Company showcases property-based design and optimization of orally bioavailable degraders targeting KAT2A/B
NEWTON, Mass., Aug. 19, 2024 (GLOBE NEWSWIRE) -- Auron Therapeutics, a biotechnology company focused on developing next-generation targeted therapies by identifying and inhibiting the oncogenic cell states of cancer, today shared preclinical data showcasing the strength of the company’s medicinal chemistry capabilities. These discovery research data, presented at the American Chemical Society (ACS) Annual Meeting, are from the company’s lead program targeting KAT2A/B, a histone acetyltransferase driving multiple cancer types.
“Our AURIGIN platform maps tumor cells against normal developmental pathways to identify targets like KAT2A/B, which are hijacked by cancerous cells to maintain a highly plastic, proliferative state,” said David Millan, Ph.D., Chief Scientific Officer of Auron. “We’ve designed, iterated, and optimized small molecule degraders of KAT2A/B that achieve picomolar degradation potency, high selectivity, and oral bioavailability, leading to tumor growth inhibition and a more differentiated cell state in primary tumor models. These data underscore our extensive medicinal chemistry capabilities, which we’re applying to our second and third programs and using to fuel our future pipeline.”
As presented, Auron scientists initially identified tool compounds, such as AUR101, that the company used to validate the role of KAT2A/B in disease pathology for both acute myeloid leukemia (AML) and small cell lung cancer (SCLC). As shown with AUR101, degradation of KAT2A/KAT2B inhibits growth and induces cell state change towards a more terminally differentiated state across both AML and SCLC models. While AUR101 had the desired in vitro potency, it lacked adequate in vivo properties, leading Auron scientists to design compounds with better properties to advance into in vivo models.
Auron researchers identified a set of improved tool degraders, including AUR1545, which exhibited even greater potency and selectivity, and with significant improvements in unbound exposure levels enabling in vivo studies. AUR1545’s enhanced properties resulted in rapid and selective degradation of KAT2A/B, tumor growth inhibition, and induction of epithelial differentiation in in vivo SCLC models. To support advancement toward clinical candidate selection, further optimization of AUR1545 resulted in more potent, and orally bioavailable degraders of KAT2A/KAT2B.
Late-stage medicinal chemistry optimization ultimately led Auron to select AUTX-703 as its lead KAT2A/B degrader candidate. AUTX-703 is an oral, potent, selective degrader currently in IND-enabling studies. Auron is on-track to submit an Investigational New Drug (IND) application in late 2024 for initiation of clinical development in early 2025. AUTX-703 is being developed for the treatment of AML, SCLC and other high-grade neuroendocrine carcinomas.
About Auron Therapeutics
Auron Therapeutics is a patient-centered, platform-powered, product-driven oncology company. Auron is leading the next generation of targeted cancer therapies by identifying and inhibiting the oncogenic cell states of cancer. Auron pioneered its AURIGIN™ platform, which uses AI and machine learning to compare normal cell states with cancerous cell states to identify novel cancer targets, optimal development models, and biomarkers to facilitate proper patient selection. Using AURIGIN, the Company is building a pipeline of small molecule targeted therapies, led by AUTX-703, which is being developed for the treatment of both solid tumors, including small cell lung cancer and neuroendocrine prostate cancer, and hematologic malignancies, including acute myeloid leukemia. For more information, please visit aurontx.com.
Contact:
Renee Leck
THRUST Strategic Communications
renee@thrustsc.com
