Olema Pharmaceuticals (OLMA) investor relations material

Lead asset and clinical strategy

• Palazestrant is a complete estrogen receptor antagonist with high exposure and favorable tolerability, designed for ER-positive, HER2-negative breast cancer.

• Two phase III trials are ongoing: OPERA-01 (second/third-line, fully enrolled, readout in Q1 2027) and OPERA-02 (first-line, enrolling well).

• OPERA-01 targets both ESR1 mutant and wild-type populations, aiming to address unmet needs in both.

• Phase II data showed 5.5 months median PFS in wild-type and 7.3 months in mutant ESR1, exceeding prior benchmarks.

• Combination with ribociclib in phase II showed 15.5 months median PFS, outperforming other SERD/CDK4/6 combos.

Competitive landscape and differentiation

• Other oral SERDs have shown benefit mainly in ESR1 mutant patients; palazestrant aims for efficacy in both mutant and wild-type.

• Complete antagonism and high exposure are believed to drive broader efficacy.

• Differentiation in the mutant setting would require >2 months PFS prolongation; phase II data suggest this is achievable.

• Recent competitor trials (persevERA, SERENA-4) were statistically negative in first-line settings, highlighting unmet need.

• No protocol changes to OPERA-02 yet, pending review of new control arm data from SERENA-4.

Pipeline expansion and collaborations

• OP-3136, a KAT6 inhibitor, showed favorable tolerability and single-agent activity in breast and prostate cancer.

• Combination trials with fulvestrant and palazestrant in breast cancer are ongoing, with data expected in H1 next year.

• Collaboration with Bayer to test OP-3136 with NUBEQA in prostate cancer, targeting androgen inhibitor resistance.

• Clinical trial collaboration with Pfizer on atirmociclib (CDK4 inhibitor) is fully enrolled; data timing to be determined.

• Market opportunities for these assets are estimated at $5 billion (second/third-line breast), $10+ billion (first-line), and several billion in prostate cancer.