Bayer-backed Affini-T snags $175M to enter increasingly crowded KRAS-cancer field

Affini-T Therapeutics CEO Jak Knowles, M.D., is no stranger to the kind of startups that draw early capital, having once been vice president of venture investments for Bayer’s VC arm, Leaps by Bayer. But now, he’s the one asking for money, and his former employer is ready to dole it out.  

Led by Vida Ventures and Leaps, Affini-T now has $175 million in new fundraising to build out a suite of engineered T-cell receptors (TCRs) to tackle solid tumors, with sights set on human trials by next year. The money will go toward fleshing out the company's platform and bringing “multiple” programs into the clinic, according to a Tuesday release. 

The brainchild of Phil Greenberg, M.D., at the Fred Hutchinson Cancer Research Center in Seattle, Affini-T’s platform works by using engineered TCRs to spawn more robust CD4 and CD8 T cells. The company believes this will pioneer a new wave of T cells that can target solid tumors, an area where cell therapy has so far failed to make consistent inroads.

The company’s oncology program is targeting the KRAS gene, which, when mutated, is a sign of cancer cells. Once cancer cells acquire the mutation, they get “addicted” to it, Knowles said in an interview with Fierce Biotech. 

“Without it, they don’t survive as well,” he said. “We actually can’t find any evidence of a cell losing KRAS mutation.” 

Knowles pointed to other companies targeting the KRAS G12C mutation—Amgen and Mirati—as evidence of the gene’s potential as a therapeutic target but noted that the small molecules both companies are using are unlikely to be applicable to other mutations. Amgen's Lumakras is approved for KRAS-mutated non-small cell lung cancer, while Mirati's adagrasib is in late-stage clinical trials for the same indication and others. Eli Lilly also recently got back into the KRAS field with plans to enter phase 1 testing later this year with a new candidate for solid tumors. 

Cell therapy, on the other hand, has more promise, according to Knowles. 

That theory is being tested immediately, with the company’s two lead oncology programs targeting KRAS’s G12V and G12D mutations. An indication hasn’t been formally named yet, but Knowles said the company is focused on colorectal, lung and pancreatic cancers, the latter of which has been found to have the KRAS gene in 95% of tumor cells.

Jürgen Eckhardt, M.D., head of Leaps—Knowles’ former boss—said Affini-T’s promise in solid tumors is what excited the firm. 

“The solid tumor space really is not yet solved by cell therapy,” he said. “That’s I think how and why we got excited in Affini-T, because we believe this is a great approach that could potentially help solve the solid tumor issue.” 

Eckhardt also echoed that it’s been a close relationship between Leaps and Affini-T from the jump. The technology behind the biotech was first identified at the Fred Hutch back when Knowles worked at the firm, and he ultimately chose to leave to build the company.   

Looking ahead, Knowles anticipates having both oncology programs in the clinic by next year, but he wouldn’t commit to a timeline for applying for human trials. He added that the company plans to speak to regulators later this year.