BridgeBio Oncology Therapeutics (BBOT) Oppenheimer 36th Annual Healthcare Life Sciences Conference summary

Pipeline strategy and scientific approach

• Focus on RAS-driven tumors with in-house discovered and developed programs targeting optimal inhibition through direct on/off state binding and selective pathway modulation.

• Three main assets: BBO-8520 (KRAS G12C on/off inhibitor), BBO-818 (pan-KRAS inhibitor), and BBO-10203 (RAS PI3Kα breaker), each designed for distinct but complementary mechanisms.

• BBO-8520 achieves potent inhibition of both on and off states, showing a 65% response rate and strong durability with improved safety.

• BBO-818 extends the approach to pan-KRAS inhibition, targeting additional alleles like G12D and G12V, with early data indicating promising efficacy and safety.

• BBO-10203 is a first-in-class protein-protein interaction inhibitor, blocking RAS activation of PI3Kα without causing hyperglycemia, expanding combination opportunities.

Combination therapy rationale and clinical data

• Emphasis on rational combinations, leveraging strong therapeutic index and combinability with standard of care agents such as pembrolizumab and cetuximab.

• BBO-8520 demonstrates high efficacy and low liver toxicity as monotherapy and in combination with pembrolizumab, with all first-line patients responding and minimal adverse events.

• Pan-KRAS inhibitor BBO-818 shows potential for combination with EGFR inhibitors in colorectal cancer, aiming to avoid side effects seen with less selective agents.

• BBO-10203 enables combinations in HER2-amplified, hormone receptor-positive, and KRAS mutant settings, with preclinical and early clinical data supporting simultaneous MAPK and PI3Kα inhibition.

• No hyperglycemia or glucose restrictions observed with BBO-10203, differentiating it from other PI3Kα inhibitors and broadening its addressable patient population.

Competitive differentiation and future outlook

• On/off inhibition approach with BBO-8520 allows for higher active dosing in combination settings, overcoming limitations of off-only inhibitors.

• Pan-KRAS strategy avoids toxicity associated with pan-RAS or cyclophilin-binding inhibitors, with no rash or mucositis observed in early data.

• BBO-10203's mutant-agnostic mechanism allows targeting both KRAS and PI3Kα mutations, potentially expanding the eligible patient pool significantly.

• All three programs are set for key data readouts in the second half of the year, with additional combination data expected into 2026.

• Strong cash position ($425M at year-end) supports ongoing and future clinical development and combination trials.