EX-99.4 5 ef20035537_ex99-4.htm EXHIBIT 99.4

Exhibit 99.4
GH Research PLC (NASDAQ: GHRS) November 2024 Corporate Presentation 1

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 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. 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 expectations related to the clinical hold on the GH001 IND, including plans and expectations for progressing any nonclinical programs and any other work to lift the clinical hold and the timing required to lift such clinical hold; 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. Disclaimer Regarding Forward-Looking Statements 2

Stage of Development PROGRAMS INDICATION PRECLINICAL PHASE 1 PHASE 2a PHASE 2b PHASE 3 CURRENT STATUS MILESTONES GH001Mebufotenin for inhalation administration Treatment-Resistant Depression (TRD) Phase 2b RDBPC DB phase completed Phase 1 PK trial with proprietary device ongoing Phase 2b OLE completion in Q1 Phase 1 PK trial completion Lift FDA clinical hold in the US GH002Mebufotenin for i.v. administration Psychiatric or Neurological Disorder Phase 1 HV trial completed Update on next steps OTHER INDICATIONS GH001 Postpartum Depression (PPD) Phase 2a POC Completion in Q4 Bipolar II Disorder* (BDII) Phase 2a POC Completion in Q4 3 Complete Ongoing *Bipolar II disorder with a current major depressive episode Abbreviations: i.v. = intravenous; RDBPC = Randomized, Double-Blind, Placebo-Controlled; PK = Pharmacokinetics; OLE = Open-Label Extension; FDA = U.S. Food and Drug Administration; HV = Healthy Volunteer; POC = Proof-of-Concept Pipeline Cash, cash equivalents, other financial assets and marketable securities were $193.8 million as of September 30, 2024

The Problem for Patients with Depression Established Therapies are Slow-Acting ... Remission Rates in TRD < 15% 4 (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 2 or more prior therapies = TRD Adapted from Trivedi et al., Am J Psychiatry 2006 and Rush et al., Am J Psychiatry 2006 Abbreviations: TRD = Treatment-Resistant Depression

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 and US 5 Company estimates based on sources 1,2,3 Abbreviations: MDD = Major Depressive Disorder Sources: 1) NIMH major depression statistics; 2) Wittchen et al., Eur Neuropsychopharmacol 2011; 3) Rush et al., Am J Psychiatry 2006

SPRAVATO® has been established as a $1-5Bn drug in interventional psychiatry Quarterly sales, $M; Estimated annual WAC of $32,400 Estimated 40 administration visits per year: In-clinic Mandatory 2-hour post-dose monitoring No driving or operating heavy machinery until next day No psychotherapeutic intervention required -4.0 Approved for TRD in Conjunction with an Oral AD -4.0 MADRS Points Mean Δ to Control Group Abbreviations: MADRS = Montgomery–Åsberg Depression Rating Scale; TRD = Treatment-Resistant Depression; LS = Least Square; AD = Antidepressant; WAC = Wholesale Acquisition Cost aBaseline mean MADRS = 37 Sources: 1) Popova et al., Am J Psychiatry 2019; 2) Institute for Clinical and Economic Review (ICER) Final Evidence Report, 2019; 3) SPRAVATO® Prescribing Information; 4) Johnson & Johnson Quarterly Earnings Reports, 2022-2024 a (TRANSFORM-2 Trial Primary Endpoint, Difference of LS Means) 6

The GH001 Aspirational Profile Maximize Day 2 Response Rate ✔✔✔✔ ✔ Maximize Day 8 Response Rate ✔✔✔✔ ✔ Minimize In-Clinic, Post-Administration Monitoring ≤ 1 hour ≥ 2 hours Minimize Post-Discharge Restrictions None No driving or operating machinery until the next day after a restful sleep Optimize Fewer Administration Visits / Greater Durability ✔✔✔✔ ✔ SPRAVATO® GH001 features based on clinical data generated to-date, and treatment model as per the protocol currently being investigated in GH001-TRD-201 SPRAVATO features based on Ph3 clinical trial data, and treatment model as per FDA label (1) and Johnson & Johnson Access, Coding and Reimbursement Guidelines (2) Sources: 1) SPRAVATO® Prescribing Information; 2) Johnson & Johnson Spravato Access, Coding and Reimbursement Guide GH001 Treatment objectives 7 2024© GH Research PLC

80% less patient time required with GH001 8 GH001 Based on ICER estimate Based on Phase 2b trial design Abbreviations: ICER = Institute for Clinical and Economic Review Sources: 1) Johnson & Johnson Spravato Access, Coding and Reimbursement Guide; 2) ICER Spravato Final Evidence Report; 3) Janssenscience.com, Dosage and Administration of Spravato, Duration of Therapy; 4) Negaro et al. Health Affairs Scholar. 2023 Patient time required over a year (hours, in-clinic and travel time) Assumptions: GH001: assumes 6 or 12 treatment sessions, 3x doses per treatment session (maximum possible), 3h for dosing & monitoring, 20min wrap-around time (based on SPRAVATO® delivery model (1)), 45min travel time each way (4) SPRAVATO®: Assumes 40 treatment sessions, as per standard initiation protocol of 8 & 4 sessions in months 1 & 2, respectively, and ICER assumed maintenance treatment frequency of 2.86 treatments per month for months 3-12 (1,2,3); 2h20 per treatment session inclusive of wrap-around time, based on Spravato delivery model (1); 45min travel time each way (4) Note: To-date, no head-to-head comparisons of any competing products to any of our product candidates in any clinical trial have been completed ~80% less time with 6 hypothetical treatment visits in a year At least 60% with a hypothetical maximum of 12 treatment visits 29 2024© GH Research PLC

GH001-HV-1032 (Healthy Volunteers) GH001 6 mg (n=8+2 placebo) GH001 12 mg (n=8+2 placebo) GH001 18 mg (n=8+2 placebo) GH001 IDR (6, 12, 18 mg)up to 3 doses, 1h interval (n=8) GH001 IDR (6, 12, 18 mg) up to 3 doses, 2h interval (n=8) 9 Completed GH001 Clinical Trials: Trial Design GH001-HV-1011 (Healthy Volunteers) IDR Part (Open-Label) D1 D7 D0 GH001 IDR (6, 12, 18 mg)up to 3 doses, 3h interval (n=4) n=18 GH001 12 mg (n=4) GH001 2 mg (n=4) GH001 6 mg (n=6) GH001 18 mg (n=4) Single-Dose Part (Open-Label) Single-Dose Part (Double-Blind) IDR Part (Open-Label) GH001-TRD-1023 (Treatment-Resistant Depression) Phase 1 (Single-Dose, Open-Label) Phase 2 (IDR, Open-Label) GH001 12 mg (n=4) GH001 18 mg (n=4) GH001 IDR (6, 12, 18 mg) up to 3 doses, 3h interval (n=8) Abbreviations: D = Day; h = Hour; IDR = Individualized dosing regimen; TRD = Treatment-Resistant Depression. Sources: 1) Reckweg JT, et al. Eur Psychiatry. 2022; 2) GH Research, Data on file; 3). Reckweg JT, et al. Front. Psychiatry. 2023 D7 D30 D0 D1 D7 D0

GH001-TRD-102 | Efficacy of the GH001 IDRPhase1/2 trial of GH001 in TRD (completed) 10 Abbreviations: MADRS = Montgomery–Åsberg Depression Rating Scale; IDR = Individualized dosing regimen aBaseline mean MADRS = 32. Sources: 1) Reckweg JT, et al. Front. Psychiatry. 2023. Hour 2 Day 1 Day 7 GH001 p=0.0018 p<0.0001 p<0.0001 Baselinea Key results1: 87.5% (7/8) patients achieved remission by Day 7 Mean change from baseline in MADRS score was -24.4 at day 7 2024© GH Research PLC

Safety and Tolerability of GH001 in Completed TrialsGH001-HV-1011, GH001-HV-1032, and GH001-TRD-1023 11 Safety Parameters, n (% of population) Overall Population (n=78) Any TEAE 50 (64%) Headache 19 (24%) Anxiety 12 (15%) Nausea 8 (10%) Fatigue 7 (9%) Any Serious AE 0 (0%) Any AE leading to trial/drug withdrawal 0 (0%) Death 0 (0%) TEAEs by Severity, no. of events Overall Population (n=78) Total number of TEAEs 105 Mild TEAEs 97 Moderate TEAEs 8 Severe TEAEs 0 Abbreviations: AE = Adverse event; TEAE = Treatment-emergent adverse event. Sources: 1) Reckweg JT, et al. Eur Psychiatry. 2022; 2) GH Research, Data on file; 3) Reckweg JT, et al. Front. Psychiatry. 2023. Overall, inhalation of GH001 was well tolerated across completed trials with no severe or serious adverse events reported and with TEAEs observed in 64.1% of subjects 92.4% of TEAEs were mild in severity No noteworthy changes in vital signs were observed; transient increases in heart rate and blood pressure shortly after GH001 administration were not clinically significant Safety assessments, including laboratory analyses, psychiatric scales, electrocardiogram, and cognitive function tests showed no clinically meaningful changes

(Initiated) Phase 2b Trial inTreatment-Resistant DepressionGH001-TRD-201 12 EudraCT Number: 2022-000574-26

GH001-TRD-201 Trial DesignPhase 2b trial in patients with TRD, n=801 13 Abbreviations: D = Day; h = Hour; BL = Baseline; IDR = Individualized dosing regimen; M = Month; MADRS = Montgomery–Åsberg Depression Rating Scale; OLE = Open-label extension; TRD = Treatment-resistant depression. a The double-blind phase was a fixed duration of 7 days (± 1 day) after an IDR with visits on D0, D1 and D7. After the double-blind phase there was a variable duration until a potential GH001 IDR in the OLE. bDuring the OLE, additional clinic visits can be scheduled if required for medical reasons. cThe GH001 IDR consists of up to 3 increasing doses (6, 12, 18 mg) and the placebo IDR consists of up to three placebo doses. 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. Sources: 1) NCT05800860. (2024). A Trial of GH001 in Patients With Treatment-Resistant Depression. ClinicalTrials.gov. Accessed August 23, 2024. Double-Blind Phasea n=80 Randomization 1:1 GH001 IDRc Placebo IDRc Up to 5 GH001 IDRs may be administered during the OLE as needed, based on specific re-treatment criteria BL Open-Label Extension Phaseb 2h Open-label Extension Phase (OLE)b Day 0 Primary Endpoint ΔMADRS Day 7 During the OLE, patients attend scheduled assessment visits at day 15, month 1,2,3,4,5 & 6 Additional clinic visits can be scheduled if required for medical reasons MADRS assessment Double-Blind Phasea Month 6 D1 Day 1 2024© GH Research PLC

Three-Layer Protection Strategy 14 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, 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 LAYER 3: TECHNICALComplex bioequivalence for systemically-acting inhalation/intranasal products with high intra- and inter-subject variability Abbreviations: FDA = U.S. Food and Drug Administration; EMA = European Medicines Agency; i.v. = intravenous; i.m. = intramuscular; s.c. = subcutaneous

Board of Directors & Executive Management 15 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, Ireland, Co-founder Aaron Cameron MSc, MBA Chief Operating Officer Velichka (Villy) Valcheva MD, MSc Chief Executive Officer