Neuren Pharmaceuticals Limited · ASX:NEU
Neuren Pharmaceuticals — Bioshares Biotech Summit 2011
18 slides from Neuren Pharmaceuticals's conference presentation, Jul 22, 2011
Slide 1: Regulatory strategy behind a novel treatment for traumatic brain injury
Neuren Pharmaceuticals For personal use only Regulatory strategy behind a novel treatment for traumatic brain injury Bioshares Biotech Summit July 2011
Slide 2: Forward Looking Statement
Forward Looking Statement For personal use only This presentation contains forward looking statements that involve risks and uncertainties. Although we believe that the expectations reflected in the forward looking statements are reasonable at this time, Neuren can give no assurance that these expec
Slide 3: Annual TBI incidence and patient disposition (US)
Annual TBI incidence and patient disposition (US) Oral therapy For personal use only Oral therapy? Intravenous therapy 3
Slide 4: Background on US Army TBI program
Background on US Army TBI program For personal use only • TBI is the second leading cause of death and disability in combat; >70% mild • Army Medical Research and Materiel Command (USAMRMC) is the lead US agency involved in TBI R&D • Acute TBI research focuses on two goals: neuroprotection and preve
Slide 5: Integrated, logical strategy = life cycle risk management
Integrated, logical strategy = life cycle risk management For personal use only Mechanism of action Therapeutic strategy Regulatory strategy Commercial strategy 5
Slide 6: Mechanism of action: inflammatory cytokine inhibition
Mechanism of action: inflammatory cytokine inhibition For personal use only Gene expression Protein expression 6
Slide 7: Mechanism of action: dose-dependent neuroprotection
Mechanism of action: dose-dependent neuroprotection For personal use only 2 hr post-injury treatment 4 hr post-injury treatment (72 hr recovery ) (72 hr recovery ) 7
Slide 8: Mechanism of action: dose-dependent prevention of seizures
Mechanism of action: dose-dependent prevention of seizures For personal use only Excitoxicity Inflammation Neuronal Death • NMDA • Pro-inflammatory • Necrosis activation cytokine elevation • Apoptosis • Ca influx • Free radical production 0 hr 6 hr 24 hr 72 hr NNZ-2566 # of NCS/rat/hour Time post pM
Slide 9: Therapeutic strategy
Therapeutic strategy For personal use only • Synthetic analogue of naturally occurring neuroprotective peptide—the brain’s response to injury • Prevent secondary brain injury—damage to cells adjacent to the primary injury (penumbra) • Blocking the inflammatory response inhibits cell death (apoptosis
Slide 10: Preclinical research directly informs clinical trial design
Preclinical research directly informs clinical trial design Neuroprotection in multiple models: For personal use only • Bolus dosing + infusion enhances efficacy and extends therapeutic time window ➡ Bolus dosing and infusion in Phase II trial Anti-seizure actions against non-convulsive and convulsi
Slide 11: Regulatory framework
Regulatory framework For personal use only • Kefauver Harris Amendment to the Federal Food, Drug and Cosmetic Act (Requirement for drug manufacturers to provide proof of the effectiveness and safety before approval) • 21CFR312.84 Risk-benefit analysis in review of marketing applications for drugs to
Slide 12: TBI regulatory strategy
TBI regulatory strategy Approach to FDA Pathway For personal use only • Any validated endpoint plus a functional measure is approvable • Prevention of post-injury seizures is approvable alone • No a priori standard for magnitude of effect; must be “clinically meaningful” • Acceptability of explorato
Slide 13: Phase II Protocol Designed to Deliver Definitive Data
Phase II Protocol Designed to Deliver Definitive Data For personal use only • Double-blind, placebo controlled, rising dose • 260 acute, non-penetrating TBI patients (Glasgow Coma Scale 4-12) • Patients 16-75 years old • Randomized 2:1 drug to placebo • Administration of drug within 8 hours of injur
Slide 14: Why drugs fail
Why drugs fail For personal use only H. Kubinyi. Drug Research: Myths, Hype and Reality, Nature Reviews Drug Discovery (2003). 14
Slide 15: NNZ-2566: TBI profile largely de-risked
NNZ-2566: TBI profile largely de-risked Pharmacokinetics, lack of efficacy, animal toxicity, and adverse events For personal use only in man are the leading causes of failure in drug development Miscellaneous (5%) Pharmacokinetics (39%) • Manufacturing—fully validated; suitable for Phase III; simple
Slide 16: Orphan Disease model
Orphan Disease model TBI is not an orphan disease (incidence >200,000), but… For personal use only • Significant risk and cause of mortality and permanent disability • No approved or effective therapy • Significant unmet need • Priority target for FDA, US Army and NIH Regulatory flexibility • Benefi
Slide 17: NNZ-2566—a growing franchise
NNZ-2566—a growing franchise Intravenous administration For personal use only Moderate to severe TBI Stroke Cardiac arrest Perinatal asphyxia Penetrating brain injury Non-convulsive seizures in other CNS injuries/conditions Oral administration Mild TBI Rett Syndrome/autism spectrum disorders Post-st
Slide 18: Further Information
Further Information For personal use only Larry Glass, CEO +1 (301) 941 1830 [email protected] New Zealand Level 2, 57 Wellington Street Freemans Bay 1011, Auckland New Zealand +64 (9) 3700 200 1 800 259 181 (Australia Freephone) USA 3 Bethesda Metro Center, Suite 700 Bethesda, Maryland 20814
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