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Roche lines up at Synta’s CRACM gate
February 2009
by Lloyd Dunlap  |  Email the author
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LEXINGTON, Mass.—In the search for an effective, non-toxic orally administered anti-inflammatory drug, Synta Pharmaceuticals Corp. and Roche have announced the formation of a strategic alliance that could bring Synta $1.025 billion dollars over the term of the agreement. In return for funding research to be conducted by Synta, Roche will receive worldwide rights to develop and commercialize certain products identified during a two-year research period. Synta retains certain co-development and co-promotion rights. All preclinical, clinical, and commercial costs will be paid by Roche.

Synta will receive $9 million for the first two years' research, plus another $25 million in upfront cash, license fees and committed research support. Other payouts include up to $245 million for the initial product and up to half that amount for two additional products. Commercialization milestones of up to $170 million could be earned for each of three products. Synta will also receive tiered royalties on sales of all approved, marketed products.

Roche echoes Synta's claim that it's the leader in small-molecule drug development of calcium release-activated calcium modulator (CRACM) channel inhibitors. Dr. Satwant Narula, head of Roche's inflammation discovery group, acknowledges that the company has had its eye on Synta for a few years. She notes CRACM inhibitors work via a "very different kind of molecular target." Though at the early stages, she adds that "the partnership is based on our excitement. The biology looks very interesting and Synta is the leader."

In preclinical models, the CRACM inhibitors discovered by Synta potently and selectively inhibit the secretion of pro-inflammatory factors such as TNF-alpha and IL-2, with minimal effects on other cells or signaling pathways.

In fact, according to Narula, mast cells, macrophages, dendritic cells and others also can be targeted, making this new category of oral disease-modifying agents effective for treating rheumatoid arthritis and a broad range of other autoimmune and inflammatory diseases, including asthma, chronic obstructive pulmonary disease (COPD), allergy and transplant rejection.

"The science behind this target is very exciting and compelling," states Dr. Safi Bahcall, Synta's president and CEO. "CRACM is a unique gate that lets in calcium which immune cells depend upon to activate the immune systems. If you modulate this flow, you can affect the immune response. This agreement underscores both the potential of our novel ion channel inhibitors and the ability of the Synta drug discovery platform to generate high-quality, first-in-class drug candidates."

Bahcall recites the well-known limitations of current anti-inflammatory therapies, which include long-term toxicity and drug resistance, injectable dosage forms in many cases, and oral agents that tend to be non-specific and therefore highly toxic.

Another benefit to Synta of the agreement with Roche was that it allows the smaller company to "broaden its bandwidth" in Bahcall's term, to tackle oncology programs that have been on the backburner. "We want to move the program forward as rapidly as possible," he adds. "and the fit with Roche, including the intangibles, was excellent right from the beginning. It's the right thing for patients as well as being the right thing for Synta." For Roche, he says, "If we're successful it could be the biggest thing since Genentech." Lead compounds are now in animal testing and Bahcall hopes to have a drug in the clinic next year. DDN
 
Code: E020921

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