GH Research PLC provided updates and guidance on its clinical development program for GH001, its proprietary inhalable mebufotenin (5-MeO-DMT) product candidate, in treatment-resistant depression (TRD). Development Strategy: As previously announced, following successful completion of Phase 1/2 trial of GH001 in patients with TRD (GH001-TRD-102), company is recruiting for a European multi-center, randomized, double-blind, placebo-controlled Phase 2b trial of GH001 in patients with TRD (GH001-TRD-201), where GH001 is administered using an externally-sourced inhalation device. Separately, company submitted, in the third quarter of 2023, an Investigational New Drug Application (IND) for GH001 with the U.S. Food and Drug Administration (FDA), with the purpose to initiate a Phase 1 healthy volunteer clinical pharmacology trial, where GH001 is administered using proprietary aerosol delivery device (GH001-HV-106).

The trial, subject to regulatory clearance from the FDA, is designed to support bridging to the clinical data generated with the externally-sourced inhalation device company currently use in European Phase 2b trial such that company can initiate, subject to data and regulatory clearance, a subsequent global Phase 3 pivotal program using proprietary device. Update and Guidance on European Phase 2b Clinical Trial of GH001 in Patients with TRD: Company multi-center, randomized, double-blind, placebo-controlled Phase 2b trial of GH001 in patients with TRD (GH001-TRD-201) is now approved in seven European countries and is expected to recruit approximately 80 patients across approximately 20 sites. The primary objective of the trial is to determine the efficacy of 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 is 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. With 14 sites initiated and additional site initiations scheduled, Company is now in a position to provide guidance on completion of the double-blind phase of this trial, which is expected to occur in the third quarter of 2024, with top-line data available in the third or the fourth quarter of 2024. Update on IND for GH001: The Company recently submitted an IND for GH001 with the FDA.

At the end of the 30-day review period, the FDA advised that it had placed IND on clinical hold due to ?21 CFR 312.42(b)(1)(iv): Insufficient information to assess risks to human subjects?. The FDA indicated that a letter with additional details will be issued within 30 days.