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 15, 2015
NEOSTEM, INC.
(Exact Name of Registrant as Specified in Charter)
Delaware (State or Other Jurisdiction of Incorporation) | 001-33650 (Commission File Number) | 22-2343568 (IRS Employer Identification No.) |
420 Lexington Avenue, Suite 350, New York, New York 10170
(Address of Principal Executive Offices)(Zip Code)
(212) 584-4180
Registrant's 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):
o | Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425) |
o | Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12) |
o | Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b)) |
o | Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c)) |
Item 7.01 Regulation FD Disclosure.
On Monday, March 16, 2015, NeoStem, Inc., a Delaware corporation (the “Company” or “NeoStem”), issued a press release announcing that updated efficacy and safety results from the one-year follow-up for its Phase 2 PreSERVE AMI study and additional analyses of certain functional tests were presented at ACC.15, the American College of Cardiology’s 64th Annual Scientific Session and Expo, in San Diego, California. A copy of the press release is attached hereto as Exhibit 99.1. The data as presented by Dr. Arshed A. Quyyumi, the Lead Principal Investigator of our PreSERVE AMI Study, at the ACC Expo, is also attached hereto as Exhibit 99.2.
Additionally, NeoStem intends, from time to time, to present and/or distribute to the investment community and utilize at various industry and other conferences a slide presentation. The slide presentation is accessible on NeoStem’s website at www.neostem.com and is attached hereto as Exhibit 99.3. NeoStem undertakes no obligation to update, supplement or amend the materials attached hereto as Exhibit 99.3.
In accordance with General Instruction B.2 of Form 8-K, the information in this Item 7.01 of this Current Report on Form 8-K, including Exhibits 99.1, 99.2 and 99.3, shall not be deemed “filed” for the 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 it be deemed incorporated by reference in any filing under the Exchange Act or the Securities Act of 1933, as amended, except as shall be expressly set forth by reference in such a filing.
Forward Looking Statements
This Current Report on Form 8-K, including Exhibits 99.1 and 99.3 hereto, contain “forward-looking” statements within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements are typically preceded by words such as “believes,” “expects,” “anticipates,” “intends,” “will,” “may,” “should,” or similar expressions, although some forward-looking statements are expressed differently. Forward-looking statements represent the Company's management's judgment regarding future events. Although the Company believes that the expectations reflected in such forward-looking statements are reasonable, the Company can give no assurance that such expectations will prove to be correct. All statement other than statements of historical fact included in the Current Report on Form 8-K are forward-looking statements. The Company cannot guarantee the accuracy of the forward-looking statements, and you should be aware that the Company's actual results could differ materially from those contained in the forward-looking statements due to a number of factors, including the statements under "Risk Factors" contained in the Company's reports filed with the Securities and Exchange Commission.
Item 9.01 Financial Statements and Exhibits
(d) Exhibits
Exhibit No. | Description |
99.1 | Press Release dated March 16, 2015* |
99.2 | Pre-SERVE AMI ACC Expo Slide Presentation* |
99.3 | Slide presentation of NeoStem, Inc. dated March 2015* |
*Exhibits 99.1, 99.2 and 99.3 are furnished as part of this Current Report on Form 8-K.
SIGNATURES
Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.
NEOSTEM, INC. | ||||
By: | /s/ Catherine M. Vaczy | |||
Name: | Catherine M. Vaczy, Esq. | |||
Title: | General Counsel | |||
Dated: March 16, 2015
Exhibit 99.1
NeoStem Announces PreSERVE AMI Clinical Trial One-Year Follow-Up Results
Results support previous observation of dose-dependent signals across multiple endpoints
New York, NY (March 16, 2015) - NeoStem, Inc. (NASDAQ:NBS), a biopharmaceutical company developing novel cell based personalized medicine therapies, announced today the presentation of updated efficacy and safety results from the one-year follow-up for its Phase 2 PreSERVE study and additional analyses of certain functional tests at ACC.15, the American College of Cardiology’s 64th Annual Scientific Session and Expo, in San Diego, California. The one-year follow-up results are defined as all data accumulated until the last patient enrolled completed 12 month follow-up. Thus, the results actually represent data from patients with a median follow-up of 18 months.
The PreSERVE study is NeoStem’s clinical trial evaluating NBS10 which is being developed to treat damaged heart muscle following an acute myocardial infarction. One-year follow-up safety data collected thus far supports the trial’s 6 month results presented at the American Heart Association’s Scientific Sessions in November 2014. The ACC presentation contained updated safety and exploratory efficacy data and additional analyses conducted on left ventricular ejection fraction (LVEF) data. Clinical Endpoint Committee adjudication of major adverse cardiac events (MACE) was performed on the 6 month data reported previously and was not performed for new events (occurring between 6 and 12 months). The next prescribed adjudication of MACE is currently planned at the end of patient follow-up. At 12-month follow-up, no meaningful safety or tolerance differences were observed between treatment and control groups. In this updated analysis, no additional deaths were reported in the treatment or control groups beyond those previously reported in the six month analysis. In addition, in post hoc subset analyses based on the number of cells patients received, serious adverse event (SAE) frequency continues to show numerical improvement at all cell doses when compared to control.
No additional SPECT data were collected at one year follow-up. As an exploratory measure of efficacy, PreSERVE looked at reduction of infarct size at six months. Patients receiving 20 million cells or more experienced a decrease in infarct size of 41% vs 24% for patients in the control group.
Based on the one-year follow-up results, the company and its scientific advisors believe that the study results suggest:
• | Intracoronary administration of autologous CD34+ cells appears safe and well-tolerated; |
• | A signal for a mortality benefit; and |
• | A signal for reduction in the frequency of serious adverse events (SAEs) in higher dose groups. |
“We believe that these data, when coupled with the six month data on MACE and LVEF that we previously reported, are encouraging and show the possibility that higher doses of CD34 cells may provide benefit to patients post-STEMI,” said Dr. Douglas Losordo, Chief Medical Officer of NeoStem. “Further consideration of these data, in consultation with our medical advisory board, should lead us to a determination of the next steps for the development of this program in the second half of 2015.”
“While small in number, we are encouraged by the fewer mortality events observed for treated patients versus control patients as of the date of this 12 month follow-up. In addition, we are very encouraged by the persistence of reduced serious adverse event rates and evidence for improved infarct healing and left ventricular function,” said Dr. Arshed A. Quyyumi, Professor of Medicine at Emory University and Lead Principal Investigator of the PreSERVE AMI study, who made the presentation at ACC.15. “In addition,
the failure of SPECT imaging to document changes at the 6 month interim analysis, despite signs of clinical benefit in multiple parameters, suggests that this technique is not applicable in this setting.”
These highlights should be read in conjunction with a full and complete copy of the data as contained in the ACC presentation, which data can be viewed by visiting the NeoStem website at www.Neostem.com/media/events/ and on the Securities and Exchange Commission website at www.sec.gov.
About NeoStem's Ischemic Repair Program
NeoStem is developing CD34 cell-based therapies to address damage to tissue caused by ischemia. Ischemia occurs when the supply of oxygenated blood in the body is restricted. The Company's Ischemic Repair Program seeks to reverse the damage caused by this restriction through the development and formation of new blood vessels. The Program's lead product candidate in this area is NBS10, a chemotactic hematopoietic stem cell product comprised of autologous bone marrow-derived CD34/CXCR4 cells selected to treat damaged heart muscle following AMI (severe heart attack). NBS10 is thought to work by increasing microvascular blood flow in the heart muscle via the development and formation of new blood vessels, thereby reversing the restriction of blood supply caused by a heart attack and rescuing at-risk cardiac tissue from eventual cell death.
About the PreSERVE AMI Clinical Trial
PreSERVE AMI is a randomized, double-blind, placebo-controlled clinical trial of intracoronary infusion of autologous CD34 cells in patients with left ventricular dysfunction post-ST elevation myocardial infarction (STEMI). The trial included 161 subjects at 60 sites in the United States, randomized 1:1 between treatment and placebo arms. Eligible patients presented with acute STEMI, had successful stenting of the infarct-related artery and had left ventricular dysfunction 4 days after AMI. Primary endpoints include occurrence of SAEs and MACE (defined as cardiovascular death, re-infarction, heart failure hospitalization, and coronary revascularization) through 3 year follow-up, and 6-month change in myocardial perfusion (RTSS) measured quantitatively by gated SPECT myocardial perfusion imaging. Secondary endpoints include cardiovascular magnetic imaging resonance (CMR) to measure left ventricular ejection fraction (LVEF), left ventricular end-systolic volume (LVESV), left ventricular end-systolic diameter (LVEDV). Infarct size (baseline and six months) was an exploratory endpoint.
About NeoStem, Inc.
NeoStem is a biopharmaceutical company pursuing the preservation and enhancement of human health globally through the development of novel cell based personalized medicine therapeutics that prevent, treat or cure disease. The Company is developing therapies based on three platform technologies (immune-oncology, ischemic repair and immunomodulation) with a lead, late-stage (Phase 3, 2 and 2, respectively) clinical program for each. The combination of a rich therapeutics pipeline and an externally recognized in-house center for cell therapy process development and manufacturing has created an organization with unique capabilities for accelerated and efficient product development. www.neostem.com
Forward-Looking Statements
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements reflect management's current expectations, as of the date of this press release, and involve certain risks and uncertainties. Forward-looking statements include statements herein with respect to the successful execution of the Company's business strategy, the Company's ability to develop and grow its business, the successful development of cellular therapies with respect to the Company's research and development and clinical evaluation efforts in connection with the Company's Targeted Immunotherapy Program, Ischemic Repair Program , Immune Modulation Program and other cell therapies, especially NBS10, the future of the regenerative medicine industry and the role of
stem cells and cellular therapy in that industry, and the performance and planned expansion of the Company's contract development and manufacturing business as well as its efforts to expand its capabilities into the cell therapy tools market. The Company's actual results could differ materially from those anticipated in these forward-looking statements as a result of various factors. Factors that could cause future results to materially differ from the recent results or those projected in forward-looking statements include the "Risk Factors" described in the Company's Annual Report on Form 10-K filed with the Securities and Exchange Commission ("SEC") on March 2, 2015, and in the Company's other periodic filings with the SEC. The Company's further development is highly dependent on future medical and research developments and market acceptance, which is outside of its control. While 6 month and 12 month data have been collected, those data are subject to ongoing analysis, and results reported at this time are preliminary. There can be no assurance that further analysis may not reveal negative, or less promising, results.
CONTACT: NeoStem, Inc.
Eric Powers
Manager of Communications and Marketing
Phone: +1-212-584-4173
Email: epowers@neostem.com
PreSERVE-AMI: A Randomized, Double-Blind, Placebo Controlled Clinical Trial of Intracoronary Infusion of Autologous CD34+ Cells (NBS10) in Patients with Left Ventricular Dysfunction Post STEMI Arshed Quyyumi1, Dean Kereiakes2, David Shavelle3, Timothy Henry4, Ali Denktas5, Ahmed Abdel-Latif6, Catalin Toma7, Gregory Barsness8, Stephen Frohwein9, Richard Schatz10, Martin Cohen11, Charles Davidson12, Nabil Dib13, Marc Klapholz14, Gary Schaer15, Alejandro Vasquez16, Andrew Pecora17, Thomas Moss17, Pamela Hyde17, Anna Maria Kanakaraj17, Le Dich17, Vitaly Druker17, Candice Junge17, Robert Preti17, Douglas Losordo17 1Emory Clinical Cardiovascular Research Institute, Cardiology Division, Emory University School of Medicine, Atlanta, GA 2The Christ Hospital Heart and Vascular Center, Cincinnati, OH 3University of Southern California, Los Angeles, CA 4Cedars-Sinai Heart Institute, Los Angeles, CA 5Baylor College of Medicine/Michael E Debakey VA Medical Center, Houston, TX 6University of Kentucky, Lexington, KY 7University of Pittsburgh Medical Center, Pittsburgh, PA 8University of Pittsburgh Medical Center, Pittsburgh, PA 9Emory St. Josephs Hospital, Atlanta, GA 10Scripps Health, La Jolla, CA 11Westchester Medical Center, Valhalla, NY 12Bluhm Cardiovascular Institute Northwestern Memorial Hospital, Chicago, IL 13Heart Sciences Center, Gilbert, AZ 14Rutgers University, New Jersey Medical School, Newark, NJ 15Rush University Medical Center, Chicago, IL 16Huntsville Hospital, Huntsville, AL 17Neostem Inc., New York, NY www.clinicaltrials.gov Identifier: NCT01495364
The PreSERVE AMI Study: Funding Sources & Disclosures Conflict of Interest Disclosures • Quyyumi: NeoStem Advisory Board member Funding Source • Study funded by NeoStem, Inc. 2
Background • Recent meta-analysis of unselected bone marrow mononuclear cell therapy after STEMI suggest that there may be no impact on LVEF changes and MACE1 • Clinical studies evaluating the therapeutic potential of cells selected for CD34 expression have demonstrated a consistent favorable impact on outcomes2-5 • Phase 1 study of autologous CD34+ cells (NBS10) provided initial evidence of feasibility and safety and suggested a threshold dose of 10 million CD34 cells for bioactivity6 3 1. Gyongyosi M et al. Circ Res 2015: CIRCRESAHA.114.304346. 2. Vrtovec B et al Circ Res. 2013 Jan 4;112(1):165-73. 3. Lezaic L et al. J Card Fail 2015; 21: 145-152. 3. Losordo DW et al. Circ Res. 2011 Aug 5;109(4):428-36. 4. Losordo DW et al. Circ Cardiovasc Interv. 2012 Dec;5(6):821-30.5. Poglajen G et al. Circ Cardiovasc Interv. 2014 Aug;7(4):552-9. 6. Quyyumi AA et al; Am Heart J. 2011 Jan;161(1):98-105.
PreSERVE Study Design 4 DESIGN Randomized (1:1), Phase 2, double blind, placebo controlled trial in patients with acute STEMI and low LVEF PRIMARY ENDPOINTS • Incidence rates of SAEs and MACE • Change in myocardial perfusion (RTSS) measured quantitatively by gated SPECT MPI at 6 months KEY SECONDARY ENDPOINTS LVEF – change from baseline and preservation at 6 months KEY EXPLORATORY ENDPOINTS Change from baseline in infarct size; hospitalization STUDY SIZE 161 patients, 60 centers in United States TREATMENT Single dose CD34+ cells via infarct related artery with minimum dose for release ≥10M (million) ±20% CONTROL Matching infusion with placebo
PreSERVE: Eligibility INCLUSION CRITERIA • Acute ST elevation myocardial infarction. • Stenting within 3 days of chest pain • LVEF ≤48% by CMR or ≤45% by SPECT after 4 days • Wall motion abnormality associated with the target lesion • NYHA heart failure class I, II or III. EXCLUSION CRITERIA • STEMI > 4 days before stenting. • Cardiogenic shock • Severe aortic stenosis. • Re-occlusion of the infarct related artery (IRA) prior to the infusion. • Planned revascularization during the next 6 months. 5
PreSERVE Sites 6 Investigator Name Site Arshed Quyyumi Emory Alejandro Vasquez Heart Center Research Dean Kereiakes The Christ Hospital Marc Klapholz UMDNJ-Newark Kenichi Fujise Univ. Texas - Galveston Nandish Thukral Methodist San Antonio Gary Schaer Rush University Medical Center Robert Iwaoka Presbyterian CVI Research Ahmed Abdel-Latif U. of Kentucky, Gill Heart Institute Vijaykumar Kasi Orlando Health Vernon Anderson U. of Texas HSC - Houston Roger Gammon Austin Heart PLLC Stephen Frohwein St Joseph's Research Institute Tim Henry Minneapolis Heart Richard Schatz Scripps-La Jolla Tanvir Bajwa Aurora Health Nabil Dib Mercy Gilbert Medical Center Catalin Toma UPMC Presbyterian Michael Tamberella CaroMont Heart Pradyumna Tummala Northeast Georgia Heart Center Charles Davidson Northwestern University Gregory Barsness Mayo Clinic - Minnesota Virender Sethi Hackensack University Tarek Helmy University of Cincinnati David Shavelle Keck School of Medicine-USC Fadi El-Ahdab CV Group Central Lynchburg Martin Cohen Westchester Medical Center Gerald Koenig Henry Ford Carl Pepine University of Florida-Gainesville Vincent Pompili Ohio State University Robert Frankel Maimonides Medical Center- Brooklyn Mark Vesely University of Maryland Investigator Name Site Theodore Schreiber Detroit Receiving/Harper Hospital Mazen Abu-Fadel U. of Oklahoma HSC Emerson Perin Texas Heart Institute David Fortuin Mayo Clinic - Arizona Luis Gruberg Stony Brook University Hospital Charles Lambert Florida Hospital Massoud Leesar University of Alabama- Birmingham Joseph Wu Stanford University Howard Eisen Drexel University Lawrence Barr Advocate Health Elm Hurst Buddhadeb Dawn Kansas U. Medical Center Amit Patel University of Utah Christopher Gange MetroWest Medical Center Paul Gordon Miriam Hospital Richard Rothschild St. John's Regional Hospital Peter Kerwin Advocate Health Oakbrook Hitinder Gurm U. Michigan Michael Imburgia Louisville Cardiology Kimberly Skelding Geisinger Medical Center Vijay Iyer Buffalo General Hospital Frank McGrew Stern Cardiovascular Foundation/Baptist Hospital Zachary Hodes St. Vincent Medical Group Augusto Prichard Medstar Heart Institute Michael Ragosta UVA Health System Cardiology Research Barry Bertolet Cardiology Associates Research LLC Majid Qazi Detroit Clinical Reseach Center PC Paul Huang Swedish Medical Center
PreSERVE: Study Protocol 7 1. Patient presents with chest pain + STEMI Day 1 2. Stenting and usual medical Rx Day 1 - 3 5. Patient Bone Marrow Harvested Day 4-9 6. CD34+CXCR4 + immunomagnetic separation Day 5-10 Day 6-11 7. Intracoronary injection: CD34+ Cells/Placebo 3. Enrolled if EF ≤ 48% CMR Day 4 8. MACE and Cardiac function measures 6 Months 4. Patient randomized to Treatment or Control •SAE, MACE •RTSS •LVEF 9. MACE •Mortality •AMI •Admission for CHF •Vascular events 12, 18, 24, 36 Months Day 4 Copyright ©2009 BMJ Publishing Group Ltd. Mollmann, H. et al. Heart 2009;95:508-514 Figure 2 Application of stem cells into infarcted tissue by intracoronary transplantation. Cells are delivered over the lumen of an inflated over-the-wire balloon catheter placed in the reopened infarct artery. MI, infarcted myocardium.
PreSERVE-AMI Screened (N = 281) • Patients with STEMI and successful stent placement • LVEF ≤ 48% by CMR or ≤ 45% by SPECT measured ≥ 4 days after stent Underwent BM Harvest (n = 96) CD34+ cells infusion (n = 78) CD34+ cells (NBS10; n = 100) Underwent BM harvest (n = 88) Placebo infusion (n = 83) Placebo (n= 95) Allocation Bone Marrow Harvest and Infusion Randomized (n=195) Enrollment 8 Follow-up Efficacy and Safety Analysis Intent-to-Treat (n=100) Modified Intent-to-Treat (n=78) Per Protocol (n=75) Intent-to-Treat (n=95) Modified Intent-to-Treat (n=83) Per Protocol (n=81) Screen Failure (n = 86) Did not undergo BM harvest (n=11) • Death (n=2); • Withdrawal (n=6); • Screen Failure (n=2); • AE (n=1) Post-harvest, no infusion (n=23) • Cell product did not meet release criteria (n=16); • AE (n=6); • Withdrawal (n=1)
Baseline Characteristics 9 Treated NBS10 (N=78) Placebo (N=83) P-value* Demographics Age; mean ± SD 57.1 ± 10.1 56.4 ± 10.1 0.65 Female; n (%) 12 (15%) 17 (20%) 0.4 Race; White, n (%) 56 (72%) 62 (75%) 0.87 CV Risk Factors Hypertension (%) 53 (68%) 56 (67%) 0.80 Diabetes (%) 27 (35%) 19 (23%) 0.1 Hyperlipidemia (%) 13 (17%) 17 (20%) 0.82 NYHA Class*; mean ± SD 1.8 ± 0.6 1.9 ± 0.7 0.59 CV Medical History Prior CABG; n(%) 2 (3%) 2 (2%) 0.95 Prior PCI; n(%) 15 (19%) 15 (18%) 0.85 Prior CHF; n(%) 11 (14%) 11 (13%) 0.88 Prior MI; n(%) 13 (17%) 15 (18%) 0.34 Index AMI/PCI Infarct size (grams); mean ± SD 33.8 ± 17.4 38.6 ± 19.5 0.16 Pre-discharge LVEF (%); mean ± SD 34.3 ± 7.3 34.1 ± 8.4 0.90 LVEDV index; mean ± SD 98.0 ± 25.6 91.9 ± 20.8 0.12 LVESV index; mean ± SD 61.2 ± 23.6 58.5 ± 19.9 0.46 Time from symptoms to stent (min); mean ± SD 931 ± 1277 569 ± 864 0.041 Time from stent to infusion (days); mean ± SD 9.3 ± 1.23 9.4 ± 1.43 0.60 *P-values for quantitative characteristics are based on a t-test. P-values for categorical characteristics are based on a Chi-square test.
PreSERVE Status • One year follow-up completed for all subjects in December 2014 • Median follow-up time: 18 months • Primary endpoints and key secondary endpoints after all subjects completed 6 months follow-up (one year median follow-up) presented at AHA 10
Preserve: Cardiac Death 11 P ro b abili ty o f sur v iv a l MEDIAN FOLLOW-UP: 18 MONTHS No treatment group deaths to date* mITT Population **P-value calculated using a z-test. ‡P-value calculated using log rank test * As of March 13, 2015 0% 1% 2% 3% 4% 5% 3.6% (N=3) 0% (N=0) Treatment N=78 Control N=83 P=0.04** Days P=0.055‡ Control Treatment 200 400 600 800 1000 1200
PreSERVE: Major Adverse Cardiovascular Events 12 MACE= Death, MI, CHF Hospitalization, Revascularization Ctrl N=83 <14M N=47 >14M N=31 >20M N=15 Parameter Parameter Estimate (SE)* P-Value‡ Infused CD34+ Dose -1.11E-7 (5.769E-8) 0.055 ‡Multiple regression model with MACE modeled as a function of time from pain to stent and infused CD34+ cell dose. Influence of dose corrected for time to stent 14% 14% 17% 10% 7% Tmt N=78 MEDIAN FOLLOW-UP: 12 MONTHS CD34 dose-dependent reduction in MACE Incidence (mITT)
PreSERVE: Serious Adverse Events 1.2 0.9 1.1 0.6 0.7 0 0.2 0.4 0.6 0.8 1 1.2 1.4 Control <14M >14M >20M P ro p o rt io n o f e v e n ts (n o rma li z e d b y t o ta l s u b jects ) Tmt SAE frequency normalized by total subjects per group Control (N=83) Treatment (N=78) <14M (N=47) >14M (N=31) >20M (N=15) Any SAE 99 71 53 18 11 P=0.059 *P values based on two sample t-test using Satterthwaite method. P=NS for tmt, <14M and >20M vs control. SAE = any untoward medical occurrence that results in death or is life-threatening MEDIAN FOLLOW-UP: 18 MONTHS (mITT)
PreSERVE: Hospitalization during Follow- up 14 160.5 165.6 164.4 167.5 167.6 Control N=83 <14M N=46 >14M N=29 >20M N=14 P = 0.04* P = 0.04* *P values based on two sample t- test using Satterthwaite method Tmt N=75 T im e ( d a y s ) A li v e an d O u t o f Hos p ita l Parameter Parameter Estimate (SE)* P-Value* CD34+ Cell Dose 1.6E-7(8.0E-7) 0.053 Time to Stent 1.3E-4(5.2E-4) 0.8 ANCOVA with time alive and out of hospital as outcome, cell dose, and time to stent as covariate MEDIAN FOLLOW-UP: 12 MONTHS
PreSERVE: Myocardial Perfusion • Improvement in clinically relevant endpoints not mirrored by change in SPECT perfusion • Results indicate that SPECT myocardial perfusion is not a suitable surrogate 15 SPECT Resting Total Severity Score (RTSS) Change from Baseline to 6 months (mITT) Placebo CD34 P-value RTSS Mean Change from Baseline (±SD) -149.6 ± 221.1 -142.7 ± 257.8 NS
4.9 4.1 3.1 5.8 10.2 PreSERVE: Left Ventricular Ejection Fraction Change from Baseline to 6 months (mITT) CMR (SPECT when unavailable) 16 Control (N=80) <14M (N=45) >14M (N=15) >20M (N=13) L V E F c h an g e fro m b a seli n e ( % ) P < 0.05* Tmt (N=73) Parameter Parameter Estimate (SE) P-Value CD34+ Cell Dose 2.21 (1.084) 0.045† CD34+ CXCR4+ cell Dose 4.8E-7 (2.1E-7) 0.062‡ Multiple regression† and ANOVA‡ models *P-values are based on a t-test of the means Influence of dose corrected for time to stent
PreSERVE: Infarct Size Change from Baseline to 6 months(CMR only; mITT) -24% -23% -16% -35% -41% -50% -40% -30% -20% -10% 0% 17 Control N=54 <14M N=28 >14M N=17 >20M N=7 P = NS for all dose groups vs control Influence of dose corrected for time to stent Parameter Parameter Estimate (SE) P-Value CD34+ cell Dose -1.4E-6 (5.9E-7) 0.02 ANCOVA with infarct size change from baseline as outcome, infarct size at baseline, cell dose, and time to stent as covariate Tmt N=45
PreSERVE Sites 18 Investigator Name Site Arshed Quyyumi Emory Alejandro Vasquez Heart Center Research Dean Kereiakes The Christ Hospital Marc Klapholz UMDNJ-Newark Kenichi Fujise Univ. Texas - Galveston Nandish Thukral Methodist San Antonio Gary Schaer Rush University Medical Center Robert Iwaoka Presbyterian CVI Research Ahmed Abdel-Latif U. of Kentucky, Gill Heart Institute Vijaykumar Kasi Orlando Health Vernon Anderson U. of Texas HSC - Houston Roger Gammon Austin Heart PLLC Stephen Frohwein St Joseph's Research Institute Tim Henry Minneapolis Heart Richard Schatz Scripps-La Jolla Tanvir Bajwa Aurora Health Nabil Dib Mercy Gilbert Medical Center Catalin Toma UPMC Presbyterian Michael Tamberella CaroMont Heart Pradyumna Tummala Northeast Georgia Heart Center Charles Davidson Northwestern University Gregory Barsness Mayo Clinic - Minnesota Virender Sethi Hackensack University Tarek Helmy University of Cincinnati David Shavelle Keck School of Medicine-USC Fadi El-Ahdab CV Group Central Lynchburg Martin Cohen Westchester Medical Center Gerald Koenig Henry Ford Carl Pepine University of Florida-Gainesville Vincent Pompili Ohio State University Robert Frankel Maimonides Medical Center- Brooklyn Mark Vesely University of Maryland Investigator Name Site Theodore Schreiber Detroit Receiving/Harper Hospital Mazen Abu-Fadel U. of Oklahoma HSC Emerson Perin Texas Heart Institute David Fortuin Mayo Clinic - Arizona Luis Gruberg Stony Brook University Hospital Charles Lambert Florida Hospital Massoud Leesar University of Alabama- Birmingham Joseph Wu Stanford University Howard Eisen Drexel University Lawrence Barr Advocate Health Elm Hurst Buddhadeb Dawn Kansas U. Medical Center Amit Patel University of Utah Christopher Gange MetroWest Medical Center Paul Gordon Miriam Hospital Richard Rothschild St. John's Regional Hospital Peter Kerwin Advocate Health Oakbrook Hitinder Gurm U. Michigan Michael Imburgia Louisville Cardiology Kimberly Skelding Geisinger Medical Center Vijay Iyer Buffalo General Hospital Frank McGrew Stern Cardiovascular Foundation/Baptist Hospital Zachary Hodes St. Vincent Medical Group Augusto Prichard Medstar Heart Institute Michael Ragosta UVA Health System Cardiology Research Barry Bertolet Cardiology Associates Research LLC Majid Qazi Detroit Clinical Reseach Center PC Paul Huang Swedish Medical Center
Thank you for your attention 19
BACK UP SLIDES 20
Time to Cardiac Death (ITT Population) 21 MEDIAN FOLLOW-UP: 18 MONTHS Pro b a b ilit y of surv iva l Days since informed consent 200 400 600 800 1000 1200 P=0.008‡ ‡P-value calculated using log rank test ‡ P-value calculated using log rank test
Time to First Hospitalization (mITT) 22 MEDIAN FOLLOW-UP: 12 MONTHS Pro b a b ilit y of b e in g a liv e a n d o u t of h o sp ita l >20M >14M Control
1 Corporate Presentation NASDAQ: NBS Transforming Personalized Medicine David J. Mazzo, PhD Chief Executive Officer March 2015
Forward-looking statements 2 This presentation contains “forward-looking” statements within the meaning of the Private Securities Litigation Reform Act of 1995, as well as historical information. Such forward-looking statements involve known and unknown risks, uncertainties and other factors which may cause our actual results, performance or achievements, or industry results, to be materially different from anticipated results, performance or achievements expressed or implied by such forward-looking statements. When used in this presentation, statements that are not statements of current or historical fact may be deemed to be forward-looking statements. Without limiting the foregoing, the words “plan,” “intend,” “may,” “will,” “expect,” “believe,” “could,” “anticipate,” “estimate,” or “continue” or similar expressions or other variations or comparable terminology are intended to identify such forward-looking statements, although some forward-looking statements are expressed differently. We remind readers that forward- looking statements are merely predictions and therefore inherently subject to uncertainties and other factors and involve known and unknown risks that could cause the actual results, performance, levels of activity or our achievements or industry results, to be materially different from any future results, performance levels of activity or our achievements or industry results expressed or implied by such forward-looking statements. Such forward looking statements appear in this presentation. Factors that could cause our actual results to differ materially from anticipated results expressed or implied by forward-looking statements include, among others: • our ability to obtain sufficient capital or strategic business arrangements to fund our operations and expansion plans, including meeting our financial obligations under various licensing and other strategic arrangements, the funding of our clinical trials for product candidates in our development programs for our Targeted Cancer Immunotherapy Program, our Ischemic Repair Program and our Immune Modulation Program, and the commercialization of the relevant technology; • our ability to build and maintain the management and human resources infrastructure necessary to support the growth of our business; • our ability to integrate our acquired businesses successfully and grow such acquired businesses as anticipated, including expanding our PCT business internationally; • whether a large global market is established for our cellular-based products and services and our ability to capture a meaningful share of this market; • scientific and medical developments beyond our control; • our ability to obtain and maintain, as applicable, appropriate governmental licenses, accreditations or certifications or comply with healthcare laws and regulations or any other adverse effect or limitations caused by government regulation of our business; • whether any of our current or future patent applications result in issued patents, the scope of those patents and our ability to obtain and maintain other rights to technology required or desirable for the conduct of our business; our ability to commercialize products without infringing the claims of third party patents; • whether any potential strategic or financial benefits of various licensing agreements will be realized; • the results of our development activities, especially: • the results of our planned Intus Phase 3 clinical trial of NBS20 being developed to treat metastatic melanoma; • the results of our PreSERVE Phase 2 clinical trial of NBS10 being developed to treat acute myocardial infarction for which we released initial data on November 17, 2014 and for which all 6 and 12 month data has been collected; however it is subject to ongoing analysis, and currently reported results, although promising, are preliminary and there can be no assurance that further analysis may not reveal negative, or less promising, results; • our ability to complete our other planned clinical trials (or initiate other trials) in accordance with our estimated timelines due to delays associated with enrolling patients due to the novelty of the treatment, the size of the patient population and the need of patients to meet the inclusion criteria of the trial or otherwise; and • the other factors discussed in “Risk Factors” in our Form 10-K filed with the Securities and Exchange Commission (“the SEC”) on March 2, 2015, and elsewhere in the Annual Report on Form 10-K. The factors discussed herein, including those risks described in Item 1A. “Risk Factors” in the Company's Annual Report on Form 10-K filed with the SEC on March 2, 2015 and in the Company's other periodic filings with the Securities and Exchange Commission (the “SEC”) which are available for review at www.sec.gov under “Search for Company Filings” could cause actual results and developments to be materially different from those expressed or implied by such statements. All forward-looking statements attributable to us are expressly qualified in their entirety by these and other factors. Readers are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof. Except as required by law, the Company undertakes no obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise.
NeoStem financial metrics 3 MARKET METRICS MARKET CAPITALIZATION1 $150.0 M STOCK PRICE2 $3.90 52 WEEK RANGE2 $3.08 - $7.75 FLOAT1 33.7M INSIDER HOLDINGS1 12.1% FINANCIAL METRICS REVENUE3 $17.9M (FY 2014) CASH4 $26.3M COMMON SHARES OUTSTANDING1 38.3 M WARRANTS1 3.5 M (avg. warrant exercise price of $14.12) OPTIONS1 6.4 M (avg. option exercise price of $7.44) 1. As of March 12, 2015 (based on shares outstanding on March 12, 2015) 2. As of March 12, 2015 3. For the year ended December 31, 2014 4. As of December 31, 2014 (includes cash, cash equivalents and marketable securities)
Transforming cells into therapies 4
NeoStem’s PCT: Industry-recognized single source premier services Center of excellence for process development, engineering and manufacturing 5 PRODUCT & PROCESS DEVELOPMENT MANUFACTURING CELL & TISSUE PROCESSING LOGISTICS STORAGE & DISTRIBUTION EXPERT CONSULTATION & REGULATORY SUPPORT ENGINEERING & AUTOMATION
At a glance 6 Highly experienced management and scientific team Proprietary platform technologies yielding a diversified, balanced pipeline targeting critical unmet needs in large global markets and near-term development milestones Immunotherapy platform applicable across multiple solid tumors with Fast Track and Orphan Drug Designations and a SPA for a phase 3 study in metastatic melanoma Cell therapy platform applicable in multiple cardiovascular indications with ongoing Phase 2 study for acute myocardial infarction – compelling and consistent interim results Immunomodulation therapy platform targeting autoimmune disorders with FDA cleared phase 2 study in adolescents with type I diabetes Internal center of excellence (PCT) with bicoastal facilities and proven capabilities innovating discovery, development, manufacturing and delivery of cell-based therapies
Experienced executive team 7 David J. Mazzo, PhD Chief Executive Officer Over 30 years experience in all aspects of large and emerging global biotech/biopharma company operations and successful international drug development Robert S. Vaters, MBA President and Chief Financial Officer Over 25 years financial and management experience in a variety of healthcare, biotechnology, biologics, medical device and pharmaceutical companies Douglas W. Losordo, MD Chief Medical Officer A leader in cell therapy research and development and renowned cardiologist with noteworthy academic and industry credentials Robert A. Preti, PhD President of NeoStem’s PCT A leading authority on cell-based therapy engineering with unique development and commercialization experience Robin L. Smith, MD, MBA Executive Chairman Extensive background in healthcare, business development and management; led NeoStem 2006-2014
Robust, diversified and balanced pipeline 8 PRECLINICAL PHASE 1 PHASE 2 PHASE 3 Acute myocardial infarction - STEMI : NBS10 Type I diabetes: NBS03D Metastatic melanoma: NBS20 (USAN = eltrapuldencel-T) Fast Track & Orphan Drug Designations with Special Protocol Assessment Granted
Robust, diversified and balanced pipeline 9 PRECLINICAL PHASE 1 PHASE 2 PHASE 3 Metastatic melanoma: NBS20 (USAN = eltrapuldencel-T) Acute myocardial infarction - STEMI : NBS10 Type I diabetes: NBS03D
10 Fast Track designation Orphan Drug designation Special Protocol Assessment NBS20: (USAN = eltrapuldencel-T) Metastatic melanoma
Numerous non-synonymous mutations • Unique patient-specific antigenic fingerprints • Ideal target for autologous immunotherapy Stage III recurrent/stage lV metastatic melanoma 11 Brain Lung Bone Liver 1. American Cancer Society, 2014 SEER 2. For Stage IV metastatic melanoma - AJCC Cancer Staging 2010 (based on 17 academic centers) (Five year data for recently approved melanoma immunotherapies is not yet reflected) 3. GBI Research – 2013 PREVALENCE AND UNMET MEDICAL NEED ~20,000 estimated new cases per year in U.S.1 DISTANT METASTASES ~10,000 deaths per year in U.S.1 ~15% five-year survival rate2 ~$1 billion U.S. market size3 Small Bowel Cutaneous and Soft Tissue Lymph Nodes
Current metastatic melanoma therapies insufficient 12 CURRENTLY APPROVED THERAPIES 2 Year Survival 5 Year Survival DTIC (GENERIC) JCO 1999, JCO 2000 9-20% 4% INTERLEUKIN-2 (PROMETHEUS LABS) JCO 2002 25% 15% IPILIMUMAB (BMS) NEJM 2010 24% 20% ANTI-PD11 (BMS AND MERCK) Clin Oncol 2014 40-50% N/A VEMURAFENIB (ROCHE) Engl J Med 2012 Est. 20% N/A THERAPEUTIC CANDIDATES T-VEC (AMGEN – P3) Clin Oncol 2013 40% N/A TUMOR INFILTRATING LYMPHOCYTES (LION - P2) Clin Cancer Res 2011 40% 29% 1. Includes both nivolumab and pembrolizumab 2. Survival rates for patients with Stage IV (distant metastatic disease), calculated from time of treatment
13 Process times are approximate Isolation of cancer initiating cells Expansion and irradiation Incubate with irradiated tumor _ cells for antigen presentation Dendritic cell production Leukapheresis Monocyte isolation Surgical excision NBS20 uniquely targets cancer initiating cells by leveraging the patient’s own immune system Preparation of NBS20 - stimulating immune response 6 TO 8 WEEKS PLUS 2 WEEKS QC 1 DAY PLUS 2 WEEKS QC 6 DAYS
0% 20% 40% 60% 80% 100% 0 10 20 30 40 50 60 P e rc ent S u rv iv in g Months Phase 2: multiple trials; consistent, compelling data 14 Dillman, et al. Journal Immunotherapy 2012 Historical control for distant metastases 0% 20% 40% 60% 80% Control Group Irradiated Tumor Cells Treatment Group 2-YEAR OVERALL SURVIVAL 42 patient randomized P2 trial p = 0.007; Hazard ratio = 0.27 Treatment considered safe and generally well tolerated ― Minor local injection site reactions 72% 31% N=24 N=18 50% observed 5-year survival rate Treatment considered safe and generally well tolerated ― Minor local injection site reactions Dillman, et al. Cancer Biother Radiopharm 2009 Historical control for distant metastases: Balch J Clin Oncol 2009 N=54 5-YEAR OVERALL SURVIVAL 54 patient single arm P2 trial 2 Y ea rs 73% Treatment 10% 25%
The Intus study: phase 3 with SPA and orphan drug and fast track designations 15 DESIGN Single randomized, double blind, placebo controlled trial for stage III recurrent or stage IV metastatic melanoma for registration PRIMARY ENDPOINT Overall survival POWERING 80% power to detect 37.5% reduction in risk of death RELATION TO STANDARD THERAPIES Adjunctive (clinical practice based trial) STUDY SIZE Planned 250 eligible patients across approximately 50 sites (US, Canada, Australia, New Zealand) TREATMENT Autologous dendritic cells loaded with antigen from proliferating autologous tumor cells + GM-CSF CONTROL Peripheral blood mononuclear cells obtained from pheresis product + GM-CSF
Timeline to BLA 16 1Q 2015 Initiate Screening 4Q 2017 Interim Results after 99 Deaths 2Q 2015 First Patient Randomized 2Q 2018 Projected BLA Submission based on successful interim analysis 2Q 2019 Final Study Results 4Q 2019 Projected BLA Submission 4Q 2016 Enrollment Completed 2015 2016 2017 2018 2019 Study continues to 162 deaths Total trial cost to earliest projected BLA: ~$45 million
Multi-billion dollar lifecycle opportunity Potential application across multiple solid tumor types 17 LUNG CANCER (Feasibility of cell lines from biopsies initiated) COLON CANCER (Feasibility of cell lines planned) OVARIAN CANCER (US FDA approved phase 2 protocol, cell line feasibility established) HEPATOCELLULAR CARCINOMA (LIVER) (8 HCC patients with HBV treated, no toxicity) GLIOBLASTOMA MULTIFORME (BRAIN)
Robust, diversified and balanced pipeline 18 PRECLINICAL PHASE 1 PHASE 2 PHASE 3 Acute myocardial infarction - STEMI : NBS10 Type 1 diabetes: NBS03D Metastatic melanoma: NBS20 (USAN = eltrapuldencel-T)
19 NBS10: ST segment elevation myocardial infarction (STEMI)
Acute myocardial infarction (STEMI) 20 1. Pedersen, Journal of the American College of Cardiology, 2014 and NeoStem modeling PREVALENCE AND UNMET MEDICAL NEED STEMI patients are at high risk of progressive deterioration in heart muscle function leading to Major Adverse Cardiac Events (MACE) ~65,000 STEMI patients/year in U.S. (successfully stented) later experience heart failure1 Infarcted Zone Peri-infarct Zone
NBS10 – Leveraging the body’s natural repair mechanism to preserve heart muscle function 21 CD34/CXCR4 from bone marrow CD34 cell laying down new blood vessels CD34/CXCR4 SDF gradient CD34+ cells have been shown to induce the development of new blood vessels, preventing tissue death by improving blood flow NBS10 = CD34+ cells extracted from the patient’s bone marrow, treated to maximize potency and then delivered directly to the infarct site via a routine catheter lab procedure
PreSERVE study: enrolled phase 2 study in follow-up 22 DESIGN Randomized (1:1), Phase 2, double blind, placebo controlled trial for post-AMI (STEMI) patients PRIMARY ENDPOINTS AND KEY SECONDARY ENDPOINT Change in cardiac perfusion from baseline to 6 months (exploratory) Incidence rates of SAEs and MACE (regulatory – AMI) LVEF change from baseline to 6 months (regulatory – heart failure) KEY INCLUSION CRITERIA Confirmation of ST Elevation MI; ejection fraction < 48% at day 4 by CMR; state-of-the-art care post stenting STUDY SIZE 161 patients, 60 centers in United States TREATMENT Single dose via infarct related artery with minimum dose for release ≥10M (million) ±20% CD34+ cells. Actual dose determined by intrinsic number of cells in marrow and processing success rate CONTROL Matching infusion with placebo
PreSERVE 6 & 12-month interim conclusions* 23 CD34 cell dose-dependent trend in reduction of MACE — Signal for a mortality benefit (12 month data) Signal for reduction in frequency of SAEs in higher dose groups (12 month data) CD34 cell dose-dependent trend in improvement of left ventricular ejection fraction and reduction in infarct size No correlation between experimental endpoint of perfusion and treatment Favorable trends in clinical events encourage continued development Results inform regarding important design parameters for next development steps *Based on data collected at 6 months except where noted
PreSERVE: MACE incidence (median follow-up 12 mos) 24 CD34 DOSE-DEPENDENT TREND IN REDUCTION OF MACE 14% 17% 10% 7% SIGNAL FOR A MORTALITY BENEFIT MACE= Death, MI, CHF Hospitalization, Revascularization. Control N=83 <14M N=47 >14M N=31 >20M N=15 0% 1% 2% 3% 4% 5% N=83 3.6% 0% (N=0) Pooled Treatment P = 0.04 No treatment group deaths reported to date* First time dose response demonstrated in this patient population Control * As of Mar. 13, 2015
1.2 1.1 0.6 0.7 0 0.2 0.4 0.6 0.8 1 1.2 1.4 PreSERVE: SAE incidence (median follow-up 18 mos) 25 SIGNAL FOR REDUCTION IN FREQUENCY OF SAES IN HIGHER DOSE GROUPS P ropo rtion of e ve n ts (n o rmali zed b y to tal s u b je cts ) P = 0.059 First time dose response demonstrated in this patient population Control N=83 <14M N=47 >14M N=31 >20M N=15
PreSERVE: LVEF change from baseline at 6 mos. 26 4.9% 3.1% 5.8% 10.2% Control <14M >14M >20M CD34 CELL DOSE-DEPENDENT TREND IN IMPROVEMENT OF LVEF LVE F chan g e f rom baseline ( % ) P < 0.05 First time dose response demonstrated in this patient population
-24% -16% -35% -41% -50% -40% -30% -20% -10% 0% PreSERVE: Infarct size change (baseline to 6 mos.) 27 Control <14M >14M >20M CD34 CELL DOSE-DEPENDENT TREND IN REDUCTION OF INFARCT SIZE % Me a n c ha n g e f rom baseli n e First time dose response demonstrated in this patient population
Next steps for ischemic repair program 28 NEXT POTENTIAL DEVELOPMENT STEPS IN OTHER INDICATIONS • Phase 2 in chronic heart failure • Phase 2 in critical limb ischemia STEMI NEXT DEVELOPMENT STEPS • March 2015: • 2H 2015: • March 2016: • March 2017: One-year data Determine next development steps based on PreSERVE interim results and consultation with medical advisors (potentially Phase 2B/3 trial) Two-year data Three-year data, end of study
Multi-billion dollar lifecycle opportunity Potential application across several cardiovascular indications 29 CHRONIC HEART FAILURE CRITICAL LIMB ISCHEMIA
Robust, diversified and balanced pipeline 30 PRECLINICAL PHASE 1 PHASE 2 PHASE 3 Acute myocardial infarction - STEMI : NBS10 Type I diabetes: NBS03D Metastatic melanoma: NBS20 (USAN = eltrapuldencel-T)
31 NBS03D: Diabetes Mellitus Type-1 (T1D)
Diabetes Mellitus Type-1 (T1D): an autoimmune disease 32 1. Hamman RF, et al. Diabetes Care. 2014; Sosenko JM, et al. Diabetes Care. 2008; Palmer JP. Diabetes/metabolism research and reviews. 2009 2. The DIAMOND Project Group. Diabetic Medicine. 2006;23:857-866. PREVALENCE AND UNMET MEDICAL NEED • 18,000 children under 20 in U.S. with new onset T1D per year1 • 3% annual growth rate worldwide2 • No curative treatments for T1D, only lifelong insulin therapy • Diabetes is leading cause of kidney failure, new cases of adult blindness and non- traumatic lower-limb amputations Beta Cells T Regulatory Cell T Effector Cell-Mediated Killing of Beta Cells T Effector Cell T Regulatory Cell Defense of Beta Cells
33 NORMAL IMMUNE SYSTEM: IMMUNE BALANCE TREG INFUSION T regulatory cells T effector cells Blood draw from patient Manufacturing including expansion Infusion of Treg therapy to patient Preparation of NBS03D – restoring immune balance and function INFUSION of TREGs BALANCE REGAINED AUTOIMMUNITY: IMMUNE IMBALANCE Natural polyclonal T regulatory cells
Regulatory T Cell therapy appears to be safe and well tolerated in adults1 34 1. Gitelman et al, American Diabetes Association Abstract, 2014 DESIGN U.S. UCSF/Yale open label Phase 1 study, 4-dose escalation cohorts PATIENTS 14 adult patients with established T1D RESULTS • Preliminary data indicates safety and tolerability • Established manufacturing feasibility • Implied sustainability of effect • Infused Tregs were stable and detected in peripheral circulation for >6 months Is o tope la b le d T re g s Days Post Infusion Each Line Corresponds to an Individual Subject
0 0.2 0.4 0.6 0.8 1 1.2 Day O Month 4 One Year 0% 20% 40% 60% 80% 100% Control Group Treatment Group Regulatory T Cell therapy preserves beta cell function in children1 35 Marek-Trzonkowska, N t al. Clinical Immunology 2014 1. Children aged 5-18 administered 1 (10 or 20 mil cells/kg) or 2 doses (total 30 mil cells/kg) of Tregs REMISSION RATE AT 12 MONTHS FASTING C-PEPTIDE LEVELS C -p e pt id e ( n g /m l) 67% 20% Mean Treatment Mean Control Complete insulin independence Remission No Remission
The Trutina study: phase 2 in adolescents with T1D1 36 DESIGN Double blind, placebo controlled, randomized (1:1:1) for adolescent patients with recent onset T1D ages 12 to 18 PRIMARY ENDPOINT Preservation of C-peptide at 52 weeks in comparison to placebo POWERING 80% power to detect 50% attenuation of the decline in mixed meal tolerance test stimulated c-peptide in comparison to placebo, adjusted for baseline STUDY SIZE 111 subjects to be enrolled across ~11 US sites TREATMENT 2 dose groups of NBS03D (single dose autologous ex-vivo expanded polyclonal T Regulatory cell therapy): 10 and 20 million cells/kg CONTROL Matching infusion 1. Study cleared by FDA to proceed based on efficacy data in children establishing prospect of direct benefit
Trutina study timeline 37 Y1 Month 1 First subject first visit Year One Year Two Year Three Year Four Year Five Y1 Month 2 First subject randomized Y2 Q2 51st subject randomized* Y3 Q2 Last subject randomized Y3 Q3 Interim analysis topline results Y4 Q3 One-year topline results Y5 Q3 Two-year topline results *One-year visit of 51st subject triggers interim analysis Expected cost of trial: ~$22.5 million
Multi-billion dollar lifecycle opportunity Potential application across multiple autoimmune and allergic diseases 38 STEROID RESISTANT ASTHMA MULTIPLE SCLEROSIS (MS) CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD) INFLAMMATORY BOWEL DISEASE GRAFT VS. HOST DISEASE
Investment summary 39 Highly experienced management and scientific team Proprietary platform technologies yielding a diversified, balanced pipeline targeting critical unmet needs in large global markets and near-term development milestones Immunotherapy platform applicable across multiple solid tumors with Fast Track and Orphan Drug designations and a SPA for a phase 3 study in metastatic melanoma Cell therapy platform applicable in multiple cardiovascular indications with ongoing Phase 2 study for acute myocardial infarction – compelling and consistent interim results Immunomodulation therapy platform targeting autoimmune disorders with FDA cleared phase 2 study in adolescents with type I diabetes Internal center of excellence (PCT) with bicoastal facilities and proven capabilities innovating discovery, development, manufacturing and delivery of cell-based therapies
Corporate Presentation NASDAQ: NBS March 2015 Transforming Personalized Medicine Contact: Eric Powers, Manager of Communications & Marketing Phone: 212.584.4173 Email: epowers@neostem.com Web: www.neostem.com