Our pipeline leverages our proprietary ocular delivery technologies, which are designed to maintain potent and effective drug levels in ocular tissue for up to 12 months and potentially longer, to improve patient compliance, reduce healthcare burdens and ultimately improve clinical outcomes.
Our delivery technologies are depot formulations of microparticles containing biodegradable polymers such as poly (lactic-co-glycolic acid), or PLGA. We demonstrated in animal studies and in our Phase 1/2a clinical trial that our microparticles are well-tolerated in the eye.
Our microparticles are designed to aggregate after intravitrael, or IVT, injection upon exposure to the vitreous fluid at body temperature to form a depot at the bottom of the eye, outside of the visual axis. The microparticles then gradually release the active ingredient at a variable rate depending on the exact composition of the polymer and biodegrade into lactic acid, glycolic acid and PEG that are naturally cleared from the body.
- We are developing our lead product candidate, GB-102, an inhibitor of multiple neovascular pathways, for the IVT treatment of retinal diseases, including wet AMD, with a six-month dosing regimen. GB-102, is a microparticle depot formulation of the anti-VEGF sunitinib.
- We are using our proprietary technologies to also develop GB-401, a novel treatment for primary open angle glaucoma, or POAG, with a dosing regimen of up to six months. GB-401 is a depot formulation of a proprietary inactive pro-drug ester of a beta-adrenergic receptor inhibitor, injected intravitreally as infrequently as every six months to reduce IOP.
- We are also developing GB-103, a longer-acting formulation of sunitinib with the potential to deliver therapeutic drug levels to the retinal tissue for up to twelve months from a single IVT injection. We are in the process of assessing clinical development options for once-per-year dosing for the treatment of retinal diseases.
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.
We are in the process of optimizing our GB-103 formulation, which will inform the timing and design of the clinical development program to explore indications in diabetic retinopathy.