Youdao Biologics' First-in-Class Pan-Cancer Therapy NTS071 Granted IND Approval in China for TP53 Y220C-Mutated Solid Tumors

NTS071 is a small-molecule allosteric reactivator with a novel chemical scaffold that selectively binds to the p53 Y220C mutant protein, enhancing its thermal stability and thereby improving the ability of the mutant protein to bind to DNA, restoring the transcriptional activity and tumor-suppressing function of the mutant p53.

NTS071 is driven by NUTSHELL's self-developed AI+ allosteric molecule platform ALLOSTARTM, combining sophisticated structure-based drug design and molecular optimization technology.Demonstrates Best-in-Class preclinical properties among similar products targeting this site.：

• NTS071 has picomolar-level biochemical activity,20 times superior to the clinical molecule PC14586 of the original research company PMV targeting the same target.。

• NTS071 demonstrated better stability in liver microsomes and hepatocytes across all species, and showed favorable results in preclinical PK tests across all species.Lower in vivo clearance and higher oral exposure than PC14586；

• NTS071 has a relatively low plasma protein binding rate and a higher proportion of free drug, which is beneficial for supporting in vivo efficacy.

• NTS071 AlsoResolved the inhibition issue of PC14586 on CYP3A4, with a lower risk in terms of drug interaction effects.

• NTS071 also demonstrated good safety in various non-clinical toxicology studies and has a very large safety window.

Currently, NTS071 has been tested in multiple CDX and PDX xenograft animal models carrying the p53 Y220C mutation.Demonstrated dose-dependent antitumor activity in vivo, these models include various types of cancer such as ovarian cancer, lung cancer, gastric cancer, breast cancer, head and neck cancer, esophageal cancer, pancreatic cancer, and bladder cancer. Therefore, NTS071 can serve as a potential treatment for cancers carrying the p53 Y220C mutation.Pan-cancer Treatment Methods。

Moreover, compared to PC14586, NTS071 demonstrated superior performance in all in vivo models tested.Exhibit significantly lower effective doses or superior efficacy at the same dose., which is expected to address the issue of PC14586's excessively high dosage in clinical practice.（RP2D 2000 mg）And the issue of limited drug efficacy, achieving better therapeutic outcomes.

Notably, in April 2025,NUTSHELL Therapeutics Inc. Announces FDA IND Approval for Clinical Trials in the United States