Cell & Gene Therapy Investor Day April 17, 2018 1 Safe Harbor - PowerPoint PPT Presentation

Cell & Gene Therapy Investor Day April 17, 2018 1

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. Although we believe that we have a reasonable basis for each forward-looking statement contained in this presentation, we caution you that forward-looking statements are not guarantees of future performance and that our actual results of operations, financial condition and liquidity, and the development of the industry in which we operate may differ materially from the forward-looking statements contained in this presentation as a result of, among other factors, the factors referenced in the “Risk Factors” section of our Annual Report on Form 10-K for the year ended December 31, 2017 filed with the Securities and Exchange Commission on April 2, 2018, Form 10-K for the period ended September 30, 2017, and in other reports filed with the SEC. In addition, even if our results of operations, financial condition and liquidity, and the development of the industry in which we operate are consistent with the forward- looking statements contained in this presentation, they may not be predictive of results or developments in future periods. Any forward- looking statements that we make in this presentation speak only as of the date of such statement, and we undertake no obligation to update such statements to reflect events or circumstances after the date of this presentation, except as required bylaw. 2

Highlights: Lead Programs NSI-566: ALS, c-Spinal Cord Injury, c-Stroke – Neural stem cell therapy – Targeting paralysis with biological activity in across 3indications – Functional restorative effects shown in primate model • Rosenzweig et al., Nat Med. 2018 Feb 26 – Favorable regulatory environment: US, Japan, China – Partnering efforts underway for continuingdevelopment NSI-189: MDD – Novel neurogenic small molecule approach – Positive, randomized placebo-controlled Phase 1b in MDD – Phase II Exploratory Study in Major Depressive Disorder(MDD) • Key metrics: – Montgomery-Asberg Depression Rating Scale (MADRS) primary endpoint – Secondary endpoints: – Physician and Patient reported – Cognition • Long-term durability data anticipated in 1H 2018 • Strong IP position through 2035 3

NSI-566: Targeting Paralysis – Program Overviews Chronic Spinal CordInjury ALS Ischemic Stroke MARKET CONSIDERATIONS MARKET CONSIDERATIONS MARKET CONSIDERATIONS - Orphan condition - 1.8 million with paralysis due to stroke in - 1.5 million with paralysis due to spinal - NSI-566 granted orphan status by FDA the US* cord injury in the US* - 17,000 new injuries peryear - No treatment to reverse paralysis - Rapid accelerating disease/poor - No treatment options prognosis - Majority of patients not aware of the stroke until well after the event - Limited treatment options Opportunity for RMAT designation (21 st - Current therapies require access within - PROGRAM OVERVIEW Century Cures Act) hours of event - USCD funded - Phase I cSCI Group A 4 Thoracic PROGRAM OVERVIEW AISA-A complete spinal cord injury PROGRAM OVERVIEW - Phase 1 open-label, non-GCP dose- - Transplantation into spinal cord of ALS - Phase I cSCI Group B 4 Cervical AISA- A complete spinal cord injury – First patients escalation, feasibility & safety study for the treatment of paralysis from subject enrolled - Phase 1 & Phase 2a dose-escalation, chronic motorstroke safety studies completed - Patient profile: Stable patients 3-24 KEYTAKEAWAYS - 30 subjects with 2-6 years ofsafety months post-event with stable hemi- - Stem cell treatment was safe andwell- Data paralysis tolerated - Additional matched pairs analysis - N = 9 - No serious adverse events with historic data set (PROACT) Follow up – 1 year post-surgery - Self-reported ability to contract some insightful - muscles below the level of injury in - Secondary endpoints include improved one of the four subjects treated was KEYTAKEAWAYS recovery confirmed via clinical and - Procedure and treatment iswell- KEYTAKEAWAYS electrophysiological follow-up tolerated - Treatment well-tolerated examinations - Long-term cell graft survival (2.5years) - Innovative transplantation (platform/brain proven at autopsy injectioncannula) system developed *Prevalence and Causes of Paralysis — United States, 2013. Armour, B.S. et al. (2016) Am J Public Health. 106: 1855-1857. 4

NSI-566 Shows Restorative Effects of Human Neural Stem Cell Grafts on the Primate Spinal Cord ▪ NSI-566 shown to have restorative function in primate paralysis model ▪ NSI-566 transplantation resulted in measurable improvement in forelimb function 5

NSI-566: a stable human neural stem cell line — allogeneic, off-the-shelf, stable, synaptic integration — to bridge, regenerate, repair, protect a b Graft Rosenzweig et al., Nat Med. 2018 Feb 26. doi: 10.1038/nm.4502 6

NSI-566: ALS Phase I & II: 2-Year Follow-Up vs Historical Data ALSFRS-R Ph1/2 PRO-ACT N Mean (SD) N Mean (SD) t-test 36·5 ± 5·4 38·1 ± 4·7 Baseline 21 1108 0·17 30·6 ± 6·5 32·5 ± 7·6 6 months 18 974 0·25 30·5 ± 9 28·3 ± 9·3 12 months 14 655 0·37 31·8 ± 8·1 24·6 ± 10·4 18 months 11 165 0·016 30·1 ± 8·6 24·0 ± 10·2 24 months 11 86 0·048 ALS/SURV Ph1/2 PRO-ACT N Median (IQR) N Median (IQR) Wilcoxon Baseline 21 38 (31,40) 1108 39 (35,42) 0·12 6 months 20 29·5 (23,35·5) 1012 33 (27,38) 0·11 12 months 18 26·5 (16,35) 792 26 (15,35) 0·82 18 months 17 27 (1·2yr,36) 351 1·4yr (0·8yr,24) 0·028 24 months 19 23 (1·2yr,33) 306 1·2yr (0·8yr,10) 0·0038 NSI-566 therapy as a treatment for ALS is safe. Additional analysis of the efficacy is helpful for future study design and it indicates efficacy on ALSFRS beginning at 18 months. 7

NSI-566: Chronic Stroke--Phase I Data at 12 Months Fugl-Meyer Motor Score Change from Baseline (+/- SEM) Meaningful Clinical Benefits: >10 points of improvement in Fugl-Meyer Motor Score Post Treatment (months, 0-12) NIH Stroke Scale Modified Rankin Scale Change from Baseline Change from Baseline (+/- SEM) (+/- SEM) Post Treatment (months, 0-12) Post Treatment (months, 0-12) NSI-566: Phase 1 open-label, non-GCP dose-escalation, feasibility & safety study for the treatment of paralysis from chronic motorstroke 8

Cell & Gene Therapy Investor Day April 17, 2018 9