On April 17, 2026 Olema Pharmaceuticals, Inc. ("Olema" or "Olema Oncology", Nasdaq: OLMA), a clinical-stage biopharmaceutical company focused on the discovery, development, and commercialization of targeted therapies for breast cancer and beyond, reported new preclinical data for palazestrant, a complete estrogen receptor antagonist (CERAN) and selective estrogen receptor degrader (SERD), alone and in combination with OP-3136, a novel small molecule that potently and selectively inhibits acetyltransferase 6 (KAT6) inhibitor. The data will be presented in two poster presentations at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting taking place April 17-22 in San Diego, California.

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"We are very excited to share, for the first time ever, data that confirm the mechanism by which palazestrant completely blocks estrogen receptor transcription and signaling by recruiting the corepressor protein NCoR1," said David C. Myles, Ph.D., Chief Scientific Officer of Olema Oncology. "Further, the synergistic anti-tumor activity of OP-3136 combined with palazestrant in preclinical models highlights the role that both complete ER antagonism and KAT6 inhibition play in addressing acquired resistance associated with metastatic disease. We are pleased to continue to explore the potential of this combination in our ongoing Phase 1 study of OP-3136 and look forward to announcing top-line data from our Phase 3 OPERA-01 trial of palazestrant monotherapy, which is anticipated this fall."

Poster Presentation Details
Title: Palazestrant directly recruits the corepressor protein NCoR1 in vitro leading to complete antagonism of estrogen receptor alpha
Poster/Abstract: 2950
Session: Experimental and Molecular Therapeutics: Cellular Responses to Anticancer Drugs
Date/Time: April 20, 2026, from 2:00pm-5:00pm PT / 5:00pm-8:00pm ET

Key findings:

Palazestrant completely blocks estrogen-driven transcription and demonstrates robust anti-tumor activity in vitro.
In a split-luciferase assay, palazestrant was shown to fully recruit the corepressor, NCoR1, enabling complete estrogen receptor (ER) antagonism.
In both ESR1 wild-type and mutant models, palazestrant more potently suppressed ER-regulated and cell-cycle genes, including PGR and GREB1, than selective estrogen receptor modulators (SERMs), delivering complete inhibition of tumor cell proliferation without partial agonist effects.

These findings position palazestrant as a differentiated endocrine therapy designed to achieve deeper, more consistent ER pathway suppression in estrogen receptor-positive, human epidermal growth factor receptor 2-negative (ER+/HER2-) breast cancer.

Title: Palazestrant, a CERAN, in combination with OP-3136, a KAT6 inhibitor, synergistically downregulates cell proliferation and metastasis related gene signatures
Poster/Abstract: 2949
Session: Experimental and Molecular Therapeutics: Cellular Responses to Anticancer Drugs
Date/Time: April 20, 2026, from 2:00pm-5:00pm PT / 5:00pm-8:00pm ET

Key findings:

Combining OP-3136 with palazestrant drives synergistic anti-tumor activity in in vivo ER+/HER2- breast cancer models, which is mediated by suppression of cell-cycle and estrogen receptor-driven oncogenic signaling processes.
The combination of OP-3136 plus palazestrant downregulates genes associated with MYC, E2F, and G2M more effectively than either agent alone or OP-3136 in combination with fulvestrant.
Combining OP-3136 with palazestrant or fulvestrant suppresses expression of genes associated with MTORC1 signaling, indicating that targeting KAT6 and ER-alpha can suppress mechanisms of acquired resistance.

These findings provide a strong biological rationale for advancing palazestrant in combination with OP-3136 for the treatment of ER+ metastatic breast cancer.

Copies of these posters will be available on the Publications page of Olema’s website in alignment with the AACR (Free AACR Whitepaper) embargo. Additional information, including abstracts, is available on the AACR (Free AACR Whitepaper) Annual Meeting website.

(Press release, Olema Oncology, APR 17, 2026, View Source [SID1234664508])