Olema Oncology KAT6 Inhibitor Compounds Demonstrate Potent Anti-Tumor Activity

Oct 12, 2023

Preclinical data to be presented at the 2023 AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics

SAN FRANCISCO, Oct. 12, 2023 (GLOBE NEWSWIRE) -- 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 women’s cancers, today announced new preclinical data regarding the discovery of novel compounds targeting KAT6, an epigenetic target that is dysregulated in breast and other cancers. These data will be presented today at a poster session at the 2023 AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics (ANE 2023) in Boston, Massachusetts.  

The poster, titled “The discovery of potent KAT6 inhibitors that demonstrate anti-tumor activity in preclinical models of ER+ breast cancer”, describes the discovery and preclinical characterization of orally bioavailable, potent KAT6A and KAT6B-selective inhibitors developed by Olema in collaboration with Aurigene Oncology. The poster highlights that:

  • Olema KAT6 compounds were selective and potent against KAT6A and KAT6B (<20 nM IC50) with >250-fold selectivity over other KAT family members, including the essential genes KAT5 and KAT8.
  • In KAT6-amplified and overexpressing breast cancer cell lines, Olema KAT6 compounds strongly inhibited cell proliferation whereas KAT6-low cell lines were insensitive to the compounds.
  • Olema KAT6 inhibitor compounds caused dose-dependent tumor growth inhibition and tumor regression comparable to or better than a positive-control patented KAT6 inhibitor.
  • Olema KAT6 inhibitor compounds are orally bioavailable with desirable pharmacokinetics.
  • Olema KAT6 inhibitor compounds demonstrate histone target engagement and efficacy, as well as synergism with palbociclib or palazestrant (OP-1250).

“The dysregulation of KAT6 activity is observed across breast and other cancers, and inhibition of the KAT6 histone acetyltransferase enzyme reduces breast cancer cell proliferation through downregulation of genes involved in estrogen receptor signaling and other signaling pathways,” said David C. Myles, Ph.D., Chief Discovery and Non-Clinical Development Officer of Olema Oncology. “As noted in our poster today, the KAT6 inhibitors we are developing have demonstrated attractive potency and selectivity at inhibiting KAT6-amplified estrogen-receptor-positive (ER+) breast cancer cells, both wild-type and ESR1 mutated. Additionally, the compounds demonstrated synergistic activity in combination with CDK4/6 inhibitors and endocrine agents such as palazestrant (OP-1250).”

Olema’s KAT6 program has been developed in collaboration with Aurigene Oncology. A copy of the poster is available on Olema’s website under the Science section.

About Olema Oncology
Olema Oncology is a clinical-stage biopharmaceutical company focused on the discovery, development and commercialization of targeted therapies for women’s cancers. Olema’s lead product candidate, palazestrant (OP-1250), is a proprietary, orally-available small molecule with dual activity as both a complete estrogen receptor (ER) antagonist (CERAN) and a selective ER degrader (SERD). It is currently being evaluated both as a single agent in an ongoing Phase 2 clinical trial, and in combination with CDK4/6 inhibitors (palbociclib and ribociclib) and a PI3Ka inhibitor (alpelisib), in patients with recurrent, locally advanced or metastatic ER-positive (ER+), human epidermal growth factor receptor 2-negative (HER2-) breast cancer. Palazestrant has been granted FDA Fast Track designation for the treatment of ER+/HER2- metastatic breast cancer that has progressed following one or more lines of endocrine therapy with at least one line given in combination with a CDK4/6 inhibitor. Olema is headquartered in San Francisco and has operations in Cambridge, Massachusetts. For more information, please visit us at www.olema.com, or follow us on Twitter and LinkedIn.

Forward Looking Statements

Statements contained in this press release regarding matters that are not historical facts are “forward-looking statements” within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. Words such as “anticipate,” “expect,” “will,” “may,” “goal,” “potential” and similar expressions (as well as other words or expressions referencing future events, conditions or circumstances) are intended to identify forward-looking statements. These statements include those related to Olema’s preclinical program, including the potential beneficial characteristics of its KAT6 inhibitor compounds and its applicability to breast and other cancers, and the potential synergistic activity of Olema’s KAT6 inhibitor compounds with CDK4/6 inhibitors or palazestrant (OP-1250). Because such statements deal with future events and are based on Olema’s current expectations, they are subject to various risks and uncertainties, and actual results, performance or achievements of Olema could differ materially from those described in or implied by the statements in this press release. These forward-looking statements are subject to risks and uncertainties, including, without limitation, those discussed in the section titled “Risk Factors” in Olema’s Quarterly Report on Form 10-Q for the quarter ended June 30, 2023, and future filings and reports that Olema makes from time to time with the U.S. Securities and Exchange Commission. Except as required by law, Olema assumes no obligation to update these forward-looking statements, including in the event that actual results differ materially from those anticipated in the forward-looking statements.

Geoffrey Mogilner, Vice President, Investor Relations and Communications