Slide 1: Corporate Presentation
1 Corporate Presentation GH Research PLC (NASDAQ: GHRS) GH Research August 2023 2023© GH Research PLC
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 only and not for any other purpose. Nothing contained in this presentation is, or should be construed as, a recommendation, promise or representation by t
Slide 3: Seeking Ultra-Rapid, Durable Remissions in Depression
Seeking Ultra-Rapid, Durable Remissions in Depression 3 2023© GH Research PLC
Slide 4: Stage of Development
Stage of Development PROGRAMS INDICATION PRECLINICAL PHASE 1 PHASE 2a PHASE 2b PHASE 3 CURRENT STATUS GH001Mebufotenin (5-MeO-DMT)for inhalation administration Treatment-Resistant Depression (TRD) Phase 2b RDBPC trial initiated(GH001-TRD-201) Bipolar II Disorder* (BDII) Phase 2a POC trial initiated(
Slide 5: The Problem for Patients with Depression
... Remission Rates in TRD < 15% Established Therapies are Slow-Acting ~33% no remission despite 4 treatment steps Adapted from Trivedi et al., Am J Psychiatry 2006 and Rush et al., Am J Psychiatry 2006 TRD, Treatment-Resistant Depression Average time to remission is ~6 weeks (STAR*D study, Remissio
Slide 6: Large and Open Depression Market in the EU and US
Large and Open Depression Market in the EU and US 6 First Line MDD Second Line MDD Treatment-Resistant Depression (TRD) Patients cycle through ineffective therapies for TRD Diagnosed: ~48M Treated (pharmacotherapy ± psychotherapy): ~24M Non-response to first line: ~13M Non-response to two prior line
Slide 7: Mebufotenin (5-MeO-DMT) and GH001
Mebufotenin (5-Methoxy-N,N-Dimethyltryptamine, 5-MeO-DMT) Naturally-occurring psychoactive substance from tryptamine class Highly potent agonist on 5-HT1A and 5-HT2A receptors GH001 (Mebufotenin administration via a proprietary pulmonary inhalation approach) Psychoactive effects with ultra-rapid ons
Slide 8: GH001 Individualized Dosing Regimen (IDR)
GH001 Single Dose: Inter-Person Variability GH001 Individualized Dosing Regimen (IDR):Maximization of Ultra-Rapid and Durable Remissions MADRS score MADRS score MADRS score MADRS score Dose 1 Dose 1 Dose 2 Dose 3 Dose 2 Dose 1 No remission Remission Remission Remission Remission Hypothetical Patient
Slide 9: Phase 1 Trial in Healthy Volunteers GH001-HV-101 (Completed)
Phase 1 Trial in Healthy Volunteers GH001-HV-101 (Completed) 9 Clinicaltrials.gov ID: NCT04640831 2023© GH Research PLC
Slide 10: Design of Phase 1 Trial in Healthy Volunteers (GH001-HV-101)
GH001 Administration Day 1 Day 7 GH001 2 mg (n=4) GH001 6 mg (n=6) GH001 12 mg (n=4) GH001 18 mg (n=4) HV (n=18) Part A (Single Dose) Part B (IDR) Primary Endpoint: Safety until day 7 Peak Experience Scale (PE Scale)1 HV (n=4) Primary Endpoint: Safety until day 7 Peak Experience Scale (PE Scale)1 GH
Slide 11: Part A and Part B – Safety
Study Safety Group review No SAEs All ADRs mild, except two moderate (*) All ADRs resolved spontaneously Inhalation well-tolerated No noteworthy changes in vital parameters, except for temporary, non-clinically relevant increase in heart rate and blood pressure shortly after administration of GH001
Slide 12: Part A – Peak Experience Dose-Effects and Inter-Person Variability
Average fordose group PE Scale PEThreshold Part A – Peak Experience (PE) Dose-Effectsand Inter-Person Variability 12 PE, Peak Experience 2023© GH Research PLC
Slide 13: Part B – Peak Experience Effect of IDR
PEThreshold Part B – Peak Experience (PE)Effect of Intraday Individualized Dosing Regimen (IDR) 13 PE, Peak Experience 2023© GH Research PLC
Slide 14: Phase 1/2 Trial in Treatment-Resistant Depression GH001-TRD-102 (Completed)
Phase 1/2 Trial in Treatment-Resistant Depression GH001-TRD-102 (Completed) 14 Clinicaltrials.gov ID: NCT04698603 2023© GH Research PLC
Slide 15: Design of Phase 1/2 Trial in TRD (GH001-TRD-102)
Key Assessments MADRS H2 PE Scale Safety MADRS D1 Cognitive function Safety MADRS D7 Cognitive function Safety GH001 Administration Day 1 Day 7 Design of Phase 1/2 Trial in TRD (GH001-TRD-102) 15 1Defined as inadequate response to at least two adequate courses of pharmacological therapy or one adequ
Slide 16: Phase 1 and Phase 2 – Safety
Phase 1 (Single Dose) and Phase 2 (IDR) – Safety 16 2023© GH Research PLC Study Safety Group review No SAEs All ADRs mild, except three moderate* All ADRs resolved spontaneously Inhalation well-tolerated No noteworthy changes in vital parameters, except for temporary, non-clinically relevant increas
Slide 17: Phase 1 (Single Dose) – Efficacy (MADRS)
MADRS Remission / Response / Improvement Rate Day 7 Phase 1 (Single Dose) – Efficacy (MADRS) 17 PE, Peak Experience; MADRS, Montgomery–Åsberg Depression Rating ScaleMADRS remission = MADRS of ≤10; MADRS response = Reduction of ≥50% from baseline in MADRS; MADRS any improvement = any reduction from b
Slide 18: Phase 2 (IDR) – Efficacy (MADRS)
Phase 2 (IDR) – Efficacy (MADRS) 18 2023© GH Research PLC MADRS Remission / Response / Improvement Rate Day 7 Primary endpoint met: 7 of 8 patients (87.5%) had a MADRS remission at day 7, p<0.0001 7 of 8 patients had a PE and 6 of those had a MADRS remission at day 7 PE, Peak Experience; MADRS, Mont
Slide 19: Phase 2 (IDR) – Efficacy (MADRS Change from Baseline)
Phase 2 (IDR) – Efficacy (MADRS Change from Baseline) 2023© GH Research PLC Baseline1 Hour 2 Day 1 Day 7 GH001 19 p=0.0018 p<0.0001 p<0.0001 Primary endpoint met: 7 of 8 patients (87.5%) had a MADRS remission at day 7, p<0.0001 7 of 7 remissions from day 1 and4 of 7 remissions from 2 hours 1Baseline
Slide 20: MADRS and PE – Improved Outcome in Phase 2 (IDR) vs Phase 1
MADRS and PE – Observed Improved Outcome in Phase 2 (IDR) vs Phase 1 (Single Dose) Phase 2 (IDR) Phase 1 (Single Dose) 12 mg Phase 1 (Single Dose) 18 mg MADRS Remission Rate Day 7 87.5% (7 of 8) 50% (2 of 4) 25% (1 of 4) Mean MADRS Change Day 7 -24.4 (-76%) -21.0 (-65%) -12.5 (-40%) Rate of PE 87.5%
Slide 21: Phase 1 Clinical Pharmacology Trial GH001-HV-103 (Completed)
Phase 1 Clinical Pharmacology Trial in Healthy Volunteers GH001-HV-103 (Completed) 21 2023© GH Research PLC Clinicaltrials.gov ID: NCT05163691
Slide 22: Design of Phase 1 Clinical Pharmacology Trial (GH001-HV-103)
GH001 Administration Day 7 GH001 6 mg (n=8+2 placebo) GH001 12 mg (n=8+2 placebo) GH001 18 mg (n=8+2 placebo) HV (n=30) Single-Dose Part IDR Part HV (n=16) GH001 IDR6, 12, 18 mg to achieve PE (up to 3 doses, 1h interval, n=8) Key Assessments Safety Pharmacokinetics PE Scale Cognitive function Safety
Slide 23: Single Dose and IDR – Safety and Further Results
Safety Review No SAEs All ADRs mild All ADRs resolved spontaneously Inhalation well-tolerated No noteworthy changes in vital parameters, except for temporary, non-clinically relevant increase in heart rate and blood pressure shortly after administration of GH001 No clinically relevant changes in ECG
Slide 24: Phase 2b Trial in Treatment-Resistant Depression GH001-TRD-201 (Initiated)
Phase 2b Trial in Treatment-Resistant Depression GH001-TRD-201 (Initiated) 24 2023© GH Research PLC EudraCT Number: 2022-000574-26
Slide 25: Design of Phase 2b Trial in TRD (GH001-TRD-201)
Design of Phase 2b Trial in TRD (GH001-TRD-201) 2023© GH Research PLC 25 GH001 IDR Placebo IDR n=80 Randomization 1:1 Up to 5 GH001 IDRs may be administered during the OLE pro re nata (PRN), based on specific re-treatment criteria D0 MADRS Primary Endpoint ΔMADRS (per FDA guidance for rapid-acting a
Slide 26: Three-Layer Protection Strategy
LAYER 1: REGULATORY EXCLUSIVITY FDA: 5 years (+2.5 years paragraph IV stay) EMA: 10 years (+1 year for new indication) LAYER 3: TECHNICALComplex bioequivalence for systemically-acting inhalation/intranasal products with high intra- and inter-subject variability LAYER 2: PATENTS Patent families filed
Slide 27: Board of Directors & Executive Management
Board of Directors & Executive Management 27 Florian Schönharting Michael Forer MSc Chairman of the Board, Co-founder BA, LLB Vice-Chairman of the Board 2023© GH Research PLC Dermot Hanley Duncan Moore BSC, MBA Board Member MPhil, PhD Board Member Theis Terwey PD Dr. med. CEO, Co-founder Julie Ryan
Slide 28: Scientific Advisors
Scientific Advisors 28 Michael Thase M.D. Professor of Psychiatry, Perelman School of Medicine University of Pennsylvania Madhukar Trivedi M.D. Professor of Psychiatry, UT Southwestern Medical Center Mark Zimmerman M.D. Professor of Psychiatry and Human Behavior, Brown University Eduard Vieta Prof.
Slide 29: Anticipated Milestones and Financial Overview
Anticipated Milestones and Financial Overview GH001 Complete multi-center, randomized, double-blind, placebo-controlled Phase 2b trial in TRD Submit U.S. IND for GH001 in Q3 2023 and initiate Phase 1 clinical pharmacology trial with proprietary aerosol delivery device in Q4 2023 Complete proof-of-co
Slide 30: Seeking Ultra-Rapid, Durable Remissions in Depression
Seeking Ultra-Rapid, Durable Remissions in Depression 30 2023© GH Research PLC