GH Research (GHRS) highlights GH001 TRD Phase 2b results data

Rhea-AI Filing Summary

GH Research PLC reported detailed Phase 2b data for GH001, an inhaled synthetic 5‑MeO‑DMT, in adults with treatment‑resistant depression. In the double‑blind part, GH001 led to a least squares mean reduction in MADRS depression score that was −15.5 points greater than placebo at Day 8, with an effect size (Cohen’s d) of −2.0, and a remission rate (MADRS ≤10) of 57.5% after a single dose. Among open‑label extension completers, remission reached 73.0% at Month 6 after a mean of four treatments.

GH001 also reduced global illness severity: CGI‑S scores improved by an LS mean of −2.4 versus 0.1 for placebo at Day 8, with a −2.5 LS mean difference, and a −3.0 mean CGI‑S change by Month 6 in extension completers. Anxiety symptoms improved, with an LS mean HAM‑A change of −11.1 for GH001 versus −1.0 for placebo at Day 8 and a −10.0 LS mean difference, and a −13.3 mean HAM‑A change at Month 6. Quality of life (Q‑LES‑Q‑SF) increased, with a 20.6‑point LS mean improvement versus −0.8 for placebo at Day 8 and a 24.8‑point mean gain at Month 6. GH001 was generally well tolerated over up to six months, with mostly mild or moderate treatment‑emergent adverse events and no reported flashbacks, suicidal intent, or suicidal behavior.

Insights

Biotech clinical-trials analyst

GH001 showed rapid, large, and durable improvements in depression, anxiety, and quality of life with generally favorable tolerability.

The Phase 2b data describe GH001, an inhaled synthetic 5‑MeO‑DMT, in treatment‑resistant depression where current options are limited. In the randomized double‑blind portion, GH001 achieved a least squares mean MADRS reduction that was −15.5% greater than placebo at Day 8, with a large effect size (Cohen’s d = −2.0). Remission (MADRS ≤10) occurred in 57.5% of patients after a single GH001 dose, and among open‑label extension completers remission reached 73.0% at Month 6 after a mean of four treatments.

Secondary measures aligned with the primary outcome. Global illness severity (CGI‑S) improved by an LS mean of −2.4 for GH001 versus 0.1 for placebo at Day 8, a −2.5 point LS mean difference, and a −3.0 mean change at Month 6 in extension completers. Anxiety symptoms on HAM‑A improved by −11.1 for GH001 versus −1.0 for placebo at Day 8, a −10.0 LS mean difference, with a −13.3 mean change at Month 6, spanning both psychic and somatic domains. Quality of life (Q‑LES‑Q‑SF) rose by 20.6 points versus −0.8 for placebo at Day 8 and by 24.8 points at Month 6 across multiple life domains.

Tolerability is an important element. Treatment‑emergent adverse events occurred in 72 of 81 patients and were mostly mild or moderate; two severe treatment‑related events in the extension phase resolved, and one serious migraine episode was reported as not related to treatment. No flashbacks, suicidal intent, or suicidal behavior were observed. The median psychoactive effect lasted 11 minutes, and 99% of visits saw patients deemed discharge‑ready by one hour, which may be relevant to future care-setting decisions if the program advances.

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 2026.

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

GH Research PLC (the “Company”) will participate in the Promising Targets Oral Session at the 64^th American College of Neuropsychopharmacology (ACNP) annual meeting (the “Congress”) where it will present results related to its GH001-TRD-201 clinical trial. The Congress is scheduled to take place from January 12-15, 2026, in Nassau, Bahamas.

A copy of the presentation to be presented by Prof Michael E. Thase during the Congress is attached hereto as Exhibit 99.1.

The fact that this presentation is being made available should not be deemed an admission as to the materiality of any information contained in the material. The information contained in the presentation is being provided as of January 13, 2026, 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.

1

EXHIBIT INDEX

99.1 Presentation to be presented by Prof Michael E. Thase with Title: GH001 Improves Illness Severity, Anxiety Symptoms, and Quality of Life in Patients with Treatment-Resistant Depression

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: January 13, 2026
	By:	/s/ Julie Ryan
	Name:	Julie Ryan
	Title:	Vice President, Finance

3

Exhibit 99.1

 1  GH001 Improves Illness Severity, Anxiety Symptoms, and Quality of Life in Patients with Treatment-Resistant Depression  Michael E. Thase, MD  Department of Psychiatry, University of Pennsylvania and Corporal Michael J. Crescenz Veterans Affairs Medical Center, Philadelphia, PA, USA  Co-authors: Bernhard T. Baune, Narcís Cardoner, Kelly Doolin, Rosa Maria Dueñas Herrero, Luboš Janů, John R. Kelly, Rachael Maclsaac, Shane J. McInerney, Alexander Nawka, Tomáš Páleníček, Víctor Pérez Sola, Andreas Reif, Claire Sweeney, Madhukar H. Trivedi, Velichka Valcheva, Eduard Vieta, Wiesław J. Cubała 

 Author  Disclosures  Michael E. Thase  Consultant – Axsome, Clexio Biosciences, Gerson Lehrman Group, GH Research, Janssen, Johnson & Johnson, Lundbeck, Luye Pharma, Merck, Otsuka, Pfizer, Sage, Seelos Therapeutics, Sunovion, and Takeda. Grant Support – Acadia, Alkermes, Axsome, Intra-Cellular Therapies, Janssen, Myriad, National Institute of Mental Health, Otsuka, Patient-Centered Outcomes Research Institute (PCORI), and Takeda. Royalties – American Psychiatric Press, Inc., Guilford Publications, Herald House, Wolters Kluwer, and W. W. Norton & Company. Spouse’s Employment – Dr. Diane Sloan is a Senior Vice President of OPEN Health, which does business with many companies  Bernhard T. Baune  Consultant – National Health and Medical Research Council (Australia). Honoraria – Angelini, AstraZeneca, Biogen, BMS, Boehringer Ingelheim, Johnson & Johnson, LivaNova, Lundbeck, Medscape, Otsuka, Pfizer, Roche, Servier, Sumitomo Pharma, Sunovion, Teva, and Wyeth. Advisory Boards – Biogen, Boehringer Ingelheim, Janssen-Cilag, LivaNova, Lundbeck, Medscape, Novartis, Otsuka, and Teva. Research Grants from Private Industries or Nonprofit Funds – AstraZeneca, BMBF (Germany), BMG (Germany), DFG (Germany), ERA PerMed, Fay Fuller Foundation, Horizon Europe (European Union), James & Diana Ramsay Foundation (Adelaide), Johnson & Johnson, Lundbeck, La Marató de TV3, National Health and Medical Research Council (Australia), Sanofi-Synthélabo, and Wellcome Trust (UK)  Narcís Cardoner  Grants – Spanish Ministry of Health, Spanish Ministry of Science and Innovation (CIBERSAM), Strategic Plan for Health Research and Innovation (PERIS) 2016–2020, RecerCaixa, and La Marató de TV3. Honoraria – Adamed, Elsevier, Exeltis, Janssen, Lundbeck, Pfizer, and Servier. Advisory Boards – Angelini, Esteve, Janssen, Lundbeck, Novartis, Pfizer, and Viatris. Lectures/Meetings – Janssen, Lundbeck, and Pfizer  Kelly Doolin  Employee and Shareholder – GH Research  Rosa Maria Dueñas Herrero  Principal Investigator – Beckley Psytech and GH Research. Subinvestigator – Compass  Luboš Janů  Principal Investigator – GH Research  John R. Kelly  Principal Investigator – Compass, GH Research, and Transcend Therapeutics. Consultant – Clerkenwell Health. Grant Funding – Health Research Board (ILP-POR-2022-030, DIFA-2023-005, KTA-2024-002)  Rachael Maclsaac  Employee and Shareholder – GH Research  Alexander Nawka  Principal Investigator – GH Research  Disclosures (1 of 2)  2 

 Author  Disclosures  Tomáš Páleníček  Principal Investigator – Compass, GH Research, MAPS, and Ketabon. Shares – Psychedelická klinika s.r.o., Společnost pro podporu neurovědního výzkumu s.r.o., and AVI-X Aviation Experts s.r.o. Founder – PSYRES (Psychedelic Research Foundation). Consultant – CB21 Pharma and GH Research  Víctor Pérez Sola  Consultant, Honoraria, or Grants – AB-Biotics, AstraZeneca, Bristol Myers Squibb, CIBERSAM, FIS-ISCiii, Janssen Cilag, Lundbeck, Medtronic, Otsuka, and Servier  Andreas Reif  Honoraria for Lectures and/or Advisory Boards – AbbVie, Boehringer Ingelheim, Cyclerion, Compass, GH Research, Janssen, LivaNova, Medice, MSD, Newron, Sage/Biogen, and Shire/Takeda. Research Grants – Medice and Janssen  Claire Sweeney  Employee and Shareholder – GH Research  Madhukar H. Trivedi  Consultant – Acadia, Alkermes, Alto Neuroscience, Axsome, BasePoint Health Management, Biogen, Cerebral, Circular Genomics, Compass, Daiichi Sankyo, GH Research, GreenLight VitalSign6, Heading Health, Janssen, Legion Health, Merck, Mind Medicine, Myriad Neuroscience, Naki Health, Neurocrine Biosciences, Noema Pharma, Orexo, Otsuka America, Otsuka Europe, Otsuka Pharmaceutical Development & Commercialization, Praxis Precision Medicines, PureTech LYT, Relmada Therapeutics, Sage, Seaport Therapeutics, Signant Health, Sparian Biosciences, Titan Pharmaceuticals, Takeda, and WebMD. Grant/Research Funding – American Foundation for Suicide Prevention, NCATS, NIDA, NIMH, Patient-Centered Outcomes Research Institute (PCORI), Blue Cross Blue Shield of Texas, SAMHSA, and the DoD. Editorial Compensation – Elsevier and Oxford University Press  Velichka Valcheva  Employee and Shareholder – GH Research  Eduard Vieta  Grants – AB-Biotics, AbbVie, Almirall, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Celon, Cephalon, Dainippon Sumitomo Pharma, Elan, Ferrer, GH Research, GlaxoSmithKline, Janssen, Lilly, Lundbeck, Orion, Otsuka, Pfizer, Sanofi Aventis, Servier, Sunovion, and Takeda. Honoraria – Abbott, AbbVie, Angelini, AstraZeneca, Bristol Myers Squibb, Cambridge University Press, Elsevier, Farmindustria, Ferrer, Galenica, GlaxoSmithKline, Janssen, Johnson & Johnson, Lilly, Lundbeck, Oxford University Press, Otsuka, Pfizer, Sanofi Aventis, and Viatris. Advisory Boards – AbbVie, Angelini, AstraZeneca, Biogen, Biohaven, Bristol Myers Squibb, Celon, Compass, Ferrer, GH Research, Gedeon Richter, HMNC, Idorsia, Janssen, Johnson & Johnson, Jazz, Lilly, Lundbeck, Merck Sharp & Dohme, Novartis, Organon, Otsuka, Pfizer, Roche, Sage, Sanofi Aventis, Servier, Shire, Sunovion, Takeda, and Teva  Wiesław J. Cubała  Grants – Acadia, Angelini, Beckley Psytech, GH Research, HMNC Brain Health, Intra-Cellular Therapies, Janssen, MSD, Neumora, Novartis, Otsuka, Recognify Life Sciences. Honoraria – Angelini, GH Research, Janssen, and Novartis. Advisory Boards – Douglas Pharmaceuticals, GH Research, Janssen, MSD, and Novartis (relationships reported within the last three years)  Disclosures (2 of 2)  3 

 Patients with TRD, representing ~30% of patients treated for MDD,1 frequently report anxiety symptoms and greater impairment in HRQoL versus patients with treatment-responsive MDD2-4  Current therapies for TRD are limited,4 and there is a large unmet need for treatments that are well tolerated and offer rapid therapeutic benefit and long-term remission  GH001, a synthetic form of mebufotenin (5-MeO-DMT) for pulmonary inhalation, has been well tolerated in early-stage trials5,6 and shows potential to induce rapid remission of depressive symptoms in patients with TRD6  4  Background  Abbreviations: 5-MeO-DMT = 5‐methoxy‐N,N‐dimethyltryptamine; CGI-S = Clinical Global Impression – Severity; HAM-A = Hamiliton Rating Scale for Anxiety; HRQoL = Health-related quality of life; MDD = Major depressive disorder; Q-LES-Q-SF = Quality of Life, Enjoyment, and Satisfaction Questionnaire-Short Form; TRD = Treatment-resistant depression.   1. Kubitz N, et al. PLoS One. 2013;8(10):e76882. 2. Johnston KM, et al. J Affect Disord. 2019;242:195-210. 3. Rathod S, et al. J Affect Disord. 2022;300:551-562. 4. McIntyre RS, et al. World Psychiatry. 2023;22:394-412. 5. Reckweg J, et al. Front Pharmacol. 2021;12:760671. 6. Reckweg JT, et al. Front Psychiatry. 2023;14:1133414.  We examined the effects of GH001 on depressive symptoms and secondary efficacy endpoints (CGI-S, HAM-A, and Q-LES-Q-SF) from the Phase 2b trial, for up to 6 months, in patients with TRD 

 For re-treatment (up to five GH001 IDRsa), the patient must have met one of the following criteria:   MADRS score >18   MADRS score >10 and ≤18 and MADRS score ≤10 not observed at Day 8 of the prior treatment or at any visit since  MADRS score >10 and ≤18 and MADRS score >18 observed since the most recent observation of MADRS score ≤10  5  Trial Schematic  Open-Label Extension (OLE; Part 2)  N=81  Randomization 1:1  GH001 IDRa  Placebo IDRa   BL  2H  Day 1  Primary endpoint   ΔMADRS  Day 8  During the OLE, patients attended visits at Day 15, Month 1, 2, 3, 4, 5 & 6c  Additional clinic visits could be scheduled if required for medical reasons  Month 6  D2  Day 2  Double-Blind Part  (Part 1)b  This trial was conducted under the supervision of qualified healthcare professionals, providing psychological support per standard of care, but without any planned psychotherapeutic intervention before, during, or after dosing  aA second or third dose was administered if the previous dose was well tolerated according to the trial physician’s judgement (based on vital signs and adverse events) and if the patient did not achieve an intense psychoactive effect (peak experience; defined as a mean score of ≥75 on the Peak Experience Scale) following the previous dose. bEfficacy assessments were carried out by independent blinded raters in the double-blind part. cPatients also attended assessment visits on Day 2 (telephone call) and Day 8 (in-person) after each re-treatment.   Abbreviations: BL = Baseline; CGI-S = Clinical Global Impression – Severity; D = Day; HAM-A = Hamiliton Rating Scale for Anxiety; H = Hour; IDR = Individualized dosing regimen; MADRS = Montgomery–Åsberg Depression Rating Scale; Q-LES-Q-SF = Quality of Life, Enjoyment, and Satisfaction Questionnaire-Short Form.   ClinicalTrials.gov. https://clinicaltrials.gov/study/NCT05800860, Accessed November 13, 2025.   All patients directly transitioned from the double-blind part to the OLE  Efficacy Assessments  MADRS and CGI-S  MADRS, CGI-S, HAM-A, Q-LES-Q-SF  

 6  Eligibility Criteria  aCurrent MDE confirmed by the Mini-International Neuropsychiatric Interview.   Abbreviations: DSM-5 = Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition; HAM-D-17 = 17-Item Hamilton Depression Rating Scale; MDD = Major depressive disorder; MDE = Major depressive episode; MGH-ATRQ = Massachusetts General Hospital – Antidepressant Treatment Response Questionnaire; MGH-SAFER = Massachusetts General Hospital – Structured Assessment for Evaluation of Risk; TRD = Treatment-resistant depression. 

 7  Baseline Characteristics  Abbreviations: BMI = Body mass index; CGI-S = Clinical Global Impression – Severity; HAM-A = Hamilton Rating Scale for Anxiety; HAM-D-17 = 17-Item Hamilton Depression Rating Scale; MADRS = Montgomery–Åsberg Depression Rating Scale; Q-LES-Q-SF = Quality of Life, Enjoyment, and Satisfaction Questionnaire-Short Form; SD = Standard deviation.  GH001 (n=40)  Placebo (n=41)  Overall (N=81)  Baseline Demographics  Age, years, mean (SD)  41.6 (11.4)  43.9 (10.9)  42.8 (11.2)  Sex, female, n (%)  24 (60.0)  22 (53.7)  46 (56.8)  Race, White, n (%)  40 (100)  41 (100)  81 (100)  BMI, kg/m2, mean (SD)  24.8 (4.3)  27.5 (6.3)  26.2 (5.5)  Previously used any psychedelic (lifetime), n (%)  4 (10.0)  5 (12.2)  9 (11.1)  Baseline Disease Characteristics  HAM-D-17 total score, mean (SD)  24.9 (2.6)  24.6 (2.3)  24.8 (2.5)  MADRS total score, mean (SD)  29.0 (5.4)  28.2 (4.6)  28.6 (5.0)  CGI-S score, mean (SD)  4.8 (0.7)  5.0 (0.6)  4.9 (0.7)  HAM-A total score, mean (SD)  21.1 (6.5)  21.2 (6.1)  21.1 (6.2)  Q-LES-Q-SF total score, mean (SD)  27.9 (9.0)  25.3 (8.1)  26.6 (8.6) 

 LS mean difference vs placebo: −15.5 (P<0.0001)  Effect size: Cohen’s d = −2.0  LS Mean (±SE) Change from Baseline in MADRS Total Score  BL  2H  Day 2  Day 8  Primary Endpoint: GH001 Led to −15.5 Mean MADRS Reduction from Baseline on Day 8a Compared with Placebo in the Double-Blind Part  aFDA Guidance notes that efficacy with rapid-acting antidepressants generally should be demonstrated within 1 week, supporting a primary efficacy endpoint within this timeframe.  Abbreviations: BL = Baseline; FDA = Food and Drug Administration; H = Hour; LS = Least squares; MADRS = Montgomery–Åsberg Depression Rating Scale; OLE = Open-label extension; SE = Standard error.  GH001 (n=40)  Placebo (n=41)  8  The remission rate (MADRS total score ≤10) was 57.5% on Day 8 in patients who received a single dose of GH001 in the double-blind part and 73.0% in OLE completers at Month 6 after a mean of four treatments 

 9  Global Illness Severity Assessment  CGI-S Scale1  Abbreviations: CGI-S = Clinical Global Impression – Severity.  1. Guy W. US Department of Health, Education, and Welfare. 1976:217-222.  CGI-S is a clinician-rated assessment of illness severity  Assessed by a blinded independent rater  Total score range, 1−7 (higher scores indicate more severe illness) 

 10  More Patients Had Improvement in Global Illness Severity from Baseline at Day 8 with GH001 vs Placebo in the Double-Blind Part  Percentages are for each baseline category within treatment.   Abbreviations: CGI-S = Clinical Global Impression – Severity; LS = Least squares; SE = Standard error.  Percentage of Patients in Each CGI-S Category at Baseline and Day 8  GH001 (n=40)  Placebo (n=41)  LS Mean (SE) Change in CGI-S Score from Baseline at Day 8  GH001 (n=40)  Placebo (n=41)  −2.4 (0.2)  0.1 (0.2)  LS mean difference vs placebo:   −2.5 (P<0.0001) 

 11  OLE Completers Reported Improved Global Illness Severity at Month 6  Abbreviations: CGI-S = Clinical Global Impression – Severity; OLE = Open-label extension; SD = Standard deviation.  Percentage of Patients in Each CGI-S Category at Baseline and Month 6  OLE Completers (n=63)  Change from Baseline in CGI-S Score at Month 6   (n=63 OLE completers)  Mean (SD)  P Value  −3.0 (1.4)  <0.0001 

 12  Anxiety Assessment  HAM-A Scale1,2  Abbreviations: HAM-A = Hamiliton Rating Scale for Anxiety.  1. Hamilton M. Br J Med Psychol. 1959;32:50-55. 2. Marks RM, et al. Exp Clin Psychopharmacol. 2022;30(6):841-852.   HAM-A is a clinician-rated assessment of anxiety symptoms  Assessed by a blinded independent rater  Total score range, 0−56 (higher scores indicate worse anxiety)  The 14 items of the HAM-A scale were analyzed within psychic and somatic domains (score ranges, 0–28):  Psychic symptoms  Anxious mood  Insomnia  Behavior at interview  Tension  Intellectual (cognitive)  Fears  Depressed mood  Somatic symptoms  Somatic (muscular)  Respiratory  Autonomic  Somatic (sensory)  Gastrointestinal  Cardiovascular  Genitourinary 

 13  LS Mean (SE) Change in HAM-A Total Score from Baseline at Day 8  GH001 (n=40)  Placebo (n=41)  −11.1 (1.0)  −1.0 (1.0)  LS mean difference vs placebo:   −10.0 (P<0.0001)  GH001 Improved Psychic and Somatic Anxiety Symptoms vs Placebo Based on HAM-A Scores at Day 8 in the Double-Blind Part  Mean (SD) Change from Baseline in HAM-A Domain Score at Day 8  Psychic Symptomsa  Somatic Symptomsb  aIncludes anxious mood, tension, fears, insomnia, intellectual (cognitive), depressed mood, and behavior at interview items. bIncludes somatic (muscular), somatic (sensory), cardiovascular symptoms, respiratory symptoms, gastrointestinal symptoms, genitourinary symptoms, and autonomic symptoms items.  Abbreviations: HAM-A = Hamiliton Rating Scale for Anxiety; LS = Least squares; SD = Standard deviation; SE = Standard error. 

 14  OLE Completers Reported Improved Psychic and Somatic Anxiety Symptoms at Month 6  OLE Completers (n=63)  aIncludes anxious mood, tension, fears, insomnia, intellectual (cognitive), depressed mood, and behavior at interview items. bIncludes somatic (muscular), somatic (sensory), cardiovascular symptoms, respiratory symptoms, gastrointestinal symptoms, genitourinary symptoms, and autonomic symptoms items.  Abbreviations: HAM-A = Hamiliton Rating Scale for Anxiety; OLE = Open-label extension; SD = Standard deviation.  Change from Baseline in HAM-A Total Score at Month 6   (n=63 OLE completers)  Mean (SD)  P Value  −13.3 (7.2)  <0.0001  Psychic Symptomsa  Somatic Symptomsb  Mean (SD) Change from Baseline in HAM-A Domain Score at Month 6 

 15  Quality of Life Assessment  Q-LES-Q-SF Scale1,2  aThe total score reported for the double-blind part and the open-label extension is based on the abbreviated version of the Q-LES-Q-SF (which omits two questions about medication and overall life satisfaction); however, the by-domain presentation includes all 16 items. bThe domains were developed as part of an ad hoc analysis; the Q-LES-Q-SF does not have an official subscale scoring system. cThe percentages for each domain are normalized to reflect the relative proportionality of responses, accounting for the differing number of items per domain. dIncludes mood, overall sense of well-being, and overall life satisfaction items. eIncludes family relationships, social relationships, and sex drive/interest/performance items. fIncludes physical health, ability to function in daily life, ability to get around physically items. gIncludes work, ability to do work/hobbies, household activities, leisure time activities, living/housing situationship, economic status, and medication items.  Abbreviations: Q-LES-Q-SF = Quality of Life, Enjoyment, and Satisfaction Questionnaire-Short Form.  1. Endicott J, et al. Psychopharmacol Bull. 1993;29:321-326. 2. Riendeau RP, et al. Qual Life Res. 2018;27:2953-2964.  Q-LES-Q-SF is a patient-reported scale that measures the degree of enjoyment and satisfaction experienced by patients in various areas of daily life  The 16 items of the Q-LES-Q-SF score are rated on a 1 to 5 scale, with higher scores being indicative of greater enjoyment or satisfactiona  Total score range, 14−70a  Q-LES-Q-SF scale items were analyzed within four domains (score ranges, 20−100)b,c  Mood and psychological well-beingd  Social and relationship lifee  Physical health and abilityf  Work, housing, leisure, and daily functioningg 

 16  LS Mean (SE) Change in Q-LES-Q-SF Total Score from Baseline at Day 8  GH001 (n=37)  Placebo (n=40)  20.6 (1.8)  –0.8 (1.7)  LS mean difference vs placebo:   21.4 (P<0.0001)  GH001 Led to Improvements in Quality of Life Across Multiple Domains vs Placebo at Day 8 in the Double-Blind Part   Mean Percentage (SD) Change from Baseline in Q-LES-Q-SF Domain Score at Day 8a  The Q-LES-Q-SF domains were developed as part of an ad hoc analysis; the Q-LES-Q-SF does not have an official subscale scoring system. aThe percentages for each domain are normalized to reflect the relative proportionality of responses, accounting for the differing number of items per domain. bIncludes mood, overall sense of well-being, and overall life satisfaction items. cIncludes family relationships, social relationships, and sex drive/interest/performance items. dIncludes physical health, ability to function in daily life, ability to get around physically items. eIncludes work, ability to do work/hobbies, household activities, leisure time activities, living/housing situationship, economic status, and medication items.  Abbreviations: LS = Least squares; SD = Standard deviation; SE = Standard error; Q-LES-Q-SF = Quality of Life, Enjoyment, and Satisfaction Questionnaire-Short Form.  Mood and   psychological   well-beingb  Social and   relationship lifec  Physical health   and abilityd  Work, housing, leisure, and daily functioninge 

 17  The Q-LES-Q-SF domains were developed as part of an ad hoc analysis; the Q-LES-Q-SF does not have an official subscale scoring system. aThe percentages for each domain are normalized to reflect the relative proportionality of responses, accounting for the differing number of items per domain. bIncludes mood, overall sense of well-being, and overall life satisfaction items. cIncludes family relationships, social relationships, and sex drive/interest/performance items. dIncludes physical health, ability to function in daily life, ability to get around physically items. eIncludes work, ability to do work/hobbies, household activities, leisure time activities, living/housing situationship, economic status, and medication items.  Abbreviations: OLE = Open-label extension; Q-LES-Q-SF = Quality of Life, Enjoyment, and Satisfaction Questionnaire-Short Form; SD = Standard deviation.   Mean Percentage (SD) Change from Baseline in Q-LES-Q-SF Domain Score at Month 6a  OLE Completers (n=63)  Mood and   psychological   well-beingb  Social and   relationship lifec  Physical health   and abilityd  Work, housing, leisure, and daily functioninge  OLE Completers Reported Improved Quality of Life at Month 6  Change from Baseline in Q-LES-Q-SF Total Score at Month 6  (n=63 OLE completers)  Mean (SD)  P Value  24.8 (14.1)  <0.0001 

 18  GH001 Administration Was Well Tolerated in Patients with TRD up to 6 Months  aTwo severe treatment-related TEAEs were reported in the OLE; affect lability occurred shortly after administration of GH001 and resolved within 4 minutes and one event of migraine, considered a serious TEAE not related to treatment, started 73 days after the patient’s most recent (fourth) administration of GH001.  Abbreviations: OLE = Open-label extension; TEAE = Treatment-emergent adverse event; TRD = Treatment-resistant depression.  TEAEs were observed in 72/81 (88.9%) patients and were mostly mild or moderatea; one non–treatment-related serious TEAE was reported  No TEAEs of flashbacks, suicidal intent, or suicidal behavior occurred  The median duration of psychoactive effects after GH001 administration was 11 minutes  Patients were deemed discharge-ready by 1 hour post-dose at 99% of visits  

 Conclusions  19  In patients with TRD, GH001 led to significant reductions in global illness severity from baseline to Day 8 versus placebo; these improvements with GH001 were maintained at Month 6 in those who completed the OLE  Significant improvements in anxiety symptoms across psychic and somatic domains were also observed with GH001 treatment at Day 8 that were maintained at Month 6  GH001 also led to significantly improved quality of life across multiple domains from baseline to Day 8 and at Month 6  In patients with TRD, GH001 was generally well tolerated, with no re-administration challenges  Abbreviation: OLE = Open-label extension; TRD = Treatment-resistant depression.  

 20  Acknowledgments  This trial was sponsored by GH Research Ireland Limited  The sponsor would like to thank the participants in the trial  The sponsor would also like to thank the investigators who conducted this trial  Under the guidance of the authors, medical writing and editorial support were provided by Brian Brennan, PhD, of GH Research, and Gina Daniel, PhD, of OPEN Health 

FAQ

What did GH Research PLC (GHRS) disclose about GH001 in this 6-K?

GH Research PLC disclosed Phase 2b clinical data for GH001, an inhaled synthetic 5‑MeO‑DMT, in patients with treatment‑resistant depression. The company shared that GH001 produced rapid and statistically significant improvements in depressive symptoms, global illness severity, anxiety, and quality of life, with effects maintained up to six months in open‑label extension completers, and was generally well tolerated.

How effective was GH001 in improving depression scores in the Phase 2b trial?

In the double‑blind part of the trial, GH001 led to a least squares mean reduction in MADRS depression score that was −15.5 points greater than placebo at Day 8, with an effect size of Cohen’s d = −2.0. The remission rate, defined as MADRS ≤10, was 57.5% on Day 8 after a single GH001 dose, and 73.0% at Month 6 among open‑label extension completers after a mean of four treatments.

What impact did GH001 have on anxiety symptoms and global illness severity?

GH001 significantly improved global illness severity and anxiety. On the CGI‑S scale, the LS mean change at Day 8 was −2.4 with GH001 versus 0.1 with placebo, a −2.5 LS mean difference, and a −3.0 mean change at Month 6 in extension completers. On the HAM‑A anxiety scale, GH001 produced an LS mean change of −11.1 versus −1.0 for placebo at Day 8, a −10.0 LS mean difference, and a −13.3 mean change at Month 6, with improvements across both psychic and somatic symptom domains.

How did GH001 affect quality of life in patients with treatment-resistant depression?

Quality of life, measured by the Q‑LES‑Q‑SF, improved markedly with GH001. At Day 8, the LS mean change from baseline in total score was 20.6 for GH001 versus −0.8 for placebo, an LS mean difference of 21.4. Among open‑label extension completers, the mean change in Q‑LES‑Q‑SF total score at Month 6 was 24.8, with improvements reported across mood and psychological well‑being, social and relationship life, physical health and ability, and work, housing, leisure, and daily functioning domains.

What safety and tolerability findings were reported for GH001 over six months?

GH001 was described as generally well tolerated in patients with treatment‑resistant depression for up to six months. Treatment‑emergent adverse events occurred in 72 of 81 (88.9%) patients and were mostly mild or moderate. Two severe treatment‑related TEAEs in the open‑label extension resolved, and one serious migraine event was considered not related to treatment. No treatment‑emergent adverse events of flashbacks, suicidal intent, or suicidal behavior were reported. The median duration of psychoactive effects was 11 minutes, and patients were deemed discharge‑ready by one hour post‑dose at 99% of visits.

What was the design of the GH001 Phase 2b trial in treatment-resistant depression?

The trial included a randomized double‑blind part (Part 1) where patients received GH001 or placebo via an individualized dosing regimen, with the primary endpoint being change in MADRS score at Day 8. All patients then directly transitioned into an open‑label extension (Part 2), with up to five GH001 retreatments allowed under prespecified MADRS‑based criteria. Assessments included MADRS and CGI‑S in the double‑blind part, and MADRS, CGI‑S, HAM‑A, and Q‑LES‑Q‑SF throughout the open‑label extension up to Month 6.