Search the web
Welcome, Guest
[Sign Out, My Account]
EDGAR_Online

Quotes & Info
Enter Symbol(s):
e.g. YHOO, ^DJI
Symbol Lookup | Financial Search
CUR > SEC Filings for CUR > Form 10-Q on 9-May-2016All Recent SEC Filings

Show all filings for NEURALSTEM, INC.

Form 10-Q for NEURALSTEM, INC.


9-May-2016

Quarterly Report


ITEM 2. MANAGEMENT'S DISCUSSION AND ANALYSIS OF FINANCIAL CONDITION AND RESULTS OF OPERATIONS

Statements in this Quarterly Report that are not strictly historical are forward-looking statements and include statements about products in development, results and analyses of pre-clinical studies, clinical trials and studies, research and development expenses, cash expenditures, and alliances and partnerships, among other matters. You can identify these forward-looking statements because they involve our expectations, intentions, beliefs, plans, projections, anticipations, or other characterizations of future events or circumstances. These forward-looking statements are not guarantees of future performance and are subject to risks and uncertainties that may cause actual results to differ materially from those in the forward-looking statements as a result of any number of factors. These factors include, but are not limited to, risks relating to our ability to conduct and obtain successful results from ongoing clinical trials, commercialize our technology, obtain regulatory approval for our product candidates, contract with third parties to adequately test and manufacture our proposed therapeutic products, protect our intellectual property rights and obtain additional financing to continue our development efforts. Some of these factors are more fully discussed, as are other factors, in our Annual Report on Form 10-K for the fiscal year ended December 31, 2015, filed with the SEC, as well as in the section of this Quarterly Report entitled "Risk Factors" and elsewhere herein. We do not undertake to update any of these forward-looking statements or to announce the results of any revisions to these forward-looking statements except as required by law.

We urge you to read this entire Quarterly Report on Form 10-Q, including the "Risk Factors" section, the financial statements, and related notes. As used in this Quarterly Report, unless the context otherwise requires, the words "we," "us," "our," "the Company," "Neuralstem" and "Registrant" refers to Neuralstem, Inc. and its subsidiaries. Also, any reference to "common shares," "common stock," or "shares" refers to our $.01 par value common stock. The information contained herein is current as of the date of this Quarterly Report (March 31, 2016), unless another date is specified. We prepare our interim financial statements in accordance with U.S. GAAP. Our financials and results of operations for the three-month period ended March 31, 2016 are not necessarily indicative of our prospective financial condition and results of operations for the pending full fiscal year ending December 31, 2016. The interim financial statements presented in this Quarterly Report as well as other information relating to our company contained in this Quarterly Report should be read in conjunction and together with the reports, statements and information filed by us with the United States Securities and Exchange Commission or SEC.

Our Management's Discussion and Analysis of Financial Condition and Results of Operations or MD&A, is provided in addition to the accompanying financial statements and notes to assist readers in understanding our results of operations, financial condition and cash flows. Our MD&A is organized as follows:

Executive Overview - Discussion of our business and overall analysis of financial and other highlights affecting the Company in order to provide context for the remainder of MD&A.

Trends & Outlook - Discussion of what we view as the overall trends affecting our business and overall strategy.

Critical Accounting Policies- Accounting policies that we believe are important to understanding the assumptions and judgments incorporated in our reported financial results and forecasts.

Results of Operations- Analysis of our financial results comparing the three-month periods ended March 31, 2016 to the comparable period of 2015.

Liquidity and Capital Resources- An analysis of cash flows and discussion of our financial condition and future liquidity needs.

Executive Overview

We are focused on the research, development and commercialization of central nervous system therapies based on our proprietary human neuronal stem cells and our stem-cell derived small molecule compounds. We are headquartered in Germantown, Maryland and have a wholly-owned subsidiary in China, Suzhou Neuralstem Biopharmaceutical Co. Ltd., or Neuralstem China.

Our technology base has produced three primary assets: Our NSI-189 small molecule program, our NSI-566 stem cell therapy program and our novel and proprietary new chemical entity screening platform.

Our 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. In addition, this ability to generate human neural stem cell lines provides a platform for chemical screening and discovery of novel compounds that we believe may stimulate the brain's capacity to generate neurons, potentially reversing pathologies associated with certain central nervous system (CNS) conditions. This proprietary screening platform led to our discovery of NSI-189.

We have developed and maintain what we believe is a strong portfolio of patents and patent applications that form the proprietary base for our research and development efforts. We own or exclusively license over 110 U.S. and foreign issued patents and over 40 U.S. and foreign patent applications in the field of regenerative medicine, related to our stem cell technologies as well as our small molecule compounds.

We believe our technology base, in combination with our expertise, and collaborative projects with major research institutions, could facilitate the development and commercialization of products for use in the treatment of a wide array of central nervous system disorders including neurodegenerative conditions and regenerative repair of acute disease.

There can be no assurances that we will ultimately produce any viable products or processes or that our screen platform will lead to the discovery of any additional product candidates. Even if we are able to produce a commercially viable product, there are strong competitors in this field and our products may not be able to successfully compete against them.

All of our research efforts to date are at the pre-clinical or clinical stage of development. We are focused on leveraging our key assets, including our intellectual property, proprietary technology, scientific team and facilities, to advance our technologies and clinical programs. In addition, we are pursuing strategic collaborations with members of academia and industry to further advance and discover additional product candidates.

Recent Developments

Business Highlights

In January 2016, we announced an initiative to pursue collaborations for our stem cell therapy programs in order to utilize additional expertise, expedite clinical and regulatory pathways and secure alternative funding.

In February 2016, we strengthened our management team with the appointment of Richard Daly as our President and Chief Executive Officer.

In May 2016, we completed a public offering of our securities which resulted in gross proceeds of $8.0 million and net proceeds of approximately $7,420,000.

Clinical Highlights

In March 2016, we commenced our NSI-189 Phase 2 clinical trial for the treatment of Major Depressive Disorder (MDD).

Small Molecule Pharmaceutical Compounds Clinical Development

Lead asset, NSI-189 Phase 2 clinical trial for the treatment of MDD.

In March 2016, we commenced our NSI-189 Phase 2 clinical trial for the treatment of MDD. The double-blind, randomized, placebo-controlled, 220 subject study is expected to enroll the first subject in the second quarter of 2016.

Stem Cells

Cell Therapy Platform Clinical Development

In January 2016, Dr. Karl Johe, Founder and Chief Scientific Officer, presented at the Phacilitate Cell & Gene Therapy World Conference. He concluded that the collective trial data analysis showed the cells consistently demonstrated biological activity in all three program indications: Amyotrophic Lateral Sclerosis or ALS, chronic spinal cord injury (cSCI), and motor deficits due to ischemic stroke.

NSI-566 Phase 1 safety trial for the treatment of cSCI

In January 2016, we reported preliminary six-month follow-up Phase 1 safety data on all four subjects. The stem cell treatment demonstrated feasibility and safety. 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. This study was completed with the collaboration of the UCSD School of Medicine, supported by the UCSD Sanford Stem Cell Clinical Center.

NSI-566 Phase 1 and 2 safety trials for the treatment of ALS

In September 2015, nine-month Phase 2 and combined Phase 1 and Phase 2 data on the NSI-566 trial in ALS were presented at the American Neurological Association Annual Meeting by the 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. In January 2016, we announced that we are in discussions with various governmental, State and non-profit organizations regarding funding grants for the next trial; the initiation of the trial will be dependent upon significant funding from such sources.

NSI-566 Phase 1 safety trial for the treatment of motor deficits in stroke

We completed dosing the third planned cohort in a Phase 1 clinical trial at BaYi Brain Hospital in Beijing. The trial is being conducted by Neuralstem China, at BaYi Brain Hospital in Beijing, China.

Financial Condition

Our Cash and Cash Equivalent balances of approximately $7.6 million as of March 31, 2016 are only sufficient to fund operations through June 2016. We will require additional capital to continue to develop our pre-clinical and clinical development operations. We cannot assure you that we will be able to secure additional financing or that the expected income will materialize. Several factors will affect our ability to raise additional funding, including, but not limited to market conditions, interest rates and, more specifically, our progress in our exploratory, preclinical and future clinical development programs.

On May 06, 2016, we closed a public offering of 20,000,000 shares of common stock and 20,000,000 common stock purchase warrants at a public offering price of $0.40 per each share and common stock purchase warrant. We received aggregate gross proceeds of $8.0 million and net proceeds of approximately $7,420,000 from the offering. The warrants allow the holder to purchase one share of common stock, have an exercise price of $0.40 per share and a term of 5 years. This offering was made pursuant to our shelf registration statement that was declared effective by the SEC on June 19, 2014 (Registration No. 333-196567).

The public offering in May 2016 has provided us with sufficient funds to finance operations at least through December 31, 2016.

Pre-Clinical and Clinical Programs and Development

In January 2016, we announced a strategic refocusing to concentrate our resources on the NSI-189 small molecule program. As part of this refocusing, we announced that we will seek external funding to defray all, or substantially all, of the costs associated with the NSI-566 stem cell therapy program. We cannot say when, if ever, we will be able to achieve this goal.

We have devoted substantially all our efforts to the pre-clinical and clinical development of our small molecule compounds and our stem cell therapeutics. Below is a description of our most advanced clinical programs, their intended indication, current stage of development and our expected future development plans:

[[Image Removed]]

Status*

(1) Phase 2 MDD clinical trial results are expected to be provided during 2H17

(2) Second Indication to be determined in 2Q16 at which time we will provide an update.

(3) Ongoing preclinical studies in NSI-189 and other undisclosed compounds. Multiple NSI-189 proof of principal studies and publications to be submitted in 2016.

(4) Active efforts to pursue partnerships or alternative funding such as through grants for NSI-566 (stem cell).

NSI - 189 (small molecule)

Major Depressive Disorder (MDD)

Major depressive disorder, or MDD (also known as recurrent depressive disorder, clinical depression, major depression, unipolar depression, or unipolar disorder), is a mental disorder characterized by episodes of all-encompassing low mood accompanied by low self-esteem and loss of interest or pleasure in normally enjoyable activities. MDD affects approximately 14.8 million American adults, or about 6.7 percent of the U.S. population age 18 and older in a given year. Additionally, the incidence of first line therapy failure creates a robust market for branded molecules in second/third line therapy. These factors combine to create a significant opportunity for a differentiated therapeutic agent.

NSI-189 is being developed for the treatment of major depressive disorder and other psychiatric and/or cognitive impairment indications associated with hippocampal atrophy. NSI-189 is the lead compound in our neurogenic small molecule drug platform. We believe that NSI-189 may provide an effective treatment for patients suffering from MDD by promoting neurogenesis.

Pre-Clinical Development

The inhibition of adult hippocampal neurogenesis has been implicated in a number of diseases that affect cognition and/or emotion such as major depressive disorder. As part of our research, we focused on compounds that were shown to enhance the baseline level of neurogenesis in normal healthy young mice. We believe that by enhancing baseline neurogenesis and accordingly, increasing hippocampal neurogenesis, we can decrease the effects of central nervous system or CNS diseases. Additionally, we believe that a compound that stimulates in vitro neurogenesis, enhances in vivo neurogenesis, increases hippocampal volume, and exerts anti-depressive effects on animals will be well suited for treating major depressive disorder. During our pre-clinical research, we identified NSI-189 as seeming to stimulate all four activities. Pre-clinical testing of this compound at multiple doses showed antidepressant activity at 10, 30, and 100mg/kg doses with rapid bioavailability in the brain. Histology analysis of the mouse brains suggested a bell-shaped dose-response curve, 10mg/kg and 30mg/kg being optimal for pharmacologically active concentrations and with higher doses not necessarily yielding larger biological effects.

Clinical Development - MDD

Phase 1a

In February 2011, we commenced a Phase 1 clinical trial (Phase 1a portion), NSI-189, at California Clinical Trials, LLC, in Glendale, California. The purpose of the Phase 1a portion of the trial was to evaluate the safety of the drug in healthy volunteers. The Phase 1a portion tested a single oral administration of NSI-189 in 24 healthy volunteers and was completed in October of 2011. The Phase 1a study showed that NSI-189 had demonstrated no gender difference in exposure profiles and no difference in drug exposure (Area Under the Curve (AUC) and half-life (t1/2)) between fasted and fed states. It also showed attractive pharmaceutical properties such as good solubility, high permeability, single crystalline polymorph with optimized salt form.

Phase 1b

In December of 2011, we received authorization from the FDA to commence the Phase 1b randomized, dose-escalating, placebo controlled clinical trial for the treatment of MDD. The purpose of the Phase 1b portion of the clinical trial was to determine the drug safety and tolerability in three dosages in diagnosed MDD patients. The Phase 1b portion consisted of subjects with MDD receiving daily doses for 28 consecutive days with an eight-week observation period. The trial was completed in November 2013 and met its primary endpoints of safety and tolerability and showed a promising reduction in depressive and cognitive symptoms across the secondary, exploratory endpoints.

In our Phase 1b study, tolerability and efficacy of NSI-189, a benzylpiperizine-aminiopyridine neurogenic compound for treating MDD were examined. This was a double-blind, randomized, placebo-controlled, multiple-dose study with three cohorts. The first cohort received 40 mg QD (n=6) or placebo (n=2), the second cohort 40 mg BID (n=6) or placebo (n=2), and the third cohort 40 mg TID (n=6) or placebo (n=2). Twenty-four subjects with MDD were recruited, with the diagnosis and severity confirmed through remote interviews. Eligible patients received NSI-189 or placebo for 28 days in an inpatient setting with assessments for safety, pharmacokinetics (PK), pharmacodynamics (PD), and efficacy. Outpatient follow-up visits were conducted until Day 84 ( 3). In this study, NSI-189 was relatively well tolerated at all doses, and no serious adverse effects. NSI-189 AUC increased in a dose-related and nearly proportional manner across the 3 cohorts with a half-life of 17-20 hours. In the Phase 1b study, the exploratory clinical efficacy measurements, including Symptoms of Depression Questionnaire (SDQ), Montgomery-Asberg Depression Scale (MADRS), Clinical Global Impressions - Improvement (CGI-I), and The Massachusetts General Hospital (MGH) Cognitive and Physical Functioning Questionnaire (CPFQ), showed a promising reduction in depressive and cognitive symptoms across all measures for NSI-189, with significant improvement in the SDQ and CPFQ, and a medium to large effect size for all measures. These improvements persisted during the follow-up phase. NSI-189 showed potential as a treatment for MDD despite the small sample size of each cohort.

Phase 2

In March 2016, we commenced our NSI-189 Phase 2 clinical trial for the treatment of MDD. This study is a double-blind, placebo-controlled study of NSI-189 among out-patients with major depressive disorder and will consist of a screening period of 14-28 days and a randomized treatment. Approximately 220 subjects who meet eligibility during the screening period will be randomized to initiate a 12-week, double-blind treatment with NSI-189 80mg/day (provided as 40 mg BID), NSI-189 40 mg/day QD, or placebo. We have contracted with 12 sites within the US who have the track record of enrolling high quality MDD subjects. The primary endpoint will be Montgomery-Asberg Depression Rating Scale (MADRS). The secondary endpoints will consist of: Symptoms of Depression Questionnaire (SDQ), The Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire (MGH CPFQ), 17-item Hamilton Rating Scale for Depression (HAMD17), Clinical Global Impressions - Severity and Improvement (CGI-S, CGI-I), Cogstate Brief Battery, and Cogscreen Battery. Other pre-specified outcome measures will include Blood Diagnostics Panel of major depressive disorder as a biomarker and Massachusetts General Hospital Sexual Functioning Inventory (MGH SFI) as a safety endpoint. This study is powered to achieve 80% confidence level with two-sided statistical significance value (p) of 0.05 or less while assuming Cohen's effect size (d) of 0.5. We believe this study could serve as one of the two registration studies required for marketing approval by the US FDA. The results are expected in the second half of 2017. The study Principal Investigator will be Maurizio Fava, M.D. Slater Family Professor of Psychiatry at Harvard Medical School, Massachusetts General Hospital. For information on the trial please visit https://clinicaltrials.gov/show/NCT02695472.

NSI - 566 (Stem Cells)

Amyotrophic Lateral Sclerosis (ALS)

Amyotrophic lateral sclerosis, or ALS, is a disease of the nerve cells in the brain and spinal cord that control voluntary muscle movement. Approximately 6,400 people in the U.S. are diagnosed with ALS each year. The incidence of ALS is two per 100,000 people, and it is estimated that more than 20,000 Americans may be living with ALS at any given time. In ALS, nerve cells (neurons) waste away or die, and can no longer send messages to muscles. This eventually leads to muscle weakening, twitching, and an inability to move the arms, legs, and body. The condition slowly gets worse. When the muscles in the chest area stop working, it becomes hard or impossible to breathe. NSI-566 is under development as a potential treatment for ALS by providing cells designed to nurture and protect the patients' remaining motor neurons; and possibly repair some motor neurons which have not yet died but which are diseased. We have received orphan designation by the FDA for NSI-566 in ALS.

Clinical Development - ALS

Phase 1

In January 2010, we commenced the Phase 1 trial of NSI-566 in ALS at Emory University in Atlanta Georgia. The purpose of the Phase 1 trial was to evaluate the safety and transplantation technique of our proposed treatment and procedure. The dosing of patients in the Phase 1 trial, as designed, was completed in August of 2012.

Phase 2

We commenced our Phase 2 clinical trial for ALS in September of 2013. The transplantation portion of the trial was completed in August of 2014 and the observation period of six months after the last surgery concluded in January 2015. The Phase 2 ALS clinical trial met the primary safety endpoints and established what we believe to be the maximum safe tolerated dose of 16 million cells delivered in 40 injections. In September 2015, nine-month Phase 2 and combined Phase 1 and Phase 2 data on the NSI-566 trial in amyotrophic lateral sclerosis was presented at the American Neurological Association 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. We are in discussions with the FDA regarding a larger registration directed, controlled trial.

In January 2016, we announced that we were in discussions with various governmental, state and non-profit organizations regarding funding grants for a registration directed, controlled trial and that initiation of such a trial would, in part, be dependent upon significant funding from such sources. To date, substantially all of the clinical costs of our ALS studies have been funded by such grants.

Chronic Spinal Cord Injury

A spinal cord injury, or SCI, generally refers to any injury to the spinal cord that is caused by trauma instead of disease although in some cases, it can be the result of diseases. It is estimated that there are 12,500 new cases of SCI per year and that at any given time, it is estimated around 276,000 US spinal cord patients in 2014.people in the United States that are living with SCI. Chronic spinal cord injury refers to the time after the initial hospitalization. SCI's are most often traumatic, caused by lateral bending, dislocation, rotation, axial loading, and hyperflexion or hyperextension of the cord or cauda equina. Motor vehicle accidents are the most common cause of SCIs, while other causes include falls, work-related accidents, sports injuries, and penetrations such as stab or gunshot wounds. In certain instances, SCIs can also be of a non-traumatic origin, as in the case of cancer, infection, intervertebral disc disease, vertebral injury and spinal cord vascular disease. We believe that NSI-566 may provide an effective treatment for chronic spinal cord injury by "bridging the gap" in the spinal cord circuitry created in traumatic spinal cord injury and providing new cells to help transmit the signal from the brain to points at or below the point of injury.

Clinical Development - Chronic Spinal Cord Injury

Phase 1

During the first quarter of 2013, we received authorization from the FDA to commence our proposed Phase 1 clinical trial to treat chronic spinal cord injury. The entire trial took place at The University of California, San Diego. The trial commenced during the third quarter of 2014 and the first subject was treated in October 2014. The study enrolled four AIS A thoracic-spinal cord injury subjects (motor and sensory complete), one-to-two years post-injury at the time of stem cell treatment. In January 2016 at the Phacilitate Cell & Gene Therapy World Conference, we reported six-month follow-up data on all four subjects. 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 subjects treated. All patients will be followed for five years. To date, substantially all of the clinical costs of this study have been funded by grants arranged through the University of California, San Diego.

Motor Deficits Due to Ischemic Stroke

Ischemic strokes, the most common type of stroke, occur as a result of an obstruction within a blood vessel supplying blood to the brain. Approximately 15 million people worldwide suffer from stroke of which it is estimated that 87% are ischemic stroke. Post-stroke motor deficits include paralysis in arms and legs and can be permanent. We believe that NSI-566 may provide an effective treatment for restoring motor deficits resulting from ischemic stroke by both creating new circuitry in the area of injury and through repairing and nurturing diseased cells to improve function in patients.

Clinical Development - Motor Deficit Due to Ischemic Stroke

Phase 1

In the fourth quarter of 2013 we commenced a human clinical trial for treatment of motor deficits due to ischemic stroke. The trial is being conducted by Neuralstem China, at BaYi Brain Hospital in Beijing, China utilizing NSI-566. The trial authorization encompasses a Phase 1 clinical trial design and will test the safety of direct injections of NSI-566 into the brain. The Phase 1 trial is a safety trial designed to evaluate the maximum safe tolerated dose. We have completed dosing all three planned cohorts for a total of nine subjects, three subjects in each cohort. To date, we have funded substantially all of the costs associated with the Ischemic Stroke program.

Our Technologies

Stem Cells

Our technology enables the isolation and large-scale expansion of regionally specific, human neural stem cells from all areas of the developing human brain and spinal cord, thus enabling the generation of physiologically relevant human neurons of all types. We believe that our stem cell technology will assist the body in producing new cells to replace malfunctioning or dead cells as a way to treat disease and injury. Many significant and currently untreatable human diseases arise from the loss or malfunction of specific cell types in the body. Our focus is the development of effective methods to generate replacement cells from neural stem cells. We believe that replacing damaged, malfunctioning or dead neural cells with fully functional ones may be a useful therapeutic strategy in treating many diseases and conditions of the central nervous system. We own or exclusively license over 50 U.S. and foreign issued patents and over 30 U.S. and foreign patent applications related to our stem cell technologies.

Small Molecule Pharmaceutical Compounds

Utilizing our proprietary stem cell derived, screening capability, we have developed and patented a series of small molecule compounds. We believe the low molecular weight organic compounds can efficiently cross the blood/brain barrier. In mice, research indicated that the small molecule compounds both stimulate neurogenesis of the hippocampus and increase its volume. Our collaborators at Massachusetts General Hospital have presented the human data from the MDD trial which showed clinically meaningful and statistically significant improvement in depressive and cognitive scales. We believe the small molecule compounds may assist promoting synaptogenesis or neurogenesis in the human hippocampus documented in indications such as MDD.

. . .

  Add CUR to Portfolio     Set Alert         Email to a Friend  
Get SEC Filings for Another Symbol: Symbol Lookup
Quotes & Info for CUR - All Recent SEC Filings
Copyright © 2017 Yahoo! Inc. All rights reserved. Privacy Policy - Terms of Service
SEC Filing data and information provided by EDGAR Online, Inc. (1-800-416-6651). All information provided "as is" for informational purposes only, not intended for trading purposes or advice. Neither Yahoo! nor any of independent providers is liable for any informational errors, incompleteness, or delays, or for any actions taken in reliance on information contained herein. By accessing the Yahoo! site, you agree not to redistribute the information found therein.