Olema Pharmaceuticals (OLMA) Morgan Stanley 22nd Annual Global Healthcare Conference summary

Evolving treatment paradigm for ER-positive, HER2-negative breast cancer

• Standard first-line remains CDK4/6 inhibitor plus aromatase inhibitor, with ribociclib preferred for survival benefit.

• Post-progression, treatment options become less defined, with a menu of endocrine therapies and combinations considered.

• There is a significant unmet need for effective therapies after CDK4/6 progression to delay chemotherapy and maintain quality of life.

• New agents like palazestrant and KAT6 inhibitor OP-3136 are being developed to address these gaps.

Limitations of current therapies and opportunities for innovation

• Aromatase inhibitors do not fully suppress estrogen receptor activity, especially in patients with ESR1 mutations.

• SERDs have not overcome key limitations due to incomplete antagonism and poor combinability with CDK4/6 inhibitors.

• Palazestrant offers complete antagonism and high combinability, with no significant drug-drug interactions at full doses.

• Next-generation CDK4 and CDK2 selective agents are being watched, but efficacy improvements over current CDK4/6 inhibitors remain unproven.

Clinical development and trial updates

• OPERA-01, a global phase III trial of palazestrant, is enrolling well and expected to read out in 2026.

• The trial targets both ESR1 mutant and wild-type populations, aiming for broader applicability without the need for mutation testing.

• Phase II ribociclib and palazestrant combination trial completed enrollment, with compelling tolerability and efficacy data; further updates expected late 2024 or early 2025.

• Expanded data on KAT6 inhibitor OP-3136, including preclinical and combination results, will be presented at ENA in October, with IND filing planned by year-end.