Our proprietary technologies are designed to allow sustained delivery of pharmacologic agents to the eye in a well-controlled and tolerable manner to achieve extended duration of effectiveness.
We aim to extend duration of effectiveness — with the goal of improving patient compliance, reducing healthcare burden and ultimately improving clinical outcomes.
Graybug’s polymer delivery systems are designed to form a depot near the bottom of the eye, outside of the visual axis, by either an injectable implant or as microparticles that aggregate after intravitreal (IVT) injection. Our biodegradable drug products gradually release the active ingredient at a rate designed to provide the desired treatment durability. They then biodegrade into lactic acid, glycolic acid and polyethylene glycol, all of which are then naturally cleared from the body.
- GB-401 is a sustained release beta-blocker, designed to be injected twice-per-year to reduce intraocular pressure (IOP) in patients with primary open angle glaucoma (POPG). If approved, GB-401 could represent a significant paradigm shift in the way physicians treat POAG, addressing the patient compliance problem that exists with current therapies while improving visual outcomes.
- GB-102 is a twice-per-year intravitreally delivered formulation of sunitinib for the treatment of wet age-related macular degeneration (wet AMD). We believe that GB-102 is differentiated from the current standard of care which requires more frequent dosing (up to 12 times per year), and primarily targets one neovascular pathway (VEGF-A) by delivering a sustained and durable dose of sunitinib – a pan-VEGF inhibitor – to the vitreous while blocking VEGF-B, C and D in addition to VEGF-A. We believe durable and sustained drug delivery of a single dose offered by GB-102 could provide improved visual outcomes for patients with wet AMD, better patient quality-of-life and reduce disease-monitoring requirements.
- Graybug continues to enhance its technology platform and has initiated the development of additional formulations, which have the potential to preserve the durability while minimizing the risk of interfering with vision. These new and enhanced formulations, including injectable implants, also have the potential to simplify the drug reconstitution process as well as minimize the injection technique variability.
GB-103 is intended to be a longer-acting version of GB-102 with the potential to maintain therapeutic drug levels in the retinal tissue for up to 12 months from a single intravitreal injection. We believe that GB-103’s potential 12-month durability and reduction in frequency of injections could significantly improve the standard of care for diabetic retinopathy patients.
In preclinical models, GB-103 demonstrated longer sustained drug levels of sunitinib in ocular tissues in comparison to GB-102.
In vivo drug release in rabbit eyes
Drug levels in target tissues
The figure on the left illustrates the in vivo correlation of drug release kinetics in a rabbit vitreous comparing GB-102 (blue, circles) with GB-103 (pink squares). The estimated 12-month duration of GB-103 results from 10 months release from our proprietary microparticles plus an estimated additional two months in which sunitinib is released from the RPE melanin, extending drug presence in target tissues. The longer duration is accomplished through adjusting the properties of our biodegradable polymer.
The figures on the right illustrate in vivo tissue drug levels of sunitinib from a single injection of either GB-103 (red, squares) or GB-102 (blue, circles) in a rabbit eye. High levels of sunitinib that are many folds above the KiVEGF are observed in the retina (left) and RPE/choroid (right) throughout the entire studies. Ki is the inhibitory constant and reflects how much drug is required to block the receptor. Drug tissue levels that are higher than the Ki indicate that there is theoretically sufficient drug concentration available to block the action of the receptor.