Rexaceract

BETHESDA, Md., July 16, 2026 (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 provided the following letter to shareholders from the Company’s President and CEO, Gene Mack: To our valued Shareholders, As we progress through 2026 and look ahead to delivering continued significant progress, I want to thank you for your steadfast support of Gain Therapeutics. The year has been one of meaningful scientific progress as we achieved critical inflection points related to the clinical development of rexaceract, formerly known as GT-02287, the Company’s lead drug candidate – a disease modifying therapy for Parkinson’s disease (PD). We continue to work towards our goal of offering a potentially first-in-category therapy for people with Parkinson’s disease with or without a GBA1 genetic mutation, a therapy that could be a paradigm-shifting treatment for this therapeutic class. I believe we are well-positioned to reach this transformative milestone, not only for our Company but for patients and their families worldwide. Commitment to Advancing Rexaceract for Parkinson’s Disease Parkinson’s disease remains the second most prevalent neurodegenerative disorder after Alzheimer’s disease, yet available treatments are limited to managing symptoms rather than altering disease progression. Our immediate focus remains the clinical development of rexaceract to address this unmet need, as we endeavor to create a new backbone of therapy for Parkinson’s disease that slows or stops the progression of symptoms. The results – both from our Phase 1b study of rexaceract and open-label extension - continue to support our hypothesis for the drug candidate and its mechanism of action and we continue to observe safety and tolerability through five months of treatment. We also continue to see strong engagement in the open-label extension. All 16 participants who entered the ongoing Phase 1b extension study remained on study at Day 150, and following the most recent review on July 6, 2026, an independent Data Monitoring Committee recommended the study continue without modification. While longer term outcomes in this dosing extension are anticipated to read out in October 2026, we have already released encouraging data from Part 1 and Part 2 of the study which includes the first 90 days (3 months) administration of rexaceract, during which reduction in cerebrospinal fluid (CSF) levels of glucosylsphingosine (GluSph) in patients with elevated levels at baseline correlated with an early clinical benefit. That response is largely maintained after at least five months of administration, while the entire cohort of 16 patients can be categorized as non-progressors at both three and five months regardless of baseline characteristics. We look forward to the next updates at 270 days and 360 days, which will occur over the summer and at the conclusion of the study in October 2026. IND Authorization, INN Acceptance, and Next Steps for Rexaceract With Investigational New Drug (IND) authorization in hand, our clinical team is now working diligently to commence our Phase 2 study in people with Parkinson’s disease, which we anticipate starting in the third quarter of 2026. The FDA’s decision to authorize the IND application follows positive Phase 1 results in both healthy volunteers and people with Parkinson’s disease, in which rexaceract was well-tolerated and demonstrated both biomarker and clinical evidence of activity. Following the recent acceptance of “rexaceract” as the International Nonproprietary Name (INN) for GT-02287, all references made to GT-02287 within the program will transition to this established nonproprietary name. The planned Phase 2 study of rexaceract is expected to enroll participants with early Parkinson’s disease across sites in the United States, Australia, and Europe. Our Clinical Advisory Board, which consists of leaders in the field of movement disorders and neurodegenerative diseases, has been very active in bolstering our development efforts. In addition to our Clinical Advisory Board, we have engaged a number of experienced consultants to further support the design of our Phase 2 clinical trial. Their expertise in clinical trial methodology, regulatory affairs, biostatistics, and study operations has already informed key protocol decisions, including patient selection, endpoint development, and statistical planning. This collaborative approach is intended to strengthen the overall study design and position the program for successful execution. New Biomarkers as a Validation for Rexaceract MoA in Parkinson’s Disease The glucocerebrosidase (GCase) substrate GluSph is considered a significant biomarker for Gaucher’s disease, and an emerging biomarker for Parkinson’s disease. Recently, we observed that after 90 days of treatment with rexaceract in participants with elevated baseline levels of GluSph in CSF at baseline, GluSph decreased a marked amount - by an average of 81%. Elevated GluSph, a hallmark of GCase dysfunction, has been shown to increase the aggregation of α-synuclein as well as to impair mitochondrial function and other intracellular processes in neurons. We believe this first-ever observation following the administration of a GCase modulator to Parkinson’s disease patients is indicative of central nervous system (CNS) target engagement and increased GCase activity in the brain. Furthermore, in individuals with high levels of CSF GluSph at baseline, levels of DOPA decarboxylase (DDC) decreased following 90 days of treatment with rexaceract. DDC is responsible for converting levodopa into dopamine in the brain and is elevated in the CSF of people with Parkinson’s disease – likely due to dopaminergic neuron dysfunction. After 150 days of treatment, participants with elevated baseline GluSph demonstrated greater clinical benefit than those with low baseline levels, with a difference of 4.8 points in the sum of MDS-UPDRS Part II and III scores. Coupled with the stabilization or improvement of MDS-UPDRS scores that we have observed across the overall study population and reports of anecdotal improvements in functional areas such as gait and smell, we strongly believe we are engaging the underlying biology of the disease and seeing early signs of efficacy. GT-04686 and Pipeline Update We have also been making strides advancing a second product candidate in the pipeline, GT-04686, and recently presented preclinical evidence of its activity in both in vitro and in vivo models. Results showed an increase in GCase activity and lipid substrate depletion in patient fibroblasts harboring both mutated and wildtype GBA1, as well as restoration of motor and non-motor function in an animal model of Parkinson’s disease. GT-04686 is a structurally distinct allosteric GCase chaperone and will be the next program in our pipeline advancing towards clinical development. While GT-04686 demonstrates robust activity in Parkinson’s models of disease, we will be evaluating the candidate in other neurodegenerative disease models and, by year-end, expect to select the initial therapeutic indication for this candidate’s development. Current activities are focused on optimizing the program and generating the data necessary to support IND-enabling studies, including refinement of the target product profile, preclinical pharmacology, manufacturing readiness, and development planning. These efforts are intended to position GT-04686 for a successful transition into formal IND-enabling development and, ultimately, clinical evaluation. As we continue to advance our lead clinical candidate, rexaceract, we believe GT-04686 represents an important opportunity to expand our pipeline of GCase-targeting allosteric modulators and create additional long-term value for shareholders. Organizational update In recognition of their leadership and contributions to the Company’s progress in advancing the clinical development of rexaceract as well as expanding the company's pipeline, our Board of Directors has unanimously approved the promotion of Joanne Taylor and Terenzio Ignoni to Chief Scientific Officer and Chief Operating Officer, respectively. Dr. Joanne Taylor has over 30 years’ experience in the pharmaceutical industry. She joined Gain Therapeutics in September 2020 and has been Gain’s Senior Vice President, Research since 2022. Previously, she served as Vice President, Head of Neuroscience for Prescient Healthcare Group where she led its neuroscience business (comprising neurology, psychiatry, ophthalmology, rare diseases and pain), and supported the portfolio, clinical and regulatory strategies of a wide array of global top 25 pharmaceutical company clients. She also served as Director of External Research, Neuroscience, and previously as a senior group leader and scientist at Eisai’s London Research Laboratories and European Headquarters where she directed global teams in the discovery of novel therapeutic strategies for neurological conditions, with a particular focus on Alzheimer’s, multiple sclerosis, and Parkinson’s diseases. There she later led neuroscience portfolio reviews to identify areas of major focus and investment, as well as partnering activities with academia and biotech. Dr. Taylor received a Ph.D. in Developmental Neuroscience from King’s College and completed a postdoctoral fellowship and senior research post at the ETH in Zurich. Terenzio Ignoni joined Gain Therapeutics in June 2021 as Senior Vice President, Quality and CMC, with over 25 years in pharmaceutical development and quality leadership, and has served as Senior Vice President, Technical Operations and Development since April 2022, leading the transition of Gain Therapeutics from research to a clinical-stage company. Before Gain Therapeutics, Terenzio held the position of Vice President, Quality at Jazz Pharmaceuticals, where he led the approval process of DEFITELIO® (defibrotide sodium) in the US, Latin America, Japan, among other jurisdictions. Before Jazz, he held leadership positions at Gentium S.p.A. (integrated into Jazz Pharmaceuticals) and Zambon Group, Italy. Terenzio holds a five-year Master's-level degree in Chemistry and Pharmaceutical Technology from the University of Turin, with a Pharm.D. qualification, and is a certified EU Qualified Person (QP). Finally, we would like to thank Dr. Jonas Hannestad for his dedicated contribution to the early clinical development of rexaceract and playing an integral role in the IND filing process for rexaceract. We are grateful for Jonas’ leadership and commitment over the past two years and wish him all the best as he moves on to pursue other interests as of July 2026. Over the next several weeks we will be engaging with key opinion leaders in Parkinson’s disease, potential partners, and our broader scientific and clinical advisory boards as we finalize the design of our Phase 2 clinical program that is expected to begin during the third quarter of 2026. Capital Position As of March 31, 2026, we had approximately $16.5M in cash and cash equivalents, which we expect will fund operations into 2Q27, based on current operating plans, including the completion of the Phase 1b open-label extension in October and initiation of a Phase 2 during 3Q26. We continue to partially offset our operating burn with capital available through our ATM facility while further engaging in ongoing discussions with potential licensing partners as well as evaluating other sources of financing that can help us ensure clinical development of rexaceract remains a priority regardless of any partnering structure. Looking Ahead We are very encouraged by the observations trending from the 150-day dosing period of our Phase 1b clinical trial and believe that the neuroprotective effect demonstrated in pre-clinical models of Parkinson’s disease will translate to human participants with Parkinson’s disease. We recently had the opportunity to present to investors and stakeholders at AD/PD 2026 and the 3rd International GBA1 Meeting 2026 and the latest data were well received. We also recently met with our partners at the Michael J. Fox Foundation who are working closely with us to best contextualize, validate, and optimize our latest data and we are grateful for their continued support. With IND authorization paving the way for initiation of Phase 2 clinical development in the U.S., we are prepared to execute and unlock significant value for the rexaceract development program. We are deeply appreciative of the continued support from the Parkinson’s disease community, including scientific leaders, and, most importantly, the patients who place their trust in us as we work to address the underlying mechanisms of this disease. At Gain, we are firmly committed to making inroads for people living with Parkinson’s disease. I am continually inspired by the dedication of our team, grateful for our stakeholders, and thankful for the opportunity to pursue this mission together. We appreciate your ongoing support and look forward to keeping you informed as we continue to make progress with a potentially first-in-class therapy for Parkinson’s disease. Sincerely, Gene Mack President & Chief Executive Officer About Rexaceract Gain Therapeutics’ lead drug candidate rexaceract, formerly GT-02287, is in clinical development for the treatment of Parkinson’s disease (PD) with or without a GBA1 mutation. The orally administered, brain-penetrant small molecule is a beta-glucocerebrosidase (GCase) positive allosteric modulator, antiparkinsonian, small molecule that restores the function of the lysosomal enzyme GCase which becomes misfolded and impaired due to mutations in the GBA1 gene, the most common genetic abnormality associated with PD, or other age-related stress factors. In preclinical models of PD, rexaceract restored GCase enzymatic function, reduced endoplasmic reticulum stress, lysosomal and mitochondrial pathology, aggregated α-synuclein, neuroinflammation and neuronal death, as well as plasma neurofilament light chain (NfL) levels, a biomarker of neurodegeneration. In rodent models of both GBA1-PD and idiopathic PD, rexaceract was shown to rescue deficits in motor function and gait and prevent the development of deficits in complex behaviors such as nesting. Compelling preclinical data in models of both GBA1-PD and idiopathic PD, demonstrating a disease-modifying effect after administration of rexaceract, suggest that rexaceract may have the potential to slow or stop the progression of Parkinson’s disease. Results from a Phase 1 study of rexaceract in healthy volunteers demonstrated favorable safety and tolerability, plasma and CNS exposures in the projected therapeutic range, and target engagement with an increase in GCase activity among those receiving rexaceract at clinically relevant doses. Rexaceract is currently being evaluated in a Phase 1b clinical trial for the treatment of Parkinson’s disease with or without a GBA1 mutation. The primary endpoint of the trial, which enrolled participants across seven sites in Australia, is to evaluate the safety and tolerability of rexaceract after three months of dosing in people with Parkinson’s disease. The Phase 1b study extension allows participants to continue to be treated with rexaceract for up to a total of 12 months. Gain’s lead program in Parkinson’s disease has been awarded funding support early in its development 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, rexaceract is currently being evaluated for the treatment of Parkinson’s disease with or without a GBA1 mutation in a Phase 1b clinical trial. Rexaceract has further potential in Gaucher’s disease, dementia with Lewy bodies, and Alzheimer’s disease. Gain has multiple undisclosed preclinical assets targeting lysosomal storage disorders, metabolic diseases, and solid tumors. Gain’s unique approach enables the discovery of novel, allosteric small molecule modulators that can restore or disrupt protein function. Deploying its highly advanced Magellan™ 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 StatementsThis 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, statements regarding: the development of the Company’s current or future product candidates; expectations regarding the timing of patient enrollment and the completion and timing of results from a Phase 1b clinical study for rexaceract, including any extension studies; the timing of any submissions to the FDA or other regulatory bodies and agencies; the timing of the commencement of the Phase 2 clinical study for rexaceract; the ability for the Company to enroll patients in its planned Phase 2 clinical study for rexaceract; the Company’s ability to replicate positive results from earlier preclinical studies or clinical trials in current or future clinical trials; the Company’s expected cash runway, capital resources, liquidity and financing plans; the Company’s business development activities, strategic collaborations, licensing opportunities and financing activities; the advancement, prioritization and timing of the Company’s pipeline programs, including GT-04686; and the potential therapeutic and clinical benefits of the Company’s product candidates. 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 Form 10-K for the year ended December 31, 2025 and other filings made with the SEC. 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 because of new information, future events or otherwise. Investors:Gain Therapeutics, Inc. Apaar Jammu Manager, Investor Relations and Public Relationsajammu@gaintherapeutics.com LifeSci Advisors LLCChuck PadalaManaging Directorchuck@lifesciadvisors.com Media:Russo Partners LLC Nic Johnson and Elio Ambrosionic.johnson@russopartnersllc.comelio.ambrosio@russopartnersllc.com(760) 846-9256

帕金森病目前尚无法彻底治愈，但通过新型药物可以有效延缓疾病进展、改善症状并减少运动并发症。根据当前临床研究与药物研发进展，延缓帕金森病进展的新型药有以下几类： 一、疾病修饰治疗（DMT）新药（针对病因/病理，延缓神经退变） 1、GLP-1受体激动剂：如利司那肽（Liraglutide）、艾塞那肽（Exenatide）等。这类药物具有神经保护作用，能减轻神经炎症、保护多巴胺能神经元，在早期帕金森病中显示出延缓运动障碍进展的潜力。 2、α-突触核蛋白（α-syn）靶向药物：如普拉西珠单抗（Prasinezumab）。通过中和细胞外致病蛋白、阻断病理蛋白在脑内的传播，延缓疾病病理进展，对快速进展型早期帕金森病有延缓作用。 3、LRRK2激酶抑制剂：如BIIB122。通过抑制LRRK2激酶活性，改善帕金森病预后，防止或遏制帕金森病进展引起的运动和非运动障碍积累。 4、GBA靶向药物：如GT-02287。通过恢复葡萄糖脑苷脂酶（GCase）功能，减少聚集的α-突触核蛋白和神经元死亡，改善运动功能，延缓疾病进展。 5、Tau/α-syn聚集抑制剂：如ANLE138B。通过抑制蛋白质病理性聚集，阻止神经元退行性变，延缓疾病进展。 二、新型症状治疗药物（通过优化给药或精准调控，延缓病情恶化） 1、新型左旋多巴长效/缓释制剂：如IPX203（左旋多巴/卡比多巴长效缓释制剂）。通过24小时平稳释药，维持稳定的血药浓度，减少“开关”波动和异动症，从药代动力学层面延缓病情恶化。 2、新型多巴胺受体激动剂：如Tavapadon（选择性D1/D5受体部分激动剂）。精准调控受体活性，稳定神经传导，减少药效波动，延缓运动症状的进展，且副作用较小。 3、新型MAO-B抑制剂： 如沙芬酰胺（Safinamide）。通过抑制多巴胺降解并调节谷氨酸释放，改善运动症状并减少“关期”时间，延缓病情进展。 4、新型COMT抑制剂： 如奥匹卡朋（Opicapone）。通过延长左旋多巴的疗效并减少运动波动，延缓中晚期患者病情的恶化。 三、其他在研/前沿新型药物靶向蛋白降解剂（PROTAC）： 1、如ARV-102。通过降解LRRK2蛋白，减少神经毒性，延缓疾病进展。 2、多肽疗法：如HER-096。模拟大脑多巴胺神经营养因子（CDNF）活性，修复纹状体损伤，延缓疾病进展。 注：以上部分新型药物（如部分靶向药、长效制剂）可能仍处于临床试验阶段或刚获批上市，具体用药方案需由神经内科专业医生根据患者的具体病情、病程及耐受性进行个体化评估，切勿自行用药。 四、延缓帕金森进展的老药有： 1.单胺氧化酶B型抑制剂（MAO-B抑制剂）代表药物： 司来吉兰（Selegiline） 、雷沙吉兰（Rasagiline）。 作用机制：通过抑制单胺氧化酶B的活性，减少脑内多巴胺的代谢降解，从而增加脑内多巴胺水平，改善运动症状。 同时，这类药物具有抗氧化和神经保护机制，能减少多巴胺能神经元的氧化损伤，延缓神经退行性变，对早期或初治患者延缓疾病进展有较好效果。 2.多巴胺受体激动剂（DA）代表药物： 普拉克索（Pramipexole） 、罗匹尼罗（Ropinirole） 。 作用机制：通过直接激活多巴胺受体，模拟多巴胺作用，改善运动症状。 早期小剂量使用可延迟左旋多巴的用量，减少左旋多巴代谢产物对神经元的潜在毒性，部分药物具有神经保护作用，有助于延缓疾病进展。 3.儿茶酚-O-甲基转移酶抑制剂（COMT抑制剂）代表药物： 恩他卡朋（Entacapone）、 奥吡卡朋（Opicapone）。 作用机制：常与左旋多巴联用，通过抑制左旋多巴在外周的代谢，增加左旋多巴进入脑内的量，稳定血浆药物浓度，延长左旋多巴的疗效。 通过减少“剂末恶化”和症状波动，减轻神经负荷，从而延缓病情的快速恶化。 4.金刚烷胺（Amantadine） 作用机制：通过促进多巴胺释放并抑制其再摄取，改善少动、强直、震颤等症状，对帕金森病继发的异动症有明确的改善作用。 通过改善异动症和稳定症状，有助于优化患者整体状态，延缓因并发症导致的病情加速进展。 我帕金森多年，一直搭配服用此类药物：刚开始服（进囗的森福罗），后来换成（进口的司来吉兰）直到现。 帕金森病患者别光光的单一服用多巴类药物，应该尽早搭配延缓进展代表性的此类药物。会效果更佳，药效更长，根据我个人经验，我觉得此类药物有一定的作用。 帕金森病患者朋友们，看看你们目前所服用的药里有以上此类药物吗？欢迎大家前来评价区分享和讨论。