Insilico Medicine, a clinical-stage company utilizing generative AI for drug discovery, announced it has received FDA IND clearance for ISM5939. This potential best-in-class oral small molecule inhibitor targets ENPP1 for solid tumor treatment. This milestone marks the 10th AI-driven molecule exclusively developed by Insilico to gain clinical trial clearance. ENPP1, an ecto-nucleotide pyrophosphatase, is crucial in purinergic signaling, affecting immune, cardiovascular, neurological, and hematological function. High ENPP1 levels correlate with metastasis and poor outcomes in various tumors. Inhibiting ENPP1 boosts the immune system's anti-tumor effects by regulating extracellular cGAMP, activating the cGAS-STING pathway. In May 2023, Insilico designated ISM5939 as a preclinical candidate (PCC) for ENPP1, promising for cancer immunotherapy. Preclinical data show ISM5939's strong anti-tumor effectiveness in in vivo studies, along with a favorable safety profile and suitable in vitro ADMET and in vivo pharmacokinetics. Sujata Rao, M. D. , Insilico's Chief Medical Officer, expressed anticipation for the clinical results of ISM5939, noting its safety and combination therapy potential, which could significantly expand cancer treatment options. Supported by Chemistry42, Insilico's proprietary chemistry engine part of Pharma. AI, Insilico identified a lead compound with a novel structure within 3 months, after optimization by their medicinal chemists. The AI-driven drug discovery sector needs real-world validation.

Insilico has proven its AI platform's potential through milestones, with 10 AI-enabled drug candidates achieving IND approvals. The company is committed to further validating its in-house R&D pipeline clinically and advancing AI-powered drug discovery for patients worldwide, according to Feng Ren, Ph. D. , Co-CEO and Chief Scientific Officer. In 2016, Insilico introduced the use of generative AI for novel molecule design in a scholarly journal, establishing a foundation for the Pharma. AI platform. Since then, Insilico has integrated technical advances into Pharma. AI, now a generative AI solution across biology, chemistry, medicine development, and science research. With Pharma. AI's help, Insilico has nominated 20 preclinical candidates and received IND clearance for 10 molecules since 2021. In early 2024, Insilico published a Nature Biotechnology paper detailing the journey from AI algorithms to Phase II clinical trials for ISM001_055, their lead drug with an AI-discovered target and designed structure. Insilico recently reported positive results from a Phase IIa trial (NCT05938920), where ISM001_055 showed favorable safety and tolerability at all doses, with a dose-dependent response in forced vital capacity (FVC) after 12 weeks.