing for the development of several PPAR agonist compounds with different profiles that specifically address the needs of distinct patient populations.

"Wyeth is entering into this collaboration with Plexxikon as a key step in our strategy to expand our efforts in the development of new drugs for diabetes and other metabolic disorders. Plexxikon's PPAR pan-agonist drug PLX204 has the potential to address the regulation of cholesterol and glucose levels along with an improved safety profile, all in one medicine," said Frank Walsh, senior vice president and head of discovery, Wyeth Research.

In parallel, Plexxikon and Wyeth will develop Plexxikon's most advanced PPAR compound, PLX204 for the treatment of type 2 diabetes. PLX204 modulates the function of three related targets - PPAR alpha, delta and gamma. Therefore, PLX204 is expected to regulate levels of glucose, triglycerides, free fatty acids, HDL (good cholesterol) as well as energy expenditure, in a once-daily pill. In contrast, current treatment regimens require several drugs be taken concurrently to fully manage the various metabolic imbalances seen in diabetic patients. Plexxikon has recently completed a single dose non-IND study in humans to profile the pharmokinetic properties of PLX204, in preparation for a planned IND filing. Follow-on compounds will be tailored to a subset of patients in the pre-diabetic and diabetic population.

Plexxikon's proprietary Scaffold-Based Drug Discovery platform is being applied to build therapeutic franchises in metabolic and cardiovascular disease, inflammation and oncology.