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To see if their drug worked, Gain scientists investigated the animals’ ability to build nests—a complex behavior that requires a high degree of mental function. Mouse models of GBA1 Parkinson’s disease that are treated with Gain Therapeutics’ clinical-stage drug appear to have better cognitive function and lower disease biomarkers than untreated animals. The biotech unveiled new preclinical data for the candidate, dubbed GT-02287, at the Federation of European Neuroscience Societies (FENS) Forum June 27.  “These data further confirm our conviction that GT-02287 can slow or stop progression of Parkinson’s disease and given the cognitive decline observed in GBA1 Parkinson’s patients, we hope that we can one day deliver this drug to those that need it and help them improve their everyday life,” Joanne Taylor, Ph.D., senior vice president of research at Gain, said in a press release.  To perform the study presented at FENS, the researchers used daily doses of toxins to induce the murine equivalent of GBA1 Parkinson’s disease. Eight days after they initiated the toxins, they began injecting a group of them once a day with GT-02287. They continued to administer both the toxin and the Parkinson’s drug for 20 more days in that group, while an untreated control group received only the toxins. To see whether the drug worked, Gain scientists investigated the animals’ ability to build nests—a complex behavior that requires a high degree of mental function—along with their motor skills, which Gain looked at in an earlier study, too. They found the mice with Parkinson’s that were given GT-02287 built nests that looked similar to those of healthy animals, while the nests of mice that didn’t receive treatment were poorly constructed. The differences lined up with relative levels of neurodegeneration biomarkers, too: Treated mice had lower amounts of the proteins neurofilament light chain, alpha-synuclein, GFAP and Iba-1 in their brains.  “These data further support the potential of GT-02287 as a disease-modifying therapy for the treatment of [GBA1 Parkinson’s disease] that is already clinically established, including improvement in activities of daily living and cognition,” Gain’s poster read.  GT-02287 restores the function of an enzyme called glucocerebrosidase, or GCase, which is found in the lysosomes of neurons. Under normal conditions, the enzyme breaks down a lipid called glucosylceramide. But certain mutations in GCase’s encoding gene, GBA1, prevent it from functioning properly. That ultimately results in the buildup of alpha-synuclein and other inflammatory molecules, leading to Parkinson’s disease. GBA1 mutations are the most common gene variants associated with the condition.  So far, GT-02287 appears to be safe in healthy people, as data from an early phase 1 study showed in April. Gain anticipates starting a three-month phase 1b trial in 20 to 30 GBA1 Parkinson's disease patients in the second half of 2024, with a readout in the first half of 2025, according to a corporate presentation given in June. 

BETHESDA, Md., June 27, 2024 (GLOBE NEWSWIRE) -- Gain Therapeutics, Inc. (Nasdaq: GANX) (“Gain”, or the “Company”), a clinical-stage biotechnology company leading the discovery and development of the next generation of allosteric small molecule therapies, today announces the presentation of a poster at the Federation of European Neuroscience Societies (FENS) Forum 2024. The poster describes improvement in cognitive performance and activities of daily living associated with administration of GT-02287 the Company’s lead novel allosteric therapeutic candidate in a mouse model of GBA1-Parkinson's disease (GBA1-PD). FENS Forum 2024 is being held June 25–29, 2024 in Vienna, Austria. “These data further confirm our conviction that GT-02287 can slow or stop progression of Parkinson’s disease and given the cognitive decline observed in GBA1 Parkinson’s patients, we hope that we can one day deliver this drug to those that need it and help them improve their everyday life. As we are completing our Phase 1 clinical study, we look forward to evaluating this drug in patients suffering from this chronic and debilitating disease with no adequate treatment options,” commented Dr. Joanne Taylor, Senior Vice President of Research at Gain Therapeutics. “FENS Forum 2024 is an important opportunity for us to continue discussing our differentiated approach to addressing GBA1 Parkinson’s disease and further discourse and collaboration with the neuroscience community.” The poster, titled, “GT-02287, a Clinical-Stage GCase Enhancer, Improves Activities of Daily Living and Cognitive Performance in a Preclinical Model of GBA1 Parkinson’s disease,” which will be presented on-site on June 27th by Dr. Beatriz Calvo-Flores Guzman and available online the same day demonstrates how GT-02287 improves nest-building performance and motor performance in a mouse model of GBA1-PD. Nest building in rodents is a natural and spontaneous behavior that closely resembles the tasks of daily living and cognitive performance in humans. GT-02287 was administrated orally once daily from day eight in a mouse model of GBA1-PD, which utilizes a combination of α-synuclein pre-formed fibril (PFF) administration and glucocerebrosidase (GCase) activity lowering with conduritol beta epoxide (CBE). Nest-building performance was assessed by scoring the quality of the nest and motor function was tested in the wire hang test at day 28. Plasma NfL, and brain aggregated alpha-synuclein, Iba-1, and GFAP levels were also measured. The results suggest that GT-02287 can rescue deficits in complex behaviors in which cognitive function is involved in a GBA1 Parkinson’s disease model in addition to improving motor function deficits in this model as reported previously and this is reflected in appropriate biomarker changes. A PDF of the poster presented at the FENS Forum 2024 conference is available on the Science & Technology section of the Company’s website at . About FENS Forum Founded in 1998 at the first Forum of European Neuroscience, the Federation of European Neuroscience Societies (FENS) is the main organization for neuroscience in Europe. FENS currently represents 40 national and single-discipline neuroscience societies across 31 European countries and more than 22,000 member scientists. FENS promotes neuroscience research to policymakers, funding bodies and the general public, both regionally and internationally. FENS promotes excellence in neuroscience research and facilitates exchanges and networking between neuroscientists within the European Research Area and beyond. About GT-02287 Gain Therapeutics’ lead drug candidate, GT-02287, is in clinical development for the treatment of GBA1 Parkinson’s disease (GBA1-PD). The orally administered, brain-penetrant small molecule is an allosteric protein modulator that restores the function of the lysosomal protein enzyme glucocerebrosidase (GCase) which becomes misfolded and impaired due to a GBA1 gene mutation, the most common genetic abnormality associated with PD. In preclinical models of PD, GT-02287 restored GCase enzymatic function, reduced aggregated α-synuclein, neuroinflammation and neuronal death, increased dopamine levels and improved motor function and cognitive performance. Additionally, GT-02287 significantly reduced plasma neurofilament light chain (NfL) levels, an emerging biomarker for neurodegeneration. 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 – Swiss Innovation Agency. About Gain Therapeutics, Inc. Gain Therapeutics, Inc. is a clinical-stage biotechnology company leading the discovery and development of next generation allosteric therapies. Gain’s lead drug candidate GT-02287 for the treatment of GBA1 Parkinson’s disease, is currently being evaluated in a Phase 1 clinical trial. Leveraging AI-supported structural biology, proprietary algorithms, and supercomputer-powered physics-based models, the company’s Magellan™ drug discovery platform can identify novel allosteric binding sites on disease-implicated proteins, pinpointing pockets that cannot be found or drugged with current technologies. Its AI and machine-learning tools and virtual screening capabilities leverage the emerging on-demand compound libraries covering vast chemical spaces of trillions of compounds to identify and select suitable small molecule hits for experimental validation. Gain’s unique approach enables the discovery of novel, allosteric small molecule modulators that can restore or disrupt protein function. Deploying its highly advanced platform, Gain is accelerating drug discovery and unlocking novel disease-modifying treatments for untreatable or difficult-to-treat disorders including neurodegenerative diseases, rare genetic disorders and oncology. Forward Looking Statements This release contains “forward-looking statements” made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. These statements are typically preceded by words such as “believes,” “expects,” “anticipates,” “intends,” “will,” “may,” “should,” or similar expressions. These forward-looking statements reflect management’s current knowledge, assumptions, judgment and expectations regarding future performance or events. Although management believes that the expectations reflected in such statements are reasonable, they give no assurance that such expectations will prove to be correct or that those goals will be achieved, and you should be aware that actual results could differ materially from those contained in the forward-looking statements. Forward-looking statements are subject to a number of risks and uncertainties, including, but not limited to, risks associated with market conditions and the satisfaction of customary closing conditions related to the offering and uncertainties related to the offerings and the use of proceeds from the offerings. For a further description of the risks and uncertainties that could cause actual results to differ from those expressed in these forward-looking statements, as well as risks relating to the Company’s business in general, please refer to the Company’s prospectus supplement to be filed with the SEC, and the documents incorporated by reference therein, including the Company’s Form 10-K for the year ended December 31, 2023 and Form 10-Q for the quarter ended March 31, 2024. All forward-looking statements are expressly qualified in their entirety by this cautionary notice. You are cautioned not to place undue reliance on any forward-looking statements, which speak only as of the date of this release. We have no obligation, and expressly disclaim any obligation, to update, revise or correct any of the forward-looking statements, whether as a result of new information, future events or otherwise. Investor Contact: CORE IR (516) 222-2560 ir@gaintherapeutics.com Media Contacts: Russo Partners Nic Johnson and Elio Ambrosio nic.johnson@russopartnersllc.com elio.ambrosio@russopartnersllc.com (212) 845-4242

MISSISSAUGA, ON, May 29, 2023 /CNW/ - Hoffmann-La Roche Limited (Roche Canada) today announced that it has successfully completed negotiations with the pan-Canadian Pharmaceutical Alliance (pCPA) for VABYSMO® (faricimab injection), indicated for the treatment of neovascular (wet) age-related macular degeneration (AMD) and diabetic macular edema (DME),1 two of the leading causes of vision loss among Canadians.1 "Securing a letter of intent with the pCPA for VABYSMO is incredible news for patients and the vision loss community," said Larissa Moniz, Director, Research and Mission Programs, Fighting Blindness Canada. "We encourage the provinces to recognize the benefit that VABYSMO can bring to nAMD and DME patients, and prioritize public access for eligible Canadians." VABYSMO is the first treatment for wet AMD and DME in Canada that acts by targeting both VEGF-A and Ang-2, two key drivers of vascular instability that have been associated with vision-threatening retinal conditions.2,3,4,5 This unique dual MoA is made possible by Roche's antibody engineering expertise. "This milestone is a critical step towards providing access to VABYSMO for Canadians living with vision loss from nAMD and DME," said Varun Chaudhary, Chief of Ophthalmology and Professor of Surgery, Hamilton Regional Eye Institute, McMaster University. "VABYSMO has demonstrated promising results in terms of efficacy, safety and durability of effect for both these diseases, and expedited public access for Canadians in need of this treatment is of paramount importance." VABYSMO was reviewed and positively recommended by Canada's Health Technology Assessment bodies, including The Canadian Agency for Drugs and Technologies in Health (CADTH) in the fall of 2022, as well as Institut national d'excellence en santé et en services sociaux (INESSS) earlier in 2023, for the treatment of nAMD and DME. As a next step, Roche Canada is committed to continuing to work with other provincial jurisdictions to make VABYSMO available as soon as possible through public drug plans. About VABYSMO® (faricimab injection) VABYSMO is a humanized bispecific immunoglobulin G1(IgG1) antibody that acts through inhibition of both Ang-2 and vascular endothelial growth factor A (VEGF-A). By inhibiting VEGF-A, faricimab suppresses endothelial cell proliferation, neovascularization and vascular permeability. By inhibiting Ang-2, faricimab is thought to increase vascular stability and desensitize blood vessels to the effects of VEGF-A. Ang-2 levels are increased in some patients with wet AMD and DME.2 About Wet Age-Related Macular Degeneration Age-related macular degeneration (AMD) is a condition that affects the macula, the part of the eye that provides sharp, central vision needed for activities like reading, driving, recognizing faces and seeing in colour,3 and is a leading cause of vision loss among Canadians, affecting approximately 2.5 million Canadians.4 Wet, or neovascular AMD is an advanced form of the disease that can cause rapid and irreversible vision loss if left untreated5, and affects approximately 250,000 Canadians.6 Wet AMD is caused by growth of abnormal blood vessels, also referred to as choroidal neovascularization (CNV), into the macula. These vessels leak fluid and blood and cause scar tissue that destroys the central retina.7 If left untreated, this process results in a deterioration of sight over a period of months to years.8 About Diabetic Macular Edema Affecting an estimated 15.7 per cent of Canadians with diabetes, diabetic macular edema (DME) is a vision-threatening retinal condition associated with blindness and decreased quality of life when left untreated.9 DME occurs when damaged blood vessels in the retina leak into and cause swelling in the macula – the central area of the retina responsible for the sharp vision needed for reading and driving.10 The number of people with DME is expected to grow as the prevalence of diabetes increases.11 About Roche Canada Patients and science are at the heart of everything we do. At Roche, our passion for science and our commitment to relentlessly pursuing the impossible for patients has made us one of the world's leading pharmaceutical, in vitro diagnostics, and healthcare technology companies. And we're adding our expertise in new areas, such as artificial intelligence, real world data collection and analysis and collaborating with many different sectors and industries. We're an innovator across major disease areas, including oncology, infectious diseases, diabetes, ophthalmology, and diseases of the central nervous system. Roche Canada was founded in 1931 and employs more than 1,800 people across the country through its Pharmaceuticals division in Mississauga, Ontario as well as its Diagnostics and Diabetes Care divisions in Laval, Quebec. For more information, please visit , or follow Roche Canada on LinkedIn, or on Twitter @RocheCanada. SOURCE Roche Canada