Target Disease:Glaucoma

Glaucoma is an optic neuropathy that is characterized by the progressive degeneration of the optic nerve, leading to visual impairment.

Primary Open Angle Glaucoma

About Primary Open
Angle Glaucoma (POAG)

POAG is the most common type of glaucoma, in which the eye pressure increases because the fluid cannot drain properly from the eye. Though the specific mechanism of neuronal damage in POAG has not been fully identified, progressive visual field loss is often associated with intraocular pressure (IOP).

LEARN MORE ABOUT GB-401 in Primary Open Angle Glaucoma

How Glaucoma develops

In the healthy eye, the ciliary body produces fluid that circulates through the pupil and drains in the corner, or the angle, of the eye where the cornea and iris meet.

In POAG, pressure in the eye can increase if there is increased fluid production and/or decreased drainage in the angle leading to elevated IOP.

Chronically elevated IOP can lead to neuronal degeneration and retinal ganglion cell death with resulting disruption of the visual pathway.

PREVALENCE OF
GLAUCOMA

Glaucoma

2.7 / 76

Million
us

Million
worldwide

Glaucoma is a leading cause of irreversible vision loss affecting
approximately 76 million people worldwide and 2.7 million people in the US.
POAG is the most common form of glaucoma.

Greater Compliance In
Glaucoma Is Considered A
Large Unmet Need

Approximately 50% of patients stop taking their glaucoma medications
within the first six months of treatment initiation due to various reasons, including forgetfulness, lack of disease awareness and/or cost.

About 30% of patients often require more than one medication.
Poor adherence to glaucoma medication regimens has been documented in numerous independent studies, particularly in patients on two or more prescription eye drops.

15-20% of glaucoma patients progress to blindness within 15-20 years of diagnosis.
As glaucoma progresses slowly and causes few symptoms, patients often do not adhere to their medication regimens as prescribed until the disease has progressed to the point of significant vision loss. As a result, despite the availability of medication to treat glaucoma, progressive visual loss and blindness still often occur.

Solving The Unmet Need For
Patients With Glaucoma

Our goal is to provide sustained reduction of elevated IOP associated with POAG to increase compliance for patients and improve the medical management of glaucoma. We believe that GB-401 has the potential to provide sustained reduction in IOP for at least six months, thus eliminating the need for frequent patient-instilled eye drops.

The Pipeline

GB-401

GB-401 is a first-in-class implant formulation containing a novel prodrug of timolol injected intravitreally with a proprietary applicator, targeting twice-yearly treatment.

GB-401 is formulated with our biodegradable polymer implant technology for controlled release of the beta blocker and is designed to be administered intravitreally once every six months. The twice per year regimen will increase patient compliance, has better tolerability and likely results in better treatment outcomes.

The prodrug in the GB-401 is a proprietary new chemical entity. Upon exposure to water under physiological conditions, the prodrug is released from the implant and is converted into the active beta-blocker by hydrolysis.

The polymer biodegrades into normal metabolic by-products of lactic and glycolic acid and is naturally cleared from the eye.

Our implant formulation of GB-401 is designed to provide controlled drug release within the eye that minimizes the risk for systemic exposure of the beta-blocker. The figure on the right illustrates sustained in vitro drug release from the GB-401 implant for 120 days at 37° C.

GB-401 preclinical study results

We have successfully completed both in vitro and in vivo preclinical studies to evaluate the potential pharmacokinetics of GB-401.

In a rat model for ocular hypertension, a single intravitreal injection of the GB-401 pro-drug formulation led to sustained IOP reduction that appeared to be at least as potent as twice daily administration of topical beta-blocker 0.5% ophthalmic solution for 28 days

In a rat model

In a rat model for ocular hypertension, a single intravitreal injection of the GB-401 pro-drug formulation led to sustained IOP reduction that appeared to be at least as potent as twice daily administration of topical beta-blocker 0.5% ophthalmic solution for 28 days

Sustained IOP reduction in RAT MODEL

A microparticle formulation of the GB-401 prodrug demonstrated sustained IOP reduction

This figure 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 IVT administration of a GB-401 prodrug formulation, 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.

Single injection intravitreal route and comparator topical eye drop (rat OHT model)

In rabbit eyes, we observed gradual biodegradation of the GB-401 implant over a period of 24 weeks, suggesting a potential durability of six months in human eyes

In rabbit eyes

In rabbit eyes, we observed gradual biodegradation of the GB-401 implant over a period of 24 weeks, suggesting a potential durability of six months in human eyes

durability in rabbit eyes

GB-401 implant is well tolerated and demonstrates durability in rabbit eyes

These images represent color fundus photographs from different animals at different timepoints.

In a preclinical study in rabbits, the biodegradability of the GB-401 implant was visually assessed over a period of 24 weeks. Similar to prior experiences with GB-102 microparticles, which demonstrated a durability of six months for approximately half of the patients studied in clinical trials while appearing to be nearly biodegraded within approximately four months in rabbits, the GB-401 implants also appeared to be substantially biodegraded in rabbit eyes within four months post injection.

These images represent color fundus photographs
from different animals at different timepoints.

We believe that GB-401 has the potential to provide sustained reduction in IOP for up to six months, thus eliminating the need for frequent patient-instilled eye drops and potentially improving patient compliance in this vision-threatening disease.