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 September, 2022.
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:
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Form 20-F
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☒
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Form 40-F
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☐ |
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): ☐
On September 22, 2022, at the Interdisciplinary Conference on Psychedelic Research 2022, an investigator will present data related to a Phase 1/2 clinical trial of GH001 (GH001-TRD-102) conducted by GH Research PLC (the “Company”). A copy of the
presentation is attached hereto as Exhibit 99.1.
Additionally, on September 23, 2022, an investigator will present data at a poster session related to a Phase 1 clinical trial of GH001 (GH001-HV-101) conducted by the Company. A copy of the poster is attached hereto as Exhibit 99.2.
The fact that these materials are 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 these materials is being provided
as of September 21, 2022 and the Company does not undertake any obligation to update these materials in the future or to update forward-looking statements to reflect subsequent actual results.
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EXHIBIT INDEX
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Exhibit No.
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Description
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Presentation for September 2022
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Poster for September 2022
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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.
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GH Research PLC
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Date: September 21, 2022
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By:
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/s/ Julie Ryan
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Name:
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Julie Ryan
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Title:
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Vice President, Finance
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Exhibit 99.1
A Phase 1/2 Trial of GH001, a Vaporized 5-Methoxy-N,N-Dimethyltryptamine Formulation, inPatients with
Treatment-Resistant Depression (TRD) 1 Clinicaltrials.gov ID NCT04698603 GH001-TRD-102 ICPR 2022 Johannes Reckweg1, Cees van Leeuwen1, Cécile Henquet2, Thérèse van Amelsvoort2, Natasha Mason1, Riccardo Paci1, Theis Terwey3, Johannes
G Ramaekers1 Faculty of Psychology and Neuroscience, Maastricht University, Maastricht, Netherlands School Mental Health and Neuroscience, Maastricht University, Maastricht, Netherlands GH Research, Dublin, Ireland
Grants The study was funded by GH Research Advisory Board/Consultant Johannes Reckweg and Jan
Ramaekers work as consultants for GH Research 2 GH001-TRD-102 ICPR 2022 Disclosures
... 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 Average time to remission is ~6 weeks (STAR*D study, Remission Rate Over Time, Treatment Step 1 = Citalopram) (STAR*D study,
Remission Rates Treatment Steps 1 to 4) 3 2 or more prior therapies = TRD The Problem for Patients with Depression GH001-TRD-102 ICPR 2022
5-MeO-DMT (5-Methoxy-N,N-Dimethyltryptamine) Naturally-occurring psychoactive substance from
tryptamine class Highly potent agonist on 5-HT1A and 5-HT2A receptors Psychoactive effects with ultra-rapid onset (within seconds) and short duration (5 to 30 min) GH001 (5-MeO-DMT administration via a proprietary inhalation
approach) Intraday individualized dosing regimen (IDR) for maximization of ultra-rapid remissions Single visit initial treatment, with no structured psychotherapy 5-MeO-DMT and GH001 4 5-MeO-DMT GH001-TRD-102 ICPR 2022
5-MeO-DMT and Peak Experiences High propensity to induce peak experiences (PE) Feelings of ego
dissolution Experience of unity or oneness Profound and meaningful May be a surrogate marker for therapeutic effects Assessed through proprietary Peak Experience Scale Three visual analogue scales (0 – 100): Intensity Loss of
control Profoundness PE defined as total average of ≥ 75 5 GH001-TRD-102 ICPR 2022
Phase 1 Trial in Healthy Volunteers (GH001-HV-101, n=22) GH001 single doses of 2 mg, 6 mg, 12 mg, 18
mg and GH001 IDR (6, 12, 18 mg intra-subject dose escalation) No SAEs, all ADRs mild (except two moderate), all ADRs resolved spontaneously, inhalation well-tolerated GH001 single dose with psychoactive effect dose response but high
inter-subject variability GH001 IDR controls inter-subject variability achieving a PE1 in all healthy volunteers 6 Clinicaltrials.gov ID NCT04640831; Reckweg et al, 2021 IDR, Individualized Dosing Regimen; 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). PE Scale PE Threshold GH001-TRD-102 ICPR 2022
GH001 Single Dose: GH001 Individualized Dosing Regimen (IDR): More Chances for Remission 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) Designed to Achieve Ultra-Rapid and Durable Remissions 7 MADRS score Dose 1 GH001-TRD-102 ICPR
2022 MADRS, Montgomery-Åsberg Depression Rating Scale
Key Assessments MADRS 2-hrs PE Scale Safety MADRS 1-day Cognitive function Safety MADRS
7-day Cognitive function Safety GH001 Administration Day 1 Day 7 Phase 1/2 Trial in TRD (GH001-TRD-102, n=16) 8 PE, Peak Experience; MADRS, Montgomery-Åsberg Depression Rating Scale;IDR, Individualized Dosing Regimen 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 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) GH001-TRD-102 ICPR 2022
Phase 1 (Single Dose) – Efficacy (MADRS) 9 2 of 4 patients in the 12 mg group and 1 of 4 patients in
the 18 mg group had a MADRS remission at day 7 2 of 4 patients in the 12 mg group had a PE and both had a MADRS remission at day 7, 0 of 4 patients in the 18 mg group had a PE PE, Peak Experience; MADRS, Montgomery-Åsberg Depression Rating
Scale, MADRS remission, MADRS of ≤10; MADRS response, Reduction of ≥50% from baseline in MADRS; S, Screening; D0-B, Day 0 Baseline; D0-H2, Day 0 2 hours. MADRS Remission, Response, Improvement Rate at Day 7 MADRS from Screening to Day
7 GH001-TRD-102 ICPR 2022
Phase 2 (IDR) – Efficacy (MADRS) 10 PE, Peak Experience; MADRS, Montgomery-Åsberg Depression Rating
Scale; MADRS remission, MADRS of ≤10; MADRS response, Reduction of ≥50% from baseline in MADRS; S, Screening; D0-B, Day 0 Baseline; D0-H2, Day 0 2 hours. 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 MADRS Remission, Response, Improvement Rate at Day 7 MADRS from Screening to Day 7 GH001-TRD-102 ICPR 2022
Phase 1 (Single Dose) and Phase 2 (IDR) – Safety 11 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 missingIDR, Individualized Dosing Regimen; C-SSRS, Columbia-Suicide Severity Rating Scale ADRs Phase 1 (Single Dose) Phase 2
(IDR) ADRs 12 mg (N=4) 18 mg (N=4) IDR1 (N=8) MedDRA Preferred Term n 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) 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” GH001-TRD-102 ICPR 2022
12 GH001 allows rapid and individualized dosing optimization A single dosing day with GH001 IDR
achieved a rapid (within 24 hours) and sustained full remission (7 days) of symptoms of depression in 7/8 patients (87.5%) with TRD GH001 was well tolerated, and no serious adverse events were reported Contacts GH Research: info@ghres.com
/ clinicaltrials@ghres.com Maastricht University: johannes.reckweg@maastrichtuniversity.nl / j.ramaekers@maastrichtuniversity.nl Twitter: @PIMaastricht Conclusions GH001-TRD-102 ICPR 2022
Exhibit 99.2
INTRODUCTION 5-Methoxy-N,N-Dimethyltryptamine (5-MeO-DMT) is a potent, fast-acting,
naturally-occurring psychoactive tryptamine1. It is predominantly found in the bufotoxin of the Sonoran Desert toad2 and was first synthesized in 19363. It acts on the 5-HT1A and 5-HT2A receptors, and it has been suggested that the
5-HT1A subtype is functionally dominant4. 5-MeO-DMT has been used in recreational or self-exploratory contexts2. 5-MeO-DMT has been reported to be proficient in eliciting so called peak psychedelic experiences (PE). These are states
during an intense psychedelic experience that are defined by feelings of ego dissolution and experiences of oneness or unity. These can be very profound and meaningful experiences, which may correlate with therapeutic outcomes. In the
current study, 5-MeO-DMT was administered via inhalation as GH001, a novel vaporized 5-MeO-DMT formulation. AIMS The primary aim of the study was to investigate safety, tolerability and dose-related psychoactive effects of GH001 in
healthy volunteers. Additional aims were to assess the impact of GH001 on cognition, mood, and well-being, as well as to determine the best dosing regimen to reliably elicit a PE. METHODS The study was comprised of two single-arm
parts, where Part A (n=18) consisted of four single dose levels (2 mg, 6 mg, 12 mg, 18 mg). Part B (n=4) was comprised of an individualized dosing regimen (IDR), of up to three increasing doses on a single day (6 mg, 12 mg, 18 mg). The
part B consecutive doses were only administered if the previous dose did not elicit a PE. This was assessed using a proprietary novel PE scale (PES), consisting of 3 visual analogue scales. Aside from a (medical) screening and the
single administration day, follow up visits were conducted on day 1 and day 7 after the dosing day. A total of 22 healthy volunteers (9 female, 13 male) aged 18 to 42 years (M=29, SD=6.08) with a history of prior psychedelic use
participated in the study. To avoid expectancy effects, participants were not informed about the identity of the study drug until completion of the study. Measures of the psychedelic experience (PES, EDI, MEQ, CEQ, 5D-ASC) were
analyzed using ANOVAs with single factor Dose (5 levels: 2, 6, 12, 18 mg and IDR). The cognitive tests (DSST, PVT, PMT), measures of well-being (DASS-21, SWLS, FFMQ, CADSS, BPRS), and vital signs were analysed using GLM RM-ANOVAs with
the factors Dose (5 levels) and Time (3 levels: Baseline, post-administration, 7-day follow up). RESULTS Psychedelic experience ANOVAs indicated a significant effect of 5-MeO-DMT Dose on ratings of the PES (F4,17 = 9.302, p <
.001, ηp2 = 0.686), EDI (F4,17 = 6.925, p = .002, ηp2 = 0.62), MEQ (F4,17 = 8.026, p = .001, ηp2 = 0.654), and Reduction of Vigilance as assessed with the 5D-ASC (F4,17 = 4.023, p = .018, ηp2 = 0.486). The effects of dose on ratings of
Oceanic Boundlessness approached significance (F4,17 = 2.901, p = .053, ηp2 = 0.406). Planned contrasts indicated higher mean ratings of the psychedelic experience at higher doses compared to the lowest dose of 2 mg. A Phase 1,
Dose-Ranging Trial to Assess the Safety and Psychoactive Effects of a Vaporized 5-Methoxy-N,N-Dimethyltryptamine Formulation (GH001) in Healthy Volunteers Reckweg JT1*, Mason NL1, van Leeuwen C1, Toennes SW2, Terwey TH3, Ramaekers JG1
*presenting author 1Department of Neuropsychology & Psychopharmacology, Faculty of Psychology & Neuroscience, Maastricht University, Maastricht, the Netherlands 2Institute of Legal Medicine, University of Frankfurt,
Frankfurt, Germany 3GH Research, Dublin, Ireland Correspondence to:J. G. Ramaekers or J. T. Reckwegj.ramaekers@maastrichtuniversity.nl johannes.reckweg@maastrichtuniversity.nl Department of Neuropsychology & PsychopharmacologyT
(JGR) +31 43 388 1951 T (JTR) +31 43 388 1530 Maastricht UniversityP.O. Box 6166200 MD Maastricht, the Netherlands Disclosure statement: The study was funded by GH Research, Dublin, Ireland Figure 1 Mean (SE) and individual
retrospective ratings of the acute psychedelic experience (PES, EDI, MEQ, CEQ) per dose level. Average of ≥75 on PES indicated a PE. In part A, four participants reported a peak experience (i.e., PES rating ≥75%): one participant at
the 6 mg dose, two participants at the 12 mg dose, one participant at the 18 mg dose. In part B, all four participants in the IDR group reached a PE; one participant after first dose (6 mg), two after second dose (6 mg + 12 mg), and one
participant after three doses (6 mg + 12 mg + 18 mg). Cognition and well-being For the measures on cognition and well-being, no clinically relevant effects of Dose or TimexDose were observed. The factor Time reached significance for
the SLWS, BPRS, and the Amnesia and Derealization subscales of the CADSS. Safety and tolerability All doses were considered safe and well-tolerated. There were no dropouts and no serious adverse events (AEs) reported. There were two
AEs of moderate severity (fatigue, heart rate increase) with all other AEs being mild (e.g. nausea, headache, anxiety), and all AEs resolved spontaneously. There were no significant effects of Dose on measures of systolic/diastolic
blood pressure or heart rate and only a non-clinically significant effect of Time (p=.003), reflecting a mild decrease in heart rate from baseline to 3 hours post-administration (heart rate remained within normal range). Plasma
concentrations Plasma concentrations of 5-MeO-DMT were very low at 1 hour post-administration and barely measureable at 3 hours post-administration. Bufotenin concentrations were below limit of detection (0.006 ng/ml) at all time
points. Psychopharmacology in Maastricht Figure 2 Mean (SE) and individual CADSS and DASS ratings per dose level. CONCLUSION Administration of GH001 was well tolerated Short duration of effects support safety profile -Individual
variability for dose-related effects IDR may be preferable for clinical applications that aim to optimize therapeutic response References 1Shulgin, A., and Shulgin, A. (1997). Tryptamines I Have Known and Loved: The Chemistry
Continues. Berkeley, CA: Transform Press. 2Weil, A. T., & Davis, W. (1994). Bufo alvarius: A potent hallucinogen of animal origin. Journal of Ethnopharmacology, 41, 1–8.3Hoshino, T., and Shimodaira, K. (1936). Über Die Synthese Des
Bufotenin-Methyl-Äthers (5-Methoxy-N-Dimethyl-Tryptamin) Und Bufotenins (Synthesen in Der Indol-Gruppe. Xv). Bull. Chem. Soc. Jpn. 11, 221–224. doi:10.1246/bcsj.11.221 4Krebs-Thomson, K., Ruiz, E. M., Masten, V., Buell, M., and Geyer,
M. A. (2006). The Roles of 5-HT1A and 5-HT2 Receptors in the Effects of 5-MeO-DMT on Locomotor Activity and Prepulse Inhibition in Rats. Psychopharmacology (Berl). 189, 319–329. doi:10.1007/s00213-006-0566-1
INTRODUCTION 5-Methoxy-N,N-Dimethyltryptamine (5-MeO-DMT) is a potent, fast-acting,
naturally-occurring psychoactive tryptamine1. It is predominantly found in the bufotoxin of the Sonoran Desert toad2 and was first synthesized in 19363. It acts on the 5-HT1A and 5-HT2A receptors, and it has been suggested that the 5-HT1A
subtype is functionally dominant4. 5-MeO-DMT has been used in recreational or self-exploratory contexts2. 5-MeO-DMT has been reported to be proficient in eliciting so called peak psychedelic experiences (PE). These are states during an
intense psychedelic experience that are defined by feelings of ego dissolution and experiences of oneness or unity. These can be very profound and meaningful experiences, which may correlate with therapeutic outcomes. In the current study,
5-MeO-DMT was administered via inhalation as GH001, a novel vaporized 5-MeO-DMT formulation. AIMS The primary aim of the study was to investigate safety, tolerability and dose-related psychoactive effects of GH001 in healthy volunteers.
Additional aims were to assess the impact of GH001 on cognition, mood, and well-being, as well as to determine the best dosing regimen to reliably elicit a PE. METHODS The study was comprised of two single-arm parts, where Part A (n=18)
consisted of four single dose levels (2 mg, 6 mg, 12 mg, 18 mg). Part B (n=4) was comprised of an individualized dosing regimen (IDR), of up to three increasing doses on a single day (6 mg, 12 mg, 18 mg). The part B consecutive doses were
only administered if the previous dose did not elicit a PE. This was assessed using a proprietary novel PE scale (PES), consisting of 3 visual analogue scales. Aside from a (medical) screening and the single administration day, follow up
visits were conducted on day 1 and day 7 after the dosing day. A total of 22 healthy volunteers (9 female, 13 male) aged 18 to 42 years (M=29, SD=6.08) with a history of prior psychedelic use participated in the study. To avoid expectancy
effects, participants were not informed about the identity of the study drug until completion of the study. Measures of the psychedelic experience (PES, EDI, MEQ, CEQ, 5D-ASC) were analyzed using ANOVAs with single factor Dose (5 levels: 2,
6, 12, 18 mg and IDR). The cognitive tests (DSST, PVT, PMT), measures of well-being (DASS-21, SWLS, FFMQ, CADSS, BPRS), and vital signs were analysed using GLM RM-ANOVAs with the factors Dose (5 levels) and Time (3 levels: Baseline,
post-administration, 7-day follow up). RESULTS Psychedelic experience ANOVAs indicated a significant effect of 5-MeO-DMT Dose on ratings of the PES (F4,17 = 9.302, p < .001, ηp2 = 0.686), EDI (F4,17 = 6.925, p = .002, ηp2 = 0.62), MEQ
(F4,17 = 8.026, p = .001, ηp2 = 0.654), and Reduction of Vigilance as assessed with the 5D-ASC (F4,17 = 4.023, p = .018, ηp2 = 0.486). The effects of dose on ratings of Oceanic Boundlessness approached significance (F4,17 = 2.901, p = .053,
ηp2 = 0.406). Planned contrasts indicated higher mean ratings of the psychedelic experience at higher doses compared to the lowest dose of 2 mg. A Phase 1, Dose-Ranging Trial to Assess the Safety and Psychoactive Effects of a Vaporized
5-Methoxy-N,N-Dimethyltryptamine Formulation (GH001) in Healthy Volunteers Reckweg JT1*, Mason NL1, van Leeuwen C1, Toennes SW2, Terwey TH3, Ramaekers JG1 *presenting author 1Department of Neuropsychology & Psychopharmacology, Faculty
of Psychology & Neuroscience, Maastricht University, Maastricht, the Netherlands 2Institute of Legal Medicine, University of Frankfurt, Frankfurt, Germany 3GH Research, Dublin, Ireland Correspondence to:J. G. Ramaekers or J. T.
Reckwegj.ramaekers@maastrichtuniversity.nl johannes.reckweg@maastrichtuniversity.nl Department of Neuropsychology & PsychopharmacologyT (JGR) +31 43 388 1951 T (JTR) +31 43 388 1530 Maastricht UniversityP.O. Box 6166200 MD Maastricht,
the Netherlands Disclosure statement: The study was funded by GH Research, Dublin, Ireland Figure 1 Mean (SE) and individual retrospective ratings of the acute psychedelic experience (PES, EDI, MEQ, CEQ) per dose level. Average of ≥75 on
PES indicated a PE. In part A, four participants reported a peak experience (i.e., PES rating ≥75%): one participant at the 6 mg dose, two participants at the 12 mg dose, one participant at the 18 mg dose. In part B, all four participants in
the IDR group reached a PE; one participant after first dose (6 mg), two after second dose (6 mg + 12 mg), and one participant after three doses (6 mg + 12 mg + 18 mg). Cognition and well-being For the measures on cognition and well-being,
no clinically relevant effects of Dose or TimexDose were observed. The factor Time reached significance for the SLWS, BPRS, and the Amnesia and Derealization subscales of the CADSS. Safety and tolerability All doses were considered safe and
well-tolerated. There were no dropouts and no serious adverse events (AEs) reported. There were two AEs of moderate severity (fatigue, heart rate increase) with all other AEs being mild (e.g. nausea, headache, anxiety), and all AEs resolved
spontaneously. There were no significant effects of Dose on measures of systolic/diastolic blood pressure or heart rate and only a non-clinically significant effect of Time (p=.003), reflecting a mild decrease in heart rate from baseline to
3 hours post-administration (heart rate remained within normal range). Plasma concentrations Plasma concentrations of 5-MeO-DMT were very low at 1 hour post-administration and barely measureable at 3 hours post-administration. Bufotenin
concentrations were below limit of detection (0.006 ng/ml) at all time points. Psychopharmacology in Maastricht Figure 2 Mean (SE) and individual CADSS and DASS ratings per dose level. CONCLUSION Administration of GH001 was well
tolerated Short duration of effects support safety profile -Individual variability for dose-related effects IDR may be preferable for clinical applications that aim to optimize therapeutic response References 1Shulgin, A., and
Shulgin, A. (1997). Tryptamines I Have Known and Loved: The Chemistry Continues. Berkeley, CA: Transform Press. 2Weil, A. T., & Davis, W. (1994). Bufo alvarius: A potent hallucinogen of animal origin. Journal of
Ethnopharmacology, 41, 1–8.3Hoshino, T., and Shimodaira, K. (1936). Über Die Synthese Des Bufotenin-Methyl-Äthers (5-Methoxy-N-Dimethyl-Tryptamin) Und Bufotenins (Synthesen in Der Indol-Gruppe. Xv). Bull. Chem. Soc. Jpn. 11, 221–224.
doi:10.1246/bcsj.11.221 4Krebs-Thomson, K., Ruiz, E. M., Masten, V., Buell, M., and Geyer, M. A. (2006). The Roles of 5-HT1A and 5-HT2 Receptors in the Effects of 5-MeO-DMT on Locomotor Activity and Prepulse Inhibition in
Rats. Psychopharmacology (Berl). 189, 319–329. doi:10.1007/s00213-006-0566-1