The company is at the forefront of placental-based cell therapy applications. In addition to other accomplishments, the company is now preparing for a proposed Phase III trial of its PLX-PAD cells in the treatment of critical limb ischemia (CLI).
Interview with Dr. Racheli Ofir, VP of Research & IP at Pluristem Therapeutics
Cade Hildreth: What is your background and how did you get involved with Pluristem?
Dr. Racheli Ofir: I did my PhD and post-doc in cellular and developmental biology at the Technion in Haifa. I joined Pluristem 9 years ago and am responsible for the research activity of the company including efficacy and safety studies of Pluristem placenta-derived cells, as well as revealing the underlying mechanism of action of the cells.
Cade Hildreth: What is Pluristem’s core technology and what are its benefits?
Dr. Racheli Ofir: Pluristem’s core technology are placenta-derived cells that are being developed as a real ‘off-the-shelf’ therapeutic product for critical high unmet need indications, where there are limited or no alternative treatment options available. For example, Pluristem’s lead product, PLX PAD is in clinical development for diseases such as critical limb ischemia (CLI) and hip fractures. With CLI, PLX PAD will be used to reduce the likelihood of a major amputation in these patients, who are typically elderly and suffering from chronic co-morbidities.
With the hip fracture indication, Pluristem is targeting an indication that has a very high rate of mortality at one year. Our cells will allow these often elderly patients to get up and moving faster post-surgery. One of the lead causes of complications and deaths in the elderly post- surgery is that they are not ambulatory.
Cade Hildreth: What are PLX cells?
Dr. Racheli Ofir: PLX cells are a patented ‘off-the-shelf’ cell therapy product that requires no tissue matching prior to administration. PLX cells are produced from the cells of human placentas that are donated by mothers who have delivered healthy, full-term babies. PLX cells secrete therapeutic proteins in response to signals produced by damaged tissues. The proteins can trigger the body to use its own physiologic processes to address serious conditions, such as ischemia, muscle trauma, damaged bone marrow, and inflammation.
Cade Hildreth: What makes PLX-R18 unique and how does Pluristem manufacture it?
Dr. Racheli Ofir: Each PLX cell product is designed with a distinct secretion profile, in order to target specific indications. PLX-R18 is designed to secrete a range of therapeutic proteins that protect and regenerate bone marrow and also influence the immune system.
Pluristem’s PLX-R18 is active in two programs: the first one is to treat patient who were exposed to high levels of radiation; the second program was recently cleared for clinical studies with the FDA to support incomplete bone marrow engraftment following bone marrow transplantation. There are no good counter-measurement to treat ARS post exposure to radiation.
The hematologic component of ARS results from damage to the bone marrow and is characterized by acute decreases in red and white blood cell and platelet counts, which can lead to infection, hemorrhage and death. PLX-R18 demonstrated improvement in the recovery of white blood cell, red blood cell, and platelet levels in animals exposed to high levels of radiation.
The cells secrete a broad array of cytokines such as MCP-1, IL-6 and IL-8 that contribute to the reconstitution of the hematopoietic system.
Pluristem’s cell products are each manufactured at the company’s own facility within patented bioreactors which provide the cells with a three-dimensional microenvironment in which to grow. Although they all originate from placental cells, each PLX product has a different therapeutic secretion profile and characterization. These differences are achieved by precisely controlling the environment in which the cells are cultured.
PLX-R18 cells are grown in a very specific environment that is generated and maintained in the bioreactors, and this environment determines the specific characteristics of the product. Pluristem uses the high surface-to-volume ratio of three dimensional (3D) non-woven scaffolds in its bioreactors, resulting in a system which is many times more efficient than the current 2D methods of cell culturing.
Cade Hildreth: What role is the NIH playing in the development of PLX-R18?
Dr. Racheli Ofir: The NIH’s National Institute of Allergy and Infectious Diseases (NIAID) supports the ARS program of PLX-R18. R18 as a potential treatment for Acute Radiation Syndrome. On February 16, 2016, Pluristem announced that the NIH is initiating studies in large animals to evaluate dosing for PLX-R18 as a medical counter measure in the treatment of the hematologic components of Acute Radiation Syndrome (ARS). Once the optimal dose is determined in large animals, a pivotal trial could be conducted using this data and the results used to apply for marketing authorization of PLX-R18 for this indication under the Animal Rule regulatory pathway.
The NIH’s NIAID has previously communicated its interest in supporting and conducting the pivotal trial. FDA approval of PLX-R18 for ARS could generate U.S. government interest in stockpiling it for use in the case of a nuclear disaster, since PLX cell products are ideally suited for rapid initiation of treatment of large populations. Our cells do not require tissue matching prior to administration, and can be administered quickly via intramuscular injection.
Cade Hildreth: Why did Pluristem choose to focus on placenta-based cell therapy products?
Dr. Racheli Ofir: Pluristem was a leader in recognizing over ten years ago the unique characteristics of the placenta. These characteristics include low immunogenicity, no HLA typing, the ability to do repeat dosing, and more. The scientific community now recognizes the unique benefits of the placenta and that is why the NIH launched a well-funded placenta project.
Cade Hildreth: What motivated Pluristem to enter the defense technology space?
Dr. Racheli Ofir: In times of global threats, the free world is looking for global solution. When we discovered the beneficial properties of our PLX-R18 cells to recover from ARS, we saw it as our duty and privilege to make available to the world a counter measurement to one of our serious current threats. PLX-R18’s properties make it a potentially ground-breaking treatment for the hematologic component of acute radiation syndrome (ARS).
Cade Hildreth: What other markets does Pluristem serve outside of defense technology?
Dr. Racheli Ofir: Pluristem has products in development for the Cardiovascular, Orthopedic, Women’s Health, and Cancer/Hematology applications.
Cade Hildreth: What are your 3-5 year goals for the Pluristem?
Dr. Racheli Ofir: In the coming 3-5 years, our goal is to continue our progress to position our cell therapy and first line treatment for a variety of diseases, in addition to making Pluristem the world’s leader in cell-based solutions. We would like to see our PLX products approved for marketing in the major markets (US, Japan, EU), bringing cures and well-being to millions of patients around the globe.
Cade Hildreth: What trends are you observing within the cell therapy market? How might these trends affect Pluristem?
Dr. Racheli Ofir: One trend that we are observing is that many regulators are now understanding the need to encourage and promote new regenerative technologies in order to support the aging population. We can see this happening in Japan and Europe, where the regulators passed clear and decisive legislation in support of regenerative medicine. This is why Pluristem is very active and engaged in these territories.
We also have observed widespread recognition that cell therapy products have arrived, including more product approvals in the past year and multiple products in late-stage development. Consequently, we should be seeing a wave of cell therapy products being approved and made available to patients over the next few years.
Cade Hildreth: What types of partnerships, collaborations, or investments interest Pluristem?
Dr. Racheli Ofir: Pluristem is interested in partnerships with pharma companies to bring our product to the market for multiple indications as quickly as possible.
Cade Hildreth: How can people get in touch to learn more about Pluristem?
Dr. Racheli Ofir: Anyone can reach us at karinek@pluristem.com or at racheli@pluristem.com