Olema Pharmaceuticals, Inc. announced that Molecular Cancer Therapeutics, an American Association for Cancer Research journal, has selected as a featured article a data publication that describes the distinct properties of palazestrant (OP-1250). The paper, titled ?Palazestrant (OP-1250), a Complete Estrogen Receptor Antagonist, Inhibits Wild-type and Mutant ER-positive Breast Cancer Models as Monotherapy and in Combination?, describes the scientific background underlying the design, discovery and optimization of palazestrant. As part of the discovery and optimization process, palazestrant was assessed across an extensive series of biochemical, cell culture, and in vivo assays comparing it with other antiestrogens and compounds that are either approved for use by the FDA or are currently in clinical development, including aromatase inhibitors, selective ER modulators (SERMs), traditional SERDs, and proteolysis-targeting chimeras (PROTACs).

As a CERAN, palazestrant has a distinct mechanism of action (MOA), and though it actively degrades the ER, the paper shows that degradation alone is not a reliable mechanism to drive the efficacy of an endocrine agent. In mouse xenograft models, palazestrant demonstrated excellent pharmacokinetics, was well tolerated, showed synergy with CDK4/6 inhibitors, and was highly effective at reducing tumor growth in both wild-type and ESR1-mutant ER+ breast cancer. In addition, in an ESR1-mutant intercranial xenograft model, palazestrant inhibited tumor growth and improved survival of animals with CNS metastases, even after stopping drug treatment.