Chinese pharmaceutical company Nutshell Therapeutics (Shanghai) Co Ltd announced on Sunday that it has received IND clearance from the US Food and Drug Administration (FDA) to initiate a Phase 1 clinical trial in the United States for NTS071, a novel small molecule allosteric reactivator targeting p53 Y220C mutation with a novel scaffold.

NTS071 selectively binds to the p53 Y220C mutant protein, improving its thermal stability, thereby enhancing the mutant protein's ability to bind with DNA and restoring its transcriptional activity as well as tumour-suppressing function.

NTS071 was discovered by leveraging Nutshell's proprietary AI driven allosteric small molecule drug discovery platform ALLOSTAR. NTS071 exhibited dose-dependent in vivo anti-tumour activity in multiple CDX and PDX models harbouring p53 Y220C mutation, spanning a number of different cancer types, including ovarian cancer, lung cancer, gastric cancer, breast cancer, head and neck cancer, oesophageal cancer, pancreatic cancer and bladder cancer. Therefore, NTS071 has the potential to be a tumour-agnostic therapy for patients carrying p53 Y220C mutation.

Compared to PC14586, NTS071 has shown significantly lower effective doses or better efficacy at the same dose level in all comparative preclinical in vivo studies, implying that NTS071 may overcome the limitation of its competitor that has a higher dose requirement, thereby potentially achieving better therapeutic effects. NTS071 is anticipated to initiate a Phase 1 clinical trial in the second half of 2025 and is expected expected to benefit patients with solid tumours harbouring this mutation.