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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 January, 2025.
 
Commission File Number: 001-40530

GH Research PLC
(Exact name of registrant as specified in its charter)

Joshua Dawson House
Dawson Street
Dublin 2
D02 RY95
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
    

INFORMATION CONTAINED IN THIS REPORT ON FORM 6-K

On January 10, 2025, GH Research PLC (the “Company”) announced primary endpoint met in two phase 2a POC trials with GH001 and completion of all FDA requests to address IND hold with no findings of respiratory toxicity in non-rodents, and made available an updated investor presentation on its website. A copy of the press release is exhibited hereto as Exhibit 99.1 and a copy of the investor presentation is attached hereto as Exhibit 99.2.

The fact that this press release and investor 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 investor presentation is being provided as of January 10, 2025, 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.

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INCORPORATION BY REFERENCE

This Report on Form 6-K (other than Exhibit 99.2 hereto), including Exhibit 99.1 hereto, shall be deemed to be incorporated by reference into the registration statement on Form S-8 (Registration No. 333-270422) and the registration statement on Form F-3 (Registration No 333-270418) of the Company and to be a part thereof from the date on which this report is filed, to the extent not superseded by documents or reports subsequently filed or furnished.

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EXHIBIT INDEX

Exhibit No.
Description
Press release dated January 10, 2025
Corporate Presentation for January 2025

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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 10, 2025
  
   
 
By:
/s/ Julie Ryan
 
Name:
Julie Ryan
 
Title:
Vice President, Finance

 
4
Exhibit 99.1

GH Research Announces Primary Endpoint Met in Two Phase 2a POC Trials with GH001 and Completion of All FDA Requests to Address IND Hold with No Findings of Respiratory Toxicity in Non-Rodents
 

 •
Primary endpoint met in phase 2a POC trial in postpartum depression with a MADRS reduction from baseline of –35.4 points (p<0.0001, n=10) and 100% of patients in remission at Day 8
 

 •
Primary endpoint met in phase 2a POC trial in bipolar II disorder with a current major depressive episode with a MADRS reduction from baseline of –16.8 points (p=0.0099, n=6) and 33% of patients in remission at Day 8
 

 •
In both trials, GH001 was well tolerated and no treatment-related serious adverse events were reported
 

 •
Inhalation toxicology study in a non-rodent species was completed with no histology findings in the respiratory tract of any dogs in the study at any dose level
 

 •
Additional inhalation toxicology study in rats was completed supporting our position that respiratory tract histology findings are rat specific
 

 •
Our response to FDA’s request for additional device design verification information is being prepared
 

 •
Full response to the IND hold planned to be submitted in mid-2025
 

 •
Top-line data from our randomized, double-blind, placebo-controlled Phase 2b trial in TRD on track to be announced in Q1 2025
 
Dublin, Ireland, January 10, 2025 – 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.
 
Primary Endpoint Met in Phase 2a Proof-of-Concept Trial in PPD
 
The primary endpoint of the Phase 2a proof-of-concept (POC) trial for GH001 in postpartum depression (PPD) was met with a significant reduction from baseline of –35.4 points (96.3%) in Montgomery–Åsberg Depression Rating Scale (MADRS) total score on Day 8 after administration of GH001 (p<0.0001). On Day 8, 100% of patients were in remission (MADRS ≤ 10).
 
GH001 led to an ultra-rapid antidepressant effect with a significant reduction in MADRS score at 2 hours after administration of –31.4 points (p<0.0001) and on Day 2 of –36.0 points (p<0.0001).
 
The trial recruited 10 patients with PPD. All patients were administered an individualized dosing regimen (IDR) of up to three escalating doses of GH001. There was no psychotherapeutic intervention in this trial. The mean total MADRS score on Day 8 was 1.3 and all 10 patients were in remission.
 
GH001 was well tolerated and no treatment-related serious adverse events were reported. All treatment-emergent adverse events (TEAEs) were mild or moderate.
 
Primary Endpoint Met in Phase 2a Proof-of-Concept Trial in BDII
 
The primary endpoint of the Phase 2a POC trial for GH001 in bipolar II disorder with a current major depressive episode (BDII) was met with a significant reduction from baseline of –16.8 points (51.9%) in MADRS total score on Day 8 after administration of GH001 (p=0.0099). On Day 8, 33.3% of patients were in remission (MADRS ≤ 10).
 
GH001 led to an ultra-rapid antidepressant effect with a reduction in MADRS score at 2 hours after administration of –16.3 points (p=0.0006) and on Day 2 of -13.3 points (p=0.0299).
 
The trial recruited 6 patients with BDII. All patients were administered an IDR of up to three escalating doses of GH001.  There was no psychotherapeutic intervention in this trial.
 
GH001 was well tolerated and no treatment-related serious adverse events were reported. The majority of TEAEs were mild or moderate and there were no reported TEAEs of hypomania or mania.
 
Update on IND for GH001
 
As previously announced, our Investigational New Drug Application (IND) for GH001 administered using our proprietary aerosol delivery device has been placed on clinical hold by the U.S. Food and Drug Administration (FDA), with the FDA requesting that we provide (i) an inhalation toxicology study in a non-rodent species and an additional inhalation toxicology study in rats, (ii) additional device design verification information and (iii) updates to our investigator brochure, to resolve the hold.
 
The requested additional inhalation toxicology study in a non-rodent species has now been completed. The pathology report concludes that there are no histology findings in the respiratory tract of any dogs at any dose level evaluated in the study.
 
The requested additional inhalation toxicology study in rats has now been completed which showed histology findings consistent with our previously completed study in rats. This supports our position that these findings are rat specific.
 
Based on previously announced FDA interactions, the response to their request for additional device design verification information is being prepared and, together with the completion of the inhalation toxicology studies, provides the final piece of information requested by the agency.
 
We are preparing to engage with the FDA in advance of providing a full response to the IND hold which we plan to submit in mid-2025.
 
Business Updates
 
GH001 in Patients with TRD
 
As previously announced, we completed enrolment of the double-blind phase of our randomized, double-blind, placebo-controlled Phase 2b trial in 80 treatment-resistant depression (TRD) patients in the third quarter of 2024, with top-line data on track to be announced in the first quarter of 2025. This trial also includes a 6-month open-label extension which is on track for completion of last patient visit in the first quarter of 2025.
 
Cash Position
 
Cash, cash equivalents, other financial assets and marketable securities were $182.6 million as of December 31, 2024, compared to cash, cash equivalents, other financial assets and marketable securities of $222.7 million as of December 31, 2023.
 
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 therapies for the treatment of patients with treatment-resistant depression (TRD).
 
About GH001
 
Our lead product candidate, GH001, is formulated for mebufotenin administration via a proprietary inhalation approach. Based on the observed clinical activity in our completed phase 1/2 GH001-TRD-102 trial, where 87.5% of patients with TRD achieved ultra-rapid remission with our GH001 individualized single-day dosing regimen in the Phase 2 part of the trial, we believe that GH001 has the potential to change the way TRD is treated today.
 
About Notation for Trial Timepoints
 
In relation to our clinical trials we have previously referred to the day of dosing as Day 0 (D0), the day after dosing as Day 1 (D1), and the seventh day after dosing as Day 7 (D7). In this press release, and going forward, we shall refer to the day of dosing as Day 1 (D1), the day after dosing as Day 2 (D2) and the seventh day after dosing as Day 8 (D8).
 
Forward-Looking Statements
 
This press release contains statements that are, or may 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, 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

 GH Research PLC (NASDAQ: GHRS)  January 2025  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  Completed  OTHER INDICATIONS  GH001  Postpartum Depression (PPD)  Phase 2a POC  Completed  Bipolar II Disorder* (BDII)  Phase 2a POC  Completed  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 $182.6 million as of December 31, 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  ✔✔✔✔  ✔  Optimize  Day 8 Primary Endpoint  ✔✔✔✔  ✔  Optimize  Fewer Administration Visits / Greater Durability  ✔✔✔✔  ✔  Minimize  Post-Discharge Restrictions  None  No driving or operating machinery until the next day after a restful sleep  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  7  2025© GH Research PLC 
 
 >75% reduction in administration visits with GH001  8  GH001  Based on ICER estimate  Based on Phase 2b trial design  Administration visits in 6 months  1-6 visits  Assumptions:  SPRAVATO®: Assumes 23 administration visits, 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 3-6 (1,2,3);   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  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  23 visits  2025© 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 Phase 1 Clinical Trials: Trial Design  GH001-HV-1011  (Healthy Volunteers)  IDR Part (Open-Label)  D2  D8  D1  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   D8  D31  D1  D2  D8  D1 
 
 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 2  Day 8  GH001  p=0.0018  p<0.0001  p<0.0001  Baselinea  Key results1:  87.5% (7/8) patients achieved remission by Day 8  Mean change from baseline in MADRS score was -24.4 at day 8  2025© GH Research PLC 
 
 Safety and Tolerability of GH001 in Completed Phase 1 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 D1, D2 and D8. 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 1  Primary Endpoint   ΔMADRS  Day 8  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 2  2025© 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