GHRS 6-K
GH Research PLC (GHRS)
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, 2024.
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 September 3, 2024, GH Research PLC (the “Company”) issued a press release announcing the appointment of Dr. Velichka “Villy” Valcheva to Chief Executive Officer. A copy of the press release is attached hereto as Exhibit 99.1.
On September 3, 2024, the Company made available an updated investor presentation on it’s website. A copy of the investor presentation is attached hereto as Exhibit 99.2.
The fact that this press release and presentation 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 the press release and presentation is being provided as of September 3, 2024, and the Company does not undertake any obligation to update the press release and presentation in the future or to update forward-looking statements to reflect subsequent actual results.
EXHIBIT INDEX
| Exhibit No. | Description |
|---|---|
| 99.1 | Press release dated September 3, 2024 |
| --- | --- |
| 99.2 | Investor Presentation for September 2024 |
| --- | --- |
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: September 3, 2024 | ||
| By: | /s/ Julie Ryan | |
| Name: | Julie Ryan | |
| Title: | Vice President, Finance |
Exhibit 99.1
GH Research Announces Appointment of Dr. Velichka “Villy” Valcheva to Chief Executive Officer
DUBLIN, Ireland, September 03, 2024 - GH Research PLC (Nasdaq: GHRS), a clinical-stage biopharmaceutical company dedicated to transforming the treatment of psychiatric and neurological disorders, today announced the promotion of Dr. Velichka “Villy“ Valcheva, MD, MSc. to Chief Executive Officer of the Company. Dr. Valcheva succeeds PD Dr. med. Theis Terwey, co-founder of GH Research.
Dr. Valcheva has more than 20 years of experience in various leadership roles in the pharmaceutical and biotech industries. Dr. Valcheva joined the company in August 2023 and has served as the Company’s Chief Medical Officer since February 2024 having leadership responsibility, among other things, for the execution of the Company’s clinical development programs. She joined us from Albireo, where, in her position as VP and Head of Medical Affairs International, she played a pivotal role in the company’s late-stage development, scientific communication, regulatory approvals by the U.S. Food and Drug Administration and EMA as well as gaining market access in multiple markets of the rare disease medicine Bylvay. Dr. Valcheva holds a Masters in Pharmaceutical Medicine from Trinity College Dublin, Ireland as well as a Dr. Med. from University of Medicine – Plovdiv, Bulgaria.
Florian Schönharting, Chairman of the Board of Directors, GH Research, said: “We are very pleased to promote Dr. Valcheva to Chief Executive Officer. As Chief Medical Officer, she has proven her operating and execution skills, and she has the experience base and track record to lead GH Research through its next stage of development to achieve our goal of providing effective therapies for patients suffering from depression. I would also like to thank Theis for his dedication, passionate commitment and scientific rigor applied to our mission since we founded the Company together.”
Dr. Valcheva, Chief Executive Officer, GH Research, added: “Since joining GH Research last year, I have worked tirelessly to realize the potential of our product candidates to help patients with depression. As we’re screening the remaining patients for our phase 2b trial in treatment-resistant depression, we’re on track for completion of enrolment in September this year. Additionally, our phase 1 healthy volunteer study using our proprietary device is now actively enrolling in the UK. I’m excited to lead the company through the next phase of development. The foundation that Theis has laid will always be a part of GH Research.”
“Taking part in the founding of GH Research and leading it in its mission has been a great honor for me and I look forward to seeing the company continue to advance its cause,” said departing CEO, Dr. Terwey.
About GH Research PLC
GH Research PLC is a clinical-stage biopharmaceutical company dedicated to transforming the treatment of psychiatric and neurological disorders. GH Research PLC's initial focus is on developing its novel and proprietary mebufotenin (5-MeO-DMT) therapies for the treatment of patients with treatment-resistant depression (TRD).
GH Research PLC's annual report on Form 20-F filed with the U.S. Securities and Exchange Commission for the year ended December 31, 2023 is available at www.ghres.com and shareholders may receive a hard copy free of charge upon request.
Forward-Looking Statements
This press release contains statements that are, or may be deemed to be, forward-looking statements. All statements other than statements of historical fact included in this press release, including statements regarding our future results of operations and financial position, business strategy, product candidates, medical devices required to deliver these product candidates, research pipeline, ongoing and currently planned preclinical studies and clinical trials, regulatory submissions and approvals and their effects on our business strategy, including our plans and expectations related to addressing the clinical hold on the GH001 IND, research and development costs, cash runway, timing and likelihood of success, as well as plans and objectives of management for future operations, are forward-looking statements. Forward-looking statements appear in a number of places in this press release and include, but are not limited to, statements regarding our intent, belief or current expectations. Forward-looking statements are based on our management’s beliefs and assumptions and on information currently available to our management. Such statements are subject to risks and uncertainties, and actual results may differ materially from those expressed or implied in the forward-looking statements due to various factors, including, but not limited to, those described in our filings with the U.S. Securities and Exchange Commission. No assurance can be given that such future results will be achieved. Such forward-looking statements contained in this press release speak only as of the date hereof. We expressly disclaim any obligation or undertaking to update these forward-looking statements contained in this press release to reflect any change in our expectations or any change in events, conditions, or circumstances on which such statements are based unless required to do so by applicable law. No representations or warranties (expressed or implied) are made about the accuracy of any such forward-looking statements.
Investor Relations:
Julie Ryan
GH Research PLC
Exhibit 99.2
GH Research PLC (NASDAQ: GHRS) September 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
SeekingUltra-Rapid, Durable Remissionsin Depression 3
Stage of Development PROGRAMS INDICATION PRECLINICAL PHASE 1 PHASE 2a PHASE 2b PHASE 3 CURRENT STATUS MILESTONES GH001Mebufotenin (5-MeO-DMT) for inhalation administration Treatment-Resistant Depression (TRD) Phase 2b RDBPC & Phase 1 PK trial with proprietary device ongoing Phase 2b DB phase completion in Q3 GH002Mebufotenin (5-MeO-DMT) for i.v. administration Psychiatric or Neurological Disorder Phase 1 HV trial completed Update on next steps GH003Mebufotenin (5-MeO-DMT) for nasal administration Psychiatric or Neurological Disorder Pre-clinical development Complete preclinical development OTHER INDICATIONS GH001 Postpartum Depression (PPD) Phase 2a POC Completion in Q4 GH001 Bipolar II Disorder* (BDII) Phase 2a POC Guidance to be communicated 4 Complete Ongoing *Bipolar II disorder with a current major depressive episode 5-MeO-DMT, 5-Methoxy-N,N-Dimethyltryptamine; i.v., intravenous; RDBPC, Randomized, Double-Blind, Placebo-Controlled; POC, Proof-of-Concept; HV, Healthy Volunteer Pipeline
The Problem for Patients with Depression Established Therapies are Slow-Acting ... Remission Rates in TRD < 15% 5 (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 ~33% no remission despite 4 treatment steps 2 or more prior therapies = TRD Adapted from Trivedi et al., Am J Psychiatry 2006 and Rush et al., Am J Psychiatry 2006 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 6 Company estimates based on: https://www.nimh.nih.gov/health/statistics/major-depression.shtml; Wittchen et al., The size and burden of mental disorders and other disorders of the brain in Europe 2010, European Neuropsychopharmacology (2011); Rush et al., Acute and Longer-Term Outcomes in Depressed Outpatients Requiring One or Several Treatment Steps: A STAR*D Report, Am J Psychiatry 2006MDD, Major Depressive Disorder
GH001 & GH002 7 API Mebufotenin (5-MeO-DMT) Pharmacology 5-HT1A/5-HT2A agonist Route Pulmonary inhalation (GH001) or IV administration (GH002) Psychoactive effect Ultra-rapid onset (within seconds) and short duration (<30 min) Dose Individualized dosing regimen (IDR) of 1 to 3 doses in a single visit Visit duration 1 to 3-hours, no additional visits for psychotherapy or structured psychological support
Individualized Dosing Regimen (IDR) for Maximization of Ultra-Rapid and Durable Remissions 8 Single Dose: Inter-Person Variability Individualized Dosing Regimen (IDR):Maximization of Ultra-Rapid and Durable Remissions MADRS score MADRS score MADRS score MADRS score Dose 1 Dose 1 Dose 2 Dose 3 Dose 2 Dose 1 No remission Remission Remission Remission Remission Hypothetical Patient 1 Hypothetical Patient 2 Hypothetical Patient 3 Hypothetical Patient 1 Hypothetical Patient 2 No remission No remission No remission Dose 1 MADRS score Dose 1 MADRS, Montgomery-Åsberg Depression Rating Scale
Phase 1 Trial of GH001 in Healthy Volunteers GH001-HV-101 9 (Completed) Clinicaltrials.gov ID: NCT04640831
Design of Phase 1 Trial of GH001 in Healthy Volunteers (GH001-HV-101) 10 GH001 2 mg (n=4) GH001 6 mg (n=6) GH001 12 mg (n=4) GH001 18 mg (n=4) HV (n=18) Part A (Single Dose) Primary Endpoint: Safety until day 7 Peak Experience Scale (PE Scale)1 Part B (IDR) HV (n=4) Primary Endpoint: Safety until day 7 Peak Experience Scale (PE Scale)1 GH001 IDR6, 12, 18 mg to achieve PE (up to 3 doses, 3h interval) Day 0GH001 inhaled Day 1 Day 7 Key Assessments Safety PE Scale Cognitive function Safety Safety Cognitive function 1The PE Scale averages answers scored by the subject by marking a visual analogue scale between 0 and 100 for the following three questions: 1. How intense was the experience; 2. To what extent did you lose control; 3. How profound (i.e., deep and significant) was the experience? HV, Healthy Volunteer; PE, Peak Experience; IDR, Individualized Dosing Regimen
Part A (Single Dose) and Part B (IDR) – Safety 11 Study Safety Group review No SAEs All ADRs mild, except two moderate (*) All ADRs resolved spontaneously Inhalation well-tolerated No noteworthy changes in vital parameters, except for temporary, non-clinically relevant increase in heart rate and blood pressure shortly after administration of GH001 No clinically relevant changes in safety laboratory analyses, psychiatric symptom scales or measures of cognitive function ADRs Part A (Single Dose) Part B (IDR) ADRs 2 mg (n=4) 6 mg (n=6) 12 mg (n=4) 18 mg (n=4) IDR1 (n=4) MedDRA Preferred Term Number of Events n n n n Abnormal dreams 1 Anxiety 1 1 Clumsiness 1 Confusional state 1 Euphoric mood 1 Fatigue 1 1* Feeling hot 1 Flashback 1 Hallucination 1 Head discomfort 1 Headache 2 1 1 Heart rate increased 1* Hyperacusis 1 Insomnia 1 Mental fatigue 1 Nausea 2 1 1 2 Vision blurred 1 SAE, Serious Adverse Event; ADR, Adverse Drug Reaction, an adverse event with a relationship code to the investigational product of definite, probable, or possible, or where code is missing; IDR, Individualized Dosing Regimen 16 mg (n=1); 6-12 mg (n=2); 6-12-18 mg (n=1)
Part A – Peak Experience (PE) Dose-Effectsand Inter-Person Variability 12 Average fordose group PE Scale PE Threshold PE, Peak Experience
Part B – Peak Experience (PE)Effect of Intraday Individualized Dosing Regimen (IDR) 13 PE Threshold PE, Peak Experience
(Completed) Phase 1/2 Trial of GH001 in Treatment-Resistant DepressionGH001-TRD-102 14 Clinicaltrials.gov ID: NCT04698603
15 Design of Phase 1/2 Trial of GH001 in TRD (GH001-TRD-102) Phase 1 (Single Dose) Phase 2 (IDR) GH001 12 mg (n=4) GH001 18 mg (n=4) TRD1 (n=8) Primary Endpoint: Safety until day 7 TRD1 (n=8) Primary Endpoint: MADRS remission day 7 (MADRS≤10) GH001 IDR6, 12, 18 mg to achieve PE (up to 3 doses, 3h interval) TRD, Treatment-Resistant Depression; PE, Peak Experience; MADRS, Montgomery-Åsberg Depression Rating Scale; IDR, Individualized Dosing Regimen; H, Hour; D, Day 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 Key Assessments MADRS H2 PE Scale Safety MADRS D1 Cognitive function Safety MADRS D7 Cognitive function Safety Day 0GH001 inhaled Day 1 Day 7
Phase 1 (Single Dose) and Phase 2 (IDR) – Safety 16 ADRs Phase 1 (Single Dose) Phase 2 (IDR) ADRs 12 mg (n=4) 18 mg (n=4) IDR1 (n=8) MedDRA Preferred Term Number of Events n n Abdominal discomfort 1 Anxiety 2 Depressive symptom 1* Dizziness 1 Feeling abnormal 1 1 Flashback 1 1 2 Headache 2 1 3 Muscle discomfort 1 Muscle spasms 1 Nausea 2* Paresthesia 1 Sensory disturbance 3 SAE, Serious Adverse Event; ADR, Adverse Drug Reaction, an adverse event with a relationship code to the investigational product of definite, probable, or possible, or where code is missing; IDR, Individualized Dosing Regimen; C-SSRS, Columbia-Suicide Severity Rating Scale; MADRS, Montgomery-Åsberg Depression Rating Scale 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 relevant 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”
Phase 1 (Single Dose) – Efficacy (MADRS) 17 2 of 4 (50%) in the 12 mg group and1 of 4 (25%) in the 18 mg group had a MADRS remission at day 7 2 of 8 patients had a PE and both had a MADRS remission at day 7 MADRS Remission / Response / Improvement Rate Day 7 PE, Peak Experience; MADRS, Montgomery–Åsberg Depression Rating ScaleMADRS remission = MADRS of ≤10; MADRS response = Reduction of ≥50% from baseline in MADRS; MADRS any improvement = any reduction from baseline in MADRS
Phase 2 (IDR) – Efficacy (MADRS) 18 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 Day 7 PE, Peak Experience; MADRS, Montgomery–Åsberg Depression Rating ScaleMADRS remission = MADRS of ≤10; MADRS response = Reduction of ≥50% from baseline in MADRS; MADRS any improvement = any reduction from baseline in MADRS
Phase 2 (IDR) – Efficacy (MADRS Change from Baseline) 19 Hour 2 Day 1 Day 7 GH001 p=0.0018 p<0.0001 p<0.0001 Primary endpoint met: 7 of 8 patients (87.5%) had a MADRS remission at day 7, p<0.0001 7 of 7 remissions from day 1 and4 of 7 remissions from 2 hours Baseline1 1Baseline mean MADRS=32
MADRS and PE – Observed Improved Outcome in Phase 2 (IDR) vs Phase 1 (Single Dose) 20 Phase 2 (IDR) Phase 1 (Single Dose) 12 mg Phase 1 (Single Dose) 18 mg MADRS Remission Rate Day 7 87.5% (7 of 8) 50% (2 of 4) 25% (1 of 4) Mean MADRS Change Day 7 -24.4 (-76%) -21.0 (-65%) -12.5 (-40%) Rate of PE 87.5% (7 of 8) 50% (2 of 4) 0% (0 of 4) Mean PE Score 90.4 (at final dose) 58.2 59.1 PE, Peak Experience; MADRS, Montgomery-Åsberg Depression Rating Scale; IDR, Individualized Dosing Regimen
(Initiated) Phase 2b Trial inTreatment-Resistant DepressionGH001-TRD-201 21 EudraCT Number: 2022-000574-26
Design of Phase 2b Trial in TRD (GH001-TRD-201) 22 GH001 IDR Placebo IDR n=80 Randomization 1:1 Up to 5 GH001 IDRs may be administered during the OLE pro re nata (PRN), based on specific re-treatment criteria D0 MADRS Primary Endpoint ΔMADRS (per FDA guidance for rapid-acting antidepressants*) D1 D7 B H2 Scheduled Visit Double-Blind Phase Open-label Extension Phase (OLE) D14 M2 M3 M4 M5 M6 M1 During the OLE, additional clinic visits can be scheduled if required for medical reasons D0 D1 D7 B H2 PRN The bold solid lines indicate the fixed duration of 7 days (± 1 day) after an IDR with visits on D0, D1 and D7. The bold dotted line indicates the variable duration until a potential GH001 IDR in the OLE. The GH001 IDR consists of up to 3 increasing doses (6, 12, 18 mg) and the Placebo IDR consists of up to three placebo doses, to achieve a peak experience, given at a 1H interval. As in previously completed trials, the GH001-TRD-201 trial will be conducted under the supervision of a healthcare provider, but without any planned psychotherapeutic interventions before, during, or after dosing. IDR, Individualized Dosing Regimen; PRN, pro re nata (as needed); B, Baseline; H, Hour; D, Day; M, Month. *FDA draft guidance for industry “Major Depressive Disorder: Developing Drugs for Treatment”
Three-Layer Protection Strategy 23 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 (5-MeO-DMT), including: Novel uses in various disorders (including inhaled, nasal, buccal, sublingual, i.v., i.m., s.c. routes) Novel aerosol compositions of matter Novel manufacturing methods and novel salt forms Novel device-related aspects LAYER 3: TECHNICALComplex bioequivalence for systemically-acting inhalation/intranasal products with high intra- and inter-subject variability
Board of Directors & Executive Management 24 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
Scientific Advisors 25 Michael Thase M.D. Professor of Psychiatry, Perelman School of Medicine University of Pennsylvania Madhukar Trivedi M.D. Professor of Psychiatry, UT Southwestern Medical Center Mark Zimmerman M.D. Professor of Psychiatry and Human Behavior, Brown University Eduard Vieta Prof. Dr. Head, Psychiatry Unit, Hospital Clínic de Barcelona Michael Bauer Prof. Dr. rer. nat. Dr. med. Chair, Department of Psychiatry and Psychotherapy, Technische Universität Dresden Malek Bajbouj Prof. Dr. med. Head, Center for Affective Neuroscience, Charité, Berlin Johannes Ramaekers Prof. Dr. Professor, Faculty of Psychology and Neuroscience of Maastricht University
Anticipated Milestones and Financial Overview GH001 Complete double-blind phase of European Phase 2b trial in TRD in Q3 2024; complete open-label extension phase in Q1 2025 Complete Phase 2a trial in PPD in Q4 2024; Complete nonclinical studies and prepare device design verification information to support response to clinical hold on U.S. IND for GH001 administered using our proprietary aerosol delivery Complete Phase 1 clinical pharmacology trial with proprietary aerosol delivery device in Europe GH002 Complete review of next development steps GH003 Complete preclinical development Financial Overview Cash, cash equivalents, other financial assets and marketable securities were $204.5 million as of June 30, 2024 We believe existing cash, cash equivalents, other financial assets and marketable securities will be sufficient to fund operating expenses and capital expenditure requirements into 2026 26
AppendixAdditional Completed Trials 27
(Completed) Phase 1 Clinical Pharmacology Trial of GH001 in Healthy Volunteers GH001-HV-103 28 Clinicaltrials.gov ID: NCT05163691
Design of Phase 1 Clinical Pharmacology Trial of GH001 in Healthy Volunteers (GH001-HV-103) 29 Day 0 GH001 inhaled Day 7 GH001 6 mg (n=8+2 placebo) GH001 12 mg (n=8+2 placebo) GH001 18 mg (n=8+2 placebo) HV (n=30) Single-Dose Part IDR Part HV (n=16) GH001 IDR6, 12, 18 mg to achieve PE (up to 3 doses, 1h interval, n=8) Key Assessments Safety Pharmacokinetics PE Scale Cognitive function Safety Cognitive function Safety Day 30 GH001 IDR6, 12, 18 mg to achieve PE (up to 3 doses, 2h interval, n=8) Primary Endpoint: Pharmacokinetic profile of mebufotenin (5-MeO-DMT) and bufotenin HV, Healthy Volunteer; PE, Peak Experience;IDR, Individualized Dosing Regimen
Single Dose and IDR – Safety and Further Results Safety Review No SAEs All ADRs mild All ADRs resolved spontaneously Inhalation well-tolerated No noteworthy changes in vital parameters, except for temporary, non-clinically relevant increase in heart rate and blood pressure shortly after administration of GH001 No clinically relevant changes in ECG, safety laboratory analyses, peak flow, cognitive function or psychiatric symptom scales, including the C-SSRS Further Results Pharmacokinetic analyses and psychoactive effect assessments (PE Scale) support that an interval down to 1 hour between individual doses of the IDR is feasible for future clinical trials 30 ADRs Single-dose IDR 6 mg (n=8) 12 mg (n=8) 18 mg (n=8) Placebo (n=6) 1h interval (n=8)1 2h interval (n=8)2 MedDRA Preferred Term Number of Events n n n n n Abnormal dreams 1 Chest discomfort 1 Crying 2 2 Dizziness 1 Dry mouth 1 Dyskinesia 1 Fatigue 1 2 1 Headache 3 1 1 1 Hypoesthesia oral 1 Paresthesia oral 1 Retching 1 Somnolence 1 Tachycardia 2 Tension 1 Tremor 1 SAE, Serious Adverse Event; Adverse Drug Reaction, or ADR, an adverse event with a relationship code to the investigational product of definite, probable, or possible, or where code is missing; IDR, Individualized Dosing Regimen; C-SSRS, Columbia-Suicide Severity Rating Scale; PE, Peak Experience 16 mg (n=1), 6-12 mg (n=3); 6-12-18 mg (n=4)26-12 mg (n=3); 6-12-18 mg (n=5)
(Completed) Phase 1 Clinical Pharmacology Trial of GH002 in Healthy Volunteers GH002-HV-105 31 Clinicaltrials.gov ID: NCT05753956
Design of Phase 2 Trial of GH002 in Healthy Volunteers (GH002-HV-105) 32 GH002 0.25 mg (n=6+2 placebo) GH002 4 mg (n=6+2 placebo) GH002 8 mg (n=6+2 placebo) GH002 10 mg (n=6+2 placebo) HV (n=56) Part A (Single Dose) Primary Endpoints: Safety until day 7 Pharmacokinetic profile Part B (IDR) HV (n=8) Primary Endpoints: Safety until day 7 Pharmacokinetic profile GH002 IDR2, 4, 6 mg to achieve PE (up to 3 doses, 1h interval) Day 0 GH002 i.v. Day 7 Key Assessments Safety Pharmacokinetics PE Scale Cognitive function Safety Cognitive function HV, Healthy Volunteer; PE, Peak Experience; IDR, Individualized Dosing Regimen GH002 1 mg (n=6+2 placebo) GH002 6 mg (n=6+2 placebo) GH002 2 mg (n=6+2 placebo)
Single Dose and IDR – Safety and Further Results 33 Safety review No SAEs All ADRs mild, except one moderate (*) No noteworthy changes in vital parameters, except for temporary, non-clinically relevant increase in heart rate and blood pressure shortly after administration of GH002 No clinically relevant changes in ECG and safety laboratory analyses No clinically relevant changes in psychiatric symptoms scales, except for changes associated with the ADRs of emotional distress and poor quality sleep Further Results Potent psychoactive effects (PsE) with ultra-rapid onset and short duration were observed. The pharmacokinetic profile correlated with the ultra-rapid profile of the PsE. ADRs Single Dose IDR ADRs 0.25 mg (n=6) 1 mg (n=6) 2 mg (n=6) 4 mg (n=6) 6 mg (n=6) 8 mg (n=6) 10 mg (n=6) Placebo (n=14) 1 1h interval (n=8) 2 MedDRA Preferred Term Number of Events Abnormal dreams 1 Body temperature increased 1 Chest discomfort 1 Cold sweat 1 Dizziness 2 1 1 Dyspnoea 1 Emotional distress 1 1* Fatigue 2 1 1 1 Grunting 2 Headache 1 1 2 Head discomfort 1 1 1 Muscle spasms 2 Muscle twitching 1 Nausea 1 1 2 1 2 Neck pain 1 Pain in extremity 2 Poor quality sleep 1 Sleep disorder 1 Vomiting 1 1 1 1 1 n=2 subjects received placebo in each dose group 2 2 mg (n=4); 2-4 mg (n=2); 2-4-6 mg (n=2) SAE, Serious Adverse Event; Adverse Drug Reaction, or ADR, an adverse event with a relationship code to the investigational product of definite, probable, or possible, or where code is missing; IDR, Individualized Dosing Regimen
SeekingUltra-Rapid, Durable Remissionsin Depression 34