UNITED STATES

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): March 12, 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, 2nd 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 7.01Regulation FD Disclosure.

 

On March 12, 2015, Neuralstem, Inc. (“Company”) presented data from the Phase II trial of NSI-566 spinal cord-derived neural stem cells for the treatment of amyotrophic lateral sclerosis (ALS) at the Barclays Global Health Care Conference in Miami, Florida. The clinical trial met primary safety endpoints and established a maximum tolerated dose of 16 million cells delivered in 40 injections. Additionally, secondary efficacy endpoints such as the ALSFRS (a standard clinical test to evaluate functional status of ALS patients) and grip strength at nine months post-surgery were also evaluated. A copy of the slides presented at the conference is attached to this report as Exhibit 99.01. The slides can also be viewed on the Company’s website at www.neuralstem.com. An audio copy of the presentation is also available on the Company’s website.

 

The information contained in this Item 7.01 to this Current Report on Form 8-K and the exhibit attached hereto pertaining to this item shall not be deemed to be “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended (the “Exchange Act”), or otherwise subject to the liabilities of that section, nor shall such information or such exhibits be deemed incorporated by reference in any filing under the Securities Act of 1933, as amended, or the Exchange Act, except as shall be expressly set forth by specific reference in such a filing. The information set forth in the exhibits to this Form 8-K relating to this item 7.01 shall not be deemed an admission as to the materiality of any information in this report that is required to be disclosed solely to satisfy the requirements of Regulation FD.

 

 

Item 8.01Other Events.

 

On March 12, 2015, the Company announced that top line data from the Phase II trial of NSI-566 spinal cord-derived neural stem cells for the treatment of amyotrophic lateral sclerosis (ALS) at the Barclays Global Health Care Conference in Miami, Florida. The clinical trial met primary safety endpoints and established a maximum tolerated dose of 16 million cells delivered in 40 injections. Additionally, secondary efficacy endpoints such as the ALSFRS (a standard clinical test to evaluate functional status of ALS patients) and grip strength at nine months post-surgery were also evaluated. A copy of the press release is attached to this report as Exhibit 99.02

 

 

Item 9.01.Financial Statements and Exhibits.

       

Exhibit

No.

  

  

Description

  
99.01   Slides presented on March 12, 2015  
99.02   Press Release dated March 12, 2015  

 

 

 
 

 

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.

 

Dated: March 12, 2015

 

  NEURALSTEM, INC
       
  By:   /s/ I. Richard Garr  
     

I. Richard Garr

Chief Executive Officer

 

 

 

 

 
 

 

INDEX OF EXHIBITS

 

       

Exhibit

No.

  

  

Description

  
99.01   Slides presented on March 12, 2015  
99.02   Press Release dated March 12, 2015  

 

 

 

 



Exhibit 99.01

 

Barclay’s Global Healthcare Conference March 12, 2015

 
 

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 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 . 2 Neuralstem , Inc. Safe Harbor Statement

 
 

Neuralstem Technology 3 Neuralstem's technology enables the isolation, expansion and controlled differentiation of neural stem cells into mature, physiologically relevant human neurons and glial cells. Spinal Cord Hippocampus GABAergic Cholingergic Midbrain Dopaminergic • Discovered at NIH • Regionally specific CNS neural stem cells : brain and spinal cord • Fully characterized: • Expanded under defined conditions: no animal - derived reagents, serum or feeder cells • Reproducible differentiation: constitutive behavior of cells • FDA cGMP manufacturing • Worldwide patents

 
 

Neuralstem Overview Midbrain Neuralstem’s proprietary dual platform technology uses regionally specific neural stem cells for the development of CNS cell therapies and small molecule drug discovery. Neuralstem’s proprietary platform technology Transplantation Cell Therapies NSI - 566 Cell transplantation: Spinal Cord Delivery Platform Lead Indication: ALS Drug Screening Small Molecules NSI - 189 Novel neurogenic MOA, oral formulation Lead Indication: Major Depressive Disorder 4

 
 

Neuralstem Pipeline 5 One Technology, Two Neurogenic Platforms, Multiple Indications Compound / Indication Preclinical Phase 1 Phase 1b Phase 2 Phase 2b Data Small Molecule NSI-189 US Major Depression Disorder P2 start 2Q15 NSI-189 US Cognitive Deficit in Schizoprenia PIb start mid15 Cell Therapy NSI-566 US Amyotrophic Lateral Sclerosis Controlled P2 start 2015 NSI-566 US Chronic Spinal Cord Injury P1b data 4Q15 NSI-566 China Ischemic Stroke P2 start 2015 NSI-566 South Korea Acute Spinal Cord Injury Awaiting IND approval NSI-523.IGF Alzheimer's Disease Efficacy in animal data

 
 

Human Proof of Concept Safe and tolerable: • Completed 49 cell therapy transplantations world wide • No toxicity Biological Activity: • Definitive evidence of long - term cell survival via DNA fingerprinting • Synaptic integration – nursing, protecting and “bridging the gaps” Three ongoing clinical trials: • Amyotrophic Lateral Sclerosis (ALS): Phase 2 • Chronic Spinal Cord Injury ( cSCI ): Phase Ib • Ischemic Stroke: Phase I/II NSI - 566: Physiologically relevant human neural stem cells 6 Cell Therapy

 
 

NSI - 566/ALS Phase I Long Term ALSFRS - R Data 7 Phase Ib Patient Follow - up: 1200 day efficacy data • Patients 10, 11, 12, received ten lumbar and five cervical injections of 100,000 cells each • Safe and well tolerated; Average hospital stay 3 - 4 days • Proof of “Activity” – cells provide neurotrophic support acting as “nurse cells” in motor neuron pools in the spinal cord • L ong term cell survival in 6 autopsy patients Annals Of Clinical And Translational Neurology, Glass et.al

 
 

NSI - 566 Lead Program: Amyotrophic Lateral Sclerosis 8 Phase II ALS 9 M onth Data Primary Endpoints x NSI - 566 cells and surgery are well tolerated x Maximum tolerate dose: 400,000 cells per injection, 20 injections for each lumbar and cervical surgery Secondary Endpoints Investigating ALSFRS - R and subset muscle groups correlated to injection sites • ALSFRS - R: rating scale of 12 functional activities • H and grip (bilateral): lower arm muscular strength • Seated vital capacity: breathing Goals • Identify likely responders and refine patient population • Increase confidence of providing a meaningful therapeutic benefit

 
 

NSI - 566 Lead Program: Amyotrophic Lateral Sclerosis 9 Phase II ALS Trial Design Phase 2 : 11 subjects entered, all cervical injections • 1 - 3 (A): 5 bilateral inj ; 200,000 cells/ inj : 2 million cells • 4 - 6 (B): 10 inj /side: 200,000 cells/ inj : 4 million cells • 7 - 9 (C): 10 inj /side: 300,000 cells/ inj : 6 million cells • 10 - 12 (D): 10 inj /side: 400,000 cells/ inj : 8 million cells 13 - 15 (E) Final cohort receives bilateral lumbar (8 million) followed by bilateral cervical (8 million) injections for 16 million cells

 
 

ALS Phase II 9 month data 10 Statistically significant between responders and non - responders - 47 % response rate to the stem cell treatment Responder measurements • ALSFRS: 7 of 15 patients had a near - zero slope of decline or positive slope • Grip Strength : 7 of 15 patients had a near - zero decline, or positive strengthening

 
 

ALS Phase II 9 month data 11

 
 

ALS Phase II 9 month data 12 • Responders ’ disease progression was - 0.007 point per day • N on - responders ’ disease progression was - 0.1 point per day • Measurement : an average slope of decline of ALSFRS Statistical Significant Reduction in ALSFRS Slope

 
 

ALS Phase II 9 month data 13 • Statistically significant difference of 93% versus 35% of the baseline score retained by the responders versus non - responders • Responders scored an average ALSFRS score of 37 • Non - responders scored an average ALSFRS score of 14

 
 

ALS Phase II 9 month data 14 Seated Vital Capacity : responders remained within 94% of scores vs. 71% for non responders

 
 

ALS Phase II Control study 15 ALS Phase II Results • NSI - 566 cells and surgery are well tolerated • Identified max tolerated dose • 47% responder rates • Predictive responder profile ALS Phase II Control Study • ~ 50 patients • 9 month follow - up • L umbar and cervical injections, total 16 million cells • Enhanced screening protocol • Refined responder patient population • Multiple endpoints including ALSFRS, grip strength, vital capacity

 
 

Neurogenic Small Molecule Platform 16 NSI - 189: First - in - class Neurogenic Small Molecule Drug, Reversing Hippocampal Atrophy Screening human hippocampal s tem c ells Biological Activity » increase in synaptic connection » neurogenesis in the human hippocampus Major Depressive Disorder (MDD) • Phase II commencement 2Q15: ~150 patients, 20 centers, 90 day dosing, 6 month follow - up Cognitive Deficit in Schizophrenia • NSI - 189 Pipeline Expansion • Phase Ib commencement: mid 2015

 
 

Stages of Neurogenesis 17

 
 

Screening Path 18 10,269 small molecule compounds primary screen 16 neurogenic compounds in vitro 16 tested in acute toxicity in mice 15 tested for neurogenesis in healthy, adult mice 7 orally active neurogenic leads 1 development candidate selection NSI - 189

 
 

• SDQ combined treatment group showed statistically significant improvement (p=0.02) • Clinically meaningful reduction in depressive & cognitive symptoms (40mg, 80mg) • P ersistent efficacy over the non - dosing 8 - week follow - up period 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 Questionnaire (SDQ) p=0.09 d=0.95 Study Day 0 20 40 60 80 100 Montgomery and Asberg Depression Rating Scale 5 10 15 20 25 30 Placebo NS-189 NS-189 1x per day NS-189 2x per day NS-189 3x per day p=0.19 d=0.84 Montgomery - Asberg Depression Rating Scale (MADRS) Day 28 Day 84 NSI - 189 MDD Phase Ib Clinically Meaningful Results 19

 
 

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 • Significant effect size in cognitive function improvement; improvement persisted over 8 - week follow up period • NSI - 189 CPFQ was significantly better than the placebo group (p=0.01) at Day 28; Large effect size of 0.94 Cognitive and Physical Functioning Questionnaire (CPFQ) Day 28 Day 84 NSI - 189 MDD Phase Ib Clinically Meaningful Results All: A Phase 1B, Randomized, Double - Blind, Placebo - Controlled, Multiple - Dose Escalation Study Evaluating the Effects of NSI - 189 Phosp hate, a Neurogenic Compound, in Patients with Major Depressive Disorder (MDD) , presented June 2014, by Maurizio Fava, M.D., Karl Johe , Ph.D., Lev G. Gertsik , MD, Larry Ereshefsky , PharmD , Bettina Hoeppner , Ph.D., Martina Flynn, David Mischoulon , M.D., Ph.D., Gustavo Kinrys , M.D., and Marlene Freeman, M.D 20

 
 

NSI - 189 MDD Phase Ib Biomarkers Quantitative EEG ( qEEG ) measurements, electrophysical biomarker : • Day 28 statistical significance • Significantly increased brain wave patterns in the hippocampal region 10 Plasma biomarkers : • Identified a rapid response • C onsistent with therapeutic effects shown by the traditional clinical measures • (A1AT , Apo C3, BDNF, Cortisol, EGF, MPO, Prolactin , Resistin , sTNFR2 and TSH) High - frequency alpha at Day 28: 10 - 12 Hz 21 A Phase 1B, Randomized, Double - Blind, Placebo - Controlled, Multiple - Dose Escalation Study Evaluating the Effects of NSI - 189 Phosp hate, a Neurogenic Compound, in Patients with Major Depressive Disorder (MDD) , presented June 2014, by Maurizio Fava, M.D., Karl Johe , Ph.D., Lev G. Gertsik , MD, Larry Ereshefsky , PharmD , Bettina Hoeppner , Ph.D., Martina Flynn, David Mischoulon , M.D., Ph.D., Gustavo Kinrys , M.D., and Marlene Freeman

 
 

NSI - 189 Program Expansion • Phase Ib to commence mid 2015 • Hippocampal atrophy well documented in this patient population • Psychotic and hallucinations are distinct from cognitive deficit • High unmet patient population; limited therapies available • 3.5 million (1%) of Americans diagnosed 22 NSI - 189 for the treatment of cognitive deficit in schizophrenia The National of Mental Health (NIMH)

 
 

Neuralstem Timeline 23 NSI - 189 neurogenic small molecule platform Phase II MDD commence in 2Q15 Phase Ib full data; Dr. Maurizio Fava publication Phase Ib cognitive deficit in schizophrenia commence mid2015 NSI - 566 cell therapy platform Phase II ALS full data 1H15 Phase II ALS expected commence mid 2015 Phase Ib cSCI currently enrolling, data 4Q15 Phase I/II ischemic stroke expect to roll over into Phase II 2015

 



Exhibit 99.02

 

 

 

 

 

NEURALSTEM ANNOUNCES TOPLINE RESULTS OF PHASE II ALS TRIAL

 

 

GERMANTOWN, MD, March 12, 2015 -- Neuralstem, Inc. (NYSE MKT: CUR) announced top line data from the Phase II trial of NSI-566 spinal cord-derived neural stem cells under development for the treatment of amyotrophic lateral sclerosis (ALS). The study met primary safety endpoints. The maximum tolerated dose of 16 million transplanted cells and the surgery was well tolerated.

 

Secondary efficacy endpoints at nine months post-surgery indicate a 47% response rate to the stem cell treatment, as measured by either near-zero slope of decline or positive slope of ALSFRS score in seven out of 15 patients and by either a near-zero decline, or positive strengthening, of grip strength in seven out of 15 patients. Grip strength is an indicator of direct muscle strength of the lower arm. ALSFRS is a standard clinical test used to evaluate the functional status of ALS patients. The average ALSFRS score for responders at 9 months after treatment was 37. Non-responders scored an average of 14. These scores represent 93%, versus 35%, of the baseline score retained, respectively, by the responders versus non-responders at 9 months, which is a statistically significant difference. As measured by an average slope of decline of ALSFRS, responders’ disease progression was -0.007 point per day, while non-responders’ disease progression was -0.1 per day, which was again statistically significant. Lung function as measured by Seated Vital Capacity shows that responder patients remained within 94% of their starting scores, versus 71% for non-responder patients. The trial met its primary safety endpoints. Both the surgery and cells were well-tolerated, with one patient experiencing a surgical serious adverse event.

 

“In this study, cervical intervention was both safe and well-tolerated with up to 8 million cells in 20 bilateral injections,” said Karl Johe, PhD, Neuralstem Chief Scientific Officer. “The study also demonstrated biological activity of the cells and stabilization of disease progression in a subset of patients.   As in the first trial, there were both responders and non-responders within the same cohort, from patients whose general pre-surgical presentation is fairly similar.  However, we believe that through the individual muscle group measurements, we may now be able to differentiate the responders from the non-responders.  

 

“Our therapy involves transplanting NSI-566 cells directly into specific segments of the cord where the cells integrate into the host motor neurons. The cells surround, protect and nurture the patient’s remaining motor neurons in those various cord segments. The approximate strength of those remaining motor neuron pools can be measured indirectly through muscle testing of the appropriate areas, such as in the grip strength tests.  We believe these types of endpoints, measuring muscle strength, will allow us to effectively predict patients that will respond to treatment, adding a sensitive measure of the therapeutic effects after treatment. Testing this hypothesis will be one of the primary goals of our next trial.” The full data is being compiled into a manuscript for publication.

 

 
 

 

"We believe the top-line data are encouraging,” said 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 System, and an unpaid consultant to Neuralstem. “We were able to dose up to 16 million cells in 40 injections, which we believe to be the maximum tolerated dose.  As in the first trial, the top-line data show disease stabilization in a subgroup of patients. Perhaps equally as important, we believe the top-line data may support a method of differentiating responders from non-responders, which we believe will support our efforts as we move into the next, larger controlled trial expected to begin this summer.”

 

“The top-line data look very positive and encouraging. If this proportion of patients doing well after treatment can be corroborated in future therapeutic trials, it will be better than any response seen in any previous ALS trials,” said site principal investigator, Jonathan D. Glass, MD, Director of the Emory ALS Center. “Elucidating which factors define a patient who may have a therapeutic response to the stem cell treatment will be the next key challenge. We are hopeful that a set of predictive algorithms can be established to help pre-select the responders in our future trials.”

 

“We were very excited to participate as a site in this clinical trial,” said Merit Cudkowicz, MD, Chief of Neurology, Massachusetts General Hospital and Co-Chair of the Northeast ALS Consortium (NEALS). “We are hopeful with respect to the top-line results and we need to move swiftly and safely forward to confirm the responder effect and identify people who might benefit from this treatment approach.”

 

The open-label, dose-escalating trial treated 15 ambulatory patients, divided into 5 dosing cohorts, at three centers, Emory University Hospital in Atlanta, Georgia, the ALS Clinic at the University of Michigan Health System, in Ann Arbor, Michigan, and Massachusetts General Hospital in Boston, Massachusetts, and under the direction of principal investigator (PI), 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 System. Dosing increased from 1 million to 8 million cells in the cervical region of the spinal cord. The final trial cohort also received an additional 8 million cells in the lumbar region of the spinal cord.

 

The company anticipates commencing a later-stage, multicenter trial of NSI-566 for treatment of ALS in 2015. Neuralstem has received orphan designation by the FDA for NSI-566 in ALS.

 

About Neuralstem

 

Neuralstem's patented technology enables the production of multiple types of central nervous system stem cells in FDA GMP commercial quantities. These stem cells 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, or Lou Gehrig’s disease). The primary endpoints were met in Phase II. 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. NSI-566 is also in clinical development to treat neurological diseases such as ischemic stroke and acute spinal cord injury.

 

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, 2013 and Form 10Q, for the period ended September 30, 2014.

 

# # #

 

 

Contact:

Neuralstem – Investor Relations:

Danielle Spangler 301.366.1481

 

Planet Communications - Media Relations:

Deanne Eagle 917.837.5866

 

MDC Group - Investor Relations:

Susan Roush 747.222.7012

David Castaneda 414.351.9758