Insilico Medicine Nominates AI-Designed ISM9077 as Preclinical Candidate for Ocular Disease and Aging-Related Inflammation
Insilico Medicine has nominated ISM9077, an artificial intelligence-designed inhibitor of an undisclosed “Target Y,” as a preclinical candidate for dry age-related macular degeneration (dry AMD), uveitis and dry eye disease. The Hong Kong-listed biotechnology company describes the molecule as a potential first-in-class, “pipeline-in-a-drug” therapy because the same biological mechanism could potentially be developed across ophthalmology, inflammatory disorders and diseases associated with aging. The announcement represents Insilico’s 32nd preclinical candidate nomination since 2021.
ISM9077 was created using Chemistry42, Insilico’s generative chemistry platform, which combines structure-based drug design with machine-learning models for molecular generation, activity prediction and compound optimization. According to the company, researchers first characterized the binding pocket of Target Y using in-house co-crystal structures. Generative models then proposed new chemical structures designed to fit the target while balancing pharmacophore alignment, three-dimensional shape, drug-like properties and molecular novelty.
The discovery program also used an AI model trained to predict target-specific activity, allowing researchers to prioritize compounds before extensive laboratory testing. After successive cycles of synthesis, biological evaluation and optimization, the team selected ISM9077 for its activity across species, permeability and exposure characteristics. Insilico says crystallographic studies supported the proposed binding mode and that the molecule has a novel structure with low patent risk. However, the company has not disclosed the identity of Target Y, leaving the precise molecular pathway behind the program confidential.
In preclinical experiments, ISM9077 showed activity following both oral dosing and topical eye-drop administration. The compound reportedly demonstrated favorable oral bioavailability, low-to-moderate clearance in vivo and retinal concentrations between two and 5.5 times higher than plasma levels. These findings are important for ocular drug development, where the blood-retina barrier can restrict delivery to tissues involved in disease. The molecule’s permeability and retinal exposure may support a non-invasive eye-drop formulation, while its oral activity could offer an alternative route for treating conditions involving inflammation beyond the eye.
The strongest results were reported in models of dry AMD, a degenerative retinal disorder and a leading cause of irreversible central vision loss in older adults. Insilico says ISM9077 improved retinal structure and visual function, producing efficacy approximately three times greater than an available therapy on selected study endpoints. The company also reported superior histopathological outcomes, indicating more pronounced improvements in tissue-level disease features. These findings remain limited to animal studies and will require independent validation before the molecule’s relevance to human disease can be established.
In separate uveitis models, ISM9077 reduced ocular inflammation, lowered the release of inflammatory cytokines and helped restore retinal function. Uveitis can damage multiple parts of the eye and, in severe cases, contribute substantially to visual impairment. In dry-eye experiments, the compound increased tear production and reduced corneal inflammation with a rapid onset of action. Insilico reported that these effects exceeded those observed with cyclosporine A, a commonly used treatment for dry eye, although comparisons between preclinical models and clinical standard-of-care medicines should be interpreted cautiously.
The company believes Target Y may connect ocular inflammation with broader biological processes involved in aging. Chronic, low-grade inflammation is implicated in a wide range of conditions, including neurodegenerative disease, inflammatory bowel disease, cardiovascular disorders, metabolic dysfunction-associated steatohepatitis and obesity. By modulating a pathway involved in pathological inflammation, ISM9077 could potentially be developed for multiple indications rather than a single eye disorder. This “dual-purpose” strategy is central to Insilico’s approach of combining disease treatment with interventions aimed at extending healthspan, although evidence for any longevity benefit has not yet been demonstrated in humans.
Insilico also reported a favorable safety profile and a wide safety margin in its preclinical testing. The company has not released detailed toxicology data, exposure limits or the full design of the safety studies, so the significance of the findings cannot yet be independently assessed. Before human trials can begin, ISM9077 will need to undergo formal investigational new drug-enabling studies, including more extensive toxicology, pharmacokinetic characterization, manufacturing development and formulation testing. The feasibility of an eye-drop formulation will depend on factors such as solubility, ocular retention, tissue tolerability and sustained delivery to the retina.
The nomination highlights the growing role of generative AI in early drug discovery, but it also illustrates the distance between computational design and clinical success. Insilico says its programs typically reach preclinical candidate selection within 12 to 18 months, compared with an estimated 2.5 to four years for many conventional early-stage programs, using between 60 and 200 synthesized and tested molecules per program. Of the company’s 32 nominated candidates, 13 have reportedly received investigational new drug approval or clearance. ISM9077 now joins that development pipeline, with its future determined by the rigor of upcoming studies and whether its promising activity in ocular disease models translates into safe and effective treatment for patients.
Subject of Research: AI-designed ISM9077, a potential first-in-class Target Y inhibitor for ocular diseases, inflammatory disorders and aging-related conditions.
Article Title: Insilico Medicine Nominates AI-Designed ISM9077 as Preclinical Candidate for Ocular Disease and Aging-Related Inflammation
Web References: https://www.insilico.com/ ; https://mediasvc.eurekalert.org/Api/v1/Multimedia/79c2d45a-427d-41ce-91f9-fabf5f119cbd/Rendition/low-res/Content/Public
Image Credits: Insilico Medicine
Keywords: Generative AI, artificial intelligence, drug discovery, ISM9077, Insilico Medicine, ocular diseases, dry age-related macular degeneration, dry AMD, uveitis, dry eye disease, inflammation, aging, retinal disease, preclinical candidate, Chemistry42, Target Y, biotechnology, ophthalmology
Tags: aging-related inflammation treatmentAI-designed drug candidatecross-species drug activity predictiondry age-related macular degeneration therapygenerative chemistry platforminflammatory disorder drug candidatesmachine learning in drug discoverymolecular optimization using AIpipeline-in-a-drug approachpreclinical ophthalmology therapiesstructure-based drug designTarget Y inhibitor development
