Insilico Nominates AI-Designed ISM9077 for Ocular Disease With Eye-Drop Ambitions

ISM9077 joins Insilico's nomination streak

Insilico Medicine has nominated ISM9077 as a preclinical candidate for inflammatory and degenerative ocular diseases, including dry age-related macular degeneration (dry AMD), uveitis, and dry eye disease. The company disclosed the nomination in coverage by Drug Target Review, describing an AI-designed small molecule aimed at a proprietary target the firm calls Target Y.

Insilico said ISM9077 becomes its 32nd preclinical candidate nominated since 2021, with 13 subsequently receiving IND approval or clearance.

How the molecule was built

Insilico reports using its Chemistry42 generative chemistry platform with structure-based design. Researchers mapped the target binding pocket from co-crystal structures, then used generative models to propose molecules scored on pharmacophore fit, drug-likeness, three-dimensional shape, and structural novelty. An AI model specific to Target Y prioritized compounds for testing through iterative optimization rounds.

Co-CEO and CSO Feng Ren emphasized formulation flexibility: Insilico believes ISM9077 could support eye-drop delivery, not only oral dosing — a potential adherence advantage in chronic ocular disease.

Founder and co-CEO Alex Zhavoronkov framed the program as part of Insilico's "dual-purpose strategy" linking specific disease targets to aging biology, noting Target Y is "strongly implicated in ageing, longevity and multiple age-related conditions."

Preclinical claims — and the gap to clinic

Insilico reported preclinical activity across species with both oral and topical routes. The company cited retinal exposure between two and 5.5 times plasma levels, favorable oral bioavailability, and low-to-moderate clearance.

In dry AMD models, Insilico said ISM9077 improved retinal structure and visual function, claiming roughly three times the efficacy of currently available therapy on key endpoints alongside histopathology gains. In uveitis models, it reported reduced inflammation and cytokine release; in dry-eye models, increased tear production with rapid onset and performance versus cyclosporine A.

ISM9077 remains preclinical. Insilico states the candidate must complete development and regulatory testing before any clinical trial can begin. Insilico estimates its AI-driven path typically reaches preclinical nomination in 12–18 months, compared with its 2.5–4 year estimate for traditional early discovery.

Context in a verification-heavy month

The nomination lands as Insilico's rentosertib program — an AI-identified TNIK inhibitor for idiopathic pulmonary fibrosis — entered Phase III testing in China after Phase IIa results published in Nature Medicine. Separately, a Nature Reviews Drug Discovery perspective published August 7, 2026 cautioned that AI drug-discovery tools still show "disappointingly limited" clinically relevant impact despite extensive benchmarking.

ISM9077 is therefore another data point in the pipeline — not evidence that AI discovery has cleared the clinic. The test is whether Target Y biology survives IND-enabling work and first-in-human dosing with toxicology and formulation constraints eye drops impose.

Sources

• Drug Target Review — Insilico Medicine nominates AI-designed ISM9077 for ocular diseases (2026)
• GxP News — First AI-discovered drug for fatal lung disease enters final trial phase (August 10, 2026)
• Nature Reviews Drug Discovery — Artificial intelligence in drug discovery — what it is, where we stand and the path forward (August 7, 2026)