Neuren Pharmaceuticals Limited · ASX:NEU
Neuren Pharmaceuticals — 2006 ATACCC Conference
17 slides from Neuren Pharmaceuticals's conference presentation, Aug 14, 2006
Slide 1: Clinical Development Strategy for NNZ-2566 in Traumatic Brain Injury
( n euren 1) 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
Slide 5: Glypromate® and NNZ-2566
Glypromate® and NNZ-2566 IGF-1 VIQCUY CT seca eo
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 TCU sre none
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 | ~- Orally b
Slide 9: NNZ-2566 is neuroprotective
NNZ-2566 is neuroprotective No seizures in NNZ-2566 treated rats [20 Control (Seizure rats, n = 9) EZ Control (Non-Seizure rats, n = 19) ME NNZ-2566 (0.3 mg/kg/h, i.v., n = 25) 4, *P<0.01 Neuronal Damage Score a 1 ott : : : : Striatum CAI -2 CAS CA4 DG Cortex Brain Region VQCUY CT seca ote
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 o
Slide 11: Study 1: Phase II (severe)
Study 1: Phase Il (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
Slide 12: Study (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
Slide 13: Study (severe) Cohort Comparisons
Study 1 (severe) Cohort Comparisons Historical cohorts ~ Maas et al. Lancet Neurology 2006 - Vespa etal. J Neurosurgery 2002 — Vespa etal. J Neurosurgery 1999 — Hebb et al. J Neurotrauma (submitted) 2006 Mortality at 30 days GOSE at 6 months Percent time of elevated intracranial pressure Neuropsycho
Slide 14: Study 2: Phase II (mild-moderate)
Study 2: Phase Il (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) s — Interim analysis of efficacy and safety with ~50 completed patient
Slide 15: NNZ-2566 Oral (single dose)
NNZ-2566 Oral (single dose) MCAO-Induced Ischaemic Brain Damage: Effect of Oral NNZ-2566 120 5 100 4 Damage (mm2)} [o>] Oo 40 4 20 | ek 0 _ fa Veh 15 60 NNZ-2566 (mg/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
Slide 16: NNZ-2566 Oral (2 doses)
NNZ-2566 Oral (2 doses) Infarct Area Unpaired t test P value P<0.0001 P value summary iad Are means signif. different? (P < 0.05) Yes One- or two-tailed P value? Two-tailed t, df 1=6.621 df=21 Mean Infarct Area + SEM (mm2) Vehicle NNZ2566 Effect of microemulsion NNZ2566 given orally at 2 and 4 hours
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