Olema Pharmaceuticals, Inc. announced preliminary clinical results from a Phase 1/2 clinical study of OP-1250, the Company's complete estrogen receptor (ER) antagonist (CERAN) and selective ER degrader (SERD) in development for the treatment of metastatic breast cancer. These results, as of September 2, 2022, were presented at a poster session of the 34th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics (ENA 2022) in Barcelona, Spain. The poster, titled “Preliminary Phase 1/2 results from OP-1250-001, a study of OP-1250, an oral CERAN/SERD, in patients with advanced and/or metastatic estrogen receptor (ER)-positive, HER2-negative breast cancer (NCT04505826)”, highlighted that: Across 68 patients at 60 mg and 120 mg once daily oral dosing, OP-1250 was well tolerated with attractive pharmacokinetics (PK) and drug exposure levels approximately 20 times that of fulvestrant at the 120 mg dose.

OP-1250 demonstrated strong anti-tumor activity and durable benefit with 41% of patients seeing reductions in target tumor lesions, and 6 partial responses (4 confirmed and 2 unconfirmed) out of 57 efficacy-evaluable patients. As of the data cut-off of September 2, 2022, 68 patients with recurrent, locally advanced or metastatic ER+/HER2- breast cancer were treated across two doses of 60 mg and 120 mg orally once per day. This group was heavily pretreated with 69% having received 2 or more prior lines of therapy and 32% having received prior chemotherapy.

Almost all patients (96%) received prior treatment with a cyclin-dependent kinase 4/6 (CDK4/6) inhibitor, and 65% received prior treatment with fulvestrant. Of 46 patients whose circulating tumor DNA (ctDNA) was assessed, 59% had activating mutations in ESR1 at baseline.