Gh Research Plc · NASDAQ:GHRS
Gh Research — Investor Presentation (September 2024)
34 slides from Gh Research's investor presentation, Sep 3, 2024
Slide 1: GH Research PLC September 2024 Corporate Presentation
GH Research PLC (NASDAQ: GHRS) September 2024 Corporate Presentation 1
Slide 2: Disclaimer and 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 the presenter or GH Research or any director, emp
Slide 3: Seeking Ultra-Rapid, Durable Remissions in Depression
SeekingUltra-Rapid, Durable Remissionsin Depression 3
Slide 4: Stage of Development
Stage of Development PROGRAMS INDICATION PRECLINICAL PHASE 1 PHASE 2a PHASE 2b PHASE 3 CURRENT STATUS MILESTONES GH001Mebufotenin (5-MeO-DMT) for inhalation administration Treatment-Resistant Depression (TRD) Phase 2b RDBPC & Phase 1 PK trial with proprietary device ongoing Phase 2b DB phase complet
Slide 5: The Problem for Patients with Depression
The Problem for Patients with Depression Established Therapies are Slow-Acting ... Remission Rates in TRD < 15% 5 (STAR*D study, Remission Rate Over Time, Treatment Step 1 = Citalopram) (STAR*D study, Remission Rates Treatment Steps 1 to 4) Average time to remission is ~6 weeks ~33% no remission des
Slide 6: Large and Open Depression Market in the EU and US
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 lines: ~9M Large and Open Depression Market in the EU an
Slide 7: GH001 & GH002 API Mebufotenin (5-MeO-DMT)
GH001 & GH002 7 API Mebufotenin (5-MeO-DMT) Pharmacology 5-HT1A/5-HT2A agonist Route Pulmonary inhalation (GH001) or IV administration (GH002) Psychoactive effect Ultra-rapid onset (within seconds) and short duration (<30 min) Dose Individualized dosing regimen (IDR) of 1 to 3 doses in a single visi
Slide 8: Individualized Dosing Regimen (IDR) for Maximization of Ultra-Rapid and Durable Remissions
Individualized Dosing Regimen (IDR) for Maximization of Ultra-Rapid and Durable Remissions 8 Single Dose: Inter-Person Variability 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
Slide 9: Phase 1 Trial of GH001 in Healthy Volunteers (GH001-HV-101)
Phase 1 Trial of GH001 in Healthy Volunteers GH001-HV-101 9 (Completed) Clinicaltrials.gov ID: NCT04640831
Slide 10: Design of Phase 1 Trial of GH001 in Healthy Volunteers
Design of Phase 1 Trial of GH001 in Healthy Volunteers (GH001-HV-101) 10 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) Primary Endpoint: Safety until day 7 Peak Experience Scale (PE Scale)1 Part B (IDR) HV (n=4) Primary Endpoint: Safety until da
Slide 11: Part A and Part B – Safety Study
Part A (Single Dose) and Part B (IDR) – Safety 11 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 blo
Slide 12: Part A – Peak Experience Dose-Effects and Inter-Person Variability
Part A – Peak Experience (PE) Dose-Effectsand Inter-Person Variability 12 Average fordose group PE Scale PE Threshold PE, Peak Experience
Slide 13: Part B – Peak Experience Effect of Intraday IDR
Part B – Peak Experience (PE)Effect of Intraday Individualized Dosing Regimen (IDR) 13 PE Threshold PE, Peak Experience
Slide 14: Phase 1/2 Trial of GH001 in Treatment-Resistant Depression
(Completed) Phase 1/2 Trial of GH001 in Treatment-Resistant DepressionGH001-TRD-102 14 Clinicaltrials.gov ID: NCT04698603
Slide 15: Design of Phase 1/2 Trial of GH001 in TRD
15 Design of Phase 1/2 Trial of GH001 in TRD (GH001-TRD-102) Phase 1 (Single Dose) Phase 2 (IDR) GH001 12 mg (n=4) GH001 18 mg (n=4) TRD1 (n=8) Primary Endpoint: Safety until day 7 TRD1 (n=8) Primary Endpoint: MADRS remission day 7 (MADRS≤10) GH001 IDR6, 12, 18 mg to achieve PE (up to 3 doses, 3h in
Slide 16: Phase 1 and Phase 2 – Safety
Phase 1 (Single Dose) and Phase 2 (IDR) – Safety 16 ADRs Phase 1 (Single Dose) Phase 2 (IDR) ADRs 12 mg (n=4) 18 mg (n=4) IDR1 (n=8) MedDRA Preferred Term Number of Events n n Abdominal discomfort 1 Anxiety 2 Depressive symptom 1* Dizziness 1 Feeling abnormal 1 1 Flashback 1 1 2 Headache 2 1 3 Muscl
Slide 17: Phase 1 (Single Dose) – Efficacy (MADRS)
Phase 1 (Single Dose) – Efficacy (MADRS) 17 2 of 4 (50%) in the 12 mg group and1 of 4 (25%) in the 18 mg group had a MADRS remission at day 7 2 of 8 patients had a PE and both had a MADRS remission at day 7 MADRS Remission / Response / Improvement Rate Day 7 PE, Peak Experience; MADRS, Montgomery–Ås
Slide 18: Phase 2 (IDR) – Efficacy (MADRS)
Phase 2 (IDR) – Efficacy (MADRS) 18 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 MADRS Remission / Response / Improvement Rate Day 7 PE, Peak Experience; MADRS, Montgomery–Åsberg Depressi
Slide 19: Phase 2 (IDR) – Efficacy (MADRS Change from Baseline)
Phase 2 (IDR) – Efficacy (MADRS Change from Baseline) 19 Hour 2 Day 1 Day 7 GH001 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 Baseline1 1Baseline mean MADRS=32
Slide 20: MADRS and PE – Observed Improved Outcome in IDR vs Single Dose
MADRS and PE – Observed Improved Outcome in Phase 2 (IDR) vs Phase 1 (Single Dose) 20 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
Slide 21: Phase 2b Trial in Treatment-Resistant Depression GH001-TRD-201
(Initiated) Phase 2b Trial inTreatment-Resistant DepressionGH001-TRD-201 21 EudraCT Number: 2022-000574-26
Slide 22: Design of Phase 2b Trial in TRD
Design of Phase 2b Trial in TRD (GH001-TRD-201) 22 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 antidepressants*) D1 D7
Slide 23: Three-Layer Protection Strategy
Three-Layer Protection Strategy 23 LAYER 1: REGULATORY EXCLUSIVITY FDA: 5 years (+2.5 years paragraph IV stay) EMA: 10 years (+1 year for new indication) LAYER 2: PATENTS Granted patents and patent applications relating to mebufotenin (5-MeO-DMT), including: Novel uses in various disorders (includin
Slide 24: Board of Directors & Executive Management
Board of Directors & Executive Management 24 Florian Schönharting Michael Forer MSc Chairman of the Board, Co-founder BA, LLB Vice-Chairman of the Board Dermot Hanley Duncan Moore BSc, MBA Board Member MPhil, PhD Board Member Julie Ryan FCA, MAcc, BComm VP, Finance Magnus Halle BSc Managing Director
Slide 25: Scientific Advisors
Scientific Advisors 25 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 26: Anticipated Milestones and Financial Overview
Anticipated Milestones and Financial Overview GH001 Complete double-blind phase of European Phase 2b trial in TRD in Q3 2024; complete open-label extension phase in Q1 2025 Complete Phase 2a trial in PPD in Q4 2024; Complete nonclinical studies and prepare device design verification information to s
Slide 27: Appendix: Additional Completed Trials
AppendixAdditional Completed Trials 27
Slide 28: Phase 1 Clinical Pharmacology Trial of GH001 in Healthy Volunteers
(Completed) Phase 1 Clinical Pharmacology Trial of GH001 in Healthy Volunteers GH001-HV-103 28 Clinicaltrials.gov ID: NCT05163691
Slide 29: Design of Phase 1 Clinical Pharmacology Trial of GH001 (GH001-HV-103)
Design of Phase 1 Clinical Pharmacology Trial of GH001 in Healthy Volunteers (GH001-HV-103) 29 Day 0 GH001 inhaled 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
Slide 30: Single Dose and IDR – Safety and Further Results
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 administrati
Slide 31: Phase 1 Clinical Pharmacology Trial of GH002 in Healthy Volunteers
(Completed) Phase 1 Clinical Pharmacology Trial of GH002 in Healthy Volunteers GH002-HV-105 31 Clinicaltrials.gov ID: NCT05753956
Slide 32: Design of Phase 1 Trial of GH002 in Healthy Volunteers (GH002-HV-105)
Design of Phase 2 Trial of GH002 in Healthy Volunteers (GH002-HV-105) 32 GH002 0.25 mg (n=6+2 placebo) GH002 4 mg (n=6+2 placebo) GH002 8 mg (n=6+2 placebo) GH002 10 mg (n=6+2 placebo) HV (n=56) Part A (Single Dose) Primary Endpoints: Safety until day 7 Pharmacokinetic profile Part B (IDR) HV (n=8)
Slide 33: Single Dose and IDR – Safety and Further Results
Single Dose and IDR – Safety and Further Results 33 Safety review No SAEs All ADRs mild, except one moderate (*) No noteworthy changes in vital parameters, except for temporary, non-clinically relevant increase in heart rate and blood pressure shortly after administration of GH002 No clinically rele
Slide 34: Seeking Ultra-Rapid, Durable Remissions in Depression
SeekingUltra-Rapid, Durable Remissionsin Depression 34