Neuren Pharmaceuticals Limited · ASX:NEU
Neuren Pharmaceuticals — 2006 ATACCC Conference
17 slides from Neuren Pharmaceuticals's conference presentation, 2006
Slide 1: Clinical Development Strategy for NNZ-2566 in Traumatic Brain Injury
Neuren Pharmaceuticals Clinical Development Strategy for NNZ-2566 in Traumatic Brain Injury 2006 ATACCC Conference Larry Glass
Slide 2: Program overview
Program overview “The combined research approach of brain trauma scientists, subject matter experts, and a pharmaceutical drug development company will provide a unique opportunity for conducting advanced pre-clinical research in seizure control, neuroprotection and brain injury.”* “The ultimate goa
Slide 3: Neuren background
Neuren background Drug development company targeting neuroprotectants for cognitive impairment, traumatic brain injury, Parkinson’s disease and Alzheimer’s disease Strong portfolio – 6 families of compounds – 2 drugs in clinic for acute CNS indications Company operations – Neuren Ltd (Auckland
Slide 4: Collaborators and Advisors
Collaborators and Advisors Frank Tortella, PhD (Army; neuropharmacologist) COL Geoffrey Ling, MD, PhD (Army; neurologist) COL James Ecklund, MD (Army; neurosurgeon) Ron Hayes, PhD (Banyan/U of Florida; neuropharmacologist) Paul Vespa, MD (UCLA; neurointensivist) Jamie Cooper, MD (NTRI, M
Slide 5: Glypromate and NNZ-2566
Glypromate® and NNZ-2566 neuren
Slide 6: Glypromate
Glypromate® N-terminal tripeptide of IGF-1 (gly-pro-glu) Discovered during research into neuroprotective role of IGF- 1 in brain-injured neonates Drug-like molecule (MW: 301 g/mol) Wide therapeutic window in stroke models No adverse effects in animals at maximum feasible dose (MFD) No in
Slide 7: Multiple modes of action
Multiple modes of action Inhibits caspase-3 dependent apoptosis Inhibits microglial activation Protects astrocytes as well as neurons Inhibits secondary necrosis Preserves neuronal function 7
Slide 8: NNZ-2566
NNZ-2566 Molecule – Glypromate® analog (gly-2 methyl-pro-glu) – Improved pharmacokinetics – Inexpensive to manufacture and formulate; good stability – Similar efficacy, therapeutic window in animal models – Comparable safety profile in safety pharmacology/toxicology studies and Phase I – Orally bi
Slide 9: NNZ-2566 is neuroprotective
NNZ-2566 is neuroprotective No seizures in NNZ-2566 treated rats Control (Seizure rats, n = 9) Control (Non-Seizure rats, n = 19) NNZ-2566 (0.3 mg/kg/h, i.v., n = 25) 4 ** P < 0.01 Neuronal Damage Score 3 2 1 0 Striatum CA1-2 CA3 CA4 DG Cortex Brain Region 9
Slide 10: Clinical development goals
Clinical development goals Drug for acute treatment of TBI that… – Reduces neurological damage and sequelae – Has a reasonable (2+ hrs) therapeutic window – Can be administered safely to all TBI patients (mild to severe; penetrating and closed-head) – Can be administered prior to or without CT or
Slide 11: Study 1: Phase II (severe)
Study 1: Phase II (severe) Open-label, observational study in TBI patients with GCS 4-8 to evaluate… – Safety – Penetration of drug to injured brain – Preliminary evidence of efficacy in modifying acute disease/injury processes Within subjects and cohort comparison analyses Drug administered w
Slide 12: Study 1 (severe) Within-subjects comparisons
Study 1 (severe) Within-subjects comparisons Incidence of hypotension Percent time of elevated intracranial pressure Mean global EEG percent alpha variability (PAV) score Incidence of epileptiform activity/non-convulsive seizures Biomarkers (measured in CSF at 24, 36, 72, 96 hrs) – Alpha I
Slide 13: Study 1 (severe) Cohort Comparisons
Study 1 (severe) Cohort Comparisons Historical cohorts – Maas et al. Lancet Neurology 2006 – Vespa et al. J Neurosurgery 2002 – Vespa et al. J Neurosurgery 1999 – Hebb et al. J Neurotrauma (submitted) 2006 Mortality at 30 days GOSE at 6 months Percent time of elevated intracranial pressure
Slide 14: Study 2: Phase II (mild-moderate)
Study 2: Phase II (mild-moderate) Randomized, double-blind, placebo controlled, dose-escalation study in patients with GCS 9-15 to evaluate safety and efficacy Intended enrollment = 200 (3:2 active : placebo randomization) Interim analysis of efficacy and safety with ~50 completed patients D
Slide 15: MCAO-Induced Ischaemic Brain Damage: Effect of Oral NNZ-2566
NNZ-2566 Oral (single dose) MCAO-Induced Ischaemic Brain Damage: Effect of Oral NNZ-2566 120 100 Damage (mm2) 80 60 40 ** 20 ** 0 Veh 15 30 60 NNZ-2566 (m g/kg p.o.; 3 h post-stroke) ** P < 0.01, ANOVA with Dunnett’s post-hoc test. Group sizes: Veh (9), 15 mg/kg (8), 30 mg/kg (8), 60 mg/kg (7) 15
Slide 16: NNZ-2566 Oral (2 doses) Infarct Area
NNZ-2566 Oral (2 doses) Infarct Area 125 Mean Infarct Area ± SEM Unpaired t test 100 P value P<0.0001 P value summary *** Are means signif. different? (P < 0.05) Yes (mm2) 75 One- or two-tailed P value? Two-tailed t, df t=6.621 df=21 50 25 0 Vehicle NNZ2566 Effect of microemulsion NNZ2566 given oral
Slide 17: Conclusion
Conclusion Excellent progress on TBI program Moving toward clinical trials in 2007 Active Army and civilian involvement in clinical trial design Separate clinical trials planned for severe and mild to moderate head injury Potential for Fast Track designation and Orphan Drug status for seve