AI-designed drug granted US FDA IND approval
The US FDA have just granted initial investigational new drug (IND) approval of ISM3091 for the treatment of patients with solid tumors.
Cancer is a leading cause of global deaths and is becoming an increasing burden on public health. Worldwide, cancer causes approximately one in six deaths; in 2020 there were ~10 million cancer deaths, and this number is only predicted to grow along with the population. Among these cancers, solid tumors account for approximately 90% of adult cancers.
The victim
USP1 is a gene encoding a deubiquitinase with several significant regulator functions in the DNA damage response. This gene is thought to play an important role in cancer progression and is thus a promising anticancer target.
The assailant
ISM3091 is a novel orally available highly selective, potent small molecule inhibitor of USP1. Preclinical studies have demonstrated its potential against targeting a wide range of tumor lineages, with particularly strong anti-proliferative activity against BRCA1 mutant cells as well as in HRR-proficient models. Additionally, this drug has the exciting potential to combat PARP inhibitor resistance, which is an ever-important issue in cancer therapy.
ISM3091 was designed with Insilico Medicine’s machine learning platform, termed Chemistry42. The AI platform combines medicinal chemistry and computational technologies with AI to design novel drugs, and is trained and modeled on huge datasets of chemical, biological and textual information collected over many years. This allows investigators to develop molecules with favorable properties using ligand-based and structure-based drug design.
The future
On May 25, 2023, Insilico Medicine announced its recent FDA initial IND approval of ISM3091 for the treatment of patients with solid tumors. The drug, developed by Insilico Medicine, is the first time that the AI-driven drug discovery company has received approval for an oncology program to progress to clinical validation testing.
The drug will be tested in both the US and China in an open-label, multicenter Phase I clinical trial (scheduled to begin in July 2023) to evaluate the tolerability, safety and efficacy of ISM3091 in treating patients with advanced solid tumors. If successful, information from this trial will then be used to optimize the drug dose for further testing in Phase II trials.
