Preclinical Studies Demonstrate Galimedix’s GAL-101 Shows Neuroprotective Effect from Toxic Amyloid-Beta in Dry AMD and Glaucoma Models
Galimedix Therapeutics presented data demonstrating its novel, first-in-class, investigational compound GAL-101 provides neuroprotection from misfolded amyloid beta molecules aggregating into toxic forms in vitro, neutralizing their ability to be toxic to neural tissues.
Further, investigators discovered that peak levels from a single delivery of the compound may provide sustained detoxification. The poster was presented at the Association for Research in Vision and Ophthalmology (ARVO) annual meeting in Vancouver, British Columbia, Canada from April 28 to May 2, 2019.
“The unique mechanism of action of GAL-101 has been shown to reduce the levels of amyloid beta present in the retina, thereby both preventing neurodegeneration and increasing the chances of preventing vision loss. However, this poster further demonstrates that a single peak administration of the compound by eye drops may also provide a sustained detoxifying effect in dry AMD and glaucoma patients,” Dr. Hermann Russ, lead author of the paper and Chief Scientific Officer of Galimedix, said in a company news release. “These preclinical data, combined with a positive result in the phase 1 study have made it possible for us to move rapidly toward a phase 2 program for which we will provide updates when available.”
In the poster, investigators reported that eye drops of GAL-101 in repeated monkey models resulted in concentrations in the retina rapidly reaching levels far in excess of the threshold for initiating the peak-related pharmacological effect, and remained in those levels for at least four hours. Furthermore, in age-related macular degeneration (AMD) mouse models with substantial amyloid beta deposits in the retina accumulated during many months, GAL-101 eye drops when given for 1-3 months resulted in substantially less amyloid beta deposits, and simultaneously reduced the levels of C-complement response, which is considered a central factor leading to the progression of dry AMD.
About GAL-101
GAL-101 is a proprietary compound designed to prevent the formation of all forms of toxic amyloid beta oligomers, by binding with high affinity to the misfolded amyloid beta monomers before they can form toxic soluble oligomers. These then rapidly conglomerate into amorphous, non-beta-sheet formations, which we call “clusters,” which are innocuous. Interestingly, once GAL-101 concentration reaches effective levels it “triggers” formation of the “clusters,” which then have shown the capacity to collect additional misfolded amyloid beta monomers even in the absence of additional GAL-101 molecules, through a self-propagation mechanism. This novel “trigger effect,” protected by Galimedix’ patent portfolio, results in a sustained effect lasting far longer than the time a single administration of the drug remains at therapeutic levels in the retina, potentially allowing for a convenient interval application regimen for patients. Thus, GAL-101 drops may potentially provide sustained prevention of formation of toxic amyloid beta oligomers in the retina, leading to a reduction of complement response and their consequent damage. Thus GAL-101 could contribute to slowing or stopping progression, and possible restoration of neural function depressed by the chronic toxic attack.