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 February, 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
GH Research PLC (the “Company”) will participate in a corporate panel and hold one-on-one investor meetings during the 44^th^ Annual TD Cowen Health Care Conference, which is scheduled to take place from March 4-6, 2024 in Boston, Massachusetts.
On February 29, 2024, the Company reported its full year 2023 financial results, provided business updates, 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 presentation is attached hereto as Exhibit 99.2.
The fact that this press release and 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 presentation is being provided as of February 29, 2024, and the Company does not undertake any obligation to update the press release or 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 99.1 and Exhibit 99.2 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333-270418) of GH Research PLC and to be a part thereof from the date on which this report is filed, to the extent not superseded by documents or reports subsequently filed or furnished.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 |
|---|---|
| 99.1 | Press release dated February 29, 2024 |
| 99.2 | Corporate Presentation for February 2024 |
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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: February 29, 2024 | ||
| By: | /s/ Julie Ryan | |
| Name: | Julie Ryan | |
| Title: | Vice President, Finance |
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Exhibit 99.1
GH Research Reports Full Year 2023 Financial Results and Provides Business Updates
| • | Phase 2b clinical trial of GH001 in patients with treatment-resistant depression on track for expected completion of double-blind phase in Q3 2024 |
|---|---|
| • | Phase 2a clinical trial of GH001 in postpartum depression on track for expected completion in Q3 2024 |
| --- | --- |
| • | Successfully completed Phase 1, dose-ranging clinical pharmacology trial of intravenous GH002 in healthy volunteers |
| --- | --- |
| • | Additional patents granted in Europe |
| --- | --- |
| • | Cash, cash equivalents, other financial assets and marketable securities of $222.7 million expected to provide cash runway into 2026 |
| --- | --- |
DUBLIN, Ireland, Feb 29, 2024 (GLOBE NEWSWIRE) -- GH Research PLC (Nasdaq: GHRS), a clinical-stage biopharmaceutical company dedicated to transforming the treatment of psychiatric and neurological disorders, today reported financial results for the year ended December 31, 2023, and provided updates on its business.
Business Updates
GH001 in Patients with TRD
GH001, our proprietary inhalable mebufotenin (5-MeO-DMT) product candidate, is currently being investigated in a multi-center, randomized, double-blind, placebo-controlled Phase 2b trial in approximately 80 patients with treatment-resistant depression (TRD) (GH001-TRD-201).
We have now initiated approximately 20 sites across seven European countries, and continue to see strong recruitment, supporting the expected completion of the double-blind phase of this trial in the third quarter of 2024, with top-line data expected to be available in the third or the fourth quarter of 2024. In this trial, GH001 is administered using an externally-sourced inhalation device. Consistent with previously completed trials, GH001 is administered on a single initial dosing day, without additional mandated visits for psychotherapy or psychological support before or after dosing.
GH001 in Patients with PPD and BDII
GH001 is also currently being investigated in proof-of-concept clinical trials in patients with postpartum depression (PPD) (GH001-PPD-203) and in patients with bipolar II disorder with a current depressive episode (BDII) (GH001-BD-202).
As announced in November 2023, both trials were recruiting slower than anticipated, in part due to the closure, for business reasons, of one of the two sites activated in each trial. Subsequently, we have implemented measures to strengthen recruitment of both trials, including the addition of further clinical trial sites. For the trial in patients with PPD (GH001-PPD-203), we now expect completion and availability of top-line data in the third quarter of 2024. For the trial in patients with BDII (GH001-BD-202), we need to further assess the impact of these measures on recruitment before we can provide an updated timeline.
GH002
Our Phase 1, dose-ranging clinical pharmacology trial of GH002 (GH002-HV-105), our proprietary intravenous mebufotenin (5-MeO-DMT) product candidate, in healthy volunteers has been successfully completed in the fourth quarter of 2023. Top-line results demonstrate that GH002 was well-tolerated and produced potent and ultra-rapid psychoactive effects.
This trial enrolled 64 healthy volunteers into a double-blind, placebo-controlled part where 56 subjects received single doses of GH002 or placebo in seven dose groups, and an open-label part where 8 subjects received an individualized dosing regimen (IDR) of up to three escalating doses of GH002 on a single day with a scheduled 1-hour interval between doses. The follow-up period was 7 days. GH002 was administered without additional mandated visits for psychological support before or after dosing. In this trial GH002 was found to be well-tolerated with no severe or serious adverse events. GH002 demonstrated potent pharmacodynamic (PD) effects, as assessed by psychoactive effect intensity, with an ultra-rapid onset and a short duration of the psychoactive experience. The pharmacokinetic (PK) profile of GH002 correlated with the ultra-rapid profile of the psychoactive effects.
Further trial results are described in our corporate presentation, which is available in the investor section on our website. The analyses of the PK/PD relationship and various other secondary endpoints are ongoing and will inform the further clinical development strategy for GH002.
Intellectual Property Updates
As announced in January 2024, the European Patent Office (EPO) has granted patent EP3927337 to GH Research with claims directed to mebufotenin (5-MeO-DMT) or a pharmaceutically acceptable salt thereof for use in treating patients diagnosed with major depressive disorder (MDD) and treatment-resistant forms of MDD, such as TRD. This patent is now effective, with an expiry date of no earlier than 2040, and is expected to cover all mebufotenin and mebufotenin salt products marketed to treat MDD and TRD, including but not limited to products administered through pulmonary inhalation, intravenous and intranasal routes.
More recently, the European Patent Office has granted two more patents to GH Research. Newly granted patent EP4313945 is directed to crystalline hydrobromide salt of mebufotenin, and will have an effective date of March 13, 2024, and an expiry date of no earlier than 2043. Newly granted patent EP3986864 is directed to a specific method of purifying mebufotenin, and will have an effective date of March 13, 2024, and an expiry date of no earlier than 2040.
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.
We are working to respond to the FDA’s requests and we have initiated the requested nonclinical studies and are preparing the requested device design verification information. In addition, we have recently requested a meeting with the FDA to discuss certain aspects of the FDA’s feedback.
We intend to provide an update regarding the IND response submission and the planned Phase 1 healthy volunteer clinical pharmacology trial (GH001-HV-106) in the second quarter of 2024. In parallel, to mitigate a potential delay to the GH001 program, we are also progressing preparations to potentially conduct the Phase 1 healthy volunteer clinical pharmacology trial (GH001-HV-106) in Europe.
Full Year 2023 Financial Highlights
Cash position
Cash, cash equivalents, other financial assets and marketable securities were $222.7 million as of December 31, 2023, compared to cash, cash equivalents and marketable securities of $251.7 million as of December 31, 2022. Other financial assets are comprised of money market funds, and marketable securities are comprised of investment grade bonds. We believe that our existing cash, cash equivalents, other financial assets and marketable securities will be sufficient for us to fund our operating expenses and capital expenditure requirements into 2026.
Research and development expenses
R&D expenses were $29.8 million for the year ended December 31, 2023, compared to $20.5 million for the full year 2022. The increase was primarily due to an increase in clinical trial expenses, increased expenses relating to our technical development, and increased employee expenses to support these activities. These increases have been partly offset by a decrease in nonclinical and regulatory expenses.
General and administrative expenses
G&A expenses were $11.4 million for the year ended December 31, 2023, compared to $10.1 million for the full year 2022. The increase was primarily due to higher professional fees, communications and IT costs and facility expenses, as well as increased employee expenses. These were partly offset by a decrease in insurance costs.
Net loss
Net loss was $35.6 million, or $0.68 loss per share, for the year ended December 31, 2023, compared to $22.5 million, or $0.43 loss per share, for the full year 2022.
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).
About GH001
Our lead product candidate, GH001, is formulated for mebufotenin (5-MeO-DMT) administration via a proprietary inhalation approach. With GH001, we have completed two Phase 1 healthy volunteer clinical trials and a Phase 1/2 clinical trial in patients with TRD. Based on the observed clinical activity, where 87.5% of patients with TRD were brought into an ultra-rapid remission with our GH001 individualized single-day dosing regimen in the Phase 2 part of the trial, we believe that GH001 has potential to change the way TRD is treated today. GH001 is currently in a multi-center, randomized, double-blind, placebo-controlled Phase 2b trial in patients with TRD and in two Phase 2a proof-of-concept trials in patients with bipolar II disorder and a current depressive episode and in patients with postpartum depression.
About GH002 and GH003
GH002 is our mebufotenin (5-MeO-DMT) product candidate formulated for administration via a proprietary intravenous approach. We have completed a Phase 1 trial of GH002 in healthy volunteers. GH003 is our mebufotenin (5-MeO-DMT) product candidate formulated for administration via a proprietary intranasal administration approach. GH003 is currently in preclinical development. We anticipate developing GH002 and GH003 within our focus area of psychiatric and neurological disorders.
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 for discussions with the FDA and the outcomes and resolution of such discussions related to 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
GH RESEARCH PLC
Consolidated Statement of Comprehensive Income (Unaudited)
(in thousands, except share and per share amounts)
| 2022 | |||
| ’000 | ’000 | ||
| Operating expenses | |||
| Research and development | (29,821 | (20,484 | |
| General and administration | (11,401 | (10,070 | |
| Loss from operations | (41,222 | (30,554 | |
| Finance income | 8,978 | 1,166 | |
| Finance expense | (723 | (123 | |
| Movement of expected credit loss | 1 | (121 | |
| Foreign exchange (loss)/gain | (2,621 | 7,176 | |
| Total other income | 5,635 | 8,098 | |
| Loss before tax | (35,587 | (22,456 | |
| Tax charge/(credit) | — | — | |
| Loss for the year | (35,587 | (22,456 | |
| Other comprehensive (expense)/income | |||
| Items that may be reclassified to profit or loss | |||
| Fair value movement on marketable securities | (95 | 558 | |
| Currency translation adjustment | 2,528 | (7,132 | |
| Total comprehensive loss for the year | (33,154 | (29,030 | |
| Attributable to owners: | |||
| Loss for the year | (35,587 | (22,456 | |
| Total comprehensive loss for the year | (33,154 | (29,030 | |
| Loss per share | |||
| Basic and diluted loss per share (in ) | (0.68 | (0.43 |
All values are in US Dollars.
GH RESEARCH PLC
Consolidated Balance Sheet (Unaudited)
(in thousands)
| At December 31, | ||||
|---|---|---|---|---|
| 2023 | 2022 | |||
| ’000 | ’000 | |||
| ASSETS | ||||
| Current assets | ||||
| Cash and cash equivalents | 78,420 | 165,955 | ||
| Other financial assets | 55,615 | — | ||
| Marketable securities | 27,525 | — | ||
| Other current assets | 2,529 | 2,586 | ||
| Total current assets | 164,089 | 168,541 | ||
| Non-current assets | ||||
| Marketable securities | 61,142 | 85,724 | ||
| Property, plant and equipment | 1,069 | 97 | ||
| Total non-current assets | 62,211 | 85,821 | ||
| Total assets | 226,300 | 254,362 | ||
| LIABILITIES AND EQUITY | ||||
| Current liabilities | ||||
| Trade payables | 3,490 | 1,868 | ||
| Lease liability | 343 | — | ||
| Other current liabilities | 2,868 | 2,678 | ||
| Total current liabilities | 6,701 | 4,546 | ||
| Non-current liabilities | ||||
| Lease liability | 631 | — | ||
| Total non-current liabilities | 631 | — | ||
| Total liabilities | 7,332 | 4,546 | ||
| Equity attributable to owners | ||||
| Share capital | 1,301 | 1,301 | ||
| Additional paid-in capital | 291,463 | 291,448 | ||
| Other reserves | 4,651 | 2,595 | ||
| Foreign currency translation reserve | (10,507 | (13,035 | ||
| Accumulated deficit | (67,940 | (32,493 | ||
| Total equity | 218,968 | 249,816 | ||
| Total liabilities and equity | 226,300 | 254,362 |
All values are in US Dollars.
Exhibit 99.2
GH Research PLC (NASDAQ: GHRS) February 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 these 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, the timing required to lift such clinical hold and for discussions with the FDA and the outcomes and resolution of such discussions; 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 GH001Mebufotenin (5-MeO-DMT)for inhalation administration Treatment-Resistant Depression (TRD) Phase 2b RDBPC trial initiated(GH001-TRD-201) Bipolar II Disorder* (BDII) Phase 2a POC trial initiated(GH001-BD-202) Postpartum Depression (PPD) Phase 2a POC trial initiated(GH001-PPD-203) GH002Mebufotenin (5-MeO-DMT) for i.v. administration Psychiatric or Neurological Disorder Phase 1 HV trial completed(GH002-HV-105) GH003Mebufotenin (5-MeO-DMT) for nasal administration Psychiatric or Neurological Disorder Pre-clinical development ongoing 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
Mebufotenin (5-MeO-DMT) and GH001 7 Mebufotenin (5-Methoxy-N,N-Dimethyltryptamine, 5-MeO-DMT) Naturally-occurring psychoactive substance from tryptamine class Highly potent agonist on 5-HT1A and 5-HT2A receptors GH001 (Mebufotenin administration via a proprietary pulmonary inhalation approach) Psychoactive effects with ultra-rapid onset (within seconds) and short duration (5 to 30 min) High propensity to induce peak experiences (PE), which may be a surrogate marker for therapeutic effects Intraday individualized dosing regimen (IDR) for maximization of ultra-rapid and durable remissions Single visit initial treatment, without additional mandated visits for psychotherapy or psychological support before or after dosing Potential for convenient and infrequent retreatment Mebufotenin (5-MeO-DMT) Foundational IP
GH001 – Individualized Dosing Regimen (IDR) for Maximization of Ultra-Rapid and Durable Remissions 8 GH001 Single Dose: Inter-Person Variability GH001 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 Theis Terwey PD Dr. med. CEO, Co-founder Julie Ryan ACA, 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 Medical 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 multi-center, randomized, double-blind, placebo-controlled Phase 2b trial in TRD in Q3 2024, and provide top-line data in Q3 or Q4 2024 Complete Phase 2a trial in PPD and provide top-line data in Q3 2024 Provide update on U.S. IND clinical hold and planned Phase 1 clinical pharmacology trial with proprietary aerosol delivery device in Q2 2024 GH002 Complete analysis of Phase 1 clinical pharmacology trial in healthy volunteers GH003 Complete preclinical development Financial Overview Cash, cash equivalents, other financial assets and marketable securities were $222.7 million as of December 31, 2023 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