BridgeBio Pharma has spun its Rolodex to fund a subset of its sprawling list of opportunities. Busy with launch and late-phase activities, BridgeBio has secured $200 million to equip a cancer-focused offshoot to push a pipeline led by a KRAS inhibitor through early-phase tests.
In 2017, TheRas, which is now doing business as BridgeBio Oncology Therapeutics (BBOT), struck a deal with Leidos Biomedical Research that led to the licensing of a KRAS G12C inhibitor and two other assets. TheRas was a wholly owned subsidiary of BridgeBio for years but required limited funding, with R&D expenses related to the Leidos agreements totaling $3.6 million in 2023.
Now, with one asset in the clinic and two approaching human testing, BridgeBio has decided to spin the molecules out to create BBOT and bring outside investors on board. The funding gives BBOT the “runway to achieve significant clinical inflection points over the next 18-24 months,” BridgeBio said.
BBOT began a phase 1 trial of KRAS G12C inhibitor BBO-8520 in non-small cell lung cancer last month. The start date of the study, which will test the molecule as a single agent and in combination with Keytruda, puts the program years behind approved KRAS drugs sold by Amgen and Bristol Myers Squibb. But BBOT and its backers contend a feature of BBO-8520 could lead to better efficacy.
KRAS cycles between an “on” and “off” state. Amgen’s Lumakras and BMS' Krazati target the off state, as does Roche’s challenger divarasib. BBOT believes molecules also need to inhibit KRAS in its on state to achieve optimal target coverage and prevent adaptive mechanisms of resistance.
BBOT’s preclinical tests suggest BBO-8520 has advantages over Amgen, BMS and Roche’s molecules. And the biotech's researchers saw responses when the molecule was administered after the development of resistance to Lumakras.
The spinout is working to generate human data on BBO-8520 while preparing to move two other assets into the clinic. BBO-10203 is designed to block an interaction between RAS and PI3Ka. In doing so, the molecule may inhibit a tumor signaling pathway without causing the high blood sugar that affects people on PI3Kα inhibitors. BBOT is aiming to start enrolling patients in a clinical trial this year.
A pan-KRAS inhibitor, BBO-11818, is following close behind. Like Lumakras and Krazati, BBOT’s lead drug candidate only targets a subset of patients with KRAS mutations. BBO-11818 is designed to target the on and off states of multiple forms of KRAS, potentially making it effective in more patients. BBOT is aiming to file to study the molecule in humans next year.
Eli Wallace, Ph.D., and Pedro Beltran, Ph.D., will oversee the programs as BBOT’s CEO and chief scientific officer, respectively. Wallace joined BridgeBio as CSO in residence for oncology in 2019. Beltran arrived the following year to work with Wallace on programs targeting RAS biology.
The financing round was led by Cormorant Asset Management and co-led by Omega Funds. Affiliates of Deerfield Management, GV, EcoR1 Capital, Wellington Management, Enavate Sciences, Surveyor Capital, Aisling Capital, Casdin Capital and Longwood Fund also participated. Securing outside investment frees BridgeBio to spend its cash on launching acoramidis and enrolling patients in a clutch of phase 3 studies.