Neuren Pharmaceuticals Limited · ASX:NEU
Neuren Pharmaceuticals — Investor Presentation (August 2007)
31 slides from Neuren Pharmaceuticals's investor presentation, Aug 23, 2007
Slide 1: Company Overview
For personal use only Company Overview _______________ August 2007
Slide 2: Company Overview
Company Overview New Zealand company; listed on the ASX; operations in NZ and US For personal use only Strong drug discovery, clinical development, clinical trial management 3 new chemical entities in clinical trials for 4 CNS indications – Glypromate® Phase III for post-operative cognitive im
Slide 3: Product Candidate Pipeline
Product Candidate Pipeline n tio al r ing n al lis a y i c d u o i c ia For personal use only er lin cy at e t ti lin log y 3 c v C d f ac u la -C e 1 e 2 se er o - e ic a li d u e c o s s a m sc Pr Eff Va Le a an rm Pr oxi ha a Ph m Di M Fo P Ph Co T Glypromate® Cognitive impairment post-cardiac su
Slide 4: Anticipated Milestones
Anticipated Milestones For personal use only 2007 Announce NNZ-2566 (IV) Phase Ib results in Nov. 2007 2008 Initiate NNZ-2566 (IV) Phase II in mild-to-mod. TBI in early 2008 Initiate NNZ-2566 (IV) Phase IIa in severe TBI Perform Glypromate® Phase III interim safety analysis Initiate Motiva™ Phase II
Slide 5: Neuren's Lead Product Candidates in 2009
Neuren’s Lead Product Candidates in 2009 Potentially 2 For personal use only 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 impairment
Slide 6: Glypromate Pivotal Phase III (First of Two Phase IIIs)
Glypromate® Pivotal Phase III (First of Two Phase IIIs) Design Randomized, double-blind, placebo-controlled For personal use only 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 a
Slide 7: Previous Glypromate Clinical Trials
Previous Glypromate® Clinical Trials Phase IIa Phase I For personal use only 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 ≥
Slide 8: S100 as an Early Biomarker for Brain Damage
S100 as an Early Biomarker for Brain Damage “S100 protein is an early marker For personal use only of cerebral damage. It is released after cardiac surgery performed under cardiopulmonary bypass (CPB). Its level is correlated with the duration of CPB, deep circulatory arrest and aorta cross-clamping
Slide 9: Glypromate Phase IIa: S100 Biomarker Data
Glypromate® Phase IIa: S100 Biomarker Data For personal use only % Decrease in S100 (6 hrs post-CPB) 0% -10% -20% -30% -40% -50% -60% -70% -80% -70.3% -75.8% -79.0% -90% Placebo 1 mg/kg/hr 3 mg/kg/hr (n=10) (n=11) (n=12) 9
Slide 10: Glypromate Phase III Trial Rationale
Glypromate® Phase III Trial Rationale CABG/CPB inherently controls treatment parameters For personal use only – Time of injury is known (i.e., at point of aorta unclamping) – No ambiguity in diagnosis and ability to control time at which therapy is initiated (i.e., unlike stroke trials) – Each pat
Slide 11: Glypromate
Glypromate® Small molecule For personal use only tripeptide cleaved from IGF-1 Readily crosses blood brain barrier(1) Rapidly cleared Inexpensive to synthesize (1) Guan et al. Neuroprotective effects of the N-terminal tripeptide of insulin-like growth factor-1, glycine-proline-glutamate (GPE
Slide 12: Glypromate Exhibits Multiple Mechanisms of Action
Glypromate® Exhibits Multiple Mechanisms of Action(1) Inhibition of inflammatory cytokines For personal use only Inhibition of apoptosis Inhibition of microglial activation Prevention of delayed or secondary necrosis Protection of astrocytes Protection of neurons and neuronal function (1
Slide 13: Glypromate in HI Model of Acute Brain Injury
Glypromate® in HI Model of Acute Brain Injury For personal use only Glypromate treatment 7 - 11 h post HI injury (3 mg/kg/h i.v. infusion) Vehicle (n = 17) 4 Glypromate (n = 19) Tissue Damage Score P < 0.001 3 2 1 0 Striatum CA1/2 CA3 CA4 DG Cortex Brain Region 13
Slide 14: Glypromate in MCAO Model of Acute Brain Injury
Glypromate® in MCAO Model of Acute Brain Injury For personal use only 4 Control (n = 15) 50 Control (n = 15) Size of infarct (mm 2) % Body weight gain (3/18 rats died) 2 Glypromate (n = 16) 40 Glypromate (n = 16) 0 (0/16 rats died) 30 -2 (P = 0.004) (P = 0.02) -4 20 -6 10 -8 0 -10 Control Glypromate
Slide 15: Glypromate Effect on Functional Recovery in HI Model
Glypromate® Effect on Functional Recovery in HI Model Improved behavioral outcome For personal use only Improved neurological outcome Improved histological outcome 6 Glypromate® 5 Left/Right ratio of time take to contact patch Neurological score 5 Saline control 4 Glypromate® Normal Saline 4 3
Slide 16: Glypromate: Why CABG and Valves?
Glypromate®: Why CABG and Valves? CABG and CPB result in over 350,000 patients with For personal use only 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
Slide 17: NNZ-2566
NNZ-2566 Orally available analogue of Glypromate® For personal use only Initially being developed in IV formulation – Phase Ib trial currently enrolling healthy volunteers with data expected in Nov. 2007 – Drug was safe and well tolerated in Phase Ia trial in 28 healthy volunteers Partnership
Slide 18: NNZ-2566 is highly neuroprotective
NNZ-2566 is highly neuroprotective For personal use only 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 Global HI model; IV administration 18
Slide 19: Traumatic Brain Injury Cascade
Traumatic Brain Injury Cascade For personal use only Excitoxicity Inflammatory Processes Neuronal Death • NMDA activation • Pro-inflammatory • Necrosis • Ca influx cytokine elevation • Apoptosis • Free radical production 19
Slide 20: For personal use only
NCS frequency 30 For personal use only 25 20 # of NCS/rat 15 10 * * 5 0 Vehicle 3 10 100 Dose (mg/kg) followed by 3mg/kg/h x 12h infusion 20
Slide 21: NNZ-2566: Non-Convulsive Seizure Time Course
NNZ-2566: Non-Convulsive Seizure Time Course 5 For personal use only Vehicle 4 3mg/kg bolus 10mg/kg bolus # of NCS/rat/hour 100mg/kg bolus 3 2 1 0 1 2 3 4 5 6 7 8 9 Time post pMCAo (hours) 21
Slide 22: Inflammatory & Apoptosis-Associated Gene Expression
Inflammatory & Apoptosis-Associated Gene Expression Inflammation-Related Genes Apoptosis-Related Genes For personal use only TNF-alpha (12 h) 0.25 Bax (4h) 0.2 0.15 * 0.01 0.1 0.005 * 0.05 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
Slide 23: Phase IIa (severe: GCS 4-8)
Phase IIa (severe: GCS 4-8) For personal use only Open label, dose escalation study in ~65 patients Within-patient and historical cohort comparisons 20 mg/kg bolus + 72 hour continuous infusion (2 doses) Endpoints – Mortality – Non-convulsive seizures and other EEG abnormalities – Biomarkers
Slide 24: Phase II (mild-moderate: GCS 9-15)
Phase II (mild-moderate: GCS 9-15) Double-blind, placebo controlled, dose escalation study in For personal use only ~180 patients admitted for ≥ 24 hours 20 mg/kg bolus + up to 24 hour continuous infusion (2 doses) Endpoints – Cognitive function panel (CDR) – Profile of Mood States – Disabilit
Slide 25: Motiva (nefiracetam)
Motiva™ (nefiracetam)(1) Novel cyclic GABA derivative For personal use only Belongs to class of compounds called acetams – Approved acetams had sales of over US$700 MM in 1H 2007 Studied in 1,700+ patients in Phase I, IIa and IIb trials – No drug-related adverse safety or toxicity Two comple
Slide 26: Hamilton Acquisition Terms
Hamilton Acquisition Terms On July 31, 2007, entered into binding term sheet to For personal use only acquire Hamilton Pharmaceuticals – Upon closing, will issue US$4.4 MM in ordinary shares to Vivo Ventures, Index Ventures and CNF Investments – Upon closing, Vivo and CNF will invest US$3.0 MM in
Slide 27: Partnering Strategy
Partnering Strategy Committed to out-licensing or co-development For personal use only strategies Existing development partnerships with Metabolic Pharmaceuticals and U.S. Army Three material transfer agreements executed – NNZ-2591 – Anti-TFF mAbs – Peripheral nervous system indications outsid
Slide 28: Key Financial Metrics
Key Financial Metrics Cash: US$3.5 MM (NZ$4.5 MM) as of June 30, 2007 For personal use only Cash spending: – 6 months ended June 30, 2007: US$4.7 MM (NZ$6.1 MM)(1) – Projected cash spend: US$1.1 MM per month Pending investment from Vivo Ventures and CNF Investments(2) – US$3.0 MM in note conve
Slide 29: Projected Financial Assumptions
Projected Financial Assumptions Glypromate® For personal use only – Peak forecast sales $237 MM – Peak forecast market penetration 12.5% – Estimated cost of goods 11% NNZ-2566 (IV and oral) – Peak forecast sales $341 MM – Peak forecast market penetration 18% – Estimated cost of goods 17% 29
Slide 30: Management Team with Proven Execution Experience
Management Team with Proven Execution Experience Name/Title Prior Experience For personal use only David Clarke Former CEO of South Auckland Health Limited (leading Chief Executive Officer public hospital system in New Zealand) Dr. Douglas Wilson Former SVP of Medicine and Regulatory Affairs and Chi
Slide 31: For personal use only
(neuren ) pharmaceuticals pharmaceuticals
Neuren Pharmaceuticals — Investor Presentation (August 2007) on 6ix