The FDA approved an Investigational New Drug (IND) application for NTS071, a novel oral small molecule specifically designed to target the p53 Y220C mutation. The drug is expected to enter Phase 1 clinical trials in the second half of 2025. Its mechanism involves binding to the mutant p53 protein, stabilizing it, and restoring its ability to bind DNA and suppress tumor growth—effectively reactivating a key tumor suppressor function lost in Y220C-mutant cancers.
Developed using an AI-powered drug discovery platform, this candidate has shown strong preclinical performance. It is 20 times more potent than the leading alternative, achieving picomolar-level activity, with improved pharmacokinetics such as better stability, reduced clearance, and higher oral exposure in animal models. Importantly, it avoids common drug-drug interaction issues seen in its competitor, such as CYP3A4 inhibition, making it more suitable for patients on complex treatment regimens. Toxicology studies suggest a favorable safety profile.
This therapy is being positioned as a tumor-agnostic option, targeting the Y220C mutation across multiple cancer types—including ovarian, lung, breast, pancreatic, and prostate cancer. Although the mutation is less common in prostate cancer, its presence in certain patients could make them eligible for trials and future treatment. Preclinical data has demonstrated dose-dependent tumor shrinkage in several models, and the drug appears more effective at lower doses than existing alternatives.