Olema Pharmaceuticals (OLMA) investor relations material

Lead asset and clinical development

• Palazestrant is a complete estrogen receptor antagonist in two Phase 3 trials for metastatic breast cancer, with both monotherapy and combination therapy arms.

• A frontline study will combine palazestrant with ribociclib (Kisqali) in a 1,000-patient trial, and Phase 2 data supporting this will be presented at ESMO.

• The OPERA-01 trial (third-line) will read out in the second half of next year, comparing palazestrant monotherapy to standard-of-care in 500 patients.

• Palazestrant has shown strong activity in both ESR1-mutant and wild-type patients, with a seven-month benefit in mutants and five months in wild-type in Phase 2.

• The FDA requires at least a two-month PFS benefit for approval in both mutant and wild-type populations.

Differentiation and competitive landscape

• Other oral SERDs have shown limited benefit in wild-type patients, while palazestrant demonstrates efficacy in both ESR1-mutant and wild-type settings.

• The OPERA-01 trial design excludes prior chemotherapy and enriches for endocrine-sensitive patients by requiring a minimum of six months on prior endocrine therapy.

• Palazestrant is the only oral SERD showing consistent wild-type activity in both monotherapy and combination settings.

• Combination trials with ribociclib and palbociclib have shown no drug-drug interactions or increased adverse events, unlike competitors.

• Median PFS of 13 months was announced for palazestrant plus ribociclib, with further updates expected at ESMO.

Combination strategies and future plans

• Palazestrant is being combined with multiple targeted agents, including CDK4/6 inhibitors, PI3K inhibitors, and mTOR inhibitors.

• A new combination trial with Pfizer’s CDK4 inhibitor (atiraciclib) is planned to explore next-generation strategies.

• The commercial opportunity in frontline metastatic breast cancer is significant, with the goal to extend PFS from two to three years.

• Ongoing and upcoming trials aim to demonstrate superiority over aromatase inhibitors in the frontline setting.

• The company is closely watching results from Roche’s and AstraZeneca’s frontline SERD/CDK4/6 trials for indirect benchmarks.