BridgeBio Oncology Therapeutics (BBOT) 44th Annual J.P. Morgan Healthcare Conference summary

Key clinical data and program updates

• 8520, a direct KRAS G12C on-off inhibitor, showed a 65% response rate and 83% six-month durability in NSCLC, with a differentiated safety profile, especially regarding liver toxicity, both as monotherapy and in combination with pembrolizumab.

• Early signals in STK11/KEAP1 co-mutant patients were highly encouraging, with all five dosed patients responding, addressing a significant unmet need.

• BBO-11818, a pan-KRAS inhibitor, demonstrated anti-tumor activity and a confirmed partial response in a heavily pretreated pancreatic cancer patient, with a favorable safety profile and dose-proportional pharmacokinetics.

• BBO-10203, a novel RAS PI3K alpha breaker, achieved all phase 1 monotherapy objectives, including full target engagement, no hyperglycemia, and a differentiated safety profile, with combination cohorts now open.

• All three programs are ahead of schedule, with additional data sets and combination studies planned for the remainder of 2026.

Differentiation and competitive positioning

• 8520’s on-state inhibition mechanism enables lower drug levels, improved potency, and a superior safety profile compared to off inhibitors, especially in combination with pembrolizumab.

• Off inhibitors require dose reductions due to liver toxicity, while 8520 maintains efficacy at full doses with less toxicity.

• 818’s selectivity for KRAS over HRAS/NRAS allows higher inhibition levels without common toxicities, and it is the first pan-KRAS inhibitor to show a confirmed response in pancreatic cancer.

• 203’s unique mechanism avoids hyperglycemia and is agnostic to mutational status, opening a large patient population for combination therapies.

• The portfolio’s differentiation in efficacy and safety positions it as potentially best-in-class in crowded KRAS G12C and pan-KRAS spaces.

Combination strategies and future plans

• Internal combinations of KRAS inhibitors (8520, 818) with the breaker (203) are prioritized, with clinical combinations opening in 2024.

• Preclinical models show synergistic tumor regression with these combinations, and the safety profile supports clinical translation.

• Combination cohorts with standard of care (e.g., pembrolizumab, trastuzumab, fulvestrant, FOLFOX/BEV) are open or planned in multiple tumor types.

• Willingness to explore combinations with approved or in-development external agents for proof of concept.

• Upcoming data catalysts include more combination and monotherapy data across all programs, with a focus on safety and efficacy in hard-to-treat populations.