1 Proprietary data of Pluristem Therapeutics Inc. Forward Looking Statement This presentation concerning Pluristem Therapeutics may include forwardlooking statements which represent Pluristem Therapeutics' expectations or beliefs regarding future events. I caution that such statements involve risks and uncertainties that may cause actual results to differ materially from those in the forward-looking statements. Consequently, all such forward-looking statements are qualified by the cautionary language and risk factors set forth in Pluristem Therapeutics' periodic and other reports filed with the SEC. There can be no assurance that the actual results, events or developments referenced in such forward-looking statements will occur or be realized. Pluristem Therapeutics assumes no obligation to update these forwardlooking statements to reflect actual results, changes in assumptions or changes in factors affecting such forward-looking statements. www.pluristem.com 2 Proprietary data of Pluristem Therapeutics Inc. Corporate Overview • • • • • • • • 3 Biotechnology company (NasdaqCM: PSTI, TASE: PSTI) Two Phase I and one Phase I/II study demonstrated safety and significant efficacy of PLX-PAD in different indications Large Phase II study (n=150) and a Phase I study are ongoing Utilizes placenta-derived cell products to treat variety of inflammatory and ischemic conditions First-in-class 3D cell culturing technology for efficient, controlled production of different cell products in commercial quantities Active with regulators in the USA, EU, Korea, Australia and Israel 165 employees (17 PhD, 3 MD) IP Ownership: 34 granted patents and ~120 pending applications Proprietary data of Pluristem Therapeutics Inc. PLX-PAD CMC approved by 5 Regulatory agencies Approval Manufacturing facility and PLX-PAD CMC (3D culturing) for Phase II/III and marketing approved by FDA, PEI (Germany), EMA, Korean & Israeli regulatory agencies Batch-to-Batch comparability confirmed, multiple donors NasdaqCM: PSTI 4 Proprietary data of Pluristem Therapeutics Inc. PLX Technology 5 Proprietary data of Pluristem Therapeutics Inc. Active Clinical Programs 6 Proprietary data of Pluristem Therapeutics Inc. Ongoing Clinical Trials 7 • Intermittent Claudication (IC): Phase II multinational, randomized, double blind, placebo controlled study. Primary End Point: Maximal Walking Distance (MWD) at 12 months compared to baseline, N=150 • Pulmonary Arterial hypertension (PAH): - Phase I, open label, dose escalation study. Primary End Point: safety & efficacy at weeks 6 and 12, and at 12 months, N=9 Proprietary data of Pluristem Therapeutics Inc. Strong Clinical Data Muscle Injury following Total Hip Replacement N=20 8 Proprietary data of Pluristem Therapeutics Inc. Demography (mITT) 9 Placebo (n=7) 150 M PLX-Pad (n=7) 300 M PLX-PAD (n=6) Age (y) 64.3±6.4 65.4±5.9 64.5±7.4 Height (cm) 167.3±3.4 167.6±8.6 176.2±4.2 Weight (kg) 73.6±8 78.9±21.9 88.7±9.7 BMI (kg/m2) 26.3±2.8 27.5±5.9 28.7±4.2 Proprietary data of Pluristem Therapeutics Inc. Demography (mITT) Placebo (n=7) 150 M PLX-PAD (n=7) 300 M PLX-PAD (n=6) Caucasian 7 (100) 7 (100) 6 (100) Female 6 (86) 3 (43) 1 (17) 3 (43) 4 (57) 3 (50) Once weekly 5 (71) 7 (100) 3 (50) Twice weekly 0 0 1 (17) Never 2 (29) 0 2 (33) Smoking habits Ex and current smoker Alcohol 10 Proprietary data of Pluristem Therapeutics Inc. MVIC* (Nm) Mean (±SE) Gluteus Medius MVIC at Day 0 60 50 40 30 20 10 0 Placebo 150M PLX-PAD *Maximal Voluntary Isometric Contraction moment of the injured side **Nm – Newton Metres 11 Proprietary data of Pluristem Therapeutics Inc. 300M PLX-PAD Strong Data on Efficacy in Muscle injury Following Total Hip Replacement Improvement of 500% P=0.0067 12 Proprietary data of Pluristem Therapeutics Inc. Correlation Between Improvement in the Muscle Force of Injured and Contralateral Leg Injured (operated) 13 Contralateral (non–operated) Proprietary data of Pluristem Therapeutics Inc. Can IM injection of PLX cells generate a systemic effect ? 14 Proprietary data of Pluristem Therapeutics Inc. PLX-PAD Dose Dependent Effect Following IM Administration Operated limb 60.0 Blood flow 50.0 60.0 Placebo 0.01*10^6 1*10^6 40.0 30.0 20.0 40.0 30.0 20.0 10.0 10.0 0.0 0.0 day 1 day 7 day 14 day 21 0.01 x 106 cells and 1 x 106 show a similar effect No adverse effect of excess cells 15 Placebo 0.01*10^6 0.05*10^6 0.25*10^6 1*10^6 50.0 Blood Flow 70.0 Contralateral limb day 1 day 7 day 14 day 21 Dose reduction below 1 x 106 results in a dose dependent reduction in efficacy Proprietary data of Pluristem Therapeutics Inc. Suggested MoA of PLX-PAD in Muscle Trauma Proangiogenic Immunomodulatory Antifibrotic Protrophic 16 Proprietary data of Pluristem Therapeutics Inc. Muscle Fiber Diameter - Measured by Muscle Biopsy - Day 1 Mean Fiber Diameter (µ) Mean (±SE) Fiber Diameter at Day 1 (mITT) 70 60 50 40 30 20 10 0 Placebo 17 150M PLX-PAD Proprietary data of Pluristem Therapeutics Inc. 300M PLX-PAD Change from Day 1 to Week 12 in Mean Fiber Diameter as Measured by Muscle Biopsy Change in Mean Fiber Diameter (µ) Change in Mean (±SE) Fiber Diameter at Week 12 6 150M vs. Placebo : p=0.1862 300M vs. Placebo : p=0.2486 150M vs. 300M: p=0.8373 4 2 0 -2 -4 -6 -8 -10 Placebo 18 150M PLX-PAD Proprietary data of Pluristem Therapeutics Inc. 300M PLX-PAD Suggested MoA of PLX-PAD cells (pre-clinical finding) Inflammation (essential for regeneration) IL-6 Proteins secreted by PLX-PAD Satellite cells proliferation HGF TGFβ Satellite cells activation HGF Satellite cells migration HGF TGFβ MMPs Satellite cells differentiation VEGF (into myotubes) Angiogenesis (essential for regeneration) VEGF (into myofibers) 19 ECM remodeling after injury MMPs TIMPs Proprietary data of Pluristem Therapeutics Inc. Muscle of PLX-PAD treated animals after treatment Muscle Recovery in process Regenerated muscle tissue Rows of myoblast nuclei indicating regenerative hyperplasia 20 Proprietary data of Pluristem Therapeutics Inc. PLX-PAD and Angiogenesis  PLX-PAD promotes endothelial cell proliferation  PLX-PAD secretion of angiogenesis-related factors is manipulated by hypoxic conditions  PLX-PAD recruits pericytes and endothelial cells in an in-vivo plug assay  PLX-PAD-secreted factors promote tube formation in-vitro 21 Proprietary data of Pluristem Therapeutics Inc. Possible explanation for the difference in therapeutic effect of 150 vs 300 million cells 22 Proprietary data of Pluristem Therapeutics Inc. Difference in therapeutic effect of 150M vs 300M 23 • This result could be explained by the relatively small sample size and higher Day 0 values observed for the treatment groups • No significant difference in efficacy detected between the 150M and 300M cell groups. The 2 treated groups did better over the Placebo group. • Difference in the interactions between the cell and the patient’s body and between the cells themselves depending on the concentrations of the cells that are administered Proprietary data of Pluristem Therapeutics Inc. Can cell therapy become the next generation of biological therapeutic products? 24 Proprietary data of Pluristem Therapeutics Inc. Cell therapy “must haves” to become the next biological products • Demonstrate significant improvements in clinical studies • Regulatory approvals – FDA, PEI (Germany), South Korea, Australia & Israel • Specific cell products (PLX-PAD, PLX-R18, etc.) • In-house manufacturing (high margins) • Out-license deals- United therapeutics Inc. & CHA Bio (Korea) • Comprehensive IP ownership – 34 granted patents, about 120 pending applications 25 Proprietary data of Pluristem Therapeutics Inc. Management Team Zami Aberman Chairman & CEO Yaky Yanay President & COO Efrat Livne-Hadass VP Human Resources Hillit Mannor Shachar, M.D., M.B.A. VP Business Development Boaz Gur-Lavie CFO Ohad Karnieli, Ph.D., M.B.A. VP Technology & Manufacturing Racheli Ofir, Ph.D. VP Research & Intellectual Property Esther Lukasiewicz Hagai, M.D., Ph.D. VP Clinical & Medical Affairs Sagi Moran VP Operations Orly Amiran VP Quality Assurance Karine Kleinhaus, M.D., MPH Divisional VP, North America 26 Proprietary data of Pluristem Therapeutics Inc. 27 Proprietary data of Pluristem Therapeutics Inc.