FDA Clears Nutshell Therapeutics' NRF2 Degrader NTS231

Nutshell Therapeutics announced in a press release that the U.S. Food and Drug Administration (FDA) cleared its investigational new drug application for NTS231, allowing clinical development in the United States. The company describes NTS231 as the first NRF2 degrader from China and the second globally to enter clinical development.

NTS231 was discovered using the company's AI based ALLOSTAR platform. The molecule binds to KEAP1 and promotes formation of the KEAP1 CUL3 E3 ligase complex, causing NRF2 degradation and suppressing NRF2 signaling.

In preclinical studies, NTS231 showed dose dependent antitumor activity in models of lung, esophageal, and head and neck cancers. Combination studies tested the candidate with chemotherapy, targeted therapies, and antibody drug conjugates, while toxicology studies lasting 28 days assessed its safety in rats and dogs.