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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 March, 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”) provided business updates on March 2, 2023 by way of a press release and an updated corporate presentation. 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 press release and 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 press release and the presentation is being provided as of March 2, 2023 and the Company does not undertake any obligation to update the press release or presentation in the future or to update forward-looking statements to reflect subsequent actual results.

1
EXHIBIT INDEX

Exhibit No.
Description
Press release dated March 2, 2023
Corporate Presentation for March 2023

2
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: March 2, 2023
  
   
 
By:
/s/ Julie Ryan
 
Name:
Julie Ryan
 
Title:
Vice President, Finance


 3
Exhibit 99.1


GH Research Reports Full Year 2022 Financial Results and Provides Business Updates

DUBLIN, Ireland., March 2, 2023 (GLOBE NEWSWIRE) -- GH Research PLC (Nasdaq: GHRS), a clinical-stage biopharmaceutical company dedicated to transforming the treatment of psychiatric and neurological disorders, today reported financial results for the full year ended December 31, 2022 and gave updates on its business.
 
Business Updates
 
We are pleased to report that we have recently initiated our multi-center, randomized, double-blind, placebo-controlled Phase 2b trial of GH001 in treatment-resistant depression (TRD) (GH001-TRD-201). GH001 is our proprietary inhalable mebufotenin (5-MeO-DMT) product candidate.
 
We expect to recruit approximately 80 patients for this trial across several European countries. The primary objective will be to determine the efficacy of our single-day individualized dosing regimen (IDR) of GH001 compared with placebo in improving depressive symptoms as assessed by the mean change from baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) at the end of the 7-day double-blind phase. The double-blind phase will be followed by a 6-month open-label extension phase where all patients can receive treatment with the GH001 IDR as-needed, based on the patient’s clinical status. Further trial design details are described in our updated corporate presentation, which is available in the investor section on our website.
 
Recent Business Highlights
 
In January 2023, we reported development progress in respect of our proprietary aerosol delivery device and our expectation that we will submit an IND for GH001, delivered with this proprietary device, in the third quarter of 2023. The IND-opening study is expected to 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.
 
We also reported, in January 2023, the recent initiation of our randomized, double-blind, placebo-controlled, dose-ranging clinical pharmacology trial of GH002 in healthy volunteers (GH002-HV-105). GH002 is our mebufotenin (5-MeO-DMT) product candidate formulated for administration via a proprietary intravenous approach. We expect to complete this trial in the fourth quarter of 2023.
 
Furthermore, we reported the recent expansion of our patent portfolio, to include 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.
 
We also announced 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.
 
Full Year 2022 Financial Highlights
 
Cash position
 
Cash, cash equivalents and marketable securities were $251.7 million as of December 31, 2022, compared to cash of $276.8 million as of December 31, 2021. Marketable securities are comprised of investment grade bonds. We believe that our existing cash, cash equivalents and marketable securities will be sufficient for us to fund our operating expenses and capital expenditure requirements into 2026.
 
Research and development expenses
 
R&D expenses were $20.5 million for the year ended December 31, 2022, compared to $8.6 million for the full year 2021. The increase was primarily due to increased activities relating to our technical development, clinical trials and increased employee expenses to support these activities.
 
General and administrative expenses
 
G&A expenses were $10.1 million for the year ended December 31, 2022, compared to $6.5 million for the full year 2021. The increase was primarily due to higher insurance costs, an increase in professional costs as well as increased employee expenses.
 
Net loss
 
Net loss was $22.5 million, or $0.432 loss per share, for the year ended December 31, 2022, compared to $9.2 million, or $0.211 loss per share, for the full year 2021.
 
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).
 
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 individualized single-day dosing regimen in the Phase 2 part of the trial, we believe that GH001 has potential to change the way TRD is treated today. GH001 is currently in a multi-center, randomized, double-blind, placebo-controlled Phase 2b trial of GH001 in treatment-resistant depression (TRD). 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.
 
About GH002 and GH003
 
GH002 is our mebufotenin (5-MeO-DMT) product candidate formulated for administration via a proprietary intravenous 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. We anticipate developing GH002 and GH003 in subpopulations and confined use scenarios within our focus area of psychiatric and neurological disorders.
 
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, cash runway, business strategy, product candidates, proprietary medical devices, 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 press release speak only as of the date hereof. 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
 
GH RESEARCH PLC
 
Consolidated Statement of Comprehensive Income (Unaudited)
 
(in thousands, except share and per share amounts)


  
Year ended
December 31,
  

 
2022
    
2021
  

 
$’000
    
$’000
  

               
Operating expenses
                
Research and development
    
(20,484
)
    
(8,553
)
General and administration
    
(10,070
)
    
(6,547
)
Loss from operations
    
(30,554
)
    
(15,100
)
                 
Net finance income/(expense)
    
922
      
(9
)
Foreign exchange gain
    
7,176
      
5,907
  
Total finance income
    
8,098
      
5,898
  
                 
Loss before tax
    
(22,456
)
    
(9,202
)
Tax charge/(credit)
    
—
      
—
  
Loss for the year
    
(22,456
)
    
(9,202
)
                 
Other comprehensive income/(expense)
                
Items that may be reclassified to profit or loss
                
Fair value movement on marketable securities
    
558
      
—
  
Currency translation adjustment
    
(7,132
)
    
(6,103
)
Total comprehensive loss for the year
    
(29,030
)
    
(15,305
)
                 
Attributable to owners:
                
Loss for the year
    
(22,456
)
    
(9,202
)
Comprehensive loss for the year
    
(29,030
)
    
(15,305
)
                 
Loss per share
                
Basic and diluted loss per share (in USD)
    
(0.432
)
    
(0.211
)

GH RESEARCH PLC
 
Consolidated Balance Sheet (Unaudited)
 
(in thousands)
 
   
At December 31,
  
   
2022
    
2021
  
   
$’000
    
$’000
  
ASSETS
                
Current assets
                
Cash and cash equivalents
    
165,955
      
276,776
  
Other current assets
    
2,586
      
3,066
  
Total current assets
    
168,541
      
279,842
  
Non-current assets
                
Marketable securities
    
85,724
      
—
  
Property, plant and equipment
    
97
      
82
  
Total non-current assets
    
85,821
      
82
  
Total assets
    
254,362
      
279,924
  
                 
LIABILITIES AND EQUITY
                
Current liabilities
                
Trade payables
    
1,868
      
883
  
Other current liabilities
    
2,678
      
1,866
  
Total current liabilities
    
4,546
      
2,749
  
Total liabilities
    
4,546
      
2,749
  
                 
Equity attributable to owners
                
Share capital
    
1,301
      
1,301
  
Additional paid-in capital
    
291,448
      
291,448
  
Other reserves
    
2,595
      
366
  
Foreign currency translation reserve
    
(13,035
)
    
(5,903
)
Accumulated deficit
    
(32,493
)
    
(10,037
)
Total equity
    
249,816
      
277,175
  
Total liabilities and equity
    
254,362
      
279,924
  

 
Exhibit 99.2

 1  Corporate Presentation  GH Research PLC (NASDAQ: GHRS)  GH Research  March 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  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(GH001-BD-202)  Postpartum Depression (PPD)  Phase 2a POC trial initiated(GH001-PPD-203)  GH002Mebufotenin (5-MeO-DMT) for i.v. administration   Psychiatric or Neurological Disorder  Phase 1 HV trial initiated(GH002-HV-105)  GH003Mebufotenin (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 major depressive episode  5-MeO-DMT, 5-Methoxy-N,N-Dimethyltryptamine; i.v., intravenous; RDBPC, Randomized, Double-Blind, Placebo-Controlled; POC, Proof-of-Concept; HV, Healthy Volunteer   Complete  Ongoing 
 
 ... 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, 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 Neuropsychopharmacology (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 2006MDD, 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  GH001 (Mebufotenin administration via a proprietary pulmonary inhalation approach)  Psychoactive effects with ultra-rapid onset (within seconds) and short duration (5 to 30 min)  High propensity to induce peak experiences (PE), which may be a surrogate marker for therapeutic effects  Intraday individualized dosing regimen (IDR) for maximization 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 IDR6, 12, 18 mg to achieve PE  (up to 3 doses, 3h interval)  Key Assessments  Safety  PE Scale  Cognitive function  Safety  Safety  Cognitive function  1The PE Scale averages answers scored by the subject by marking a visual analogue scale between 0 and 100 for the following three questions: 1. How intense was the experience; 2. To what extent did you lose control; 3. How profound (i.e., deep and significant) was the experience?  Design of Phase 1 Trial in Healthy Volunteers (GH001-HV-101)  10  2023© GH Research PLC  HV, Healthy Volunteer; 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)  ADRs  2 mg (n=4)  6 mg (n=6)  12 mg (n=4)  18 mg (n=4)  IDR1 (n=4)  MedDRA Preferred Term  Number of Events  n  n  n  n  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  16 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 product of definite, probable, or possible, or where code is missing; IDR, Individualized Dosing Regimen 
 
 Average fordose group  PE Scale  PEThreshold  Part A – Peak Experience (PE) Dose-Effectsand Inter-Person Variability  12  PE, Peak Experience  2023© GH Research PLC 
 
 PEThreshold  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  1Defined 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)  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 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)  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  Muscle discomfort  1  Muscle spasms     1     Nausea        2*  Paresthesia        1  Sensory disturbance  3  16-12 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 product 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 
 
 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 baseline in MADRS.  2023© GH Research PLC  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 
 
 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 ScaleMADRS remission = MADRS of ≤10; MADRS response = Reduction of ≥50% from baseline in MADRS; MADRS any improvement = any reduction from baseline in MADRS.. 
 
 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 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 IDR6, 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 IDR6, 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 Volunteer; 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  SAE, Serious Adverse Event; Adverse Drug Reaction, or ADR, an adverse event with a relationship code to the investigational product of definite, probable, or 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  n  n  n  n  n  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        16 mg (n=1), 6-12 mg (n=3); 6-12-18 mg (n=4)26-12 mg (n=3); 6-12-18 mg (n=5) 
 
 Phase 2b Trial in  Treatment-Resistant Depression  GH001-TRD-201  (Initiated)  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 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  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 GH001 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 draft guidance for industry “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: TECHNICALComplex 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 uses in various disorders (including inhaled, nasal, buccal, sublingual, i.v., i.m., s.c. routes)   Novel aerosol compositions of matter  Novel manufacturing methods and novel salt forms   Novel device-related​ aspects  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  Complete multi-center, randomized, double-blind, placebo-controlled Phase 2b trial in TRD  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, cash equivalents and marketable securities was $251.7 million as of December 31, 2022  We believe existing cash, cash equivalents and marketable securities will be sufficient to fund operating expenses and capital expenditure requirements into 2026  29  2023© GH Research PLC 
 
 Seeking  Ultra-Rapid, Durable Remissions  in Depression  30  2023© GH Research PLC