A Phase II, Randomized, Double-Blind, Multicenter, Multinational, Placebo-Controlled, Parallel-Groups Study to Evaluate the Safety and Efficacy of

Intramuscular Injections of Allogeneic PLX-PAD Cells for the Treatment of Subjects

With Intermittent Claudication (IC)

(1) Center for Vascular Medicine & Department of Medicine – Section Angiology, University Hospital Carl Gustav Carus at the Technische Universität Dresden, Germany

(2) Department of Angiology, Asklepios Klinik St. Georg, Hamburg, Germany(3) Pluristem Ltd., Haifa, Israel(4) Division of Cardiology, Duke University Health System, Durham, NC, USA

Norbert Weiss(1), Sigrid Nikol(2), Yael Rosen(3), Dan Peres(3), Zami Aberman(3), Manesh R Patel(4), for the PLX-PAD Study Group

BACKGROUND

• Intermittent claudication (IC) due to peripheral arterial diseaseimpairs function and quality of life and is associated withincreased cardiovascular morbidity and mortality.

• Endovascular or surgical revascularization improves symptoms,but leads to an increased amputation rate. Limited non-invasivetherapies exist. Previous angiogenesis trials to improve IC werenegative.

• Intramuscular administration of placenta-derived adherentstromal cells (PLX-PAD) increased angiogenesis and blood flowin a murine hind-limb ischemia model, and demonstrated to besafe in clinical phase I studies.

MATERIALS & METHODS

Placenta

Technology

Allogeneic off-the-shelf

Simple IM administration

Adaptive slow release secretion of cytokines

Long term regenerative effect

Ethically accepted Rich & Diverse Highly potent Young donors Unlimited source Easy to collect

MATERIALS & METHODS – PROPOSED MOA

• Immunomodulatory cytokines which support the induction of M2 macrophages and elevate the level of circulating regulatory T cells leading to elevation in IL-10 and resolution of inflammation.

• Factors which directly support angiogenesis and muscle regeneration.

• Enzymes with antioxidant activity, which can protect blood vessels from oxidative damage.

• ECM remodeling enzymes which enable regeneration.

STUDY OBJECTIVES & ENDPOINTS

OBJECTIVE: To evaluate the optimal dosing regimen, efficacy and safety of intramuscular injections of PLX-PAD cells in patients with IC, Rutherford categories 2-3, due to femoro-popliteal disease (NCT01679990)

• Primary efficacy endpoint:Change in Log-Maximum Walking Distance (Log-MWD) at week 52 compared to baseline

• Key secondary endpoint:Change in Log-MWD at week 52 in patients treated with 2 administrations of PLX-PAD originating from different placentae compared to baseline

• Safety

KEY INCLUSION - EXCLUSION CRITERIA

INCLUSION • 45 to 85 years of age.• Peripheral artery disease, secondary

to atherosclerosis, • with moderate to severe claudication,• resting ankle-brachial index

(ABI) < 0.80 or ABI < 0.90 with >20% decrease in exercise or (TBI) < 0.60,

• significant (>50%) stenosis of infra-inguinal arteries.

• Screening MWD between 1 and 10 minutes.

• Optimal medical treatment.

EXCLUSION• Advanced dis. - Rutherford category 4-6.• Failed procedure within one month.• Planned revascularization. • Buerger’s disease.• Uncontrolled hypertension / DM.• Life-threatening ventricular arrhythmia. • Abnormal labs: Creat, Liver Panel, CBC. • MI/unstable angina, (TIA)/Stroke, severe

CHF, prosthetic heart valve, severe pulmonary dis., infection, of malignancy, Asthma, Immunocompromised.

• Allergies to IMP.• (HIV), syphilis, active hepatitis B,

or hepatitis C infection.

STUDY DESIGN, IP & CLINICAL SITESDouglas Denham, DO Clinical Trials of Texas, Inc. David L Fried, MD Omega Medical ResearchJames Hampsey, MD Tampa Bay Medical research

Alan T Hirsch, MD Clinical and Translational Science Institute University of Minnesota

William Schulyer Jones, MD Duke UniversityNadarajah Janaki, M.D Aiyan Diabetes CenteBret Weichmann, MD Florida Research NetworkRobert L. Wilensky, MD Hospital of the University of PennsylvaniaKathleen Cullen, MD DMI Research, Inc.Malcolm Foster, MD Turkey Creek Medical CenterKaren J. Ho, MD Northwestern University

James B. Gosset, MD Medical College of WisconsinFarrell Owen Mendelsohn, MD Cardiology, P.C.Berthold Amann, MD Franziskus-Krankenhaus, Berlin

Norbert Weiss, MD Universitätsklinikum Carl Gustav Carus, Dresden

Sigrid Nikol, MD ASKLEPIOS Klinik St. Georg, Hamburg Holger Reinecke, MD Universitätsklinikum Münster

Oliver Müller, MD Universitätsklinikum Heidelberg Medizinische

Thomas Zeller, MD Universtiäts-Herzzentrum Freiburg und Bad-Krozingen

Christine Espinola-Klein, MD Universitätsmedizin der Johannes Gutenberg-Universität Mainz

Reuven Zimlichman, MD Edith Wolfson Medical CenterAsaf Rabin, MD Horev CenterSang Hoon Kim, MD CHA Bundang Medical CenterYou Sun Hong, MD Ajou University School of MedicineWeonyong Lee, MD Hallym University Sacred Heart HospitalSung Woon Chung, MD Pusan National University HospitalKwang-Jo Cho, MD Dong-A University Hospital

Do Kyun Kim, MD National Health Insurance Service IlsanHospital

BASELINE DEMOGRAPHICS

Variable Statistics

PBO-PBO (n=52)

300M-PBO (n=39)

150M-150M (n=38)

300M-300M (n=51)

ALL-PLX (n=128)

Total (n=180)

Age (yrs) 65.9 ± 9.89 66.3 ± 8.24 66.2 ± 8.01 64.4 ± 7.97 65.5 ± 8.05 65.6 ± 8.6 Sex, [n (%)] Female 13 (25.0) 8 (20.5) 10 (26.3) 9 (17.6) 27 (21.1) 40 (22.2) Male 39 (75.0) 31 (79.5) 28 (73.7) 42 (82.4) 101 (78.9) 140 (77.8) Race [n (%)] Asian 6 (11.5) 5 (12.8) 5 (13.2) 5 (9.8) 15 (11.7) 21 (11.7) Black or African American 6 (11.5) 7 (17.9) 2 (5.3) 5 (9.8) 14 (10.9) 20 (11.1) White/Caucasian 40 (76.9) 27 (69.2) 31 (81.6) 41 (80.4) 99 (77.3) 139 (77.2) Hispanic or Latino 0 0 0 1 (2.0) 1 (0.8) 1 (0.6) BMI (kg/m2) 28.4 ± 5.75 27.8 ± 4.22 27.7 ± 3.56 28.9 ± 5.5 28.2 ± 4.61 28.3 ± 4.46 Smoking [n (%)] 49 (94.2) 36 (92.3) 35 (92.1) 48 (94.1) 119 (93.0) 168 (93.3) Diabetes Mellitus [n (%)] 25 (48.1) 15 (38.5) 11 (28.9) 21 (41.2) 47 (36.7) 72 (40.0) Hypertension [n (%)] 41 (78.8) 33 (84.6) 31 (81.6) 41 (80.4) 105 (82.0) 146 (81.1) Hyperlipidemia [n (%)] 20 (38.5) 14 (35.9) 15 (39.5) 21 (41.2) 50 (39.1) 70 (38.9)

BASELINE CHARACTERISTICS (CONT‘D)Placebo-Placebo 300×106-

Placebo150×106-150×106

300×106-300×106 Total PLX Total

ABI treated legN 49 37 37 48 122 171

Mean + SD 0.6 ± 0.1 0.6 ± 0.2 0.6 ± 0.1 0.6 ± 0.2 0.6 ± 0.2 0.6 ± 0.2

ABI contralateral leg

N 49 37 36 46 119 168

Mean + SD 0.8 ± 0.2 0.8 ± 0.2 0.8 ± 0.2 0.8 ± 0.2 0.8 ± 0.2 0.8 ± 0.2

Baseline MWDN 52 39 38 51 128 180

Mean + SD 295.1 ± 141.0 251.4 ± 116.8 338.1 ± 144.8 289.0 ± 138.0 292.1 ± 137.2 293.0 ± 137.9

Baseline ICDN 52 39 38 51 128 180

Mean + SD 121.3 ±74.5 134.7 ± 89.4 157.1 ± 94.2 123.6 ± 75.1 136.9 ± 86.0 132.4 ± 82.9

Hemoglobin A1c (HbA1c)

N 43 30 32 40 145

Mean + SD 46.13 ± 11.75 43.93 ± 9.90 43.38 ± 9.84 44.34 ± 8.71 44.58 ± 10.13

SF 36 physical role score

N 49 37 37 48 122 171

Mean + SD 37.0 ± 6.0 36.0 ± 7.7 36.2 ± 6.4 37.6 ± 5.1 36.7 ± 6.4 36.8 ± 6.2

RESULTS: CHANGE IN MAXIMUM WALKING DISTANCE

For the 300-300 arm: • change from baseline

at week 52 = 32.7%; p=0.0008

(N=153)

RESULTS: CHANGE IN MAXIMUM WALKING DISTANCE USA

* p = 0.050** p = 0.035, 0.00096

RESULTS: PLX-PAD FROM 2 DONOR IN THE 300-300 GROUP

* p = 0.032, 0.014** p = 0.019, 0.015*** p = 0.044, 0.017

CLINICALLY DRIVEN REVASCULARIZATION BY WEEK 65

At least 1 RevascularizationEvent n (%)

PBO-PBO(N=50)

300M-PBO(N=37)

150M-150M(N=37)

300M-300M(N=48)

300M-300M(N=11)

2 DonorsWeek 65 6 (12.0) 6 (16.2) 7 (18.9) 3 (6.3) 0 (0)

Hazard Ratio* 1.50 1.64 0.51 NA

95% CI 0.48, 4.66 0.55, 4.88 0.13, 2.05

p-value 0.485 0.376 0.345

Odds Ratio** 1.52 1.77 0.49 NA

95% CI 0.36, 6.36 0.45, 7.15 0.07, 2.49

p-value 0.716 0.515 0.527

C-REACTIVE PROTEIN & HEMOGLOBIN A1c (HbA1c)

* p = 0.040** p = 0.038, 0.0012

Estimate SE P-Value

All patients -3.121 1.827 0.0898

PLX-PAD from 2 donors

-7.770 3.087 0.0155

CRP HbA1c

PLX-PAD-1204-01(IC) - Week 65ANCOVA of Change from Baseline in HbA1C (mmol/mol)Difference of Adjusted Means

300M-300M - PBO-PBO

SAFETY - ADVERSE EVENTS

PBO-PBO(n=51)

300-PBO(n=36)

150-150(n=37)

300-300(n=48)

Death 0 % 0 % 0 % 2.1 %Major amputations 3.9 % 0 % 0 % 0 %Malignancies 7.8 % 5.6 % 10.8 % 2.1 %Infections 33.3 % 22.2 % 32.4 % 33.3 %Injection site pain

hematoma leading to discontinuation

39.2 %9.8 %0 %

30.6 %2.8 %2.8 %

40.5 %5.4 %2.7 %

47.9 %6.3 %4.2 %

Peripheral vascular disorders 29.4 % 27.8 % 27.0 % 22.9 %Cardiac disorders 9.8 % 11.1 % 8.1 % 6.3 %Neurologic disorders 27.5 % 13.9 % 18.9 % 20.8 %Blood and lymphatic disorders 9.8 % 8.3 % 2.7 % 2.1 %Renal disorders 9.8 % 8.3 % 5.4 % 6.3 %Ophthalmologic disorders 11.8 % 5.6 % 5.4 % 4.2 %Respiratory tract disorders 17.6 % 2.8 % 10.8 % 8.3 %Abnormal lab findings 13.7 % 8.3 % 8.1 % 6.3 %Gastrointerstinal disorders 23.5 % 25.0 % 18.9 % 20.8 %Musculosceletal disorders 39.2 % 41.7 % 35.1 % 31.1 %Psychiatric disorders 7.8 % 5.6 % 0 % 4.2 %

CONCLUSIONS

• PLX-PAD treatment demonstrated increased MWD at 52 weeks compared to baseline for all doses across all territories

• PLX-PAD high dose (300X106 x 2) demonstrated superiority over other tested regimes

• In the USA high-dose PLX-PAD demonstrated superiority over placebo to increase MWD at 52 weeks

• High-dose PLX-PAD composed of 2 administrations, each from a different donor demonstrated superiority over placebo across all territories

• IM administration of PLX-PAD cells was safe and well tolerated• A phase III clinical trial will test the efficacy and safety of two

administrations of PLX-PAD from different donors in patients with CLI unsuitable for revascularization

THANK YOU!