GAIN THERAPEUTICS'

GAIN THERAPEUTICS' CEO MATTHIAS ALDER ISSUES LETTER TO SHAREHOLDERS

AND PROVIDES OPERATIONAL UPDATE

BETHESDA, Md., Jan. 31, 2024 (GLOBE NEWSWIRE) -- Gain Therapeutics,

Inc. (Nasdaq: GANX) ("Gain," or the "Company"), a biotechnology company leading the discovery and development

of allosteric small molecule therapies, today releases the following letter to stockholders from its President and Chief Executive Officer

Dear Fellow Stockholders,

With the start of a new year, I want to take a moment to reflect on

Gain's progress over the last 12 months and to share our strategy and plans for 2024.

Research and development of pharmaceutical products for the treatment

of neurodegenerative diseases has seen tremendous progress in recent years, with the approval of new drugs for the treatment of Alzheimer's

disease, multiple sclerosis and ALS. The pharmaceutical industry is taking note as evidenced by the recent acquisition of Cerevel Therapeutics

for $8.7 billion by AbbVie, and the acquisition of preclinical-stage Caraway Therapeutics by Merck with an announced deal value of $610

In Parkinson's disease, the second most common neurodegenerative

disease after Alzheimer's disease, new insights into the root cause of the disease have led to a number of drug candidates advancing

in clinical development, but there are no approved therapies available to patients that can slow or stop the progression of the disease.

At Gain, we seek to address this high unmet medical need with our clinical-stage lead drug candidate GT-02287, which we believe has disease-modifying

potential for the treatment of Parkinson's disease and other neurodegenerative diseases.

Successful Transition to a Clinical-Stage Biotech Company

In 2023, we advanced GT-02287 through preclinical development and initiated

the company's first clinical trial in September 2023 on time and on plan. The Phase 1 clinical trial is a single center, randomized,

double-blind, placebo-controlled, single-ascending dose (SAD) and multiple-ascending dose (MAD) study to evaluate the safety and tolerability

of GT-02287 administered orally in healthy adults. The dose escalation of the SAD phase is underway, and the MAD phase of the study is

expected to begin in Q1 2024. The SAD/MAD part of the Phase 1 clinical trial is expected to be completed by mid-2024 with results expected

to be reported in the second half of the year.

In Q3 2024, we plan to start treatment of a cohort of 12-15 Parkinson's

patients as an extension of the ongoing Phase 1 clinical trial to establish a biomarker-based clinical proof of concept, replicating the

effects of GT-02287 on biomarkers we have observed in our preclinical in vivo studies. We expect data from this study to be achieved in

late 2024 or early 2025 ahead of starting a Phase 2 clinical trial in the first half of 2025.

Cutting-Edge Science and Best-in-Class Preclinical Data Package

In 2023, we made several data presentations of results of our

GBA1 program in preclinical models of Parkinson's disease and Alzheimer's disease. For example, we presented new data

demonstrating a reduction of the plasma neurodegeneration biomarker NfL after administration of GT-02287 in a GBA1 Parkinson's

disease model at the International Congress of Parkinson's Disease and Movement Disorders last August. NfL is an emerging

biomarker of neurodegeneration that was recently accepted by the FDA as a surrogate endpoint in the agency's accelerated

approval of a drug for the treatment of certain ALS patients. In that same preclinical model, GT-02287 also restored

-glucocerebrosidase (GCase) enzymatic function, reduced aggregated -synuclein, neuroinflammation and neuronal death,

increased dopamine levels and improved motor function.

We presented additional data on our allosteric GCase modulators at

the March 2023 International Conference on Alzheimer's and Parkinson's Diseases. In that poster presentation, we showed results

that we believe support the disease-modifying potential of allosteric GCase regulators for the treatment of Alzheimer's disease.

Finally, we presented results of a preclinical model that we believe support the disease-modifying potential of a GCase-targeting small

molecule for neuronopathic Gaucher disease at last year's 19th Annual WORLDSymposium. The data generated in an animal model

of neuronopathic Gaucher disease show that GT-02329 restores GCase activity, depletes accumulation of toxic lipid substrates, reduces

neuroinflammation, and improves neuromuscular function.

Additionally, we published data in PLOS ONE on our allosteric small

molecule modulators of the GLB1 enzyme showing significantly restored -Gal function and reduced intracellular toxic substrates as

part of our program for GM1 gangliosidosis. These results were generated in collaboration with the Institute for Research in Biomedicine

in Bellinzona, Switzerland.

In 2024, we expect to present further data on GT-02287 from preclinical

models at scientific conferences, starting with the 20th Annual WORLDSymposium being held February 4-9, 2024, in San Diego, CA.

At that conference, we will present new in vitro and in vivo data that were accepted as a late-breaker abstract titled, "GT-02287,

a clinical stage GCase enhancer, displays neuroprotection and restores motor function in preclinical models of Parkinson's disease

following delayed administration." In addition, the abstract was selected for an oral presentation at the conference on February

Based on the preclinical data we have generated with GT-02287 across

numerous in vitro and in vivo models of Parkinson's disease, we believe that GT-02287 has a best-in-class preclinical profile with

evidence of improving the entire disease cascade caused by GCase dysfunction and offering the potential to slow or even stop the progression

of this devastating neurodegenerative disease.

During the course of 2023, we significantly upgraded our computational

drug discovery platform. The platform now provides for an integrated, efficient workflow of existing and newly added tools and programming

technologies that enable the identification of new binding sites on proteins and screening of the 50+ billion chemical spaces that have

become available through providers like Enamine. Over the last 18 months, we also expanded the application of the platform beyond its

original focus of enhancing and restoring enzyme function to new modalities that disrupt the function of target proteins.

Based on the added capabilities and expanded application, we feel

that the original platform name SEE-Tx (Site-specific Enzyme Enhancement Therapy) no longer adequately represents our platform

technology. Magellan, the name of our next-generation platform, reflects its enhanced capabilities that enable the exploration of

new protein biology and a vast chemical space to discover new allosteric small molecule therapies. Based on the unique combination

of physics-based models and integrated AI/ML-enhanced virtual screening capabilities, we believe Magellan is highly differentiated

in the field of computational drug discovery platforms and positions us to continue building our own pipeline of potential

first-in-class drug candidates. In addition, we are excited about the prospect of deploying Magellan in drug discovery

collaborations with academic institutions, biotechnology companies, CROs, and pharma companies, and will provide updates on our

progress in these efforts throughout 2024.

Cash Runway into 2025

In late November 2023, we completed a CMPO/PIPE financing that raised

gross proceeds of $10.1 million. Based on our operational plans, we are now positioned to fund our operations into 2025, which we expect

will enable the achievement of a biomarker-based clinical proof of concept of GT-02287 in the previously mentioned Phase 1 patient cohort.

In addition, we received grants totaling approximately $3.4 million during the year to fund R&D activities for our pipeline programs.

In 2024, we plan to continue tapping into grant opportunities to provide non-dilutive funding for our pipeline programs.

Strategic Partnering and Business Development

In 2023, we continued our active engagement with potential industry

partners for our pipeline programs and platform technology. Following the J.P. Morgan Healthcare conference in early January, I am optimistic

about our strategic partnering efforts, and we will continue to pursue opportunities for one or more of our R&D assets, whether for

our lead drug candidate GT-02287, our earlier pipeline programs, or the Magellan platform or a combination thereof. We believe that potential

transactions for any of our assets could provide significant non-dilutive funding and/or increase the inherent value of Gain by advancing

partnered programs through value inflection points.

Organizational Development

With the transition from a discovery and research-stage company to

a clinical-stage biotech company, we are continuously evaluating the organization and adding new skills required to achieve our goals

in the next 2-3 years while maintaining our focus on prudent cash management. Our new status as a clinical company has necessitated the

search for a Chief Medical Officer who will be charged with advancing the development of the clinical strategy for GT-02287 and leading

the clinical development team and related functions at Gain. We look forward to updating you once we have secured the appropriate candidate.

Also, individual career objectives can lead to changes in organizations. Unfortunately, we are saying goodbye to Dr. Xavi Barril, our

current Chief Technology Officer, who has been instrumental in guiding the evolution of our computational drug discovery platform. Xavi

is leaving the world of academia as a professor at the University of Barcelona and his part-time engagement with Gain to join a major

pharmaceutical company. As we wish him luck, the Magellan platform remains in good hands with an experienced team led by Dr. Elena Cubero,

who has been working with Xavi and the platform over the last 10 years.

In 2024, we expect to achieve a series of important value inflection

points with Gain, which are summarized below:

I look forward to updating you as we progress Gain's business

and programs throughout this year and thank you for your continued support along the way to providing new treatments for debilitating

neurodegenerative diseases.