Convenient, noninvasive administration via oral tablets or eye drops, ideally suited to the needs of patients.
Excellent clinical safety and tolerability demonstrated in Phase 1.
Prevents formation of entire spectrum of possible toxic Aβ oligomers while removing existing ones, resulting in neuroprotection and functional improvement.
Potential to reverse an already-established neurotoxic process demonstrated in vitro and in vivo.
Increasing evidence of role of toxic Aβ species in the pathogenesis of age-related macular degeneration (AMD), one of the leading causes of adult blindness
In the past 10 years, considerable attention has been paid to the significant role Aβ oligomers play in retinal disease. Increasing evidence indicates that these toxic Aβ species are likely involved in the pathogenesis of age-related macular degeneration (AMD), a neurodegenerative disease of the eye that affects around 200 million patients worldwide and has emerged as the leading cause of adult blindness in the US and industrialized countries. Multiple studies link Aβ with key stages of AMD progression and support its role in driving degenerative processes in the aging macula.
Limited treatment options and dry AMD growth call for practical solutions
Most people, around 80% – 90%, with AMD have the “dry” form of the condition, the early history in the decline in which retinal cells in the central area – the macula – slowly degenerate and can lead to blindness.
Dry AMD has been a challenging-to-treat disease. Today, highly inconvenient ocular injections are used, but no immediate benefit is detected by the patient, leaving a need for new treatments that are not only safer and more effective but also easy for patients to use, such as oral and topical formulations.
Stages of AMD
Topical GAL-101: A potential game changer set to enter Phase 2 trial with strong partner
For all these reasons, Galimedix and its partner, Théa Open Innovations, have prioritized the development of GAL-101 as an early treatment of dry AMD. GAL-101 is Galimedix’s most advanced compound, ready to enter Phase 2 testing. Delivered topically as an eye drop, it is designed to provide a convenient and safe treatment, targeting toxic Aβ.
An oral capsule formulation of GAL-101 is also in development.
GAL-101 has demonstrated compelling efficacy in relevant ophthalmic pre-clinical models, protecting neuronal retinal cells from toxic damage, and an excellent safety and tolerability profile in Phase 1 testing.Pre-clinical data in dry AMD show clearance of toxic Aβ in the retina, the key to restoring function
Chronic topical treatment with GAL-101 solution (0.5% or 2%, 3 µL, 3 times a day for 3 months injected intravitreally) decreased the heavy deposition of Aβ along the retinal pigment epithelium (RPE) / Bruch’s membrane (red staining) in 24-month-old C57BL/6 mice – a murine model of AMD. Interestingly, as a consequence, the hyperactivation of complement C3b (green staining), which is co-localized with the Aβ deposits, is also reduced markedly, even though GAL-101 has no direct affinity to C3b.Solid Phase 1 safety results pave way for Phase 2 clinical trials in dry AMD and further ophthalmology indications
A Phase 1 safety study with GAL-101 eye drops was successfully completed in 40 healthy subjects and 30 glaucoma patients as a randomized, double-blind, placebo-controlled single center study. All subjects received GAL-101 eye-drops over 16 days up to the maximum dose possible, i.e., thrice daily three drops in a row with 5-minute intervals using either placebo solution, 5 mg/ml GAL-101 (0.5%) or 20 mg/ml GAL-101 (2%) in an ascending dose regimen.
The results of this study demonstrated an excellent safety and tolerability profile of the GAL-101 eye drops and the Phase 1 study protocol was accepted by FDA and considered sufficient to support the start of larger clinical studies in glaucoma and dry AMD patients.
Toxic amyloid beta (Aβ) leads to vision loss in glaucoma
Glaucoma, a leading cause of irreversible blindness worldwide, is characterized by the progressive death of nerve cells that transfer visual information from the eye to the brain. While commonly linked simply to the effects of raised intraocular pressure (IOP), a growing amount of data suggest the disease shares common pathogenic mechanisms with other neurodegenerative conditions, such as Alzheimer’s disease, strongly associated with the formation of toxic Aβ oligomers. Multiple studies implicate Aβ in the development of the characteristic progressive retinal ganglion cell (RGC) apoptosis and consequential disconnection of the eye from the brain.
Many patients do not benefit from current treatment options
Although drug, laser, and surgical incision treatments are available to address glaucoma, all current approaches work by lowering IOP. However, the majority of Asian glaucoma patients and over 30% of patients in the Western World do not have elevated IOP (so-called normal tension glaucoma or NTG), resulting in very limited efficacy with today’s regimens.
Additionally, even in a significant subset of glaucoma patients with elevated IOP and subsequent treatment, glaucoma-related vision loss continues, despite IOP lowering.
Stages of Glaucoma
Topical GAL-101: Creating a new treatment paradigm to fulfill substantial unmet need
With over 90% neuroprotective efficacy shown in relevant glaucoma pre-clinical models, Galimedix’s Phase 2-ready compound GAL-101, holds great promise to be the first glaucoma therapy that directly addresses the disease via neuroprotection, providing an option for the many patients for whom treatments alleviating IOP are ineffective. Delivered as an eye drop, it is designed to be a convenient and safe treatment and thus ideally suited to slowing the progression of chronic diseases like glaucoma, in which long-term therapeutic efficacy is dependent on patient compliance over many years.
An oral capsule formulation of GAL-101 is also in development.
GAL-101 has demonstrated compelling efficacy in relevant ophthalmic pre-clinical models, protecting neuronal retinal cells from toxic damage, and an excellent safety and tolerability profile in Phase 1 testing.Over 90% neuroprotection confirmed in animal models of glaucoma
GAL-101 has been tested extensively in pre-clinical models of glaucoma, such as the Morrison rat model, in which acute episcleral vein occlusion with hypertonic saline leads to IOP. In control animals, this elevated IOP caused about 20% of retinal ganglion cells (RGCs) to die within 3-16 weeks, whereas less than 1% of RGC’s died in animals treated with GAL-101, whether administered via eye drops (2%, 3µL), subcutaneous (60-240 mg/kg) or intravitreal (0.1 mg/ml, 3 µL) injection.
In repeat experiments, independent laboratories reproducibly obtained over 90% neuroprotection, with good correlation to reduced optic nerve degeneration, despite an elevated IOP, and showed a sustained effect from single day treatment of over 6 weeks.Phase 1 successfully completed showing excellent safety and tolerability profile, paving the way for further development in ophthalmology indications
A Phase 1 safety study with GAL-101 eye drops was successfully completed in 40 healthy subjects and 30 glaucoma patients, in a randomized, double-masked, placebo-controlled single center study. All subjects received GAL-101 eye drops over 16 days up to the maximum dose possible, i.e., thrice daily three drops in a row with 5-minute intervals using either placebo solution, 5 mg/ml GAL-101 or 20 mg/ml GAL-101 in an ascending dose regimen.
The results of this study demonstrated an excellent safety and tolerability profile of the GAL-101 eye drops. All 70 randomized subjects completed the study and adverse events occurred at low frequencies across the treatment and control groups. As with preclinical experiments, no influence of the drug on IOP was observed, and no interaction with IOP lowering treatments was seen. Plasma concentrations were barely detectable, establishing a comfortable safety margin compared to the animal toxicology studies.
Therapeutic strategies targeting amyloid-β bring breakthroughs in fight against Alzheimer’s disease
While the causes of Alzheimer’s disease (AD) are still not fully understood, one hallmark of the condition is the accumulation of protein deposits called amyloid-β (Aβ) in the brain. After decades of failed drugs development attempts, recent approvals based on statistically significant, clinically meaningful Phase 3 data with Aβ-targeting antibodies (aducanumab, lecanemab, donanemab) have marked a new era in treating this debilitating disease, validating the importance of toxic Aβ oligomers and protofibrils as a key target.
However, while progress has been made with the introduction of these Aβ-targeting antibodies, they also have notable safety issues and a challenging route of administration, resulting in a remaining need for more efficacious, safer, and easier-to-use treatments for the 55 million people worldwide living with AD.
Small molecule GAL-201 designed to overcome limitations of current therapies
To avoid known pitfalls of today’s drugs, Galimedix is developing the small molecule GAL-201, belonging to a new pharmacological class of Aβ aggregation modulators, that acts upstream of most other Aβ-targeting agents.
In contrast to antibodies that eliminate toxic oligomers only after their formation, require parenteral administration and have poor access to the central nervous system (CNS), GAL-201 is specifically designed to address Aβ before it turns into toxic oligomers. In pre-clinical testing, GAL-201 has been shown to prevent and eliminate all forms of toxic Aβ species.Robust and consistent pre-clinical data support advancing GAL-201 as AD treatment
In pre-clinical models, GAL-201 has been shown to cross the blood-brain barrier after oral administration and enter brain interstitial fluid (ISF) in pharmacological active concentrations. In addition, GAL-201 has also been shown to be fully efficacious after subcutaneous administration in long-term potentiation (LTP) studies. These findings are further supported by patch clamp studies, where GAL-201 is able to keep the membrane potential stable in the presence of toxic Aβ species. Moreover, LTP studies demonstrate its ability to block Aβ toxicity for neurons and supporting the compound’s ability to prevent Aβ toxicity upon its preincubation as well as reverse established Aβ toxicity (functional recovery).
Notably, GAL-201’s Aβ-detoxifying activity has been shown to be long-lasting after just a single application of GAL-201.