GH Research (GHRS) Status Update summary

Trial design and patient selection

• Phase IIb double-blind trial with open-label extension evaluated GH001 in treatment-resistant depression, focusing on safety and efficacy endpoints.

• Individualized dosing regimen with up to three escalating doses per day and retreatment based on MADRS scores and clinical assessment.

• Rigorous patient selection included independent diagnostic confirmation and measures to minimize placebo effect.

• 81 patients enrolled; 40 received GH001, 41 received placebo; majority were female with severe or moderate depression and low prior psychedelic exposure.

• Psychotherapeutic intervention was not included in the trial protocol.

Efficacy results

• GH001 achieved a placebo-adjusted mean MADRS reduction of -15.5 points at day eight, highly statistically significant (p<0.0001).

• Remission rate at day eight was 57.5% for GH001 versus 0% for placebo (p<0.0001); response and remission rates were consistently superior to placebo at all time points.

• Rapid onset of efficacy observed as early as two hours post-dose, with sustained effects at day two and day eight.

• All secondary endpoints (CGI-S, HAM-A, Q-LES-Q-SF) showed significant improvements in illness severity, anxiety, and quality of life.

• Compared to Spravato, GH001 demonstrated larger effect sizes and higher remission rates in cross-trial comparisons.

Safety and tolerability

• No serious adverse events reported in double-blind or open-label phases; all treatment-emergent adverse events were mild or moderate and resolved quickly.

• Most common adverse events included nausea, salivary hypersecretion, paresthesia, headache, and dysgeusia.

• No clinically significant changes in vital signs, no dissociation or sedation at discharge, and over 97% of patients were discharge-ready within one hour.

• No evidence of treatment-emergent suicidal ideation or behavior; only one brief visual hallucination reported.

• No severe events or flashbacks observed.