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December 2020 COMPANY PRESENTATION Inspired by Life
December 2020
COMPANY PRESENTATION
Inspired by Life
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This presentation contains express or implied forward-looking statements within the Private Securities LitigationReform Act of 1995 and other U.S. Federal securities laws. For example, we are using forward-looking statementswhen we discuss the expected timing of obtaining regulatory approval for our various patient trials and clinical datareadout, proposed trials that may occur in the future, the timing and implementation of our collaborations withvarious partners and the execution of definitive agreements relating to such collaborations and the potentialbenefits and impact our products could have on improving patient health care. These forward-looking statementsand their implications are based on the current expectations of our management only, and are subject to a numberof factors and uncertainties that could cause actual results to differ materially from those described in the forward-looking statements. The following factors, among others, could cause actual results to differ materially from thosedescribed in the forward-looking statements: changes in technology and market requirements; we may encounterdelays or obstacles in launching and/or successfully completing our clinical trials; our products may not be approvedby regulatory agencies, our technology may not be validated as we progress further and our methods may not beaccepted by the scientific community; we may be unable to retain or attract key employees whose knowledge isessential to the development of our products; unforeseen scientific difficulties may develop with our process; ourproducts may wind up being more expensive than we anticipate; results in the laboratory may not translate toequally good results in real clinical settings; results of preclinical studies may not correlate with the results ofhuman clinical trials; our patents may not be sufficient; our products may harm recipients; changes in legislation;inability to timely develop and introduce new technologies, products and applications; loss of market share andpressure on pricing resulting from competition, which could cause our actual results or performance to differmaterially from those contemplated in such forward-looking statements. Except as otherwise required by law, weundertake no obligation to publicly release any revisions to these forward-looking statements to reflect events orcircumstances after the date hereof or to reflect the occurrence of unanticipated events. For a more detaileddescription of the risks and uncertainties affecting us, reference is made to our reports filed from time to time withthe Securities and Exchange Commission
Forward Looking Statements
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Pluristem At a Glance Nasdaq (PSTI), TASE (PSTI)
Platform technology with advanced clinical pipeline• Development for muscle injuries, inflammatory diseases and
hematological deficiencies• Diverse clinical pipeline with 3 clinical readouts expected in the
coming year
Industrial scale in-house GMP manufacturing facility• High quality cell products at a commercial scale• Manufacturing process approved by key regulators• Advanced cold chain logistical capabilities
Off-the-shelf placenta-derived cell products• No blood or tissue matching required• Young, highly potent and ethical source
Financial position• Cash: ~$53 million (as of Sept. 30, 2020)• European Investment Bank of €50 million non-dilutive financing
Strong IP portfolioOver 120 granted patents globally
Global presenceISRAEL | U.S. | EU
To develop innovative cell therapies at the highest standard for unmet medical needs, designed to improve the quality of life for millions of patients worldwide.
Our Commitment
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Placenta-Derived Cells
• Young donors after full-term delivery, undergoing an elective caesarean section
• Ethically accepted
1 placenta » 20,000 patients
Rich & diverse
Unlimited source & easy to collect
Mesenchymal-like adherent stromal cells
Pro-angiogenic & immunoregulatory
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Manufacturing Technology:
• Patented technology platform with wide applications
• Marketing scale 3D technology applied in all of our clinical trials
• Cost-effective, market-ready industrialized platform
• Automated, efficient and validated technology• Scalable and tech-transferable technology for
additional capacity• GMP certified • No dependency on third party manufacturing
subcontractor
Manufacturing Process Approved by:
Proven:
• Batch-to-batch consistency• Comparability • Off-the-shelf biopharmaceutical: No special
preparation required
State-of-the-art3D bioreactor cell expansion system, designed to mimic the human body
In-house Commercial-Scale Manufacturing Facility
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Thawing Device Storage
Advanced cold chain logistics
Quality Control
ManufacturingCell
HarnessingProcess
DevelopmentClinical
Development Cold Chain
GMPManufacturing
1 placentacan treat ~ 20,000patients
Regulatory Approvalsin EU, USA, Israel, South Korea &Japan
IMInjection Shipment
Controlled automatedscalable 3D manufacturing facility
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Full Vertical Solution: From Raw Material to the Patient’s Bed
Wide Application of Placenta Cells
Market-Ready Scalable Technology
Platform
Off-the-shelf, Allogeneic Line
of Products
Simple IMAdministration
Adaptive Slow Secretion of
Cytokines
Long-term Regenerative
Effect
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From the Miracle of Birth to Regenerative Medicine for All
Inflammation Muscle regeneration
» »
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Clinical Pipeline
*Via FDA Animal Rule
PRECLINICAL PHASE I PHASE II PHASE IIIFUNDING/ PartnerLOCATIONINDICATIONFOCUSPRODUCT
PLX-PAD
Muscle Injuries
Inflammatory Diseases
Muscle Regeneration following Hip Fracture U.S., Europe, Israel
ARDS associated with COVID-19
Chronic Graft Versus HostDisease
U.S., Europe, Israel
Israel
Hematological Deficiencies
Acute Radiation Syndrome*
Hematopoietic Recovery Following Hematopoietic Cell Transplantation (HCT)
U.S.
U.S., Israel
PLX-R18
PLX-PADMuscle Regeneration
PLX-PAD is designed to stimulate muscle regeneration –gain muscle strength and volume
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There are currently no approved treatments for post-operative regeneration of injured or weak skeletal muscle
Muscle Regeneration Following Hip Fracture• As the population ages, the number of hip fractures continues to
increase
• Worldwide, the total number of hip fractures is expected to surpass 6million by the year 2050*
• Hip fracture often leads to serious long-term complications, includingpain, functional decline and disability**
• Up to 36% mortality rate after one year due to immobility associateddiseases***
*Kannus P, Parkkari J, Sievänen H, et al. Epidemiology of hip fractures**Simran Mundi, et. al. 2014***Jorma Panula, et. al. 2011
Contralateral(non–operated)
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Phase I/II Study of PLX-PAD for Muscle Injury Following Total Hip Replacement
Change in Volume Improvement of 300%
P=0.004
Change in Strength Improvement of 500%
P=0.0067
Change in Strength Improvement of 4000%
P=0.012
• PLX-PAD demonstrated a significant increase in muscle strength & volume compared to placebo
• First study to show efficacy of cell therapy in skeletal muscle injury
Muscle Regeneration
Muscle Regeneration Phase III Study Design
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Design Phase III, randomized, Double-Blind, Placebo-controlled
Study population Patients suffering from muscle injury following arthroplasty for hip fracture
Countries U.S., Germany, UK, Denmark, IsraelSample size 240 patientsDoses tested 150M cells vs. placebo (randomization ratio 1:1)Administration IM injections in the operated leg on the day of surgeryPrimary efficacy endpoint Short Physical Performance Battery (SPPB) score at week 26Main secondary & exploratory efficacy endpoints
Muscle strength, muscle mass & volume, hospitalization time, lower extremity measure
Follow-up length 26 (efficacy), 52 weeks (safety)
Approximately 70% of the study’s population enrolled
€ 7.6 million grant from the EU Horizon 2020 program
PLX-PADARDS Associated with COVID-19
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One of the most common causes of death from COVID-19
ARDS (Acute Respiratory Distress Syndrome) Associated with COVID-19
Clinical programs• Phase II studies in the U.S., Europe and Israel• Expanded Access Program in the U.S.• Per Patient Compassionate Use Program in Israel
PLX-PAD cells have immunomodulatory and cytoprotective properties which may play a meaningful role in mitigating the tissue-damaging effects of COVID-19 on the lungsPre-clinical support• Improve oxygenation and reduce lung fibrosis in an
ARDS murine model• Decrease the pro-inflammatory M1 and increase the
anti-inflammatory M2 macrophages • Reduce pro-inflammatory cytokine production: TNF-α,
INF-γ and IL-17A from stimulated PBMCs• Induce secretion of the anti-inflammatory cytokines IL-
10 and IL-1Ra, both inhibitors of the pro-inflammatory cytokine IL-1 from monocytes
• Induce an increase in regulatory T (Treg) cells
of patients were discharged alive from the hospital compared to 3.3%(38 out of 1151 patients)*
Survival rate87.5%
75.0%
ARDS Associated with COVID-19 Data
of patients were off any mechanical ventilation
62.5%
Encouraging results from Compassionate Use Programs in the U.S. & in Israel28-day follow-up for the first 8 ventilator-dependent COVID-19 patients (Reported May 2020)
* In data published in the NY area during March-April 2020 for patients requiring mechanical ventilation and discharged alive – Richardson S et al. Presenting Characteristics, Comorbidities, and Outcomes Among 5700 Patients Hospitalized with COVID-19 in the New York City Area. JAMA 2020. doi:10.1001/jama.2020.6775
** Barkama et al. 2020 Placenta-Derived Cell Therapy to Treat Patients with Respiratory Failure due to COVID-19 In press
Changes in C-Reactive Protein (CRP) test evaluating liver response to inflammation**
Blood CRP decreased
dramaticallyin all patients
following PLX-PAD treatments
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PLX-R18Hematological Deficiencies
Incomplete Hematopoietic Recovery Following Hematopoietic Cell Transplantation (HCT)
Incomplete hematopoietic recovery following HCT is a significant life-threatening condition with patients being vulnerable to infections and bleeding• Current treatment for incomplete hematopoietic recovery after transplantation includes administration of
factors stimulating blood cell growth.
• Significant number of patients do not respond to these growth factors and may require frequent blood product transfusions, exposing them to transfusion-related risks such as allo-sensitization and infections
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Hematological Programs
Phase I – Incomplete Hematopoietic Recovery Following Hematopoietic Cell Transplantation (HCT)Patient enrolment completed (N=21)Topline results for Phase I clinical trial expected in Q1 2021 calendar year • Initial results from 19 patients treated with PLX-R18 demonstrated*:
• Significant clinical improvements in Hb, ANC, and PLT among the high-dose cohort• PLX-R18 was found to be safe and well-tolerated
Hematological Programs
19*Paper: Safety and Demonstrated Efficacy of Placenta-Derived Cell Therapy PLX-R18 in Subjects with Incomplete Hematopoietic Recovery Following Hematopoietic Cell Transplantation: A Phase I International Multi-Center Study (confex.com)
Presented at The 62nd ASH Annual Meeting and Exposition, see link: PowerPoint Presentation (pluristem.com)
Acute Radiation Syndrome (ARS)• Studies conducted and funded by U.S. government (NIH, DOD)• FDA has cleared Pluristem’s Investigational New Drug (IND)
application for PLX-R18 in the treatment of ARS in case of nuclear events
• FDA Orphan Drug Designation
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PLX-R18is designed to stimulate the regeneration of damaged bone marrow to produce blood cells (white, red and platelets)
PLX-R18 as a Treatment for ARS (via the FDA Animal Rule), Series of studies conducted by the U.S. National Institutes of Health (NIH), testing PLX-R18 as a potential treatment for ARS
Hematological Programs
• EIB signed a €50 million non-dilutive financing agreement with Pluristem• Purpose:
To support Pluristem’s research and development in the EU to further advance its regenerative celltherapy platform, and to assist moving the products in its pipeline to market
A special focus on clinical development of PLX cells as a treatment for complications associatedwith COVID-19
EIB will support up to 50% of the cost of the project• Will be available for a period of 3 years, in three tranches, subject to the achievement of certain
clinical, regulatory and scaling up milestones: first tranche consisting of €20 million, second of €18million and the third €12 million. First Tranche of €20 million expected in H1/2021.
• Will be payable to the EIB in a single payment following five years from the disbursement of the firstand second tranches and in two annual payments starting on the fourth year from disbursement of thethird tranche, with each tranche having an interest rate of between 3%-4%
• EIB would be entitled to receive royalties from future revenues for a period of seven years starting2024, at a rate of 0.2% to 2.3%, pro-rated to the amounts that the Company received
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The European Investment Bank (EIB) –€50 Million Non-Dilutive Financing
Regulatory Scientific Collaborations & Partnering
Over 80 Clinical Sites in the Europe, Israel and USA
Funding
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Significant Support from Leading Organizations
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Chen Franco-YehudaCFO
Liran Shani, MDVP Clinical & Medical Affairs
Efrat Livne-HadassVP Human Resources
Lior RavivVP Operations & Development
Efrat KaduriDirector of Marketing & Business Development
Orly AmiranVP Quality Assurance
Racheli Ofir, Ph.D. VP Research & Intellectual Property
Yaky YanayCEO & President
Zami AbermanExecutive Chairman
Management Team
