Company: GHRS
Filing Date: 2025-07-29
Form Type: 20-F/A
Source: 0001140361-25-027850
Chunk: 30

Company: GH Research PLC
Filing Date: 2025-07-29
Form: 20-F/A
Chunk 30
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 and Mitigation Strategy, or REMS, that may be required by the FDA or comparable requirements in other jurisdictions to ensure 
 the benefits of an individual product outweigh its risks;                                                                                                                                                                                   |

| • | unfavorable acceptance of our product candidates or clinical trial data by the patient or medical communities or third-party payors; |

| • | failure of our third-party contractors or investigators to comply with regulatory requirements or otherwise meet their contractual obligations in a timely manner, or at all; |

| • | delays and changes in regulatory requirements, policy and guidelines, including the imposition of additional regulatory oversight around clinical testing generally or with respect to our technology in particular; or |

| • | varying interpretations of data by the FDA, EMA or other comparable foreign regulatory authorities. |

We do not have complete control over many of these factors, including certain aspects of technical drug product and device development, nonclinical development, clinical development and the regulatory submission process, potential threats to our intellectual property rights and our manufacturing, marketing, distribution and sales efforts or that of any future collaborator. 14 Table of Contents GH001 is designed to deliver mebufotenin to the patient via inhalation of an aerosol into the lungs. This aerosol is defined by specific properties to be pharmaceutically acceptable, such as its purity, and to achieve efficient uptake of mebufotenin into the systemic circulation, such as its particle size distribution. The generation of this mebufotenin aerosol requires a drug product and a device with specific performance characteristics and properties, and it is therefore anticipated that GH001 and the specific device will be considered a drug-device combination product by the FDA, EMA or other comparable foreign regulatory authorities. For GH002, which is our intravenous mebufotenin formulation, such classification will depend on our final choice for its commercial presentation. Products that are considered to be drug-device combination products will require review and coordination by the drug and device centers within the FDA, or other comparable foreign regulatory authorities or notified bodies prior to initiation of clinical trials and prior to marketing approval, which may delay such trials or marketing approval. Under FDA regulations, combination products are subject to current good manufacturing practice, or cGMP, requirements applicable to both drugs and medical devices, including the Quality System, or QS, and regulations applicable to medical devices. Combination products are also subject to the Medical Device Regulation 2017/745, or MDR, which requires coordination between the drug and the device regulatory laws and regulators. Problems associated with the drug product or device component of the