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Page 1: Company Presentation - Pluristem Therapeutics › wp-content › uploads › 2016 › 04 › ...Lior Raviv VP Operations & Development Orly Amiran VP Quality Assurance 24 LiranShani,

Company PresentationFebruary 2020

Page 2: Company Presentation - Pluristem Therapeutics › wp-content › uploads › 2016 › 04 › ...Lior Raviv VP Operations & Development Orly Amiran VP Quality Assurance 24 LiranShani,

This presentation contains express or implied forward-looking statements within the Private Securities Litigation Reform Act of 1995 and other U.S. Federalsecurities laws. For example, we are using forward-looking statements when we discuss the expected timing of obtaining regulatory approval for our variouspatient trials and clinical data readout, proposed trials that may occur in the future, the timing and implementation of our collaborations with various partnersand the execution of definitive agreements relating to such collaborations and the potential benefits and impact our products could have on improving patienthealth care. These forward-looking statements and their implications are based on the current expectations of our management only, and are subject to anumber of factors and uncertainties that could cause actual results to differ materially from those described in the forward-looking statements. The followingfactors, among others, could cause actual results to differ materially from those described in the forward-looking statements: changes in technology and marketrequirements; we may encounter delays or obstacles in launching and/or successfully completing our clinical trials; our products may not be approved byregulatory agencies, our technology may not be validated as we progress further and our methods may not be accepted by the scientific community; we may beunable to retain or attract key employees whose knowledge is essential to the development of our products; unforeseen scientific difficulties may develop withour process; our products may wind up being more expensive than we anticipate; results in the laboratory may not translate to equally good results in real clinicalsettings; results of preclinical studies may not correlate with the results of human clinical trials; our patents may not be sufficient; our products may harmrecipients; changes in legislation; inability to timely develop and introduce new technologies, products and applications; loss of market share and pressure onpricing resulting from competition, which could cause our actual results or performance to differ materially from those contemplated in such forward-lookingstatements. Except as otherwise required by law, we undertake no obligation to publicly release any revisions to these forward-looking statements to reflectevents or circumstances after the date hereof or to reflect the occurrence of unanticipated events. For a more detailed description of the risks and uncertaintiesaffecting us, reference is made to our reports filed from time to time with the Securities and Exchange Commission

Forward looking Statement

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Page 3: Company Presentation - Pluristem Therapeutics › wp-content › uploads › 2016 › 04 › ...Lior Raviv VP Operations & Development Orly Amiran VP Quality Assurance 24 LiranShani,

• Cell therapy company focused on Regenerative Medicine

• Several Off-the-shelf placenta-derived cell product candidates

• Two ongoing Phase III studies in ischemia associated with diabetes complications and in muscle regeneration

• Favorable safety profile and efficacy data from hundreds of patients treated worldwide

• Best-in-class cell manufacturing technology producing highest quality cell products at a commercial scale

• Strong IP portfolio (over 120 granted & allowed patents)

• Publicly listed in Nasdaq and TASE

• Cash and cash equivalents ~$17.5 million (as of Dec. 31, 2019)

• Full time employees: 150

Pluristem Therapeutics

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Page 4: Company Presentation - Pluristem Therapeutics › wp-content › uploads › 2016 › 04 › ...Lior Raviv VP Operations & Development Orly Amiran VP Quality Assurance 24 LiranShani,

Complexity of the diseaseInnovative treatments are needed to treat complex diseases

The Economic ImpactSome of the world’s largest economies are nowfacing subsequent increases in health-care costs.

The Human ImpactAging is often associated with debilitating medicalconditions, many of which are still unmet needs.

Longer lifespansLifespan has increased significantly, Nearly 2 billion people across the world are expected to be over 60 years old by 2050 (World Health Organization)

The Need for Cell Therapy

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Page 5: Company Presentation - Pluristem Therapeutics › wp-content › uploads › 2016 › 04 › ...Lior Raviv VP Operations & Development Orly Amiran VP Quality Assurance 24 LiranShani,

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Placenta-Derived Cells

• Ethically accepted• Rich & diverse• Pro-angiogenic & Immunoregulatory • Young donors • Unlimited source & easy to collect• Ability to manufacture treatments for

over 20,000 patients per placenta

The Placenta Project wasLaunched by the US NationalInstitutes of Health (NIH) in 2013to further explore the role of theplacenta in health and disease

http://www.the-scientist.com/?articles.view/articleNo/43618/title/The-Prescient-Placenta/

Page 6: Company Presentation - Pluristem Therapeutics › wp-content › uploads › 2016 › 04 › ...Lior Raviv VP Operations & Development Orly Amiran VP Quality Assurance 24 LiranShani,

Marketing-ready Industrialized Technology Platform

Manufacturing Process Approved by:6

State-of-the-art, proprietary bioreactor systemwhich provides a 3D micro-environment for cellsthat mimics the human body condition

Controlled, automated, efficient and scalablemanufacturing technology

Marketing ready, cost effective industrializedplatform

Controlling the conditions within our bioreactorsallows us to produce several unique patentedproducts

Page 7: Company Presentation - Pluristem Therapeutics › wp-content › uploads › 2016 › 04 › ...Lior Raviv VP Operations & Development Orly Amiran VP Quality Assurance 24 LiranShani,

PLURISTEM in one slide

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Placenta

Technology

Allogeneic off-the-shelf

Simple IM administration

Adaptive slow release secretion of cytokines

Long term regenerative effect

Page 8: Company Presentation - Pluristem Therapeutics › wp-content › uploads › 2016 › 04 › ...Lior Raviv VP Operations & Development Orly Amiran VP Quality Assurance 24 LiranShani,

Indication ProductCandidate

Location Pre-Clinical Phase I Phase II Phase IIIFunding

Clinical Pipeline

via FDA Animal Rule

Critical Limb Ischemia

Intermittent Claudication

Muscle Regeneration following Hip Fracture

Acute Radiation Syndrome*

PLX-PAD

PLX-PAD

PLX-PAD

PLX-R18

Graft Versus Host Disease PLX-PAD

Incomplete recovery following bone marrow transplantation PLX-R18

U.S., Europe Israel

U.S., Europe South Korea,

Israel

U.S., Europe Israel

U.S.

Israel

U.S., Israel

* FDA Orphan Drug Designation

*

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Extensive pre-clinical data in various indications; such as ischemic stroke, TNBC, CNS

Page 9: Company Presentation - Pluristem Therapeutics › wp-content › uploads › 2016 › 04 › ...Lior Raviv VP Operations & Development Orly Amiran VP Quality Assurance 24 LiranShani,

PLX-PAD

Peripheral Arterial Disease

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Page 10: Company Presentation - Pluristem Therapeutics › wp-content › uploads › 2016 › 04 › ...Lior Raviv VP Operations & Development Orly Amiran VP Quality Assurance 24 LiranShani,

• CLI is caused by fatty deposits in leg arteries that obstruct blood flow• Risk factors include smoking, diabetes, obesity, cardiovascular problems and hypertension• CLI patients suffer from severe pain, skin wounds, tissue necrosis and poor quality of life• High risk of leg amputation and death• Up to 35% of patients are unsuitable or will not benefit from revascularization

Peripheral Arterial Disease - Critical Limb Ischemia (CLI)

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PLX-PAD is designed to treat CLI by reducing inflammation and stimulate the growth of blood vessels to bring oxygenated blood to ischemic tissue

5 Year Mortality Rate Inpatient & Outpatient Treatment Costs by Rutherford Category

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Clinical Development in Peripheral Arterial Disease

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Completed two Phase I studies in CLI- U.S. & Germany (N=27) Good safety profile Increase in tissue perfusion, 60% reduction in the risk for death or amputation Dose identification- two treatments of 300 million cells, two months apart

Completed Phase II study in intermittent claudication (IC)- U.S., Germany, S. Korea & Israel Good safety profile Significant increase in walking distance , reduction in surgical events and HbA1c and CRP levels Confirmation of Phase III design including- dose (300m cells), dose regimen (2 administrations)

Ongoing Phase III study in CLI- U.S., Europe & Israel (N=246) Completed enrollment of half of the study’s population (n=123) in April 2019. EU Adaptive

Pathways Program allows for an interim analysis following 12 months follow-up, which may allow for conditional marketing approval in Europe

(N=172)

Page 12: Company Presentation - Pluristem Therapeutics › wp-content › uploads › 2016 › 04 › ...Lior Raviv VP Operations & Development Orly Amiran VP Quality Assurance 24 LiranShani,

Ongoing CLI Phase III Study - Overview

Design Phase III, randomized, Double-Blind, Placebo-controlled (2:1)

Study population CLI subjects with minor tissue loss, unsuitable for revascularization

Countries Germany, UK, U.S., Poland, Hungary, Czech republic, Bulgaria, Macedonia, Israel

Sample size 246 patients

Doses tested 300M cells vs. Placebo (randomization ratio 2:1)

Administration IM injections in the affected leg, 2 treatments at 8-week interval

Primary efficacy endpoint Time to occurrence of major amputation of leg or death (AFS)

Main Secondary & exploratory efficacy endpoints

Composite efficacy endpoint; Pain; Complete wound healing; Quality-of-life; Adjudicated amputations; TcPO2; cytokine levels

Follow Up length 52 Weeks

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€ 7.6 million grant from the EU Horizon 2020 program

Page 13: Company Presentation - Pluristem Therapeutics › wp-content › uploads › 2016 › 04 › ...Lior Raviv VP Operations & Development Orly Amiran VP Quality Assurance 24 LiranShani,

Disclaimer: The results presented above are a small sample of the ongoing trial, chosen by the principal investigator, and are not representative of the full trial population. These results may not be typical and could be materially different from the results reported at the completion of the trial. Investors are cautioned to consider this sample data at their own risk.

Before 1st treatment Before 2nd treatmentPatient #1

Patient #2

After 1 year FU

Patient #3

Ongoing CLI Phase III Study

• CLI Expanded Access Program cleared by FDA to enroll patients unsuitable for inclusion in the ongoing Phase 3 clinical trial

• Program to enroll an initial 100 CLI Rutherford Category 5 patients

• FDA approved cost recovery for the treatment

CLI Expanded Access Program (EAP)

Page 14: Company Presentation - Pluristem Therapeutics › wp-content › uploads › 2016 › 04 › ...Lior Raviv VP Operations & Development Orly Amiran VP Quality Assurance 24 LiranShani,

PLX-PAD

Muscle Regeneration

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Page 15: Company Presentation - Pluristem Therapeutics › wp-content › uploads › 2016 › 04 › ...Lior Raviv VP Operations & Development Orly Amiran VP Quality Assurance 24 LiranShani,

PLX-PAD is designed to stimulate muscle regeneration –gain muscle strength and volume15

There are currently no approved treatments for post-operative regeneration of injured or weak skeletal muscle

* Source: Simran Mundi, Bharadwaj Pindiprolu, Nicole Simunovic, Mohit Bhandari

Muscle Regeneration Following Hip Fracture

• Hip fracture often results in serious long-term complications,including pain, functional decline and disability

• Up to 30% of hip fracture patients die within 1 year due toimmobility associated diseases

• Annual treatment costs in the U.S. are between $10 to $15billion, and are expected to rise due to aging population

• Attributable costs for hip fracture are $80,000, demonstratingthe cost burden of long term care after fracture

Page 16: Company Presentation - Pluristem Therapeutics › wp-content › uploads › 2016 › 04 › ...Lior Raviv VP Operations & Development Orly Amiran VP Quality Assurance 24 LiranShani,

Contralateral(non–operated)

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Muscle RegenerationPhase I/II Study of PLX-PAD for Muscle Injury Following Total Hip Replacement (N=20)

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

Page 17: Company Presentation - Pluristem Therapeutics › wp-content › uploads › 2016 › 04 › ...Lior Raviv VP Operations & Development Orly Amiran VP Quality Assurance 24 LiranShani,

Ongoing Muscle Regeneration Phase III Study

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, Israel

Sample size 240 patients

Doses tested 150M cells vs. Placebo (randomization ratio 1:1)Administration IM injections in the operated leg on the day of surgery

Primary efficacy endpoint Short Physical Performance Battery (SPPB) score at week 26

Main Secondary & exploratory efficacy endpoints

Muscle strength, muscle mass & volume, hospitalization time, lower extremity measure

Follow Up length 26 (efficacy), 52 weeks (safety)

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€ 7.4 million grant from the EU Horizon 2020 program

Page 18: Company Presentation - Pluristem Therapeutics › wp-content › uploads › 2016 › 04 › ...Lior Raviv VP Operations & Development Orly Amiran VP Quality Assurance 24 LiranShani,

PLX-R18

Hematological Deficiencies

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Page 19: Company Presentation - Pluristem Therapeutics › wp-content › uploads › 2016 › 04 › ...Lior Raviv VP Operations & Development Orly Amiran VP Quality Assurance 24 LiranShani,

• 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

• Phase I - Incomplete Hematopoietic Recovery Following Hematopoietic Cell Transplantation (HCT) N= 24 Open-label trial, allows for interim data analysis Clinical sites in U.S & Israel FDA Orphan Drug Designation Data from first two cohorts showed PLX-R18 led to increased production of

platelets & red blood cells, ultimately reducing the number of required transfusions

Hematological Programs

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PLX-R18 is designed to stimulate the regeneration of damaged bone marrow to produce blood cells (white, red and platelets)

Page 20: Company Presentation - Pluristem Therapeutics › wp-content › uploads › 2016 › 04 › ...Lior Raviv VP Operations & Development Orly Amiran VP Quality Assurance 24 LiranShani,

Acute Radiation Syndrome (ARS) – The Need

ARS occurs following acute exposure to very high levels of radiation and involves severe lethalinjuries to the bone marrow as well as to other organs and systems within the body• Screening- PLX-R18 release a combination of therapeutic proteins in response to the patient’s

needs and doesn’t require pre-screening• Treatment in mass casualty event- PLX-R18 can be quickly administered by simple

intramuscular injections and does not require genetic or tissue matching, suitable to treat largenumber of victims exposed

• Comprehensive therapy- currently approved MCMs are all myeloid colony stimulating factors(increase white blood cells only), and may lead to severe side effects. PLX-R18 stimulates theregeneration of all three blood lineages

Page 21: Company Presentation - Pluristem Therapeutics › wp-content › uploads › 2016 › 04 › ...Lior Raviv VP Operations & Development Orly Amiran VP Quality Assurance 24 LiranShani,

PLX-R18 as Treatment for ARS (via the FDA Animal Rule)

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Series of studies conducted by the U.S. National Institutes of Health (NIH), testing PLX-R18 as apotential treatment for ARS

Page 22: Company Presentation - Pluristem Therapeutics › wp-content › uploads › 2016 › 04 › ...Lior Raviv VP Operations & Development Orly Amiran VP Quality Assurance 24 LiranShani,

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Regulatory support

Governmental agencies collaborators

Significant Regulatory and Government Support

Targeted projects in the coming year

Page 23: Company Presentation - Pluristem Therapeutics › wp-content › uploads › 2016 › 04 › ...Lior Raviv VP Operations & Development Orly Amiran VP Quality Assurance 24 LiranShani,

Pluristem keeps IP and manufacturing rights in all collaborations

Partnerships and Collaborations

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Page 24: Company Presentation - Pluristem Therapeutics › wp-content › uploads › 2016 › 04 › ...Lior Raviv VP Operations & Development Orly Amiran VP Quality Assurance 24 LiranShani,

Zami AbermanExecutive Chairman

Efrat Livne-Hadass VP Human Resources

Racheli Ofir, Ph.D.VP Research & Intellectual Property

Chen Franco-YehudaCFO

Yaky YanayPresident & CEO

Management Team

Efrat KaduriDirector of Marketing & Business Development

Lior RavivVP Operations & Development

Orly AmiranVP Quality Assurance

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Liran Shani, M.D.Acting VP Clinical & Medical Affairs

Page 25: Company Presentation - Pluristem Therapeutics › wp-content › uploads › 2016 › 04 › ...Lior Raviv VP Operations & Development Orly Amiran VP Quality Assurance 24 LiranShani,

[email protected] Israel +972-74-710-8600U.S. +1-347-973-2098

www.Pluristem.com

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