Olema Pharmaceuticals, Inc.

Olema is a clinical-stage biopharmaceutical company focused on discovering, developing, and commercializing next-generation targeted therapies for breast cancer and other conditions. The company develops novel therapies by understanding endocrine-driven cancers, nuclear receptors, and mechanisms of acquired resistance. Its lead product candidate, palazestrant (formerly OP-1250), is an orally-available small molecule that acts as both a complete estrogen receptor (ER) antagonist (CERAN) and a selective ER degrader (SERD). Palazestrant is currently being investigated in patients with recurrent, locally advanced or metastatic ER-positive (ER+), human epidermal growth factor receptor 2-negative (HER2-), breast cancer. In pre-clinical models, palazestrant binds and completely blocks ER-driven transcriptional activity in both wild-type and mutant forms of metastatic ER+ breast cancer. In clinical studies involving more than 400 patients, palazestrant has shown strong anti-tumor activity, attractive pharmacokinetics, prolonged drug exposure, favorable tolerability, and combinability with cyclin-dependent kinase (CDK) 4/6 inhibitors (CDK4/6i) with no significant drug-drug interaction. Olema is advancing palazestrant through late-stage clinical development as a monotherapy and in combination with other targeted agents. In November 2023, the company initiated OPERA-01, a pivotal Phase 3 clinical trial of palazestrant as a monotherapy in second/third-line ER+/HER2- metastatic breast cancer. In combination, palazestrant is being investigated in multiple Phase 1/2 studies with CDK4/6 inhibitors (palbociclib or ribociclib), a phosphatidylinositol 3 kinase alpha (PI3Ka) inhibitor (alpelisib), a mechanistic target of rapamycin (mTOR) inhibitor (everolimus), and a CDK4 inhibitor (atirmociclib). In October 2025, at the European Society for Medical Oncology (ESMO), updated results were presented from the ongoing Phase 1b/2 clinical trial of palazestrant in combination with ribociclib in patients with ER+/HER2- advanced or metastatic breast cancer.