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Item 1. Business

2021-09-13 compared with 2020-09-10 · 734 added, 691 removed, 49 unchanged (97% of the section changed)

Current Business

are a leading developer of placenta-based cell therapy product candidates for the treatment of multiple ischemic, inflammatory

and hematologic conditions.

Our operations are focused on the research, development, manufacturing, conducting clinical trials

and business development of cell therapeutics and related technologies.

We are currently enrolling patients in

two Phase III studies:

one for critical limb ischemia, or CLI, and another for muscle recovery following surgery for hip fracture.

In addition, we are focusing on other indications such as acute radiation syndrome, or ARS, incomplete recovery following bone

marrow transplantation, Steroid-Refractory Chronic Graft Versus Host Disease, or cGVHD, and intermittent claudication, or IC.

received clearance from the U.S.

Food and Drug Administration, or the FDA, and the German health regulatory agency, the Paul Ehrlich

Institute, or the PEI, to conduct a Phase II study evaluating PLX cells for the treatment of severe cases of the COVID-19 coronavirus,

or COVID-19, complicated by Acute Respiratory Distress Syndrome, or ARDS.

We have treated several patients in Israel and in the

United States suffering from severe ARDS associated with COVID-19 under a compassionate use program.

In addition, the FDA has cleared

our Expanded Access Program, or EAP, for the use of our PLX-PAD cells to treat up to 100 patients suffering from ARDS caused by

COVID-19 outside of our ongoing Phase II COVID-19 study in the U.S.

We believe that each of these indications is a severe unmet

medical need.

PLX cells are derived from a class of

placental cells that are harvested from donated placenta at the time of full term healthy delivery of a baby.

PLX cell products

require no tissue or blood matching prior to administration.

They are produced using our proprietary three-dimensional expansion

Our manufacturing facility complies with the European, Japanese, Israeli, South Korean and the FDA’s current

Good Manufacturing Practice, or cGMP, requirements and has been inspected and approved by the European and Israeli regulators for

production of PLX-PAD for late stage trials.

We have also granted manufacturer/importer authorization and cGMP Certification by

Israel’s Ministry of Health.

If we obtain FDA and other regulatory approvals to market PLX cells, we expect to have in-house

production capacity to grow PLX cells in commercial quantities.

Research and Development - In-House Clinical

Manufacturing”

for additional information.

goal is to make significant progress with our clinical pipeline and our clinical trials in order to ultimately bring innovative,

potent therapies to patients who need new treatment options.

We expect to demonstrate a real-world impact and value from our pipeline,

technology platform and commercial-scale manufacturing capacity.

Our business model for commercialization and revenue generation

includes, but is not limited to, direct sale of our products, partnerships, licensing deals, and joint ventures with pharmaceutical

were incorporated in Nevada in 2001, and we have a wholly owned subsidiary in Israel called Pluristem Ltd.

and a wholly owned

subsidiary in Germany called Pluristem GmbH.

therapy is an emerging field within the regenerative medicine area.

The characteristics and properties of cells vary as a function

of tissue source and growth conditions.

The human placenta from which our PLX cells are derived provides an uncontroversial source

of non-embryonic, adult cells and represents an innovative approach in the cell therapy field.

The different factors that PLX

cells release suggest that the cells can be used therapeutically for a variety of ischemic, inflammatory, autoimmune and hematological

cells do not require tissue matching prior to administration.

This allows for the development of ready-to-use / “off-the-shelf”

allogeneic products.

We develop, and intend to commercialize,

cell therapy production technologies and products that are derived from the human placenta after a full term delivery of a healthy

Our PLX cells are adherent stromal cells, or ASCs, that are expanded using a proprietary 3D process.

This system utilizes

a synthetic scaffold to create an artificial 3D environment where placental-derived stromal cells can grow.

Our automated proprietary

3D, cGMP approved, process enables the large-scale monitored and controlled production of reproducible, high quality cell products

and is capable of manufacturing a large number of PLX doses originating from different placentas.

Additionally, our current manufacturing

process, which has scaled up as compared to previous years, has demonstrated batch-to-batch consistency, an important manufacturing

challenge for biological products.

primary objective is to be the leading provider of allogeneic placenta based cell therapy products that are true off-the-shelf

products that do not require any matching or additional manipulation prior to administration.

From the physician’s and patient’s

perspective, we believe that our PLX products are comparable to any other product delivered in a vial.

Our PLX products are administered

using a standard needle and syringe.

Our PLX products are in clinical stage development for multiple indications.

first product candidate, PLX-PAD, is currently in a Phase III multinational clinical trial in CLI, in a Phase III multinational

clinical trial in recovery following surgery for hip fracture, and in a Phase II clinical trial in the treatment of severe COVID-19

cases complicated by ARDS.

We have also completed Phase II multinational clinical trial in IC and a Phase I/II is currently conducted

with our PLX-PAD by Tel Aviv Sourasky Medical Center (Ichilov Hospital) for the treatment of Steroid-Refractory cGVHD.

second product candidate, PLX-R18, is under development in the United States for ARS via the FDA Animal Rule regulatory pathway,

as well as in a Phase I trial in the United States and Israel for incomplete hematopoietic recovery following hematopoietic cell

transplantation, or HCT.

We developed an additional product candidate,

PLX-Immune, which is under pre-clinical development for treatment of certain types of human cancer.

In January 2018, we announced

the publication of a peer-reviewed article in a journal which examined the effect of PLX-Immune cells on the proliferation of over

50 lines of human cancerous cells.

Data showed that the PLX-Immune cells exhibited an anti-proliferative effect on a wide range

of human cancer cell types, with a strong inhibitory effect on various lines of breast, colorectal, kidney, liver, lung, muscle

and skin cancers.

We have also conducted a pre-clinical trial of female mice harboring human triple negative breast cancer.

this study, the results showed a statistically significant reduction in tumor size as well as complete tumor remission in 30% of

treated recipients.

believe that using the placenta as a unique cell source, combined with our innovative research, development and high-quality manufacturing

capabilities, will be the “engine”

that drives this platform technology towards the successful development of additional

PLX cell therapy products and indications.

Clinical Development Product Candidates

Peripheral and Cardiovascular Diseases

Peripheral and Cardiovascular Diseases –

We are investigating the use of PLX-PAD cells for the treatment of peripheral

arterial disease, or PAD, including IC and CLI.

May 2015, our CLI clinical development program was selected for the EMA’s Adaptive Pathways Project.

The goal of the project

is to improve timely access for patients to new medicines.

During our fiscal year ended June 30, 2017, the FDA and several EU

regulatory agencies cleared our application to begin the pivotal Phase III trial of PLX-PAD cells in the treatment of CLI for

patients with minor tissue loss (Rutherford Category 5) who are unsuitable for revascularization.

This multinational Phase III

trial is being conducted in the United States, Europe and Israel.

In September 2017, we announced that the FDA granted a fast

track designation to our ongoing Phase III study of PLX-PAD for the treatment of CLI.

The FDA’s fast track designation is

a process designed to facilitate the development and expedite the review of drug to treat serious conditions and unmet medical

With fast track designation, there is an increased possibility for a priority review by the FDA of PLX-PAD cells for the

treatment of CLI.

the FDA’s and EMA’s advice and recommendations, we implemented the following items into the study design and the interim

data readout:

primary endpoint for the interim analysis will be identical to the full study endpoint, a comparison between the PLX-PAD treated

group and the placebo treated group of the number of days from randomization to occurrence of major amputation of the index leg

full study analysis will be based on 82 events.

Each event is defined as occurrence of major amputation of the index leg or death

while the interim readout will be conducted based on a minimum of 45 events, which have already occurred.

FDA cleared our EAP for the use of our PLX-PAD cell treatment in patients with CLI and we initiated the EAP in April 2019.

the terms of the EAP, an initial cohort of 100 Rutherford-5 CLI patients who are ineligible for inclusion under our ongoing Phase

III study protocol can be enrolled and treated.

have completed two Phase I safety/dose-escalating clinical trials for CLI, one in the United States and one in Germany.

CLI trials demonstrated that no blood type or human leukocyte antigen matching is required, and that the administration of PLX-PAD

cells is safe, even if two doses are administered to a patient on two different occasions.

In addition, PLX-PAD cells are potentially

effective in reducing the frequency of amputations in CLI patients.

Generally, the FDA and the EMA require the primary endpoint

for pivotal CLI clinical trials to be Amputation Free Survival, or AFS, at one year.

The pooled data from the two studies we conducted

suggest an AFS rate at one year of 86% in PLX-treated patients versus an AFS ranging between 48% to 66% in patients from placebo

arms in other CLI trials.

June 2018, we announced the results from our 172 patients, randomized, double blind, placebo controlled, and multinational Phase

II clinical trial in IC.

Analysis of the Phase II IC data, which was announced on November 2018, confirmed the optimal dosing

regimen of PLX-PAD in the treatment of PAD - two administrations of 300 million cells, each originating from a different donor.

This is also the treatment regimen being administered to patients in the Company’s ongoing multinational Phase III study

in CLI, a more severe stage of PAD.

PLX-PAD treated patients showed a good safety profile in the study.

April 2015, Japan’s PMDA approved our large-scale manufacturing methods and quality for PLX-PAD cells for use in clinical

In August 2015, the PMDA granted safety clearance to PLX-PAD cells for use in clinical trials in Japan, and in December

2015 we reached an agreement with the PMDA on the design of the final trial needed to apply for conditional marketing approval

of PLX-PAD cells in the treatment of CLI.

Currently, as part of our strategy to focus on our active clinical trials and marketing

readiness, we have not initiated clinical trial activities in Japan.

Indications –

In April 2018, we announced that the FDA cleared our IND for our Phase III trial for recovery following

surgery for hip fracture.

This multinational Phase III trial is being conducted in the United States, Europe and Israel.

confirmed that recovery following surgery for hip fracture is eligible for the Adaptive Pathways Project as well.

Phase III trial protocol and design was based on our phase I/II, randomized, double-blind, placebo-controlled study (n=20) to

assess the safety and efficacy of intramuscular injections of allogeneic PLX-PAD cells for the regeneration of injured gluteal

musculature after total hip replacement has been conducted in Germany under the approval of PEI.

In this study, PLX-PAD cells

or placebo were administered into the traumatized gluteal muscle during total hip replacement surgery.

The study results met its

primary efficacy endpoint, change in maximal voluntary isometric contraction force of the gluteal muscle at six months after total

hip replacement.

Patients treated with PLX-PAD had a significantly greater improvement of maximal voluntary muscle contraction

force than the placebo group (p=0.0067).

In addition, the study demonstrated that PLX-PAD was safe and well tolerated by the patients.

COVID-19 Complicated by ARDS –

In May 2020, the FDA cleared our IND application for the Phase II study of our PLX cells in the treatment of severe COVID-19 cases

complicated by ARDS and we initiated the study in June 2020.

The U.S trail is randomized, double-blind, placebo-controlled, multicenter,

parallel-group 140 patient study is evaluating the efficacy and safety of intramuscular injections of PLX-PAD for the treatment

Our Current Business

We are a biotechnology company

focused in the field of regenerative medicine, and a leading developer of placenta-based cell therapy product candidates for the treatment

of multiple inflammatory, muscle injuries and hematologic conditions.

Our operations are focused on the research, development, manufacturing,

conducting clinical trials and business development of cell therapeutics and related technologies.

Placental expanded, or PLX,

cells are derived from a class of placental cells that are harvested from donated placenta at the time of full term healthy delivery of

The cells are grown using our proprietary three-dimensional expansion technology and can be administered to patients off the-shelf,

without blood or tissue matching prior to administration.

PLX cells are believed to release a range of therapeutic proteins in response

to the patient’s condition, such as inflammation, muscle trauma, hematological disorders and radiation damage.

We are conducting several

multinational clinical studies which consist of a Phase III clinical study in muscle recovery following surgery for hip fracture and two

Phase II clinical studies in Acute Respiratory Distress Syndrome, or ARDS, associated with COVID-19 in the United States, Europe and Israel.

In addition, we are focusing on other clinical programs in the hematological field such as a Phase I clinical study for incomplete recovery

following bone marrow transplantation in the United States and Israel, an investigator-led Phase I/II Chronic Graft versus Host Disease,

or cGVHD, study in Israel, and Acute Radiation Syndrome, or ARS, under the U.S.

Food and Drug Administration, or FDA, animal rule.

believe that each of these indications is a severe unmet medical need.

Our manufacturing facility

complies with the European, Japanese, Israeli, South Korean and the FDA’s current Good Manufacturing Practice, or cGMP, requirements

and has been inspected and approved by the European and Israeli regulators for production of PLX-PAD for late stage trials.

been granted manufacturer/importer authorization and cGMP Certification by the Israeli Ministry of Health, or MOH.

If we obtain FDA and

other regulatory approvals to market PLX cells, we expect to have in-house production capacity to grow PLX cells in commercial quantities.

Our goal is to make significant

progress with our clinical pipeline and our clinical studies in order to ultimately bring innovative, potent therapies to patients who

need new treatment options.

We expect to demonstrate a real-world impact and value from our pipeline, technology platform and commercial-scale

manufacturing capacity.

Our business model for commercialization and revenue generation includes, but is not limited to, licensing deals,

joint ventures with pharmaceutical companies, direct sale of our products, and partnerships.

We were incorporated in Nevada

in 2001, and we have a wholly owned subsidiary in Israel called Pluristem Ltd., or the Israeli Subsidiary, and a wholly owned subsidiary

in Germany called Pluristem GmbH.

Scientific Background

Cell therapy is an emerging

field within the regenerative medicine area.

The characteristics and properties of cells vary as a function of tissue source and growth

The human placenta from which our PLX cells are derived provides an uncontroversial source of non-embryonic, adult cells and

represents an innovative approach in the cell therapy field.

The different factors that PLX cells release suggest that the cells can be

used therapeutically for a variety of ischemic, inflammatory, autoimmune and hematological deficiencies.

PLX cells do not require tissue matching

prior to administration, which allows the development of ready-to-use / “off-the-shelf” allogeneic products.

Our Technology

We develop, and intend to

commercialize, cell therapy production technologies and products that are derived from the human placenta after a full-term delivery of

a healthy baby.

Our PLX cells are adherent stromal cells that are expanded using a proprietary three-dimensional, or 3D, process.

system utilizes a synthetic scaffold to create an artificial 3D environment where placental-derived stromal cells can grow.

Our automated

proprietary 3D, cGMP approved, process enables the large-scale monitored and controlled production of reproducible, high quality cell

products and can manufacture a large number of PLX doses.

Additionally, our current manufacturing process, which has scaled up as compared

to previous years, has demonstrated batch-to-batch consistency, an important manufacturing challenge for biological products.

Product Candidates

Our primary objective is to

be the leading provider of allogeneic placenta-based cell therapy products that are true off-the-shelf products that do not require any

matching or additional manipulation prior to administration.

From the physician’s and patient’s perspective, we believe that

our PLX products are comparable to any other product delivered in a vial.

Currently, our PLX products are administered intramuscular,

or IM, using a standard needle and syringe.

Our first product candidate,

PLX-PAD, is composed of maternal cells originating from the placenta.

PLX-PAD is currently being used in a Phase III multinational clinical

study in recovery following surgery for hip fracture, and in two Phase II clinical studies in ARDS associated with COVID-19 in the United

States, Europe and Israel.

We have also conducted a pivotal

Phase III multinational clinical study in the use of PLX-PAD for the treatment of Critical Limb Ischemia, or CLI, which we terminated

in December 2020, and in a Phase II multinational clinical study in Intermittent Claudication, or IC.

PLX-PAD is also under clinical

development in collaboration with Tel Aviv Sourasky Medical Center (Ichilov Hospital) through an investigator initiated study, and used

in a Phase I/II for the treatment of Steroid-Refractory cGVHD.

Our second product candidate,

PLX-R18, is composed of fetal cells originated from the placenta.

We have completed enrollment in our first in human

Phase I clinical study in incomplete hematopoietic recovery following hematopoietic cell transplantation, or HCT, in the United States

Through our collaboration

in the United States with the National Institutes of Health, or NIH, and the U.S.

Department of Defense, or DoD, we are also developing

a solution for ARS following or before exposure to massive radiation via the FDA Animal Rule regulatory pathway.

Modified PLX cells

In the last decade, we developed

an allogeneic platform based on cells originated from the fetal and maternal cell from the placenta, and by using this platform we can

produce large quantities of high-quality cells in automated and robust manufacturing suitable for cGMP environment.

As a platform technology

company, we are currently developing additional product candidates, which are modified or induced PLX cells:

Induced PLX cells:

using cells from the placenta, induced with inflammatory cytokines, to transiently alter their secretion profile.

Modified PLX cells using CRISPR

CRISPR is a unique technology that opens the door for precise gene editing of cells.

Using such technology can initiate the

next evolution in cell therapy by allowing the reprograming of cells for specific needs.

Our aim is to incorporate the genetic engineering

techniques into our cell manufacturing platform in order to develop large scale allogenic engineered PLX products designed for specific

We believe that using the

placenta as a unique cell source, combined with our innovative research, development and high-quality manufacturing capabilities, will

be the “engine” that drives this platform technology towards the successful development of additional PLX cell therapy products

and indications.

Our Clinical Development Product Candidates

Orthopedic Indications .

Following FDA and European Medicine Agency, or EMA, clearance, a multinational Phase III study is currently being conducted in the United

States, Europe and Israel.

The primary endpoint of this study is the Short Physical Performance Battery (SPPB), a test for lower leg performance

and functional status.

The study is planned to include 240 patients and will assess efficacy at six months and a year, as well as safety

for up to two years.

Currently, over 95% of the study patients have been enrolled in this study.

Our Phase III study

protocol and design was based on our phase I/II, randomized, double-blind, placebo-controlled study (n=20) to assess the safety and efficacy

of IM injections of allogeneic PLX-PAD cells for the regeneration of injured gluteal musculature after total hip replacement had been

conducted in Germany under the approval of PEI.

In this study, PLX-PAD cells or placebo were administered into the traumatized gluteal

muscle during total hip replacement surgery.

The study results met its primary efficacy endpoint, change in maximal voluntary isometric

contraction force of the gluteal muscle at six months after total hip replacement.

Patients treated with PLX-PAD had a significantly greater

improvement of maximal voluntary muscle contraction force than the placebo group (p=0.0067).

In addition, the study demonstrated that

PLX-PAD was safe and well tolerated by patients.

COVID-19 Complicated by

In May 2020, the FDA cleared our Investigational New Drug Application, or IND, for a Phase II study of our PLX-PAD cells for

treatment of severe COVID-19 cases complicated by ARDS and we initiated the study in June 2020.

study is a randomized, double-blind,

placebo-controlled, multicenter, parallel-group intended to evaluate the efficacy and safety of IM injections of PLX-PAD for the treatment

of severe COVID-19 cases complicated by ARDS.

The primary endpoint is the number of ventilator free days during the main 28-day

study period.

Safety and survival follow-up will be conducted at week 8, 26 and 52.

Secondary efficacy endpoints include all-cause

mortality, duration of mechanical ventilation, ICU free-days, and hospitalization free-days.

In addition, the FDA has cleared our

EAP for the use of our PLX-PAD cells to treat ARDS caused by COVID-19 outside of our ongoing Phase II COVID-19 study in the U.S.

The EAP will include up to 100 patients with the resulting data being collected and evaluated alongside our existing clinical trial

In August 2020, the PEI cleared our Phase

II study in Germany titled, “A Randomized, Controlled, Multicenter, Parallel-Group Phase II Study to Evaluate the Efficacy

and Safety of Intramuscular Injections of PLX PAD for the Treatment of severe COVID-19,”

relating to the treatment of patients

hospitalized with severe cases of COVID-19 complicated by ARDS.

Forty patients hospitalized with severe cases of COVID-19 complicated

by ARDS will be enrolled in the study.

The primary endpoint is the number of ventilator free days during the 28-days following

Secondary efficacy endpoints include all-cause mortality, duration of mechanical ventilation, ICU free-days, and hospitalization

Safety and survival follow-up will be conducted until week 52.

In addition, the FDA has cleared our Expanded Access Program,

or EAP, for the use of our PLX-PAD cells to treat ARDS caused by COVID-19 outside of the Phase II COVID-19 complicated by ARDS study in

the United States.

The EAP approval was for up to 100 patients.

In August 2020, the PEI cleared

our Phase II study in Germany titled, “A Randomized, Controlled, Multicenter, Parallel-Group Phase II Study to Evaluate the Efficacy

and Safety of Intramuscular Injections of PLX PAD for the Treatment of severe COVID-19,” relating to the treatment of patients hospitalized

with severe cases of COVID-19 complicated by ARDS.

The primary efficacy endpoint of the study is the number of ventilator free days during

the 28 days from day 1 through day 28 of the study.

Safety and survival follow-up will be conducted at day 60, week 26 and week

Following HCT –

PLX-R18 is also under development in the United States and Israel for the treatment of incomplete

hematopoietic recovery following HCT.

This Phase I study of PLX-R18 in HCT, as previously announced, has successfully enrolled

20 patients in the United States and Israel.

We expect to provide top line efficacy results in the first quarter of calendar 2021.

In addition, the FDA granted orphan drug designation to our PLX cell therapy for the treatment of graft failure and incomplete

hematopoietic recovery following HCT.

We have conducted several animal studies for the evaluation of PLX-R18 for the treatment of ARS, in collaboration

with the National Institute of Allergy and Infectious Diseases, or the NIAID.

National Institutes of Health, or NIH,

funded and conducted a pilot study in NHPs to evaluate the therapeutic effect of PLX-R18 on hematological aspects of ARS.

2017, we announced results of the NHPs pilot study for PLX-R18 as a treatment for ARS.

Although study size was not designed to

show significance, results showed a trend toward improved survival of PLX-R18 treated animals compared to control, placebo treated

The study, conducted and funded by the NIAID, was designed to assess the safety and efficacy of PLX-R18 following intramuscular

injection into irradiated and non-irradiated NHPs.

Efficacy measures included survival as well as hematological parameters which

are affected by exposure to high levels of radiation as may occur in a nuclear accident or attack.

These data will help the design

of a pivotal study to fulfill the requirements for a Biologics License Application, or BLA, submission under the FDA’s Animal

Rule regulatory pathway.

plan to continue the discussions with the different government agencies with the goal of receiving their support for pivotal studies

in large animals as well as conducting the safety studies required in order to file BLA for this indication.

October 2017, we announced that the FDA granted us an orphan drug designation for our PLX-R18 cell therapy for the prevention

and treatment of ARS.

April 2018, we announced that the FDA approved our IND application for PLX-R18 cell therapy in the treatment of ARS.

The IND allows

us to treat victims who may have been acutely exposed to high dose radiation due to nuclear attack or accident.

December 2015, we also signed a Memorandum of Understanding for a collaboration with Fukushima Medical University, Fukushima Global

Medical Science Center.

The purpose of the collaboration is to develop our PLX-R18 cells for the treatment of ARS, and for morbidities

following radiotherapy in cancer patients.

In June 2018, we reported positive animal data from studies conducted in collaboration

with Fukushima Medical University evaluating PLX-R18 cells as a treatment for radiation damage to the gastrointestinal, or GI,

tract and bone marrow.

Data from these studies showed that PLX-R18 cells significantly increased survival rates, preserved GI

stem cells activity that enhance the recovery of the GI system and prevented severe damage to the intestinal lining, suggesting

PLX-R18 potential as a multi-organ therapy for ARS.

July 2019, we presented positive results from a series of studies of our PLX-R18 cell therapy product conducted by the U.S.

of Defense’s, or DoD, Armed Forces Radiobiology Research Institute, part of the Uniformed Services University of Health

The studies were designed to evaluate PLX-R18 as a potential prophylactic countermeasure against ARS administered prior

to radiation exposure.

These animal studies demonstrate that PLX-R18, administered 24 hours before radiation exposure, and again

72 hours after exposure, resulted in a significant increase in survival rates, from 4% survival rate in the placebo group to 74%

in the treated group.

In addition, the data shows an increase in recovery of blood lineages and a favorable safety profile.

histopathological analysis and hematopoietic progenitor clonogenic assay of tissues collected show a significant increase in bone

marrow cell numbers and improved regenerative capability into all blood lineages.

Steroid-Refractory

cGVHD –

In September 2017, we signed

an agreement with Tel Aviv Sourasky Medical Center (Ichilov Hospital) to conduct a clinical Phase I/II trial of PLX-PAD cell therapy

for the treatment of Steroid-Refractory cGVHD.

This trial is an investigator initiated study.

As such, Tel Aviv Sourasky Medical

Center supports the study and is responsible for its design and implementation.

and Clinical Affairs Strategy

cell therapy development strategy is to hold open and frequent discussions with regulators at all stages of development from preclinical

trials to more advanced regulatory stages.

We utilize this strategy in working with the FDA, the EMA, Germany’s PEI as well

as other European national competent authorities, the Israeli Ministry of Health, or MOH and Japan’s PMDA, and we are also

working with the Ministry of Food and Drug Safety, or MFDS, of South Korea.

Adaptive Pathways Project is part of the EMA’s efforts to improve timely access for patients to new therapies.

treatments with the potential to heal serious conditions with an unmet medical need, and may reduce the time to a medicine’s approval

or to its reimbursement for targeted patient groups.

The pilot is open to clinical programs in early stages of development only.

We have applied early to this program and have been selected for it.

September 2017, we announced that the FDA granted “Fast Track”

designation for PLX-PAD in CLI.

The FDA’s Fast

Track designation is a process designed to facilitate the development and expedite the review of drugs to treat serious conditions

and unmet medical needs.

With Fast Track designation, there is an increased possibility for a priority review by the FDA of PLX-PAD

cells for the treatment of CLI.

January 2018, we announced that the FDA cleared our EAP for the use of our PLX-PAD cell treatment in patients with CLI.

the use of an investigational medical product outside of clinical trials and is usually granted in cases where patients are unsuitable

for inclusion under the study protocol and the patient’s condition is life-threatening with an unmet medical need.

of the EAP, our PLX-PAD cell therapy is available to a limited number of CLI patients in the United States who are unsuitable

for revascularization and cannot take part in our ongoing Phase III clinical trial.

August 2020, we announced that the FDA cleared our EAP for the use of our PLX-PAD cells to treat ARDS caused by COVID-19 outside

of our ongoing Phase II COVID-19 study in the U.S.

The program provides a pathway for patients that are not eligible for inclusion

in the Phase II clinical trial to be treated with PLX-PAD cells and will include up to 100 patients.

The resulting data will be

collected and evaluated alongside our existing clinical trial.

Impact of COVID-19 - In managing our ongoing global clinical

trials, as well as our daily operations, in the midst of the COVID-19 global pandemic, we are taking all necessary precautions

for the safety and well-being of patients, healthcare providers involved in our trials, and our employees.

We are continuing our

operational and manufacturing activities, subject to the directives of the Israeli Ministry of Health, with a dedicated team on

site at our facilities.

In addition, we are using remote work technologies that enable other activities to be conducted without

the need for a physical presence in our facilities.

Our allogenic, off-the-shelf approach and our advanced manufacturing capabilities

enabled us to complete the manufacturing of the entire stock of PLX cells needed to complete all of our current clinical trials

We currently hold supplies of PLX cells in inventory in Israel, and in secure storage facilities in Europe and the U.S.

In addition, we are following the FDA and EMA guidelines regarding the management of clinical trials during COVID-19

understand that our success will depend, in part, on maintaining our intellectual property, and therefore we are committed to

protecting our technology and product candidates with patents and other methods described below.

are the sole owner of 128 issued patents and approximately 60 pending patent applications in the United States, Europe, China

and Japan, as well as in additional countries worldwide, including Israel, countries in the Far East and South America (in calculating

the number of issued patents, each European patent validated in multiple jurisdictions was counted as a single patent).

April 2016, the Subsidiary entered into a licensing agreement with TES Holdings Co., Ltd., a venture company derived from the

University of Tokyo, to obtain a key patent in Japan to cover the treatment of ischemic diseases with placental cell therapy.

This license is subject to future single low-digit royalties from sales of our product for treatment in the field of ischemic

diseases in Japan, until expiry of the patent in 2023.

This license follows the grant of two key patents to us by the Japanese

Patent Office, which address three dimensional methods for expanding placental and adipose cells, and specified cell therapies

produced from placental tissue using these methods.

February 2017, Pluristem Ltd.

signed an agreement with founders of a certain patent for a five year option to purchase the certain

patent for an amount of 1 million Euro.

The agreement includes yearly payments of Euro 75,000, Euro 75,000 and Euro 100,000 in

February 2017, 2018 and 2019, respectively, which have been paid.

We are entitled to terminate the agreement for convenience upon

providing the founders 30 days prior notice.

April 2019, we filed a U.S.

provisional patent application titled “Methods and Compositions for Producing Cannabinoids,”

which covers the use of our state-of-the-art, proprietary 3-D cell culturing technology for the potential manufacturing of cannabinoid-producing

In April 2020, we filed a Patent Cooperation Treaty, or PCT, application with respect to the technology.

March 2020, we filed a U.S.

provisional patent application titled “Methods and Compositions for Treating Viral Infections

and Sequelae Thereof,”

which covers the use of placental ASC for treating coronavirus infections and sequelae thereof.

May 2020, a related Israeli patent application was filed.

on the well-established understanding that the characteristics and therapeutic potential of a cell product are largely determined

by the source of the cells and by the methods and conditions used during their culturing, our patent portfolio includes different

types of claims that protect the various unique aspects of our technology.

multi-national portfolio of patent and patent applications includes the following claims:

the 28-days from day one through day 28 of the study.

Secondary efficacy endpoints include all-cause mortality, duration of mechanical

ventilation, ICU free-days, and hospitalization free-days.

Safety and survival follow-up will be conducted until week 52.

patients in Europe and Israel under this protocol.

July 8, 2021, we announced that we are bringing our COVID-19 complicated by ARDS Phase II studies in the United States, Europe and Israel

to clinical readout.

The analysis will be based on 89 patients enrolled.

We expect to announce the topline results of the readout during

the fourth quarter of 2021.

We also announced that we will not pursue the previously announced plans in December 2020 to expand our COVID-19

program in Mexico in collaboration with Innovare R&D SA de CV.

Following HCT .

This Phase I study of PLX-R18 in HCT, has completed enrollment of 21 patients in the United States and Israel.

study is designed to assess the safety of PLX-R18 by assessing adverse events, safety labs and vital signs in patients receiving different

doses of PLX-R18.

We expect to complete one year follow up for all patients in September 2021.

In April 2021, we announced topline

results of this study.

The 21 patients enrolled in the United States and Israel were at least three months after the HCT procedure (median:

236 days) and had low blood counts in at least one blood cell lineage.

They were assigned to one of three treatment arms:

cells/kg, two million cells/kg or four million cells/kg.

Each patient received two treatments of the assigned dose.

Data from the six-month follow-up

were available for 14 of the 21 treated patients and demonstrated that (i) PLX-R18 was well-tolerated with a favorable safety profile;

(ii) statistically significant improvement from baseline counts was observed in all cohorts for hemoglobin and platelet counts (p<0.05)

and the patients in the high dose arm (4 million cells/kg) exhibited statistically significant improvements in all three blood cell lineages

(iii) approximately 60% of patients exhibited improvements in all three blood cell lineages:

hemoglobin, neutrophil and platelet

counts that are above the initial criteria for inclusion in the study and (iv) 13 patients were transfusion dependent at baseline;

of those became transfusion independent at 6 month follow-up and no patients who were transfusion independent at baseline became transfusion

Peripheral and Cardiovascular

We investigated the use of PLX-PAD cells for the treatment of peripheral arterial disease, or PAD, including IC and CLI.

We completed two Phase I safety/dose-escalating

clinical studies for CLI, one in the United States and one in Germany.

These CLI studies demonstrated that no blood type or human leukocyte

antigen matching is required, and that the administration of PLX-PAD cells is safe, even if two doses are administered to a patient on

two different occasions.

We conducted a pivotal Phase

III study of PLX-PAD cells in the treatment of CLI for patients with minor tissue loss (Rutherford Category 5) who are unsuitable for

revascularization.

This multinational Phase III study was conducted in the United States, Europe and Israel and enrolled 213 patients

In December 2020, the independent Data Monitoring

Committee, or DMC, issued its recommendation letter following an interim analysis relating to the CLI Phase III study.

A clinical dataset

was reviewed by the independent DMC for safety and analysis of the primary endpoint of amputation-free survival, defined as time to occurrence

of major amputation of the index leg or death.

Based on the review, the DMC concluded that the CLI study was unlikely to meet the primary

endpoint by the time of the final analysis.

Following the DMC’s recommendation, we decided to terminate the CLI study.

We have conducted several animal studies for the evaluation of PLX-R18 for the treatment of ARS, in collaboration with the National Institute

of Allergy and Infectious Diseases, or the NIAID.

The NIH, funded and conducted a pilot study in non-human primates, or NHPs, to evaluate

the therapeutic effect of PLX-R18 on hematological aspects of ARS.

In 2017, we announced results of the NHPs pilot study for PLX-R18 as

a treatment for ARS.

Although study size was not designed to show significance, results showed a trend toward improved survival of PLX-R18

treated animals compared to control, placebo treated animals.

The study, conducted and funded by the NIAID, was designed to assess the

safety and efficacy of PLX-R18 following IM injection into irradiated and non-irradiated NHPs.

Efficacy measures included survival as

well as hematological parameters which are affected by exposure to high levels of radiation as may occur in a nuclear accident or attack.

These data will help the design of a pivotal study to fulfill the requirements for a Biologics License Application, or BLA, submission

under the FDA’s Animal Rule regulatory pathway.

We plan to continue

the discussions with the different government agencies with the goal of receiving their support for pivotal studies in NHPs as well as

conducting the safety studies required in order to file BLA for this indication.

In October 2017, we announced

that the FDA granted us an orphan drug designation for our PLX-R18 cell therapy for the prevention and treatment of ARS.

In April 2018, we announced

that the FDA approved our IND application for PLX-R18 cell therapy in the treatment of ARS.

The IND allows us to treat victims who may

have been acutely exposed to high dose radiation due to nuclear attack or accident.

In December 2015, we

also signed a memorandum of understanding, or MOU, for a collaboration with Fukushima Medical University, Fukushima Global Medical Science

The purpose of the collaboration is to develop our PLX-R18 cells for the treatment of ARS, and for morbidities following radiotherapy

in cancer patients.

In June 2018, we reported positive animal data from studies conducted in collaboration with Fukushima Medical University

evaluating PLX-R18 cells as a treatment for radiation damage to the gastrointestinal, or GI, tract and bone marrow.

Data from these studies

showed that PLX-R18 cells significantly increased survival rates, preserved GI stem cells activity that enhance the recovery of the GI

system and prevented severe damage to the intestinal lining, suggesting PLX-R18 potential as a multi-organ therapy for ARS.

July 2019, we presented positive results from a series of studies of our PLX-R18 cell therapy product conducted by the DoD, Armed Forces

Radiobiology Research Institute, part of the Uniformed Services University of Health Sciences.

The studies were designed to evaluate PLX-R18

as a potential prophylactic countermeasure against ARS administered prior to radiation exposure.

These animal studies demonstrate that

PLX-R18, administered 24 hours before radiation exposure, and again 72 hours after exposure, resulted in a significant increase in survival

rates, from 4% survival rate in the placebo group to 74% in the treated group.

In addition, the data shows an increase in recovery of

blood lineages and a favorable safety profile.

Furthermore, histopathological analysis and hematopoietic progenitor clonogenic assay of

tissues collected show a significant increase in bone marrow cell numbers and improved regenerative capability into all blood lineages.

Steroid-Refractory cGVHD .

In September 2017, we signed an agreement with Tel Aviv Sourasky Medical Center (Ichilov Hospital) to conduct a Phase I/II clinical study

of PLX-PAD cell therapy for the treatment of Steroid-Refractory cGVHD.

This study is an investigator-initiated study.

As such, Tel Aviv

Sourasky Medical Center supports the study and is responsible for its design and implementation.

Regulatory and Clinical Affairs Strategy

Our cell therapy development

strategy is to hold open and frequent discussions with regulators at all stages of development from preclinical studies to more advanced

regulatory stages.

We utilize this strategy in working with the FDA, the EMA, Germany’s PEI as well as other European national competent

authorities, the MOH, Japan’s Pharmaceuticals and Medical Devices Agency, or PMDA, and also the Ministry of Food and Drug Safety,

or MFDS, of South Korea.

Intellectual Property

We understand that our success

will depend, in part, on maintaining our intellectual property, and therefore we are committed to protecting our technology and product

candidates with patents and other methods described below.

We are the sole owner of 133

issued patents and approximately 70 pending patent applications in the United States, Europe, China, Japan and Israel, as well as in additional

countries worldwide, including countries in the Far East and South America (in calculating the number of issued patents, each European

patent validated in multiple jurisdictions was counted as a single patent).

In April 2016, the Israeli

subsidiary entered into a licensing agreement with TES Holdings Co., Ltd., a venture company derived from the University of Tokyo, to

obtain a key patent in Japan to cover the treatment of ischemic diseases with placental cell therapy.

This license is subject to future

single low-digit royalties from sales of our product for treatment in the field of ischemic diseases in Japan, until expiry of the patent

This license is in addition to the grant of 13 patents to us by the Japanese Patent Office, which address three dimensional methods

for expanding placental and adipose cells, and specified cell therapies produced from placental tissue using these methods and bedside

thawing devices.

In February 2017, the Israeli

Subsidiary signed an agreement with founders of a certain patent for a five-year option to purchase a certain patent for an amount of

The agreement includes yearly payments of €75,000, €75,000 and €100,000 in February 2017, 2018 and 2019,

respectively, which have been paid.

We are entitled to terminate the agreement for convenience upon providing the founders 30 days prior

In April 2019, we filed a

provisional patent application titled “Methods and Compositions for Producing Cannabinoids,” which covers the use of

our state-of-the-art, proprietary 3D cell culturing technology for the potential manufacturing of cannabinoid-producing cells.

2020, we filed a Patent Cooperation Treaty, or PCT, application with respect to the technology.

In June 2021, national or regional phase

applications of the PCT were filed in the United States, Europe, Japan, Canada, and Israel.

In March 2020, we filed a

provisional patent application titled “Methods and Compositions for Treating Viral Infections and Sequelae Thereof,”

which covers the use of placental adherent stromal cells for treating coronavirus infections and sequelae thereof.

In May 2020, a related

Israeli patent application was filed, which was allowed in March 2021.

In March 2021, a PCT application as well as national applications

were filed in the United States and Israel.

In June 2021, national or regional phase applications of the PCT were filed in Europe and

Based on the well-established

understanding that the characteristics and therapeutic potential of a cell product are largely determined by the source of the cells and

by the methods and conditions used during their culturing, our patent portfolio includes different types of claims that protect the various

unique aspects of our technology.

Our multi-national portfolio of patent and patent

applications includes the following claims:

proprietary expansion methods for 3D stromal cells;

4 unchanged sentences

harvest, and thawing devices.

our experience with ASC-based product development, we have developed expertise and know-how in this field and have established

procedures for manufacturing clinical-grade PLX cells in our facilities.

Certain aspects of our manufacturing process are covered

by patents and patent applications.

In addition, specific aspects of our technology are retained as know-how and trade secrets

that are protected by our confidentiality agreements with our employees, consultants, contractors, manufacturers and advisors.

These agreements generally provide for protection of confidential information, restrictions on the use of materials, and an obligation

to assign to us inventions conceived during the course of performing services for us.

following table sets forth our key patents and patent applications and is not intended to represent an assessment of claims, limitations

In some cases, a jurisdiction is listed as both pending and granted for a single patent family.

This is due to pending

continuation or divisional applications of the granted case.

is a risk that our patents will be invalidated, and that our pending patent applications will not result in issued patents.

also cannot be certain that we will not infringe on any patents that may be issued to others.

See “Risk Factors - We must

further protect and develop our technology and products in order to become a profitable company”

The expiration dates

of these patents, based on filing dates, range from 2020 to 2040.

expiration dates will be determined according to extensions received based on the Drug Price Competition and Patent Term Restoration

Act of 1984 (P.L.

98-417), commonly known as the “Hatch-Waxman”

Act, that permits extensions of pharmaceutical patents

to reflect regulatory delays encountered in obtaining FDA market approval.

The Hatch-Waxman Act is based on a U.S.

and therefore only relevant to U.S.

Patent Portfolio

Jurisdictions

AND APPARATUS FOR MAINTENANCE AND EXPANSION OF HAEMATOPOIETIC STEM CELLS AND/OR PROGENITOR CELLS

PCT/US2000/02688

6, 2020 (245 days patent term adjustment)

FOR CELL EXPANSION AND USES OF CELLS AND CONDITIONED MEDIA PRODUCED THEREBY FOR THERAPY

Through our experience with

adherent stromal cell based product development, we have developed expertise and know-how in this field and have established procedures

for manufacturing clinical-grade PLX cells in our facilities.

Certain aspects of our manufacturing process are covered by patents and

patent applications.

In addition, specific aspects of our technology are retained as know-how and trade secrets that are protected by

our confidentiality agreements with our employees, consultants, contractors, manufacturers and advisors.

These agreements generally provide

for protection of confidential information, restrictions on the use of materials, and an obligation to assign to us inventions conceived

during the course of performing services for us.

The following table sets forth

our key patents and patent applications and is not intended to represent an assessment of claims, limitations or scope.

In some cases,

a jurisdiction is listed as both pending and granted for a single patent family.

This is due to pending continuation or divisional applications

of the granted case.

The expiration dates of these

patents, based on filing dates, range from 2027 to 2041.

Actual expiration dates will be determined according to extensions received based

on the Drug Price Competition and Patent Term Restoration Act of 1984 (P.L.

98-417), commonly known as the “Hatch-Waxman”

Act, that permits extensions of pharmaceutical patents to reflect regulatory delays encountered in obtaining FDA market approval.

Hatch-Waxman Act is based on a U.S.

federal law and therefore only relevant to U.S.

There is a risk that our patents

will be invalidated, and that our pending patent applications will not result in issued patents.

We also cannot be certain that we will

not infringe on any patents that may be issued to others.

See “Risk Factors - We must further protect and develop our technology

and products in order to become a profitable company.”

Our Patent Portfolio

Patent Name/ Int.

Pending Jurisdictions

Granted Jurisdictions

METHODS FOR CELL EXPANSION AND USES OF CELLS AND CONDITIONED MEDIA

PRODUCED THEREBY FOR THERAPY

PCT/IL2007/000380

Canada, China, Hong Kong, Europe, Israel, India, Japan, South Korea, Mexico, Russia, Singapore

CELLS FROM PLACENTA TISSUE AND USE THEREOF IN THERAPY

China, Hong Kong

Australia, Canada, China, Hong Kong, Europe, Israel, India, Japan, South Korea, Mexico, Russia, Singapore

March 23, 2027

ADHERENT CELLS FROM PLACENTA TISSUE AND USE THEREOF IN THERAPY

PCT/IL2008/001185

States, Brazil, China, Israel

Canada, China, Europe, Hong Kong, Israel, India, Japan, Mexico, Russia, Singapore, USA, South Africa, South Korea

OF TREATING INFLAMMATORY COLON DISEASES

United States, Israel

Australia, Brazil, Canada, China, Europe, Hong Kong, Israel, India, Japan, Mexico, Russia, United States, South Korea

September 2, 2028

METHODS OF TREATING INFLAMMATORY COLON DISEASES

PCT/IL2009/000527

States, Israel, Russia

OF SELECTION OF CELLS FOR TRANSPLANTATION

United States, Israel, Russia

METHODS OF SELECTION OF CELLS FOR TRANSPLANTATION

PCT/IL2009/000844

CELLS FROM PLACENTA TISSUE AND USE THEREOF IN THERAPY

Europe, Israel

September 1, 2029

ADHERENT CELLS FROM PLACENTA TISSUE AND USE THEREOF IN THERAPY

PCT/IL2009/000846

Canada, Europe, Hong Kong, Israel, India, Mexico, Russia, Singapore, USA, South Africa

CELLS FROM PLACENTA TISSUE AND USE THEREOF IN THERAPY

Australia, Canada, China, Europe, Hong Kong, Israel, India, Mexico, Russia, Singapore, United States

September 1, 2029

ADHERENT CELLS FROM PLACENTA TISSUE AND USE THEREOF IN THERAPY

PCT/IL2009/000845

States, Europe, Israel

STROMAL CELLS DERIVED FROM PLANCENTAS OF MULTIPLE DONORS AND USES THEREOF

United States, Europe, Israel

September 1, 2029

ADHERENT STROMAL CELLS DERIVED FROM PLANCENTAS OF MULTIPLE DONORS

AND USES THEREOF

PCT/IB2011/001413

United States

April 21, 2031

March 22, 2027

CELLS FROM PLACENTA AND USE OF SAME IN DISEASE TREATMENT

PCT/IB2010/003219

States, China, Israel

Canada, China Hong Kong, Europe, Israel, Mexico, New Zealand, United States, South Africa

AND SYSTEMS FOR HARVESTING ADHERENT STROMAL CELLS

ADHERENT CELLS FROM PLACENTA AND USE OF SAME IN DISEASE TREATMENT

PCT/IB2010/003219

Israel, United States

Canada, Europe, Israel, India, South Korea, Mexico, Singapore, United States

FOR TREATING RADIATION OR CHEMICAL INJURY

United States, Israel

Australia, Canada, China, Hong Kong, Europe, Israel, Mexico, New Zealand, United States

November 29, 2030

METHODS AND SYSTEMS FOR HARVESTING ADHERENT STROMAL CELLS

PCT/IB2012/000933

Hong Kong, Israel, Japan, South Korea, United States

MUSCLE REGENERATION USING MESENCHYMAL STEM CELLS

PCT/EP2011/058730

States, Europe, Israel

AND PROTEIN EXPRESSION PROPERTIES OF ADHERENT STROMAL CELLS CULTURED IN 3D

China, Israel

Australia, Canada, Europe, Israel, India, South Korea, Mexico, Singapore, United States

April 15, 2032

METHODS FOR TREATING RADIATION OR CHEMICAL INJURY

PCT/IB2012/000664

United States

AND METHODS FOR CULTURE OF CELLS

Europe, Hong Kong, Israel, Japan, South Korea, United States

March 22, 2032

SKELETAL MUSCLE REGENERATION USING MESENCHYMAL STEM CELLS

PCT/EP2011/058730

United States, Europe, Israel

GENE AND PROTEIN EXPRESSION PROPERTIES OF ADHERENT STROMAL CELLS

CULTURED IN 3D

PCT/IB2014/059114

States, Israel

FOR PREVENTION AND TREATMENT OF PREECLAMPSIA

Israel, United States

February 20, 2034

DEVICES AND METHODS FOR CULTURE OF CELLS

PCT/IB2013/058184

Hong Kong, Europe, Israel, Japan, South Korea, United States, South Africa

AND DEVICE FOR THAWING BIOLOGICAL MATERIAL

United States, Israel

August 31, 2033

METHODS FOR PREVENTION AND TREATMENT OF PREECLAMPSIA

PCT/IB2013/058186

Europe, Israel, India, Japan, South Korea, Russia, Singapore, United States

AND METHODS FOR GROWING AND HARVESTING CELLS PCT/IB2015/051559

States, Europe

AND COMPOSITIONS FOR TREATING AND PREVENTING MUSCLE WASTING DISORDERS

China, Hong Kong, Europe, Israel, Japan, South Korea, United States

August 31, 2033

METHOD AND DEVICE FOR THAWING BIOLOGICAL MATERIAL

PCT/IB2013/059808

OF ADHERENT STROMAL CELLS FOR ENHANCING HEMATOPOIESIS IN A SUBJECT IN NEED THEREOF

Australia, Europe, Hong Kong, Israel, India, Japan, South Korea, Russia, Singapore, United States

October 31, 2033

SYSTEMS AND METHODS FOR GROWING AND HARVESTING CELLS

PCT/IB2015/051559

States, China, Israel

ADHERENT STROMAL CELLS AND METHODS OF PRODUCING AND USING SAME

Israel, United States

March 3, 2035

METHODS AND COMPOSITIONS FOR TREATING AND PREVENTING MUSCLE WASTING

PCT/IB2015/059763

States, Europe, China, Israel

AND COMPOSITIONS FOR TREATING CANCERS AND NEOPLASMS

Israel, United States

December 18, 2035

USE OF ADHERENT STROMAL CELLS FOR ENHANCING HEMATOPOIESIS IN A SUBJECT

IN NEED THEREOF

PCT/IB2016/051585

States, Japan, Canada, Australia, Israel

AND COMPOSITIONS FOR TREATING NEUROLOGICAL DISORDERS

United States, China, Israel

March 21, 2036

ALTERED ADHERENT STROMAL CELLS AND METHODS OF PRODUCING AND USING

PCT/IB2016/053310

Europe, China, Israel

United States

AND COMPOSITIONS FOR TUMOR ASSESSMENT

METHODS AND COMPOSITIONS FOR TREATING CANCERS AND NEOPLASMS

PCT/IB2017/050868

States, Israel

AND COMPOSITIONS FOR TREATING ADDICTIONS

United States, Japan, Canada, Australia, Israel

February 16, 2037

METHODS AND COMPOSITIONS FOR TREATING NEUROLOGICAL DISORDERS

PCT/IB2018/052806

United States

AND COMPOSITIONS FOR DETACHING ADHERENT CELLS

10 2018 115 360.0

States, Israel, Germany

Israel, United States

April 23, 2038

METHODS AND COMPOSITIONS FOR TUMOR ASSESSMENT

PCT/IB2018/050984

United States, Israel

February 18, 2038

METHODS AND COMPOSITIONS FOR TREATING ADDICTIONS

PCT/IB2018/055473

Israel, United States

July 23, 2038

CONTAINING HUMAN PLACENTA-ORIGIN MESENCHYMAL CELLS AND PROCESS FOR PRODUCING VEGF USING THE CELLS JP20030579842

AND COMPOSITIONS FOR PRODUCING CANNABINOIDS

Cooperation Treaty

FOR EXPANDING ADHERENT STROMAL CELLS AND CELLS OBTAINED THEREBY

METHODS AND COMPOSITIONS FOR DETACHING ADHERENT CELLS

Germany 10 2018 115 360.0

June 25-July 3, 2038

DRUG CONTAINING HUMAN PLACENTA-ORIGIN MESENCHYMAL CELLS AND PROCESS FOR PRODUCING VEGF USING THE CELLS JP20030579842

March 28, 2023

METHODS AND COMPOSITIONS FOR PRODUCING CANNABINOIDS

PCT, Canada, Europe, Israel, Japan, United States

April 28, 2040

METHODS FOR EXPANDING ADHERENT STROMAL CELLS AND CELLS OBTAINED

PCT/IB2019/052569

Cooperation Treaty

AND COMPOSITIONS FOR TREATING SUBJECTS EXPOSED TO VESICANTS AND OTHER CHEMICAL AGENTS

Israel, Singapore, United States

March 28, 2039

METHODS AND COMPOSITIONS FOR TREATING SUBJECTS EXPOSED TO VESICANTS

AND OTHER CHEMICAL AGENTS

PCT/IB2019/055074

Cooperation Treaty

AND COMPOSITIONS FOR FORMULATING AND DISPENSING PHARMACEUTICAL FORMULATIONS

Israel, United States

June 18, 2039

METHODS AND COMPOSITIONS FOR FORMULATING AND DISPENSING PHARMACEUTICAL

PCT/IB2019/053115

Cooperation Treaty;

International:

United States

United States:

April 16, 2039

April 26, 2038

DOSAGE REGIMENS COMPRISING ADHERENT STROMAL CELLS

THERAPEUTIC DOSAGE REGIMENS COMPRISING ADHERENT STROMAL CELLS

PCT/IB2019/054828

Cooperation Treaty

Israel, United States

June 10, 2039

MODULAR BIOREACTOR

PCT/IB2019/058429

Cooperation Treaty

METHODS AND COMPOSITIONS

Europe, Israel, South Korea, Singapore, United States

October 3, 2039

THERAPEUTIC METHODS AND COMPOSITIONS

PCT/IB2019/059544

Cooperation Treaty

AND COMPOSITIONS FOR TREATING VIRAL INFECTIONS AND SEQUELAE THEREOF

States (provisional)

yet determined

and Development

initial technology, the PluriX™

Bioreactor system, was invented at the Technion - Israel Institute of Technology’s Rappaport

Faculty of Medicine, in collaboration with researchers from the Weizmann Institute of Science.

This technology has been further

significantly developed by our research and development teams over the ensuing years.

Collaborations

and Ongoing Research and Development Plans

Charité

In July 2007, we entered into a five-year

collaborative research agreement with the Berlin-Brandenburg Center for Regenerative Therapies at Charité

- University Medicine

Berlin, or Charité, which was extended from time to time through June 2022.

We and Charité

are collaborating on a

variety of indications utilizing PLX cells.

According to the agreement, we will be the exclusive owner of the technology and any

products produced as a result of the collaboration.

Charité

will receive between 1% to 2% royalties from net sales of new

developments that have been achieved during the joint development.

March 2020, we announced that we had signed a collaborative agreement with the BIH Center for Regenerative Therapy and the Berlin

Center for Advanced Therapies at Charité

University of Medicine Berlin to expand our existing framework and research agreement

and conduct a joint project evaluating the therapeutic effects of our patented PLX cell product candidates for potential treatment

of the respiratory and inflammatory complications associated with COVID-19.

Medical University

signed a memorandum of understanding, or MOU, for a collaboration with Fukushima Medical University, Fukushima Global Medical

Science Center.

The purpose of the collaboration is to develop Pluristem’s PLX-R18 cells for the treatment of ARS, and for morbidities

following radiotherapy in cancer patients.

The collaboration will proceed alongside research supported by the NIH, which is studying

PLX-R18 as a potential treatment for the hematologic component of ARS.

The MOU for a collaboration with Fukushima will be renewed

automatically on a yearly basis.

Each party is entitled to terminate the agreement for convenience upon providing the other party

30 days prior notice.

June 26, 2013, we entered into an exclusive out-licensing and commercialization agreement, or the CHA Agreement, with CHA for

conducting clinical trials and commercialization of our PLX-PAD product candidate in South Korea in connection with two indications:

the treatment of CLI and IC.

We will continue

to retain rights to our proprietary manufacturing technology and cell-related intellectual property.

first clinical trial that was performed as part of the CHA Agreement was a Phase II trial in IC.

Upon the first regulatory approval

for a PLX product in South Korea, if granted, for the specified indications, we and CHA will establish an equally owned joint

venture with the purpose of commercializing PLX cell products in South Korea.

Additionally, we will be able to use the data generated

by CHA to pursue the development of PLX product candidates outside of South Korea.

term of the CHA Agreement extends from June 24, 2013 until the later of the expiration, lapse, cancellation, abandonment or invalidation

of the last valid patent claim covering the development of the product indications.

The CHA Agreement contains customary termination

provisions, including in the event that the parties do not reach an agreement upon a development plan for conducting the clinical

termination of the CHA Agreement, the license granted thereunder will terminate, and all rights included therein will revert to

us, whereupon we will be free to enter into agreements with any other third parties for the granting of a license in or outside

South Korea or to deal in any other manner with such rights as it shall see fit in our sole discretion.

Phase III study of PLX-PAD in CLI will be a collaborative project carried out by an international consortium led by the Berlin-Brandenburg

Center for Regenerative Therapies, together with the Company and with the participation of additional third parties.

Phase III study of PLX-PAD cell therapy in the treatment of muscle recovery following surgery for hip fracture will be a collaborative

project carried out by an international consortium led by Charité, together with us and with the participation of additional

third parties.

October 2017, we entered into a collaborative project, the nTRACK, carried out by an international consortium led by Leitat.

aim of this project is to examine gold nano particles labeling of stem cells to enable assessment of cells’

in vivo persistence

and distribution in correlation to biological efficacy.

Under the project, PLX cells, labeled and non-labeled will be characterized

and examined in animal models for muscle injury.

April 2018, NIAID awarded a $2.5 million grant to Indiana University to conduct, together with us, studies of our PLX-R18 cell

therapy in the treatment of ARS.

The goal of this project is to extend the PLX-R18 ARS studies to include examination of survival

in pediatric and geriatric populations as well as the ability of PLX-R18 to alleviate delayed effects of radiation in survivors.

July 2018, we entered into a strategic collaboration agreement with Thermo Fisher Scientific Inc., or Thermo Fisher, with the

aim of advancing the fundamental knowledge of cell therapy industrialization and to improve quality control of the end-to-end

supply chain.

The collaboration will combine Thermo Fisher’s experience in cell therapy development and bioproduction scaleup

with our expertise in cell therapy manufacturing, clinical development and quality control.

November 2018, we entered into a license agreement with a subsidiary of Chart Industries, Inc., or Chart, regarding our thawing

device for cell-based therapies.

Pursuant to the terms of the agreement, Chart obtained the exclusive rights to manufacture and

market the thawing device in all territories worldwide, excluding Greater China, and we are to receive royalties from sales of

the product and supply of an agreed upon number of thawing devices.

Royalties shall commence on the date of Chart’s first

commercial sale of the thawing device.

February 2019, we entered into a collaboration with NASA’s Ames Research Center to evaluate the potential of our PLX cell

therapies in preventing and treating medical conditions caused during space missions.

Israel, United States

November 6, 2039

METHODS AND COMPOSITIONS FOR TREATING VIRAL INFECTIONS AND SEQUELAE

PCT/IL2021/050268

PCT, United States, Europe,

Israel, Mexico

First Israeli application:

Other applications:

March 11, 2041

METHODS AND COMPOSITIONS FOR AESTHETIC AND COSMETIC TREATMENT AND

STIMULATING HAIR GROWTH

PCT/IL2020/050363

PCT, United States, Europe,

Canada, China, Japan, Israel, Australia

March 26, 2040

METHODS FOR EXPANDING ADHERENT STROMAL CELLS AND CELLS OBTAINED

September 23, 2040

Research and Development

Foundational Research

Our initial technology, the PluriX™ Bioreactor system, was invented

at the Technion – Israel Institute of Technology’s Rappaport Faculty of Medicine, in collaboration with researchers from the

Weizmann Institute of Science.

This technology was acquired by us and has been further significantly developed by our research and development

teams over the ensuing years.

Collaborations and Ongoing Research and Development Plans

Charité Agreement

In July 2007, we entered into

a five-year collaborative research agreement with the Berlin-Brandenburg Center for Regenerative Therapies at Charité – University

Medicine Berlin, or Charité, which was extended from time to time through June 2022.

We and Charité are collaborating on

a variety of indications utilizing PLX cells.

According to the agreement, we will be the exclusive owner of the technology and any products

produced as a result of the collaboration.

Charité will receive between 1% to 2% royalties from net sales of new developments that

have been achieved during the joint development.

Fukushima Medical University

We signed an MOU for a collaboration

with Fukushima Medical University, Fukushima Global Medical Science Center.

The purpose of the collaboration is to develop Pluristem’s

PLX-R18 cells for the treatment of ARS, and for morbidities following radiotherapy in cancer patients.

The collaboration will proceed

alongside research supported by the NIH, which is studying PLX-R18 as a potential treatment for the hematologic component of ARS.

MOU for a collaboration with Fukushima will be renewed automatically on a yearly basis.

Each party is entitled to terminate the agreement

for convenience upon providing the other party 30 days prior notice.

CHA Agreement

June 26, 2013, we entered into an exclusive out-licensing and commercialization agreement, or the CHA Agreement, with CHA for conducting

clinical studies and commercialization of our PLX-PAD product candidate in South Korea in connection with two indications:

the treatment

of CLI and IC.

We will continue to retain rights to our proprietary manufacturing technology and cell-related intellectual property.

first clinical study that was performed as part of the CHA Agreement was a Phase II study in IC.

Upon the first regulatory approval for

a PLX product in South Korea, if granted, for the specified indications, we and CHA will establish an equally owned joint venture with

the purpose of commercializing PLX cell products in South Korea.

Additionally, we will be able to use the data generated by CHA to pursue

the development of PLX product candidates outside of South Korea.

The term of the CHA Agreement

extends from June 24, 2013 until the later of the expiration, lapse, cancellation, abandonment or invalidation of the last valid patent

claim covering the development of the product indications.

The CHA Agreement contains customary termination provisions, including in the

event that the parties do not reach an agreement upon a development plan for conducting the clinical studies.

Upon termination of the CHA

Agreement, the license granted thereunder will terminate, and all rights included therein will revert to us, whereupon we will be free

to enter into agreements with any other third parties for the granting of a license in or outside South Korea or to deal in any other

manner with such rights as it shall see fit in our sole discretion.

The Phase III study of PLX-PAD

in CLI was conducted as a collaborative project carried out by an international consortium led by the Berlin-Brandenburg Center for Regenerative

Therapies, together with the Company and with the participation of additional third parties.

Our Phase III study of PLX-PAD

cell therapy in the treatment of muscle recovery following surgery for hip fracture is a collaborative project carried out by an international

consortium led by Charité, together with us and with the participation of additional third parties.

In October 2017, we entered

into a collaborative project, the nTRACK, carried out by an international consortium led by Leitat.

The aim of this project is to examine

gold nano particles labeling of stem cells to enable assessment of cells’ in vivo persistence and distribution in correlation to

biological efficacy.

Under the project, PLX cells, labeled and non-labeled will be characterized and examined in animal models for muscle

Indiana University

In April 2018, NIAID awarded

a $2.5 million grant to Indiana University to conduct, together with us, studies of our PLX-R18 cell therapy in the treatment of ARS.

The goal of this project is to extend the PLX-R18 ARS studies to include examination of survival in pediatric and geriatric populations

as well as the ability of PLX-R18 to alleviate delayed effects of radiation in survivors.

Thermo Fisher

In July 2018, we entered into

a strategic collaboration agreement with Thermo Fisher Scientific Inc., or Thermo Fisher, with the aim of advancing the fundamental knowledge

of cell therapy industrialization and to improve quality control of the end-to-end supply chain.

The collaboration enables us to combine

Thermo Fisher’s experience in cell therapy development and bioproduction scaleup with our expertise in cell therapy manufacturing,

clinical development, and quality control.

Chart Industries

In November 2018, we entered

into a license agreement with a subsidiary of Chart Industries, Inc., or Chart, regarding our thawing device for cell-based therapies.

Pursuant to the terms of the agreement, Chart obtained the exclusive rights to manufacture and market the thawing device in all territories

worldwide, excluding Greater China, and we are to receive royalties from sales of the product and supply of an agreed upon number of thawing

Royalties shall commence on the date of Chart’s first commercial sale of the thawing device.

In February 2019, we entered

a collaboration with NASA’s Ames Research Center to evaluate the potential of our PLX cell therapies in preventing and treating

medical conditions caused during space missions.

Department of Defense

August 2017, we announced that a pilot study of our PLX-R18 cell therapy was initiated by the U.S.

The study is examining

the effectiveness of PLX-R18 as a treatment for ARS prior to, and within the first 24 hours of exposure to radiation.

2019, we presented positive results from a series of studies of our PLX-R18 cell therapy product conducted by the U.S.

are members of a large-scale research initiative, the RESTORE project which has received funding of Euro 1,000,000 (approximately

$1,100,000) from the European Union’s Horizon 2020 research and innovation program, to submit a full grant application for

the development and advancement of transformative therapeutics.

At this time, due to COVID-19, there is no open call for full

The members of the RESTORE project continue to collaborate in attempt to collectively submit the grant application once

such call is available.

June 2020, we announced that we were selected as a member of the CRISPR-IL consortium, a group funded by the IIA.

CRISPR-IL brings

together the leading experts in life science and computer science from academia, medicine, and industry, to develop AI based end-to-end

In August 2017, we announced

that a pilot study of our PLX-R18 cell therapy was initiated by the DoD.

The study examined the effectiveness of PLX-R18 as a treatment

for ARS prior to, and within the first 24 hours of exposure to radiation.

In July 2019, we presented positive results from a series of

studies of our PLX-R18 cell therapy product conducted by the DoD.

We are members of a large-scale

research initiative, the RESTORE project which has received funding of €1,000,000 (approximately $1,100,000) from the European Union’s

Horizon 2020 research and innovation program, to submit a full grant application for the development and advancement of transformative

therapeutics.

Currently, due to COVID-19, there is no open call for full proposal.

The members of the RESTORE project continue to collaborate

in attempt to collectively submit the grant application once such call is available.

In June 2020, we announced

that we were selected as a member of the CRISPR-IL consortium, a group funded by the IIA.

CRISPR-IL brings together the leading experts

in life science and computer science from academia, medicine, and industry, to develop Artificial Intelligence, or AI, based end-to-end

genome-editing solutions.

These next-generation, multi-species genome editing products for human, plant, and animal DNA, have

applications in the pharma, agriculture, and aquaculture industries.

These next-generation, multi-species genome editing products for human, plant, and animal DNA, have applications

in the pharma, agriculture, and aquaculture industries.

CRISPR-IL is funded by the IIA with a total budget of approximately $10,000,000

$10,000,000 of which, an amount of approximately $480,000 is a direct grant allocated to us, for a period of 18 months, with a

potential for extension of an additional 18 months and additional budget from the IIA.

CRISPR-IL participants include leading

companies, and medical and academic institutions.

Arab Emirates-based Abu Dhabi Stem Cells Center

In August 2020, we signed a non-binding

MOU with the United Arab Emirates-based Abu Dhabi Stem Cells Center, a specialist healthcare center focused on cell therapy and

regenerative medicine.

The aim of the collaboration is to capitalize on each party’s respective areas of expertise in cell

The parties have agreed to exchange research results, share samples, join usage of equipment and testing, and other

essential activities related to advancing the treatment and research of cell therapies for a broad range of medical conditions,

including COVID-19.

plan to continue to collaborate with universities, academic institutions, and corporate partners worldwide to fully leverage our

expertise and explore the use of our cells in other indications.

Clinical Manufacturing

have the in-house capability to perform clinical cell manufacturing.

Our state-of-the-art Good Manufacturing Practice, or GMP,

grade manufacturing facility in Haifa has been in use since February 2013 for the main purpose of clinical grade, large-scale

manufacturing.

The facility’s new automated manufacturing process and products were approved for production of PLX-PAD for

clinical use by the FDA, EMA, Korean MFDS, PMDA and the Israeli MOH.

Our second product, PLX R18, was cleared by the FDA and the

Israeli Ministry of Health for clinical use.

Furthermore, the site was inspected and approved by an EU qualified person (European

accreditation body), approving that the site and production processes meet the current GMP for the purpose of manufacturing clinical

grade products.

site was also inspected and approved by Israel’s Ministry of Health and we received a cGMP Certification and manufacturer-importer

authorization.

obtain the human placentas used for our research and manufacturing activities from various hospitals in Israel after receiving

a written informed consent by the mother and pathogen clearance.

Any medical waste related to the use of placentas is treated

in compliance with local environmental laws and standards.

June 2019, we announced that we developed a serum-free formulation to support the manufacturing of cell therapy products.

serum-free formulation was developed using our deep understanding in cell therapy industrial scale production standards, and the

quality methods designed to support implementation in Phase III development and marketing.

Achieving this significant technological

challenge is expected to provide us with large-scale, highly-consistent production capacity with operational independency from

third party suppliers for standard serum, an expensive and quantity limited product.

PLX-R18 is the first product candidate that

we intend to manufacture using the serum-free media, which is expected to be followed by PLX-PAD.

development, manufacturing, and marketing of our cell therapy product candidates are subject to the laws and regulations of governmental

authorities in the United States and the European Union as well as other countries in which our products will be marketed in the

future like Japan, Israel and South Korea.

In addition, the manufacturing conditions are specifically inspected by the Israeli

Ministry of Health.

FDA in the United States and the EMA in Europe must approve the product for marketing.

Furthermore, various governmental statutes

and regulations also govern or influence testing, manufacturing, safety, labeling, storage and record keeping related to such

products and their marketing.

Governments in other countries have similar requirements for testing and marketing.

process of obtaining these approvals and the subsequent compliance with appropriate statutes and regulations require the expenditure

of substantial time, resources and money.

There can be no assurance that our product candidates will ultimately receive marketing

approval, or, if approved, will be reimbursed by public and private health insurance.

are several stages every drug has to go through during its development process.

of which, an amount of approximately $480,000 is a direct grant allocated to us, for an initial period of 18 months, with a potential

for extension of an additional 18 months, or the Second Period, with additional budget from the IIA.

In August 2021, we submitted

an additional budget for the Second Period.

The CRISPR-IL consortium program does not require us to pay royalties to the IIA.

United Arab Emirates-based Abu Dhabi Stem Cells

In August 2020, we signed

a non-binding MOU with the United Arab Emirates-based Abu Dhabi Stem Cells Center, a specialist healthcare center focused on cell therapy

and regenerative medicine.

The aim of the collaboration is to capitalize on each party’s respective areas of expertise in cell therapies.

The parties have agreed to exchange research results, share samples, join usage of equipment and testing, and other essential activities

related to advancing the treatment and research of cell therapies for a broad range of medical conditions, including COVID-19.

We plan to continue to collaborate

with universities, academic institutions, and corporate partners worldwide to fully leverage our expertise and explore the use of our

cells in other indications.

In-House Clinical Manufacturing

We have the in-house capability

to perform clinical cell manufacturing.

Our state-of-the-art Good Manufacturing Practice, or GMP, grade manufacturing facility in Haifa

has been in use since February 2013 for the main purpose of clinical grade, large-scale manufacturing.

The facility’s new automated

manufacturing process and products were approved for production of PLX-PAD for clinical use by the FDA, EMA, MFDS, PMDA and the MOH.

second product, PLX-R18, was cleared by the FDA and the MOH for clinical use.

Furthermore, the site was inspected and approved by an European

Union qualified person (European accreditation body), approving that the site and production processes meet the current GMP for the purpose

of manufacturing clinical grade products.

The site was also inspected and approved by the MOH and we received

a cGMP Certification and manufacturer-importer authorization.

We obtain the human placentas

used for our research and manufacturing activities from various hospitals in Israel after receiving a written informed consent by the

mother and pathogen clearance.

Any medical waste related to the use of placentas is treated in compliance with local environmental laws

and standards.

In June 2019, we announced

that we developed a serum-free formulation to support the manufacturing of cell therapy products.

This serum-free formulation was developed

using our deep understanding in cell therapy industrial scale production standards, and the quality methods designed to support implementation

in Phase III development and marketing.

Achieving this significant technological challenge is expected to provide us with large-scale,

highly consistent production capacity with operational independency from third party suppliers for standard serum, an expensive and quantity

limited product.

PLX-R18 is the first product candidate manufactured using the serum-free media.

Government Regulation

The development, manufacturing,

and future marketing of our cell therapy product candidates are subject to the laws and regulations of governmental authorities in the

United States, Europe and Israel, as well as other countries in which our products may be marketed in the future like Japan, and South

In addition, the manufacturing conditions are specifically inspected by the MOH.

The FDA and the EMA must approve

products prior to marketing.

Furthermore, various governmental statutes and regulations also govern or influence testing, manufacturing,

safety, labeling, storage and record keeping related to such products and their marketing.

Governments in other countries have similar

requirements for testing and marketing.

The process of obtaining these

approvals and the subsequent compliance with appropriate statutes and regulations require the expenditure of substantial time, resources

There can be no assurance that our product candidates will ultimately receive marketing approval, or, if approved, will be

reimbursed by public and private health insurance.

There are several stages every drug undergoes during

its development process.

Among these are:

● Performance

of nonclinical laboratory and animal studies to assess a drug’s biological activity and

to identify potential safety problems, and to characterize and document the product’s

chemistry, manufacturing controls, formulation, and stability.

In accordance with regulatory

requirements, nonclinical safety and toxicity studies are conducted under Good Laboratory

Practice requirements to ensure their quality and reliability;

of nonclinical laboratory and animal studies to assess a drug’s biological activity and to identify potential safety concerns,

and to characterize and document the product’s chemistry, manufacturing controls, formulation, and stability.

In accordance with

regulatory requirements, nonclinical safety and toxicity studies are conducted under Good Laboratory Practice, requirements to

ensure their quality and reliability;

manufacture of the product according to GMP regulations and standards;

adequate and well-controlled human clinical trials in compliance with Good Clinical Practice,

or GCP, to establish the safety and efficacy of the product for its intended indication;

post-marketing clinical testing and surveillance of the product after marketing approval,

which can result in additional conditions on the approvals or suspension of clinical

of a drug for clinical trials in humans and approval of marketing are sovereign decisions

of states, made by national, or, in case of the European Union, international regulatory competent authorities.

Regulatory Process in the United States

the United States, our product candidates are subject to regulation as a biological product under the Public Health Service Act

and the Federal Food, Drug and Cosmetic Act.

The FDA, regulating the approval of clinical trials and marketing applications in

the United States, generally requires the following steps prior to approving a new biological product either for clinical trials

adequate and well-controlled human clinical studies in compliance with Good Clinical Practice, or GCP, to establish the safety and efficacy

of the product for its intended indication;

post-marketing clinical testing and surveillance of the product after marketing approval, which can result in additional conditions on

the approvals or suspension of clinical use.

Approval of a drug for clinical

studies in humans and approval of marketing are sovereign decisions of states, made by national,

or, in case of the European Union, international regulatory competent authorities.

The Regulatory Process in the United States

In the United States, our

product candidates are subject to regulation as a biological product under the Public Health Service Act and the Federal Food, Drug and

Cosmetic Act.

The FDA, regulating the approval of clinical studies and marketing applications in the United States, generally requires

the following steps prior to approving a new biological product for use either for clinical studies

or for commercial sale:

of an IND Application, which must become effective before clinical testing in humans

approval of Institutional Review Boards, or IRBs, of research institutions or other clinical

sites to introduce the drug candidate into humans in clinical trials;

may grant approval for EAP prior to the completion of clinical trials ,

in order to allow access for the investigational drug, for patients that are excluded

from the study.

may grant priority review status, in order to expedite the BLA review process.

of a Fast Track designation allows access for the request of priority review.

to the FDA of a BLA for marketing authorization of the product, which must include adequate

results of pre-clinical testing and clinical trials;

of BLA with a proof of efficacy that is based only on animal studies, where human efficacy

studies cannot be conducted because the conduct of such trials is unethical and field

trials after an accidental or deliberate exposure are not feasible.

review of the BLA in order to determine, among other things, whether the product is safe

and effective for its intended uses;

inspection and approval of the product manufacturing facility at which the product will

be manufactured.

Regulatory Process in Europe

the European Union, our investigational cellular products are regulated under the Advanced Therapy Medicinal Product regulation,

a regulation specific to cell and tissue products.

of an IND Application, which must become effective before clinical testing in humans can begin;

approval of Institutional Review Boards, or IRBs, of research institutions or other clinical sites to introduce the drug candidate into

humans in clinical studies;

may grant approval for EAP prior to the completion of clinical studies , in order to allow

access for the investigational drug, for patients that are excluded from the study;

may grant priority review status to expedite the BLA review process.

Obtaining a Fast Track designation allows access for

the request of priority review;

of a BLA for marketing authorization of the product, which must include adequate results of pre-clinical testing and clinical studies;

of BLA with a proof of efficacy that is based only on animal studies is feasible in instances where human efficacy studies cannot be

conducted because the conduct of such studies is unethical and field studies after an accidental or deliberate exposure are not feasible;

review of the BLA in order to determine, among other things, whether the product is safe and effective for its intended uses;

inspection and approval of the product manufacturing facility at which the product will be manufactured.

The Regulatory Process in Europe

In the European Union, our

investigational cellular products are regulated under the Advanced Therapy Medicinal Product regulation, a regulation specific to cell

and tissue products.

This European Union regulation requires:

a Clinical Trial Application for each European country involved in the clinical trial.

The application may be filed via a centralized procedure, which makes it possible to

obtain a coordinated assessment of an application for a clinical trial that is to take

place in several European countries;

approval of affiliated ethics committees to test the investigational product into humans

in clinical trials;

and well-controlled clinical trials to establish the safety and efficacy of the investigational

product for its intended use;

our investigational cellular products are regulated under the Advanced Therapy Medicinal

Product regulation, the application for marketing authorization to the EMA is mandatory

within the 28 member states of the EU.

The EMA is expected to review and approve the

April 2015, the EMA designated PLX-PAD as a tissue-engineered product.

May 2015, we were selected by EMA for development of PLX-PAD cells via the EMA Adaptive Pathways Project.

April 2019, the Pediatric Committee of the EMA granted PLX-PAD a waiver for the requirement to submit a pediatric investigational

plan for treatment of peripheral ischemia.

general, the approval procedure varies among countries, and may involve additional preclinical testing and clinical trials.

requirements and time required may differ from those required for FDA or EMA approval.

Each country may impose certain procedures

and requirements of its own.

Most countries other than the United States, the European Union and Japan are willing to consider

requests for marketing approval only after the product had been approved for marketing by either the FDA, the EMA or the PMDA.

The decision regarding marketing approval is made following the submission of a dossier that is thoroughly assessed and critically

Japan, we have completed the required regulatory interactions with the PMDA, prior to the submission of clinical trial notification,

in the framework of the new regulations for regenerative therapy effective in November 2014, which promote expedited approval

for regenerative therapies that are being developed for seriously debilitating/life-threatening indications.

in the United States, as well as in the European Union, clinical testing involves a three-phase process, although the phases may

In Phase I, clinical trials are conducted with a small number of healthy volunteers, or patients in cases of ethical

issues with using healthy volunteers, and are designed to provide information about product safety and to evaluate the pattern

of drug distribution and metabolism within the body.

Phase II, clinical trials are conducted with a homogenous group of patients afflicted with the specific target disease, in

order to determine preliminary efficacy, optimal dosages and expanded evidence of safety.

In some cases, an initial trial is conducted

in diseased patients to assess both preliminary efficacy and preliminary safety and patterns of drug metabolism and distribution,

in which case it is referred to as a Phase I/II trial.

Phase III clinical trials are generally large-scale, multi-center,

controlled trials conducted with a heterogeneous group of patients afflicted with the target disease, in order to provide statistically

valid proof of efficacy, as well as safety and potency.

The Phase III trials represent the trials that are considered for confirmation

of efficacy and safety and are the most important ones for the approval.

In some circumstances, a regulatory agency may require

Phase IV, or post-marketing trials if it feels that additional information needs to be collected about the drug after it

is on the market.

all phases of clinical development, regulatory agencies require extensive monitoring and auditing of all clinical activities,

clinical data and clinical trial investigators to minimize risks.

The sponsor of a clinical trial is required to submit an annual

safety report to the relevant regulatory agencies, in which serious adverse events must be reported, and also to submit in an

expedited manner any individual serious adverse events that are suspected to be related to the tested drug.

An agency may, at

its discretion, re-evaluate, alter, suspend, or terminate the clinical trial based

upon the data that have been accumulated to that point and its assessment of the risk/benefit ratio to the patient.

presently employ a total of 146 full-time employees and 12 part-time employees, of whom, 120 full-time employees and 12 part-time

employees are engaged in research and development, manufacturing and clinical trials.

regenerative medicine field is characterized by intense competition, as global pharma players are becoming more engaged in the

cell therapy field based on the advancements made in clinical trials and due to the new favorable regenerative medicine legislation

in certain regions.

We face competition from both allogeneic and autologous cell therapy companies, academic, commercial and research

institutions, pharmaceutical companies, biopharmaceutical companies, and governmental agencies.

Some of the clinical indications

we currently have under development are also being investigated in preclinical and clinical programs by others.

there are hundreds of companies in the regenerative medicine space globally, there are multiple participants in the cell therapy

field based in the United States, Europe, Japan, Korea, and Australia such as Athersys Inc., Celularity Inc., Tigenix NV (acquired

by Takeda), SanBio Inc.

and Mesoblast Ltd.

Among other things, we expect to compete based upon our intellectual property portfolio,

our in-house manufacturing efficiencies and capabilities, and the efficacy of our products.

Our ability to compete successfully

will depend on our continued ability to attract and retain experienced and skilled executives, scientific and clinical development

personnel, to identify and develop viable cellular therapeutic candidates, and exploit these products commercially.

the magnitude of the potential opportunity for cell therapy, we expect competition in this area to intensify.

information about us is contained on our Internet website at www.pluristem.com.

Information on our website is not incorporated

by reference into this report.

Under the “SEC Filings”

and “Financial Information”

sections, under the “Investors

& Media”

section of our website, we make available free of charge our Annual Reports on Form 10-K, Quarterly Reports

on Form 10-Q, Current Reports on Form 8-K, and amendments to those reports filed or furnished pursuant to Section 13(a) of the

Securities Exchange Act of 1934, as amended, or the Exchange Act, as soon as reasonably practicable after we electronically file

such material with, or furnish it to, the SEC.

Our reports filed with the SEC are also made available on the SEC’s website

at www.sec.gov.

The following Corporate Governance documents are also posted on our website:

Code of Business Conduct and Ethics,

Trading Policy and the Charters for each of the Committees of our Board of Directors, or the Board.

a Clinical Trial Application for each European country involved in the clinical study.

The application may be filed via a centralized

procedure, which makes it possible to obtain a coordinated assessment of an application for a clinical study that is to take place in

several European countries;

approval of affiliated ethics committees to test the investigational product into humans in clinical studies;

and well-controlled clinical studies to establish the safety and efficacy of the investigational product for its intended use;

Since our investigational cellular products are regulated under the

Advanced Therapy Medicinal Product regulation, the application for marketing authorization to the EMA is mandatory within the 28 member

states of the European Union.

The EMA is expected to review and approve the MAA.

In May 2015, we were selected

by the EMA for development of PLX-PAD cells via the EMA Adaptive Pathways Project.

Other Regulations

In general, the approval procedure

varies among countries, and may involve additional preclinical testing and clinical studies.

The requirements and time required may differ

from those required for FDA or EMA approval.

Each country may impose certain procedures and requirements of its own.

Most countries other

than the United States, the European Union and Japan are willing to consider requests for marketing approval only after the product had

been approved for marketing by either the FDA, the EMA or the PMDA.

The decision regarding marketing approval is made following the submission

of a dossier that is thoroughly assessed and critically addressed.

In Japan, we have completed

the required regulatory interactions with the PMDA, prior to the submission of clinical study notification, in the framework of the new

regulations for regenerative therapy effective in November 2014, which promote expedited approval for regenerative therapies that are

being developed for seriously debilitating/life-threatening indications.

Clinical Studies

Typically, in the United States,

as well as in the European Union, clinical development involves a three-phase process, although the phases may overlap.

clinical studies are conducted in a small number of healthy volunteers, or patients in cases of ethical issues with using healthy volunteers

and are designed to provide information about product safety and to evaluate the pattern of drug distribution and metabolism within the

Phase II clinical studies

are conducted with a homogenous group of patients afflicted with the specific target disease, to explore preliminary efficacy, optimal

dosages and confirm the safety profile.

In some cases, an initial study is conducted in patients to assess both preliminary efficacy and

preliminary safety and patterns of drug metabolism and distribution, in which case it is referred to as a Phase I/II study.

clinical studies are generally large-scale, multi-center, controlled studies conducted with a heterogeneous group of patients afflicted

with the target disease, aiming to provide statistically significant support of efficacy, as well as safety and potency.

The Phase III

studies are considered confirmatory for establishing the efficacy and safety profile of the drug and are critical for approval.

circumstances, a regulatory agency may require Phase IV, or post-marketing studies in case additional information needs to be collected

after the drug is on the market.

During all phases of clinical

development, regulatory agencies require extensive monitoring and auditing of all clinical activities, clinical data and clinical study

sites investigators to minimize risks and ensure high quality and integrity of the collected data.

The sponsor of a clinical study is

required to submit an annual safety report to the relevant regulatory agencies, in which serious adverse events are reported, and also

to submit in an expedited manner any individual serious adverse events that are suspected to be related to the tested drug and are unexpected

with its use.

An agency may, at its discretion, re-evaluate, alter, suspend, or terminate the clinical study

based upon the data that have been accumulated to that point and its assessment of the risk/benefit ratio to the patient.

As of June 30, 2021, we employed

a total of 153 full-time employees and nine part-time employees, of whom, 129 full-time employees and nine part-time employees are engaged

in research and development, manufacturing and clinical development.

The regenerative medicine

field is characterized by intense competition, as global and local pharma players are becoming more engaged in the cell therapy field

based on the advancements made in clinical studies and due to the new favorable regenerative medicine legislation in certain regions.

We face competition from both allogeneic and autologous cell therapy companies, academic, commercial and research institutions, pharmaceutical

companies, biopharmaceutical companies, and governmental agencies.

Some of the clinical indications we currently have under development

are also being investigated in preclinical and clinical programs by others.

While there are hundreds of

companies in the regenerative medicine space globally, there are multiple participants in the cell therapy field based in the United States,

Europe, Japan, Korea, and Australia such as Athersys Inc., Celularity Inc., Tigenix NV (acquired by Takeda), SanBio Inc.

and Mesoblast

Among other things, we expect to compete based upon our intellectual property portfolio, our in-house manufacturing efficiencies

and capabilities, and the efficacy of our products.

Our ability to compete successfully will depend on our continued ability to attract

and retain experienced and skilled executives, scientific and clinical development personnel, to identify and develop viable cellular

therapeutic candidates, and exploit these products commercially.

Given the magnitude of the potential

opportunity for cell therapy, we expect competition in this area to intensify.

Impact of COVID-19

In managing our ongoing global clinical studies, as well as our daily

operations, in the ongoing COVID-19 global pandemic, we are taking all necessary precautions for the safety and well-being of patients,

healthcare providers involved in our studies, and our employees.

We are continuing our operational and manufacturing activities, subject

to the directives of the MOH, with a dedicated team on site at our facilities.

In addition, the majority of our employees have been vaccinated

and we are using remote work technologies that enable the mitigation of office staff while allowing other activities to be conducted without

the need for a physical presence in our facilities.

The COVID-19 global pandemic caused delays in enrollment of some of our clinical studies.

Despite these impacts, we currently hold supplies of PLX cells in inventory in Israel, and in secure storage facilities in Europe and

In addition, we are following the FDA and EMA guidelines regarding the management of clinical studies during COVID-19.

the impact of the COVID-19 global pandemic is constantly evolving, and we may experience further impacts on our daily operations, including

the need for employees to potentially self-isolate based on potential exposure to the virus, difficulties for our employees in travelling

abroad, and delays in our clinical trials and our ongoing research work with various hospitals and academic institutions.

Available Information

Additional information about

us is contained on our Internet website at www.pluristem.com.

Information on our website is not incorporated by reference into this report.

Under the “SEC Filings” and “Financial Information” sections, under the “Investors& Media” section

of our website, we make available free of charge our Annual Reports on Form 10-K, Quarterly Reports on Form 10-Q, Current Reports on Form

8-K, and amendments to those reports filed or furnished pursuant to Section 13(a) of the Securities Exchange Act of 1934, as amended,

or the Exchange Act, as soon as reasonably practicable after we electronically file such material with, or furnish it to, the SEC.

reports filed with the SEC are also made available on the SEC’s website at www.sec.gov.

The following Corporate Governance documents

are also posted on our website:

Code of Business Conduct and Ethics, Trading Policy and the Charters for each of the Committees of our

Board of Directors, or the Board.

Compared sentence by sentence after normalising whitespace, quotation marks, case and digits, so re-formatting and restated figures do not read as changed language. Wording changes appear as one removal and one addition. The current filing and the prior one are authoritative.

What changed 10-K

Item 1. Business