Insilico Medicine has announced the initiation of a Phase I clinical trial for ISM001_055, an anti-fibrotic small molecule inhibitor developed using its artificial intelligence (AI) platform, Pharma.AI, for the treatment of idiopathic pulmonary fibrosis (IPF). This marks a significant milestone as it represents the first time a drug developed from scratch using AI has entered Phase I clinical trials.
The Phase I trial is a double-blind, placebo-controlled, single and multiple ascending dose study designed to evaluate the safety, tolerability, and pharmacokinetic profile of ISM001_055. The study will enroll 80 healthy volunteers across 10 cohorts, with the primary endpoints focused on determining the maximum tolerated dose and establishing dosage recommendations for future Phase II studies.
AI-Powered Drug Discovery
The journey from initial concept to Phase I clinical trial took Insilico Medicine just under 30 months and approximately $2.6 million. This is a stark contrast to the traditional drug discovery process, which typically takes several years and costs billions of dollars. The company's AI-powered platform, Pharma.AI, facilitated the rapid identification of a novel pan-fibrotic target and the design of a drug candidate with a unique mechanism of action.
The AI-driven approach involved several key modules:
- PandaOmics: This target discovery module was trained on omics and clinical datasets related to tissue fibrosis, annotated by age and sex. It identified relevant targets using deep feature synthesis, causality inference, and de novo pathway reconstruction. A natural language processing (NLP) engine assessed target novelty and disease association by analyzing millions of data files.
- Chemistry42: This generative chemistry module was used to design a library of small molecules that bind to the novel intracellular target revealed by PandaOmics. Chemistry42 creates drug-like molecular structures with appropriate physicochemical properties.
- Inclinico: AI was used to monitor the effects of the drug in healthy volunteers.
ISM001-055: A Novel Anti-fibrotic Agent
ISM001-055 demonstrated promising results in preclinical studies, including in vitro biological studies and pharmacokinetic and safety assessments. The compound improved myofibroblast activation, a key contributor to the development of fibrosis. Notably, ISM001-055's target is novel and potentially relevant in a broad range of fibrotic indications.
In in vivo studies, the ISM001 series of molecules showed activity in improving fibrosis in a Bleomycin-induced mouse lung fibrosis model, leading to improvements in lung function. The compounds also demonstrated a good safety profile in a 14-day repeated mouse dose range-finding study.
Idiopathic Pulmonary Fibrosis (IPF)
Idiopathic Pulmonary Fibrosis is a chronic and progressive disease characterized by the stiffening and scarring of lung tissue, primarily affecting older adults. The disease leads to a gradual decline in lung function and can ultimately result in life-threatening pulmonary failure. Current therapies offer limited options for patients, highlighting the urgent need for new and effective treatments.
Implications for the Future of Drug Discovery
This achievement by Insilico Medicine underscores the potential of AI to revolutionize drug discovery and development. By leveraging AI, the company has significantly reduced the time and cost associated with bringing a novel drug candidate to clinical trials. This success may pave the way for a new era of AI-driven pharmaceutical research, accelerating the development of innovative therapies for a wide range of diseases.
