Slide 1: Safety and Efficacy of GH001 in Treatment-Resistant Depression: Phase 2b Results
Safety and Efficacy of GH001 in Treatment-Resistant Depression: Results From a Phase 2b, Double-Blind, Randomized Controlled Trial Michael E. Thase, MD Department of Psychiatry, University of Pennsylvania, and Corporal Michael J. Crescenz Veterans Affairs Medical Center, Philadelphia, PA Coauthors:
Slide 2: Author Disclosures (1 of 2)
Author Disclosures Michael E. Thase Grants – Acadia, Alkermes, Axsome, Intra-Cellular Therapies, Janssen, National Institute of Mental Health, Otsuka, Patient-Centered Outcomes Research Institute (PCORI), and Takeda. Advisory Boards – Autobahn Therapeutics, Axsome, Clexio Biosciences, Gerson Lehrman
Slide 3: Author Disclosures (2 of 2)
Author Disclosures Tomáš Páleníček Principal investigator – Compass, GH Research, MAPS, and Ketabon. Shares – Psychedelická klinika s.r.o., Společnost pro podporu neurovědního výzkumu s.r.o., and AVI-X Aviation Experts s.r.o. Founder – PSYRES (Psychedelic Research Foundation). Consultant – CB21 Phar
Slide 4: Background
4 Background TRD affects approximately 30% of patients treated for MDD1 Current therapies for TRD are limited and there is a large unmet need for treatments that offer rapid and sustained effects Mebufotenin (5-methoxy-N,N-dimethyltryptamine [5-MeO-DMT]) is a non-selective serotonin (5-HT) agonist w
Slide 5: Eligibility Criteria
5 Eligibility Criteria aCurrent MDE confirmed by the MINI. DSM-5 = Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition; HAM-D-17 = 17-Item Hamilton Depression Rating Scale; MDD = Major depressive disorder; MDE = Major depressive episode; MGH-ATRQ = Massachusetts General Hospital Ant
Slide 6: Trial Schematic
For re-treatment (up to five GH001 IDRs), the patient must have met one of the following criteria: MADRS score >18 MADRS score >10 and ≤18 and MADRS score ≤10 not observed at Day 8 of the prior treatment or at any visit since MADRS score >10 and ≤18 and MADRS score >18 observed since the most recent
Slide 7: Patient Disposition and Characteristics in the Double-Blind Part
7 Patient Disposition and Characteristics in the Double-Blind Part aUp to three doses of GH001 or placebo were administered to each patient. bIncludes all patients who received respective dose of GH001 or placebo, irrespective of total dose. BMI = Body mass index; HAM-D-17 = 17-Item Hamilton Depress
Slide 8: Primary Endpoint: GH001 Led to Mean MADRS Reduction of −15.5 on Day 8 vs Placebo
Primary Endpointa: GH001 Led to Mean MADRS Reduction From Baseline of −15.5 on Day 8 vs Placebo LS mean difference vs placebo: −15.5 (P<0.0001) Effect size: Cohen’s d = −2.0 LS Mean (±SE) Change From Baseline in MADRS Total Score aFDA Guidance notes that efficacy with rapid-acting antidepressants ge
Slide 9: Secondary Endpoints: 57.5% Remission Rate and 60.0% Response Rate at Day 8
9 Secondary Endpoints: GH001 Led to 57.5% Remission Rate and 60.0% Response Rate at Day 8 vs 0% With Placebo MADRS = Montgomery-Åsberg Depression Rating Scale; NNT = Number needed to treat. ****P<0.0001 Remission: MADRS total score ≤10 | Response: ≥50% reduction from baseline in MADRS total score 2
Slide 10: Secondary Endpoints: Improvements in Anxiety and Quality of Life vs Placebo
10 Secondary Endpoints: GH001 Led to Improvements in Anxiety and Quality of Life vs Placebo at Day 8 HAM-A Total Score Q-LES-Q-SF Total Score HAM-A = Hamilton Anxiety Rating Scale; LS = Least squares; Q-LES-Q-SF = Quality of Life Enjoyment and Satisfaction Questionnaire – Short Form. GH001 (n=40) Pl
Slide 11: Improvement in Global Illness Severity From Baseline at Day 8
11 More Patients Had Improvement in Global Illness Severity From Baseline at Day 8 With GH001 vs Placebo Percentage of Patients in Each CGI-S Category at Day 8 Percentages are for each baseline category within treatment. CGI-S = Clinical Global Impression – Severity; LS = Least squares; SE = Standar
Slide 12: Overview of Adverse Events in the Double-Blind Part
12 Overview of Adverse Events in the Double-Blind Part TEAEs were classified according to the Medical Dictionary of Regulatory Activities (MedDRA version 26.0). AESI = Adverse event of special interest; TEAE = Treatment-emergent adverse event. No TEAEs of flashbacks were reported Patients, n (%) GH0
Slide 13: MADRS Reduction Reproduced in Placebo Group With First GH001 Treatment in OLE
13 Reduction in MADRS With GH001 in Double-Blind Part Reproduced in Placebo Group With First GH001 Treatment in OLE BL = Baseline; MADRS = Montgomery-Åsberg Depression Rating Scale; OLE = Open-label extension; SE = Standard error. Double-blind Patients who received GH001 (n=40) OLE First treatment o
Slide 14: 73.0% Remission Rate at 6 Months in OLE Completers
14 73.0% Remission Rate at 6 Months in OLE Completers The OLE was completed in Q1 2025 63 completed, 18 early terminations (n=1 due to TEAE) For patients who completed the OLE: 73.0% (n=46) of patients were in remissionc at 6 months (79.4% with clinical response)d Of the 46 patients in remission, 23
Slide 15: Conclusions
Double-Blind Part The primary endpoint was met: GH001 administered as an IDR led to significant MADRS reductions from baseline to Day 8 (−15.5 vs placebo) Secondary endpoints: Remission rate of 57.5% at Day 8 (placebo, 0%), and improvements in anxiety, global disease severity, and quality of life we
Slide 16: Acknowledgments
16 Acknowledgments This trial was sponsored by GH Research The sponsor would like to thank the participants in the trial The sponsor would also like to thank the investigators who conducted this trial Under the guidance of the authors, medical writing and editorial support were provided by Brian Bre