Olema Pharmaceuticals (OLMA) Morgan Stanley 24th Annual Global Healthcare Conference summary

Differentiation of oral SERDs and palazestrant

• Palazestrant is a complete estrogen receptor antagonist with superior exposure and combinability compared to other oral SERDs, addressing key limitations like tolerability and receptor occupancy seen in competitors.

• High drug exposure enables continuous receptor inhibition, which is critical for efficacy, and palazestrant can be combined with multiple targeted agents without dose compromise or increased toxicity.

• Dose selection for palazestrant was guided by independent committee review, with both 90 mg and 120 mg doses exceeding exposure thresholds; 90 mg was chosen for further development.

• Phase II data show palazestrant outperforms competitors in both ESR1 wild type and mutant settings, with 5.5 months PFS in wild type and over seven months in mutant, suggesting potential for differentiation in upcoming phase III trials.

• OPERA-01 (monotherapy, second/third-line) and OPERA-02 (combination, first-line, endocrine-sensitive) trials are designed to validate these advantages, with OPERA-01 readout expected in Q1 2027.

Clinical trial design and market opportunity

• OPERA-02 excludes endocrine-resistant patients, focusing on endocrine-sensitive first-line population, aligning with best practices from recent competitor trials.

• Ribociclib was chosen as the backbone for OPERA-02 due to its demonstrated overall survival benefit, reflecting a shift in standard of care.

• Palazestrant’s ability to combine at full dose with various agents, including ribociclib, without increased toxicity is unique and may provide significant efficacy benefits.

• The ESR1 mutant market is estimated at $2 billion annually, while the wild type opportunity is about $3 billion, with efficacy in wild type representing a major differentiator.

• OPERA-01 and OPERA-02 target distinct patient populations, and success in these trials could unlock substantial market value.

KAT6 inhibitor pipeline and expansion

• OP-3136 is a potent, selective KAT6 inhibitor engineered to reduce KAT5/KAT8-related toxicities, with early phase I data suggesting improved tolerability and efficacy, especially in breast cancer.

• Combination with palazestrant may further enhance efficacy, and the company is one of only two with clinical KAT6 data.

• Monotherapy activity was observed in castration-resistant prostate cancer, leading to a collaboration with Bayer to combine with darolutamide, with dosing to start in Q4.

• The KAT6 opportunity in breast cancer alone is valued at over $5 billion annually, with additional upside in prostate and potentially lung cancer.

• Expansion into prostate cancer and exploration in non-small cell lung cancer diversify the pipeline and risk profile.