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): January 27, 2016

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 Items.

On January 27, 2016, Neuralstem, Inc. (the “Company”) announced that Dr. Karl Johe, Ph.D., the Company’s chief scientific officer and chairman provided an update on the Company’s ongoing NSI-566 cell therapy programs at the Phacilitate Cell & Gene Therapy World conference in Washington D.C. A copy of the press release and slides presented at the conference are attached to this report as Exhibits 99.01 and 99.02, respectively. Additionally, the slides from the presentation are also available on the Company's website at www.neuralstem.com.

Item 9.01

Financial Statement and Exhibits.

Exhibit

No.

Description

99.01

99.02

Press Release Dated January 27, 2016

Slides presented at conference

SIGNATURES

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

Date:	January 27, 2016	Neuralstem, Inc.


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

INDEX OF EXHIBITS

Exhibit

No.

Description

99.01

99.02

Press Release Dated January 27, 2016

Slides presented at conference

Exhibit 99.01

NEURALSTEM PRESENTED CELL THERAPY UPDATE AT PHACILITATE CELL & GENE THERAPY WORLD CONFERENCE

NSI-566 Trial Data Reveals Biological Activity Across Multiple Neurodegenerative Diseases: ALS, Chronic Spinal Cord Injury, and Stroke

GERMANTOWN, MD, January 27, 2016 -- Neuralstem, Inc. (Nasdaq: CUR), a biopharmaceutical company using neural stem cell technology to develop regenerative therapies and small molecule pharmaceutical drugs for CNS diseases and disorders, announced that Karl Johe, Ph.D., Neuralstem’s Chairman and Chief Scientific Officer, provided an update on the company’s ongoing NSI-566 cell therapy clinical programs at the Phacilitate Cell & Gene Therapy World conference in Washington D.C.

The presentation reviewed the company’s NSI-566 human spinal cord-derived neural stem cells investigational trials for the treatment of amyotrophic lateral sclerosis (ALS), chronic spinal cord injury (cSCI), and motor deficits due to ischemic stroke. Dr. Johe highlighted the consistent biological activity and multiple modes of therapeutic actions, including the rescue of motor neurons, motor improvement, and neuronal integration in NSI-566 animal and human clinical data. He concluded that the collective trial data analysis showed the cells consistently demonstrated biological activity in all three indications.

Neuralstem’s NSI-566 cells have been safely administered to 40 patients, in dosing ranges of 1.2 million to 24 million cells per patient, in four investigational safety trials. The consistent safety profile continues to validate Neuralstem’s physiologically relevant stem cell technology platform. The company and its collaborators from leading research institutions conclude that the data supports the advancement of clinical development in each of the three indications.

“The consistent biological activity of motor improvement by NSI-566 across multiple disease conditions in humans supports our regenerative hypothesis and is consistent with our preclinical data,” said Dr. Johe. “Based on these encouraging results, we are preparing to conduct additional clinical trials in in each of these incurable neurodegenerative indications.”

NSI-566/ALS: A review of the Phase I and Phase II trials suggested a treatment-emergent improvement of function along multiple endpoints, including improved lung capacity, muscle strength, and a slowing of ALS progression. Phase I data shows long-term graft survival with transient immunosuppression. Additionally in Phase II, the data revealed that more than 50% of the patients experienced a reduction in the ALS Functional Rating Scale (ALSFRS) decline when compared to historical data sets. The remaining subjects, the majority of which had very low grip strength at entry, did not experience a change in their rate of decline. Based on these observations, the next trial will only include patients with sufficient muscle strength remaining for potential rescue.

NSI-566/cSCI: The Phase I feasibility study involved four AIS A thoracic-spinal cord injury patients (motor and sensory complete), one-to-two years post-injury at the time of stem cell treatment. They each received 1.2 million cells in six injections around the site of the spinal cord injury. The stem cell treatment demonstrated feasibility and safety; there were no serious adverse events. A self-reported ability to contract some muscles below the level of injury was confirmed via clinical and electrophysiological follow-up examinations in one of the four patients treated. There was no change in the clinical status of the three other patients. All patients will be followed for a total of five years. Dr. Johe commented that the investigators are planning to add a second cohort of four more patients to the study.

NSI-566/Ischemic Stroke: Dr. Johe presented encouraging preliminary results from the first cohort of patients in the Phase I NSI-566 feasibility study for treatment of paralysis from stroke. The Phase I trial is designed to treat three cohorts of three post-stroke patients each, with Cohort A receiving 5 injections of 40,000 cells each; Cohort B receiving 5 injections of 80,000; and Cohort C receiving 15 injections of 80,000 cells each. The clinicians have completed dosing the second cohort. Dr. Johe added that an innovative brain injection cannula, which can safely inject higher doses of cells, was introduced into the study. The trial is being conducted at BaYi Brain Hospital in Beijing, China.

Dr. Johe’s presentation slides from the Phacilitate Cell & Gene Therapy World conference are posted on the Investor Center of the Company’s website, www.neuralstem.com.

About Neuralstem

Neuralstem's patented technology enables the commercial-scale production of multiple types of central nervous system stem cells, which are being developed as potential therapies for many central nervous system diseases and conditions.

Neuralstem's ability to generate neural stem cell lines from human hippocampus, which were used for systematic chemical screening for neurogenesis effect, has led to the discovery and patenting of molecules that Neuralstem believes may stimulate the brain's capacity to generate new neurons, potentially reversing pathophysiologies associated with certain central nervous system (CNS) conditions.

The company has completed Phase 1a and 1b 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 2 efficacy study for MDD in 2016.

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 1 study to treat paralysis due to chronic spinal cord injury, as well as in a Phase 1 study to treat paralysis from 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) protein. The treatment is currently in preclinical investigation for Alzheimer's disease (AD). In animal study reported at the 2015 Annual Meeting of the American Neurological Association, the cells improved cognition and reduced amyloid beta (Aβ) plaque load in AD mice.

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 nine months ended September 30, 2015, filed with the Securities and Exchange Commission (SEC), and in other reports filed with the SEC.

# # #

Contact:

Neuralstem – Investor Relations:

Danielle Spangler 301.366.1481

Planet Communications - Media Relations:

Deanne Eagle 917.837.5866

Exhibit 99.02

Phacilitate Cell & Gene Therapy World

January 25-27, 2016 Washington D.C.

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 27A of the Securities Act of 1933 as amended, and section 21E of the Securities Exchange Act of 1934, as amended. Such forward-looking statements are based upon Neuralstem, Inc.’s management’s current expectations, estimates, beliefs, assumptions, and projections about Neuralstem’s business and industry. Words such as “anticipates,” “expects,” “intends,” “plans,” “predicts,” “believes,” “seeks,” “estimates,” “may,” “will,” “should,” “would,” “potential,” “continue,” and variations of these words (or negatives of these words) or similar expressions, are intended to identify forward-looking statements. In addition, any statements that refer to expectations, projections, or other characterizations of future events or circumstances, including any underlying assumptions, are forward-looking statements. These forward-looking statements are not guarantees of future performance and are subject to certain risks, uncertainties, and assumptions that are difficult to predict. Therefore, our actual results could differ materially and adversely from those expressed in any forward-looking statements as a result of various risk factors. These risks and uncertainties include the risks associated with the effect of changing economic conditions, trends in the products markets, variations in Neuralstem’s cash flow, market acceptance risks, technical development risks and other risk factors detailed in Neuralstem’s Securities and Exchange Commission filings. For links to SEC documents please visit the company’s Web site: neuralstem.com.

For links to SEC documents please visit the company’s Web site: neuralstem.com.

Overview

Neuralstem’s proprietary technology uses regionally specific

neural stem cells for the development of CNS therapies.

Neuralstem (Nasdaq: CUR) founded in 1996

Human neural stem cell technology, discovered by its founding Scientist and Chairman, Karl Johe, Ph.D., while at NINDS at NIH

Issued patents worldwide

Two different product pipelines and fields:

Regenerative therapies: Injection of lab-cultured neural stem cells into CNS for treatment of neurodegenerative diseases -NSI-566 for the treatment of ALS, cSCI, & stroke

· Pharmaceuticals: Small molecule compounds for psychiatric and neurodegenerative diseases -NSI-189 for MDD 2

Dual Platform Pipeline

Lead Small Molecule Asset Targeting Depression Cell therapy targeting high unmet medical need populations

Clinical Development History/Plan of HSSC
(Human Spinal Cord-Derived Neural Stem Cells)
Cell Line	Indication	Location	Trial	ROA	Doses	Study Status
			Phase
NSI-566, CCB	ALS	USA	I	Intraspinal	0.5x10⁶/5 inj-	Completed in Feb
061005			(n=15)		1.5x10⁶/15 inj	2013

NSI-566, CCB	ALS	USA	II (n=15)	Intraspinal	2x10⁶/10 inj-	Completed in Dec
061005					16x10⁶/40 inj	2015

NSI-566, CCB	ALS	USA	IIb	Intraspinal	12x10⁶/40 inj	Update Spring 2016
141026			(n=TBD)


NSI-566, CCB	SCI-chronic (12-	USA	I	Intraspinal	1.2x10⁶/6 inj	Group A completed in
061005	24 months post		(n=8)			Jan 2016
	injury)

NSI-566, CCB	Stroke-chronic	China	I	Intracerebral	10x10⁶/15 inj-	Group C dosed
SZ	(4-24 months		(n=9)		72x10⁶/45 inj	1Q 2016
	post injury)

NSI-566, CCB	Stroke-chronic	China	II/III	Intracerebral	72x10⁶/45 inj	Planned start in 2H
SZ	(6-24 months		(n=TBD)			2016
	post injury)

Leading stem cell product:

NSI-566RSC--neural stem cells from one fetal spinal cord tissue

Manufacturing at commercially viable scale

while maintaining cell properties

cGMP, 3-tiered cell banks, fully tested & validated:

· MCB (250 vials, p6), WCB (350 vials, p9), CCB (400 vials, p12)— 2x10⁷cells/vial

· Normal karyotype – 44 + XY

NSI-566: SOD-1 Rat Model of ALS

· Koliatsos et al.,

Johns Hopkins

Marsala et al., UCSD

Xu L, et al. Neurosci Lett. 2011; 494(3): 222-6.

Xu L, et al. J Comp Neurol. 2009; 514(4):297-309.

Yan J, et al. PLoS Med. 2007 4(2): e39.

Xu L, et al. Transplantation. 2006; 82(7):865-75.

Yan J, et al. Stem Cells. 2006; 24(8):1976-85.

Hefferan MP, et al. PLoS One. 2012;7(8):e42614.

Hefferan MP, et al. Cell Transplant. 2011;20(8):1153-61.

NSI-566: Intraspinal Injections in Mini-pigs:

· Boulis et al, Emory

· Marsala et al., UCSD

Gutierrez J, et al. Neurosurgery. 2015 Oct;77(4):604-12; discussion 612.

Federici T, et al. J Vis Exp. 2012 Dec 7;(70):e4371.

Riley JP, et al. Neurosurgery. 2011 Dec;69(2 Suppl Operative):ons147-54; discussion ons155.

Raore B, et al. Spine (Phila Pa 1976). 2011;36(3):E164-71.

Dolezalova D, et al. J Comp Neurol. 2014; 522(12):2784-801.

Usvald D, et al. Cell Transplant. 2010;19(9):1103-22.

NSI-566: ALS Phase I

A Phase I, Open-label, First-in-human, Feasibility

and Safety Study of Human

Spinal Cord derived Neural Stem Cell

Transplantation for the Treatment of ALS

Eva L. Feldman¹, Jonathan D. Glass², Nicholas M. Boulis², Thais Federici², MeraidaPolak², C. Kelly²and Karl Johe³

¹University of Michigan, Ann Arbor, MI ²Emory University, ³Neuralstem, Inc

NSI-566: ROA intraspinal injections

Feldman EL, et al. Ann Neurol. 2014 Mar;75(3):363-73.

Riley J, et al. Neurosurgery. 2014 Jan;74(1):77-87.

NSI-566: Long-term graft survival with transient immunosuppression

		# of	# of	# of Days IM Meds
		days on	days on
Patient		FK506	MMF	Discontinued
number
	Gender			before death	Survival Days	% Donor DNA

1	M	177	165	216	394	0.06 – 5.40

2	M	107	503	67	572	0.18 – 0.93

3	M	259	259	0	259	0.03 – 2.39

4	M	189	192	133	325	0.07 – 4.20

5	M	94	283	638	921	0.14 – 0.67

6	F	139	134	57	196	0.06 - 0.96

FK506 = tacrolimus, MMF=mycophenolate mofetil, IM=immunomodulatory

Tadesse T, et al. Ann Clin Transl Neurol. 2014 Nov;1(11):900-8.

NSI-566 Phase I

Clear treatment-emergent improvement of function

Feldman EL, et al. Ann Neurol. 2014 Mar;75(3):363-73.

NSI-566: ALS Phase II

A Phase II, Open-label, Dose Escalation and Safety Study of Human Spinal Cord derived Neural Stem Cell Transplantation for the Treatment of Amyotrophic Lateral Sclerosis

Study Sites: University of Michigan, Emory University, Mass General Hospital

N=15 of variable disease profiles

Up to 16 million cells injected, intraspinal, C3-C5/L2-L5

NSI-566: ALS Phase II Results

50% of study patients with positive change of ALSFRS slope

NSI-566: ALS Phase II Results

40-80% of study patients better than historical dataset

ALSFRS-R FVC (% predicted) Grip strength

NSI-566 SCI: Motor improvement, scar reduction & cavity-filling effect grafted at Day 3 post-SCI

van Gorp S, et al., Stem Cell Res Ther. 2013 May 28;4(3):57.

NSI-566 SCI: Motor improvement & functional integration grafted at day 7 post-SCI in rat with complete spinal transection

Lu P, et al., Cell. 2012 Sep 14;150(6):1264-73.

NSI-566 cSCI: Phase I Safety Trial

1 – 2 years after injury

AIS A only

Group A: 4 patients with T2-T12 (completed)

Removal of instruments to enable MRI survey

1.2 x 10⁶cells in 6 bilateral injections at and below injury

6 month follow-up: No SAE

4.5 year post-study follow-up

Study Site: University of California San Diego

Next Phase I study in Group B: 4 more patients

NSI-566 cSCI: Phase I Safety Trial

Subject #4, self-reported https://www.instagram.com/p/9161Cag9vK/

NSI-566 cSCI: Phase I Safety Trial

Subject #4

25 y/o male, injury 416 days prior to stem cell treatment

Baseline: T5 Neurological AIS A Complete

Muscle Location	12-Week Visit: EMG	6- Month Visit: EMG
	Voluntary	Voluntary
	Muscle Unit Potentials	Muscle Unit Potentials
L, R rectus abdominis, T6	2-3 semi-voluntary (10cm	None
	from umbilicus)
L., R rectus abdominis, T7	None	None (L)

L., R rectus abdominis, T8	None	None (L)

L, R paraspinal, T7	None (R), Not measured	1 (L), 1 (R)
	(L)
L, R paraspinal, T8	None (R), Not measured	3-4 (L), None (R)
	(L)

NSI-566: Robust survival &neuronal differentiation in rat model of stroke

Tajiri et al., PloS One (2014) 9: e91408

NSI-566: Ameliorates Stroke – induced motor deficits in rat model of stroke

Tajiri et al., PloS One (2014) 9: e91408

NSI-566:Stroke

NSI-566 engraftment at 4 weeks post transplantation in ischemia-induced mini-pig brain

K299-HuNu K299-H&E Human NF-specific staining

NSI-566: Phase I for treatment of paralysis from chronic stroke

Single Study Site: BaYi Hospital, Beijing PLA

Open label feasibility & safety study

Cohort	Treatment	Cell	Deposits	No of	Status
ID		Number/Deposit	per Track	Cannula
				Tracks
A (n=3)	1.2x10⁷	40,000	5	3	Dosed
		cells/μL×20μL
B (n=3)	2.4x10⁷	80,000	5	3	Dosed
		cells/μL×20μL
C (n=3)	7.2x10⁷	80,000	15	3	Ongoing
		cells/μL×20μL