Company: GHRS
Filing Date: 2025-02-05
Form Type: 424B5
Source: 0001140361-25-003183
Chunk: 4

Company: GH Research PLC
Filing Date: 2025-02-05
Form: 424B5
Chunk 4
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-201). Based on observed clinical activity in these clinical trials, we believe that administration of GH001 has the potential to induce ultra-rapid remissions as measured by the Montgomery–Åsberg Depression Rating Scale, or MADRS.

#### Recent Developments
On February 3, 2025, we reported the primary endpoint was met in a randomized, double-blind, placebo-controlled Phase 2b clinical trial with GH001 in patients with TRD, which is currently ongoing in Europe.

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Results: Safety GH001 was well tolerated and no serious adverse events, or SAEs, were reported in the double-blind part of the trial.

| • | All treatment emergent adverse events, or TEAEs, were mild or moderate with no severe adverse events observed. |

| • | The most common TEAEs in patients treated with GH001 were nausea, salivary hypersecretion, paresthesia, headache, and dysgeusia. There were no TEAEs of flashbacks reported. |

| • | No clinically significant changes were observed in any of the safety laboratory analyses or vital parameters, including heart rate, blood pressure and ECG, and there were no AEs related to vital signs. |

| • | There were no TEAEs leading to study drug withdrawal or early withdrawal from the double-blind part of the trial. |

| • | No dissociative state symptoms or sedation were observed at discharge after treatment with GH001 and 97.4% of patients were discharge ready within 1 hour of the last dose. Patients were not required to observe any post-discharge restrictions. |

| • | No evidence of treatment-emergent suicidal ideation or behavior or treatment-emergent BPRS+ symptoms were observed after treatment with GH001. |

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#### TABLE OF CONTENTS
Results: Efficacy

The primary endpoint of the trial was met with a significant reduction from baseline of -15.2 points in Montgomery-Åsberg Depression Rating Scale (MADRS) total score on Day 8 after administration of GH001, compared with +0.3 points in the placebo group (difference of -15.5 points, p<0.0001).

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TABLE OF CONTENTS

All secondary endpoints in the trial were met, with results consistent with the primary endpoint. The majority of the patients treated with GH001 achieved rem