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 population with limited options.

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

• BBO-10203, a novel RAS PI3K alpha breaker, achieved all phase 1 monotherapy objectives, with no hyperglycemia or dose-limiting toxicities, and is now enrolling in three combination cohorts.

Mechanistic differentiation and safety

• 8520’s direct on-state inhibition enables lower drug levels for efficacy and prevents adaptive resistance seen with off inhibitors.

• The PK/PD disconnect allows for effective inhibition with lower systemic exposure, supporting a superior therapeutic index.

• Safety data across programs show no grade 3 or higher liver toxicity for 8520, no dose-limiting toxicities, and manageable adverse events, with GI events being most common for 818.

• 203’s mechanism avoids hyperglycemia by not inhibiting kinase activity, allowing normal glucose homeostasis and broad patient eligibility.

Competitive positioning and future plans

• 8520 and 818 are positioned as best-in-class due to efficacy and safety, with 8520 outperforming off inhibitors in response rate and tolerability, especially in combination with pembrolizumab.

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

• 203’s differentiated safety and efficacy in heavily pretreated patients, including KRAS mutant CRC and breast cancer, support its use in combination regimens.

• Internal combinations of KRAS inhibitors with the breaker are prioritized, with clinical combinations of 8520+203 and 818+203 planned for this year.

• The portfolio is ahead of schedule, with additional data catalysts expected in 2026, and the team is confident in the transformative potential of these assets.