# EDGAR Filing Document

**Accession Number:** 0001855129
**File Stem:** 0001140361-23-009566
**Filing Date:** 2023-3
**Character Count:** 37823
**Document Hash:** f9b0039ffc95a8ea463ca6887bb0005c
**Contains OCR:** False
**Source Format:** 

## Filing Content

## Filing Summary
**0001140361-23-009566.hdr.sgml**: 20230302

**ACCESSION NUMBER**: 0001140361-23-009566

**CONFORMED SUBMISSION TYPE**: 6-K

**PUBLIC DOCUMENT COUNT**: 34

**CONFORMED PERIOD OF REPORT**: 20230302

**FILED AS OF DATE**: 20230302

**DATE AS OF CHANGE**: 20230302

**FILER**: 

**COMPANY DATA:**
- **COMPANY CONFORMED NAME:** GH Research PLC
- **CENTRAL INDEX KEY:** 0001855129
- **STANDARD INDUSTRIAL CLASSIFICATION:** PHARMACEUTICAL PREPARATIONS [2834]
- **IRS NUMBER:** 000000000
- **STATE OF INCORPORATION:** L2
- **FISCAL YEAR END:** 1231

**FILING VALUES:**
- **FORM TYPE:** 6-K
- **SEC ACT:** 1934 Act
- **SEC FILE NUMBER:** 001-40530
- **FILM NUMBER:** 23696393

**BUSINESS ADDRESS:**
- **STREET 1:** 28 BAGGOT STREET
- **CITY:** LOWER DUBLIN
- **STATE:** L2
- **ZIP:** 2D02 NX43
- **BUSINESS PHONE:** 353 1 437 8334

**MAIL ADDRESS:**
- **STREET 1:** 28 BAGGOT STREET
- **CITY:** LOWER DUBLIN
- **STATE:** L2
- **ZIP:** 2D02 NX43

------

### 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 March, 2023.

#### 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:

Form 20-F <u> ☒ </u> <br> Form 40-F  

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): ☐

------

GH Research PLC (the "Company") provided business updates on March 2, 2023 by way of a press release and an updated corporate presentation. A copy of the press release is attached 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 the presentation is being provided as of March 2, 2023 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.

------

#### EXHIBIT INDEX

---

| | |
|:---|:---|
| **Exhibit No.** | **Description** |
| [99.1](brhc10049116_ex99-1.htm) | Press release dated March 2, 2023 |
| [99.2](brhc10049116_ex99-2.htm) | Corporate Presentation for March 2023 |

---

------

#### 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** | **GH Research PLC** |
| Date: March 2, 2023 |  |  |
|  | By: | /s/ Julie Ryan |
|  | Name: | Julie Ryan |
|  | Title: | Vice President, Finance |

---

------

## Exhibit 99.1

------

#### Exhibit 99.1<br>

#### <br>

#### GH Research Reports Full Year 2022 Financial Results and Provides Business Updates

DUBLIN, Ireland., March 2, 2023 (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 full year ended December 31, 2022 and gave updates on its business.

#### Business Updates
We are pleased to report that we have recently initiated our multi-center, randomized, double-blind, placebo-controlled Phase 2b trial of GH001 in treatment-resistant depression (TRD) (GH001-TRD-201). GH001 is our proprietary inhalable mebufotenin (5-MeO-DMT) product candidate.

We expect to recruit approximately 80 patients for this trial across several European countries. The primary objective will be to determine the efficacy of our single-day individualized dosing regimen (IDR) of GH001 compared with placebo in improving depressive symptoms as assessed by the mean change from baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) at the end of the 7-day double-blind phase. The double-blind phase will be followed by a 6-month open-label extension phase where all patients can receive treatment with the GH001 IDR as-needed, based on the patient's clinical status. Further trial design details are described in our updated corporate presentation, which is available in the investor section on our website.

#### Recent Business Highlights
In January 2023, we reported development progress in respect of our proprietary aerosol delivery device and our expectation that we will submit an IND for GH001, delivered with this proprietary device, in the third quarter of 2023. The IND-opening study is expected to be a Phase 1 clinical pharmacology trial in healthy volunteers (GH001-HV-106), designed to support bridging to the clinical data generated with the third-party device we currently use in our clinical trials.

We also reported, in January 2023, the recent initiation of our randomized, double-blind, placebo-controlled, dose-ranging clinical pharmacology trial of GH002 in healthy volunteers (GH002-HV-105). GH002 is our mebufotenin (5-MeO-DMT) product candidate formulated for administration via a proprietary intravenous approach. We expect to complete this trial in the fourth quarter of 2023.

Furthermore, we reported the recent expansion of our patent portfolio, to include 11 patent families that relate to various aspects of mebufotenin (5-MeO-DMT) use in a therapeutic context, including but not limited to the use of mebufotenin (5-MeO-DMT) for treatment of various disorders when administered by inhalation, or by nasal, buccal, sublingual, intravenous, intramuscular or subcutaneous routes.

We also announced the selection of mebufotenin as the International Nonproprietary Name (INN) for 5-MeO-DMT by the World Health Organization (WHO) Expert Advisory Panel on the International Pharmacopoeia and Pharmaceutical Preparations.

#### Full Year 2022 Financial Highlights
*Cash position*

Cash, cash equivalents and marketable securities were $251.7 million as of December 31, 2022, compared to cash of $276.8 million as of December 31, 2021. Marketable securities are comprised of investment grade bonds. We believe that our existing cash, cash equivalents and marketable securities will be sufficient for us to fund our operating expenses and capital expenditure requirements into 2026.

------

![](image00001.jpg)

*Research and development expenses*

R&D expenses were $20.5 million for the year ended December 31, 2022, compared to $8.6 million for the full year 2021. The increase was primarily due to increased activities relating to our technical development, clinical trials and increased employee expenses to support these activities.

*General and administrative expenses*

G&A expenses were $10.1 million for the year ended December 31, 2022, compared to $6.5 million for the full year 2021. The increase was primarily due to higher insurance costs, an increase in professional costs as well as increased employee expenses.

*Net loss*

Net loss was $22.5 million, or $0.432 loss per share, for the year ended December 31, 2022, compared to $9.2 million, or $0.211 loss per share, for the full year 2021.

#### 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 treatment-resistant depression (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 of GH001 in treatment-resistant depression (TRD). Across the GH001 program, no serious adverse events have been reported and GH001 was well tolerated at the investigated single dose levels and in the individualized dosing regimen.

#### About GH002 and GH003
GH002 is our mebufotenin (5-MeO-DMT) product candidate formulated for administration via a proprietary intravenous approach. GH002 is currently in Phase 1 clinical development. 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 in subpopulations and confined use scenarios within our focus area of psychiatric and neurological disorders.

------

![](image00001.jpg)

#### 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, cash runway, business strategy, product candidates, proprietary medical devices, research pipeline, ongoing and currently planned preclinical studies and clinical trials, regulatory submissions and approvals, research and development costs, timing and likelihood of success, as well as plans and objectives of management for future operations are forward-looking statements. Forward-looking statements appear in a number of places in this press release and include, but are not limited to, statements regarding our intent, belief or current expectations. Forward-looking statements are based on our management's beliefs and assumptions and on information currently available to our management. Such statements are subject to risks and uncertainties, and actual results may differ materially from those expressed or implied in the forward-looking statements due to various factors, including, but not limited to, those described in our filings with the U.S. Securities and Exchange Commission. No assurance can be given that such future results will be achieved. Such forward-looking statements contained in this 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

<u>investors@ghres.com</u>

------

![](image00001.jpg)

#### GH RESEARCH PLC

#### Consolidated Statement of Comprehensive Income (Unaudited)
(in thousands, except share and per share amounts)

---

| | | |
|:---|:---|:---|
|  | **Year ended**<br> **December 31,** | **Year ended**<br> **December 31,** |
|  | **2022** | **2021** |
|  | **$'000** | **$'000** |
|  **Operating expenses** |  |  |
| &nbsp;&nbsp;&nbsp; Research and development | (20484) | (8553) |
| &nbsp;&nbsp;&nbsp; General and administration | (10070) | (6547) |
|  **Loss from operations** | **(30554)** | **(15100**) |
| &nbsp;&nbsp;&nbsp; Net finance income/(expense) | 922 | (9) |
| &nbsp;&nbsp;&nbsp; Foreign exchange gain | 7176 | 5907 |
|  **Total finance income** | **8098** | **5898** |
|  **Loss before tax** | **(22456)** | **(9202)** |
| &nbsp;&nbsp;&nbsp; Tax charge/(credit) |  |  |
|  **Loss for the year** | **(22456)** | **(9202)** |
|  **Other comprehensive income/(expense)** |  |  |
|  *Items that may be reclassified to profit or loss* |  |  |
| &nbsp;&nbsp;&nbsp; Fair value movement on marketable securities | 558 |  |
| &nbsp;&nbsp;&nbsp; Currency translation adjustment | (7132) | (6103) |
|  **Total comprehensive loss for the year** | **(29030)** | **(15305)** |
|  **Attributable to owners:** |  |  |
| &nbsp;&nbsp;&nbsp; Loss for the year | (22456) | (9202) |
| &nbsp;&nbsp;&nbsp; Comprehensive loss for the year | (29030) | (15305) |
|  **Loss per share** |  |  |
| &nbsp;&nbsp;&nbsp; Basic and diluted loss per share (in USD) | (0.432) | (0.211) |

---

------

![](image00001.jpg)

#### GH RESEARCH PLC

#### Consolidated Balance Sheet (Unaudited)
(in thousands)

---

| | | |
|:---|:---|:---|
|  | **At December 31,** | **At December 31,** |
|  | **2022** | **2021** |
|  | **$'000** | **$'000** |
|  **ASSETS** |  |  |
|  **Current assets** |  |  |
| &nbsp;&nbsp;&nbsp; Cash and cash equivalents | 165955 | 276776 |
| &nbsp;&nbsp;&nbsp; Other current assets | 2586 | 3066 |
|  **Total current assets** | **168541** | **279842** |
|  **Non-current assets** |  |  |
| &nbsp;&nbsp;&nbsp; Marketable securities | 85724 |  |
| &nbsp;&nbsp;&nbsp; Property, plant and equipment | 97 | 82 |
|  **Total non-current assets** | **85821** | **82** |
|  **Total assets** | **254362** | **279924** |
|  **LIABILITIES AND EQUITY** |  |  |
|  **Current liabilities** |  |  |
| &nbsp;&nbsp;&nbsp; Trade payables | 1868 | 883 |
| &nbsp;&nbsp;&nbsp; Other current liabilities | 2678 | 1866 |
|  **Total current liabilities** | **4546** | **2749** |
|  **Total liabilities** | **4546** | **2749** |
|  **Equity attributable to owners** |  |  |
| &nbsp;&nbsp;&nbsp; Share capital | 1301 | 1301 |
| &nbsp;&nbsp;&nbsp; Additional paid-in capital | 291448 | 291448 |
| &nbsp;&nbsp;&nbsp; Other reserves | 2595 | 366 |
| &nbsp;&nbsp;&nbsp; Foreign currency translation reserve | (13035) | (5903) |
| &nbsp;&nbsp;&nbsp; Accumulated deficit | (32493) | (10037) |
|  **Total equity** | **249816** | **277175** |
|  **Total liabilities and equity** | **254362** | **279924** |

---

------

## Exhibit 99.2

------

**Exhibit 99.2**<br>

![](brhc10049116_ex99-2slide1.jpg)

1 Corporate Presentation GH Research PLC (NASDAQ: GHRS) GH Research March 2023 2023© GH Research PLC

------

![](brhc10049116_ex99-2slide2.jpg)

Disclaimer Regarding Forward-Looking Statements 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. 2 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 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. 2023© GH Research PLC

------

![](brhc10049116_ex99-2slide3.jpg)

Seeking Ultra-Rapid, Durable Remissions in Depression 3 2023© GH Research PLC

------

![](brhc10049116_ex99-2slide4.jpg)

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 initiated(GH002-HV-105) GH003Mebufotenin (5-MeO-DMT) for nasal administration Psychiatric or Neurological Disorder Pre-clinical development ongoing Pipeline 4 2023© GH Research PLC \*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 Complete Ongoing

------

![](brhc10049116_ex99-2slide5.jpg)

... 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 TRD, Treatment-Resistant Depression Average time to remission is ~6 weeks (STAR\*D study, Remission Rate Over Time, Treatment Step 1 = Citalopram) The Problem for Patients with Depression (STAR\*D study, Remission Rates Treatment Steps 1 to 4) 5 2 or more prior therapies = TRD 2023© GH Research PLC

------

![](brhc10049116_ex99-2slide6.jpg)

Large and Open Depression Market in the EU and US 6 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 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 2023© GH Research PLC

------

![](brhc10049116_ex99-2slide7.jpg)

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, with no structured psychotherapy Potential for convenient and infrequent retreatment Mebufotenin (5-MeO-DMT) and GH001 7 2023© GH Research PLC Mebufotenin (5-MeO-DMT) Foundational IP

------

![](brhc10049116_ex99-2slide8.jpg)

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 GH001 – Individualized Dosing Regimen (IDR) for Maximization of Ultra-Rapid and Durable Remissions 8 2023© GH Research PLC MADRS score Dose 1 MADRS, Montgomery-Åsberg Depression Rating Scale

------

![](brhc10049116_ex99-2slide9.jpg)

Phase 1 Trial in Healthy Volunteers GH001-HV-101 (Completed) 9 Clinicaltrials.gov ID: NCT04640831 2023© GH Research PLC

------

![](brhc10049116_ex99-2slide10.jpg)

GH001 Administration Day 1 Day 7 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) Part B (IDR) Primary Endpoint: Safety until day 7 Peak Experience Scale (PE Scale)1 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) 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? Design of Phase 1 Trial in Healthy Volunteers (GH001-HV-101) 10 2023© GH Research PLC HV, Healthy Volunteer; PE, Peak Experience; IDR, Individualized Dosing Regimen

------

![](brhc10049116_ex99-2slide11.jpg)

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 significant changes in safety laboratory analyses, psychiatric safety assessments 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&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; 1&nbsp;&nbsp;&nbsp;&nbsp; Anxiety&nbsp;&nbsp;&nbsp;&nbsp; 1 1&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;Clumsiness&nbsp;&nbsp;&nbsp;&nbsp; 1&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Confusional state&nbsp;&nbsp;&nbsp;&nbsp; 1&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Euphoric mood&nbsp;&nbsp;&nbsp;&nbsp; 1&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Fatigue&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; 1 1\* Feeling hot&nbsp;&nbsp;&nbsp;&nbsp; 1&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Flashback&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; 1&nbsp;&nbsp;&nbsp;&nbsp; Hallucination&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; 1&nbsp;&nbsp;&nbsp;&nbsp; Head discomfort&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; 1 Headache&nbsp;&nbsp;&nbsp;&nbsp; 2&nbsp;&nbsp;&nbsp;&nbsp; 1 1 Heart rate increased&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;1\*&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;Hyperacusis&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; 1&nbsp;&nbsp;&nbsp;&nbsp; Insomnia&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; 1&nbsp;&nbsp;&nbsp;&nbsp; Mental fatigue&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; 1&nbsp;&nbsp;&nbsp;&nbsp; Nausea 2 1&nbsp;&nbsp;&nbsp;&nbsp; 1 2 Vision blurred 1&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Part A (Single Dose) and Part B (IDR) – Safety 11 2023© GH Research PLC 16 mg (n=1); 6-12 mg (n=2); 6-12-18 mg (n=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

------

![](brhc10049116_ex99-2slide12.jpg)

Average fordose group PE Scale PEThreshold Part A – Peak Experience (PE) Dose-Effectsand Inter-Person Variability 12 PE, Peak Experience 2023© GH Research PLC

------

![](brhc10049116_ex99-2slide13.jpg)

PEThreshold Part B – Peak Experience (PE)Effect of Intraday Individualized Dosing Regimen (IDR) 13 PE, Peak Experience 2023© GH Research PLC

------

![](brhc10049116_ex99-2slide14.jpg)

Phase 1/2 Trial in Treatment-Resistant Depression GH001-TRD-102 (Completed) 14 Clinicaltrials.gov ID: NCT04698603 2023© GH Research PLC

------

![](brhc10049116_ex99-2slide15.jpg)

Key Assessments MADRS H2 PE Scale Safety MADRS D1 Cognitive function Safety MADRS D7 Cognitive function Safety GH001 Administration Day 1 Day 7 Design of Phase 1/2 Trial in TRD (GH001-TRD-102) 15 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 2023© GH Research PLC 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

------

![](brhc10049116_ex99-2slide16.jpg)

Phase 1 (Single Dose) and Phase 2 (IDR) – Safety 16 2023© GH Research PLC 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" 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&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;1 Anxiety&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;2 Depressive symptom&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;1\* Dizziness 1&nbsp;&nbsp;&nbsp;&nbsp; Feeling abnormal 1 1&nbsp;&nbsp;&nbsp;&nbsp; Flashback 1 1 2 Headache 2 1 3 Muscle discomfort 1 Muscle spasms&nbsp;&nbsp;&nbsp;&nbsp; 1&nbsp;&nbsp;&nbsp;&nbsp; Nausea&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;2\* Paresthesia&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;1 Sensory disturbance 3 16-12 mg (n=6); 6-12-18 mg (n=2) 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

------

![](brhc10049116_ex99-2slide17.jpg)

MADRS Remission / Response / Improvement Rate Day 7 Phase 1 (Single Dose) – Efficacy (MADRS) 17 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. 2023© GH Research PLC 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

------

![](brhc10049116_ex99-2slide18.jpg)

Phase 2 (IDR) – Efficacy (MADRS) 18 2023© GH Research PLC MADRS Remission / Response / Improvement Rate Day 7 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 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..

------

![](brhc10049116_ex99-2slide19.jpg)

Phase 2 (IDR) – Efficacy (MADRS Change from Baseline) 2023© GH Research PLC Baseline1 Hour 2 Day 1 Day 7 GH001 19 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 1Baseline mean MADRS=32

------

![](brhc10049116_ex99-2slide20.jpg)

MADRS and PE – Observed Improved Outcome in Phase 2 (IDR) vs Phase 1 (Single Dose) 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 2023© GH Research PLC 20 PE, Peak Experience; MADRS, Montgomery-Åsberg Depression Rating Scale; IDR, Individualized Dosing Regimen

------

![](brhc10049116_ex99-2slide21.jpg)

Phase 1 Clinical Pharmacology Trial in Healthy Volunteers GH001-HV-103 (Completed) 21 2023© GH Research PLC Clinicaltrials.gov ID: NCT05163691

------

![](brhc10049116_ex99-2slide22.jpg)

GH001 Administration 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 22 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 bufotenine 2023© GH Research PLC Design of Phase 1 Clinical Pharmacology Trial in Healthy Volunteers (GH001-HV-103) HV, Healthy Volunteer; PE, Peak Experience;IDR, Individualized Dosing Regimen

------

![](brhc10049116_ex99-2slide23.jpg)

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, psychiatric safety assessments, 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 Single Dose and IDR – Safety and Further Results 23 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 2023© GH Research PLC 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&nbsp;&nbsp;&nbsp;&nbsp; 1&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;Crying&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;2&nbsp;&nbsp;&nbsp;&nbsp; 2&nbsp;&nbsp;&nbsp;&nbsp; Dizziness&nbsp;&nbsp;&nbsp;&nbsp; 1&nbsp;&nbsp;&nbsp;&nbsp; Dry mouth 1&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Dyskinesia&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;1&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Fatigue 1 2 1 Headache 3 1&nbsp;&nbsp;&nbsp;&nbsp; 1 1 Hypoesthesia oral 1&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;Paresthesia oral&nbsp;&nbsp;&nbsp;&nbsp; 1 Retching 1&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;Somnolence 1&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;Tachycardia 2&nbsp;&nbsp;&nbsp;&nbsp; Tension&nbsp;&nbsp;&nbsp;&nbsp; 1 Tremor 1&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;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)

------

![](brhc10049116_ex99-2slide24.jpg)

Phase 2b Trial in Treatment-Resistant Depression GH001-TRD-201 (Initiated) 24 2023© GH Research PLC EudraCT Number: 2022-000574-26

------

![](brhc10049116_ex99-2slide25.jpg)

Design of Phase 2b Trial in TRD (GH001-TRD-201) 2023© GH Research PLC 25 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) 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" 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

------

![](brhc10049116_ex99-2slide26.jpg)

LAYER 1: REGULATORY EXCLUSIVITY FDA: 5 years (+2.5 years paragraph IV stay) EMA: 10 years (+1 year for new indication) LAYER 3: TECHNICALComplex bioequivalence for systemically-acting inhalation/intranasal products with high intra- and inter-subject variability LAYER 2: PATENTS 11 patent families filed 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 Three-Layer Protection Strategy 26 2023© GH Research PLC

------

![](brhc10049116_ex99-2slide27.jpg)

Board of Directors & Management 27 Florian Schönharting Michael Forer MSc Chairman of the Board, Co-founder BA, LLB Vice-Chairman of the Board 2023© GH Research PLC 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

------

![](brhc10049116_ex99-2slide28.jpg)

Scientific Advisors 28 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 2023© GH Research PLC

------

![](brhc10049116_ex99-2slide29.jpg)

Anticipated Milestones and Financial Overview GH001 Complete multi-center, randomized, double-blind, placebo-controlled Phase 2b trial in TRD Submit U.S. IND for GH001 with proprietary aerosol delivery device in Q3 2023 Complete proof-of-concept Phase 2a trials in BDII and in PPD in Q4 2023 GH002 Complete Phase 1 clinical pharmacology trial in healthy volunteers in Q4 2023 GH003 Complete preclinical development Financial Overview Cash, cash equivalents and marketable securities was $251.7 million as of December 31, 2022 We believe existing cash, cash equivalents and marketable securities will be sufficient to fund operating expenses and capital expenditure requirements into 2026 29 2023© GH Research PLC

------

![](brhc10049116_ex99-2slide30.jpg)

Seeking Ultra-Rapid, Durable Remissions in Depression 30 2023© GH Research PLC

------

<br>