Auron Shares Preclinical Data at ACS Annual Meeting

Auron Therapeutics, a biotechnology firm dedicated to advancing next-generation targeted therapies by identifying and inhibiting oncogenic cell states in cancer, recently shared promising preclinical data at the American Chemical Society (ACS) Annual Meeting. These findings highlight the company's sophisticated medicinal chemistry capabilities, particularly in its lead program targeting KAT2A/B, a critical histone acetyltransferase implicated in various cancer types.

David Millan, Ph.D., the Chief Scientific Officer of Auron, elaborated on the company's innovative AURIGIN platform. This platform maps tumor cells against normal developmental pathways to pinpoint targets like KAT2A/B, which cancer cells exploit to sustain a highly plastic and proliferative state. According to Dr. Millan, Auron has successfully designed, refined, and enhanced small molecule degraders of KAT2A/B. These degraders achieve picomolar degradation potency, exhibit high selectivity, and are orally bioavailable. Consequently, they lead to tumor growth inhibition and a more differentiated cell state in primary tumor models. The data underscore Auron's robust medicinal chemistry expertise, which is also being applied to the company's second and third programs to expand its future pipeline.

In the initial phase of their research, Auron scientists identified several tool compounds, such as AUR101, to validate the role of KAT2A/B in the pathology of acute myeloid leukemia (AML) and small cell lung cancer (SCLC). AUR101 demonstrated that degrading KAT2A/B inhibits growth and induces a more terminally differentiated state across both AML and SCLC models. However, while AUR101 showed potent in vitro activity, it lacked suitable in vivo properties. This limitation led Auron's researchers to develop compounds with enhanced properties suitable for in vivo models.

The team subsequently identified an improved set of tool degraders, including AUR1545, which displayed even greater potency and selectivity and significantly improved unbound exposure levels, facilitating in vivo studies. AUR1545's enhanced properties enabled rapid and selective degradation of KAT2A/B, tumor growth inhibition, and the induction of epithelial differentiation in in vivo SCLC models. To further support the progression towards clinical candidacy, Auron scientists optimized AUR1545 to achieve more potent and orally bioavailable degraders of KAT2A/B.

After extensive medicinal chemistry optimization, Auron selected AUTX-703 as its lead KAT2A/B degrader candidate. AUTX-703 is a potent, selective, and orally administered degrader currently undergoing IND-enabling studies. The company is on track to submit an Investigational New Drug (IND) application by late 2024, with plans to initiate clinical development in early 2025. AUTX-703 is being developed to treat AML, SCLC, and other high-grade neuroendocrine carcinomas.

Auron Therapeutics is a patient-focused, platform-powered, and product-driven oncology company at the forefront of developing targeted cancer therapies. The company uses its pioneering AURIGIN™ platform, which leverages AI and machine learning to compare normal and cancerous cell states, to identify novel cancer targets, optimal development models, and biomarkers for effective patient selection. Through AURIGIN, Auron is building a pipeline of small molecule targeted therapies, led by AUTX-703, aimed at treating both solid tumors, including small cell lung cancer and neuroendocrine prostate cancer, and hematologic malignancies like acute myeloid leukemia.