Insilico Medicine Doses First Patient With AI-Designed Pan-TEAD Inhibitor

Insilico Medicine, a clinical-stage biotechnology company leveraging generative AI for drug discovery, has dosed the first patient in its global Phase I trial of ISM6331, a novel pan-TEAD inhibitor for the treatment of mesothelioma and other solid tumors. The trial, conducted in both China and the United States, aims to evaluate the safety, tolerability, pharmacokinetics, and preliminary anti-tumor activity of ISM6331.

Developed using Insilico’s generative chemistry engine Chemistry42, ISM6331 features a novel non-covalent scaffold specifically engineered to restore balance in the Hippo signaling pathway. This pathway is implicated in tumor growth and progression, and the inhibition of TEAD transcription factors effectively suppresses the transcription of oncogenic genes. ISM6331’s structural optimization, guided by structure-based drug design strategies, enabled the rapid development of a compound with potent activity, high selectivity, and favorable ADMET (absorption, distribution, metabolism, excretion, and toxicity) properties.

Preclinical studies demonstrated ISM6331’s broad anti-tumor efficacy across multiple cell lines and animal models. It showed significant activity even at low doses, highlighting its therapeutic potential, while maintaining a favorable safety profile. Furthermore, ISM6331 has exhibited synergistic effects when combined with targeted therapies, chemotherapies, or immunotherapies, suggesting its capacity to overcome drug resistance and enhance treatment outcomes.

See also: Insilico Medicine's AI-Designed TEAD Inhibitor Receives IND Approval and Orphan Drug Designation from FDA

The Phase I trial consists of two parts: a dose escalation phase, which has begun with the first patient enrolled in China, and a dose optimization phase, which will follow. ISM6331 has received orphan drug designation (ODD) from the FDA for the treatment of mesothelioma, highlighting its potential to address an unmet medical need.

Feng Ren, Co-CEO and Chief Scientific Officer of Insilico Medicine, added:

“By inhibiting TEAD, ISM6331 has the potential to suppress tumor growth and progression, offering a targeted therapeutic strategy for malignancies driven by Hippo pathway alterations.”

ISM6331 is part of Insilico’s broader portfolio of over 30 assets, which includes 22 preclinical candidates and 10 molecules that have received IND clearance. The company’s lead drug candidate, ISM001-055, recently reported positive Phase IIa results in a trial for idiopathic pulmonary fibrosis.

For more information about the trial, visit ClinicalTrials.gov (NCT06566079).