Gain Therapeutics Announces Positive Results in Key Exploratory Endpoint from its Phase 1b Clinical Study of GT-02287 in People with Parkinson’s Disease

Rhea-AI Summary

Gain Therapeutics (Nasdaq: GANX) announced Phase 1b data showing first-ever reduction of glucosylsphingosine (GluSph) in cerebrospinal fluid (CSF) after 90 days of dosing with GT-02287, a GCase modulator for Parkinson’s disease. The prespecified exploratory endpoint suggests CNS target engagement and increased GCase activity. The 21-participant study had 19 completers; 15 (79%) entered a nine-month extension expected to finish in September 2026. GT-02287 was generally well tolerated and the DMC recommended continuation. A virtual KOL webinar is scheduled for Jan 6, 2026.

Positive

• First-ever GluSph reduction in CSF observed
• Study enrolled 21 participants; 19 completed 90 days
• 79% (15) continued into nine-month extension
• DMC recommended study continue with no changes
• Company has funding through Phase 1b extension and year-end 2026

Negative

• Small cohort size: only 21 participants enrolled
• No randomized clinical efficacy on MDS‑UPDRS reported yet
• Primary clinical durability and long-term benefit not yet demonstrated; extension ends Sept 2026

Key Figures

Phase 1b participants 21 participants GT-02287 Phase 1b Parkinson’s study enrollment

Completed 90-day dosing 19 participants Participants completing Part 1 (90 days) of Phase 1b

Extension continuation rate 15 participants (79%) Chose to continue in nine-month Phase 1b extension

Initial dosing period 90 days Duration of Phase 1b Part 1 dosing with GT-02287

Extension duration nine-month extension Phase 1b Part 2 treatment period

Extension end target September 2026 Anticipated conclusion of Phase 1b extension

KOL event date January 6, 2026 at 10:00 a.m. ET Planned virtual KOL webinar on GT-02287 data

Runway guidance Through year-end 2026 Management statement on funding operations timing

Market Reality Check

$3.08 Last Close

Volume Volume 1,246,675 is close to the 20-day average of 1,268,563 (relative volume 0.98). normal

Technical Price $4.05 is trading above the 200-day MA of $2.03 and within 6.68% of the 52-week high.

Peers on Argus

GANX gained 4.92% with mixed peer moves: APLT (+2.74%), CAMP (+4.7%), ALXO (+0.69%) up, while INKT (-1.68%) and MNOV (-0.68%) fell, suggesting a stock-specific reaction.

Common Catalyst Same-day peer headlines feature a CAMP4–GSK RNA collaboration and MNOV trial enrollment completion, pointing to ongoing clinical and partnership activity across neuro/biotech names.

Historical Context

Date	Event	Sentiment	Move	Catalyst
Nov 20	Preclinical data	Positive	+3.6%	Preclinical GT-02287 mitochondrial and neuronal benefit data at Neuroscience 2025.
Nov 12	Earnings & update	Positive	+10.1%	Q3 2025 results plus Phase 1b enrollment completion and initial PD clinical data.
Oct 30	Conference preview	Positive	-3.3%	Announcement of upcoming Neuroscience 2025 poster on GT-02287 mechanism.
Oct 16	Conference attendance	Positive	-3.2%	Participation in Maxim Growth Summit panel on neurodegenerative disease innovators.
Oct 09	KOL event	Positive	+0.5%	Virtual KOL event reviewing GT-02287 biomarkers and early Phase 1b data.

Pattern Detected

GANX has often reacted positively to GT-02287 data and corporate updates, but several clinical and conference milestones have seen negative or muted moves, indicating inconsistent trading responses to similar news.

Recent Company History

Over the last eight months, GANX has steadily highlighted progress for GT-02287 in Parkinson’s disease. Clinical updates included full Phase 1b enrollment and early MDS‑UPDRS stabilization, with Australian approval for up to 12 months of dosing. Preclinical posters at Neuroscience 2025 and other conferences emphasized mitochondrial and lysosomal benefits, while Q3 2025-11-12 earnings detailed cash levels and a public offering. Today’s Phase 1b biomarker readout, showing reduced GluSph in CSF, builds directly on these earlier safety and mechanism data.

Regulatory & Risk Context

Active S-3 Shelf Registration 2025-11-07

$100,000,000 registered capacity

An effective mixed shelf on Form S-3/A filed 2025-11-07 registers up to $100,000,000 of various securities for potential future issuance, providing flexibility to raise capital for working capital and general corporate purposes as development of GT-02287 advances.

Market Pulse Summary

The stock dropped -44.4% in the session following this news. A negative reaction despite encouraging CSF biomarker data would fit GANX’s history of occasional selloffs on positive clinical updates. Traders may focus on financing needs and the $100,000,000 shelf capacity rather than early-phase signals. Past patterns suggest that enthusiasm around GT-02287 has been uneven, so setbacks could reflect concern over future dilution rather than the specific Phase 1b results.

Key Terms

glucosylsphingosine (Glusph) medical

"reduction in GCase substrate glucosylsphingosine (GluSph) in cerebrospinal fluid"

A small molecule found in blood and other tissues that increases when the body cannot properly break down certain fats; clinicians and researchers measure it as a biological marker of disease activity. For investors it matters because changes in this marker can show whether a drug or treatment is working, help speed diagnosis, guide regulatory decisions, and influence the commercial value of therapies — like a car’s check‑engine light signaling when repairs or improvements make a real difference.

cerebrospinal fluid (CSF) medical

"GluSph in CSF, a first-ever observation following the administration"

Cerebrospinal fluid (CSF) is a clear liquid that surrounds and cushions the brain and spinal cord, providing protection and helping to remove waste. Although it is a medical term, in a financial context, understanding how resources and support flow within a system can be similar to how CSF circulates and maintains the health of the nervous system. Recognizing such fundamental processes can offer insights into the stability and resilience of broader systems, including financial markets.

glucocerebrosidase (GCase) medical

"reduction in glucocerebrosidase (GCase) substrate in cerebrospinal fluid"

Glucocerebrosidase (GCase) is a naturally occurring enzyme that helps cells break down a specific fatty molecule inside their internal “recycling centers”; if GCase activity is low, that fat can accumulate and harm cells. Investors pay attention because genetic changes or reduced GCase function are linked to certain inherited and neurodegenerative diseases, so therapies, tests or trial results targeting GCase can strongly influence biotech valuations and clinical outlooks.

alpha synuclein medical

"Elevated GluSph, a hallmark of GCase dysfunction, has been shown to increase the aggregation of alpha synuclein"

A protein found in brain cells that can misfold and clump together, damaging the cells’ ability to work properly; these clumps are a hallmark of several neurodegenerative diseases. Investors pay attention because measuring or targeting this protein is a major path for new diagnostics and treatments, and progress or setbacks in that research can strongly affect the value and risk of companies developing related drugs — similar to how fixing a key engine part can make or break an automaker’s prospects.

mitochondrial function medical

"has been shown to increase the aggregation of alpha synuclein and to impair mitochondrial function"

Mitochondrial function describes how well mitochondria — the cell’s tiny power plants — produce energy and keep cells healthy. Investors watch it because many drugs, diagnostics and safety tests target or rely on healthy mitochondria; changes in mitochondrial function can signal a treatment’s effectiveness, side effects, or a new market opportunity in diseases tied to energy failure. Think of it as a company’s engine performance indicator for biological systems.

data monitoring committee (DMC) medical

"The data monitoring committee (DMC) has recommended that the Phase 1b study continue"

An independent panel of medical and statistical experts that watches over the safety and reliability of a clinical trial while it’s running. Like a referee who can recommend changes or stop the trial to protect participants or preserve trustworthy results, its findings and decisions matter to investors because they can change the odds, timing and regulatory path for a drug or device, directly affecting a company’s value.

MDS-UPDRS scores medical

"observing the effect of GT-02287 treatment on MDS-UPDRS scores in the participants"

The MDS‑UPDRS scores come from a standardized clinical scale (Movement Disorder Society–Unified Parkinson’s Disease Rating Scale) used to measure the severity and progression of Parkinson’s symptoms, including movement, daily function, and treatment effects. For investors, changes in these scores in clinical trials act like a ruler showing whether a drug or device meaningfully improves patients’ lives; larger, sustained score improvements are strong evidence of potential clinical benefit and regulatory or market value.

Phase 1b medical

"Importantly, the change observed in GluSph in CSF was a prespecified exploratory endpoint of this Phase 1b study"

"Phase 1b" is an early stage in testing a new medical treatment or vaccine, where it is given to a small group of people to evaluate its safety and determine the right dose. For investors, this phase signals progress in development, indicating the treatment is advancing through initial safety checks, which can influence expectations for future success and potential market impact.

AI-generated analysis. Not financial advice.

Results showed CNS target engagement with reduction in GCase substrate glucosylsphingosine (GluSph) in cerebrospinal fluid (CSF), a prespecified endpoint

The reduction in GluSph in CSF, a first-ever observation following the administration of a GCase modulator to PD patients, suggests increased GCase activity in the brain, which is expected to impact the progression of Parkinson’s disease (PD)

KOL event planned for early January to discuss the results; registration information herein

BETHESDA, Md., Dec. 18, 2025 (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 evidence, for the first time in Parkinson’s Disease (PD), of a reduction in glucocerebrosidase (GCase) substrate in cerebrospinal fluid (CSF).

Decreased GluSph in CSF is an indication of increased GCase activity in the brain

All individuals with elevated levels of glucosylsphingosine (GluSph) in the CSF displayed large decreases back towards levels observed in healthy individuals after 90 days of treatment with GT-02287. Importantly, the change observed in GluSph in CSF was a prespecified exploratory endpoint of this Phase 1b study. Elevated GluSph, a hallmark of GCase dysfunction, has been shown to increase the aggregation of alpha synuclein and to impair mitochondrial function and other intracellular processes in neurons.

Gene Mack, president and CEO of Gain Therapeutics, commented on the results, stating, “We are excited by the unfolding biomarker evidence of GT-02287 activity and central nervous system target engagement. To our knowledge, GT-02287 is the first GCase modulator to demonstrate a reduction of GluSph in CSF in people with PD, providing downstream evidence of GCase enhancement in the brain. Further, we believe that reduction in brain GluSph levels will have a direct impact on neuronal health and translate to clinically observable improvements.”

Mr. Mack continued, “With a capital position sufficient to fund operations through the end of the Phase 1b extension and year-end 2026, we look forward to presenting longer follow-up from the study at the AD/PD™ conference in March 2026, observing the effect of GT-02287 treatment on MDS-UPDRS scores in the participants who continued in the nine-month extension, and determining the durability of some of the anecdotal signs of early functional improvement.”

GT-02287 Phase 1b Study

Part 1 (90 days of dosing) of the ongoing Phase 1b study has concluded. The Phase 1b study enrolled 21 participants; 19 completed the 90-day dosing period, and 15 (79%) chose to continue in the nine-month extension (Part 2) portion of the study that is anticipated to conclude in September 2026.

Consistent with the initial Phase 1b data presented at the International Congress of Parkinson’s Disease and Movement Disorders in October 2025, GT-02287 continues to be generally well-tolerated over 90 days of dosing at plasma exposures within the projected therapeutic range. The data monitoring committee (DMC) has recommended that the Phase 1b study continue with no changes.

Upcoming Virtual KOL Event on GT-02287

Gain Therapeutics will host a webinar “Understanding GCase Substrates in Parkinson’s Disease: Perspectives on Biomarkers and Disease Modification, Contextualizing emerging biomarker data from the Phase 1b clinical study of GT-02287”, featuring key opinion leaders Roy Alcalay, M.D., M.Sc., and Peter Lansbury, Ph.D., on Tuesday, January 6, 2026 at 10:00 a.m. ET to discuss the results announced today and host a question-and-answer session. Additional details about the event will be issued closer to the event in a separate press release. To register, please click here.

About GT-02287
Gain Therapeutics’ lead drug candidate, 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 an allosteric enzyme modulator that restores the function of the lysosomal enzyme glucocerebrosidase (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, GT-02287 restored GCase enzymatic function, reduced ER 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, GT-02287 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 GT-02287, suggest that GT-02287 may have the potential to slow or stop the progression of Parkinson’s disease.

Results from a Phase 1 study of GT-02287 in healthy volunteers demonstrated favorable safety and tolerability, plasma and CNS exposures in the projected therapeutic range, and target engagement with an increase in glucocerebrosidase (GCase) activity among those receiving GT-02287 at clinically relevant doses.

GT-02287 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 GT-02287 after three months of dosing in people with Parkinson’s disease. The recently commenced Phase 1b study extension allows participants to continue to be treated with GT-02287 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, GT-02287 is currently being evaluated for the treatment of Parkinson’s disease with or without a GBA1 mutation in a Phase 1b clinical trial. GT-02287 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 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, statements regarding: the development of the Company’s current or future product candidates including GT-02287; expectations regarding the completion and timing of results from a Phase 1b clinical study for GT-02287, including any extension studies; expectations regarding the timing of patient enrollment for a Phase 1b clinical study for GT-02287, including any extension studies; the timing of any submissions to the FDA or other regulatory bodies and agencies; 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, 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 because of new information, future events or otherwise.

Investors:
Gain Therapeutics, Inc. 
Apaar Jammu 
Manager, Investor Relations and Public Relations
ajammu@gaintherapeutics.com

LifeSci Advisors LLC
Chuck Padala
Managing Director
chuck@lifesciadvisors.com

Media:
Russo Partners LLC
Nic Johnson and Elio Ambrosio
nic.johnson@russopartnersllc.com
elio.ambrosio@russopartnersllc.com
(760) 846-9256

FAQ

What evidence did Gain Therapeutics (GANX) report on December 18, 2025 for GT-02287?

They reported a prespecified exploratory reduction in CSF GluSph after 90 days, indicating CNS target engagement.

How many participants completed the 90-day Phase 1b study of GT-02287 (GANX)?

19 of 21 participants completed the 90-day dosing period.

What proportion of GT-02287 Phase 1b participants continued into the extension for GANX?

15 participants, equal to 79%, elected to continue into the nine-month extension.

When will GANX's GT-02287 Phase 1b extension conclude and when is the KOL webinar?

The extension is anticipated to conclude in September 2026; the KOL webinar is on January 6, 2026 at 10:00 a.m. ET.

Did Gain Therapeutics report safety findings for GT-02287 in the Phase 1b study?

Yes; GT-02287 was reported to be generally well tolerated over 90 days at projected therapeutic plasma exposures.

Does the December 18, 2025 announcement show clinical benefit on Parkinson’s symptoms for GANX?

No definitive clinical benefit on MDS‑UPDRS was reported; durability and symptomatic effects will be evaluated in the extension.