PO.ET09.06 · 实验与分子治疗

Characterization of CGT1263, a KRAS (ON/OFF) inhibitor clinical candidate with selectivity for mutant KRAS over HRAS and NRAS

编号 410 展板 13 时间 4/19 02:00–05:00 区域 Section 17 主讲 John Fischer

分会场 Novel Antitumor Agents 1

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作者与单位

John Fischer, Kim Alley, Karyn Bouhana, Richard Brizendine, Paul Carlson, Mark Chicarelli, Michelle Crow, Brad Fell, Jennifer Fulton, Anna Guarnieri, Jackie Harrison, Ravi Jalluri, Amber Johnson, Keith Koch, Cori Malinky, Macedonio J. Mejia, Brad Newhouse, Scott Niman, Rob Rieger, John Robinson, Mareli Rodriguez, Leah Salituro, Vinny Scarato, Aaron Smith, Francis Sullivan, Yang Wang, Shannon Winski, Silas Wood, Yeyun Zhou

Cogent Biosciences, Inc, Boulder, CO

摘要 Abstract

Oncogenic KRAS mutations occur across multiple cancer types, including pancreatic, lung, and colorectal malignancies. While allele-specific KRAS inhibitors have demonstrated clinical benefit in patients, the majority of KRAS mutant cancers remain without effective therapies. Recent efforts to address this disparity have resulted in the identification of pan KRAS inhibitors that target clinically relevant mutations and alterations. Herein, we highlight the clinical candidate CGT1263, a novel pan KRAS inhibitor that engages both the active (ON) and inactive (OFF) states of KRAS while sparing HRAS and NRAS inhibition. CGT1263 demonstrates robust anti-proliferative activity across a tumor spheroid panel of KRAS altered cell lines. In vivo characterization of CGT1815, the prodrug of CGT1263, includes steady state pharmacokinetics across species, pharmacodynamics, and efficacy in KRAS altered mouse tumor models.

利益披露 Disclosure

J. Fischer, Cogent Biosciences, Inc. Employment, Stock, Stock Option. K. Alley, Cogent Biosciences, Inc. Employment, Stock, Stock Option. K. Bouhana, Cogent Biosciences, Inc. Employment, Stock, Stock Option. R. Brizendine, Cogent Biosciences, Inc. Employment, Stock, Stock Option. P. Carlson, Cogent Biosciences, Inc. Employment, Stock, Stock Option. M. Chicarelli, Cogent Biosciences, Inc. Employment, Stock, Stock Option. M. Crow, Cogent Biosciences, Inc. Employment, Stock, Stock Option. B. Fell, Cogent Biosciences, Inc. Employment, Stock, Stock Option. J. Fulton, Cogent Biosciences, Inc. Employment, Stock, Stock Option. A. Guarnieri, Cogent Biosciences, Inc. Employment, Stock, Stock Option. J. Harrison, Cogent Biosciences, Inc. Employment, Stock, Stock Option. R. Jalluri, Cogent Biosciences, Inc. Employment, Stock, Stock Option. A. Johnson, Cogent Biosciences, Inc. Employment, Stock, Stock Option. K. Koch, Cogent Biosciences, Inc. Employment, Stock, Stock Option. C. Malinky, Cogent Biosciences, Inc. Employment, Stock, Stock Option. M. J. Mejia, Cogent Biosciences, Inc. Employment, Stock, Stock Option. B. Newhouse, Cogent Biosciences, Inc. Employment, Stock, Stock Option. S. Niman, Cogent Biosciences, Inc. Employment, Stock, Stock Option. R. Rieger, Cogent Biosciences, Inc. Employment, Stock, Stock Option. J. Robinson, Cogent Biosciences, Inc. Employment, Stock, Stock Option. M. Rodriguez, Cogent Biosciences, Inc. Employment, Stock, Stock Option. L. Salituro, Cogent Biosciences, Inc. Employment, Stock, Stock Option. V. Scarato, Cogent Biosciences, Inc. Employment, Stock, Stock Option. A. Smith, Cogent Biosciences, Inc. Employment, Stock, Stock Option. F. Sullivan, Cogent Biosciences, Inc. Employment, Stock, Stock Option. Y. Wang, Cogent Biosciences, Inc. Employment, Stock, Stock Option. S. Winski, Cogent Biosciences, Inc. Employment, Stock, Stock Option. S. Wood, Cogent Biosciences, Inc. Employment, Stock, Stock Option. Y. Zhou, Cogent Biosciences, Inc. Employment, Stock, Stock Option.

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