Dive Brief:

• A group of well-known biotechnology investors is putting $200 million into a newly launched spinout of BridgeBio Pharma developing drugs that target two common cancer genes.
• BridgeBio Oncology Therapeutics, which was previously organized as a BridgeBio subsidiary called TheRas, will advance three drug candidates. Two aim at cancers driven to growth by mutations in a gene called KRAS, while the other blocks signaling between two proteins often involved in tumor development.
• Comorant Asset Management led the financing, along with Omega Funds. Nine other venture firms participated, including Deerfield Management and GV.

Dive Insight:

Up until not that long ago, BridgeBio Oncology Therapeutics would have had a more difficult pitch to investors.

Cancer drug researchers for decades had sought to pin down the oncogene KRAS, errors in which were identified as common catalysts for tumors of the lungs, colon and pancreas. Their efforts were universally unsuccessful, earning KRAS a reputation as “undruggable.”

A 2013 paper by scientists at the University of California, San Francisco, helped crack the code, suggesting how to target with drugs a “pocket” on a certain kind of mutated KRAS protein. Their work led to a new wave of drug development, one which eventually produced Amgen’s Lumakras, approved in the U.S. in 2021, and Mirati Therapeutics’ Krazati, cleared the following year. 

With those drugs available, BridgeBio Oncology Therapeutics doesn’t need to convince anyone that drugging KRAS is possible. Instead, its pitch centers on how to build a better KRAS drug.

Its most advanced candidate is designed, like Lumakras and Krazati, to bind to a type of mutated KRAS protein to shut down the growth signals that swell tumors. Unlike Lumakras and Krazati, the candidate, dubbed BB-8520, can bind to the protein in its active state, as well as when its inactive. (Lumakras and Krazati binding to inactive KRAS prevents the protein from cycling back on.)

“We actually inhibit the protein that signals, the active protein,” said Eli Wallace, BridgeBio Oncology Therapeutics’ CEO. “Really what’s driving the tumor is that on stage.”

Wallace noted, too, how the most common resistance mechanisms to the current KRAS inhibitors involve increased time in the active stage.

BB-8520 is already in clinical testing, with a Phase 1 study of people with lung cancer underway this month.

It has company, however. Frontier Medicines recently raised $80 million to fund, in part, development of a drug that also targets the on and off states of the KRAS protein. 

BridgeBio Oncology Therapeutics has another KRAS inhibitor, one designed to bind to several different mutated types of KRAS protein, that’s earlier in development. The company plans to ask early next year for regulatory clearance to begin testing.

Also in its pipeline is another kind of cancer drug. Called BBO-10203, it’s what Wallace described as a protein-protein interaction inhibitor, meant to block the cellular conversation between proteins called RAS and PI3Ka. Muting this signaling should help slow tumor growth, as PI3Ka mutations are found in many types of cancer.

The company hopes to begin enrolling patients into a trial of BBO-10203 later this year.

BridgeBio Pharma is built on a “hub-and-spoke” model, acting as a parent for a web of biotech subsidiaries. The company has used this approach to launch other spinouts, like QED Therapeutics and Adrenal Therapeutics. It’s also reacquired one, Eidos Therapeutics, to get full ownership of a medicine for an uncommon heart disease.

“The [hub-and-spoke] system at BridgeBio … really makes this transition fairly seamless, because the employees, the assets, they’re all in a standalone group, so the separation is fairly seamless to an independent company,” Wallace said.

All three of BridgeBio Oncology Therapeutics’ drugs were previously listed in BridgeBio Pharma’s pipeline, tied into its TheRas subsidiary.

BridgeBio Pharma director Frank McCormick will chair BridgeBio Oncology Therapeutics’ board, and BridgeBio Pharma CEO Neil Kumar will serve as a director. About 50 people will work for the new company, Wallace said.

The company expects its funding to provide an operating runway of 18 to 24 months. 

Editor’s note: This story has been updated with additional detail.