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Gain Therapeutics, Inc. Announces Positive Topline Data in Patient-derived iPSC Study Evaluating STAR Compounds as a Treatment for Gaucher and Parkinson’s Disease

GT-02287and GT-02329 compounds display positive effects on GCase activity and related parameters
Study results demonstrate an increase in GCase protein levels with transport to the lysosomes and decrease of glucosylceramide and α-synuclein-p129 levels
Comprehensive study results to be presented at Michael J. Fox Foundation’s upcoming Innovating from Drug Discovery to the Clinic: Novel Approaches to PD Therapeutic Development webinar
IND-initiating study planned for Q4’21

BETHESDA, Md., September 8, 2021 (GlobeNewswire) – Gain Therapeutics, Inc. (Nasdaq: GANX) (“Gain”, or the “Company”), a biotechnology company focused on identifying and optimizing allosteric binding sites never before targeted in neurodegenerative diseases and lysosomal storage disorders, today announced topline data from the Company’s study, conducted at the University of Maryland School of Medicine (UMSOM). The study, evaluating two lead Structurally Targeted Allosteric Regulators (STARs) compounds – GT-02287 and GT-02329 – for the treatment of Gaucher and GBA1 Parkinson’s Disease, demonstrated positive effects on all tested phenotypes.


Ricardo Feldman, Ph.D., Associate Professor of Microbiology and Immunology at the University of Maryland School of Medicine, stated, “Our laboratory is using human induced pluripotent stem cells (iPSC) derived from patients with GD and GBA-associated Parkinson’s disease to test the efficacy of the two lead STAR chaperones developed by Gain Therapeutics. Our studies in iPSC-derived cortical and dopaminergic neurons from neuronopathic Gaucher Disease patients show that these compounds increase the levels of GCase protein, its transport to the lysosome, and its enzymatic activity. In dopaminergic neurons, the two lead STAR chaperones also decrease the levels of α-synuclein-p129, demonstrating their potential to treat GBA1-associated Parkinson’s Disease.”


“These data are extremely exciting, as it further demonstrates the potential of GT-02287 and GT-02329 and expands the body of evidence supporting our Site-Directed Enzyme Enhancement Therapy (SEE-Tx™) drug discovery platform,” said Eric Richman, Chief Executive Officer of Gain. “We plan to fully evaluate the results of this study and present a complete data set on the upcoming Michael J. Fox Foundation’s Innovating from Drug Discovery to the Clinic: Novel Approaches to PD Therapeutic Development webinar. In addition, we anticipate initiating IND-enabling studies for Gaucher / Parkinson’s Disease in the fourth quarter of this year.”


Gain identified the two lead STAR candidates (GT-02287 and GT-02329) through its proprietary SEE-Tx™ platform. The compounds were characterized in assays to potentially help Parkinson’s patients with GBA1 gene mutations as well as patients whose glucocerebrosidase (GCase) protein is misfolded due to ageing cellular processes. This previous work was supported through grants from The Michael J. Fox Foundation (MJFF) and the Silverstein Foundation for Parkinson’s with GBA.


Mutations in GBA1, the gene encoding the lysosomal enzyme GCase, are among the most commonly known genetic risk factors for the development of Parkinson’s Disease and related synucleinopathies. GBA1 mutations are causative for the rare autosomal storage disorder Gaucher Disease and may lead to degradation of the protein, disruptions in lysosomal targeting and diminished performance of the enzyme in the lysosome. Patients with Gaucher Disease including heterozygous carriers are at increased risk of developing Parkinson’s Disease and Dementia with Lewy Bodies.


The study conducted in collaboration with Ricardo A. Feldman, Ph.D., Associate Professor of Microbiology and Immunology at UMSOM and lead investigator, is using human induced pluripotent stem cells (iPSC) for Gaucher and Parkinson’s Disease modeling and drug discovery. Gain’s candidate molecules GT-02287 and GT-02329 have been initially assessed in this unique “disease-in-a-dish” iPSC model derived from Gaucher type 2 and 3 patient cells.


Topline data from collaboration with University of Maryland School of Medicine on GBA-associated Parkinson’s Disease in iPSC model. The two STAR compounds achieved the following results:

  • Displayed positive effects on key biological read-outs such as GCase activity, GCase protein levels, GCase transport to the lysosomes, glucosylceramide and depletion of P-alpha-synuclein: all parameters that are related to disease onset and progression
  • Increased GCase enzyme activity
  • Increased GCase protein levels and transport to the lysosome in cortical neurons
  • Decreased GluCer accumulation in cortical neurons
  • Increased GCase protein levels and transport to the lysosome in dopaminergic neurons
  • Decreased α-synuclein-p129 levels in dopaminergic neurons

“We appreciate the close collaboration with Dr. Feldman and the University of Maryland School of Medicine in this important area of research,” said Manolo Bellotto, Ph.D., General Manager at Gain. “The topline data demonstrates that our STARs compounds open a new potential approach for direct treatment of GBA1 Parkinson’s Disease by guiding misfolded forms of the GCase enzyme to their proper shape and restoring enzymatic activity. This is an exciting validation of our platform technology and a promising potential therapeutic opportunity for patients suffering from these debilitating diseases.”

The combined data from Gain Therapeutics and Dr. Feldman’s laboratory suggest that STARs bind to novel allosteric binding sites identified using Gain’s proprietary SEE-Tx™ drug discovery platform, stabilize, and restore enzymatic activity to misfolded GCase. In these studies, the restoration of GCase activity resulted in the depletion of the toxic phosphorylated and aggregated forms of α-synuclein and a reversal of the neurodegenerative process resulting in improved locomotor activity in Parkinson’s Disease model in rats. Given that STARs are small molecule therapies, they have significant advantages over the current standard of care for disorders associated with protein misfolding, including most enzyme replacement therapies and gene therapies. They can be administered as a simple oral pill and can reach organs and tissues not typically accessible through current therapeutic options, including the brain, bone and cartilage. As well, the Company believes that STARs are relatively easy and cost-effective to manufacture.

“These encouraging results show promise for this approach to correct dysfunction in the GBA1 pathway, a leading target for Parkinson’s drug development,” said Marco Baptista, PhD, MJFF Vice President of Research Programs. “We look forward to hearing more on next steps to advance these potential therapies further in testing and closer to patients whose greatest unmet need is a treatment to slow or stop disease progression.”

Learn more about Gain Therapeutics, Inc.

Learn more about the University of Maryland School of MedicineNow and Dr. Feldman’s research.

Learn more about The Michael J. Fox Foundation for Parkinson’s Research

Forward-Looking Statements

Any statements in this release that are not historical facts may be considered to be “forward-looking statements.” Forward-looking statements are based on management’s current expectations and are subject to risks and uncertainties which may cause results to differ materially and adversely from the statements contained herein. Such statements include, but are not limited to, statements regarding the market opportunity for Gain’s product candidates, and the business strategies and development plans of Gain. Some of the potential risks and uncertainties that could cause actual results to differ from those expected include Gain’s ability to: make commercially available its products and technologies in a timely manner or at all; enter into strategic alliances, including arrangements for the development and distribution of its products; obtain intellectual property protection for its assets; accurately estimate and manage its expenses and cash burn and raise additional funds when necessary. Undue reliance should not be placed on forward-looking statements, which speak only as of the date they are made. Except as required by law, Gain does not undertake any obligation to update any forward-looking statements to reflect new information, events or circumstances after the date they are made, or to reflect the occurrence of unanticipated events.

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