As a co-founder and CEO of Cellect Biotechnology (TASE:CLBD), Dr. Shai Yarkoni has more than 15 years of clinical and management experience in the biopharmaceutical industry. He is the founder of five start-ups in the life-sciences field, and serves on the board of noted institutes in Israel and the world. Prior to founding Cellect, he was CEO of Target-In, and CTO and VP R&D of Collgard Biopharmaceutical, a tissue therapeutics company. Dr. Yarkoni is a board certified Ob/Gyn and is the author of over 60 scientific papers. In this interview with BioTuesdays.com, he discusses Cellect’s unique approach to facilitating immune stem cell selection for bone marrow transplantation.
Let’s begin with a brief history of the company.
Cellect was founded in 2011 by myself, Dr. Nadir Askenasy, who is now our chief scientist, and Kasbian Chirich, our financial and business leader, in order to develop commercial medical applications on the basis of our functional stem cell selection technology. In July 2013, we completed a reverse merger into a TASE-listed company and to date, we have raised more than ILS 20 million. Our technology is the result of 15 years of academic research, largely by Dr. Askenasy, and is protected by several patent families in the U.S., Europe, Israel and elsewhere.
Can you summarize your platform technology?
We have proved in extensive lab and animal studies that the use of apoptosis can largely increase the stem cell concentration in samples taken from bone marrow donors, as well as umbilical cord blood. Our platform technology enables functional selection of a wide variety of stem cells, with many potential applications. It is based on the game changing perception that the functional properties of stem cells should be used to develop superior identification, selection and utilization of stem cells. The technology is designed to harness the critical function of sensitivity to specific apoptosis agents, or programmed cell death. While these molecules induce apoptosis in mature cells, they spare stem cells. This differential sensitivity can be used to dramatically improve the outcome of bone marrow transplantation mainly by eliminating severe adverse effects, and by facilitating engraftment, while providing significant reduction in the costs of treatment. Our first product under development is a medical device for the bone marrow transplant market to treat blood cancers, as well as other markets where there is a need for stem cell selection.
Can you give us a primer on stem cell transplantation?
This is a medical procedure where stem cells reconstruct and replace damaged tissues and organs – a potential cure for a wide range of diseases and disorders. Bone marrow cell transplantation is actually transplantation of multipotent hematopoietic stem cells derived from bone marrow, peripheral blood, or umbilical cord blood chaperoned by mature cells that currently can hardly be separated from the stem cells. These cells are the main cause of adverse events frequently seen in bone marrow transplantation. Stem cell transplants are used to replace bone marrow that has been destroyed by cancer or autoimmune disease, chemotherapy, or radiation therapy. Hematopoietic stem cell transplants have been in use for several decades, and have improved substantially over the years. However, the procedure poses significant issues with morbidity and toxicity, and precludes its wide therapeutic use. Because of the risks and side effects associated with the procedure, these transplants are currently performed as a last resort for intractable hematological malignancies and on a limited basis to correct inborn immune deficiencies.
How does your technology fit with your business strategy?
As a first step, we are focused on achieving a relatively quick validation of the technology in a significant market. That’s why we selected an application that reduces the risks in bone marrow transplant for leukemia patients. The most common life-threatening condition following a transplant is Graft versus Host Disease (GvHD), where immune system cells from a donor attack the body of the recipient patient. In parallel to validating the technology, we are developing a wide range of applications, including diabetes and solid organ transplantation, for a broad spectrum of market segments, up to and including all production and research processes for stem cell-based products. We believe that in 10 years, our process will be integrated into the production procedure of stem cell-based products and be an essential part of regenerative medicine.
Can you update your collaboration with the Entegris?
About 6 months ago we started collaborating with a U.S.-based company called Entegris. It is a market leader in the field of high-end, polymer-based products and is currently expending its life sciences portfolio. The synergy between their chemical and manufacturing capability in polymer-based products and our biological understanding, as well as patent coverage, highlights the potential for a strong collaboration and a win-win situation. We are jointly applying for a large bi-national grant and are considering other commercial considerations of the activity.
What is your lead product?
Our first product under development is a specialized off-the-shelf infusion bag coated with apoptotic ligands for use within the process of preparing the graft for bone marrow transplantation. These ligand proteins initiate an apoptosis process leading to elimination of mature somatic cells that give rise to GvHD, while sparing progenitor stem cells that facilitate engraftment. Therefore, we are creating the first functional selection system of stem cells for medical use. Based on the same concept we are also developing another line of products for the life science research market, which consists of test tubes with an apoptotic inner coating for stem-cells selection. I would like to emphasize that in using our products and procedure, there is a significantly shorter procedure time and lower procedure costs, compared with current procedures.
What’s the clinical status of your technology?
We have established proof-of-concept for the technology in animals and in human cells, and have built a comprehensive IP portfolio protecting its development. In our animal studies, using various sources of hematopoietic cells, mortality rates for GvHD were dramatically reduced. There was a significant reduction of cells that attack the immune system and an increase in the percentage of stem and progenitor cells in the sample. In addition, we saw preservation of successful engraftment and maintenance of an anti-tumor effect.
What is the next step in your clinical development?
We are currently preparing a first-in-human trial this year with our process of functional selection of stem cells. The first study is taking the donor’s graft and incubating it with FasL, washing and transplanting it. This is planned as a Phase 1/2 open label study with 12 leukemia patients, to be conducted in Israel. The primary endpoint is safety. This Phase 1/2 study covers both GvHD as an adverse effect of bone marrow transplant, so it is a safety issue, but also the target of our treatment. As a secondary endpoint, we will also evaluate time to engraftment, again aiming to show that unlike other cell selection processes, the reduction in GvHD does not lead to delayed engraftment, another safety issue.