NEW ORLEANS, June 8, 2026
insitro announced new preclinical findings from its lead metabolic dysfunction-associated steatohepatitis (MASH) program, demonstrating that its AI-discovered therapeutic candidate CTRO-1013 produced anti-fibrotic effects beyond reducing liver fat accumulation. The data, presented at the American Diabetes Association (ADA) 86th Scientific Sessions, provide additional evidence supporting IRS1 inhibition as a potential therapeutic strategy for treating both liver fat accumulation and fibrosis progression in patients with MASH. The findings strengthen the scientific rationale for advancing CTRO-1013 through IND-enabling studies and into first-in-human clinical trials later this year.
AI-Driven Discovery Identifies IRS1 as a High-Value MASH Target
Using its proprietary Virtual Human™ platform, insitro analyzed extensive human genetic, imaging, biomarker, and clinical datasets to identify IRS1 as the strongest liver-fat associated genetic signal among more than 480 evaluated targets. Further analyses revealed that the association between IRS1 and liver fibrosis persisted even after adjusting for liver fat levels, suggesting that IRS1 may influence fibrotic disease progression through mechanisms that extend beyond steatosis. These findings positioned IRS1 as a promising target capable of addressing both metabolic dysfunction and liver scarring, two key drivers of disease progression in MASH.
CTRO-1013 Demonstrates Anti-Fibrotic and Liver-Protective Effects
The company evaluated liver-targeted IRS1 silencing using CTRO-1013 across multiple preclinical models. In an industry-standard fibrogenic mouse model, treatment significantly reduced circulating biomarkers linked to fibrosis progression and liver cell injury, including TIMP-1 and CK-18. Liver-targeted IRS1 inhibition also lowered liver fat levels while improving markers associated with disease severity. Additional studies demonstrated substantial reductions in hepatic IRS1 expression, de novo lipogenesis, and liver triglycerides, supporting a broad biological impact on metabolic and fibrotic pathways. Researchers noted that the anti-fibrotic effects appeared partially independent of liver-fat reduction, providing important mechanistic insight into how IRS1 modulation may alter disease progression.
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Human Genetics and Preclinical Data Support Therapeutic Potential
The ADA presentation highlighted converging evidence from both human genetic analyses and experimental validation studies. Human datasets linked IRS1 to liver fat accumulation and fibrosis risk, while laboratory studies confirmed that selective IRS1 inhibition reduced lipid accumulation in human hepatocytes and improved liver-related endpoints in animal models. In cynomolgus monkeys, liver-targeted IRS1 silencing achieved sustained target suppression for more than 90 days without disrupting glucose homeostasis, supporting the candidate’s potential safety and therapeutic profile. Collectively, these findings suggest that CTRO-1013 may offer a differentiated approach capable of targeting multiple biological drivers of MASH progression.
CTRO-1013 Moves Toward First-in-Human Clinical Development
insitro designed CTRO-1013 as a liver-targeted siRNA therapy intended to selectively silence IRS1 while minimizing systemic exposure. The company believes this targeted delivery strategy may maximize therapeutic activity within the liver while reducing the risk of unwanted effects elsewhere in the body. Ongoing mechanistic and histological studies are expected to further characterize the therapy’s impact on fibrosis biology and disease progression. Based on the strength of the genetic, cellular, and preclinical evidence generated to date, insitro is continuing IND-enabling activities and expects to initiate first-in-human clinical studies of CTRO-1013 later in 2026, marking a significant milestone for the company’s AI-driven drug discovery platform.
Source: insitro press release
