SHANGHAI, May 4, 2025 — Nutshell Therapeutics (Shanghai) Co., LTD. announced on April 23, 2025, that the FDA has cleared its IND application tobegin a Phase 1 clinical trial in the United States for NTS071, an innovative small moleculeallosteric reactivator that targets the p53 Y220C mutation.
NTS071 is an orally available small molecule allosteric reactivator with a unique structure that targets p53 Y220C. It selectively attaches to the p53 Y220C mutant protein, increasing its thermal stability. This, in turn, boosts the mutant protein’s capacity to bind with DNA, restoring its transcriptional activity and tumor-suppressing function.
Nutshell Therapeutics’ proprietary AI-driven allosteric small molecule drug discovery platform, ALLOSTAR
, facilitated the discovery of NTS071. Preclinical data suggest that NTS071 has the potential to be a best-in-class treatment for its target. NTS071 exhibited picomolar-level biochemical activity, showing it is 20 times more potent than the competitor compound PC14586. Furthermore, NTS071 demonstrated enhanced stability in liver microsomes and hepatocytes across various species. Preclinical PK studies across all tested species revealed lower in vivo clearance rates and greater oral exposure compared to PC14586. NTS071 also has a comparatively lower plasma protein binding and a higher free fraction than PC14586, which is advantageous for in vivo efficacy. Additionally, NTS071 addresses the CYP3A4 inhibition issue associated with PC14586, lowering the risk of potential drug-drug interactions. Non-clinical toxicology studies also indicate that NTS071 has a wide safety window, exhibiting an overall favorable safety profile.
NTS071 demonstrated dose-dependent in vivo anti-tumor activity in several CDX and PDX models with the p53 Y220C mutation, across different cancer types, such as ovarian, lung, gastric, breast, head and neck, esophageal, pancreatic, and bladder cancers. Therefore, NTS071 could be a tumor-agnostic treatment option for patients with the p53 Y220C mutation. Compared to PC14586, NTS071 exhibited significantly lower effective doses or enhanced efficacy at equivalent doses in all comparative preclinical in vivo studies, implying NTS071 could overcome the higher dose requirement limitation of its competitor, and potentially achieve better therapeutic effects. The Phase 1 clinical trial for NTS071 is expected to commence in the second half of 2025, with the hope of benefiting patients who have solid tumors with this mutation.
The p53 Y220C mutation is common in various solid tumors. Studies suggest there are 125,000 to 150,000 new cases globally each year, representing a substantial market opportunity. With years of experience in computation-based allosteric drug development technology and exceptional innovation capabilities, Nutshell Therapeutics believes NTS071 has the potential to excel among similar products and become the most competitive drug molecule for this target.
The NTS071 Poster from the EORTC-NCI-AACR (ENA) 2024 conference is available here:
About Nutshell
Nutshell Therapeutics () is an innovative biotech company focused on creating small molecule drugs that target historically difficult targets using allosteric mechanisms. Founded by Professor Zhang Jian, a leading expert in allosteric drug discovery, the company has built an integrated R&D platform with various dry and wet lab capabilities. For many years, the company has focused on the discovery and development of allosteric small-molecule drugs. The company has successfully raised over US$75 million from several well-known venture capital firms.
SOURCE Nutshell Therapeutics
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