COMPANY PRESENTATION January 2018 - … · January 2018 This presentation contains express or implied forward-looking statements within the Private Securities Litigation Reform Act

COMPANY PRESENTATIONJanuary 2018

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

2

Cell therapy company developing off-the-shelfplacenta-derived cell products

Entering late-stage trials in 3 indications

Multifactorial therapy releasing a range of therapeuticproteins in response to signals from patient's body

First in class 3D cell culturing technology allowing forefficient, controlled production of different cell productsin commercial quantities

Hundreds of patients treated worldwide

CORPORATE OVERVIEW

3

FINANCIAL GLANCE

4

Publicly Traded on Nasdaq and TASE [PSTI] Market Cap $̴160 million

Cash and Marketable Securities (9/30/2017) – $21.3 millionOctober 2017 Raise - $15 millionTotal - $36.3 million

Employees - 180

Non-Dilutive Grants - $27 million

Strong Collaborations and Partnerships

PLURISTEM in one slide

5

Placenta

Technology

Allogenic off-the-shelf

Simple IM administration

Adaptive slow release secretion of cytokines

long term regenerative effect

The Need forCell Therapy

Female Life Expectancy in

Developed Countries:1840-2009

Longer lifespansNearly 2 billion people across the world are

expected to be over 60 years old by 2050(World Health Organization)

6

The Economic ImpactSome of the world’s largest economies have startedfacing subsequent increases in health-care costs.Finding better ways to fund care, reducing drugexpenditure and refocusing pharmaceutical researchtowards more effective treatment is now essential

The Human ImpactAging is often associated with debilitating medicalconditions, many of which are still unmet needs.Accelerated regulatory pathways are alreadyavailable around the world to reduce the time tomarket for such therapies

7

The Need forCell Therapy

8

A CHANGE INREGULATORYENVIRONMENT

8

“Cell therapies…hold significant promise for transformative and potentially curative treatments for some of humanity’s most troubling and intractable maladies.”

FDA COMMISSIONER SCOTT GOTTLIEB, M.D., AUGUST 2017

The PLX Platform Technology

9

10

Placenta Derived Cells• Ethically accepted• Rich & Diverse• Highly potent

Pro-angiogenicImmunoregulatory

• Young donors • Unlimited source & Easy to

collect• Over 25,000 Doses of 300

million cells per placenta The Placenta Project wasLaunched by the US NationalInstitutes of Health (NIH) tofurther explore the role of theplacenta in health and disease

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

From the Miracle of Birth to Therapeutics for All

11

FDA Fast Track ApprovalFDA Expanded Access Program

EMA Adaptive Regulatory PathwayPMDA Accelerated Regulatory Pathway

Single Pivotal Study Ongoing (N=246)Program Supported By EU

Horizon 2020 Program ($8 Million)

Adaptive Regulatory Pathway

Pivotal Study To Begin 2018Program Supported By EU

Horizon 2020 Program ($8.7 Million)

CLI (PLX-PAD) Hip Fracture (PLX-PAD)

FDA Animal Rule PathwayFDA Orphan Drug Designation

Pivotal Study to Begin 2018Program Funded By U.S. Government

ARS (PLX-R18)

Reduces inflammation

Stimulates growth of collateral blood vessels

Stimulates repair of damaged muscle

PLX-PAD

Peripheral Arterial Diseases

Orthopedic Injuries

13

PLX-PAD Mechanism of Action

Indication

Critical Limb Ischemia (CLI)

Intermittent Claudication (IC)

Hip Fracture***

Acute Radiation Syndrome (ARS)

Location

U.S.Europe*

Japan**

U.S., EuropeS. Korea, Israel

U.S. Europe

U.S.

Late-stage trialsCompany Pipeline

Pre-Clinical Phase 2Phase 1 Phase 3Product

PLX-PAD

PLX-PAD

PLX-PAD

PLX-R18

Single pivotal study

* One Multinational trial- U.S- phase 3, Europe- via adaptive pathway allowing early marketing approval** Via PMDA’s accelerated regulatory pathway for regenerative therapies*** Pending FDA/EMA approval

Pivotal study via FDA Animal Rule

15

Funding

• Peripheral Arterial Disease (PAD) is caused by fatty deposits in legarteries that obstruct blood flow

• Risk factors include smoking, diabetes, heavy weight, cardiovascularproblems and hypertension

• Critical limb ischemia (CLI) patients suffer from severe pain at rest, skinwounds, tissue necrosis and poor quality of life with a high risk of legamputation and death

• Up to 40% of patients are unsuitable for revascularizationand experience up to a 40% amputation rate at 1 year*

• 5-6 million patients in U.S. and Europe suffer from CLI

• Estimated cost of treatment in U.S. alone is over $25 billion per year**

Peripheral Arterial Disease- Critical Limb Ischemia

*Source: European Society for Vascular Surgery (link)**Source: Sage Group- (link, link, link)

16

Build up of fatty substances in the wall of the artery

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, Austria

Sample size 246 patients

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

Administration Multiple IM injections in the affected leg, twice at an 8-week interval

Primary efficacy endpoint Time to occurrence of major amputation of the index 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 12-36 months

17

$8 million grant from the EU Horizon 2020 program to support Phase III trial

Regulatory Strategy

• Fast Track Designation assigned by U.S. FDA

• Regulatory Adaptive Pathway framework with the EMA

• Interim analysis of results in Phase III study may be used for the submission of CMA

• Interim analysis primary endpoint is designed to show efficacy, using composite endpoint

• We aim for a single pivotal trial for both territories for full approval

18

Expanded Access Program cleared by U.S. FDA for the treatment of CLI patients that are unsuitable for inclusion under the study protocol. Program allows for collection of real-

world data alongside the study. Pluristem may also be eligible to be compensated for the cost of treatment

Clinical Development of CLI in Japan

• Accepted to the PMDA’s accelerated regulatory pathway for

regenerative therapies

• A single 75 patient study may lead to early conditional marketing

approval and reimbursement

• Binding term sheet with Sosei CVC to establish joint venture for the

clinical development and commercialization of PLX-PAD for CLI in

Japan

19

20

Peripheral Arterial Disease - Intermittent Claudication

• Intermittent claudication (IC) is an earlier stage of PAD that can progress to CLI

• The most common symptoms are leg pain and weakness brought on by exercise, withresolution of the symptoms following rest

• PLX-PAD may present an alternative treatment option to endovascular revascularizationby stimulating the body to grow new blood vessels to bypass the blocked ones

• Recruitment completed for a Phase II study (N= 172), Data expected Q2 2018

Primary Efficacy Endpoint - Change in maximal walking distance one year after the first administration. Other endpoints include the change in initial claudication distance,

hemodynamic parameters, quality of life score and the rate of revascularization.

Phase II IC Study Multinational, randomized, double blind, placebo controlled Phase II study in the U.S., Germany, Israel, and South Korea. Patients received either two courses of 150 ×106 PLX-PAD cells, two courses of 300 ×106 cells,

two courses of placebo, or one course of 300 ×106 cells followed by placebo. In each of these study arms, the two courses were given intramuscularly (IM) , 3 months apart.

Indication

Critical Limb Ischemia (CLI)

Intermittent Claudication (IC)

Hip Fracture***

Acute Radiation Syndrome (ARS)

Late-stage trialsCompany Pipeline

Pre-Clinical Phase 2Phase 1 Phase 3Product

PLX-PAD

PLX-PAD

PLX-PAD

PLX-R18

Single pivotal study

* One Multinational trial- U.S- phase 3, Europe- via adaptive pathway allowing early marketing approval** Via PMDA’s accelerated regulatory pathway for regenerative therapies*** Pending FDA/EMA approval

Pivotal study via FDA Animal Rule

21

FundingLocation

U.S.Europe*

Japan**

U.S., EuropeS. Korea, Israel

U.S. Europe

U.S.

Injured (operated) Contralateral(non–operated)

Improvement of 4000%P=0.012

Improvement of 500%

P=0.0067

22

Muscle Regeneration- Clinical DataMuscle Injury Following Total Hip Replacement (N=20)

Phase III Hip Fracture Study

• Femoral neck fracture is the most common form of hip fracture• Annual treatment costs in the U.S. are estimated to be between $10 to

$15 billion, and are expected to rise due to the aging population, withmortality rates of up to 36%*

• Positive feedback from FDA and EMA on the proposed study design andendpoints of Phase III trial in treatment for muscle recovery followingarthroplasty for hip fracture

• PLX-PAD program in hip fracture might be eligible for BreakthroughTherapy designation and benefit from the 21st Century Cures Act as wellas the EMA’s Adaptive Pathways pilot project

23

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

$8.7 million grant from the EU Horizon 2020 program to support this Phase III trial

24

Stimulates regeneration of damaged bonemarrow to produce blood cells (white, red andplatelets)

Acute Radiation Syndrome (ARS)

Hematologic Indications

PLX-R18

PLX-R18 Mechanism of Action for Bone Marrow failure

25

Indication

Critical Limb Ischemia (CLI)

Intermittent Claudication (IC)

Hip Fracture***

Acute Radiation Syndrome (ARS)

Late-stage trialsCompany Pipeline

Pre-Clinical Phase 2Phase 1 Phase 3Product

PLX-PAD

PLX-PAD

PLX-PAD

PLX-R18

Single pivotal study

* One Multinational trial- U.S- phase 3, Europe- via adaptive pathway allowing early marketing approval** Via PMDA’s accelerated regulatory pathway for regenerative therapies*** Pending FDA/EMA approval

Pivotal study via FDA Animal Rule

26

FundingLocation

U.S.Europe*

Japan**

U.S., EuropeS. Korea, Israel

U.S. Europe

U.S.

Acute radiation Syndrome (ARS)In Preparations for pivotal study

27

Bone Marrow FailureFollowing or in support of a transplant of hematopoietic

stem cells (HCT)Ongoing Phase I study in U.S and Israel

Bone Marrow FailureAutoimmune diseases, Genetic disorders, Chemotherapy,

Radiation therapy, Side effects from treatments

PLX-R18 Programs

28

• PLX-R18 is an allogeneic, off-the-shelf product• Easy IM administration• Long shelf life• No need for prescreening - no effect if injected

to those who were not exposed to radiation• Supports recovery of all three blood lineages

(red and white blood cells and platelets)• Beneficial even when administered 48 hrs.

following exposure to radiation• Multifactorial secretion profile may treat other

injuries to tissues - potential for use in a broadspectrum of indications

Acute Radiation Syndrome (ARS)Acute exposure to very high levels of radiation causes ARS, with potentially lethal injury to multiple

organ systems including bone marrow

Collaboration on ARS with U.S. Government

Late Post Exposure

Department of Defense (DOD)Warfighter and Immediate Response

Department of Health and Human Services (DHHS)First Responders and Hospitals

Armed Forces Radiobiology Research Institute

NIAID/NIH

Chronic Phase (Months-Years)Response

Phase

Exposure

Timeline

ResearchInstitutes &

Agencies

Governmental Departments

Initial Response (hours)

Clinical Syndrome

24h

Pre-exposure

Acute Phase (Days-Weeks)

DEARE (Months-Years)ARS (Hours-Weeks)

Early Post Exposure

30

Collaboration with Fukushima Medical University to developPLX-R18 cells for the treatment of other component of ARS (GI, Lung and Skin),

and for morbidities following radiotherapy in cancer patients

Collaboration on ARS with U.S. Government

31

PLX-R18 Data - Phase I Equivalent Study (FDA Animal Rule)

Survival Weight

PLX-R18 Data - Phase II Equivalent Study (N=62) (FDA Animal Rule)

PLX-R18 treatment increased survival rates In irradiated non-human primates (NHPs)

• All doses of PLX-R18 tested showed improvements in survival rates compared to untreated groups• Two lower dosages, 4m and 10m/kg, resulted in an 85% survival rate in irradiated NHPs compared

to a 50% survival rate in untreated groups

PLX-R18 treatment of non-irradiated NHP does not effect animal survival

• PLX-R18 cells did not increase leukocyte levels in non-irradiated NHPs• No determination of an individual’s level of exposure would be required prior to treatment In

scenarios requiring the rapid treatment of large populations, such as in the case of a nuclearemergency

Study demonstrated a trend towards enhanced neutrophil and lymphocyte recovery

32

Successful transition from small to large animals as required by the FDA’s Animal Rule pathway

Placebo - 50%

20M/Kg - 67%

4/10M/Kg - 83/86%

Non irradiated and low radiation - 100% Group Females Males Females and Males Total 04+10

only

NR-00 3/3 = 100% 3/3 = 100% 6/6 = 100% 6/6 = 100%

NR-04 3/3 = 100% 3/3 = 100% 6/6 = 100%

18/18 = 100%NR-10 3/3 = 100% 3/3 = 100% 6/6 = 100%

NR-20 3/3 = 100% 3/3 = 100% 6/6 = 100%

R-00 1/3 = 33% 2/3 = 67% 3/6 = 50% 3/6 = 50%

R-04 2/3 = 67% 3/3 = 100% 5/6 = 83%

15/19 = 79%

11/13= 85%R-10 3/4 = 75% 3/3 = 100% 6/7 = 86%

R-20 2/3 = 67% 2/3 = 67% 4/6 = 67%

R-Id-00

-

3/3 = 100%

3/3 = 100%R-Id-04 3/3 = 100%

R-Id-10 3/3 = 100%

R-Id-20 3/3 = 100%

Legend:

R : RadiatedR-ID: Low RadiationNR : Non-Radiated

R-00 : Not TreatedR-04 : 4 million cells per kgR-10 : 10 million cells per kgR-20 : 20 million cells per kg

PLX-R18 Data - Phase II Equivalent Study (N=62) (FDA Animal Rule)

• Ongoing U.S. and Israeli Phase I clinical trial of R18 for the treatment of insufficient hematopoietic recovery following hematopoietic cell transplantation− N= 24− Open-label trial allows for interim data analysis

• Collaboration with the to evaluate PLX-R18 as an adjuvant therapy to umbilical cord blood transplantation in animal studies− Grant of $900,000 from Israel-U.S. Binational Industrial Research and Development

Foundation (BIRD)

• Granted European patent to cover indications related to the bone marrow’sinability to produce blood cells, such as autoimmune diseases, genetic disorders, chemotherapy, radiation therapy, and side effects from other treatments

PLX-R18 Hematological Program

34

PLX-Immune

35

Cell Expansion

3D

DownstreamDetachment,

wash, formulation,

freezing

Cell Expansion 2D

PLX-Immune Cells - Anti-Cancer Product

PLX-R18

PLX-PAD

PLX-Immune

36

Co-Inductionwith TNF-α/IFN-γ

during the last24 hours

Placenta Cell Expansion2D

ICSIntermediate cell stock250-400 vial

PLX cells had been induced with tumor necrosis factor alpha (TNF-α) and interferon-gamma (IFN-γ) to transiently alter their secretion profile

PLX-Immune Mechanism of Action

30% of treated mice had complete remission (compared to 0% in vehicle)

SubQ

Mammary Fat Pad

Suggested treatment: weekly injections

PLX – Immune are Anti-Tumorigenic in vivo

38

N=10 per group

39

PLX-Immune Cells Significantly Inhibit Cancer Cell Growth• Studies which examined the effect of PLX-Immune cells on the proliferation of over 50

lines of human cancerous cells showed anti-proliferative effect on 45% of the tested cancercell lines, with a strong inhibitory effect on various lines of breast, colorectal, kidney, liver,lung, muscle and skin cancers

• Comprehensive bioinformatics analysis identified common characteristics of the cancercell lines inhibited by PLX-immune cells which could be used in the future for screeningpatients’ tumors to identify those patients most likely to show a positive response totreatment with PLX-Immune cells

• An advanced study on female mice harboring human triple negative breast cancer showedstatistically significant reduction (p= 0.025) in mean tumor size in the PLX treated groupcompared with the untreated group, with 30% of the treated mice exhibiting completetumor remission

• A statistically significant reduction (p=0.003) was seen in the percentage of proliferatingproliferating tumor cells as well as in the level of blood vessels within the tumors

Best In Class GMP Facility

40

3D Manufacturing, In-house Cell ProductionPotential capability to manufacture up to 150,000 doses annually

41

Manufacturing Facility Approved by

42

1. Out-licensing commercialization deals with partners

2. Direct sales of indications with small patients population & high market price

3. Direct sales of our PLX-R18 product for Acute Radiation Syndrome (governments)

Commercialization Strategy

43

Pluristem keeps IP and manufacturing rights in all collaborations

Partnerships and Collaborations

Joint Venture for the South Korean market, IC indication

Conducting and Funding a trial to study the effectiveness of PLX-R18 as a treatment forARS following 24 hours from exposure

Examine the effectiveness of PLX-R18 prior to, and within the first 24 hours of exposureto radiation

Study PLX-R18 cells for the treatment of other component of ARS(GI, Lung and Skin)

Clinical studies + study PLX-R18 cells in the treatment of ARS andunderstanding of MOA

Evaluating PLX-R18 as an adjuvant therapy to umbilical cordblood transplantation

Clinical studies + research to study the unique immunology of theplacenta and the cells’ MOA

44

Investment Highlights • Publicly traded on the Nasdaq and Tel Aviv Stock Exchange [PSTI]

• Late-stage pipeline with products advancing towards commercialization and

funding by 3rd parties

• Advanced regulatory pathways that could shorten time to commercialization

• Expected near-term data readouts

• “Off the shelf” product, no HLA-matching required

• Unique multifactorial MoA supported by extensive research data

• Major technological competitive advantages

• Strong collaborations and partnerships

45

Initiate Pivotal Studies• Critical limb ischemia (CLI) - U.S., Europe (Japan yet to start)• Hip fracture - U.S., Europe• ARS

Clinical Data Readouts • Phase II Intermittent Claudication (IC)- Q2/2018 • Phase I incomplete engraftment of hematopoietic cell transplantation- open label• Pivotal study in ARS

Business Development • U.S. - Advance discussions with U.S. government regarding stockpiling of PLX-R18 for ARS• Japan - Finalize joint venture• Asia - licensing/ joint venture with partner for Asian market

Upcoming Milestones – 12 Months

46

Zami AbermanChairman & Co-CEO

Efrat Livne-Hadass VP Human Resources

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

Erez Egozi CFO

Yaky YanayPresident & Co-CEO

Management Team

Karine Kleinhaus, M.D., MPHDivisional VP, North America

Lior RavivVP Development

Orly AmiranVP Quality Assurance

47

[email protected] Israel +972-74-710-8600U.S. +1-914-512-4109

www.Pluristem.com

48