Current Report Filing (8-k)

SECURITIES AND EXCHANGE COMMISSION

WASHINGTON, D.C. 20549

FORM 8-K

CURRENT REPORT

Pursuant to Section 13 or 15(d) of the

Securities Exchange Act of 1934

Date of report (Date of earliest event reported): September 29, 2015

Neuralstem, Inc.

(Exact name of registrant as specified in Charter)

Delaware

001-33672

52-2007292

(State or other jurisdiction of

incorporation or organization)

(Commission File No.)

(IRS Employee Identification No.)

20271 Goldenrod Lane, 2^nd Floor,

Germantown, Maryland 20876

(Address of Principal Executive Offices)

(301) 366-4960

(Issuer Telephone number)

Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions (see General Instruction A.2. below):

¨ Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425)

¨ Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12)

¨ Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))

¨ Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c))

Item 8.01.

Other Events.

On September 29, 2015 Neuralstem, Inc. (“Company”) announced that Eva Feldman, MD, PhD, Director of the A. Alfred Taubman Medical Research Institute and Director of Research of the ALS Clinic at the University of Michigan Health, presented nine-month Phase II and combined Phase I and Phase II data on the NSI-566 trial in amyotrophic lateral sclerosis (ALS) at the American Neurological Association Annual Meeting on September 28, 2015. A copy of the press release and slides presented are attached to this report as Exhibits 99.01 and 99.02, respectively. Dr. Feldman also presented information at the annual meeting with regard to Human Cortical Neural Stem Cells in Alzheimer’s Disease. A copy of the slides presented are attached to this report as Exhibit 99.03.

Item 9.01

Financial Statement and Exhibits.

Exhibit Number		Description

99.01		Press Release Dated September 29, 2015
99.02		Slides Presented with regard to NSI-566
99.03		Slides Presented with regard to Alzheimer’s Disease

SIGNATURES

Pursuant to the requirements of the Securities Exchange Act of 1934, the Issuer has duly caused this Report on Form 8-K to be signed on its behalf by the undersigned hereunto duly authorized.

	NEURALSTEM, INC

	By:	/s/ I. Richard Garr
		I. Richard Garr
		Chief Executive Officer

Dated: September 29, 2015

INDEX OF EXHIBITS

Exhibit Number		Description

99.01		Press Release Dated September 29, 2015
99.02		Slides Presented with regard to NSI-566
99.03		Slides Presented with regard to Alzheimer’s Disease

Exhibit 99.01

Neuralstem Investigator Provides Phase II Update on ALS Cell Therapy at American Neurological Association Annual Meeting

GERMANTOWN, Md., Sept. 29, 2015 — Neuralstem, Inc. (Nasdaq: CUR), a biopharmaceutical company using neural stem cell technology to develop small molecule and cell therapy treatments for central nervous system diseases, announced that nine-month Phase II and combined Phase I and Phase II data on the NSI-566 trial in amyotrophic lateral sclerosis (ALS) was presented at the American Neurological Association Annual Meeting by principal investigator, Eva Feldman, MD, PhD, Director of the A. Alfred Taubman Medical Research Institute and Director of Research of the ALS Clinic at the University of Michigan Health. The data showed that the intraspinal transplantation of the cells was safe and well-tolerated throughout the escalating doses, reaching a maximum tolerated dose of 16 million cells via 20 bilateral injections. There appeared to be no acceleration in disease progression due to the therapeutic intervention.

Researchers calculated a 95% confidence limit around the slopes of decline of ALSFRSr scores, forced vital capacity (FVC) and grip strength of the ProAct historical database subjects, and evaluated if trial subjects fell within or outside those limits. 73% of Phase II patients, and 79% of combined Phase I and II patients, fell above the upper confidence limit of the ALSFRSr score. 50% of Phase I and II combined, and 40% of Phase II patients’ forced vital capacity percent predicted fell above the upper confidence limit, compared to the ProAct database. ALSFRSr scores correlated most strongly with FVC preservation, which was the target of the cervical injections. For grip strength control, researchers used the Ceftriaxone (CEF) study database, since grip strength data was not available in the ProAct database. 67% of Phase I and II combined, and 60% of Phase II patients, all at nine months post-intervention, fell above the 95% upper confidence limit.

The most common adverse event (AE) was transient post-operative pain due to surgery. One serious adverse event due to the surgical procedure was observed, but was not attributed to the cells themselves. The patient’s motor function was initially weakened and then recovered to the patient’s ALS baseline.

“Based on this encouraging safety and clinical effect, we look forward to moving to a registration-directed trial in 2016,” said Karl Johe, PhD, Chief Scientific Officer.

About the Trial

The Phase II open-label, dose-escalating trial of NSI-566 evaluated 15 ambulatory patients with ALS, averaging a mean duration of disease of 15.5 months. Participants were divided into five dosing cohorts with three patients in each, who received increasing quantities of cells in the cervical region of the spinal cord via bilateral intraspinal injections ranging from two million to eight million cells. The fifth cohort received an additional eight million cells in the lumbar region. There was no control or placebo group included in the trial. The primary endpoint of the study was the safety of the maximum tolerated dose of stem cell transplantation. Secondary efficacy endpoints included stabilization of ALS Functional Rating Scale-revised (ALSFRSr) scores, and assessment of respiratory functioning, grip strength and muscle strength. 9 of the 15 participants in Phase I and all 15 participants in Phase II were included in the 9-month data. Dr. Eva Feldman, principal investigator, is an unpaid consultant to Neuralstem.

About Amyotrophic Lateral Sclerosis (ALS)

ALS is a progressive disease that affects nerve cells, or neurons, in the brain and the spinal cord, leading to degeneration and eventual atrophy of the surrounding muscles. As the condition worsens, motor neurons die, and the brain can no longer control the affected muscles. In time, this causes the loss of patients’ ability to speak, eat, move and breathe, eventually resulting in death. It is estimated that more than 5,600 people in the U.S. are diagnosed with ALS each year, amounting to 15 new cases per day, totaling approximately 30,000 Americans living with the disease at any given time. There is currently no cure or treatment that that halts or reverses the progression of the disease.¹

About Neuralstem

Neuralstem's patented technology enables the commercial-scale production of multiple types of central nervous system stem cells, which are under development for the potential treatment of central nervous system diseases and conditions.

Neuralstem's ability to generate human neural stem cell lines for chemical screening has led to the discovery and patenting of compounds that Neuralstem believes may stimulate the brain's capacity to generate neurons, potentially reversing pathologies associated with certain central nervous system (CNS) conditions. The company has completed Phase Ia and Ib trials evaluating NSI-189, its first neurogenic small molecule product candidate, for the treatment of major depressive disorder (MDD), and is expecting to initiate a Phase II study for MDD and a Phase Ib study for cognitive deficit in schizophrenia in 2015.

Neuralstem's first stem cell product candidate, NSI-566, a spinal cord-derived neural stem cell line, is under development for treatment of amyotrophic lateral sclerosis (ALS). Neuralstem has completed two clinical studies, in a total of thirty patients, which met primary safety endpoints. In addition to ALS, NSI-566 is also in a Phase I trial in chronic spinal cord injury at UC San Diego School of Medicine, as well as in clinical development to treat ischemic stroke.

Neuralstem's next generation stem cell product, NSI-532.IGF, consists of human cortex-derived neural stem cells that have been engineered to secrete human insulin-like growth factor 1 (IGF-1). In animal data presented at the Congress of Neurological Surgeons 2014 Annual Meeting, the cells rescued spatial learning and memory deficits in an animal model of Alzheimer's disease.

For more information, please visit www.neuralstem.com or connect with us on Twitter, Facebook and LinkedIn.

Cautionary Statement Regarding Forward Looking Information:

This news release contains "forward-looking statements" made pursuant to the "safe harbor" provisions of the Private Securities Litigation Reform Act of 1995. Such forward-looking statements relate to future, not past, events and may often be identified by words such as "expect," "anticipate," "intend," "plan," "believe," "seek" or "will." Forward-looking statements by their nature address matters that are, to different degrees, uncertain. Specific risks and uncertainties that could cause our actual results to differ materially from those expressed in our forward-looking statements include risks inherent in the development and commercialization of potential products, uncertainty of clinical trial results or regulatory approvals or clearances, need for future capital, dependence upon collaborators and maintenance of our intellectual property rights. Actual results may differ materially from the results anticipated in these forward-looking statements. Additional information on potential factors that could affect our results and other risks and uncertainties are detailed from time to time in Neuralstem's periodic reports, including the Annual Report on Form 10-K for the year ended December 31, 2014, and Form 10-Q for the three and six months ended June 30, 2015, filed with the Securities and Exchange Commission (SEC), and in other reports filed with the SEC.

SOURCE Neuralstem, Inc.

For further information: Investor Relations: Danielle Spangler, 301.366.1481, Planet Communications-Media relations or Tonic Life Communications - Media relations: Jennifer Gallo (jennifer.gallo@toniclc.com), 215.928.2183, Theresa Dolge (theresa.dolge@toniclc.com), 215.928.2748.

References:

ALS Association. About ALS. Available at: http://www.alsa.org/about-als/. September 28, 2015.

Exhibit 99.02

Eva L. Feldman, M.D., Ph.D. Stephen Goutman M.D. Parag Patil M.D., Ph.D University of Michigan Jon Glass M.D. and Nicholas Boulis MD, Emory Merit Cudkowicz M.D. and Nazem Atassi M.D, Harvard Phase 2 Trial Results: (Phase II NSI - 566/ALS) Funding: Neuralstem Inc with Karl Johe Ph.D. , ALSA and NINDS

Overview of Phase 1 & 2 FDA Clinical Trials • FDA Phase 1&2 trials • 30 patients with ALS • Risk escalation • Progressively less affected patients in groups of 3 • Initial unilateral injections to bilateral injections of neural stem cells Phase 1: January 2010 - May 2013 Phase 2: October 2013 - July 2014

Trials Use Neural Spinal Stem Cells Developed and provided by Neuralstem, Inc

A1: ½ million c ells A2: 1 million cells A1/A2 L2 L3 L4 C3 C4 C5 L2 L3 L4 1 million cells ½ million cells ½ million cells 1.5 million cells B C D E Phase 1 Trial Design Slide compliments of J . Glass MD C3 C4 C5 L2 L3 L4 L2 L3 L4

MRI Measurements and Cannula Selection Cannula 3 - 5 mm 5 mm 3 - 5 mm

Stem Cell Injections

2 million cells A 4 million cells B 6 million cells C 8 million cells D C3 C4 C5 C3 C4 C5 16 million cells E L2 L3 L4 Phase 2 Design Slide compliments of J . Glass MD

Demographics: Phase 1 and 2 Trial and Published Patient Cohorts Group (n) Mean age in Years (std. dev.) Mean disease duration in months (std. dev.) % Male Phase 1+2 (24) 48.7 (10.0) 11.0 (7.6) 79.2 Phase 2 (15) 48.1 (10.4) 15.5 (5.5) 80.0 CEF (172) 54.8 (10.3) 18.6 (8.0) 58.0 ProACT (552) 55.5 (11.7) 20.6 (11.0) 64.0 Phase 1 results : Feldman EL et al Annals of Neurology 75:363 - 73, 2014

Adverse Events Related to Specific Trial Interventions in Phase 2 Causality: site PI assessment of possibly, probably or definitely related Adverse Events Serious Adverse Events Surgery 98 total / 38% 1 total / 8% Device 9 total / 3% None HSSC 14 total / 5% 1 total / 8% IM Drug 37 total / 14% 3 total / 25% Percentages do not add up to 100 because AEs may be related to some degree to more than a single variable

0 200 400 10 20 30 40 50 ALSFRS-r Days Elaspsed from 1st Surgery 304 307 309 311 312 314 301 302 305 306 308 310 313 315 303 ALSFRS - R Scores Before and After Surgery: Phase 2

Confidence Limit Analyses of Subjects Compared to ALS Historical Databases • Individual slope estimates from subjects compared to the 95 % CL of the mean slope from a historical database. • Numbers in ( ) are the % of subjects falling below/ within/above the CL for estimates at 270 days after intervention.

Confidence Limit Analyses: ALSFRS - R 14 (58%) 10 (42%) 7 (47%) 8 (53%) 11 (73%) 2 (13%) 2 (13%) 19 (79%) 3 (13%) 2 (8%)

Confidence Limit Analyses: Grip strength 16 (67%) 8 (33%) 9 (60%) 6 (40%)

Preserved FVC Correlates with ALSFRSr in Phase 2 Subjects ALSFRSr FVC Seat FVC Supine HHD Upper HHD Lower GSTLeft GST Right GST Merged ALSFRSr 1.00 0.60 0.32 0.30 0.46 0.42 0.54 0.50 FVC_Seat 0.60 1.00 0.73 0.20 0.35 0.31 0.29 0.31 FVC_Supine 0.32 0.73 1.00 - 0.32 - 0.22 0.18 0.09 0.17 HHD_Upper 0.30 0.20 - 0.32 1.00 0.58 0.41 0.42 0.41 HHD_Lower 0.46 0.35 - 0.22 0.58 1.00 0.11 0.18 0.10 GST_Left 0.42 0.31 0.18 0.41 0.11 1.00 0.79 0.95 GST_Right 0.54 0.29 0.09 0.42 0.18 0.79 1.00 0.94 GST_Merged 0.50 0.31 0.17 0.41 0.10 0.95 0.94 1.00

Summary of Phase 1 and 2 Results • 30 ALS subjects have been entered into the two trials • Intraspinal stem cell transplantation in the lumbar and cervical cord is safe • Subjects did well with up to 10 bilateral cervical and 10 bilateral lumbar injections, each with 4 X 10 5 stem cells, for a total of 16 million cells • Greater than 70% of the subjects has an ALSFRS - r that compared favorably to the largest historical data set: ProACT • FVC correlated strongly with ALSFRSr in Phase 2 subjects

Summary of Phase 1 and 2: the Way Forward • Patients are continuing to be followed • The next trial is currently being planned and will include more surgical sites and larger subject numbers • ALS clinicians and patients can find the most up to date information on the U of M ALS Clinic website www. umich - als .org • A special thank you to the participants and their families

Exhibit 99.03

Human Cortical Neural Stem Cells Expressing IGF - 1: A Novel Cellular Therapy for Alzheimer’s Disease Lisa McGinley Ph.D. and Eva L. Feldman M.D. Ph.D. University of Michigan - No disclosures Osama N. Kashlan M.D., Kevin S. Chen M.D., Elizabeth S. Bruno B.S., Karl Johe Ph.D.

AD: a Significant Public Health Concern Adapted from L . E . Herbert, et al ., Neurology, May 2013 No disease modifying therapy

Drug d evelopment & t argets • 412 trials registered 2002 - 2012 • Targets: A β , Tau, inflammation • 99.6% f ailure rate since 2002 • Alternative approaches are necessary! J . L. Cummings , et al ., Alz . Res . & Ther . , July 2014

Stem Cell Therapies… A New Era?

Human Cortical Neural Stem Cells (NSCs) NSCs supplied by Neuralstem Inc .: – N ormal cell function – Differentiate into GABAergic neurons – Produce GDNF, BDNF & increased VEGF, IGF - 1 – Neuroprotective – Survive grafting into the AD brain in vivo – Efficacy in vivo ?

Hypothesis: Grafted NSCs will improve cognitive impairment in AD. NSCs will establish and support synaptic connections and prevent neuronal loss by mitigating disease pathologies. Aims & Hypothesis Aims : 1. Determine impact of intracranial NSC transplantation in the APP/PS1 mouse 2. Assess potential efficacy in terms of cognitive benefit 3. Begin to identify possible mechanisms underlying efficacy it is was observed

Study Design MWM NOR NOR NOR NOR 28 Euthanize 12 16 22 26/27 8 APP/PS1 NSC FF Injection Groups: 1. AD + sham (+FK506) 2. AD + NSC (+FK506) 3. WT non - tg Outcome measurements: 1. Behavior – NOR, MWM 2. Tissue – Graft analysis - AD pathology Target: Fimbria Fornix

Novel Object Recognition Exploration Novel Test • Short - term non - associative memory • Longitudinal testing • Each NOR test is 2 days – Day 1 habituation (3 x 240s) – Day 2 NOR: 300s exploration & 300s novel (30 - 45 min delay) Behavioral & Functional Neuroscience Laboratory http://sbfnl.stanford.edu/

NSCs Impact Short - term Memory *p< 0 . 05 . T Test

Morris Water Maze • Spatial reference memory • Training: – Hidden platform – 5 days – 6 trials per day (6 x 60s per mouse) • Probe test: – No platform – Day 6 – One 60s trial Neuromorphics Laboratory, http://nl.bu.edu/

NSCs Impact Spatial Learning and Memory *p< 0 . 05 (one way ANOVA) Training:

NSCs Impact Spatial Learning and Memory *p< 0 . 05 (one way ANOVA) Probe test:

NSCs Migrate to the Hippocampus Unpublished data

NSCs Reduce AD Pathology ***p< 0 . 0001 , unpublished data AD + sham AD + NSC Hippocampus

Possible Mechanism: Microglial Activation? **p< 0 . 001 , unpublished data 100µm 0

Summary & Future Directions NSCs: - Survive in vivo transplantation and migrate to the hippocampus - I mprove cognition in AD mice - Reduce Aβ plaque load in AD mice - Result in increased activated microglia Next steps: - Continue to interrogate possible therapeutic mechanisms - Test in alternative AD models - Targeting and safety in large animals

Acknowledgements Feldman Lab Lisa McGinley Ph.D. Osama Kashlan M.D. Liz Bruno B.S. Kevin Chen M.D. Carey Backus B.S. Samy Kashlan M.D. John Hayes B.S. Seth Feldman Geoff Murphy Ph.D. Karl Johe Ph.D. ( Neuralstem Inc .) Tom Hazel Ph.D. ( Neuralstem Inc.) Julia Raykin Ph.D. (Georgia Tech) Funding Support A. Alfred Taubman Medical Research Institute Program for Neurology Research & Discovery Robert E. Nederlander Sr. Program for Alzheimer’s Research