Slide 1: Phase 2b Trial of GH001 in Treatment-Resistant Depression (GH001-TRD-201)
A Randomized, Double-Blind, Placebo-Controlled, Phase 2b Trial with an Open-Label Extension to Determine the Safety and Efficacy of GH001 in Patients with Treatment-Resistant Depression GH001-TRD-201 Clinicaltrials.gov ID: NCT05800860 2025© GH Research PLC, Strictly Confidential
Slide 2: Disclaimer Regarding Forward-Looking Statements
Disclaimer Regarding Forward-Looking Statements This presentation has been prepared by GH Research PLC (“GH Research”) for informational purposes Any statements contained herein that do not describe historical facts are forward-looking statements only and not for any other purpose. Nothing contained
Slide 3: Phase 2b Trial of GH001 in Patients with TRD: Design
Phase 2b Trial of GH001 in Patients with TRD: Design (GH001-TRD-201) GH001 IDR Double-Blind Part Open-label Extension (OLE) n=80 Up to 5 GH001 IDRs based on specific re-treatment criteria1 Randomization 1:1 Placebo IDR Primary Endpoint BL 2h D2 ΔMADRS MADRS assessment During the OLE, patients attend
Slide 4: Key Inclusion Criteria
Key Inclusion Criteria Patients included in this trial were required to meet the trial criteria for TRD as assessed by a study psychiatrist: ● Recurrent or single MDD episode (per DSM-5 criteria) without psychotic features, with current episode of ≤2 years (MINI*). ● Current major depressive episode
Slide 5: Measures to enrol true TRD patients and minimise placebo effect
Measures to enrol true TRD patients and minimise placebo effect Independent raters MGH-SAFER* (including remote assessment of HAM-D-17) performed by (eligibility assessment) remote, trained independent raters Patient-facing Clinical Trial Team – blinded Blinding at sites Patient – blinded Study drug
Slide 6: Patient Disposition & Characteristics
Patient Disposition & Characteristics GH001 (N=40) Placebo (N=41) Patient Disposition Completed double-blind part, n (%) 40 (100) 41 (100) Discontinued double-blind part, n (%) 0 (0) 0 (0) Age, years, mean (SD) 41.6 (11.4) 43.9 (10.9) Female, n (%) 24 (60) 22 (53.7) Race, white, n (%) 40 (100) 41 (1
Slide 7: Primary endpoint: LS Mean Change from Baseline in MADRS Total Score
Primary endpoint: GH001 led to -15.5 mean MADRS reduction from baseline on Day 8 compared with placebo (p<0.0001) 0 0.3 -1.4 -1.5 Baseline in MADRS Total Score LS Mean (±SE) of Change from -5 -10 LS mean difference -15.5 P<0.0001 -15 -15.2 -17.8 -18.6 GH001 Placebo -20 Baseline 2 hours Day 2 Day 8 A
Slide 8: Secondary endpoints: Remission and Response Rates
Secondary endpoints: GH001 Led to 57.5% Remission Rate1 at Day 8 vs 0% in Placebo **** 90% **** Percentage of patients with MADRS 82.5% 80% **** 77.5% 70.0% remission and response 70% **** **** **** 60.0% 60% 57.5% 57.5% Remission GH001 1 50% 1 Remission PBO 40% 2 Response GH001 30% Response PBO 2 2
Slide 9: Secondary endpoints: CGI-S Total Score Change
Secondary endpoints: GH001 led to CGI-S total score difference of -2.5 on Day 8 compared with placebo (p<0.0001) CGI-S reflects the severity of the patient’s illness as perceived by the clinician CGI-S Total Score 0.5 LS Mean Change from Baseline CGI-S Results GH001 Placebo P value 0.1 (N=40) (N=41)
Slide 10: Secondary endpoints: HAM-A Total Score Change
Secondary endpoints: GH001 led to HAM-A total score difference of -10.0 on Day 8 compared with placebo (p<0.0001) HAM-A assesses severity of anxiety symptoms HAM-A Total Score 0 HAM-A results GH001 Placebo P value LS Mean Change from Baseline (N=40) (N=41) -1 -2 BL total score, mean (SD) 21.1 (6.5)
Slide 11: Secondary endpoints: Q-LES-Q-SF Total Score Change
Secondary endpoints: GH001 led to Q-LES-Q-SF total score difference of 21.5 on Day 8 compared with placebo (p<0.0001) Q-LES-Q-SF measures QoL domains such as physical health, mood, work, household duties, schoolwork, leisure time activities, social and family relations, and overall well-being Q-LES-
Slide 12: MADRS Total Score Change: GH001 and Spravato
MADRS Total Score Change from Baseline: GH001 and Spravato at D2 and Primary Endpoint (difference from comparator arm) Spravato + AD vs Placebo + AD from TRANSFORM-21 GH001 vs Placebo Spravato monotherapy (84mg) vs Placebo from TRD40052 Primary Endpoint Key Secondary Endpoint Primary Endpoint Day 2
Slide 13: Remission Rates: GH001 vs Spravato Monotherapy
Secondary Endpoints: Remission1 GH001 Day 2 and Day 8 and Spravato Monotherapy (84mg) Day 2, Day 8 and Day 28 Remission Rates with Spravato Remission Rates with GH001 monotherapy (84mg) from TRD40052 100% 100% 90% 90% Percentage of patients in remission Percentage of patients in remission 80% 80% 70
Slide 14: Overall Summary of Safety
Overall Summary of Safety • GH001 was well tolerated, and no serious adverse events (SAEs) were reported. • All TEAEs were mild or moderate with no severe adverse events. • The most common TEAEs in patients treated with GH001 were nausea, salivary hypersecretion, paresthesia, headache, and dysgeusia
Slide 15: Overview of Adverse Events
Overview of Adverse Events Overview of Adverse Events: GH001 vs Placebo GH001 Placebo N=40 N=41 Pts Events Pts Events n (%) n n (%) n Five Most Common TEAEs in Patients Treated with GH001 Any TEAE1 29 (72.5) 81 3 (7.3) 7 Max severity of TEAEs2 MedDRA PT GH001 N=40 Mild 14 (35.0) 55 2 (4.9) 6 Pts Eve
Slide 16: Columbia-Suicide Severity Rating Scale (C-SSRS)
Columbia-Suicide Severity Rating Scale1 (C-SSRS) GH001, N=40 Placebo, N=41 n (%) n (%) Past 12 months Suicidal ideation (1-3) 8 (20) 11 (26.8) Suicidal ideation with intent (4-5) 0 (0) 0 (0) Suicidal behaviour (6-9) 0 (0) 0 (0) Baseline Suicidal ideation (1-3) 7 (17.5) 7 (17.1) Suicidal ideation wit
Slide 17: Open-Label Extension
Open-Label Extension Data as of January 22, 2025 2025© GH Research PLC, Strictly Confidential
Slide 18: Phase 2b Trial of GH001 in Patients with TRD: Design
Phase 2b Trial of GH001 in Patients with TRD: Design (GH001-TRD-201) GH001 IDR Double-Blind Part Open-label Extension (OLE) n=80 Up to 5 GH001 IDRs based on specific re-treatment criteria1 Randomization 1:1 Placebo IDR Primary Endpoint BL 2h D2 ΔMADRS MADRS assessment During the OLE, patients attend
Slide 19: 77.8% Remission Rate at 6 Months in OLE Completers
77.8% Remission Rate at 6 Months in OLE Completers1 (n=54) 100% Double-blind2 OLE OLE status (January 22, 2025): 9 patients ongoing, 54 completed, 18 early terminations (comparable to other antidepressant trials4; n=1 Percentage of patients in remission 90% 77.8% due to AE) 80% From the patients who
Slide 20: 83% fewer treatment visits with GH001 than with Spravato
83% fewer treatment visits with GH001 than with Spravato 4 visits1 GH001 GH001 Based on Phase 2b OLE data as of January 22, 2025 77.8% remission at 6 months2 SPRAVATO® 23 visits3 Based on ICER estimate 0 5 10 15 20 25 Treatment visits in 6 months Note: To-date, no head-to-head comparisons of any oth
Slide 21: Reduction in MADRS total score reproduced in placebo group in OLE
Reduction in MADRS total score with GH001 in DB reproduced in PBO Group with first GH001 treatment in OLE Mean MADRS Total Score from Baseline to Day 8 by First Active Treatment • All patients enrolled in the DB part of the trial directly transitioned into the OLE at the end of the DB period. • Once
Slide 22: Remission on Day 8 / Remission at 6 Months
Remission on Day 8 / Remission at 6 Months Remission1 Rate at 6 Months2 in OLE Completers3 by Day 8 First Active Treatment, Remitters / Non-Remitters4 100 91.7% Percentage of patients in remission 90 80 Patients who had remission on Day 8 70 after their first active treatment had a 60 91.7% remissio
Slide 23: MADRS Total Score Change Across Treatments in DB and OLE
MADRS Total Score Change from Baseline/Pre-dose to Day 8 Across Treatments1 in DB and OLE MADRS Total Score Change from Baseline/Pre-dose to Day 8 Across Treatments 2 OLE data as of January 22, 2025, shows GH001 leads to a consistent and rapid MADRS Change from Baseline reduction in MADRS after each
Slide 24: Overall Summary of OLE
Overall Summary of OLE • As of January 22, 2025, 9 patients (11.1%) are ongoing in the trial. 54 patients have completed the full 6-month follow-up of the OLE. • Of the 54 patients who completed the OLE: • 77.8% of patients were in remission1 (MADRS≤10) at the 6 month visit and 81.5% were responders
Slide 25: Conclusion
CONCLUSION Double-Blind • Primary Endpoint: GH001 led to MADRS reduction from baseline of -15.5 on Day 8 compared with placebo (p<0.0001). • Secondary Endpoints: All secondary endpoints results were consistent with the primary endpoint. • Safety: GH001 was well tolerated, with no serious adverse eve
Slide 26: Phase 2b Trial of GH001 in Treatment-Resistant Depression (GH001-TRD-201)
A Randomized, Double-Blind, Placebo-Controlled, Phase 2b Trial with an Open-Label Extension to Determine the Safety and Efficacy of GH001 in Patients with Treatment-Resistant Depression GH001-TRD-201 Clinicaltrials.gov ID: NCT05800860 2025© GH Research PLC, Strictly Confidential