Gh Research Plc · NASDAQ:GHRS
Gh Research — ACNP 2026 Mini Panel
43 slides from Gh Research's conference presentation, January 2026
Slide 1: Exploring the Therapeutic Potential of Mebufotenin (GH001) Across Depressive Disorders
Exploring the Therapeutic Potential of Mebufotenin (GH001) Across Depressive Disorders Chair Michael E. Thase, MD Presenters Lisa Harding, MD Kristina M. Deligiannidis, MD Roger S. McIntyre, MD, FRCPC ACNP 2026 Mini Panel
Slide 2: Panel presentations and presenters
GH001 Provides Rapid and Significant Antidepressant Effects in Patients with Treatment-Resistant Depression: Efficacy and Safety Results from a Phase 2b, Double-Blind, Randomized Controlled Trial with a 6-Month Open-Label Extension Lisa Harding, MD Mood Institute and Yale School of Medicine Milton,
Slide 3: Disclosures
Disclosures Author Disclosures Consultant – Axsome, Clexio Biosciences, Gerson Lehrman Group, GH Research, Janssen, Johnson & Johnson, Lundbeck, Luye Pharma, Merck, Otsuka, Pfizer, Sage, Seelos Therapeutics, Sunovion, and Takeda. Grant support – Acadia, Alkermes, Axsome, Intra-Cellular Therapies, Ja
Slide 4: Psychoactive Molecules as Rapid-Acting Treatment for Depression
Psychoactive Molecules as Rapid-Acting Treatment for Depression ➢ Pharmacotherapy is the first-line treatment recommendation for people with moderate to severe MDD1,2; however, there is an unmet need for rapid and effective pharmacological treatments ➢ Less than half of patients with MDD treated in
Slide 5: GH001 Overview
GH001 Overview Non-selective 5-HT agonist with high affinity GH001 for the 5-HT1A receptor3-5 Synthetic form of mebufotenin (5-MeO-DMT) for pulmonary Median duration of psychoactive effects: 11 min inhalation GH001 has been well tolerated in early-stage trials1,2 and shows Target indications: TRD, P
Slide 6: Psychoactive Molecules Are Not Alike: Pharmacology and Phenomenology
Psychoactive Molecules Are Not Alike: Pharmacology and Phenomenology LSD1,2 DMT3,4 Mebufotenin5-8 Non-selective serotonin and Mixed 5-HT1A/5-HT2A Non-selective serotonin agonist with dopamine agonist agonist high affinity for 5-HT1A Experience of Unity Experience of Unity Experience of Unity Changed
Slide 7: GH001 Provides Rapid and Significant Antidepressant Effects in Patients with TRD
GH001 Provides Rapid and Significant Antidepressant Effects in Patients with Treatment-Resistant Depression Efficacy and Safety Results from a Phase 2b, Double-Blind, Randomized Controlled Trial with a 6-Month Open-Label Extension Lisa Harding, MD Mood Institute and Yale School of Medicine Milton, C
Slide 8: Background
Background ➢ TRD remains one of the most pressing challenges in psychiatry and affects approximately 30% of patients treated for MDD1 ➢ Current therapies for TRD are limited,2 and there is a large unmet need for treatments that are well tolerated and offer rapid reductions in depressive symptoms and
Slide 9: Trial Schematic
Trial Schematic GH001 IDRa All patients directly transitioned from the double-blind part to the OLE Double-Blind Part (Part 1)b Open-Label Extension (OLE; Part 2) For re-treatment (up to five GH001 IDRsa), the patient must have met one N=81 Randomization 1:1 of the following criteria: i. MADRS score
Slide 10: Eligibility Criteria
Eligibility Criteria Patients were required to meet the trial criteria for TRD as assessed by a trial psychiatrist: Single-episode or recurrent MDD (per DSM-5 criteria) without psychotic features, with current episode of ≤2 yearsa Current MDE validated per the MGH-SAFER HAM-D-17 total score ≥20 Nonr
Slide 11: Baseline Characteristics and Patient Disposition
Baseline Characteristics and Patient Disposition N=81 Baseline Demographics Age, years, mean (SD) 42.8 (11.2) Sex, female, n (%) 46 (56.8) Race, White, n (%) 81 (100) BMI, kg/m2, mean (SD) 26.2 (5.5) Previously used any psychedelic (lifetime), n (%) 9 (11.1) Baseline Disease Characteristics HAM-D-17
Slide 12: Primary Endpoint: Mean MADRS Reduction from Baseline on Day 8
Primary Endpoint: GH001 Led to −15.5 Mean MADRS Reduction from Baseline on Day 8a Compared with Placebo in the Double-Blind Period 0 Baseline in MADRS Total Score −1.4 −1.5 0.3 −-5 LS Mean (±SE) Change from −-10 −-15 −15.2 −-20 −17.8 −18.6 GH001 (n=40) LS mean differenceb vs placebo: −15.5 (P<0.0001
Slide 13: Percentage of Patients with MADRS Remission or Response
GH001 Led to 60.0% Response Rate and 57.5% Remission Rate at Day 8 vs 0% with Placebo in the Double-Blind Period NNT=2 100 **** NNT=2 **** NNT=2 90 Percentage of Patients with MADRS 82.5% **** 77.5% NNT=2 GH001 80 NNT=2 NNT=2 **** 70.0% **** **** Placebo Remission or Response 70 57.5% 60.0% 57.5% 60
Slide 14: Reduction in MADRS in Open-Label Extension
Reduction in MADRS with GH001 in Double-Blind Part Reproduced in Placebo Group with Their First Active GH001 Treatment in the OLE Double-Blind Open-Label Extension Patients who received GH001 (n=40) First treatment of placebo group with GH001 (n=41) 35 35 Mean (±SE) MADRS Total Score Mean (±SE) MADR
Slide 15: Remission Rate at 6 Months in OLE Completers
There Was a 73% Remission Rate at 6 Months in OLE Completers 100 Double-blind OLE n=40 patients who n=63 OLE Percentage of Patients in Remissionc received GH001 completersa 80 73.0% 60 57.5% 40 20 0 Day 8 Month 6b Patients who completed the OLE received a mean of four treatments across the 6 months
Slide 16: Remission Rate at 6 Months by Initial Remission
Remission Rate at 6 Monthsa in OLE Completersb 100 90% Of patients who had Percentage of Patients in Remissionc remission on Day 8 after 80 their first GH001 treatment, 90% were in remission at 6 months 60 43.5% 40 20 0 Initial Remitters Initial Non-remitters N=40 N=23 a‘6 Months’ or ‘Month 6’ (end
Slide 17: Overview of Adverse Events in the Open-Label Extension
Overview of Adverse Events in the Open-Label Extension Patients, n (%) Overall (N=81) Overview of Adverse Events Any TEAEa 72 (88.9) Maximum severity of TEAEs Mild 28 (34.6) Moderate 42 (51.9) Severe 2 (2.5) Treatment-related TEAEs 65 (80.2) Serious TEAEs 1 (1.2) Treatment-related serious TEAEs 0 TE
Slide 18: GH001 Administration Was Well Tolerated in Patients with TRD up to 6 Months
GH001 Administration Was Well Tolerated in Patients with TRD up to 6 Months ➢ During the OLE, TEAEs were observed in 72/81 (88.9%) patients and were mostly mild or moderatea; one non−treatment-related serious TEAE (migraine) was reported ➢ No TEAEs of suicidal intent or suicidal behavior occurred ➢
Slide 19: Conclusion
Conclusion ➢ The primary endpoint was met: GH001 administered as an IDR led to significant MADRS reduction from baseline to Day 8 (−15.5 vs placebo) ➢ GH001 can maintain long-term remission in TRD, with 73.0% of patients who completed the OLE in remission at 6 months ➢ GH001 was well tolerated durin
Slide 20: GH001 and Maternal Functioning in Postpartum Depression
GH001 Is Associated with Improved Self-Reported Maternal Functioning in Patients with Postpartum Depression and Rapid Elimination from Breastmilk Kristina M. Deligiannidis, MD Feinstein Institutes for Medical Research Northwell Health Manhasset, NY, USA 20
Slide 21: Background
Background ➢ PPD is defined as an MDE with onset of mood symptoms during pregnancy or within 4 weeks following delivery1 ➢ PPD is associated with adverse effects on maternal well-being and mother-infant relationships that can negatively impact infant development2 ➢ Breastfeeding is associated with p
Slide 22: Trial Schematic
Trial Schematic 1-hour interval Dose 3a 18 mg GH001 1-hour interval Dose 2a 12 mg GH001 Patients Dose 1 with PPD 6 mg GH001 N=10 Single-day IDR Primary endpoint BL 2H D2 ΔMADRS MADRS assessment Day −60 to Day −2 Day −1 Day 1 Day 2 Day 8 Screening Pre-dosing day MADRS MADRS MADRS PK PK PK BIMF Safety
Slide 23: Eligibility Criteria
Eligibility Criteria Women aged 18–45 years were required to meet criteria for PPD as assessed by a trial psychiatrist: Diagnosis of MDDa (per DSM-5 criteria), without psychotic features, with peripartum onset MDD onset no earlier than gestation and no later than the first 4 weeks postpartum Was >4
Slide 24: Key Assessments
Key Assessments • Primary endpoint: change from baseline to Day 8 in MADRS total score MADRS1 • Total score range, 0−60 • Higher scores indicate more severe depression • Patient-centered self-report of maternal functioning BIMF2 • Total score range, 0–120 • Higher scores indicate better functioning
Slide 25: Demographics and Baseline Clinical Characteristics
Demographics and Baseline Clinical Characteristics N=10 Demographics Sex, female, n (%) 10 (100) Age, years, mean (SD) 31.6 (5.2) Ethnicity, n (%) Hispanic or Latino 1 (10.0) Not Hispanic or Latino 9 (90.0) Race, n (%) White 9 (90.0) Black or African American 1 (10.0) Parity, mean (SD) 2 (1.0) Basel
Slide 26: Primary Endpoint: Reduction in Mean MADRS Total Score in PPD
Primary Endpoint: GH001 Was Associated with Significant Reductions from Baseline on Day 8 in Mean MADRS Total Score in Patients with PPD 0 −-5 Mean (±SD) Change from Baseline −-10 At Day 8 All patients were in remission in MADRS Total Score −-15 (MADRS total score ≤10) −-20 −-25 ****P<0.0001 vs BL −
Slide 27: MADRS Total Score in Individual Patients
Primary Endpoint: GH001 Led to Substantial Reduction from Baseline on Day 8 in MADRS Total Score in All Patients with PPD 50 MADRS Total Score in Individual Patients 45 40 At Day 8 35 Mean (SD) reduction from baseline: −35.4 (5.5); P<0.0001 30 25 20 15 Remission (MADRS total score ≤10) 10 5 0 BL 2Hb
Slide 28: BIMF Total Score Improved from Baseline on Day 8
BIMF Total Score Improved by a Mean of 34.1 Points from Baseline on Day 8 120.0 *** 100.0 Mean (±SD) BIMF Total Score Better maternal functioning 56% improvement in maternal functioning 80.0 with GH001 60.0 40.0 20.0 ***P<0.001 vs BL 68.8 100.7 0.0 Baseline 1 Day 8 (n=8) (n=9) Improvement from basel
Slide 29: Mebufotenin and its Metabolites Were Rapidly Eliminated from Breastmilk
Mebufotenin and its Metabolites Were Rapidly Eliminated from Breastmilk Of the four lactating patients, three received GH001 6+12 mg and one received GH001 6+12+18 mg as part of the IDR GH001 6+12 mg (n=3) GH001 6+12+18 mg (n=1) Pre- 1h 2.5 h ~8 h Pre- 1h 2.5 h ~8 h dose post- post- post- Day 2 Day
Slide 30: Safety Summary
Safety Summary Patients, n (%) Overall (N=10) Overview of Adverse Events Any TEAE 8 (80.0) Mild 7 (70.0) Moderate 1 (10.0) Severe 0 Treatment-related TEAEs 7 (70.0) Serious TEAE 0 Death 0 TEAEs by Preferred Term Headache 5 (50.0) Abdominal pain 1 (10.0) Nausea 1 (10.0) Vomiting 1 (10.0) Diarrhea 1 (
Slide 31: Conclusions
Conclusions ➢ In adult patients with PPD enrolled in this open-label trial, GH001 as an IDR was associated with significant reduction in MADRS total score from baseline to Day 8 ➢ Improvements were observed across BIMF domains of self-reported maternal functioning ➢ Mebufotenin and its metabolites (
Slide 32: Rapid Improvement in Anhedonia Following GH001 Treatment
Rapid Improvement in Anhedonia Following GH001 Treatment in Patients with Treatment-Resistant Depression, Postpartum Depression, and Bipolar II Disorder and a Current Major Depressive Episode Roger S. McIntyre, MD, FRCPC Department of Psychiatry University of Toronto Toronto, ON, Canada 32
Slide 33: Background
Background ➢ Anhedonia is a core symptom of MDD, characterized by a lack of enjoyment from and engagement in life’s experiences, and a deficit in the ability to feel pleasure1 ➢ In patients with MDD, anhedonia at baseline is often a predictor of TRD2 ➢ Anhedonia is also associated with suicidality,3
Slide 34: Trial Schematics
Trial Schematics aIn the TRD trial, during the OLE, patients attended visits at Day 15, Month 1, 2, 3, 4, 5 & 6, and also attended assessment visits on Day 2 (telephone call) and Day 8 (in-person) after each re-treatment; MADRS assessment was performed at each visit. bMDD episode (per DSM-5 criteria
Slide 35: Anhedonia Assessment
Anhedonia Assessment MADRS 5-item anhedonia subscale ➢ The MADRS 5-item anhedonia subscale1 includes the following MADRS items: Item 1 Item 2 Item 6 Item 7 Item 8 Apparent Reported Concentration Lassitude Inability sadness sadness difficulties to feel ➢ Score range, 0−30; lower scores indicate less
Slide 36: Baseline Characteristics and Disposition
Baseline Characteristics and Disposition TRD Trial PPD Trial BDII + MDE Trial N=81 N=10 N=6 Baseline Demographics Age, years, mean (SD) 42.8 (11.2) 31.6 (5.2) 44.2 (9.3) Sex, female, n (%) 46 (56.8) 10 (100) 4 (66.7) Race, n (%) White 81 (100) 9 (90) 6 (100) Black or African American 0 1 (10) 0 BMI,
Slide 37: MADRS Anhedonia Scores in TRD Double-Blind Treatment
Patients with TRD Who Received Double-Blind Treatment with GH001 Had Rapid and Clinically Meaningfula Improvements in MADRS Anhedonia Scores MADRS Anhedonia Subscale Score MADRS Anhedonia Subscale Item Scores 5 Apparent Reported Concentration Inability GH001 (n=40) Placebo (n=41) Mean (±SD) Change f
Slide 38: Anhedonia Improvement Maintained at Month 6 in OLE Completers
Among Patients Who Completed the TRD Study OLE (n=63), Clinically Meaningfula Improvement in MADRS Anhedonia Score Was Maintained at Month 6 MADRS Anhedonia Subscale Item Scores Apparent Reported Concentration Inability sadness sadness difficulty Lassitude to feel Mean (SD) Change from Baseline at 0
Slide 39: MADRS Anhedonia Subscale Score in PPD
In Patients with PPD, Clinically Meaningfula Improvement in MADRS Anhedonia Score was Observed at Each Assessment MADRS Anhedonia Subscale Score MADRS Anhedonia Subscale Item Scores 5 Mean (±SD) Change from Baseline in MADRS Anhedonia Subscale Score GH001 (N=10) Apparent Reported Concentration Inabi
Slide 40: MADRS Anhedonia Subscale Score in BDII + MDE
Patients with BDII + MDE had Clinically Meaningfula Improvement in MADRS Anhedonia Score at Day 8 Post-Dose MADRS Anhedonia Subscale Score MADRS Anhedonia Subscale Item Scores 5 Mean (±SD) Change from Baseline in MADRS Anhedonia Subscale Score GH001 (N=6) Apparent Reported Concentration Inability sa
Slide 41: GH001 was Well Tolerated in Patients with TRD, PPD, or BDII + MDE
GH001 was Well Tolerated in Patients with TRD, PPD, or BDII + MDE ➢ No treatment-related serious TEAEs were reported across the TRD, PPD and BDII + MDE trialsa ➢ In all three trials, TEAEs were mostly mild or moderate in severity ➢ The most common TEAE in patients treated with GH001 was nausea in th
Slide 42: Conclusion
Conclusion ➢ The presented trials investigating GH001 for the treatment of TRD, PPD, and BDII + MDE demonstrated rapid reductions in MADRS anhedonia subscale scores ➢ Improvements in anhedonia subscale scores were clinically meaningful across each of the depressive disorders at Day 8 and were mainta
Slide 43: Acknowledgments
Acknowledgments ➢ These trials were sponsored by GH Research Ireland Limited ➢ The sponsor would like to thank the participants in the trials ➢ The sponsor would also like to thank the investigators who conducted these trials ➢ Under the guidance of the authors, medical writing and editorial support