Slide 1: NEWTON Phase 1/2a Study: EG-1962 vs Nimodipine in Aneurysmal SAH
Phase 1/2a Multicenter, Controlled, Randomized, Open Label, Dose Escalation, Safety, Tolerability, and Pharmacokinetic Study Comparing EG-1962 and Nimodipine in Patients with Aneurysmal Subarachnoid Hemorrhage Department of Neurosurgery, University Medical Center Mannheim, Ruprecht-Karls-University
Slide 2: Disclosure
Disclosure 2 PI worldwideScientific advisor / consultant: Edge Therapeutics
Slide 3: Aneurysmal SAH Overview
Aneurysmal SAH Overview Aneurysmal subarachnoid hemorrhage Day 0 Day 7 3
Slide 4: EG-1962: Nimodipine PLGA Microparticles
Nimodipine PLGA 70 µm microparticlesBiodegradable polymerSingle intraventricular injectionSustained-release formulation Nimodipine release for 21 daysTargeted delivery EG-1962 4
Slide 5: EG-1962 Sustained-Release Formulation
Nimodipine PLGA 70 µm microparticlesBiodegradable polymerSingle intraventricular injectionSustained-release formulation Nimodipine release for 21 daysTargeted delivery EG-1962 EG-1962 5
Slide 6: NEWTON Study Design
Phase 1/2 study: Safety, tolerability and pharmacokinetics of EG-1962 with enteral nimodipine Aneurysmal SAH Randomization Screening period EG-1962 Treatment period Follow-up period Day 0 Day 1 – 21 Day 30 Day 90 CT-scanSecondary Objective:Plasma CSF concentrations Standard of careEnteral nimodipine
Slide 7: NEWTON Demographics
EG-1962 Cohorts 1 to 6 Enteral nimodipine 100 mg 200 mg 400 mg 600 mg 800 mg 1200 mg Total Demographic Variable (N=18) (N=9) (N=9) (N=9) (N=9) (N=9) (N=9) (N=54) Age Mean 56(+/-2) 64 (+/-3) 54(+/-3) 49(+/-5) 56(+/-4) 52(+/-4) 54(+/-3) 55(+/-8) Sex, n (%) Male 5 (28%) 1 (11%) 3 (33%) 5 (56%) 6 (67%)
Slide 8: NEWTON Safety
NEWTON Safety Group Dose Deaths(unrelated) SAEs(related) Drug-related Hypotension DLTs EG-1962 100 mg 0 0 0 0 200 mg 2 0 0 0 400 mg 0 1 (Allergic Reaction) 0 1(ICP) 600 mg 0 0 0 0 800 mg 1 0 0 1 (ICP) 1200 mg 0 0 0 0 EG-1962 (n=54) All 3 (6%) 1 (2%) 0 (0%) Enteral nimodipine (n=18) 60 mg x 4 hours x
Slide 9: NEWTON Plasma Nimodipine Concentration
NEWTON Plasma nimodipine Concentration Note: Values are mean +/- …. 9
Slide 10: NEWTON Clinical Outcome
56% Favorable Outcome(n = 5) 78% Favorable Outcome(n = 7) 67% Favorable Outcome(n = 6) 44% Favorable Outcome(n = 4) 56% Favorable Outcome(n = 5) Cohort 1 (100 mg; N = 9) enteral nimodipine(N = 18) Cohort 2(200 mg; N = 9) Cohort 3(400 mg; N = 9) 0% EG-1962 related hypotension Cohort 4(600 mg; N = 9)
Slide 11: NEWTON Clinical Outcome (Cohorts 1-5)
56% Favorable Outcome(n = 5) 78% Favorable Outcome(n = 7) 67% Favorable Outcome(n = 6) 44% Favorable Outcome(n = 4) 56% Favorable Outcome(n = 5) enteral nimodipine(N = 18) 0% EG-1962 related hypotension NEWTON Clinical Outcome Dead Glasgow Outcome Scale (GOSE) – 90 Day Outcome Vegetative State Lower
Slide 12: NEWTON Exploratory Outcomes
EG-1962 Cohorts 1-5 (N = 45) NEWTON Exploratory Outcomes Vasospasm / DCI Cohort 1 (100 mg; N = 9) Enteral nimodipine(N = 18) Cohort 2(200 mg; N = 9) Cohort 3(400 mg; N = 9) Cohort 4(600 mg; N = 9) Cohort 5(800 mg; N = 9) (N = ) (5) (2) (4) (2) (2) (15) Delayed Cerebral Infarction (N = ) (1) (0) (0)
Slide 13: NEWTON Health Economics
NEWTON Health Economics Reduced ICU Length of Stay (LoS)by 3.5 days Reduced Hospital LoS by 2.5 days Median ICU LoS Median Hospital LoS (n=45) (n=45) (n=18) (n=18) 13
Slide 14: NEWTON Study Conclusions
NEWTON Study All endpoints metMTD/MFD definedNo safety concerns Improved clinical outcomeLess rescue therapyReduced ICU and hospital length of stay 14
Slide 15: Pivotal Phase Study Planned
NEWTON Study 15 Pivotal phase 3 study planned (US, Canada, Europe, Australasia)
Slide 16: Contact: Department of Neurosurgery, University Medical Center Mannheim
http://www.umm.uni-heidelberg.de/inst/nch/daniel.haenggi@medma.uni-heidelberg.de Department of Neurosurgery, University Medical Center Mannheim, Ruprecht-Karls-University Heidelberg, Germany Director: Univ. Prof. Dr. Daniel Hänggi Phase 1/2a Multicenter, Controlled, Randomized, Open Label, Dose Esca