Targeted treatments have been a game changer for cancer patients with tumor-driving mutations like ALK or EGFR. But the reality is, this group of patients is pretty small–and even then, their tumors often develop resistance to targeted drugs, or the drugs may not work at all. Kinnate Biopharma is looking to change that, and it’s just raised $98 million to push its pipeline into the clinic.
“There’s a great promise of targeted therapies, but today, only 10% of patients with cancer have a known oncogenic driver for which there is a targeted therapy available,” Kinnate CEO Nima Farzan said. “And even of that 10%, about half of them won’t respond to an existing therapy, and of that half … about half of them will eventually develop resistance.”
Kinnate is working on kinase inhibitors for two scenarios: patients who do not yet have drugs targeting their tumor-driving mutations and patients whose cancers mutate to resist targeted drugs.
“It’s great to find new drugs for oncogenic drivers, but it’s important to find the next generation of drugs to fight resistance mutations that come up,” Farzan said. “We sometimes don’t know what those resistance mutations are going to be until the drugs out there are used by a lot of people and they start to pop up.”
The series C financing, led by RA Capital Management, will drive a trio of programs toward the clinic and support research programs, too. Kinnate’s backers Foresite Capital, OrbiMed, Nextech Invest and Vida Ventures chipped in, while new investors including Viking Global Investors, Venrock Healthcare Capital Partners and Fidelity Management & Research Company also joined the round.
Kinnate’s lead program targets BRAF mutations, a well-known driver of multiple cancers. The FDA has approved a number of BRAF inhibitors, including melanoma meds Zelboraf and Tafinlar, but these target what’s called class 1 BRAF mutations. Kinnate is interested in class 2 and class 3 mutations.
“These are the mutations for which those drugs do not work. They drive the same tumor types. It has to do with something wherein class 2 and class 3 mutations are getting what are called fusions or insertion/deletions, as opposed to point mutations,” Farzan said, referring to mutations which affect a single nucleotide base, or letter, in the DNA.
“BRAF ends up creating a protein complex, a dimer, and those approved drugs target BRAF as a monomer, as a single protein not in complexes. We need to develop a drug that hits multiple aspects of the protein complex,” he added.
Kinnate believes it has cleared some of the chemical hurdles to be able to drug these complexes. It plans to start in melanoma and non-small cell lung cancer before moving onto other cancers, such as colorectal and thyroid.
Following behind is an FGFR inhibitor Kinnate is developing for patients who develop resistance to first-line FGFR meds like Johnson & Johnson’s Balversa or Incyte’s Pemazyre.
“We believe we have a next-generation drug that can both cover that initial alteration driving the disease and any resistance mutations that come up,” Farzan said.
Both programs are slated to enter the clinic in 2021. Kinnate is also working on a CDK12 inhibitor that’s a little further behind.
Kinnate is far from the only biotech taking aim at cancer resistance: Tyra Biosciences launched in January with $50 million to develop drugs targeting “molecular drivers or events” that induce resistance to targeted drugs. And ORIC Pharmaceuticals, whose name stands for overcoming resistance in cancer, pulled off a $120 million IPO to advance programs that target resistance to multiple types of cancer treatments, including chemotherapy and immunotherapy.
What sets Kinnate apart isn’t necessarily a particular approach or technology, Farzan said. Rather, it’s the combination of expertise across drug design and translational research, the leadership team’s experience, the strength of the investor group and collaborations with the likes of Massachusetts General Hospital Cancer Center and the UC San Diego Moores Cancer Center.
“The combination is what is unique, not one specific technology no one else has. The combination is what you need to develop drugs–developing drugs is a cross-functional endeavor,” Farzan said.