Olema Pharmaceuticals has announced promising preclinical data for its novel KAT6 inhibitor OP-3136, demonstrating significant anti-tumor activity across multiple solid tumor types beyond its initial breast cancer focus. The findings were presented at the American Association for Cancer Research (AACR) Annual Meeting in Chicago on April 28, 2025.
The preclinical studies revealed that OP-3136, which potently and selectively inhibits lysine acetyltransferase 6 (KAT6), showed robust anti-proliferative activity in ovarian, non-small cell lung cancer (NSCLC), and prostate cancer models, independent of KAT6 amplification or overexpression.
"These data showcase the potential of OP-3136 for the treatment of challenging cancers beyond breast cancer," said David C. Myles, Ph.D., Chief Discovery and Non-Clinical Development Officer of Olema Oncology. "OP-3136 has shown inhibition across all models explored, and we were excited to observe potent tumor growth inhibition and sustained tumor regression with OP-3136 as a monotherapy in ovarian cancer models."
Impressive Results Across Multiple Cancer Models
In the OVCAR3 ovarian cancer xenograft model, OP-3136 monotherapy achieved sustained tumor regression throughout the 28-day study period with robust tumor growth inhibition. This finding is particularly significant given the limited treatment options for advanced ovarian cancer patients.
The compound also demonstrated promising results in lung cancer, with the LCLC-97TM1 NSCLC model showing tumor growth inhibition comparable to ribociclib, a CDK4/6 inhibitor currently approved for breast cancer. When OP-3136 was combined with ribociclib, researchers observed synergistic effects and enhanced anti-tumor activity.
In prostate cancer models (22Rv1), OP-3136 inhibited tumor growth in a dose-dependent manner. When combined with docetaxel, a standard chemotherapy agent for prostate cancer, the combination resulted in enhanced anti-tumor activity compared to either agent alone.
Dr. Gopinath S. Palanisamy, who presented the findings, emphasized that the activity of OP-3136 was independent of KAT6 amplification or overexpression, suggesting broad potential applicability across different tumor types.
Mechanism of Action and Development Status
OP-3136 works by inhibiting KAT6, an epigenetic target that is dysregulated in breast and other cancers. The compound is orally available and has previously shown significant anti-proliferative activity in ER+ breast cancer models, where it demonstrated synergy with endocrine therapies and CDK4/6 inhibitors.
The U.S. Food and Drug Administration (FDA) cleared the Investigational New Drug (IND) application for OP-3136 in December 2024, and Olema is currently recruiting patients for its Phase 1 clinical trial. The study is evaluating OP-3136 both as a monotherapy and in combination regimens across multiple solid tumor types.
Expanding Treatment Horizons
These new findings significantly expand the potential therapeutic applications of OP-3136 beyond Olema's initial focus on breast cancer. The company's pipeline also includes palazestrant (OP-1250), a complete estrogen receptor antagonist and selective ER degrader currently in Phase 3 clinical trials for breast cancer.
"We are actively recruiting the Phase 1 trial of OP-3136 in multiple solid tumor types and will continue to explore its potential in other indications of high unmet need," added Dr. Myles.
The ability of OP-3136 to target multiple cancer types positions it as a potentially versatile addition to the oncology treatment landscape, particularly for difficult-to-treat solid tumors. If clinical trials confirm these preclinical findings, OP-3136 could represent a significant advancement in targeted cancer therapy.
Clinical Implications
Oncologists specializing in gynecologic, lung, and prostate cancers will be watching the clinical development of OP-3136 with interest. The compound's ability to work both as monotherapy and in combination with established treatments could provide new options for patients with limited therapeutic alternatives.
The ongoing Phase 1 trial will provide critical data on safety, tolerability, and preliminary efficacy in humans, with results likely to guide future development across multiple cancer indications. The trial design includes dose-escalation and expansion cohorts to identify optimal dosing and potential biomarkers of response.
As Olema continues to advance OP-3136 through clinical development, the oncology community awaits further data that could potentially translate these promising preclinical findings into meaningful clinical benefits for patients with difficult-to-treat solid tumors.
