UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

Washington, D.C. 20549

 

FORM 6-K

 

REPORT OF FOREIGN PRIVATE ISSUER PURSUANT TO RULE 13a-16 OR 15d-16
UNDER THE SECURITIES EXCHANGE ACT OF 1934

 

For the month of January, 2023.

 

Commission File Number: 001-40530

 

GH Research PLC

(Exact name of registrant as specified in its charter)

 

28 Baggot Street Lower

Dublin 2

D02 NX43

Ireland

(Address of principal executive office)

 

Indicate by check mark whether the registrant files or will file annual reports under cover of Form 20-F or Form 40-F:

 

Form 20-F

  Form 40-F  

 

Indicate by check mark if the registrant is submitting the Form 6-K in paper as permitted by Regulation S-T Rule 101(b)(1):

 

Indicate by check mark if the registrant is submitting the Form 6-K in paper as permitted by Regulation S-T Rule 101(b)(7):

 

 

 

 

GH Research PLC (the “Company”) will hold one-on-one investor meetings during the J.P. Morgan Annual Healthcare Meeting 2023, which is scheduled to take place from January 9-12, 2023 in San Francisco, California.

 

On January 9, 2023, the Company provided business updates by way of a press release and an updated investor presentation, which it made available on its website. A copy of the press release is attached hereto as Exhibit 99.1 and a copy of the presentation is attached hereto as Exhibit 99.2.

 

The fact that this presentation is being made available and furnished herewith should not be deemed an admission as to the materiality of any information contained in the materials. The information contained in the presentation is being provided as of January 9, 2023 and the Company does not undertake any obligation to update the presentation in the future or to update forward-looking statements to reflect subsequent actual results.

 

 

 

EXHIBIT INDEX

 

Exhibit No. Description
99.1 Press release dated January 9, 2023
99.2 Corporate Presentation for January 2023

 

 

SIGNATURE

 

Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned, thereunto duly authorized.

 

  GH Research PLC
Date: January 9, 2023  
   
  By: /s/ Julie Ryan
  Name: Julie Ryan
  Title: Vice President, Finance

 

 

Exhibit 99.1

 

 

 

GH Research Provides Business Updates and Highlights Key Upcoming Milestones

 

-Initial approvals received for Phase 2b trial of GH001 in TRD (GH001-TRD-201), initiation of this trial expected in Q1 2023

 

-Development of proprietary aerosol delivery device for GH001 progressed, IND submission with this device expected in Q3 2023

 

-Phase 1 trial of GH002 in healthy volunteers (GH002-HV-105) initiated, completion of this trial expected in Q4 2023

 

-New patent application filed, expanding patent portfolio to 11 families

 

-Mebufotenin selected by WHO as International Nonproprietary Name for 5-MeO-DMT

 

Dublin, Ireland, January 9, 2023 – GH Research PLC (Nasdaq: GHRS), a clinical-stage biopharmaceutical company dedicated to transforming the treatment of psychiatric and neurological disorders, today provided updates on its business and highlighted key upcoming milestones.

 

GH001 for the treatment of TRD

 

GH001 is our proprietary inhalable mebufotenin (5-MeO-DMT) product candidate. We have recently received initial regulatory and ethical approvals for our planned multi-center, randomized, double-blind, placebo-controlled Phase 2b trial of GH001 in treatment-resistant depression (TRD) (GH001-TRD-201). We continue to expect initiation of this trial in several European countries in the first quarter of 2023. Trial design details are described in our updated corporate presentation, which is available in the investor section on our website.

 

Proprietary aerosol delivery device for GH001

 

In 2021, we initiated the development of a proprietary aerosol delivery device for GH001 for use in our pivotal clinical trial program and for commercial use. Based on recent development progress, we now expect to submit an IND for GH001, delivered with this proprietary device, in the third quarter of 2023. The IND-opening study will be a Phase 1 clinical pharmacology trial in healthy volunteers (GH001-HV-106), designed to support bridging to the clinical data generated with the third-party device we currently use in our clinical trials. Due to the progress with our proprietary aerosol delivery device, we no longer plan to submit an IND with this third-party device.

 

GH002

 

GH002 is our mebufotenin (5-MeO-DMT) product candidate formulated for administration via a proprietary injectable approach. The previously announced randomized, double-blind, placebo-controlled, dose-ranging clinical pharmacology trial of GH002 in healthy volunteers (GH002-HV-105) has recently been initiated. We expect to complete this trial in the fourth quarter of 2023.

 

Intellectual property

 

We have recently filed a new device-related patent application, expanding our patent portfolio to 11 patent families, that relate to various aspects of mebufotenin (5-MeO-DMT) use in a therapeutic context, including but not limited to the use of mebufotenin (5-MeO-DMT) for treatment of various disorders when administered by inhalation, or by nasal, buccal, sublingual, intravenous, intramuscular or subcutaneous routes.

 

 

 

 

 

Other updates

 

We are pleased to announce the selection of mebufotenin as the International Nonproprietary Name (INN) for 5-MeO-DMT by the World Health Organization (WHO) Expert Advisory Panel on the International Pharmacopoeia and Pharmaceutical Preparations. From this point forward, we will introduce the nomenclature mebufotenin into our communications.

 

 

About GH Research PLC

 

GH Research PLC is a clinical-stage biopharmaceutical company dedicated to transforming the treatment of psychiatric and neurological disorders. GH Research PLC's initial focus is on developing its novel and proprietary mebufotenin (5-MeO-DMT) therapies for the treatment of patients with treatment-resistant depression (TRD).

 

GH Research PLC's annual report on Form 20-F filed with the U.S. Securities and Exchange Commission for the year ended December 31, 2021 is available at www.ghres.com and shareholders may receive a hard copy free of charge upon request.

 

 

About GH001

 

Our lead product candidate, GH001, is formulated for mebufotenin (5-MeO-DMT) administration via a proprietary inhalation approach. With GH001, we have completed two Phase 1 healthy volunteer clinical trials and a Phase 1/2 clinical trial in patients with treatment-resistant depression (TRD). Based on the observed clinical activity, where 87.5% of patients with TRD were brought into an ultra-rapid remission with our GH001 single-day individualized dosing regimen in the Phase 2 part of the trial, we believe that GH001 has potential to change the way TRD is treated today. Across the GH001 program, no serious adverse events have been reported and GH001 was well tolerated at the investigated single dose levels and in the individualized dosing regimen. GH001 is expected to enter Phase 2b clinical development in TRD in the first quarter of 2023.

 

 

About GH002 and GH003

 

GH002 is our mebufotenin (5-MeO-DMT) product candidate formulated for administration via a proprietary injectable approach. GH002 is currently in Phase 1 clinical development. GH003 is our mebufotenin (5-MeO-DMT) product candidate formulated for administration via a proprietary intranasal administration approach. GH003 is currently in preclinical development.

 

 

 

 

 

 

Forward-Looking Statements

 

This press release contains statements that are, or may be deemed to be, forward-looking statements. All statements other than statements of historical fact included in this press release, including statements regarding our future results of operations and financial position, our cash runway, business strategy, product candidates, research pipeline, ongoing and currently planned preclinical studies and clinical trials, regulatory submissions and approvals, research and development costs, timing and likelihood of success, as well as plans and objectives of management for future operations, are forward-looking statements. Forward-looking statements appear in a number of places in this press release and include, but are not limited to, statements regarding our intent, belief or current expectations. Forward-looking statements are based on our management’s beliefs and assumptions and on information currently available to our management. Such statements are subject to risks and uncertainties, and actual results may differ materially from those expressed or implied in the forward-looking statements due to various factors, including, but not limited to, those described in our filings with the U.S. Securities and Exchange Commission. No assurance can be given that such future results will be achieved. Such forward-looking statements contained in this document speak only as of the date of this press release. We expressly disclaim any obligation or undertaking to update these forward-looking statements contained in this press release to reflect any change in our expectations or any change in events, conditions, or circumstances on which such statements are based unless required to do so by applicable law. No representations or warranties (expressed or implied) are made about the accuracy of any such forward-looking statements.

 

Investor Relations:

Julie Ryan 

GH Research PLC

investors@ghres.com

 

 

 

Exhibit 99.2

 

 

1 Corporate Presentation GH Research PLC (NASDAQ: GHRS) GH Research January 2023 2023© GH Research PLC

 

 

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 the presenter or GH Research or any director, employee, agent, or adviser of GH Research. This presentation does not purport to be all - inclusive or to contain all of the information you may desire. This presentation does not constitute an offer to sell or the solicitation of an offer to buy securities, nor shall there be any sale of these securities in any state or jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction. 2 This presentation contains forward - looking statements, all of which are qualified in their entirety by this cautionary statement. Many of the forward - looking statements contained herein can be identified by the use of forward - looking words such as “may”, “anticipate”, “believe”, “could’, “expect”, “should”, “plan”, “intend”, “estimate”, “will”, “potential” and “ongoing”, among others, although not all forward - looking statements contain these identifying words. Any statements contained herein that do not describe historical facts are forward - looking statements that are based on management’s expectations and are subject to certain factors, risks and uncertainties that may cause actual results, outcomes, timing and performance to differ materially from those expressed or implied by such statements. These factors, risks and uncertainties include, but are not limited to: the costs and uncertainties associated with GH Research’s research and development efforts; the inherent uncertainties associated with the conduct, timing and results of nonclinical and clinical studies of GH Research’s product candidates; GH Research’s ability to obtain, maintain, enforce and defend issued patents; the adequacy of GH Research’s capital resources, the availability of additional funding and GH Research’s cash runway ; and other factors, risks and uncertainties described in GH Research’s filings with the U.S. Securities and Exchange Commission . Except as otherwise noted, these forward - looking statements speak only as of the date of this presentation, and GH Research undertakes no obligation to update or revise any of such statements to reflect events or circumstances occurring after this presentation. Because forward - looking statements are inherently subject to risks and uncertainties, some of which cannot be predicted or quantified and some of which are beyond GH Research’s control, you should not rely on these forward - looking statements as predictions of future events. The events and circumstances reflected in any such forward - looking statements may not be achieved or occur and actual results could differ materially from those projected in the forward - looking statements. GH Research cautions you not to place undue reliance on the forward - looking statements contained in this presentation. 2023© GH Research PLC

 

 

Seeking Ultra - Rapid, Durable Remissions in Depression 3 2023© GH Research PLC

 

 

Stage of Development PROGRAMS INDICATION PRECLINICAL PHASE 1 PHASE 2a PHASE 2b PHASE 3 CURRENT STATUS GH001 Mebufotenin (5 - MeO - DMT) for inhalation administration Treatment - Resistant Depression (TRD) Phase 2b CTAs submitted (GH001 - TRD - 201) Bipolar II Disorder * (BDII) Phase 2a POC trial initiated (GH001 - BD - 202) Postpartum Depression (PPD) Phase 2a POC trial initiated (GH001 - PPD - 203) GH002 Mebufotenin (5 - MeO - DMT) for i.v. administration Psychiatric or Neurological Disorder Phase 1 in HVs initiated (GH002 - HV - 105) GH003 Mebufotenin (5 - MeO - DMT) for nasal administration Psychiatric or Neurological Disorder Pre - clinical development ongoing Pipeline 4 2023© GH Research PLC * Bipolar II disorder with a current maj or d epressive ep isode 5 - MeO - DMT, 5 - Methoxy - N,N - Dimethyltryptamine; i.v. , intravenous; CTA, Clinical Trial Application; POC, P roof - of - Concept; HV, Healthy V olunteer Complete Ongoing

 

 

0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% 0 2 4 6 8 10 12 14 Cumulative Remission Rate (% Patients) Week ... Remission Rates in TRD < 15% Established Therapies are Slow - Acting 37% 31% 14% 13% 56% 62% 67% 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% 1 2 3 4 Cumulative Remission Rate (%) (line) Remission Rates (%) (bar) Treatment Step ~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, Remission Rate Over Time, Treatment Step 1 = Citalopram) The Problem for Patients with Depression (STAR*D study, Remission Rates Treatment Steps 1 to 4) 5 2 or more prior therapies = TRD 2023© GH Research PLC

 

 

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 lines: ~9M Company estimates based on: https://www.nimh.nih.gov/health/statistics/major - depression.shtml; Wittchen et al., The size and burden of mental disorders and other disorders of the brain in Europe 2010, European Neuropsychopharmaco lo gy (2011); Rush et al., Acute and Longer - Term Outcomes in Depressed Outpatients Requiring One or Several Treatment Steps: A STAR*D Report, Am J Psychiatry 2006 MDD, Major Depressive Disorder 2023© GH Research PLC

 

 

• 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 • High propensity to induce peak experiences (PE), which may be a surrogate marker for therapeutic effects • GH001 ( Mebufotenin administration via a proprietary pulmonary inhalation approach) • Psychoactive effects with ultra - rapid onset (within seconds) and short duration (5 to 30 min) • Intraday individualized dosing regimen (IDR) for m aximization of ultra - rapid and durable remissions • Single visit initial treatment, with no structured psychotherapy • Potential for convenient and infrequent retreatment Mebufotenin (5 - MeO - DMT) and GH001 7 2023© GH Research PLC Mebufotenin (5 - MeO - DMT) Foundational IP

 

 

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 1 Hypothetical Patient 2 Hypothetical Patient 3 Hypothetical Patient 1 Hypothetical Patient 2 No remission No remission No remission Dose 1 GH001 – Individualized Dosing Regimen (IDR) for Maximization of Ultra - Rapid and Durable Remissions 8 2023© GH Research PLC MADRS score Dose 1 MADRS, Montgomery - Åsberg Depression Rating Scale

 

 

Phase 1 Trial in Healthy Volunteers GH001 - HV - 101 (Completed) 9 Clinicaltrials.gov ID: NCT04640831 2023© GH Research PLC

 

 

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 GH001 IDR 6, 12, 18 mg to achieve PE (up to 3 doses , 3h interval) Key Assessments Safety PE Scale Cognitive function Safety Safety Cognitive function 1 The PE Scale averages answers scored by the subject by marking a visual analogue scale between 0 and 100 for the following th ree questions: 1. How intense was the experience; 2. To what extent did you lose control; 3. How profound (i.e., deep and significant) was t he experience? Design of Phase 1 Trial in Healthy Volunteers (GH001 - HV - 101) 10 2023© GH Research PLC HV, Healthy V olunteer; PE, Peak Experience; IDR, Individualized Dosing Regimen

 

 

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 • No clinically significant changes in safety laboratory analyses, psychiatric safety assessments or measures of cognitive function ADRs Part A (Single Dose ) Part B (IDR) 2 mg (n=4) 6 mg (n=6) 12 mg (n=4) 18 mg (n=4) IDR 1 (n=4) MedDRA Preferred Term Number of Events Abnormal dreams 1 Anxiety 1 1 Clumsiness 1 Confusional state 1 Euphoric mood 1 Fatigue 1 1* Feeling hot 1 Flashback 1 Hallucination 1 Head discomfort 1 Headache 2 1 1 Heart rate increased 1* Hyperacusis 1 Insomnia 1 Mental fatigue 1 Nausea 2 1 1 2 Vision blurred 1 Part A (Single Dose) and Part B (IDR) – Safety 11 2023© GH Research PLC 1 6 mg (n=1); 6 - 12 mg (n=2); 6 - 12 - 18 mg (n=1) SAE, Serious Adverse Event; ADR, Adverse Drug Reaction, an adverse event with a relationship code to the investigational prod uct of definite, probable, or possible, or where code is missing; IDR, Individualized Dosing Regimen

 

 

0 10 20 30 40 50 60 70 80 90 100 P4 P1 P2 P3 P9 P8 P10 P7 P5 P6 P13 P11 P14 P12 P15 P18 P17 P16 2 mg 6 mg 12 mg 18 mg Average for dose group PE Scale PE Threshold Part A – Peak Experience (PE) Dose - Effects and Inter - Person Variability 12 PE, Peak E xperience 2023© GH Research PLC

 

 

0 10 20 30 40 50 60 70 80 90 100 6 mg 6 mg 12 mg 6 mg 12 mg 6 mg 12 mg 18 mg P21 P19 P22 P20 PE Scale PE Threshold Part B – Peak Experience (PE) Effect of Intraday Individualized Dosing Regimen (IDR) 13 PE, Peak Experience 2023© GH Research PLC

 

 

Phase 1/2 Trial in Treatment - Resistant Depression GH001 - TRD - 102 (Completed) 14 Clinicaltrials.gov ID: NCT04698603 2023© GH Research PLC

 

 

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 1 D efined as inadequate response to at least two adequate courses of pharmacological therapy or one adequate course of pharmacological therapy and at least one adequate course of evidence - based psychotherapy 2023© GH Research PLC Phase 1 (Single Dose) Phase 2 (IDR) GH001 12 mg (n=4) GH001 18 mg (n=4) TRD 1 (n=8) Primary Endpoint: • Safety until day 7 TRD 1 (n=8) Primary Endpoint: • MADRS remission day 7 (MADRS≤10) GH001 IDR 6, 12, 18 mg to achieve PE (up to 3 doses, 3h interval) TRD, Treatment - Resistant Depression; PE, Peak Experience; MADRS, Montgomery - Åsberg Depression Rating Scale; IDR, Individualized Dosing Regimen; H, Hour; D, Day

 

 

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 increase in heart rate and blood pressure shortly after administration of GH001 • No clinically significant changes in safety laboratory analyses, psychiatric safety assessments or measures of cognitive function • No safety signal relating to suicidal ideation or suicidal behavior, based on C - SSRS and MADRS subscore item “suicidal thoughts” ADRs Phase 1 (Single Dose ) Phase 2 (IDR) 12 mg (n=4) 18 mg (n=4) IDR 1 (n=8) MedDRA Preferred Term Number of Events Abdominal discomfort 1 Anxiety 2 Depressive symptom 1* Dizziness 1 Feeling abnormal 1 1 Flashback 1 1 2 Headache 2 1 3 Muscle discomfort 1 Muscle spasms 1 Nausea 2* Paresthesia 1 Sensory disturbance 3 1 6 - 12 mg (n=6); 6 - 12 - 18 mg (n=2) SAE, Serious Adverse Event; ADR, Adverse Drug Reaction, an adverse event with a relationship code to the investigational prod uct of definite, probable, or possible, or where code is missing; IDR, Individualized Dosing Regimen; C - SSRS, Columbia - Suicide Severity Rating Scale; MADRS, Montgomery - Åsberg Depression Rating Scale

 

 

50% 25% 50% 50% 100% 100% 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% 12 mg (n=4) 18 mg (n=4) MADRS remission MADRS response MADRS any improvement MADRS Remission / Response / Improvement Rate Day 7 Phase 1 (Single Dose) – Efficacy (MADRS) 17 PE, Peak Experience; MADRS, Montgomery – Åsberg Depression Rating Scale MADRS remission = MADRS of ≤10; MADRS response = Reduction of ≥50% from baseline in MADRS; MADRS any improvement = any reduct ion from baseline in MADRS. 2023© GH Research PLC • 2 of 4 (50%) in the 12 mg group and 1 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

 

 

87.5% 87.5% 100% 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% Individualized Dosing Regimen MADRS remission MADRS response MADRS any improvement 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, Montgomery – Åsberg Depression Rating Scale MADRS remission = MADRS of ≤10; MADRS response = Reduction of ≥50% from baseline in MADRS; MADRS any improvement = any reduct ion from baseline in MADRS. .

 

 

- 19.3 - 27.1 - 24.4 -30 -25 -20 -15 -10 -5 0 MADRS Mean Change From Baseline Mean (n=8) Phase 2 (IDR) – Efficacy (MADRS Change from Baseline) 2023© GH Research PLC 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 and 4 of 7 remissions from 2 hours 1 Baseline mean MADRS=32

 

 

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% (7 of 8) 50% (2 of 4) 0% (0 of 4) Mean PE Score 90.4 (at final dose) 58.2 59.1 2023© GH Research PLC 20 PE, Peak Experience; MADRS, Montgomery - Åsberg Depression Rating Scale; IDR, Individualized Dosing Regimen

 

 

Phase 1 Clinical Pharmacology Trial in Healthy Volunteers GH001 - HV - 103 (Completed) 21 2023© GH Research PLC Clinicaltrials.gov ID: NCT05163691

 

 

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 IDR 6, 12, 18 mg to achieve PE (up to 3 doses, 1h interval , n=8) Key Assessments Safety Pharmacokinetics PE Scale Cognitive function Safety Cognitive function Safety 22 Day 30 GH001 IDR 6, 12, 18 mg to achieve PE (up to 3 doses, 2h interval , n=8) Primary Endpoint: • Pharmacokinetic profile of mebufotenin (5 - MeO - DMT) and bufotenine 2023© GH Research PLC Design of Phase 1 Clinical Pharmacology Trial in Healthy Volunteers (GH001 - HV - 103) HV, Healthy V olunteer; PE, Peak Experience; IDR, Individualized Dosing Regimen

 

 

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, safety laboratory analyses, peak flow, cognitive function, psychiatric safety assessments, including the C - SSRS Further Results • Pharmacokinetic analyses and psychoactive effect assessments (PE Scale) support that an interval down to 1 hour between individual doses of the IDR is feasible for future clinical trials Single Dose and IDR – Safety and Further Results 23 Adverse Drug Reaction, or ADR, an adverse event with a relationship code to the investigational product of definite, probable , o r possible, or where code is missing IDR, Individualized Dosing Regimen; C - SSRS, Columbia - Suicide Severity Rating Scale; PE, Peak Experience 2023© GH Research PLC ADRs Single - dose IDR 6 mg (n=8) 12 mg (n=8) 18 mg (n=8) Placebo (n=6) 1h interval (n=8) 1 2h interval (n=8) 2 MedDRA Preferred Term Number of Events Abnormal dreams 1 Chest discomfort 1 Crying 2 2 Dizziness 1 Dry mouth 1 Dyskinesia 1 Fatigue 1 2 1 Headache 3 1 1 1 Hypoesthesia oral 1 Paresthesia oral 1 Retching 1 Somnolence 1 Tachycardia 2 Tension 1 Tremor 1 1 6 mg (n=1), 6 - 12 mg (n=3); 6 - 12 - 18 mg (n=4) 2 6 - 12 mg (n=3); 6 - 12 - 18 mg (n=5)

 

 

Phase 2b Trial in Treatment - Resistant Depression GH001 - TRD - 201 (Initiation Expected Q1 2023) 24 2023© GH Research PLC EudraCT Number : 2022 - 000574 - 26

 

 

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 IDR s 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 B H2 Scheduled Visit Double - Blind Phase Open - label Extension Phase (OLE) The bold solid lines indicate the fixed duration of 7 days ( ± 1 day) after an IDR with visits on D0, D1 and D7. The bold dotted line indicates the variable duration until a potential GH00 1 IDR in the OLE. The GH001 IDR consists of up to 3 increasing doses (6, 12, 18 mg) and the Placebo IDR consists of up to three placebo doses, to achieve a peak experience, given at a 1H interval. As in previously completed trials, the GH001 - TRD - 201 trial will be conducted under the supervision of a healthcare provider, but without any planned psychotherapeutic interventions before, during, or after dosing. IDR, Individualized Dosing Regimen; PRN, pro re nata (as needed); B, Baseline; H, Hour; D, Day; M, Month. *FDA Guidance for I ndu stry: Major Depressive Disorder: Developing Drugs for Treatment D14 M2 M3 M4 M5 M6 M1 During the OLE, additional clinic visits can be scheduled if required for medical reasons D0 D1 D7 B H2 PRN

 

 

LAYER 1: REGULATORY EXCLUSIVITY FDA: 5 years (+2.5 years paragraph IV stay) EMA: 10 years (+1 year for new indication) LAYER 3: TECHNICAL Complex bioequivalence for systemically - acting inhalation/intranasal products with high intra - and inter - subject variability LAYER 2: PATENTS 11 patent families filed relating to mebufotenin (5 - MeO - DMT), including : • Novel aerosol compositions of matter • Novel manufacturing methods and novel salt forms • Novel uses in various disorders (including inhaled, nasal, buccal, sublingual, i.v. , i.m. , s.c. routes) • Novel device - related​ technologies Three - Layer Protection Strategy 26 2023© GH Research PLC

 

 

Board of Directors & 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 ACA, MAcc, BComm VP, Finance Magnus Halle BSc Managing Director, Ireland, Co - founder

 

 

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. Dr. Head, Psychiatry Unit, Hospital Clínic de Barcelona Michael Bauer Prof. Dr. rer. nat. Dr. med. Chair, Department of Psychiatry and Psychotherapy, Technische Universität Dresden Malek Bajbouj Prof. Dr. med. Head, Center for Affective Neuroscience, Charité, Berlin Johannes Ramaekers Prof. Dr. Professor, Faculty of Psychology and Neuroscience of Maastricht University 2023© GH Research PLC

 

 

Anticipated Milestones and Financial Overview • GH001 • Initiate multi - center, randomized, double - blind, placebo - controlled Phase 2b trial in TRD in Q1 2023 • Submit U.S. IND for GH001 with proprietary aerosol delivery device in Q3 2023 • Complete proof - of - concept Phase 2a trials in BDII and in PPD in Q4 2023 • GH002 • Complete Phase 1 clinical pharmacology trial in healthy volunteers in Q4 2023 • GH003 • Complete preclinical development • Financial Overview • Cash was $256.9 million as of September 30, 2022 • We believe existing cash will be sufficient to fund operating expenses and capital expenditure requirements into 2025 29 2023© GH Research PLC

 

 

Seeking Ultra - Rapid, Durable Remissions in Depression 30 2023© GH Research PLC