Insilico Medicine Nominates AI-Designed ISM9077 as First-in-Class Preclinical Candidate for Ocular and Inflammatory Diseases
核心洞察
Insilico Medicine (搜索) nominated ISM9077 (搜索), a potential first-in-class Target Y (搜索) inhibitor, as its 32nd preclinical candidate since 2021, designed entirely using Chemistry42's generative AI platform.
In preclinical studies, ISM9077 (搜索) demonstrated approximately three times the efficacy of currently available therapy in dry AMD models and outperformed Cyclosporine A in dry eye models.
The compound exhibits favorable oral bioavailability, retinal exposure 2 to 5.5 times plasma levels, and supports both oral and eye drop delivery with a wide safety margin.
Insilico Medicine (搜索), a clinical-stage generative AI-driven drug discovery company listed on the Hong Kong Stock Exchange (HKEX: 3696), announced on August 5, 2026, the nomination of ISM9077 (搜索) as a preclinical candidate (PCC). The AI-empowered, potential first-in-class Target Y (搜索) inhibitor is being developed for the treatment of ocular diseases including dry age-related macular degeneration (搜索) (dry AMD), uveitis (搜索), and dry eye disease (搜索), with a dual-purpose strategy that also targets the fundamental aging process.
The nomination marks Insilico's 32nd PCC since 2021, underscoring the company's ability to deliver AI-designed drug candidates at scale. While traditional early-stage drug discovery typically takes 2.5 to 4 years, Insilico has consistently reached PCC nomination in an average of just 12 to 18 months, synthesizing and testing only 60 to 200 molecules per program.
AI-Driven Molecular Design and Mechanism
ISM9077 (搜索) was designed, evaluated, and optimized using Chemistry42, Insilico's generative chemistry platform, through a structure-based drug design (SBDD) approach. The research team established binding pocket understanding and structural foundations through in-house co-crystal structures, then utilized integrated generative models for de novo design, optimizing pharmacophore fit, drug-likeness, three-dimensional shape, and structural novelty.
An AI-driven target-specific model was subsequently developed to predict molecular activity, enabling rapid screening and prioritization of generated compounds. This iterative process yielded ISM9077 (搜索), a novel AI-empowered structure with low patent risk, targeting a unique mechanism of action supported by crystallographic validation.
"ISM9077 (搜索) marks our 32nd preclinical candidate nominated since 2021, so this is an example of how generative AI delivers at scale," said Alex Zhavoronkov, PhD, Founder, CEO and CBO of Insilico Medicine (搜索). "This candidate features a novel target, a novel molecule designed from scratch, and a novel formulation possibility of eye drop."
Preclinical Efficacy Across Ocular Disease Models
In preclinical studies, ISM9077 (搜索) demonstrated robust in vivo efficacy across multiple ocular disease models following both oral administration and topical eye drop delivery. The compound exhibits favorable oral bioavailability, low-to-moderate in vivo clearance, and a retinal exposure 2 to 5.5 times that of plasma levels, along with good permeability supporting future development as an eye drop formulation.
In dry AMD models, ISM9077 (搜索) significantly improved retinal structural integrity and visual function. On key evaluation endpoints, the candidate demonstrated efficacy approximately three times that of currently available therapy, while simultaneously showing superior histopathological improvement. Dry AMD is a leading cause of irreversible central vision loss in older adults.
"Ocular diseases treatment calls for novel options, as current solutions haven't reached a balance between toxicity management, efficacy results, and dosing adherence," said Feng Ren, PhD, Co-CEO and CSO of Insilico Medicine (搜索). "ISM9077 (搜索) overcomes these limitations through AI-driven structural design, achieving superior target exposure and potential for eye drop formulation."
Across independent uveitis (搜索) models, ISM9077 (搜索) reduced ocular inflammation, suppressed the release of inflammatory cytokines, and restored retinal function. In dry eye models, the compound improved tear production and suppressed corneal inflammation with a fast onset, outperforming Cyclosporine A (CsA), the current standard-of-care. These findings validate Target Y (搜索)'s potential as a key therapeutic target addressing a broad range of inflammatory and degenerative ocular diseases.
Broad Therapeutic Potential and Market Context
The novel mechanism of ISM9077 (搜索) modulates pathological inflammation, supporting broad indication expansion into wide-ranging therapeutic areas including aging, neurodegenerative diseases, inflammatory bowel disease (搜索) (IBD), cardiovascular conditions, metabolic dysfunction-associated steatohepatitis (搜索) (MASH), and obesity. Target Y (搜索) is strongly implicated in aging, longevity, and multiple age-related conditions, aligning with Insilico's dual-purpose strategy to treat specific diseases while targeting aging and extending healthspan.
According to recent research cited by the company, the global market for ocular diseases exceeded USD 40 billion in 2025 and is projected to grow to USD 71.58 billion by 2034. Uveitis (搜索) alone accounts for more than 10% of severe visual handicaps in the United States, highlighting the significant unmet need that ISM9077 (搜索) aims to address.
Safety Profile and Delivery Advantages
ISM9077 (搜索) demonstrated a favorable safety profile marked by a wide safety margin in preclinical studies. The compound's good permeability and excellent retinal tissue exposure support the potential for novel delivery methods, including both oral administration and topical eye drop formulation. This dual-route delivery potential represents a significant advantage over current therapies that may require invasive administration, potentially improving patient adherence and quality of life.
Since 2021, Insilico has nominated 32 PCCs, 13 of which have received IND approval or clearance, demonstrating the translational momentum of the company's AI-driven pipeline.