RA Capital, Canaan help infuse $50M into Alta-incubated biotech battling acquired resistance to TKIs

Since Gleevec was approved in 2001, over 40 other tyrosine kinase inhibitors have come onto the market to treat various types of cancer. But with the proliferation of the class also came a surge of acquired resistance, where patients’ tumors mutate around the drug target and stop responding to the therapies.

Tyra Bio, a Carlsbad, CA-based biotech “purpose built” to address that problem, has just raised $50 million from Alta Partners, RA Capital Management, Boxer Capital of Tavistock Group, and Canaan.

“It’s not entirely clear what type of acquired resistance might emerge really until you get these drugs into patients,” co-founder and CEO Todd Harris told Endpoints News. “In some instances, the first generation drugs couldn’t have entirely predicted what might come along.”

But with some classes of TKIs now in their third generation, there is an increasing amount of clinical evidence and better tools to crunch them for insights into the precise mutations — insights that Tyra would take right back to the start of drug discovery and development. In the long run, the goal is for their drugs to not just be deployed when resistance emerges but to move to the frontline setting with the hope of a longer duration of response.

Harris added that the strategy has shown some promise in ALK and EGFR, but remained tight-lipped about the exact targets they are starting with, though it’s a safe bet they would first go after the most well-known ones.

Daniel Bensen, COO and co-founder, will be steering a small team alongside CSO Ronald Swanson, CFO Esther van den Boom, and Robert Hudkins, VP of chemistry, as well as Jane Arboleda, associate director of cell biology, to bring their first candidates to the clinic. An army of biotechs are in the game, many focusing on particular niches within the vast TKI space. Tyra will be looking to outpace some of them.

Jason Sheltzer of Cold Spring Harbor Laboratory, William Hahn of Dana Farber, and Jeffrey Hager, formerly of Ideaya Bio, have come on board as scientific advisors.

“Our strength is really in a nimble and highly experienced drug discovery and drug development team,” Harris said, leveraging tried and true technologies such as structured-based drug design, and patching in self-built preclinical models whenever necessary.

Harris also co-founded what eventually became Sienna Biopharma, a skin drug developer that counted Arch Ventures and Partner Fund Management as backers but nevertheless was forced to file for Chapter 11 after a bruising trial failure. The entrepreneurial lesson he learned: Finance your company for the ups and downs along the biotech road.

Alta Partners, which incubated Tyra, is ready for the long haul. The inclusion of crossover firm RA Capital also gives Harris more confidence that this one will stick. Each investor in the Series A is sending a representative to the board: Bob More of Alta Partners, Jake Simson of RA Capital, Sid Subramony of Boxer Capital and Nina Kjellson of Canaan. Mirati CMO Isan Chen and former Gates foundation exec Gilla Kaplan are the other two directors.