Neuren Pharmaceuticals Limited · ASX:NEU
Neuren Pharmaceuticals — Investor Presentation (January 2007)
32 slides from Neuren Pharmaceuticals's investor presentation, Jan 12, 2007
Slide 1: Presentation to Potential Investors and Partners
| _ Meuren) ; Presentation to Potential Investors and Partners San Francisco, January 2007 David Clarke, CEO Larry Glass, US Executive VP
Slide 2: Disclaimer
Disclaimer This presentation includes forward-looking statements that are subject to risks and uncertainties. Such statements involve known and unknown risks and important factors that may cause the actual results, performance or achievements of Neuren to be materially different from the statements
Slide 3: Value proposition
Value proposition # Solid, diverse drug pipeline with multiple commercialization opportunities ~ 2molecules in 4 clinical trials for 4 CNS indications in 2007; results in 2008/9 — Limited competition for drugs in targeted indications - Strong preclinical candidates from a proven discovery program -
Slide 4: Recent milestones
Recent milestones =» Clinical and regulatory — Glypromate® moved forward to pivotal study following FDA pre IND meeting — Glypromate® Phase 2a safety/PK study commenced 2005 — Initiation of NNZ-2566 Phase 1 safety study — Completion of Glypromate® Phase 2a safety/PK study — Completion of FDA Phase 3
Slide 5: Pipeline—significant progress in 2007
Pipeline—significant progress in 2007 Glypromate® - PCI» Glypromate ®~ CA NNZ-2566 (IV) - TBI mild-moderate_ NNZ-2566 (IV) - TBI severe Macrocyclics * Neural Regeneration Peptides - PN i Trefoil Factor Program ~ B/OC | Growth Hormone Variant - AGH __ TCU serene
Slide 6: Near-term value driver: clinical trials in 2007
Near-term value driver: 4 clinical trials in 2007 TUCO sre enon Glypromate® . Neuro- Neurological psychogical consequences consequences of of severe mild - TBI moderateTBI Phase 2a Phase 2
Slide 7: Significant market opportunities
Significant market opportunities = Multiple applications for both acute and chronic indications Acute Indications Chronic Indications + Stroke + Alzheimer’s Disease + Cardiac Surgery + Parkinson’s Disease + Cardiac Arrest + Multiple Sclerosis + Traumatic Brain Injury + Peripheral Neuropathy « Large
Slide 8: Four near-term out-licensing opportunities
Four near-term out-licensing opportunities = NEU has an extensive pipeline as a result of its Right to Own agreement with the University of Auckland = NEU has focused on developing four product lines such that they are attractive near-term out-licensing opportunities = Active discussions ongoing for
Slide 9: Scientific rationale: Targeting secondary brain injury
Scientific rationale: Targeting secondary brain injury Based on three scientific hypotheses that are now the generally accepted principles of neuroprotection: 1. The brain self-repairs and self-protects 2. There is a window of time for brain rescue 3. Brain cells die via several mechanisms __ Apopto
Slide 10: Glypromate®
Glypromate®
Slide 11: Glypromate®
Glypromate® ¢ Drug-like molecule — Small molecule (MW=301.3 g/mol) — Highly neuroprotective at nM concentrations — Readily crosses the blood brain barrier — Rapidly cleared from circulation — Simple and inexpensive to synthesize — Simple and inexpensive formulation ¢ Preclinical efficacy — Global hy
Slide 12: Multiple Modes of Action
Multiple Modes of Action = Inhibition of caspase-3 dependent apoptosis # Inhibition of microglial activation # Prevention of delayed or secondary necrosis # Protection of astrocytes and oligodendrocytes as well as neurons « Preservation of neuronal function TQUT CN psn mn
Slide 13: Glypromate Preclinical Safety and Toxicology
Glypromate Preclinical Safety and Toxicology « Safety studies ~ No selectivity issues or unwanted secondary pharmacology predicted by wide binding ~ No inhibition of CYP-450 enzymes: low risk of drug-drug interactions _ Mo in vivo effect on cardiovascular system observed with high i.v. oses ~ Clean
Slide 14: Glypromate is Neuroprotective After Acute Brain Injury
Glypromate is Neuroprotective After Acute Brain Injury Giypromate treatment 7 - 11 h post HI injury (3 mg/kg/h i.v. infusion) Gli Vehicle (n = 17) 4- [22Giypromate (n = 19) ¢ P < 0.001 B @ 37 e § 2- a a oO oe 4 We 0! 1 Striatum CA1/2 CA3 Cortex Brain Revlon VIQUT CT pee er
Slide 15: Long Term Improvements in Functional Recovery
Long Term Improvements in Functional Recovery ¢ Improved behavioral outcome * Improved neurological outcome ¢ Improved histological outcome o.§ “~ Glypromate® 5 ES . o a ® eS —— Saline control 84 Glypromate® - & L 584 *— Normal 2 —= Saline Bo 8 3 fe D> = 83 o * gs o2 P< 0.05 “>? a eg 21 gst 0 0 T I
Slide 16: Cognitive impairment in cardiac surgery
Cognitive impairment in cardiac surgery * Cost-effective trial = Timing of surgery (injury) is known = Patients serve as their own control =» Well-defined endpoint measurement = Optimized drug administration = Large unmet need; good commercial opportunity « Large market (US$1b) = No current therapy
Slide 17: Glypromate® Phase trial
Glypromate® Phase 3 trial = Glypromate® successfully completed Phase 1 and Phase 2a trials - FDA recommended submitting IND for Phase 3 ~ Significant time and cost savings ~ Safe and well-tolerated in human trials — Dose-dependent effect on $100 » First pivotal Phase 3 study - 520 patient multi-site
Slide 18: Glypromate Phase 2a in cardiac arrest
Glypromate Phase 2a in cardiac arrest « US Army to conduct trial Phase 2 Glypromate® to reduce brain injury from cardiac arrest « Army investigators to submit IND for clinical trial approval = Glypromate for the indication to be submitted for Orphan Drug and Fast Track designation « Trial could prov
Slide 19: NNZ-2566
lis, NNZ-2566
Slide 20: NNZ-2566 — Traumatic brain injury
NNZ-2566 — Traumatic brain injury # NNZ-2566 is initially being tested for neuroprotection in patients who have experienced Traumatic Brain Injury (TBI) — US Army is co-development partner — Delivered up to 70% improvement in functional outcomes — Focused on non-convulsive seizures as a key endpoint
Slide 21: Neuronal Damage Score
Neuronal Damage Score NNZ-2566 is highly neuroprotective (7 Control (Seizure rats, n = 9) EZ Control (Non-Seizure rats, n = 19) MB NNZ-2566 (0.3 mg/kg/h, i.v., n = 25) 45 *P<0.01 *P = 0.004 [Ed Vehicle MB NNZ- 2566 ie) Striatum CA1-2 CAS DG Cortex brain regions wo nN Tissue damage scores “Striatum C
Slide 22: NNZ-2566 in a Penetrating Brain Injury Model
NNZ-2566 in a Penetrating Brain Injury Model Balance Beam Test (Foot Fault Deficits) 100% - % Improvement -20% -~ Vehicle 3mg 10 mg WRAIR TBI Model (12-hour infusion) TQUT CN wenn tn
Slide 23: Attenuation of Non-Convulsive Seizures
Attenuation of Non-Convulsive Seizures Incidence Total Time Mean Time Latency (sec) (sec) (min) Vehicle 92% 1277 80.2 75.4 NNZ-2566 60% 555 48.7 208.7 percent -35% 56% -39% +133% ange TCU sre nr WRAIR MCAO Model (bolus + 12-hour infusion) 23
Slide 24: Non-Convulsive Seizure Time Course
Non-Convulsive Seizure Time Course Vehicle 3mg/kg bolus ome/ke bolus 100mg/kg bolus # of NCS/rat/hour a ; ra — Ore Time post pMCAo (hours) TCU CN penne tt
Slide 25: NNZ-2566 Oral (single dose)
NNZ-2566 Oral (single dose) MCAO-Induced Ischaemic Brain Damage: Effect of Oral NNZ-2566 120 45 100 [es] Q L Damage (mm2) oO OQ 40 | 20 ‘ak 0 eee Veh 15 30 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
Slide 26: NNZ-2591
lis, NN2Z-2591
Slide 27: NNZ-2591 — Oral treatment for Parkinson's disease
NNZ-2591 — Oral treatment for Parkinson’s disease « Meets all requirements for a CNS drug candidate — Safe, non-toxic, crosses into brain, therapeutic window ~— Stable, low cost of goods « Parkinson's disease: Long-term disease modifying effects as well as short-term » Enhances memory « Market posit
Slide 28: NNZ-2591: Chronic effects in Parkinson's disease
NNZ-2591: Chronic effects in Parkinson’s disease n euren 100 iS 7 Days Treatment “ 75 4 with NNZ-2591(i.p.) 7) oa \ shown by blue bar a3 xB 50 se) 5 3 2-4 0 0 Weeks post 6-OHDA lesion —O~ Vehicle —tl— 0.2 mg/day —*— 1 mg/day —®— & mg/day NNZ-2591 given 2 weeks after striatal lesion 1 week treatment
Slide 29: Oral Administration: Cognitive Performance
Oral Administration: Cognitive Performance n Time to platform (seconds) Acquisition —O= Saline / water = Saline / NNZ-2591 0 Scopolamine / water —l— Scopolamine / NNZ-2591 Trial Day Time (s) Time (s) 10: Probe trial: Latency to Platform Quadrant LE] Scopolamine [2 scopotamine + NNZ-2591 15 10 Time t
Slide 30: NNZ-2591 Oral Administration: Histopathology
NNZ-2591 Oral Administration: Histopathology n euren Infarct area Infarct area s 1405 . . i One-way analysis of variance wo 120-4 P value 0.0011 H P value summary “ § 100- Are means signif. different? (P < 0.05) Yes aa 50-4 Number of groups 3 4 é F 8.498 a = 60-4 R squared 0.3541 Pid £ we < 40-4 Hy
Slide 31: Commercialization strategy
Commercialization strategy 1. Risk Reduction on three levels » Science : Safety, crosses blood brain barrier, long time window, manufacturing cost, results in multiple animal models, biological rationale * Clinical trial strategy : design, endpoints, analytical methods, cost-effectiveness, partners
Slide 32: Investment proposal
Investment proposal = Well-priced # History of meeting milestones = Creative, high quality product development plans » Significant progress in 2007: — 4clinical trials (2 molecules; 4 indications) ~— 4 out-licensing opportunities (4 molecules; 4+ indications) =» Capable, supportive partners = Low op
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