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.
We are developing GB-401 as an injectable implant of our proprietary pro-drug of a beta-adrenergic receptor inhibitor, administered intravitreally as infrequently as every six months to reduce IOP. We designed GB-401 with the goal of improving glaucoma patient outcomes through increased compliance and a favorable tolerability and safety profile.
- For patients, our goal is to eliminate the need for daily eye drops required to manage elevated IOP.
- For physicians, our goal is to design a long-acting IOP-lowering treatment that can be administered in the office through IVT injections, ensuring patient compliance for up to six months.
GB-401 could also improve tolerability by reducing ocular hyperemia (red eyes due to irritation) and sunken eye (reduction in peri-orbital fat), which are common side effects for PGAs and rho-kinase inhibitors, while eliminating systemic drug exposure. Therefore, we believe our proprietary beta-blocker technology represents a validated but differentiated pharmacological approach.
We are encouraged by data from our preclinical studies to date:
- In a rat model for ocular hypertension, we observed sustained IOP reduction from a single intravitreal injection of a microparticle formulation of the GB-401 pro-drug that appeared to be at least as potent as twice daily administration of topical beta-blocker 0.5% ophthalmic solution for 28 days.
- In pigmented rabbit eyes, we observed sustained tissue levels of the beta-adrenergic receptor inhibitor for at least six months from a single intravitreal injection.
- In a six-month good laboratory practice, toxicity study in minipigs, no active beta-blocker was detected in the plasma at any dose or time point.
Single injection intravitreal route and comparator topical eye drop (rat OHT model)
Sustained therapeutic tissue drug levels for at least 6 months after single intravitreal injection
No drug was detected in plasma at any timepoint (no systemic exposure)
The figure on the left illustrates the proof of concept study in a rat ocular hypertension (OHT) model. The control group received no drug (black dotted lined). The active control group (gray bar) received twice daily topical beta-blocker 0.5% and demonstrated 10 to 15% relative reduction in IOP. Following a single administration of a microparticle formulation of GB-401 prodrug intravitreally, the low dose (green circles) and high dose (pink squares) groups demonstrated statistically significant reductions in IOP compared to baseline (p<0.05). The results suggest that intravitreal administration of a formulation containing GB-401 prodrug may be at least as potent in reducing IOP as traditional timolol eye drops.
The figure on the right illustrates tissue drug levels of the GB-401 beta-blocker from a single intravitreal injection at day one comparing low (green squares) and high dose (pink circles) in the iris-ciliary body of pigmented rabbit eyes. The levels of the beta-blocker are above the Ki required to inhibit the beta-adrenergic receptors at all recorded time points out through six months.
We plan to initiate a first-in-human, multicenter, open-label, sequential escalating dose-cohorts Phase 1/2a clinical trial evaluating the safety, tolerability and pharmacodynamic effects of a single intravitreal injection of GB-401 in patients with POAG.