Introducing: Pluri

Cells are the very fabric of our universe: Everything in this world begins and ends with cells. Technology that harnesses the innate power of cells, and their ability to expand rapidly, therefore has the potential to change the world.

We are thrilled to share a new part of our journey: our recent official name change from Pluristem to Pluri. The very definition of the word explains our new vision. “Pluri” means more, and we look forward to offering more solutions for more industries, enabled by our innovative 3D cell expansion technology platforms.

Pluri’s platforms are the new gold standard to accelerate development of cell-based solutions that will improve global quality of life and promote sustainability in a wide range of fields.

Our new business development strategy is twofold:

First, we are relying on our innovative technology to create new, revolutionary products. These cell-based products are developed to address some of the world’s most pressing issues, from sustainability to sustenance.

Second, we continue to search for partnerships that leverage our most valuable asset—that is, our technology. With this proprietary technology and with new partners at hand, we can innovate in many verticals, from cultured meat to therapeutics to agriculture technology and beyond.

Pluri pushes the boundaries of science to engineer groundbreaking cell-based products that promote global wellbeing and sustainability.

We look forward to welcoming the new era of Pluri and realizing our ambitious vision.

 

From food to pharma, Pluri improves lives today

We are now leveraging our advanced cell expansion platforms and our position as a worldwide leader in cell technology to develop, manufacture and market high quality cell-based products.

Revolutionizing food

Earlier this year, we entered a landmark collaboration with Israeli food giant Tnuva to produce cell-based meat, with our technology at the heart of the partnership.

This first joint venture in our food tech vertical is set to bring sustainable, affordable cultured food to consumers across the globe, creating its first product as soon as next year. We are uniquely poised to power the full production chain for the development and manufacture of affordable, quality cultured food.

Our partners at Tnuva believe so as well. “We chose to collaborate with Pluri (formerly Pluristem) because we believe it owns one of the most advanced cell production technologies in the world,” said Eyal Malis, CEO of Tnuva Group.

Transforming health and medicine

Since 2003, Pluri has perfected methods to expand a single placenta cell into billions of distinct cells. The cell expansion process serves to develop groundbreaking cell-based therapies that solve some of medicine’s most urgent unmet needs.

Pluri’s technology accelerates the development and approval of more targeted, personalized, and well-tolerated allogeneic treatments, with no need for genetic matching – changing the face of medicine, one cell at a time.

 

Partnership opportunities in the future

We see the potential in sharing this technology, not just the products that it creates.

Our new approach is one that highlights collaboration. Strategic partnerships and investments across different verticals can help to expedite the research, development and commercialization phase of many types of cell-based products. A collaborative approach also ensures that an expert in their respective field will drive key business decisions from decades of expertise.

Plurinuva is just the first partnership in our vertical of Plurifood. Looking ahead, we hope to continue to develop various cultured food products through partnerships.

We also aim to collaborate with companies from industries that include—but are not limited to—agriculture, biotech, and cell biology.

 

Our commitment to sustainability

As we move forward into the new era of Pluri, we are excited to continue our dedication to Environmental and Social Governance. Our new strategy will chart a more sustainable path in many different sectors of business and technology, from patient care to animal agriculture.

How does Pluri benefit the environment?

Meat cultured from cells in a laboratory setting has the potential to reduce greenhouse gases and other crucial resources by an incredible amount. Cultured meat produced using renewable energy reduces global warming impacts by up to 92 percent and reduces land use by up to 95 percent.

In a global age of overpopulation and dwindling finite resources, these environmental benefits are huge. Cultured meat is set to disrupt the global meat market.

How can Pluri promote better health and wellbeing?

Originating from the highest quality, premium cells, cultured meat could easily become the tastier and more nourishing option.

When it comes to healthcare, Pluri’s innovative therapies may offer hope to sick patients without another avenue for treatment. Our new cell therapy candidate can both give patients with bone marrow failure a chance for a better recovery and treat radiation exposure.

The potential impact on livelihood with just one cell candidate can be far-reaching, and this sentiment is true for Pluri’s products across the board. All Pluri’s cell therapies are created with people as the first consideration, meant to improve quality of life for patients in hospitals and those in recovery.

 

We are Pluri.

Our patented technology harnesses the wisdom of nature to develop and manufacture next generation cell-based products across a range of fields.

We aim to pioneer a biotech revolution to create next-generation cell-based products that improve human wellbeing, increase sustainability, and advance solutions to humanity’s greatest challenges.

We are thrilled to welcome you on our journey.

We only have one earth.

This is why we at Pluri are committed to creating a better planet on World Environment Day and every day.
These campaigns are important to shine a spotlight on our global footprint. To ensure we as a company and as individuals look and reflect on how we are taking action to make a difference to protect our planet and live sustainably. This is where technology is essential to enable this transformative change and support individuals as they commit to a better sustainable way of life. Whether that means going vegetarian or choosing electric cars to drive to work. These changes can only happen with technology supporting the way.

For us at Pluri, this is where we believe our cell-based technology platform can play a huge role to help transform industries towards environmental improvements.

Pluri’s technology can expand any cell type

Today, our PLacental eXpanded (PLX) cell therapies have treated hundreds of patients worldwide with a strong safety profile, demonstrated in the field of regenerative medicine. Yet, the power of our state-of-the-art cell-based manufacturing platform is not just limited to placental cells. Harnessing cutting-edge technologies in cell culture, tissue engineering and bioprocessing, our technology has the potential capabilities to expand and optimize cells of any type.

This opens up new possibilities to apply our technology to foodtech, agtech and other industries, where we can enable the mass-scale production of high-quality animal and plant cells with batch-to-batch consistency. The recent signing of our landmark food-tech joint venture with Tnuva Group, Israel’s largest food producer, to establish a cultured food platform, is one example of the work underway.

As humans and animals use more resources and generate more waste than ever before, our technology brings great promising implications to help protect our environment.

In the last decade, there have been huge technological advances in the food tech industry. One of these is the development of cultured meat (genuine animal meat that is produced by cultivating animal cells directly). Pluri’s cell expansion technology can be directly applied to develop cell-based meat and plant products that would have flavor similar to conventional food. This would bring huge environmental benefits.

The influence of conventional farming on our environment today

Besides the humane aspects associated with the rearing and slaughtering conditions of animals in the food industry, the livestock industry today impacts our environment in many ways.

In fact, the biggest challenge facing the industry, and as a result our environment, is from the ever-increasing consumption of animal products. Global meat production is expected to double from 229 million tons in 1999 to 465 million tons by 2050[1]!

This will have a huge impact on carbon dioxide emissions – one research paper estimates that the global livestock industry is responsible for at least 51% of the greenhouse gases emitted to the atmosphere. Furthermore, the increasing demand for animal products and the lack of land has caused the livestock industry to become the main cause for clearing forests and turning them into pasture. Production of animal food products is also the greatest agricultural cause of water pollution alongside bringing huge water wastage and the production of copious amounts of waste[2].

When we consider arable farming, a similar picture is seen. Intensive feed-crop production can lead to severe land degradation, water pollution and biodiversity losses, while expanding arable land into natural ecosystems also can have serious ecological consequences. These include the loss of biodiversity and of ecosystem services such as water regulation and erosion control. The use of fertilizers and pesticides also contaminate and degrade the environment.
But what if we could change this?

This is exactly where we believe the power of cell-based technologies, like Pluri’s, can inspire and transform.

How do cell-based meats and plants help the environment?

As our population grows, the foodtech and agtech industry must create a sustainable system that can feed the world in a way that is scalable, efficient, cost effective, and does not harm the environment.

Cell-based meat production (or cellular agriculture) provides the industry with one solution. Though large-scale cell-based meat production technologies are just getting started, the outlook is highly promising.

Two recent studies suggest that cell-based meat could cause up to 92% less global warming, 93% less air pollution and use up to 95% less land and 78% less water compared to conventional beef production.

So let’s imagine a future in which cell-based meat or plant production becomes the major source of protein. What would our world be like and how could this benefit our environment?

With less animals needing to be slaughtered, greenhouse gas emissions would be anticipated to fall, alongside less land and water used. This could also free up cropland to feed more people. This land could even be used for ecological purposes to aid reforestation for carbon sequestration or to replant. Here the capabilities of plant roots to absorb water can be used to help prevent the cycle of drought, flooding, and erosion that occurs in these areas.

With less fertilizers and pesticides, the quality of water may improve, and improvements in biodiversity may be seen which would impact the whole food chain.
The environmental benefits are vast, and it doesn’t stop there. By improving our environment, this may also have a knock-on effect with improvements in our health and wellbeing!

Enabling a better future for our environment

We at Pluri are hard at work to make this vision a reality. By combining our cell-based expertise through partnerships, we are seeking new approaches to accelerate development to create a better world for the generations to come.

However, true environmental change must come from the collective action of all of us. In the consumption choices we make here and now, as well as in the future. Only together can we build a more sustainable planet for our children.

As we honor World Environment Day, let’s remember there are billions of planets in the universe – but we have only one earth, one home.
Let’s make it the best it can be!

[1] Santo R. et al. Considering Plant-Based Meat Substitutes and Cell-Based Meats: A Public Health and Food Systems Perspective. Review Article:  Front. Sustain. Food Syst., 31 August 2020.

[2] Dopelt K. et al. Environmental Effects of the Livestock Industry: The Relationship between Knowledge, Attitudes, and Behavior among Students in Israel. Int J Environ Res Public Health. 2019 Apr; 16(8): 1359.

Key global challenges in sustainable development

Humans are the most populous large animal on earth today.  In fact, the average global human population grows by 2.6 people every second (81 million people per year).  That’s a lot of people and in fact, it means the world population could reach 8 billion by 2023!

At the same time, the number of people over 65 years of age is expected to double reaching 20% of the total population – a whopping 1.5 billion by 2050.  With more illnesses and long-term diseases as a result of aging and an associated poorer quality of life, global healthcare systems will face even greater resource pressures.

These rapidly changing dynamics mean we are now facing remarkable new global challenges. We are consuming, polluting and using more resources than ever before. Take conventional farming for example, we use more land and water to grow and raise food while also using fertilizers and pesticides that may contaminate and degrade the environment. On the other hand, we must also continue to provide healthcare with compassion and dignity for our aging population.

So how do we do this? The answer: changing the way we approach and solve these challenges. Innovation in cell-based products may provide the solution humanity needs.

Helping the planet with cell-based products

Cells are the building blocks of life. Our bodies are built from trillions of different cell types that work remarkably together in harmony to maintain our wellbeing.  In fact, life on earth begins and ends with cells. Yet the unique power of this tiny organism is only recently starting to be explored.

Over the last 15 years, we have seen considerable advances in biotechnology with breakthroughs in cell expansion and regenerative medicine. Cell therapies are important precisely because of the growing, aging population facing chronic and long-term diseases. We need to develop new solutions to regenerate and cure our bodies. This understanding led to considerable progress in the development of multiple cell-based therapies, as well as new and more effective biologics and improved approaches to regenerate damaged tissues.  Pluri’s placenta-based cell therapies are an example of these innovative products.

However, cell expansion technologies are not limited to the regenerative industry alone. This state-of-the-art technology has also led to new developments in emerging industries, for example in the food tech industry with cultured meat (genuine animal meat that is produced by cultivating animal cells directly).

With flavor similar to conventional food, cell-based meat production provides many advantages to support global sustainability.  For example, no animals are needed to be slaughtered meaning less land and water is used, fewer greenhouse gases, and a reduction in agriculture-related pollution demonstrate its environmental sustainability as well as ethical benefits with the elimination of animal cruelty.  Furthermore, cells can be altered to make food healthier, for instance, decreasing fats and increasing nutrients.

What is a cell-based product?

Cell-based products are products that contain or consist of cells or tissues from living tissue, whether human, animal, plant or fish cells that have been cultured and improved. At Pluri, we have developed a unique cell expansion platform to create various cell-based products.

Pluri’s state-of-the-art 3D cell expansion platform

Developed over the last decade, our state-of-the-art patented 3D cell expansion platform harnesses cutting-edge technologies in cell culture, tissue engineering and bioprocessing with the potential to expand and optimize cells of any type.

Our technology uses a proprietary bioreactor system, which provides a three dimensional (3D) micro-environment for our cells that is designed to mimic their natural environment.  The bioreactor is integrated into the one of the world’s most advanced, completely automated, aseptic and scalable cell manufacturing facilities.

This tightly controlled and efficient system means we can control every parameter, for example, temperature, glucose consumption and pH.  As such, the platform can alter conditions to provide cells with the most natural and optimal conditions for cell proliferation and expansion.

The bioprocessing know-how and design to scale-up

One of the biggest challenges facing cell manufacturing is scaling-up the technology for mass production.  At Pluri, we addressed this by designing and building from day one a bioprocessing approach with the capabilities to generate high-quality cell-based products on a mass scale in a cost-effective manner.

Our industrial scale GMP manufacturing facility hosts an in-house proprietary process development platform with exceptional capabilities.  This includes a proprietary serum-free media enabling highly consistent production without cost and operational reliance on third party suppliers.  The design and development of new manufacturing tools and devices, as well as cold chain methods and tools including Pluri’s Point-Of-Care Thawing Device.  For example, our advanced cold chain logistical capabilities support hundreds of cryopreserve cell shipments worldwide.

This validated and automated technology enables the production of billions of high-quality cells for mass-scale with batch-to-batch consistency.

Learning from Pluri’s pharma experience

Today, our technology applies the remarkable power of the placenta in the creation of new therapies for unmet medical needs where often no treatment exists today.

Our PLacental eXpanded (PLX) cell therapy can be administered without blood or tissue matching via a simple intramuscular injection. Our products provide potentially groundbreaking applications for treating damaged muscle, hematology deficiencies, and inflammation.

Our manufacturing processes are approved by key healthcare regulators and to date our PLX cells have treated hundreds of patients worldwide with a strong safety profile.

Harnessing cell-based products for a healthier planet

Yet, the power of Pluri’s cell-based manufacturing platform is not just limited to placental cells.  This broad, robust platform has much wider industry application. In fact, the technology can expand many different cell types, including human cells, animal cells, and even potentially plant cells.

By being able to control all parameters from upstream to downstream cell bioprocessing and produce cells on a mass scale with a low cost of goods, the platform can be harnessed to manufacture any cell type. This is not just important for every sector in the life science industry but brings much wider applications to other industries to address key global challenges.

As the pressing economic and healthcare challenges grow with an aging population, cell-based medical products offer new solutions to repair, regrow or replace damaged tissues and potentially cure diseases. As food, water and land resources must go further than ever before with a growing population, cell-based meat and plant-based meat production provide important solutions to maintain and ensure sustainability.

Partnering for greater success

So how do we make this potential better future a reality?

At Pluri, we believe in partnership. Combining expertise to enable the development of various new cell-based products for multiple applications across industries with global reach.

This can be seen with the recent signing of our landmark food-tech joint venture with Tnuva Group, Israel’s largest food producer, to establish a cultured food platform. This agreement supports Tnuva to expand their product pipeline into the field of cultured meat. While also leveraging Pluri’s state-of-the-art technology to address their cell manufacturing needs to produce cultured meat cells at scale for an affordable price.

From foodtech and agtech, to pharmaceuticals and other industries requiring mass cell production, the potential of Pluri’s technology is vast.

We are just at the beginning of exploring the microscopic universe of the cells.  So, tune into our upcoming blogs, as we step into this world of hope, wonder and opportunity.

Encouraging results from Pluri’s recent Phase 1 clinical trial not only give patients with bone marrow failure hope for a better recovery, but also reinforce the innovative cell therapy product candidate PLX-R18 as a potential treatment for radiation exposure.

The product candidate was tested in patients with incomplete hematopoietic recovery following hematopoietic cell transplantation (HCT), which may result in life-threatening failure of the bone marrow. Similarly, exposure to radiation can also result in bone marrow failure. This would mean that in the case of a nuclear fallout or other tragic radiation event, this therapy could be crucial for recovery.

The Dangers of Radiation

Even relatively low levels of radiation can cause immediate and irreversible damage to the human body, from altering our DNA to causing cancer. On the severe end of this spectrum is acute radiation syndrome (ARS), which causes potentially lethal damage to organs inside the human body.

One devastating manifestation of ARS is failure of the bone marrow, which leads to a reduction in its ability to produce blood cells. This may make victims of radiation exposure vulnerable to infections and bleeding.

ARS, therefore, is a life-threatening disorder.

Unfortunately, radiation exposure is a very real risk in our world today. Healthcare providers and governments are preparing for the devastating possibility of a nuclear attack or damage to existing facilities. Our therapy carries great potential significance for current events in Europe and could potentially provide treatment for people exposed to radiation.

Treating Acute Radiation Syndrome

Pluri’s research studies evaluated PLX-R18 as a medical countermeasure either before or after exposure to radiation, and gained support from multiple U.S. governmental agencies, including the National Institutes of Health (NIH) and the Department of Defense (DoD). These agencies conducted and funded the studies to PLX-R18 as a medical countermeasure to treat the hematopoietic sub-syndrome of ARS, and as a potential prophylactic countermeasure against ARS.

All our studies tested PLX-R18 via the FDA animal rule pathway, as efficacy studies are not permitted in humans for this therapy. After our promising pilot study on non-human primates, our PLX cell therapy was granted an orphan drug designation by the FDA for treating ARS.

The Orphan Drug Act provides granting special status to a drug or biological product, to treat a rare disease or condition. The benefits of achieving Orphan Drug Designation include close guidance by the FDA—which may accelerate the path to potential marketing approval—orphan drug grants, tax credits, and 7-year market exclusivity upon marketing approval.

One year later, the FDA cleared Pluri’s Investigational New Drug (IND) application for PLX-R18 for the treatment of ARS. This special application allows for the treatment of victims acutely exposed to high dose radiation due to a nuclear attack or accident.

PLX-R18 Hematology Updates

In our Phase I clinical study in patients with poor graft function following HCT, we showed positive results for the innovative therapy in the first clinical trial to study PLX-R18 in humans. Pluri CEO and President Yaky Yanay called it “a game changer.”

Current standard-of-care treatments do not lead to a satisfactory, long-term blood count stabilization, leading to recurrent infections and the need for repeated, costly blood transfusions. PLX-R18, on the other hand, is well tolerated by patients, shows a meaningful advantage as it reduces mortality from 29 to 18%, increases blood counts, and reduces the need for blood transfusions.

“We are proud of this product that might hold the key to improve quality of life, improve standard of care, save healthcare costs and possibly save lives,” Yanay said. He goes on to explain how PLX-R18 can accelerate hematopoietic recovery in sick patients, increase blood counts and reduce the need for blood transfusions.

These additional studies of PLX-R18 in both ARS and other hematological trials were conducted in collaboration with Charité Universitätsmedizin Berlin Institute of Medical Immunology, the Berlin-Brandenburg Center for Regenerative Therapies, Case Western Reserve University, Hadassah Hebrew University Medical Center, and Indiana University. All studies supported PLX-R18’s therapeutic potential to treat a variety of hematologic issues.

Pluri will continue to push the boundaries of science and engineering to create cell-based products for commercial use and improve the quality of life of people around the world.

In a press release dated April 29, 2021, we reported positive topline Phase I results in our innovative hematology program. This study, the first to evaluate PLX-R18 in humans, demonstrated that PLX-R18 had the potential to stimulate the bone marrow to generate all three blood cell lines – a meaningful advantage over other existing and proposed treatments.

The Problem:

Blood disorders can be very challenging to manage. Consider, for example, a cancer patient suffering from Acute Lymphoblastic Leukemia (ALL), who is receiving a Hematopoietic Cell Transplantation (HCT). While the transplant itself can improve his chances of survival from the cancer, there is a potential risk of poor graft function resulting in incomplete hematopoietic recovery leaving the patient with a life-threatening condition. Between 5-10% of all HCT recipients suffer from poor graft function (source: Chen 2020).

While standard-of-care treatments may temporarily improve blood counts, patients that continuously fail to maintain satisfactory blood counts may remain vulnerable to bleeding and recurrent infections. These patients will require repeated, costly blood transfusions, which are, unfortunately, only a short-term solution.

Therefore, we believe that there is a need for long-lasting treatment that has the potential to support generation of all three blood lines, red blood cells, white blood cells and platelets, thereby alleviating the dependency on blood transfusions and medications. Current standard of care does not address all three blood lines at once. Rather, patients suffering from sub-optimal bone marrow recovery may need to receive multiple treatments to address each deficiency.

PLX-R18:

Our PLX cells are derived from placentas that have been donated by women after birth. The PLX cells release a range of therapeutic proteins that trigger the body’s regenerative mechanism in response to severe medical conditions. PLX-R18 is the first product candidate manufactured using Pluri’s proprietary serum-free media in a 3-D bioreactor system, displaying our unique capability to manufacture a high quantity of cells with batch-to-batch consistency. Created from cells that originated from the fetus side of the placenta, PLX-R18 is unique in its potential to support renewal and differentiation of hematopoietic cells.

Our hematology program tested the use of PLX-R18 in HCT recipients. We were pleased to find that the PLX-R18 showed promising results. The study enrolled 21 patients in the U.S. and Israel, who 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: 1 million cells/kg, 2 million cells/kg, or 4 million cells/kg. Each patient received two treatments of the assigned dose.

The results, which included data from 14 of the 21 patients*, demonstrated that PLX-R18 had the potential to stimulate the implanted hematopoietic cells to realize their therapeutic potential and generate improved blood counts over the long term in all three blood cell lines at once – a meaningful advantage over other existing and proposed treatments. Overall, PLX-R18 was well tolerated and showed significant improvements from baseline counts in all cohorts for hemoglobin and platelet counts. Interestingly, patients in the high-dose category exhibited statistically significant improvements in all three blood cell lines.

Moving Forward:

Pluri’s Chief Medical Officer, Nitsan Halevy, believes that these results are an important step for the science of blood, or hematology. PLX-R18’s proposed hematopoietic mechanism of action, now demonstrated for the first time in humans in our Phase I HCT study, potentially opens up new therapeutic options in the fields of hematology. Building on these encouraging initial results, Pluri is refining its clinical development plans for PLX-R18 to address areas of unmet medical need.

* Data from the six-month follow-up is available for 14 of the 21 treated patients: one patient was terminated early, three patients missed the 6-month visit and three died prior to the 6-month visit (two fatal events in the 2 million cell dose, and one fatal event in the 4 million cell dose). All fatal events in the study were considered unrelated to the study treatment. Mortality rates were in line with publicly available information (references: Gao et al 2020, Halahleh et al 2021, Tang et al 2018, Sun et al. 2015, Zhao et al 2019)