Slide 1: Neural Stem Cell Technology Platform: Cell Therapy and Pharmaceuticals
Neural Stem Cell Technology Platform Cell Therapy and Pharmaceuticals August 2012 NYSE MKT: CUR
Slide 2: 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 27A of the Securities Act of 1933 as amended, and section 21E of the Securities Exchange Act of 1934, as amended. Such forward - looking st
Slide 3: Investment Highlights
Neuralstem , Inc. Investment Highlights □ Proprietary Patented Neural Stem Cell Platform Foundation for Cell Therapy and Small Molecule Programs □ NIH - discovered platform; F ully characterized, regionally specific neural stem cells □ Positive Human Data for Neural Stem Cell Therapy in ALS Patients
Slide 4: Collaborators: World-Class Clinical Partners
Neuralstem , Inc. Collaborators World - Class Clinical P artners □ ALS Trial Clinical Investigators : □ Principal Investigator: Eva L. Feldman, M.D., Ph.D. , Professor of Neurology & Director A. Alfred Taubman Medical Research Inst. of the University of Michigan Medical School; President of American
Slide 5: Management
Neuralstem , Inc. Management □ Karl Johe , PhD Co - founder, Chairman of the Board, and Chief Scientific Officer, 1997 - present □ Discoverer and developer of Human Neural Stem Cell Technology □ Staff Scientist at the NIH Laboratory of Molecular Biology of the National Institute of Neurological Diso
Slide 6: Technology: Stem Cells of the Brain and the Spinal Cord
Neuralstem Technology Stem Cells of the Brain and the Spinal Cord □ Platform technology □ Numerous cell therapy products □ Regionally specific CNS stem cells □ cGMP manufacturing □ Patented □ Issued and re - affirmed worldwide □ Fully characterized □ Expanded under defined conditions: no animal - de
Slide 7: Technology: U.S. Patents Issued and Re-affirmed Worldwide
Neuralstem Technology U.S. Patents Issued and Re - affirmed Worldwide □ U. S. Pat. No. 8,236,299 (August 2012) □ Transplantation of human n eural c ells for treatment of neurodegenerative c onditions □ U.S. Pat. No. 8,058,434 (November 2011) □ Compositions to effect neuronal growth □ U.S . Pat. No.
Slide 8: Neuralstem Technology Platform
Neuralstem Platform Cell Therapeutics’ Commercialization and Platform Roll - out 8 Neuralstem Technology Platform Direct Injection / Transplantation Into the Spinal Cord or Brain Cell Therapy Small Molecule Discovery and Development Enabled by Proprietary Stem Cell - based Screening Pharmaceuticals
Slide 9: ALS Phase I Safety Data Published and Presented: First 12 Patients
Neuralstem ALS Trial ALS Phase I Safety Data Published and Presented: First 12 Patients □ “Lumbar intraspinal injection of neural stem cells in patients with ALS: Interim results of a Phase I trial,” poster presented at American Neurological Association Annual Meeting, September 2011 □ “Lumbar Intra
Slide 10: ALS Phase I Safety Data: Key Findings
Neuralstem ALS Trial ALS Phase I Safety Data: First 17 Patients 10 □ Phase I Data Key Findings □ Successful, safe injection of NSI - 566 neural stem cells into 17 ALS patients in lumbar and/or cervical regions of spinal cords □ No complications related to cell delivery □ No toxicity related to cells
Slide 11: ALS Phase I Disease Progression: ALSFRS-R
11 Glass, et. al. STEM CELLS 2012;30:1144 – 1151 Neuralstem ALS Trial ALS Phase I Disease Progression: ALSFR - R - First 12 Patients □ The Amyotrophic Lateral Sclerosis Functional Rating Scale - Revised ( ALSFRS - R) is an instrument used by the physician for evaluating the functional status of pati
Slide 12: ALS Phase I Disease Progression: FVC
12 Glass , et. al. STEM CELLS 2012;30:1144 – 1151 Neuralstem ALS Trial ALS Phase I Disease Progression: FVC - First 12 Patients □ Forced Vital Capacity (FVC) is a lung function test that measures total lung capacity by the amount of gas contained in the lung at the end of a maximum inhalation FVC (%
Slide 13: ALS Phase I Disease Progression: HHD
13 Data: Glass, et. al. STEM CELLS 2012;30:1144 – 1151 Neuralstem ALS Trial ALS Phase I Disease Progression: HHD - First 12 Patients □ Hand - Held Dynamometer ( HHD) reflects the muscle strength. HHD (% baseline) Nonambulatory Cohorts Ambulatory Cohorts
Slide 14: ALS Phase I Clinical Trial: Cervical Phase, Return Patients
Neuralstem Cell Therapy Program (U.S.) ALS Phase I Clinical Trial: Cervical Phase, Return Patients □ Continuation of Phase I Clinical Trial □ Patient 17 is fifth of s i x patients scheduled to demonstrate the safety of cervical injections □ FDA approves return of three lumbar patients for second tre
Slide 15: ALS Phase I Clinical Trial: Cervical Phase Timing
Neuralstem Cell Therapy Program (U.S.) ALS Phase I Clinical Trial: Cervical Phase Timing □ Cervical cohort transplantations completed (5 of 6): □ First Cervical Patient #13: Nov. 2011 □ Patient #14: Feb. 2012 □ Patient #15 : April 2012 □ First Returning Patient #16: June 2012 □ Patient #17: July 201
Slide 16: Cell Therapy Program: Additional Indications
Neuralstem Cell Therapy Program (U.S.) Additional Indications □ Spinal Cord Injury (SCI) □ IND filed August 2010, on hold pending submission of rodent tumorigenicity data to FDA □ Same cells and injection procedure as ALS trial □ Chronic Stroke □ Positive proof - of - principle data from rat stroke
Slide 17: Cell Therapy Program (International)
Neuralstem Cell Therapy Program (International) Cell Therapy Product Status □ Neuralstem China : Stroke □ Phase I / II / III Trial expected to commence in January 2013 □ Wholly owned subsidiary: Neuralstem China 神脑生物医药公司 (Suzhou Neuralstem Biopharmaceutical Company, Ltd.) □ BaYi Brain Hospital in Be
Slide 18: Small Molecule Drug Program
Neuralstem Small Molecule Drug Program First - in - class Neurogenic Small Molecule Drugs □ Initially funded by U.S. DOD □ Patented neurogenic small molecule compounds: the ability to recruit endogenous neural stem cells to generate more new neurons in the adult brain □ Lead Drug in Clinical Develop
Slide 19: NSI-189 Compelling Data from Animal Studies
19 Latency to eat (sec) 0 100 200 300 400 500 600 Water Imipramine 60 mg/kg Vehicle NSI-144 NSI-150 NSI-158 NSI-189 Latency to eat (sec) 0 100 200 300 400 500 600 * * * Mean BrdU + Cells/2DG/Brain □ Behavior Assay Validated for Antidepressants □ Increased Neurogenesis in Hippocampus NSI - 189 Compel
Slide 20: NSI-189 Pre-clinical Animal Data
20 Latency to eat (sec) 0 150 300 450 600 750 900 1050 1200 Water Imipramine 60 mg/kg NSI-189 3mg/kg NSI-189 10mg/kg NSI-189 30mg/kg NSI-189 100mg/kg * * * * NSI - 189 Pre - clinical Animal Data Dose - dependent Behavior Effect and Increased Hippocampal Volume □ NSI - 189 shown to be as effective as
Slide 21: NSI-189 Clinical Data: Phase Ia Single Ascending Dose
21 Cohort Statistics C MAX ( ng /mL) T MAX ( hr ) AUC INF ( hr * ng /mL) t 1/2 ( hr ) 40mg (n=9) Mean 300 0.7 874 18 60mg (n=8) Mean 275 0.8 730 19 80mg (n=8) Mean 387 0.8 1149 17 40mg Fasting (n=10) Mean 250 0.8 1056 19.3 40mg Fed (n=10) Mean 156 2.6 1100 18.0 NSI - 189 Clinical Data Phase Ia Singl
Slide 22: NSI-189/MDD Phase Ib Clinical Trial: Depressed Patients
Neuralstem Small Molecule Drug Program NSI - 189/MDD Phase Ib Clinical Trial: Depressed Patients □ Major Depressive Disorder (MDD) – leading indication □ Phase Ib , 28 - day multiple ascending dose study, commenced June 2012 □ Other potential NSI - 189 applications □ Alzheimer’s Disease □ Cognitive
Slide 23: Clinical Programs Plan for 2012-2013
Neuralstem , Inc. Clinical Programs Plan for 2012 - 2013 23 2011 2012 2013 Cell Therapy Programs ALS (NSI - 566) Spinal Cord Injury (NSI - 566) Stroke (NSI - 566) Small Molecule Programs Major Depressive Disorder (NSI - 189) Completed Trials Core U.S. Trials Ex - U.S. Expansion Trials Phase I / Lumb
Slide 24: Catalysts: Next Months
Neuralstem , Inc. Catalysts: Next 12 Months □ Ongoing Clinical Trials □ ALS □ Phase I cervical - transplantations completion □ Phase I potential expansion, pending FDA amendment approval, to increase both number of patients treated and NSI - 566 dose □ Phase II trial application □ NSI - 189 □ Phase
Slide 25: Investment Highlights
Neuralstem , Inc. Investment Highlights □ Proprietary Patented Neural Stem Cell Platform Serves as Foundation for Cell Therapy and Small Molecule Programs □ Positive Human Data for Neural Stem Cell Therapy in ALS Patients □ Cell Therapy procedure and NSI - 566 treatment shown to be safe and well - t
Slide 26: Appendix
Neuralstem , Inc. Appendix □ ALS Phase I Trial Design □ NSI - 189/MDD Phase I Trial Design □ Cell Therapy Surgical Device □ Published Papers 26
Slide 27: ALS Phase I Trial Design
Neuralstem ALS Trial ALS Phase I Trial Design □ Primary Endpoint □ Safety □ Secondary Endpoints □ Attenuation of motor function loss □ Maintenance of respiratory capacity □ Stabilization of ALS functional rating scale □ Reduction of spasticity/rigidity if present □ Graft survival at autopsy upon mor
Slide 28: NSI-189/MDD Small Molecule Phase I Trial Design
Neuralstem NSI - 189/MDD Trial Small Molecule Phase I Trial Design □ Primary Endpoint □ Safety □ Secondary Endpoints □ Tolerability □ Pharmacokinetics □ Pharmacodynamic effects (hippocampal volume by MRI, BDNF/CRH/other factors in blood, urine biomarkers, cortisol in saliva, qEEG , MADRS, NGH Depres
Slide 29: Cell Therapy Surgical Device: Exclusive Worldwide License
Neuralstem Cell Therapy Surgical Device Exclusive Worldwide License □ Spinal Platform and Floating Cannula □ Proprietary breakthrough medical device □ Expected to be the standard in industry and research community for intraspinal procedures □ Neuralstem holds exclusive worldwide license □ Designed b
Slide 30: Technology: Published Papers
Neuralstem Technology Published Papers □ Lumbar Intraspinal Injection of Neural Stem Cells in Patients with ALS: Results of a Phase I Trial in 12 Patients. □ Glass JD, Boulis NM, Johe K, Rutkove SB, Federici T, Polak M, Kelly C, Feldman, EL, Department of Neurology, Emory University School of Medici