Material Event (Form 8-K)

Item 8.01. Other Events.

On October 1, 2026, Gain Therapeutics, Inc. (the "Company") issued a press release announcing the presentation of a poster at the International Congress of Parkinson's Disease and Movement Disorders, being held October 4-8, 2026, in Seoul, Korea. The poster outlines long-term open-label extension ("OLE") data from the Phase 1b clinical study of rexaceract showing stabilization of Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale ("MDS-UPDRS") scores over 360 days (12 months) of dosing, supporting the disease-modifying potential in Parkinson's disease ("PD"). The data, which includes safety, tolerability, and clinical scores from the Phase 1b nine-month study extension support continued development of rexaceract for PD.

As of August 31, 2026, 12 of the 13 evaluable patients have completed the full 12-month administration of rexaceract in the open-label extension, with one additional participant scheduled to complete dosing in November 2026. In the 12 evaluable participants, MDS-UPDRS motor scores were stable over the 12-month study period with rexaceract, demonstrating no clinically meaningful progression of motor symptoms on the MDS-UPDRS Parts II and III. A clinically meaningful change in PD disease progression is generally accepted to be an increase in MDS-UPDRS Part II and III together of approximately 6 points over a year, which also is the mean annual rate of disease progression among individuals with early PD. Part II of the MDS-UPDRS is patient-reported motor aspects of experiences of daily living and assesses the impact of PD on activities such as eating, dressing, walking, and other everyday functions. Part III is a clinician-assessed motor examination, evaluating features such as tremor, rigidity, bradykinesia, speech, gait, and postural stability.

The Company expects to submit a new Phase 2 study protocol to the U.S. Food and Drug Administration (the "FDA") in the coming weeks, informed by insights provided by the Phase 1b study results and recent discussion with potential partners, and initiate the Phase 2 clinical trial of rexaceract in people with Parkinson's disease in the first quarter of 2027.

Additionally, participants with both high and low baseline levels of the glucocerebrosidase ("GCase") substrate glucosylsphingosine ("GluSph") in cerebrospinal fluid ("CSF") show stabilization of MDS-UPDRS motor scores after 12 months and no clinically meaningful progression of motor symptoms observed on the MDS-UPDRS Parts II and III. Though participants with high baseline levels of CSF GluSph experienced a large decrease back towards levels observed in healthy individuals after 90 days of treatment along with a quicker observed response to rexaceract, both groups' MDS-UPDRS scores remained stable to baseline through 12 months of dosing.

Elevated GluSph is a hallmark of GCase dysfunction and has been shown to increase the aggregation of alpha synuclein and to impair mitochondrial function and other intracellular processes in neurons. A reduction in GluSph in CSF after treatment with rexaceract suggests increased GCase activity in the brain, which is expected to impact the progression of Parkinson's disease.

Preliminary long-term data suggest that rexaceract is safe and generally well tolerated over 12 months of dosing. No new safety signals were observed and overall, a lower incidence of treatment-emergent adverse events occurred in Part 2 of the study (nine-month open-label extension) compared with Part 1 (initial three-month administration).

Results from a Phase 1 study of rexaceract in healthy volunteers demonstrated favorable safety and tolerability, plasma and central nervous system ("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 PD 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 PD. The Phase 1b study extension allowed participants to continue to be treated with rexaceract for up to a total of 12 months.