AI-designed drug ISM5939 granted IND clearance for cancer clinical trials

Insilico Medicine (“Insilico”), a clinical-stage generative artificial intelligence (AI)-driven drug discovery company, announced that it has received IND clearance from FDA for ISM5939, a potential best-in-class oral small molecule inhibitor targeting ENPP1 for the treatment of solid tumors. The achievement marks the 10th AI-driven molecule self-developed by Insilico to be recognized with clearance to enter clinical trials. 

ENPP1 is an ecto-nucleotide pyrophosphatase that plays an important role in purinergic signaling that regulates immune, cardiovascular, neurological, and hematological system functions. Elevated ENPP1 expression is associated with metastasis and poor prognosis in multiple tumor types. ENPP1 inhibition enhances the anti-tumor effect of the host immune system by regulating extracellular cGAMP levels to activate the cGAS-STING pathway. 

In May 2023, Insilico Medicine announced the nomination of ISM5939 as a preclinical candidate compound (PCC) targeting ENPP1, with the potential for cancer immunotherapy. According to preclinical data, ISM5939 demonstrated robust anti-tumor efficacy in in vivo studies, while showing favorable safety profile, as well as in vitro ADMET and in vivo pharmacokinetic profiles. 

“I am looking forward to the forthcoming clinical signal of ISM5939.” says Sujata Rao, M.D., Chief Medical Officer of Insilico Medicine. “With its favorable safety window and high potential for combination therapy, it is poised to significantly broaden the spectrum of treatment options for cancer patients.” 

Powered by Chemistry42, Insilico’s proprietary generative chemistry engine affiliated to Pharma.AI, Insilico obtained the lead compound with a distinctly novel molecular structure within 3 months of project initiation, after dedicated optimization through structural modifications by Insilico’s medicinal chemists. 

The AI-driven drug discovery industry requires real-world proof-of-concept cases. At Insilico, we have showcased the potential of our proprietary AI platform through consistent milestones in our ongoing pipeline, with 10 AI-enabled drug candidates successfully obtaining IND approvals to date. We are eager to further validate the company’s in-house R&D pipeline in the clinical stage and to continue advancing AI-powered drug discovery and development for the benefit of patients worldwide.” 

Feng Ren, Ph.D., Co-CEO and Chief Scientific Officer of Insilico Medicine

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 20 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.