BridgeBio Oncology Therapeutics (BBOT) Piper Sandler 37th Annual Healthcare Conference summary

Pipeline overview and strategy

• Focus on small molecules targeting RAS and PI3K-alpha, the two most mutated oncogenes, with three in-house discovered programs in phase I clinical development.

• BBO-8520 is a KRAS G12C on/off inhibitor with high affinity for both protein states; BBO-10203 is a RAS-PI3K-alpha breaker; BBO-11818 is a pan-KRAS inhibitor.

• All programs are advancing through dose escalation, with data readouts planned for 2025 and 2026.

• $468 million in cash as of September 30, 2024, expected to fund operations into 2028 and support all three programs through key data inflection points.

• Strategic partnering will be considered for one or more programs as data matures.

BBO-8520 (KRAS G12C inhibitor) clinical progress

• Demonstrated 60% confirmed overall response rate in early monotherapy cohorts (100–300 mg QD) with no grade 3 or liver toxicities.

• Differentiated by inhibiting both on and off states of KRAS G12C, potentially overcoming resistance seen with first-generation inhibitors.

• Dose escalation ongoing up to 500 mg, including in combination with pembrolizumab, with next data update expected in Q1 2025.

• Early combination data with pembrolizumab will focus on safety and initial efficacy signals.

• Positioned as a potential combination agent of choice with checkpoint inhibitors due to favorable safety profile.

BBO-10203 (RAS-PI3K-alpha breaker) development

• Selectively inhibits PI3K-alpha signaling only when driven by RAS, aiming to avoid hyperglycemia and allow broader patient eligibility.

• Phase I enrolling HER2-amplified breast cancer, hormone receptor positive breast cancer, and KRAS mutant tumors.

• No restrictions on glucose metabolism markers in trial enrollment, highlighting differentiated safety.

• First half 2026 data will include monotherapy dose escalation and early combination results, with benchmarks set against tucatinib and standard chemotherapies.

• Target engagement and blood glucose data will be disclosed to demonstrate safety and mechanism.