Gain Therapeutics Presents Preclinical Data on its Structurally Targeted Allosteric Regulators in GBA1 Gaucher Disease at the WORLDSymposium 2022

 Source:  Gain Therapeutics, Inc. 2/8/2022

Study results demonstrate GBA1-targeted allosteric regulators increase GCase protein levels, reduce the production of inflammatory cytokines, and improve key lysosomal functions

Gain Therapeutics, Inc. (Nasdaq: GANX) (“Gain”), a biotechnology company transforming the drug discovery paradigm with structurally targeted allosteric regulators (STARs) identified with its proprietary computational discovery platform, today presented new pre-clinical data from its Gaucher Disease (GD) program. These results were highlighted in a late breaking abstract presentation at the 18^th Annual WORLDSymposium on lysosomal disease research being held February 7 – 11, 2022 at the Manchester Grand Hyatt in San Diego, California. The data generated in GD-iPSC-derived dopaminergic neurons show that the tested compounds increase the levels of GCase protein, deplete phosphorylated alpha-synuclein and increase autophagic flux.

“These data are further validation of our innovative proprietary drug discovery platform SEE-Tx^® as well as the potential of our lead compound to restore key lysosomal functions thus showing promise as a first-in-class therapy for the treatment of neuronopathic GD,” said Eric Richman, Chief Executive Officer of Gain. “We remain on target to initiate IND-enabling studies for the GD program in the fourth quarter of this year.”

The effect of STARs treatment on lysosomal function was presented from studies in two different models – the GD-iPSC-derived dopaminergic neurons, and a BE(2)-M17 dopaminergic-like neuron model expressing mutant GBA. The presentation titled “Development of Structurally Targeted Allosteric Regulators for the Treatment of Neuronopathic Gaucher Disease” demonstrated the following results:

• Orally bioavailable and brain-penetrant lead STARs have shown promising effects in relevant in vitro models of GD.
• Increased total and lysosomal GCase in WT and GD dopaminergic neurons.
• Lowered pathogenic p-α-synuclein129 in WT and GD dopaminergic neurons.
• Induced the formation of autophagosomes and increased autophagic flux, thus improving lysosomal function in WT and GD dopaminergic neurons.
• Increased GCase protein levels in GD macrophages.
• Effectively reduced the production of inflammatory cytokines by GD macrophages.

Gaucher Disease is a lysosomal storage disease characterized by deficient activity of the glucocerebrosidase enzyme (GCase) encoded by the GBA1 gene. This deficiency results in the toxic accumulation of substrates in the liver, spleen, bone marrow, and nervous system. Recent evidence shows that GBA1 mutant neurons exhibit lysosomal alterations, defective autophagic clearance, accumulation of protein aggregates, and increased vulnerability to cell death. Therefore, targeting these mechanisms could improve and even prevent neurological symptoms. Current approved treatments for GD do not cross the blood-brain barrier thus leaving a high unmet medical need for the development of novel advanced therapies that can target neuronopathic GD.

About Gain Therapeutics, Inc.
Gain Therapeutics, Inc. is transforming the drug discovery paradigm with structurally targeted allosteric regulators identified with its proprietary computational discovery platform SEE-Tx^®. The ability to identify never-seen-before allosteric targets on proteins involved in diseases across the full spectrum of therapeutic areas provides opportunities for a range of drug-protein interactions, including protein stabilization, protein destabilization, targeted protein degradation, allosteric inhibition and allosteric activation. Gain’s pipeline spans neurodegenerative diseases, lysosomal storage disorders, metabolic diseases and oncology. Gain’s lead program in Parkinson’s disease has been awarded funding support from The Michael J. Fox Foundation for Parkinson’s Research (MJFF) and The Silverstein Foundation for Parkinson’s with GBA, as well as from the Eurostars-2 joint program with co-funding from the European Union Horizon 2020 research and Innosuisse.