Exhibit 99.2

MANAGEMENT’S DISCUSSION AND ANALYSIS OF FINANCIAL CONDITION

AND RESULTS OF OPERATIONS

 

This management’s discussion and analysis is designed to provide you with a narrative explanation of our financial condition and results of operations. You should read this discussion and analysis in conjunction with our unaudited condensed consolidated interim financial statements, including the notes thereto, as of and for the three months ended March 31, 2024. You should also read this discussion and analysis in conjunction with our audited consolidated financial statements, including the notes thereto, and the section in our annual report on Form 20-F for the year ended December 31, 2023 titled “Item 3. Key Information—D. Risk Factors.”

 

Our unaudited condensed consolidated interim financial statements for the three months ended March 31, 2024, were prepared in accordance with International Accounting Standard 34, Interim Financial Reporting. The terms “dollar,” “USD” or “$” refer to U.S. dollars. We have made rounding adjustments to some of the figures included in this discussion. Accordingly, any numerical discrepancies in any table between totals and sums of the amounts listed are due to rounding.

 

Unless otherwise indicated or the context otherwise requires, all references in this discussion and analysis to “GH Research” or “GH,” the “Company,” “we,” “our,” “ours,” “us” or similar terms refer to GH Research PLC and its consolidated subsidiary.

 

Overview

 

We are a clinical-stage biopharmaceutical company dedicated to transforming the treatment of psychiatric and neurological disorders. Our initial focus is on developing our novel and proprietary mebufotenin (5-methoxy-N,N-dimethyltryptamine, or 5-MeO-DMT) therapies for the treatment of patients with treatment-resistant depression, or TRD. Mebufotenin was selected 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.

 

Our portfolio currently includes GH001, our proprietary inhalable mebufotenin product candidate, GH002, our proprietary intravenous mebufotenin product candidate, and GH003, our proprietary intranasal mebufotenin product candidate. While GH001 is currently delivered via a vaporization device produced by a third party, we are developing a proprietary aerosol delivery device. We have completed two Phase 1 healthy volunteer clinical trials for GH001 (GH001-HV-101 and GH001-HV-103), in which administration of GH001 via inhalation was observed to be well tolerated at the investigated single dose levels and in an individualized dosing regimen, or IDR, with intra-subject dose escalation within a single day. We have also completed a Phase 1/2 clinical trial in patients with TRD (GH001-TRD-102). Based on observed clinical activity in the Phase 1 part of the clinical trial, we believe that administration of a single dose of GH001 has the potential to induce ultra-rapid remissions as measured by the Montgomery-Åsberg Depression Rating Scale, or MADRS, in certain patients, driven by the ultra-rapid onset of psychoactive effects (commonly within seconds) and an intense and short-lived (commonly five to 30 minutes) psychoactive experience. Based on observed clinical activity in the Phase 2 part of the trial, we believe that administration of GH001 in an IDR with intra-subject dose escalation within a single day can further increase the MADRS remission rate as compared to a single dose of GH001.

 

We have incurred losses since inception, including losses of $7.7 million for the three months ended March 31 2024, and losses of $35.6 million and $22.5 million for the years ended December 31, 2023 and 2022, respectively. As of March 31, 2024, we had an accumulated deficit of $75.5 million. We expect to incur significant expenses and operating losses for the foreseeable future as we expand our research and development activities. In addition, our losses from operations may fluctuate significantly from quarter-to-quarter and year-to-year, depending on the timing of our clinical trials, our expenditures on other research and development activities and based on foreign currency translation differences. We anticipate that our expenses will increase significantly in connection with our ongoing activities, if and as we:

 

 

 

In addition, as we progress toward marketing approval for any of our product candidates, we also expect to incur significant commercialization expenses related to product manufacturing, marketing, sales, and distribution.

 

As a result, we will need substantial additional funding to support our continuing operations and pursue our growth strategy. Until such time as we can generate significant revenue from product sales, if ever, we expect to finance our operations through the sale of equity, debt financings or other capital sources, including potential collaborations with other companies or other strategic transactions. We cannot be certain that additional funding will be available on acceptable terms, or at all. If we fail to raise capital or enter into such agreements as and when needed, we may have to significantly delay, scale back, or discontinue the development and commercialization of one or more of our product candidates or other research and development initiatives, which could have a material adverse effect on our business, results of operations, and financial condition. We will need to generate significant revenue to achieve profitability, and we may never do so.

 

We are subject to a number of risks comparable to those of other similar companies, including dependence on key individuals; the need to develop product candidates with the required safety and efficacy profile and which support regulatory approval and are commercially viable; competition from other companies, many of which are larger and better capitalized; and the need to obtain adequate additional financing to fund the development of our product candidates.

 

Business Updates

 

Results of Operations

 

Comparison of the Three Months Ended March 31, 2024 and 2023

 

The following table summarizes our results of operations for the three months ended March 31, 2024 and 2023:

 

¹Net finance income for the three months ended March 31, 2024, comprises finance income, finance expense and expected credit losses.

 

Research and Development Expenses

 

The following table summarizes our research and development expenses for the three months ended March 31, 2024 and 2023:

 

¹ Includes share based compensation expense of $0.2 million and $0.3 million for the three months ended March 31, 2024 and 2023, respectively. 

 

The following table summarizes our research and development expenses for our product candidates for the three months ended March 31, 2024 and 2023:

 

¹ Includes expenses that relate to any combination of GH001, GH002 and/or GH003 and exploratory work for potential future candidates.

 

Research and development expenses increased by $1.4 million to $8.7 million for the three months ended March 31, 2024, from $7.3 million for the three months ended March 31, 2023. The increase is primarily due to increased expenses relating to nonclinical activities, active pharmaceutical ingredient and drug product development and manufacturing and increased clinical trial expenses. These increases have been partly offset by a decrease in expenses relating to our technical development including device development.

 

Research and development expenses for our product candidates will fluctuate from period to period primarily due to the nature and timing associated with the various lifecycle stages of each candidate.

 

Research and development expenses relating to GH001 increased by $1.4 million in the three months ended March 31, 2024, primarily due to an increase in clinical trial expenses, an increase in expenses related to nonclinical activities and active pharmaceutical ingredient and drug product development and manufacturing, partly offset by a decrease in expenses relating to technical development including device development.

 

Research and development expenses relating to GH002 increased by $0.1 million in the three months ended March 31, 2024, primarily due to an increase in active pharmaceutical ingredient and drug product development and manufacturing and partly offset by decreased clinical trial expenses.

 

General and Administrative Expenses

 

The following table summarizes our general and administrative expenses for the three months ended March 31, 2024 and 2023:

 

¹ Includes share based compensation expense of $0.1 million and $0.2 million for the three months ended March 31, 2024 and 2023, respectively.

 

General and administrative expenses decreased by $0.2 million to $2.9 million for the three months ended March 31, 2024, from $3.1 million for the three months ended March 31, 2023. The decrease is primarily due to a reduction in professional fees and insurance costs offset by an increase in employee expenses in our general and administrative functions to support our growth initiatives.

 

Net Finance Income

 

Our net finance income increased to $2.5 million for the three months ended March 31, 2024, from $1.1 million for the three months ended March 31, 2023. The increase is primarily due to an increase in finance income of $0.6 million relating to cash, cash equivalents and other financial assets, as well as an increase in the fair value gain of $0.6 million relating to our cash equivalents and other financial assets.

 

Foreign Exchange Gain/(Loss)

 

Foreign exchange gain is $1.3 million for the three months ended March 31, 2024, a movement of $3.0 million from a loss of $1.6 million for the three months ended March 31, 2023. This movement is primarily as a result of the translation of the U.S. dollar cash and other financial assets balance in the accounts of our subsidiary into its functional currency, which is the euro. During the three months ended March 31, 2024, the U.S. dollar strengthened compared to the euro, which resulted in the foreign exchange gain.

 

Liquidity and Capital Resources

 

Sources of Liquidity

 

We have incurred operating losses since inception, and we have not generated any revenue from any product sales or any other sources. We have not yet commercialized any of our product candidates, which are in various phases of technical and clinical development, and we do not expect to generate revenue from sales of any products for several years, if at all. Until such time as we can generate significant revenue from product sales, if ever, we expect to finance our operations through the sale of equity, debt financings or other capital sources, including potential collaborations with other companies or other strategic transactions. We have funded our operations to date primarily through equity financings, including our initial public offering. As of March 31, 2024, we had cash, cash equivalents, other financial assets and marketable securities of $214.0 million, compared to cash, cash equivalents and marketable securities of $222.7 million as of December 31, 2023.

 

We plan to continue to fund our operating and capital funding needs through sales of additional equity or other forms of financing. We may also consider pursuing strategic partnerships for clinical development and commercialization of our product candidates. The sale of additional equity would result in additional dilution to our shareholders.

 

Cash Flows

 

The following table provides information regarding our cash flows for the three months ended March 31, 2024 and 2023:

 

Net Cash Flows Used in Operating Activities

 

Net cash flows used in operating activities increased by $2.7 million to $9.6 million for the three months ended March 31, 2024 from $6.9 million for the three months ended March 31, 2023, due to an increase in loss from operations for the period and movement in working capital.

 

Net Cash Flows From/(Used in) Investing Activities

 

Net cash flows from investing activities for the three months ended March 31, 2024, is $8.8 million, a movement of $62.8 million from net cash flows used in investing activities of $54.0 million for the three months ended March 31, 2023. The net cash from investing activities during the three months ended March 31, 2024, comprised the receipt of proceeds from the sale of financial assets of $5.0 million and the redemption of marketable securities of $3.8 million. The net cash used in investing activities during the three months ended March 31, 2023, was primarily due to an investment in a money market fund of $54.0 million.

 

Funding Requirements

 

We expect our expenses to increase substantially in connection with our ongoing research and development activities, particularly as we advance the technical development work, nonclinical studies and clinical trials of our product candidates and the medical devices required to deliver such product candidates, such as our proprietary aerosol delivery device for GH001. In addition, if we obtain regulatory approval for any of our product candidates, we expect to incur significant commercialization expenses related to sales, marketing, manufacturing and distribution. Furthermore, we expect to continue to incur additional costs associated with operating as a public company. Until such time, if ever, as we can generate substantial product revenues, we expect to finance our cash needs through a combination of public or private equity offerings, debt financings, convertible debt financings, strategic collaborations and licensing arrangements. If we are unable to raise additional funds through equity or debt financings when needed, we may be required to delay, limit, reduce or terminate our product development or future commercialization efforts or grant rights to develop and market product candidates that we would otherwise prefer to develop and market ourselves. Our future capital requirements will depend on many factors, which are outlined in our annual report on Form 20-F for the year ended December 31, 2023, and this discussion and analysis. We believe that we have sufficient financial resources available to cover our planned cash outflows for at least the next twelve months.

 

Critical Accounting Estimates

 

There have been no material changes to the significant accounting policies and significant judgments and estimates from those referred to in the section in our annual report on Form 20-F for the year ended December 31, 2023, titled “Item 5. Operating and Financial Review and Prospects—E. Critical Accounting Estimates.”

 

Emerging Growth Company Status

 

On April 5, 2012, the Jumpstart our Business Act of 2012 (“JOBS Act”) was enacted. As an emerging growth company, or EGC, we rely on exemptions and reduced reporting requirements under the JOBS Act including exemptions from (i) providing an auditor’s attestation report on our system of internal controls over financial reporting pursuant to Section 404(b) of the Sarbanes-Oxley Act and (ii) complying with any requirement that may be adopted by the Public Company Accounting Oversight Board, regarding mandatory audit firm rotation or a supplement to the auditor’s report providing additional information about the audit and the financial statements, known as the auditor discussion and analysis.

 

We will remain classified as an EGC until the earlier of (1) the last day of the fiscal year (i) in which we have total annual gross revenue of $1.235 billion; (ii) following the fifth anniversary of the completion of our initial public offering; or (iii) in which we are deemed to be a “large accelerated filer,” which requires the market value of our ordinary shares that is held by non-affiliates to exceed $700 million as of the prior June 30^th, and (2) the date on which we have issued more than $1 billion in nonconvertible debt during the previous three-year period.

 

Recently Issued Accounting Pronouncements

 

As disclosed in note 2 to our unaudited condensed consolidated interim financial statements, there are no standards that are mandatory for the financial year beginning on January 1, 2024, that are relevant to and have had any material impact on our unaudited condensed consolidated interim financial statements. The review of the impact of new standards on our unaudited condensed consolidated interim financial statements, including the recently issued IFRS 18 “Presentation and Disclosure in Financial Statements”, which is not yet effective and which has not been early adopted by us is ongoing.

 

Risk Factors

 

There have been no material changes in our risk factors from those disclosed in our annual report on Form 20-F for the year ended December 31, 2023.

 

Cautionary Statement Regarding Forward-Looking Statements

 

This discussion contains statements that are, or may be deemed to be, forward-looking. All statements other than statements of historical fact included in this discussion, 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, 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. Many of the forward-looking statements contained in this discussion 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.

 

Forward-looking statements appear in a number of places in this discussion 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 identified under the section in our annual report on Form 20-F for the year ended December 31, 2023, titled “Item 3. Key Information—D. Risk Factors.” These risks and uncertainties include, among others, factors relating to:

 

 

 

These forward-looking statements speak only as of the date of this discussion and are subject to a number of risks, uncertainties and assumptions described under the sections in our annual report on Form 20-F for the year ended December 31, 2023, titled “Item 3. Key Information—D. Risk Factors” and “Item 5. Operating and Financial Review and Prospects” and elsewhere in our annual report and this discussion. 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 our control, you should not rely on these forward-looking statements as predictions of future events. The events and circumstances reflected in our forward-looking statements may not be achieved or occur and actual results could differ materially from those projected in the forward-looking statements. Moreover, we operate in an evolving environment. New risk factors and uncertainties may emerge from time to time, and it is not possible for management to predict all risk factors and uncertainties. Except as required by applicable law, we do not plan to publicly update or revise any forward-looking statements contained herein, whether as a result of any new information, future events, changed circumstances or otherwise.

 

In addition, statements that “we believe” and similar statements reflect our beliefs and opinions on the relevant subject. These statements are based upon information available to us as of the date of this discussion, and while we believe such information forms a reasonable basis for such statements, such information may be limited or incomplete, and our statements should not be read to indicate that we have conducted an exhaustive inquiry into, or review of, all potentially available relevant information. These statements are inherently uncertain and investors are cautioned not to unduly rely upon these statements.

 

---

Exhibit 99.3

 

GH Research Reports First Quarter 2024 Financial Results and Provides Business Updates

 

 

 

DUBLIN, Ireland, May 3, 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 first quarter ended March 31, 2024, and provided updates on its business.

Business Updates

 

GH001 in Patients with TRD

 

GH001, our proprietary inhaled 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) with approximately 20 sites across seven European countries.

 

We continue to recruit according to plan, 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. The completion of the 6-month open-label extension of this trial is expected in the first quarter of 2025.

 

In this trial, GH001 is administered using a commercially available 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 postpartum depression (PPD) (GH001-PPD-203) and in bipolar II disorder for patients with a current depressive episode (BDII) (GH001-BD-202).

 

We continue to expect GH001-PPD-203 completion and availability of top-line data in the third quarter of 2024. The BDII (GH001-BD-202) trial is recruiting slower than previously anticipated. We have recently initiated 6 additional sites in 3 European countries for this trial, and have implemented certain additional measures to support recruitment, but we need to further assess the impact of these measures on recruitment before we can provide an updated timeline.

 

GH002

 

GH002 is our proprietary intravenous mebufotenin (5-MeO-DMT) product candidate. With GH002, we have recently completed a Phase 1, dose-ranging clinical pharmacology trial in healthy volunteers (GH002-HV-105). This trial demonstrated that GH002 was well-tolerated and produced potent pharmacodynamic (PD) effects, as assessed by psychoactive effect intensity, with an ultra-rapid onset and short duration psychoactive experience. The pharmacokinetic (PK) profile of GH002 correlated with the ultra-rapid profile of the psychoactive effects.

 

The analyses of the PK/PD relationship, and various other secondary endpoints, are ongoing and will inform the further clinical development strategy for GH002.

 

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.

 

As previously announced, we have initiated the requested nonclinical studies and are preparing the requested device design verification information. With regard to the device design verification matters, we requested a meeting with the FDA to seek input on certain aspects of our response, which was granted. That interaction with the FDA will be dealt with by way of written responses, which we expect to receive from the FDA this month.

We have now submitted a clinical trial application for our planned Phase 1 healthy volunteer clinical pharmacology trial (GH001-HV-106) in Europe. This trial uses our proprietary aerosol delivery device for administration of GH001 and is designed to support bridging to the clinical data generated with the commercial device we have used, and are using, in our clinical trials to date.

First Quarter 2024 Financial Highlights

 

Cash position

 

Cash, cash equivalents, other financial assets and marketable securities were $214.0 million as of March 31, 2024, compared to cash, cash equivalents, other financial assets and marketable securities of $222.7 million as of December 31, 2023. 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 $8.7 million for the quarter ended March 31, 2024, compared to $7.3 million for same quarter in 2023. The increase was primarily due to increased expenses relating to nonclinical activities, increased expenses relating to our technical development and increased clinical trial expenses. These were partly offset by a decrease in expenses relating to our device development.

 

General and administrative expenses

 

G&A expenses were $2.9 million for the quarter ended March 31, 2024, compared to $3.1 million for the same quarter in 2023. The decrease is primarily due to a decrease in professional fees and insurance costs, partly offset by increased employee expenses.

 

Net loss

 

Net loss was $7.7 million, or $0.15 loss per share, for the quarter ended March 31, 2024, compared to $10.9 million, or $0.21 loss per share, for the same quarter in 2023.

 

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.

 

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 achieved ultra-rapid remission with our GH001 individualized single-day dosing regimen in the Phase 2 part of the trial, we believe that GH001 has the 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 postpartum depression and in patients with bipolar II disorder suffering from a current depressive episode.

 

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 areas 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

 

Condensed Consolidated Interim Statement of Comprehensive Income (Unaudited)

 

(in thousands, except share and per share amounts)

 

GH RESEARCH PLC

 

Condensed Consolidated Interim Balance Sheet (Unaudited)

 

(in thousands)

 

---