Preclinical data from lead program addressing AURIGIN-identified KAT2A/B target showed significant cell state shift and tumor growth inhibition across multiple primary cancer models
AURIGIN overview highlighted capability to identify key drivers of dysregulated cell states in cancer
Data support advancement of AUTX-703 toward planned IND submission in late 2024
Newton, MA, April 9, 2024 – Auron Therapeutics, a biotechnology company focused on developing next-generation targeted therapies by identifying and inhibiting the oncogenic cell states of cancer, today announced two poster presentations at the American Association for Cancer Research (AACR) Annual Meeting. The Company highlighted the distinct ability of its AURIGIN™ platform to identify both cell state plasticity, the proliferative state in which cancer cells grow, and the causative gene targets. In a second poster, Auron shared preclinical data from its program targeting KAT2A/B, an AURIGIN-identified histone acetyltransferase driving small cell lung cancer (SCLC), neuroendocrine prostate cancer (NEPC), and acute myeloid leukemia (AML). These data led to the nomination of AUTX-703, an orally available and selective KAT2A/B degrader development candidate, for which Auron expects to file an IND in 2024.
“Our AACR presentations highlight the unique capability of our AURIGIN platform to identify critical drivers of cancer cell state and translate that knowledge into a comprehensive development program that targets the drivers for an anti-tumor effect,” said Kate Yen, Ph.D., Founder and Chief Executive Officer of Auron. “Using AURIGIN, we identified that KAT2A/B was responsible for driving growth and proliferation of SCLC, NEPC and AML. Also with AURIGIN, we designed novel small molecule degraders of KAT2A/B that demonstrated a near-complete knockdown of the target, leading to significant cell state shift and tumor growth inhibition in primary tumor models in all three indications. I’m incredibly proud of the work by this team to generate such compelling early data and optimize the program to bring forward AUTX-703, which we are advancing in IND-enabling studies and toward IND submission later this year.”
The poster titled, "Potent and selective degradation of KAT2A and KAT2B induces profound cell state changes and inhibits growth of AML, SCLC and NEPC model systems," showed data from Auron's first-in-class program targeting KAT2A/B. In a series of experiments, Auron showed that KAT2A/B degradation inhibited tumor growth and induced a cell state change towards a more terminally differentiated state across in vitro and in vivo models of SCLC, NEPC and AML. Specifically, treatment with AUR1545, a precursor small molecule to Auron's lead development candidate AUTX-703, led to:
· Highly selective and potent degradation of KAT2A/B in the sub-nanomolar (nM) concentration range, with single-digit nM concentrations driving growth inhibition in SCLC, AML and NEPC cell lines.
· Monocytic differentiation in an AML cell line at sub-nM concentration, as well as robust tumor growth inhibition and epithelial differentiation in a SCLC cell line-derived xenograft model.
· Growth inhibition in a NEPC cell line and a primary patient organoid model of NEPC with a concomitant cell state change to a more terminally differentiated state at single-digit nM concentration.
“These data on Auron’s KAT2A/B degraders are promising, showing the potential of this novel therapeutic target to directly address the mechanisms driving tumorigenesis across a wide range of cancer types,” said Ross Levine, M.D., Co-Founder of Auron, and Senior Vice President of Translational Research at Memorial Sloan Kettering. “The understanding that cellular plasticity contributes to aggressive and treatment-resistant tumor growth underscores the need for innovative, targeted approaches. As cancer treatment advances, identifying new targets with the AURIGIN platform and using that information to develop precise, tolerable treatments addressing drivers of cancer cell states are crucial."
In a separate poster presentation titled, “AURIGIN: A comprehensive single-cell OMICs atlas of human development and an AI/ML framework to classify and identify the drivers of tumor plasticity and altered cellular state,” Auron highlighted the integration of its developmental biology expertise with AI and machine learning (ML) algorithms and multi-omics database into a platform that can compare normal cell states to cancer cell states. The two main components of AURIGIN were described: CLASSIFY, a tumor cell state ML model designed to precisely identify and group tumors by their cell state plasticity, and DRIVE, a gene cell state ML model that identifies and ranks the genes controlling cellular plasticity and provides a score based on druggability of the target. In addition to identifying targets, AURIGIN identifies optimized model systems for early program de-risking biomarkers for effective patient selection.
In addition to AUTX-703, AURIGIN has led to two early-stage programs, both for first-in-class cell state targets with a validated mechanism, one of which has been validated and one of which is in validation.
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.
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