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CalciMedica Finds a New Pathway to Fight Autoimmune Disorders

Xconomy San Diego — 

In 2005, Gonul Velicelebi was the vice president of research and drug discovery at TorreyPines Therapeutics (NASDAQ: TPTX) when scientists there determined that a molecule dubbed STIM1 played a crucial role in activating immune cells.

To Velicelebi, STIM1 was like a key that helped open a hidden pathway that scientists had been seeking for 20 years. It also opened a new path for Velicelebi, who in 2006 founded CalciMedica, a startup focused on developing a variety of small molecule drugs to suppress autoimmune and inflammatory diseases. “This is a whole new pathway for modulating immune response,” she says.

A key aspect to CalciMedica’s approach is that it appears to sidestep a buildup of toxic compounds associated with the long-term use of some drugs prescribed to prevent organ transplant rejection and to treat autoimmune diseases. “There is a huge unmet need,” Velicelebi says. “Rheumatoid arthritis alone is 2 percent of the population,” and then there is lupus and inflammatory bowel diseases, like Crohn’s disease.

The TorreyPines team had pinpointed STIM1 as a key component in calcium release-activated calcium, or CRAC, channels. Velicelebi says the CRAC channel is essential for activating T cells, a core element of the body’s immune response, and that makes the CRAC channel an ideal target for a new class of immunosuppressive drugs.

But the research fell outside TorreyPines’ focus on diseases and disorders of the central nervous system. So TorreyPines transferred its STIM1-related assets to CalciMedica in 2007, in exchange for common stock in Velicelebi’s startup, along with other potential fees and royalty payments. CalciMedica also acquired exclusive rights to Orai1, the CRAC channel discovered by researchers at Harvard Medical School’s CBR Institute for Biomedical Research. Studies have shown that Orai1 and STIM1 function together in activating the immune response.

Since then, CalciMedica’s progress in optimizing candidate compounds for a variety of autoimmune disorders enabled Velicelebi’s startup to raise a total of $7 million in 2007 from SR One, the corporate venture arm of GlaxoSmithKline, and Sanderling Ventures.  CalciMedica got a commitment for $12 million in another round of venture funding led by Biogen Idec New Ventures in November, 2008, with participation from SR One and Sanderling Ventures, $4 million of which was invested immediately. The remaining $8 million will come in two installments from all three investors as CalciMedica meets future milestones

“This is a very exciting area,” says Velicelebi, who points to a drug development partnership that rival Synta Pharmaceuticals of Lexington, MA, announced last month with Roche, the Swiss Pharmaceutical giant. Like CalciMedica, Synta is focused on developing a new class of small molecule drugs that also target CRAC channels as a way to modulate immune cell function. Satwant Narula, Roche’s Head of Discovery for Inflammation, said in a statement released at the time: “The CRACM (modulating) channel inhibitor approach has tremendous potential to treat rheumatoid arthritis and a wide range of other inflammatory diseases that have a high unmet need for oral, targeted, disease-modifying agents.” Roche agreed to pay Synta $25 million in upfront license fees under the deal, along with additional payments that could total close to $1 billion.

“It’s the potential of this strategy that has gotten the corporate interest,” Velicelebi says. “For a small, young company, I think we’re going to be OK.”