Slide 1: March 2016 Corporate Presentation
March 2016 Corporate Presentation
Slide 2: Safe Harbor Statement
NEURALSTEM, INC. Safe Harbor Statement Safe Harbor statements under the Private Securities Litigation Reform Act of 1995 : This presentation contains forward - looking statements as defined in Section 27 A of the Securities Act of 1933 as amended, and section 21 E of the Securities Exchange Act of 1
Slide 3: Proprietary Neural Stem Cell Technology
Proprietary Neural Stem Cell Technology 3 Neural Stem cell CNS platform Small Molecule Screening Safe, Novel MOA Multiple Targets Continuous Screening Cell Therapy High unmet medical need Outsourced Funding Lead Candidate: NSI - 189 Phase II MDD Lead Candidate: NSI - 566 ALS (orphan), Stroke, cSCI
Slide 4: Pipeline
Pipeline Compound / Indication Preclinical Phase | Phase II Phase Ill Status Small Molecule NsI-189 US Phase Il start Major Depression Disorder 1016 ee Data 2016 Exploratory NSI-S66 US Phase II Amyotrophic Lateral Sclerosis Completion NSI-566_ US Phase I data Chronic Spinal Cord Injury 1016 NSI-566
Slide 5: Clinical Corporate Goals
Clinical Corporate Goals 5 • MDD Ph II Trial, Data 2H 2017 • Exploration of additional safety studies NSI - 189 • Partnerships for continuing clinical development • Expedite regulatory pathways NSI - 566 • Expansion of clinical & regulatory personnel • Business development initiatives Corporate
Slide 6: Scientific Advisory Board
NSI - 189 Scientific Advisory Board 6 Dr. Maurizio Fava Harvard, MGH, Executive Vice Chair, Dept. of Psychiatry Principal Investigator: NSI - 189 Phase 2 MDD clinical trial Dr. Michael Thase Univ. of Pennsylvania, Chief. Division of Mood and Anxiety Disorders Treatment and Research Program Dr. Mark
Slide 7: Target Product Profile
NSI - 189 Target Product Profile 7 Indication Monotherapy and Adjunctive treatment of Major Depressive Disorder (MDD), with improvement of cognition Efficacy • Primary: MADRS • Key secondary: Onset of effect, s ustained effect, cognitive symptom improvement Superiority vs. active comparator at day 2
Slide 8: Clinical Results from Phase Ib
Cohort 1 N=8 (6 drug, 2 placebo) 40 mg QD Cohort 2 N=8 (6 drug, 2 placebo) 40 mg BID Cohort 3 N=8 (6 drug, 2 placebo) 40 mg TID Acute treatment: 28 days Follow up: Days 35, 42, 49, 56, 70, 84 (End - of - study) Clinical Results from NSI - 189 Phase Ib NSI - 189 Phase Ib double - blind, randomized, p
Slide 9: Clinical Results from MDD Phase Ib
Clinical Results from NSI - 189 MDD Phase Ib 9 p=0.02 d=0.90 Study Day -20 0 20 40 60 80 100 Symptoms of Depression Questionnaire 2.0 2.2 2.4 2.6 2.8 3.0 3.2 3.4 3.6 3.8 Placebo NS-189 NS-189 1x per day NS-189 2x per day NS-189 3x per day p=0.03 d=1.10 Day 84 Day 28 Symptoms of Depression Questionna
Slide 10: Clinical Results from MDD Phase Ib: Cognitive Function
p=0.01 d=0.94 Study Day -20 0 20 40 60 80 100 Cognitive and Physical Functioning Questionnaire 2.0 2.5 3.0 3.5 4.0 4.5 5.0 Placebo NS-189 NS-189 1x per day NS-189 2x per day NS-189 3x per day p<0.01 d=1.20 Day 28 Day 84 Clinical Results from NSI - 189 MDD Phase Ib 10 All: A Phase 1B, Randomized, Dou
Slide 11: qEEG Biomarker Results from MDD Phase Ib
Topographs of High Frequency alpha (10 - 12 Hz): Day 28 from Baseline Left posterior temporal (T5) (t=2.45, p=0.02) Left parietal regions (P3) (t=3.31, p=0.004) qEEG Biomarker Results from NSI - 189 MDD Phase Ib Quantitative EEG ( qEEG ) biomarker: • Increases coherence activity between prefrontal c
Slide 12: Favorable DMPK Characteristics
Favorable NSI - 189 DMPK Characteristics 12 Human PK supports QD dosing in clinic • t 1/2 is 17 - 20 hours • Total clearance is low (less than hepatic blood flow) • No gender difference in exposure profiles • No difference in AUC and t 1/2 between fasted and fed states Attractive metabolic profile •
Slide 13: Phase II MDD Trial
NSI - 189 Phase II MDD Trial 13 Study Objectives • Primary: Montgomery - Asberg Depression Rating Scale (MADRS) • Secondary: SDQ , HAMD17, CGI - S, CPFQ, SFI (sexual dysfunction), Cogscreen Battery (including Digit Symbol Coding Task), Cogstate Brief Battery Innovative Study Design • Independent , r
Slide 14: Preclinical Data
Preclinical Data 14 • Orally active, neurogenic, neuroregenerative , compound for the treatment of depression, cognitive impairment, and neurodegeneration • A new chemical entity with novel mechanism of action, molecular target yet unknown, but not mediated by SSRI or SNRI or by BDNF release or via
Slide 15: Activity at Multiple Doses in Novelty Suppressed Feeding Model
P - o - P Activity at Multiple Doses in Novelty Suppressed Feeding Model (Mouse) 15 • NSI - 189 (10 - 100mg/kg) and imipramine significantly decreased the latency to eat compared to vehicle (water) after 28 days of oral dosing but not 1 day (now shown) • No significant treatment effects on either bo
Slide 16: Activity at Multiple Doses in Novelty Suppressed Feeding Model
P - o - P Activity at Multiple Doses in Novelty Suppressed Feeding Model (Mouse) 16 Mouse brains from Novelty Suppressed Feeding Test (N=15/group) • 10mg/kg and 30mg/kg are the pharmacologically active concentrations. • Bell - shaped dose - response curve: Higher dose may not necessarily yield large
Slide 17: Building the Case for MOA
Building the Case for MOA 17 No appreciable binding activity against 52 neurotransmitter related receptors/ion channels/ enzymes – Novoscreen : Adenosine , GABA, Glutamate, Histamine, Muscarinic, Nicotinic, norepinephrine, opioid, or and serotonin receptors, Ca++, Cl - , K+ channels, PKA, PKC, CRF,
Slide 18: Rapid Bioavailability in the Brain by Oral Administration
Rapid Bioavailability in the Brain by Oral Administration 18 PK/ADME Results from Single Oral and IV Doses (mouse) Dose 10 mg/kg Oral 30 mg/kg Oral 100 mg/kg Oral Plasma Brain Plasma Brain Plasma Brain Cmax ( ng /mL plasma; ng /g brain) 116 77.8 270 169.6 8100 2063.2 Tmax (h) 0.5 0.5 0.25 0.3 0.133
Slide 19: Proprietary Drug Screening Platform
• Based on human neural stem cell differentiation in vitro • Captures large window of neurodevelopment: neurogenesis to synaptogenesis • Multiple Potential Sites of Action During Stages of Neurogenesis 19 Proprietary Drug Screening Platform Hippocampal Neural Stem Cells 1. Proliferation Immature Neu
Slide 20: Neuralstem's Library Selection: Potentially CNS-Active Compounds
Neuralstem's Library Selection: Potentially CNS - Active Compounds 20 Libraries selected to target neurogenesis – Kinases & phosphatases – Nuclear receptors – Peptide mimetics – GPCRs Five structural libraries chosen for diversity (scaffolds) Selected ~2000 compounds per library – Predict in advance
Slide 21: Screening Path to Development Candidate
21 10,269 Small Molecule Compounds through High Content Screen 16 Neurogenic Compounds in vitro 7 Orally Active Neurogenic Leads ( 3 Structural Classes) 16 Tested for Acute Toxicity in Mice 15 Tested for Neurogenesis in Healthy, Adult Mice 1 Development Candidate Selected NSI - 189 Screening Path to
Slide 22: Neuralstem's Operational Team
Neuralstem’s Operational Team 22 CMC Jim Zeller, Ph.D., API Process Chemistry 22 years in Warner - Lambert/Parke Davis/Pfizer, in Holland, MI, NDAs for gabapentin, atorvastatin, quinapril.; 12 years consulting – NDAs for carfilzomib , vismodegib , tedizolid phosphate, lifitegrast , obitecholic acid