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