MedImmune, Inc. and Infinity Pharmaceuticals, Inc. have entered into an agreement to jointly develop and commercialize novel small molecule cancer drugs targeting Heat Shock Protein 90 (Hsp90) and the Hedgehog cell-signalling pathway.

In preclinical studies, Hsp90 and the Hedgehog pathway appear to be implicated in the growth and survival of a broad range of blood-related and solid tumour types. IPI-504, the most advanced of the drug candidates included in the agreement, is an Hsp90 inhibitor that has thus far been studied in two disease-focused phase 1 trials.

"Hsp90 and Hedgehog are among the most attractive targeted therapy opportunities in cancer research today, and the Infinity programs have a very strong competitive position," said Edward T. Mathers, MedImmune's executive vice president, corporate development and venture. "With IPI-504, we have a promising drug candidate with already-established preclinical in vivo proof of concept and the potential to reach the market by 2010. In collaboration with Infinity, we plan to accelerate development of the intravenous formulation of IPI-504, as well as to expand into additional tumour types. In addition, we expect to be able to commence clinical testing of the next generation oral formulation of IPI-504, as well as an oral formulation of a hedgehog inhibitor within the next 12 to 18 months."

Under the terms of the agreement, MedImmune and Infinity will share equally all costs and profits from the development and commercialization of any future products. MedImmune will provide Infinity a one-time upfront payment of $70 million for co-exclusive, shared rights to the Hsp90 and Hedgehog pathway product development programs. In addition, Infinity could receive up to an additional $430 million in milestone payments related to the companies' achieving certain late-stage clinical development and sales targets for any future products resulting from the collaboration.

For each of the Hsp90 and Hedgehog pathway programs, Infinity will retain primary responsibility for discovery, preclinical development and translational clinical development of products through proof-of-concept in humans. MedImmune and Infinity will jointly conduct clinical development through first product approval. MedImmune will lead worldwide regulatory strategy as well as sales and marketing of resulting products; Infinity retains an option to co-promote any future products in the United States, contributing up to 35 per cent of the total promotional effort.

"This collaboration with MedImmune allows Infinity to accelerate and maximize the development of our most advanced product candidates while enabling us to share fully in the potential value creation of these products," said Adelene Q. Perkins, Infinity's executive vice president and chief business officer. "We believe that MedImmune's established clinical, sales, and marketing capabilities are a strong complement to Infinity's expertise in novel small molecule drug discovery and development."

IPI-504 is Infinity's proprietary small molecule therapeutic drug candidate that, in preclinical studies, potently and selectively inhibited Hsp90, thereby killing cancer cells. Hsp90 is an emerging therapeutic target of interest for the treatment of cancer. Proteins are the mainstay of structural and signalling elements of all cells. Hsp90 functions to stabilize and maintain the activity of proteins in the cancer cell, thereby allowing a cancer cell to survive despite an abundance of misfolded and unstable proteins. Inhibition of Hsp90 has broad therapeutic potential for the treatment of patients with solid tumours and blood-related cancers, including cancers that are resistant to other drugs.

IPI-504 preferentially targets and accumulates in tumour tissues, sparing healthy tissues. In preclinical studies it has demonstrated a broad potential to treat certain cancers as both a single agent as well as in combination with existing anti-cancer drugs. The water-based formulation of IPI-504 is easy to deliver as an intravenous infusion. Infinity is currently conducting two Phase 1 clinical trials with intravenous formulations of IPI-504. In July 2005, Infinity initiated the first of these Phase 1 clinical trials in refractory multiple myeloma. In December 2005, Infinity initiated the second Phase 1 clinical trials with IPI-504 in refractory gastrointestinal stromal tumours (GIST). Infinity has also begun developing an oral formulation of IPI-504, which if successful, could be a more convenient route of administration for cancer therapy.