Neuren Pharmaceuticals Limited · ASX:NEU
Neuren Pharmaceuticals — Investor Presentation (December 2007)
38 slides from Neuren Pharmaceuticals's investor presentation, December 2007
Slide 1: Company Overview
Company Overview _______________ December 2007
Slide 2: Contents
Contents Neuren Overview Clinical Compounds Partnership Opportunities 2
Slide 3: Company Overview
Company Overview Robust product portfolio focused on psychiatric and cognitive effects of neurological injury and disease 3 drugs in late stage clinical trials for 4 central nervous system indications with efficacy results in 2009 Potentially only 1-2 more pivotal trials prior to NDA (new drug
Slide 4: Corporate Structure
Corporate Structure ASX Code: NEU Ordinary Shares on Issue: 144.7m Market Cap: A$30.4m @ $0.21 Market Cap (Fully Diluted): A$34.7m Cash as at 30/9/07 NZ$1.5m + US$3.0m convertible note (Oct 07) Significant Shareholders as at 31 Oct NEU.ASX K One W One 6.7% 0.6 ANZ Nominees 5.8% 0.55 Pfizer
Slide 5: Neuren Product Pipeline
Neuren Product Pipeline n tio al r ing n al lis a y i c d u o i c ia er lin cy at e t ti lin log y II III c v C d f ac u la -C e I e e er o - a i d u s as sc e ic l Va Le a an rm e c o a as m Di Pr Eff Fo Pr oxi Ph h h m M T P P Co Glypromate® Cognitive impairment post-cardiac surgery Motiva™ Post-s
Slide 6: Expected Efficacy Results in 4 Indications in 2009
Expected Efficacy Results in 4 Indications in 2009 Efficacy Results 2007 • US Department of Defense funding for TBI trials (expect US$4m) 2008 • Initiate NNZ-2566 (IV) Phase II in mild-to-mod. TBI • Initiate NNZ-2566 (IV) Phase II in severe TBI • Perform Glypromate® Phase III interim safety analysis
Slide 7: In 2009, 4 potential NDAs will be only 1-2 trials away
In 2009, 4 potential NDAs and registration will be only 1-2 trials away Potentially 2 Clinical data in candidates in 3 3 late-stage candidates 4 indications in indications w/in 1 in 4 clinical trials mid-2009 pivotal trial of NDA Glypromate® Post-operative cognitive Pivotal Phase III NDA Phase III i
Slide 8: Neuren's CNS Portfolio: Significant Market Opportunities
Neuren’s CNS Portfolio: Significant Market Opportunities Multiple applications for both acute and chronic indications Acute Indications Chronic Indications Stroke Alzheimer’s Disease (AD) Mild Cognitive Impairment (MCI) Parkinson’s Disease Dementia (PDD) post cardiac surgery Post stroke
Slide 9: Preclinical Pipeline Partnership Opportunities
Preclinical Pipeline Partnership Opportunities Monoclonal antibodies directed against Trefoil Factor proteins (TFFs), involved in the growth of multiple cancers Cancer program Overcomes tamoxifen resistance in breast cancer lines Partnership discussions with 3 global pharma companies Antibod
Slide 10: Management Team with Proven Execution Experience
Management Team with Proven Execution Experience Larry Glass Life sciences industry consultant with broad international Co-CEO (US) experience; former CEO of SRA Life Sciences Drug and biotech product development and management Dr. Parmjot Bains consulting experience (Fonterra Cooperative Group Ltd,
Slide 11: Contents
Contents Neuren Overview Clinical Compounds Partnership Opportunities 11
Slide 12: Glypromate Phase III Trial - Rationale for CPB Surgery
Glypromate® Phase III Trial - Rationale for CPB Surgery Controlled Time of injury is known (at point of aorta unclamping) No ambiguity in diagnosis and ability to control time at treatment which therapy is initiated (unlike stroke trials) parameters Each patient serves as own baseline Well pow
Slide 13: Glypromate: Why CABG and Valves?
Glypromate®: Why CABG and Valves? CABG and CPB result in over 350,000 patients with persistent cognitive impairment – Equivalent to the difference in function between a 40-year old and a 60-year old – >50% impaired at discharge, >20% at 6 months, >40% at 5 years(1) – Primary factor diminishing qua
Slide 14: Glypromate Trial Progress
Glypromate® Trial Progress All sites in AU, NZ and US operational and either All sites are started recruiting or ready to start operational No logistical or operational issues encountered PIs are enthusiastic and engaged 52 patients enrolled to date and sites ramping up Enrollment in line
Slide 15: Motiva (nefiracetam) Acquisition
Motiva™ (nefiracetam) Acquisition Member of well-known class of drugs with sales >US$1.5b in 2007 Well-understood mechanism of action and pharmacology Phase II/III clinical efficacy data in post-stroke patients – Statistically significant effects on apathy, global improvement, cognition – Well
Slide 16: Motiva Planned Development
Motiva™ Planned Development Two completed clinical trials in post-stroke depression in 255 patients – Statistically significant benefits Planned Development Post-stroke depression and apathy randomized, placebo-controlled, double blind trial – Enrolment within 10 days to 3 months of stroke – Eff
Slide 17: Motiva Summary
Motiva™ Summary Statistically significant Phase IIb/III data across multiple jurisdictions Strong efficacy data on administration to cortical stroke patients within 3 months “cherry pick” patients for NEU specific Phase IIb Study ================================================ Aust equities m
Slide 18: NNZ-2566
NNZ-2566 Patented analogue of Glypromate® Improved pharmacokinetics; orally available Initially being developed as an IV formulation – Phase Ib completed in Nov. 2007 – Drug safe and well tolerated in healthy volunteers Partnership with U.S. Army since 2004 for TBI – U.S. Army has proposed t
Slide 19: TBI Market Opportunity
TBI Market Opportunity • No approved therapy • No other drugs in development Multiple Sclerosis • US$3b market potential 10,400 Spinal Cord Injuries 11,000 •1.5M head injuries in US per annum HIV/AIDS 43,681 Breast Cancer 176,300 1.5 Million Head Injuries Very Severe Not Mild TBI TBI Hospital 80,000
Slide 20: TBI top priority for US Army; NNZ-2566 only drug in clinical development
TBI top priority for US Army; NNZ-2566 is the only drug in clinical development “In the past year, we have “ The US army says that 20% of its partnered with industry to soldiers and marines have suffered from discover a potent new “mild traumatic brain injury” from blows neuroprotective drug to th
Slide 21: FY 2008 Army R&D budget
FY 2008 Army R&D budget NNZ-2566 expressly written into Army Budgets US$4.0m in joint clinical development funding expected 4Q CY07 21
Slide 22: Traumatic Brain Injury Cascade
Traumatic Brain Injury Cascade Excitoxicity Inflammatory Processes Neuronal Death • NMDA activation • Pro-inflammatory • Necrosis • Ca influx cytokine elevation • Apoptosis • Free radical production NNZ-2566 sig. suppresses NNZ-2566 sig. reduces pro-apoptotic gene expression cytokine elevation NNZ-2
Slide 23: Clinical Pipeline Summary
Clinical Pipeline Summary Compound Clinical Status (CY08) Indication Est. Net Cost Glypromate® Phase III MCI US$10.0m Motiva™ Phase IIb Post Stroke Dep. US$3.0m NNZ-2566 Phase IIa Sev. TBI US$2.5m* NNZ-2566 Phase II Mild-Mod TBI US$2.5m* * Assumes US Army Funding in 4Q CY07 Mid/Late Stage Efficacy f
Slide 24: Contents
Contents Neuren Overview Clinical Compounds Partnership Opportunities 24
Slide 25: Committed to Out-Licensing/Co-Development Strategy
Committed to Out-Licensing/Co-Development Strategy NNZ-2591 (European CNS specialty pharma Three material company)—exclusive transfer Anti-TFF mAbs (global EU pharma company)— agreements negotiating exclusive executed Peripheral nervous system indications outside of CNS and peripheral neuropat
Slide 26: Value Proposition
Value Proposition Superb clinical pipeline – 3 drug compounds – 4 indications – New Drug Application 1-2 trials away Rich preclinical portfolio – Substantial partnership opportunities – Discussions underway for 3 license/co-development agreements Strong management team – Proven execution abili
Slide 27: Questions
Questions Dr Parmjot Bains, Co-CEO AUST/NZ – + 64 21 494 353 – pbains@neurenpharma.com Mr Larry Glass, Co-CEO US – + 1 301 758 2987 – lglass@neurenpharma.com www.neurenpharma.com 27
Slide 28: Scientific Appendices
Scientific Appendices pharmaceuticals pharmaceuticals
Slide 29: Glypromate
Glypromate® Small molecule tripeptide cleaved from IGF-1 Readily crosses blood brain barrier Rapidly cleared Inexpensive to synthesize 29
Slide 30: Glypromate Pivotal Phase III (First of Two Phase IIIs)
Glypromate® Pivotal Phase III (First of Two Phase IIIs) Design Randomized, double-blind, placebo-controlled Patients Approx. 600 Sites 24 in U.S., Australia and New Zealand Inclusion Criteria CABG surgery +/- valve replacement/repair with CPB Able to undergo all cognitive and ADL testing ≥50 y
Slide 31: Previous Glypromate Clinical Trials
Previous Glypromate® Clinical Trials Phase IIa Phase I Design Randomized, double-blind, Randomized, double-blind, placebo-controlled placebo-controlled Patients 33 (2 open label) 30 Inclusion CABG surgery +/- valve Healthy volunteers Criteria replacement/repair with CPB ≥60 years old Dose 1
Slide 32: Motiva efficacy data in stroke patients: Japan
Motiva™ efficacy data in stroke patients: Japan 165 patients; dosing up to 16 weeks 3 Phase IIa open- Endpoint: Global Improvement Rating (GIR) label studies GIR results: Min = 12.5%; Max = 58.8% (450 mg/day x 16 weeks) 1 Phase IIb randomised, 321 patients; 3 doses for 8 weeks; 150, 300, 450
Slide 33: Motiva efficacy data in stroke patients: US/Canada
Motiva™ efficacy data in stroke patients: US/Canada Phase IIb (under US IND) – 159 patients; 600 mg/day, 900 mg/day or placebo X 12 weeks – Primary endpoint: Hamilton Depression Scale (HAM-D) – Secondary endpoints: Apathy Scale, Symbol Digit Modality Test (SDMT), Burden Inventory (BI), other ADL a
Slide 34: NNZ-2566 Non-Convulsive Seizure Time Course
NNZ-2566 Orally available analogue of Glypromate® 5 Vehicle 4 3mg/kg bolus # of NCS/rat/hour 10mg/kg bolus 100mg/kg bolus 3 NNZ-2566 Non-Convulsive 2 Seizure Time Course 1 0 1 2 3 4 5 6 7 8 9 Time post pMCAo (hours) 34
Slide 35: NNZ-2566 Inflammatory & Apoptosis-Associated Gene Expression
NNZ- 2566 Inflammatory & Apoptosis-Associated Gene Expression Inflammation-Related Genes Apoptosis-Related Genes 0.2 5 TNF-alpha (12 h) Bax(4h) 0 .2 0.1 5 * 0.01 0 .1 0.005 * 0.0 5 0 0 Sham PBBI PBBI-NNZ Sham PBBI PBBI-NNZ IL-1beta (12h) Caspase-8 (4h) 0.15 0.2 0.15 0.1 0.1 0.05 * 0.05 * 0 0 Sham PB
Slide 36: NNZ-2566: two clinical trials
NNZ-2566: two clinical trials Phase II (severe: GCS 4-8) – Efficacy study in ~100 patients – Safety, PK and efficacy outcomes – 20 mg/kg bolus + 6mg/kg/hr 72 hour continuous infusion – Endpoints: mortality, non-convulsive seizures, biomarkers – Sites: Univ of Miami, US Army Institute of Surgical R
Slide 37: Anti-TFF Antibody Selected Animal Data
Anti – TFF Antibody Selected Animal Data 125 100 % VIABILITY 75 2B10 (lead mAb) shows a 50 strong dose-response in human gastric cancer cells 25 0 PBS 500 0 5 25 50 125 250 500 mIgG 2B10 μg/ml of antibody 125 100 2B10 effect in TFF-1 % VIABILITY 75 positive human mammary 50 cancer cells also sho
Slide 38: Anti-TFF Antibody Selected Animal Data (cont.)
Anti – TFF Antibody Selected Animal Data (cont.) TFF-1 antibody produces regression of human mammary tumour in a xenograft model 38
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