AI-Powered Drug Breakthrough: Insilico Unveils Potent FGFR2/3 Inhibitor for Solid Tumors

Insilico Medicine ("Insilico"), a generative artificial intelligence (AI)-driven clinical-stage drug discovery company, today announced the nomination of ISM8001, a novel molecule targeting FGFR2/3 for the treatment of tissue-agnostic solid tumors bringing the total number of PCCs nominated in 2023 to six.

Fibroblast growth factor receptors 2 and 3 (FGFR2/3) are parts of the FGFR family, which play a critical role in several biological processes including cell proliferation/survival, angiogenesis, by involvement in signal transduction pathways. Alterations in FGFR2/3 have been driven force in multiple types of solid tumors, mainly in urothelial carcinoma, intrahepatic cholangiocarcinoma, NSCLC, esophagogastric cancer, colorectal cancer, pancreatic cancer, endometrial cancer, making them potential targets for the treatment of tissue-agnostic solid tumors. However, there are currently limitations with approved pan-inhibitors due to the high proportion of adverse events, suboptimal response, and the acquired drug resistance.

Clinical Cancer Research reported that FGFR aberrations are present in about 7.1% of cancer patients. Currently, the pan-inhibitors are approved only for UC and ICC indications. Leveraging our pioneering generative AI platform, Insilico has devised a distinct molecular design strategy to tackle current challenges that retain the desired profiles and overcome the drawbacks of previous generations for a broader population with FGFR2/3 aberration."

Feng Ren, PhD, Co-CEO and Chief Scientific Officer of Insilico Medicine

Insilico generates a series of novel molecules with desired profiles and delivers the new generation of FGFR covalent inhibitor with the support of Chemistry42. ISM8001 is an orally available, highly selective dual inhibitor targeting FGFR2/3, and sparing FGFR1/4. The compound demonstrated superior potency in multiple FGFR2/3-driven efficacy models, and also in gatekeeper and molecular brake mutant-resistant models. It also showed favorable DMPK profiles, low efficacious dose, and desirable safety margin to support higher human dose.

"We anticipate forging collaborations with seasoned partners to propel this program towards the next milestone." said Alex Zhavoronkov, PhD, Founder, and co-CEO of Insilico Medicine. "The nomination of ISM8001 unequivocally validates the capabilities of Pharma.AI, Insilico's integrated generative AI platform. We are committed to persistently upgrading and expanding forefront technologies and AI algorithms, with an ultimate aim to expedite drug discovery pursuits and address unmet clinical needs."

Driven by generative artificial intelligence, Insilico stands at the intersection of artificial intelligence and state-of-art technologies. In 2023, The company achieved 6 wholly-owned preclinical candidate (PCC) nominations empowered by Pharma.AI, bringing the total number of PCCs nominated to 17 since 2021. Furthermore, it has propelled five programs into the clinical stage, inclusive of four in Phase 1 trials, with the most advanced being an anti-fibrosis program currently in Phase 2 trial.