The company is planning a Phase 2 trial with an optimized formulation in wet AMD that is expected to start in fourth quarter of 2022.
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 diseases (GB-601), and geographic atrophy (GB-701).
“We are very excited to move GB-102 into a Phase 2 clinical trial in wet AMD in the fourth quarter of 2022, while expanding our pipeline to address additional vision-threatening 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 readouts in 2023.”
Graybug announced in a news release that it plans to proceed with a Phase 2 clinical trial of an optimized formulation of GB-102 in wet AMD patients following successful demonstration of improved performance in an extensive battery of novel in vitro stress tests. This decision, supported by a significantly more favorable competitive landscape following recent readouts of other long-acting vascular endothelial growth factor (VEGF) inhibitors, is anticipated to result in a six-month data readout available in the third quarter of 2023.
“We are confident that our optimized formulation, together with modified patient inclusion criteria, will demonstrate efficacy similar to the current standard of care while also maintaining the unprecedented duration of up to 12 months observed in the ALTISSIMO trial,” said Parisa Zamiri, MD, PhD, chief medical officer of Graybug.
In glaucoma, poor patient compliance with eye drops frequently results in suboptimal control of intraocular pressure (IOP), and degeneration of the optic nerve, leading to 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. Initiation of a Phase 1 trial with GB-401 is planned for the first quarter of 2023, with safety and efficacy data expected to be available in the second quarter of 2023.
Graybug recently acquired RainBIO, a start-up company based in North Carolina, that developed a first-in-class gene therapy for mucopolysaccharidosis type 1 (MPS1), an inherited lysosomal storage disorder with very high prevalence of corneal clouding despite existing systemic therapies (enzyme replacement or hematopoietic stem cell transplant). GB-501 received Orphan Drug Designation from the FDA and is eligible for a Priority Review Voucher upon approval.
Preclinical studies in a dog model of MPS1 demonstrated complete and sustained clearing of the cornea in all dogs, regardless of disease severity, in less than a month following a single intrastromal injection. Two-year animal data support the potential for GB-501 to cure corneal clouding and restore vision in MPS1 patients. All patients required for the Phase 1/2a trial have been identified, IND submission is expected in the second quarter of 2023, and the data readout is expected in the fourth quarter of 2023.
Inherited retinal disorders such as retinitis pigmentosa, Leber’s congenital amaurosis, and Stargardt’s disease are the consequence of over 280 genetic mutations. To date, only one drug has been approved to address a single mutation (RPE65), which accounts for a very small fraction 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 company. Graybug is developing these cGMP analogs as first-in-class, mutation-agnostic long-acting therapeutics to treat a majority of patients with these diseases.
Geographic atrophy (GA) represents a significant unmet medical need with over five million patients worldwide suffering from this late-stage, age-related macular degeneration for which there is currently no FDA approved treatment. Recent clinical trials have indicated that targeting the complement pathway is suitable for slowing disease progression, but these investigational therapies require up to 12 injections per year.
Graybug and Insilico Medicine, a clinical-stage, end-to-end artificial intelligence (AI)-drug discovery company, recently formed a strategic partnership to leverage Insilico’s AI-driven small molecule discovery platform with Graybug’s ocular drug delivery technologies enabling GrayBug to develop a sustained-release, locally administered ocular formulation of a potent factor B inhibitor as a potential treatment for this vision-threatening disease.