Insilico Medicine Nominates AI-Designed GIPR Antagonist ISM1354

Cambridge, Mass. – September 30, 2026 -- Insilico Medicine (HKEX: 3696) has nominated ISM1354, an AI-designed small molecule GIPR antagonist, as a preclinical candidate for obesity, type 2 diabetes and potential cardiovascular applications tied to obesity-associated heart failure.

ISM1354 improves on Insilico's earlier GIPR candidate ISM0676

The company nominated ISM0676, a prior GIPR antagonist, in January, which showed up to 31.3% weight loss in combination with Semaglutide in humanized mouse models. ISM1354 retains comparable weight-loss efficacy while delivering improved pharmacokinetic and safety profiles, addressing tolerability issues that have derailed rival GIPR programs industry-wide.

Preclinical data show 18-fold greater plasma exposure than a benchmark compound

ISM1354 achieved oral bioavailability of 75-104% across mice, rats, dogs and monkeys. At matched dose levels, it delivered at least 18-fold greater plasma exposure than a clinical-stage benchmark compound.

Safety margins widen versus existing clinical-stage compounds

ISM1354 showed substantially weaker OATP1B1 inhibition than the benchmark compound and maintained cell viability at concentrations up to 200 μM in hepatocyte studies. The benchmark compound, by contrast, showed cytotoxicity with IC50 values of roughly 25 μM in human hepatocytes and 20 μM in monkey hepatocytes. A non-GLP monkey toxicology study found no significant toxicity findings and an estimated 45-fold margin of safety, supporting advancement into GLP toxicology studies.

Chemistry42 platform drove multi-objective molecular optimization

Insilico's R&D team used its Chemistry42 generative chemistry platform to balance potency, selectivity and safety, applying a DILI prediction model for upfront safety filtering and Free Energy Perturbation for affinity ranking across multiple DMTA iteration cycles. "By leveraging the highly efficient molecular generation and optimization capabilities of our Pharma.AI platform, we successfully overcame these bottlenecks in a very short time," said Feng Ren, Co-CEO and CSO of Insilico Medicine.

Pipeline output hits a record 10 preclinical candidates in nine months

Insilico nominated 10 preclinical candidates in the first nine months of 2026, a company record, bringing the cumulative total since 2021 to 34. As of mid-August, the company had logged eight clinical milestones across internal and partnered pipelines, led by Rentosertib (ISM001-055), now in Phase III trials for idiopathic pulmonary fibrosis.

First-half revenue jumps 287% to $106 million with first profitable half-year

Insilico reported approximately $106 million in total revenue for the first half of 2026, up 287% year-over-year, with adjusted net profit exceeding $51 million -- its first profitable half-year since listing. The results were driven by licensing and co-development deals with partners including Eli Lilly, Servier, Takeda, SK Biopharmaceuticals, Qilu Pharmaceutical, Hygtia Therapeutics, China Medical System and Tenacia Biotechnology. Disclosed deal value signed in 2026 alone reached approximately $7.3 billion, pushing cumulative signed deal value since 2021 to nearly $11 billion.