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Company Presentation July 2020
Company PresentationJuly 2020
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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• Cell therapy company focused on Regenerative Medicine
• Several Off-the-shelf placenta-derived cell product candidates
• Two ongoing Phase III studies in critical limb ischemia (CLI) 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 patents)
• Publicly listed on Nasdaq and TASE
• Cash: ~$44 million (as of April 30, 2020 + $15 million raised in May 2020)
• Full time employees: ~150
Pluristem Therapeutics
The Need for Cell Therapy
Complexity of the diseaseInnovative treatments are needed to treat complex diseases
The Economic ImpactSome of the world’s largest economies are now facing subsequentincreases in health-care costs.
The Human ImpactAging is often associated with debilitating medical conditions,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)
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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/
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
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
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
ARDS due to COVID-19 PLX-PAD U.S. (EU pending)
PLX-PAD
Peripheral Arterial Disease
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• 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
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)
(N=172)
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Ongoing Phase III study in CLI- U.S., Europe & Israel (N=246)
Ongoing CLI Phase III Study
More than 80% of the study’s population enrolled Awarded adaptive pathway program in the EU Expected interim readout in the beginning
of calendar Q4 2020, following conclusion of discussions with the FDA and EMA towards readout, confirming understandings, including endpoint, timing and procedures of cleaning data during COVID-19 limitations
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.
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 patientsDoses tested 300M cells vs. Placebo (randomization ratio 2:1)
Administration IM injections in the affected leg, 2 treatments at 8-week intervalPrimary 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
PLX-PAD
Muscle Regeneration
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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 tosurpass 6 million by the year 2050
• Hip fracture often leads to serious long-term complications,including pain, functional decline and disability
• Up to 36% mortality rate after one year due to immobilityassociated diseases
• Source: Simran Mundi, Bharadwaj Pindiprolu, Nicole Simunovic, Mohit Bhandari• Kannus P, Parkkari J, Sievänen H, et al. Epidemiology of hip fractures. • www.uptodate.com
Contralateral(non–operated)
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Phase 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
Muscle Regeneration
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, 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)
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€ 7.4 million grant from the EU Horizon 2020 program
• More than 60% of the study’s population enrolled
PLX-PAD
Coronavirus – COVID-19
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PLX-PAD has anti-inflammatory and immunomodulatory properties, potentially leading to reduction of inflammation and lung injury
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• The 2019 novel coronavirus (SARS-CoV-2) infection causes clusters of severe respiratory illness associated withneed for intensive care unit (ICU) admission and high mortality. Studies have revealed that pneumonia is themost common complications following SARS-CoV-2 infection, and followed by Acute Respiratory DistressSyndrome (ARDS)*
• Cytokine storm (CS) refers to excessive and uncontrolled release of pro-inflammatory cytokines, commonlypresents as systemic inflammation, multiple organ failure, and high inflammatory parameters. In coronaviruspneumonia, a large number of inflammatory cell infiltration and CS led to acute lung injury, ARDS and death**
PLX Cells as Treatment for Severe COVID-19 Cases Complicated by Acute Respiratory Distress Syndrome (ARDS)
• PLX cells may potentially reduce the incidence and/or severity of COVID-19 pneumoniaand pneumonitis leading hopefully to a better prognosis for the patients
• Good safety profile for PLX-PAD observed from clinical trials involving hundreds of patientsworldwide
• PLX cells are allogeneic mesenchymal-like cells that have immunomodulatory properties thatinduce the immune system’s natural regulatory T cells and M2 macrophages, and thus mayprevent or reverse the dangerous overactivation of the immune system
Source: *Wang 2020, Guan 2020 ; **Channappanavar 2017, Zhang 2020
• Pluristem reported (May 14, 2020) a follow up for 8 (1 in the U.S. and 7 in Israel) out of 18 ventilator-dependent COVID-19 patients, that have completed a 28-day follow up period and have been treatedunder compassionate use program in Israel and U.S.: 87.5% survival rate 75% of patients were off any mechanical ventilation 62.5% of the patients were discharged alive from the hospital
• Following the U.S. FDA clearance of Pluristem’s Investigational New Drug (IND) application for a Phase IICOVID-19 Study, the company announced the activation of clinical sites and commencement of patientenrollment in the U.S.
• A Clinical Trial Application (CTA) has been filed in Europe• We expect to provide guidelines on the expected study duration a few weeks following the
commencement of the study• Parallel Expanded access program in the U.S. and in Europe, subject to governmental financing
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28-Day Follow Up for COVID-19 Patients under Compassionate Use Program in Israel and U.S. and Phase II Clinical Study in U.S
Design Phase II, randomized, Double-Blind, Placebo-controlled
Study population Hospitalized, mechanically ventilated, adult patients suffering from respiratory failure and ARDS due to COVID-19
Countries U.S . (CTA was filed in EU)Sample size 140 patientsStudy design 600M cells - 1 administration
300M cells - 2 administrations 300M cells 1 administration + Placebo 1 administrationPlacebo - 1 administrationPlacebo - 2 administrations
Administration IM injectionsPrimary efficacy endpoint Number of ventilator free days (within 28 days)Secondary efficacy endpoints
All cause mortality; Duration of mechanical ventilation, mean improvement relative to baseline on a 7-point ordinal scale, ICU-free-days, Hospitalization-free days
Follow Up length At week 8, 26 and 5221
PLX-PAD as a Treatment for ARDS Due to COVID-19
PLX-R18
Hematological Deficiencies
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• 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)
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
• 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 associated withCOVID-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 €18 million and thethird €12 million
• Will be payable to the EIB in a single payment following five years from the disbursement of the first andsecond tranches and in two annual payments starting on the fourth year from disbursement of the thirdtranche, 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 starting 2024,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
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Regulatory support
Governmental agencies collaborators and
projects
Significant Regulatory and Government Support
Pluristem keeps IP and manufacturing rights in all collaborations
Partnerships and Collaborations
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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, MDVP Clinical & Medical Affairs
