Gilgamesh Pharma Announces Positive Topline Phase 2a Results for Blixeprodil (GM-1020) in Major Depressive Disorder

Blixeprodil, a novel, oral NMDA receptor antagonist, demonstrated rapid, robust, and durable antidepressant effects in Major Depressive Disorder

• Rapid and robust antidepressant efficacy demonstrated by a 6.3-point greater reduction in MADRS vs. placebo 24 hours after a single oral dose of blixeprodil
• Following twice weekly dosing over a 2-week period, the therapeutic benefit was durable through 28 days of follow-up without further treatment
• Safe and well-tolerated

NEW YORK, Jan. 6, 2026 /PRNewswire/ -- Gilgamesh Pharma, a clinical-stage neuroscience company focused on transforming psychiatric treatment, today announced positive topline results from its Phase 2a study of blixeprodil (GM-1020). Blixeprodil, a first-in-class oral N-methyl-D-aspartate (NMDA) receptor antagonist, demonstrated rapid, robust, and durable antidepressant effects in patients with moderate-to-severe Major Depressive Disorder (MDD).

This proof-of-concept study included 46 MDD patients in two parts. Part A was a randomized, double-blind, placebo-controlled, single-dose, cross-over study of blixeprodil 140 mg. Part B was a blinded, randomized, multiple-dose extension period of blixeprodil 140 vs. 210 mg, twice per week for 2 weeks. After conclusion of dosing in Part B, all subjects were followed for an additional 28 days.

In Part A, blixeprodil demonstrated a clinically meaningful and statistically significant reduction in the Montgomery-Åsberg Depression Rating Scale (MADRS) total score as compared to placebo at 24 hours post-dose (least-squares mean difference = -6.3; p = 0.006, effect size = 0.85), and also a clinically meaningful reduction at Day 8 (least-squares difference = -5.1; p = 0.076, effect size = 0.55). Due to large residual effect after the first dose, which carried over into the second dosing period, the efficacy analysis was limited to the first dosing period, as was pre-specified in the analysis plan.

In Part B, blixeprodil demonstrated further improvement with both the 140 and 210 mg doses. No significant differences were observed between doses. The remission rate for the combined arms was 53% at the end of Part B (Day 42), and the effect was durable during the 28-day follow-up without further treatment. These findings suggest blixeprodil has a robust and durable antidepressant effect. 

Both doses were found to be safe and well-tolerated with no SAEs and no TEAEs leading to discontinuation of treatment, including limited blood pressure increases, dissociation, and sedation. Given blixeprodil's safety profile and oral route of administration, Gilgamesh intends to pursue at-home use.

"These Phase 2a study results represent a significant milestone in our journey to transform the treatment of MDD. Blixeprodil's compelling efficacy and enhanced safety differentiate it from existing options. We are excited to advance the only novel oral NMDA receptor antagonist in clinical development into late-stage studies, where we will optimize our dosing strategy to maximize both clinical benefit and patient experience," said Jonathan Sporn, MD, CEO and Co-Founder of Gilgamesh Pharma.

"The data from this study are particularly compelling as blixeprodil demonstrates both impressive efficacy and a favorable safety profile," said Dr. Gerard Sanacora, MD, PhD, Director of the Yale Depression Research Program at Yale University School of Medicine and member of the Gilgamesh Scientific Advisory Board. "The potential for at-home administration represents a significant advancement that could dramatically improve accessibility for patients with major depression who currently face limited options for rapid-acting treatments."

Jorge A Quiroz, MD, the Chief Development and Strategy Officer of Gilgamesh Pharma, will present these results in January 2026 at the American College of Neuropsychopharmacology (ACNP) Conference.

About Blixeprodil (GM-1020): Blixeprodil is a first-in-class, orally bioavailable NMDA receptor antagonist that combines a rapid onset of action and robust efficacy with oral dosing and a favorable tolerability profile. It is currently being investigated for the treatment of MDD. Blixeprodil is a new chemical entity with issued composition of matter IP.

About Major Depressive Disorder: More than 20 million people in the U.S. suffer from MDD. Up to two-thirds of patients do not achieve remission after multiple antidepressants, each of which can take weeks to show efficacy and often cause significant side effects, including weight gain, sexual dysfunction, and flattened affect. There is an urgent need for rapid-acting, durable, effective, and well-tolerated treatments.

About Gilgamesh Pharma: Gilgamesh Pharma is a clinical-stage neuroscience company developing innovative new chemical entities to transform psychiatric care. Following the October 2025 sale of Gilgamesh Pharmaceuticals and its lead asset bretisilocin to AbbVie for up to $1.2B, Gilgamesh Pharma launched with over $100M in funding to advance its portfolio of rapid-acting, durable psychiatric therapeutics not acquired in the transaction. The company's lead program, blixeprodil, is an oral NMDA receptor antagonist entering late-stage development in 2026, designed to deliver rapid and sustained relief from depression symptoms with minimal side effects. Gilgamesh's pipeline is focused on creating treatments that move beyond symptom management toward therapies that offer meaningful and lasting improvements in patient outcomes. Learn more about the company's therapeutic pipeline at https://www.gilgameshpharmaceutical.com/. Follow Gilgamesh Pharma on LinkedIn and X.

Media Contact: [email protected]

Investor Contact: [email protected] 

SOURCE Gilgamesh Pharma