CUR Neuralstem Inc

 

 

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 11, 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))

 

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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 11, 2016, Neuralstem, Inc. (the “Company”) announced the publication of “Human Cortical Neural Stem Cells Expressing Insulin-Like Growth Factor-1: A Novel Cellular Therapy for Alzheimer’s Disease,” in Stem Cells Translational Medicine. A copy of the press release is attached to this report as Exhibit 99.01.

 

Additionally, representatives of the Company will be making investor presentations the week of January 11, 2016, including a presentation at the Biotech Showcase 2016 being held at the Parc 55 San Francisco Hotel on Tuesday, January 12, 2016. A copy of the slides to be used in such presentations is attached to this report as Exhibit 99.02.

  

Item 9.01

Financial Statement and Exhibits.

 

Exhibit No.		Description
99.01 99.02		Press Release Dated January 11, 2016 Slides for Presentation

  

 

 

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 11, 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 11, 2016 Slides for Presentation

  

 

 

 

Exhibit 99.01

 

  

 

NEURALSTEM’S PRECLINICAL ALZHEIMER’S DISEASE DATA PUBLISHED IN STEM CELLS TRANSLATIONAL MEDICINE

 

 

GERMANTOWN, MD, January 11, 2016 -- 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 publication of “Human Cortical Neural Stem Cells Expressing Insulin-Like Growth Factor-1: A Novel Cellular Therapy for Alzheimer’s Disease,” in Stem Cells Translational Medicine (http://stemcellstm.alphamedpress.org/content/early/2016/01/07/sctm.2015-0103.short?rss=1).

 

Researchers reported that HK532-IGF-1 cells differentiated into a subtype of neurons (GABA-ergic) that are dysregulated in Alzheimer’s disease (AD) and produced increased vascular endothelial growth factors (VEGF) in vitro. Additionally, they significantly increased neuroprotection, while not impacting normal cellular function. In a mouse model of Alzheimer’s disease, the cells survived transplantation into the peri-hippocampus and exhibited long-term persistence in targeted brain areas. The researchers concluded that HK532-IGF-1 cells should be further studied as a possible disease-modifying Alzheimer’s intervention. HK532-IGF-1, Neuralstem’s second stem cell product, is a proprietary line of cortical neural stem cells engineered to express insulin-like growth factor-1 (IGF-1), which has been shown to have wide-ranging neuroprotective properties.

 

“IGF-1 is a potent neuroprotective molecule that is naturally produced in our brain and body,” said Karl Johe, PhD, Chief Scientific Officer of Neuralstem and a study author. “In aging or lesioned brains, extra addition of IGF-1 may be therapeutic. Combining neural stem cell therapy with a protein therapy, in a single and permanent delivery, is a powerful new therapeutic modality. HK532-IGF-1 is the first of such second generation stem cell therapies we are developing in which the stem cells are used as stable and safe delivery vehicle of therapeutic proteins.” 

  

  

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

 

MDC Group - Investor Relations:

Susan Roush

747.222.7012

David Castaneda

414.351.9758

 

 

Exhibit 99.02

 

January 12, 2016 Biotech Showcase Corporate Presentation

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 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 2 • Founding science utilizing regionally specific stem cells • Novel small molecule drug screening platform targeting neurogenesis; identified multiple compounds • Phase II lead compound (NSI - 189) targeting major depressive disorder (MDD) • Novel neurogenic, synaptogenic MOA • Clinical stage transplantation cell therapy platform targeting: ALS, cSCI , & stroke Neuralstem’s proprietary technology uses regionally specific neural stem cells for the development of CNS therapies.

Dual Platform Pipeline 3 Lead Small Molecule Asset Targeting Depression Cell therapy targeting high unmet medical need populations

NSI - 189 Small Molecule Overview 4 NSI - 189 Small Molecule • Novel MOA increasing synaptic connections • Patent composition of matter (US Pat.No . 7,560,553) till 2029 NSI - 189 Phase II Major Depressive Disorder (MDD) • Commencement early 2016 • Data 2H 2017 Compelling early clinical data • Randomized, placebo - controlled, double blinded Phase Ib data • Excellent Safety Profile • Clinical efficacy on multiple scales; large effect size Large MDD Market • Peak Sales Forecast in G7 at 2029: US$ 1bn+ NSI - 189: First - in - class Neurogenic Small Molecule Drug

NSI - 189 Differentiation 5 N ovel neurogenic MOA • I ncreasing synaptic connections in the hippocampus • Neurogenesis in the hippocampus is linked to depression and other psychiatric and neurologic disorders No major s ide affects; better than current depression therapies • No metabolic or sexual dysfunction side effects Additional benefit in cognition f unction in MDD • Large effect size Persisted Improvements for MDD and cognition • Improvements persisted over the non - dosing 8 - week follow up period NSI - 189 is highly differentiated from current commercial depression therapies

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, 70, 84 (End - of - study) NSI - 189 Phase Ib NSI - 189 Phase Ib double - blind, randomized, placebo - controlled, multiple - dose study assessing safety and tolerability • Patients at screening could be taking an antidepressant medication(s), or have a history of taking antidepressant medication(s) in the past for their depressive disorder • At least two prior depressive episodes (including current episode ) 6

NSI - 189 MDD Phase Ib 7 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 Clinically Meaningful Results • SDQ combined treatment group showed statistically significant improvement (p=0.02) • Clinically meaningful reduction in depressive & cognitive symptoms (40mg, 80mg) • Persistent efficacy over the non - dosing 8 - week follow - up period 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 .

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 NSI - 189 MDD Phase Ib 8 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 . • 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)

NSI - 189: Biomarkers 9 Quantitative EEG ( qEEG ) biomarker: • Statistically significant change in brain waves over hippocampus and prefrontal cortex Blood biomarker panel : • Consistent with therapeutic effects shown by clinical measures MRI: • Trend for increase volume in left hippocampus High - frequency alpha at Day 28: 10 - 12 Hz 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.

NSI - 189 Phase II Trial Design 10 Study Objectives • Primary: Montgomery - Asberg Depression Rating Scale ( MADRS ) • Secondary: response and remission rates, durability effect Principal Investigator: Maurizio Fava, M.D. Slater Family Professor of Psychiatry at Harvard Medical School, Massachusetts General Hospital Sequential Comparison Parallel Trial Design* • 220 subjects, 12 sites • Three arm: 80mg (40mg BID), 40mg QD, placebo • 14 - 28 day screening including SAFER interview* • 12 week out - patient treatment period A Phase II, Double - Blind, Placebo - Controlled Study of NSI - 189 Phosphate (NS2014 - 1 ) *Fava, M. Massachusetts General Hospital Dept. of Psychiatry, Clinical Trials Network and Institute MedAvante , Inc .

Biological Activity: • Multiple mechanisms of action: neuroprotection , bridging , regeneration • Definitive evidence of long - term graft survival without immunosuppression in ALS patients NSI - 566 spinal cord stem cell - derived programs • Phase Ib Chronic Spinal Cord Injury ( cSCI ) – Funded by UCSD • Phase I/II Ischemic Stroke: Phase I/ II – BaYi Brain Hospital, Beijing PLA • Phase II Amyotrophic Lateral Sclerosis ( ALS ) – Secure grant funding for registration trial – Recent data presented in Sept 2015 Cell Therapy Overview 11 Neuralstem's technology enables the isolation, expansion and controlled differentiation of neural stem cells into mature, physiologically relevant human neurons and glial cells.

Neuralstem Catalysts 12 Program Milestones • Phase II MDD FDA Approval 1Q16 • Sept 2015 FDA protocol submission • Phase I cSCI d ata 1Q16 • Ongoing Phase I/II stroke trial 2016 • Phase II MDD d ata 2H17 Other Initiatives • Exploring additional NSI - 189 possible indications • Secure grant money for the next possible ALS clinical study