GH Research : Corporate Presentation

GH Research

Corporate Presentation

GH Research PLC (NASDAQ: GHRS)

November 2023

2023© GH Research PLC	1

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.

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.

2023© GH Research PLC	2

Seeking

Ultra-Rapid, Durable Remissions

in Depression

2023© GH Research PLC	3

Pipeline

Stage of Development

PROGRAMS	INDICATION	PRECLINICAL	PHASE 1	PHASE 2a	PHASE 2b	PHASE 3	CURRENT STATUS
	Treatment-Resistant						Phase 2b
						RDBPC trial initiated
	Depression (TRD)
						(GH001-TRD-201)
GH001
Mebufotenin (5-MeO-DMT)
for inhalation	Bipolar II Disorder*						Phase 2a
administration						POC trial initiated
	(BDII)
							(GH001-BD-202)
	Postpartum Depression						Phase 2a
						POC trial initiated
		(PPD)
							(GH001-PPD-203)
GH002	Psychiatric or						Phase 1
Mebufotenin (5-MeO-DMT)						HV trial initiated
Neurological Disorder
for i.v. administration						(GH002-HV-105)
GH003	Psychiatric or						Pre-clinical
Mebufotenin (5-MeO-DMT)						development
Neurological Disorder
for nasal administration						ongoing
	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

2023© GH Research PLC	4

The Problem for Patients with Depression

Established Therapies are Slow-Acting

(STAR*D study, Remission Rate Over Time, Treatment Step 1 = Citalopram)

Patients)	100%
90%
80%
(%	70%
Rate
60%
Remission	50%
40%		Average time to
30%	remission is ~6 weeks
Cumulative
20%
10%
0%
	0	2	4	6	8	10	12	14
				Week

Adapted from Trivedi et al., Am J Psychiatry 2006 and Rush et al., Am J Psychiatry 2006

TRD, Treatment-Resistant Depression

... Remission Rates in TRD < 15%

(STAR*D study, Remission Rates Treatment Steps 1 to 4)

	100%		~33% no remission		100%
	90%			90%	(line)
	despite 4 treatment steps
(%) (bar)	80%					80%
				Rate (%)
70%					70%
60%				67%	60%
Remission Rates			62%	Cumulative Remission
50%		56%			50%
40%	37%				40%
	31%
30%					30%
20%			14%	13%	20%
10%					10%
	0%					0%
		1	2	3	4

Treatment Step

2 or more prior therapies = TRD

2023© GH Research PLC	5

Large and Open Depression Market in the EU and US

First Line MDD

• Diagnosed: ~48M
• • Treated (pharmacotherapy ± psychotherapy): ~24M

Second Line MDD

• Non-responseto first line: ~13M

Treatment-Resistant Depression (TRD)

• Non-responseto two prior lines: ~9M

Patients cycle through ineffective therapies for TRD

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 2006 MDD, Major Depressive Disorder

2023© GH Research PLC	6

Foundational IP

Mebufotenin (5-MeO-DMT) and GH001

• Mebufotenin (5-Methoxy-N,N-Dimethyltryptamine,5-MeO-DMT)
• • Naturally-occurringpsychoactive substance from tryptamine class
  • Highly potent agonist on 5-HT1A and 5-HT2A receptors

Mebufotenin (5-MeO-DMT)

• 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

2023© GH Research PLC	7

GH001 - Individualized Dosing Regimen (IDR)

for Maximization of Ultra-Rapid and Durable Remissions

GH001 Single Dose:

Inter-Person Variability

score

Dose 1	GH001 Individualized Dosing Regimen (IDR):
	Maximization of Ultra-Rapid and Durable Remissions

Hypothetical Patient 1

MADRS score

Dose 1

No remission

Hypothetical Patient 1

MADRS

MADRS score

Remission

Dose 1

Dose 2

No remission

Hypothetical Patient 2

MADRS score

Dose 1

Remission

Hypothetical Patient 2

Hypothetical Patient 3

MADRS score

Dose 1

Dose 2

No remission

Remission

Dose 3

No remission

Remission

MADRS, Montgomery-Åsberg Depression Rating Scale

2023© GH Research PLC	8

Phase 1 Trial in Healthy Volunteers

GH001-HV-101

(Completed)

Clinicaltrials.gov ID: NCT04640831

2023© GH Research PLC	9

Design of Phase 1 Trial in Healthy Volunteers (GH001-HV-101)

Part A (Single Dose)

GH001 2 mg (n=4)

			Primary Endpoint:
	GH001	6 mg (n=6)
HV	•	Safety until day 7
(n=18)			•	Peak Experience
GH001 12 mg (n=4)
		Scale (PE Scale)1

GH001 18 mg (n=4)

Part B (IDR)

	GH001 IDR	Primary Endpoint:
HV	6, 12, 18 mg to	•	Safety until day 7
achieve PE
(n=4)	•	Peak Experience
(up to 3 doses,

3h interval)	Scale (PE Scale)1

	GH001	Day 1	Day 7
	Administration
Key Assessments	Safety	Safety	Safety
	PE Scale		Cognitive function
	Cognitive
	function
HV, Healthy Volunteer; PE, Peak Experience;				1The PE Scale averages answers scored by the subject by marking a visual analogue scale between 0 and 100 for the following three questions:
IDR, Individualized Dosing Regimen				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?

2023© GH Research PLC	10