Olema Oncology Presents New Preclinical Data Showing Anti-Tumor Activity for OP-3136 with Enhanced Palazestrant Combinations at ENA 2024

Olema Pharmaceuticals, Inc., also known as Olema Oncology, a biopharmaceutical company in the clinical stage, announced significant findings from three preclinical studies at the 36th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics (ENA 2024) in Barcelona, Spain. These findings highlight the efficacy of their compounds, OP-3136 and palazestrant, in treating breast cancer.

OP-3136, a potent inhibitor of KAT6, has demonstrated strong anti-tumor activity as a standalone treatment. Moreover, when combined with palazestrant, it showed significant synergistic effects leading to enhanced anti-tumor activity. According to Dr. David C. Myles, Chief Discovery and Non-Clinical Development Officer at Olema Oncology, these results reinforce the potential of OP-3136 as a promising new treatment for breast and other cancers. Olema plans to submit an Investigational New Drug (IND) application for OP-3136 to the US Food and Drug Administration by the end of the year.

The study titled “Combining OP-3136, a KAT6 inhibitor, with endocrine therapy and CDK4/6 inhibitor enhances anti-tumor activity in ER+/HER2- breast cancer models” presented key findings. These included OP-3136's ability to inhibit cell proliferation and its synergistic effects when used with anti-estrogens like fulvestrant and palazestrant, as well as a CDK4/6 inhibitor (ribociclib). The combination led to either tumor growth inhibition or regression in vivo in xenograft models across all treatment groups. Notably, palazestrant, when combined with OP-3136, was consistently superior to fulvestrant, enhancing anti-tumor activity and leading to tumor regression.

Palazestrant, Olema’s lead product candidate, continues to show promise in clinical settings. It is currently being evaluated as a monotherapy in the pivotal Phase 3 OPERA-01 trial and in combination with multiple targeted agents in Phase 1/2 studies. The preclinical data presented highlighted palazestrant's combinability and enhanced tumor suppression when used with everolimus and capivasertib.

The study titled “Combining palazestrant, a CERAN, and everolimus, an mTOR inhibitor, enhances tumor suppression in ER+/HER2- breast cancer models” highlighted that palazestrant and everolimus demonstrate synergy in reducing cell proliferation both in vitro and in vivo, resulting in greater anti-proliferative activity compared to each agent alone. Furthermore, combining palazestrant with everolimus led to gene signature transcriptional changes, downregulating cell cycle progression and upregulating apoptosis, supporting the clinical investigation of this combination.

Another study titled “Combining palazestrant, a CERAN, and capivasertib, a pan-AKT inhibitor, enhances tumor suppression in ER+/HER2- breast cancer models” demonstrated that palazestrant and capivasertib work synergistically to inhibit proliferation in multiple ER+ breast cancer models, both in vitro and in vivo. The combination showed superior anti-tumor efficacy compared to fulvestrant, significantly inhibiting and repressing tumor growth. Additionally, it increased the downregulation of genes associated with cell cycle progression, further supporting the clinical investigation of this combination.

Palazestrant, known as OP-1250, is an oral small molecule with dual activity as a complete estrogen receptor antagonist (CERAN) and selective estrogen receptor degrader (SERD). It is under investigation for treating ER-positive, HER2-negative breast cancer. Olema has also successfully completed IND-enabling studies for OP-3136, which is set to enter Phase 1 clinical trials in early 2025.

Olema Oncology is committed to transforming cancer treatment and improving outcomes for women with cancer. By leveraging their deep understanding of endocrine-driven cancers, Olema is advancing a pipeline of novel therapies. Their lead product, palazestrant, is in a Phase 3 clinical trial and shows promise in combination with other targeted therapies. The company is headquartered in San Francisco, with operations in Cambridge, Massachusetts.