September 10, 2008

San Francisco Business Times

Proteolix takes long view against autoimmune diseases

It's ambitious enough to develop the next generation of cancer killers. But Proteolix Inc. is stretching to take long-term aim at autoimmune diseases as well.So while the South San Francisco company tries to broaden the effectiveness of a relatively new way of fighting cancer - proteasome inhibitors - CEO Susan Molineaux hopes to extend research to develop so-called immunoproteasome inhibitors to treat problems like rheumatoid arthritis, psoriasis or Crohn's disease."It will continue to be very intriguing," Molineaux said.Proteasomes, enzymes found in cells, control the turnover of proteins in cells. Researchers found, however, that cancer cells are especially sensitive to proteasomes being blocked. Millennium Pharmaceuticals in 2003 won Food and Drug Administration approval to use Velcade, the first proteasome inhibitor, to fight multiple myeloma and, in 2006, to help treat mantle cell lymphoma.Enter Proteolix, founded in 2003 on the strength of research in the labs of Craig Crews at Yale University and Raymond Deshaies at the California Institute of Technology."Big Pharma wasn't looking at proteasome inhibitors," said Molineaux, who joined Proteolix as chief scientific officer.Together, Molineaux and the late Philip Whitcome, who had been the first hire at what would become Amgen Inc. and was Proteolix's founding CEO, refashioned the Proteolix business plan.With a clinically validated target - thanks to Velcade's approval - and a molecule from Yale, Proteolix scored $18.3 million in Series A financing in December 2003. It was a difficult period for many biotech companies to raise capital."The advantage of starting at a tough time is you become an expert in buying at auction," Molineaux said.Along with winter-green chairs recovered from a CV Therapeutics dumpster, newly acquired equipment was stored in Molineaux's garage. Eventually, the company set up shop in rented space at Fibrogen Inc., then Rinat Neuroscience, before landing its own home in South San Francisco.In the process, Proteolix won another $45 million and has pushed its lead proteasome inhibitor candidate, carfilzomib, into two Phase II studies to treat patients with relapsed multiple myeloma and a Phase I trial in lymphoma.The 85-employee company also is developing an oral version of carfilzomib.Still, research is continuing on immunoproteasome inhibitors that could open new therapeutic areas for Proteolix. It's a universe worth exploring, Molineaux said: Autoimmune disorders are broad and a therapeutic for one could be useful in another indication."It was a discussion question: Could we inhibit just that and would that be useful?" Molineaux said.In the process, Proteolix will see its burn rate increase "quite significantly," Molineaux said, but it looks to close a Series C round of funding before the end of the year.Proteolix Inc.Susan Molineaux, founder, chairman, president and CEO.Drug in development: Developing a next-generation proteasome inhibitor that could target more cancers while working on a selective immunoproteasome inhibitor, which could take on autoimmune diseases.