GH Research PLC has announced significant clinical progress for its lead candidate GH001 (mebufotenin) across multiple psychiatric conditions, with data to be presented at upcoming scientific conferences.
The Dublin-based biopharmaceutical company will showcase results from its randomized, double-blind, placebo-controlled Phase 2b clinical trial in treatment-resistant depression (TRD) at the American Society of Clinical Psychopharmacology (ASCP) Annual Meeting in Arizona from May 27-30, 2025.
Breakthrough Results in Treatment-Resistant Depression
The Phase 2b trial (GH001-TRD-201) met its primary endpoint with a Montgomery-Åsberg Depression Rating Scale (MADRS) reduction from baseline of -15.5 points compared with placebo on Day 8 (p<0.0001). This statistically significant improvement suggests GH001's potential to transform TRD treatment.
Professor Michael E. Thase, MD, from the University of Pennsylvania's Perelman School of Medicine, who will present the data, commented: "The findings from this double-blind, placebo-controlled Phase 2b trial are truly exciting and - if replicated in larger trials - could prove to be a transformative leap in our efforts to help people with treatment-resistant depression."
He added, "In clinical research there's a hierarchy of evidence and this well-controlled trial delivers robust evidence of the treatment's efficacy and safety. These findings build on prior successes studying drugs formerly pigeonholed as 'psychedelics' and bring us closer to offering real hope to patients who have exhausted other options."
Promising Results in Postpartum Depression
GH Research will also present data from a Phase 2a proof-of-concept trial evaluating GH001 in postpartum depression. According to Dr. William Gann of Sheffield Health and Social Care NHS FT (UK), the treatment was well-tolerated with no serious adverse events reported.
Most notably, all ten participants in the postpartum depression trial achieved remission by Day 8, representing a potentially significant advancement for a condition that affects many women during what should be a joyful period.
"Postpartum depression remains a critical unmet need, often leaving women feeling isolated and overwhelmed during what should be a time of joy," Dr. Gann explained. "This proof-of-concept trial represents a new beacon of hope, offering the potential for effective treatment that could transform lives."
Efficacy in Bipolar II Depression
Further expanding GH001's potential applications, the company will present results from a Phase 2a clinical trial in patients with bipolar II disorder experiencing a major depressive episode at the International Society for Bipolar Disorders (ISBD) Annual Conference in Chiba, Japan, from September 17-19, 2025.
PD Dr. med. Philipp Ritter from the University Hospital Carl Gustav Carus in Dresden, Germany, highlighted that GH001 produced a 52% mean reduction in depressive symptoms by Day 8 in this difficult-to-treat population. The treatment was administered as a single-day individualized dosing regimen via inhalation.
"Bipolar II disorder is often more chronic in its depressive course than bipolar I disorder and remains particularly difficult to treat. Available therapies frequently require weeks before clinically meaningful antidepressant effects emerge," Dr. Ritter noted. "GH001 produced a 52% mean reduction in depressive symptoms by Day 8, suggesting both rapid onset and substantial efficacy."
Importantly, the treatment showed no signs of inducing mania, a significant concern when treating bipolar depression.
Novel Mechanism and Administration
GH001 is formulated for mebufotenin administration via a proprietary inhalation approach. This novel delivery system may offer advantages over traditional oral medications for psychiatric conditions, potentially providing faster onset of action.
The company believes that based on the observed clinical activity in the Phase 2b trial, GH001 has the potential to change how treatment-resistant depression is managed in clinical practice.
Safety Profile
Safety and tolerability data from the double-blind portion of the Phase 2b trial in TRD will be presented in a late-breaking poster at the ASCP meeting. While specific safety details were not included in the announcement, the researchers' comments suggest a favorable safety profile across the various patient populations studied.
Future Directions
These promising results across multiple psychiatric conditions position GH001 as a potential breakthrough therapy for several difficult-to-treat mood disorders. The company continues to advance its clinical program, with these upcoming scientific presentations likely to generate significant interest from the medical community.
GH Research PLC is focused on developing novel and proprietary mebufotenin therapies, with an initial emphasis on treatment-resistant depression. The company trades on the Nasdaq under the ticker symbol GHRS.
