Graybug Vision Inc. today announced a strategic update on its pipeline programs GB-102 in wet age-related macular degeneration (wet AMD), GB-401 in primary open-angle glaucoma (POAG), as well as its newly acquired assets in corneal disease (GB-501 ), inherited retinal disorders (GB-601), and geographic atrophy (GB-701).
“We are very pleased to advance GB-102 into a Phase 2 clinical trial in wet AMD in Q4 2022, while expanding our pipeline to address additional vision-impairing retinal and corneal diseases with high unmet patient needs,” Fred Guerard , PharmD, CEO of Graybug, said in a statement. “We plan to use our current cash to advance GB-102, GB-401 and GB-501 to clinical levels in 2023.”
GB-102 for wet AMD
Graybug announced in a press release that it plans to proceed with a Phase 2 clinical trial of an optimized formulation of GB-102 in patients with wet AMD after successfully demonstrating improved performance in an extensive series of novel in vitro exercise tests . This decision, supported by a significantly more favorable competitive landscape following recent data on other long-acting vascular endothelial growth factor (VEGF) inhibitors, is expected to result in a six-month data display in Q3 2023.
“We are confident that our optimized formulation, together with modified patient enrollment criteria, will demonstrate efficacy similar to the current standard of care while maintaining the unprecedented duration of up to 12 months observed in the ALTISSIMO study,” said Parisa Zamiri, MD, PhD, Graybug’s Chief Medical Officer.
GB-401 for POAG
In glaucoma, poor patient compliance with eye drops often results in suboptimal intraocular pressure (IOP) control and optic nerve degeneration, resulting in irreversible vision loss. GB-401 is a potentially first-in-class implant formulation containing a novel prodrug of timolol injected intravitreally with a proprietary applicator, targeting twice-yearly treatment. A phase 1 trial of GB-401 is planned to begin in Q1 2023, with safety and efficacy data expected to be available in Q2 2023.
GB-501 for MPS1 corneal opacity
Graybug recently acquired RainBIO, a North Carolina-based start-up that has developed a first-in-class gene therapy for mucopolysaccharidosis type 1 (MPS1), an inherited lysosomal storage disease with a very high prevalence of corneal opacity despite existing systemic therapies (enzyme replacement or transplantation hematopoietic stem cells). GB-501 has received orphan drug designation from the FDA and is eligible for a Priority Review Voucher upon approval.
Preclinical studies in a canine model of MPS1 demonstrated complete and sustained clearing of the cornea in all dogs, regardless of disease severity, in less than a month after a single intrastromal injection. Two years of animal data support GB-501’s potential to heal corneal opacity and restore vision in MPS1 patients. All patients required for the Phase 1/2a study have been identified, IND submission is expected in Q2 2023 and data release is expected in Q4 2023.
GB-601 for inherited retinal disorders
Hereditary retinal diseases such as retinitis pigmentosa, Leber’s congenital amaurosis and Stargardt’s disease are the result of more than 280 genetic mutations. To date, only one drug has been approved to treat a single mutation (RPE65), which accounts for a very small proportion of IRDs, leaving the vast majority of patients without therapeutic options.
According to the company, it recently acquired a portfolio of novel cGMP analogs supported by a well-characterized mode of action and preclinical data in established RP disease models from Mireca Medicines GmbH, a German preclinical start-up. Graybug is developing these cGMP analogs as first-in-class, mutation-independent, long-acting therapeutics to treat a majority of patients with these diseases.
GB-701 for geographic atrophy
Geographic atrophy (GA) represents a significant unmet medical need with more than five million patients worldwide suffering from this late-stage age-related macular degeneration, for which there is currently no FDA-approved treatment. Recent clinical studies have shown that targeting the complement pathway is effective in slowing disease progression, but these investigational therapies require up to 12 injections per year.
Graybug and Insilico Medicine, an end-to-end artificial intelligence (AI) clinical development company, recently entered into a strategic partnership to combine Insilico’s AI-driven small molecule discovery platform with ocular drug delivery technologies of Graybug, which will enable the development of GrayBug, a sustained-release, topical ocular formulation of a potent factor B inhibitor as a potential treatment for this vision-threatening disease.