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 sp.