Results of studies of anti-cancer investigational compounds co-developed by National Cancer Institute RAS Initiative scientists at the Frederick National Laboratory for Cancer Research will be featured in a live session and a poster session at the American Association for Cancer Research Annual Meeting, April 17-22 in San Diego.
The RAS: P13Ka breaker BBO-10203 inhibits P13Ka/AKT activity in HER2+ models through non-canonical RAS signaling blockade will be presented on Tuesday, April 21 at 3:35 p.m. PT in Ballroom 6DE on the upper level of the San Diego Convention Center. Presenter is James Stice, director at BridgeBio Oncology Therapeutics (BBOT).
BBO-10203 is a “breaker” compound that blocks an intracellular RAS signaling pathway known to drive the growth of many types of RAS-related cancer, including lung and colorectal cancers. It was co-developed by the Frederick National Laboratory, BBOT and Lawrence Livermore National Laboratory.
The AACR presentation focuses on how BBO-10203 alone and in combination with other drugs acts against HER2+ breast cancer cell lines. BBO-10203 is in phase 1 clinical trials and is being evaluated in patients with HER2+ breast cancer, both alone and in combination with trastuzumab.
BBO-11818: An orally bioavailable, highly potent and selective non-covalent pan-KRAS (ON) and (OFF) inhibitor with robust anti-tumor activity in KRAS-mutant preclinical models will be presented in the poster session (section 13) on Wednesday, April 22 from 9 a.m. to noon PT. Carlos Stahlhut Espinosa of BBOT will present.
As monotherapy and in combination with several additional compounds, BBO-11818 is a potent pan-KRAS inhibitor with activity against both the GTP- and GDP-bound states of KRAS, presenting the opportunity to address a large fraction of KRAS-mutant tumors currently lacking targeted therapeutic options. BBO-11818 combined with BBO-10203, BBO-11818 and cetuximab, and BBO-11818 and anti-PD1 all show combination benefit in pre-clinical models. BBO-11818 has entered Phase 1 clinical trials for patients with various KRAS mutations in colorectal, pancreatic, and lung cancers.
RAS Initiative authors from the Frederick National Laboratory on the two abstracts include: Anna Maciag, Albert Chan, Alok Sharma, Patrick Alexander, Megan Rigby, Roger Ma, Brian Smith, Dana Rabara, Erik Larsen, David Turner, Andrew Stephen, Dhirendra Simanshu, Daniel Czyzyk and Dwight Nissley.
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