Insilico Medicine doses first patient in Phase I Trial of ISM6331 for mesothelioma

Insilico Medcine( “Insilico”) , a clinical stage generative artificial intelligence (AI)-driven biotechnology company today announced the first patient has been dosed in the global multicenter Phase I Trial of ISM6331, a novel pan-TEAD inhibitor developed from Insilico’s generative chemistry engine Chemistry42, for the treatment of mesothelioma and other solid tumors. Currently, ISM6331 is the leading oncology program among Insilico’s wholly owned AI-driven drug discovery pipelines, which was granted orphan drug designation (ODD) by the FDA for the treatment of mesothelioma.

The Phase I trial conducted concurrently in China and the United States, was designed to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics and preliminary anti-tumor activity of ISM6331 as a single agent in patients with advanced or metastatic malignant mesothelioma or other solid tumors. The study consists of two parts, a dose escalation part, with the first patient enrolled in China recently, and a dose selection optimization part which will be initiated after part 1 is completed. For more information about Insilico’s clinical trials please visit ClinicalTrials.gov (NCT06566079).

We are pleased to announce the dosing of the first patient in our Phase I ISM6331 clinical trial in mesothelioma and other solid tumors. We will also move forward to advance patient enrollment in the United States and accelerate the clinical translation to deliver innovative therapies that address unmet medical needs.”

Sujata Rao, MD, Chief Medical Officer of Insilico Medicine

As a potent pan-TEAD inhibitor, ISM6331 was developed to effectively restore the balance of the Hippo pathway and prevent the proliferation and survival of tumor cells through blocking the transcription of multiple genes that promote cancer progression. It is also expected to be used in combination with targeted therapies, chemotherapies and immunotherapies for the treatment of solid tumors, showing potential synergistic anti-tumor effects and overcoming drug resistance.

The design of ISM6331’s novel non-covalent structure was greatly accelerated during early drug discovery, guided by Chemistry42’s structure-based drug design strategy. In preclinical studies, ISM6331 demonstrated broad anti-tumor efficacy in multiple cell lines, potent activity at low doses in animal models, and a favorable safety profile with favorable ADMET characteristics. With superior efficacy and safety data, ISM6331 showed Best-in-class potential and further encouraged Insilico to advance the asset into clinical validation. 

“By inhibiting TEAD, ISM6331 has the potential to suppress tumor growth and progression, providing a targeted therapeutic strategy for malignancies driven by alterations in the Hippo pathway. ” says Feng Ren, Ph.D., Co-CEO and Chief Scientific Officer of Insilico Medicine. “We look forward to further clinical validation of ISM6331 and to translating these promising preclinical findings into tangible clinical benefits for patients.”

In 2016, Insilico first described the concept of using generative AI for the design of novel molecules in a peer-reviewed journal, which laid the foundation for the commercially available Pharma.AI platform. Since then, Insilico keeps integrating technical breakthroughs into Pharma.AI platform, which is currently a generative AI-powered solution spanning across biology, chemistry, medicine development and science research. Powered by Pharma.AI, Insilico has nominated 22 preclinical candidates in its comprehensive portfolio of over 30 assets since 2021 and has received IND clearance for 10 molecules. 

In early 2024, Insilico published a Nature Biotechnology paper presenting the entire R&D journey from AI algorithms to Phase II clinical trials of ISM001-055, the company’s lead drug pipeline with AI-discovered target and AI-designed structure. Following that, Insilico has recently announced positive preliminary results from a Phase IIa trial (NCT05938920), where ISM001-055 showed favorable safety and tolerability across all dose levels, as well as dose-dependent response in forced vital capacity (FVC), after only 12 weeks of dosage.