Slide 1: GH001 Improves Illness Severity, Anxiety Symptoms, and Quality of Life in Patients with TRD
1 GH001 Improves Illness Severity, Anxiety Symptoms, and Quality of Life in Patients with Treatment-Resistant Depression Michael E. Thase, MD Department of Psychiatry, University of Pennsylvania and Corporal Michael J. Crescenz Veterans Affairs Medical Center, Philadelphia, PA, USA Co-authors: Bernh
Slide 2: Author Disclosures (1 of 2)
Author Disclosures Michael E. Thase Consultant – Axsome, Clexio Biosciences, Gerson Lehrman Group, GH Research, Janssen, Johnson & Johnson, Lundbeck, Luye Pharma, Merck, Otsuka, Pfizer, Sage, Seelos Therapeutics, Sunovion, and Takeda. Grant Support – Acadia, Alkermes, Axsome, Intra-Cellular Therapie
Slide 3: Author Disclosures (2 of 2)
Author Disclosures Tomáš Páleníček Principal Investigator – Compass, GH Research, MAPS, and Ketabon. Shares – Psychedelická klinika s.r.o., Společnost pro podporu neurovědního výzkumu s.r.o., and AVI-X Aviation Experts s.r.o. Founder – PSYRES (Psychedelic Research Foundation). Consultant – CB21 Phar
Slide 4: Background
Patients with TRD, representing ~30% of patients treated for MDD,1 frequently report anxiety symptoms and greater impairment in HRQoL versus patients with treatment-responsive MDD2-4 Current therapies for TRD are limited,4 and there is a large unmet need for treatments that are well tolerated and of
Slide 5: Trial Schematic
For re-treatment (up to five GH001 IDRsa), the patient must have met one of the following criteria: MADRS score >18 MADRS score >10 and ≤18 and MADRS score ≤10 not observed at Day 8 of the prior treatment or at any visit since MADRS score >10 and ≤18 and MADRS score >18 observed since the most recen
Slide 6: Eligibility Criteria
6 Eligibility Criteria aCurrent MDE confirmed by the Mini-International Neuropsychiatric Interview. Abbreviations: DSM-5 = Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition; HAM-D-17 = 17-Item Hamilton Depression Rating Scale; MDD = Major depressive disorder; MDE = Major depressiv
Slide 7: Baseline Characteristics
7 Baseline Characteristics Abbreviations: BMI = Body mass index; CGI-S = Clinical Global Impression – Severity; HAM-A = Hamilton Rating Scale for Anxiety; HAM-D-17 = 17-Item Hamilton Depression Rating Scale; MADRS = Montgomery–Åsberg Depression Rating Scale; Q-LES-Q-SF = Quality of Life, Enjoyment,
Slide 8: Primary Endpoint: GH001 Led to -15.5 Mean MADRS Reduction on Day 8 vs Placebo
LS mean difference vs placebo: −15.5 (P<0.0001) Effect size: Cohen’s d = −2.0 LS Mean (±SE) Change from Baseline in MADRS Total Score BL 2H Day 2 Day 8 Primary Endpoint: GH001 Led to −15.5 Mean MADRS Reduction from Baseline on Day 8a Compared with Placebo in the Double-Blind Part aFDA Guidance notes
Slide 9: Global Illness Severity Assessment: CGI-S Scale
9 Global Illness Severity Assessment CGI-S Scale1 Abbreviations: CGI-S = Clinical Global Impression – Severity. 1. Guy W. US Department of Health, Education, and Welfare. 1976:217-222. CGI-S is a clinician-rated assessment of illness severity Assessed by a blinded independent rater Total score range
Slide 10: More Patients Had Improvement in Global Illness Severity at Day 8 with GH001
10 More Patients Had Improvement in Global Illness Severity from Baseline at Day 8 with GH001 vs Placebo in the Double-Blind Part Percentages are for each baseline category within treatment. Abbreviations: CGI-S = Clinical Global Impression – Severity; LS = Least squares; SE = Standard error. Percen
Slide 11: OLE Completers Reported Improved Global Illness Severity at Month 6
11 OLE Completers Reported Improved Global Illness Severity at Month 6 Abbreviations: CGI-S = Clinical Global Impression – Severity; OLE = Open-label extension; SD = Standard deviation. Percentage of Patients in Each CGI-S Category at Baseline and Month 6 OLE Completers (n=63) Change from Baseline i
Slide 12: Anxiety Assessment: HAM-A Scale
12 Anxiety Assessment HAM-A Scale1,2 Abbreviations: HAM-A = Hamiliton Rating Scale for Anxiety. 1. Hamilton M. Br J Med Psychol. 1959;32:50-55. 2. Marks RM, et al. Exp Clin Psychopharmacol. 2022;30(6):841-852. HAM-A is a clinician-rated assessment of anxiety symptoms Assessed by a blinded independen
Slide 13: GH001 Improved Psychic and Somatic Anxiety Symptoms vs Placebo at Day 8
13 LS Mean (SE) Change in HAM-A Total Score from Baseline at Day 8 GH001 (n=40) Placebo (n=41) −11.1 (1.0) −1.0 (1.0) LS mean difference vs placebo: −10.0 (P<0.0001) GH001 Improved Psychic and Somatic Anxiety Symptoms vs Placebo Based on HAM-A Scores at Day 8 in the Double-Blind Part Mean (SD) Chang
Slide 14: OLE Completers Reported Improved Anxiety Symptoms at Month 6
14 OLE Completers Reported Improved Psychic and Somatic Anxiety Symptoms at Month 6 OLE Completers (n=63) aIncludes anxious mood, tension, fears, insomnia, intellectual (cognitive), depressed mood, and behavior at interview items. bIncludes somatic (muscular), somatic (sensory), cardiovascular sympt
Slide 15: Quality of Life Assessment: Q-LES-Q-SF Scale
15 Quality of Life Assessment Q-LES-Q-SF Scale1,2 aThe total score reported for the double-blind part and the open-label extension is based on the abbreviated version of the Q-LES-Q-SF (which omits two questions about medication and overall life satisfaction); however, the by-domain presentation inc
Slide 16: GH001 Led to Improvements in Quality of Life Across Multiple Domains at Day 8
16 LS Mean (SE) Change in Q-LES-Q-SF Total Score from Baseline at Day 8 GH001 (n=37) Placebo (n=40) 20.6 (1.8) –0.8 (1.7) LS mean difference vs placebo: 21.4 (P<0.0001) GH001 Led to Improvements in Quality of Life Across Multiple Domains vs Placebo at Day 8 in the Double-Blind Part Mean Percentage (
Slide 17: Quality of Life Domain Improvements in OLE Completers
17 The Q-LES-Q-SF domains were developed as part of an ad hoc analysis; the Q-LES-Q-SF does not have an official subscale scoring system. aThe percentages for each domain are normalized to reflect the relative proportionality of responses, accounting for the differing number of items per domain. bIn
Slide 18: GH001 Administration Was Well Tolerated in Patients with TRD up to 6 Months
18 GH001 Administration Was Well Tolerated in Patients with TRD up to 6 Months aTwo severe treatment-related TEAEs were reported in the OLE; affect lability occurred shortly after administration of GH001 and resolved within 4 minutes and one event of migraine, considered a serious TEAE not related t
Slide 19: Conclusions
Conclusions 19 In patients with TRD, GH001 led to significant reductions in global illness severity from baseline to Day 8 versus placebo; these improvements with GH001 were maintained at Month 6 in those who completed the OLE Significant improvements in anxiety symptoms across psychic and somatic d
Slide 20: Acknowledgments
20 Acknowledgments This trial was sponsored by GH Research Ireland Limited The sponsor would like to thank the participants in the trial The sponsor would also like to thank the investigators who conducted this trial Under the guidance of the authors, medical writing and editorial support were provi