FDA greenlights AI-developed drug targeting solid tumors

Insilico Medicine, a clinical-stage biotechnology company specialising in using generative AI for drug discovery, has announced that its drug ISM5939 has received FDA Investigational New Drug (IND) clearance. ISM5939 is an innovative oral small molecule designed to target the enzyme ecto-nucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) and treat solid tumours.

ENPP1 is a key enzyme in nucleotide metabolism and purinergic signaling pathways, influencing immune responses and cancer progression. Overexpressed ENPP1 has been linked to metastasis and poor outcomes in cancers such as breast, ovarian, and lung cancer. It also diminishes the innate immune response by degrading extracellular cyclic GMP-AMP (cGAMP), crucial for activating the cGAS-STING pathway. ISM5939’s inhibition of ENPP1 preserves cGAMP levels, enhancing anti-tumor immunity by boosting immune cell infiltration and activity within the tumor microenvironment.

Generative AI in drug discovery

Developed using Insilico Medicine’s Chemistry42 platform, ISM5939 emerged from a rapid three-month lead identification process. Preclinical trials revealed its potency and selectivity in inhibiting ENPP1. In vivo studies using the MC38 tumor model demonstrated significant efficacy, with 67 percent tumor growth inhibition at a 30 mg/kg oral dose administered twice daily. Moreover, ISM5939 amplified the effects of immune checkpoint inhibitors, such as anti-PD-L1 and anti-PD-1 therapies, suggesting synergistic potential.

Phase I clinical trials on the horizon

With IND clearance secured, Insilico Medicine plans to initiate Phase I trials to evaluate ISM5939’s safety, tolerability, pharmacokinetics, and early efficacy in advanced solid tumors. These trials will also explore optimal dosing and its potential to enhance existing immunotherapies.

ISM5939 exemplifies the transformative potential of AI in developing targeted therapies against critical cancer pathways. By modulating the tumor microenvironment through ENPP1 inhibition, it aims to harness the immune system to combat cancer, paving the way for more personalised and effective treatments. This FDA approval not only validates Insilico Medicine’s AI-driven approach but also signals a breakthrough in addressing unmet medical needs in oncology with innovative technologies.