Preclinical data to be presented at the 2023 AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics
SAN FRANCISCO, CA, USA I October 12, 2023 IOlema 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.
SOURCE: Olema Oncology
Post Views: 221
Preclinical data to be presented at the 2023 AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics
SAN FRANCISCO, CA, USA I October 12, 2023 IOlema 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.
SOURCE: Olema Oncology
Post Views: 221
