Recently, I had the honor of interviewing the CEO of Gamida Cell, Dr. Yael Margolin. Headquartered in Jerusalem, Israel, Gamida Cell is best known for its innovative approaches to hematopoietic stem cell (HSC) therapeutics.
Although a small company at the time, Gamida Cell broke onto the global scene in 2003 when it announced a Phase I trial of its StemEx™ product for the treatment of leukemia and lymphoma patients.
StemEx™ was Gamida Cell’s first generation product for the ex vivo (“outside the body”) expansion of cord blood stem cells, which can be utilized in hematopoietic stem cell transplantation (HSCT) to treat high risk cancers.
Although StemEx™ did not make it beyond Phase II/III trials, this expertise in ex vivo expansion of cord blood lead to the development of Gamida Cell’s current flagship product, NiCord®, and established Gamida Cell as a global technology leader for functional expansion of cells.
Gamida Cell’s lead product, NiCord®, offers patients in need of HSCT an alternative to the existing approach of bone marrow transplant by using ex vivo expansion of cord blood.
NiCord® has an orphan drug designation. NiCord®, CordIn™ and other products under development by Gamida Cell, all utilize the company’s proprietary NAM platform technology to expand cells while preserving, and surprisingly, even enhancing their functionality.
Click here to learn more about Gamida Cell’s novel treatment approaches or read on to enjoy the interview with Dr. Yael Margolin below
Interview with Dr. Yael Margolin, CEO of Gamida Cell
Cade Hildreth: How and when was Gamida Cell founded?
Dr. Yael Margolin: Gamida Cell was founded in 1998. The company has a long history. As you probably know, the company developed its first stage product called StemEx™ in a joint venture with Teva Pharmaceuticals.
This product was an expanded cord blood unit for hematopoietic stem cell transplantation into patients with hematological malignancies. It was developed through a Phase III study.
At that point, the company shifted its focus to the development of a second generation product, which we are now developing, called NiCord®. While the development of StemEx™ was expensive, it was an excellent learning process for the company. Many members of our team today have been with the company for more than 10 years, and our experience with StemEx™ built up a strong expertise in taking a product from a technology in our lab, to a manufacturing process that is robust under GMP conditions and cost effective to manufacture.
We also developed a very deep understanding of the clinical infrastructure, established relationships with key opinion leaders in the field, and gained an understanding of the regulatory processes and tasks required to bring a biological cell product to market.
All of that has been implemented into the development of NiCord®, so its development has been very effective and rapid compared to the development of StemEx™. We know now how to avoid mistakes that we made in the development of StemEx™.
Today, I think that the expertise that we gained with StemEx™ is one of our biggest assets, in addition to our technology program and products.
Cade Hildreth: How did you become involved with Gamida Cell?
Dr. Yael Margolin: I was a partner in a venture fund in Israel called the Denali Ventures, a group that focused on investments in health care. One of the first investments that we made was in Gamida Cell in 2000.
For several years, I was on the Board of Directors for Gamida Cell, as well as for other companies. When the previous CEO decided to move on in 2004, I was offered the job.
At that time, I thought to myself, if I ever wanted to become a CEO among all the companies that I had been involved with, Gamida Cell would be the one that I would choose because it had such wonderful potential.
I decided to take the responsibility, and I have now been the CEO for 11 years now, since early 2005.
Cade Hildreth: What is the core focus of Gamida Cell?
Dr. Yael Margolin: Gamida Cell is an immuno-oncology company that uses stem cells and NK cells to develop cures for orphan indications, largely for cancer and genetic diseases.
The core technology that we developed is our proprietary NAM technology. It allows us to manufacture large number of cells, while preserving and even enhancing their functionality. As you probably know, one of the big challenges in developing cell-based products is that you need to manufacture a large number of those cells to have a therapeutic dose. But once you put them in culture, and this it is true for any type of cells, they tend to lose their functionality.
One of the strengths and the beauty of Gamida Cell’s NAM technology is that it not only preserves, but actually enhances, the functionality of expanded cells.
We’ve seen this with hematopoietic stem cells (HSCs), NK cells, and also with mesenchymal stem cells (MSCs). We are not developing a mesenchymal stem cell program at this stage because we need to focus, but in all these cell types we have seen beautiful clinical data demonstrating the capability of the NAM technology to preserve the functionality of cells.
Cade Hildreth: What were your key objectives in the development of Gamida Cell’s NiCord® product?
Dr. Yael Margolin: Our first objective when we started developing NiCord® was to expand or enrich a unit of cord blood with highly functional stem and progenitor cells, because this is the limiting factor in transplanting umbilical cord blood within the adult patient population.
Today, we know that NiCord® is not only a unit of cord blood that has been enriched with functional stem and progenitor cells, but it is also enriched with immune modulatory cells.
We now have an ongoing research program to better understand the mechanism of action of NiCord®.
However, the clinical outcomes that we are seeing cannot be explained only by the enrichment in stem and progenitor cells. There are aspects that we are observing clinically that must be associated with a more complex mechanism of action. Some of it we can explain by the immunomodulatory nature of the cell composition.
Cade Hildreth: On December 7th, 2015, Gamida Cell reported positive top line results from an international, multi-center, Phase I/II study of NiCord® for blood cancers. What are the next steps for development of NiCord®?
Dr. Yael Margolin: The final data of this Phase I/II study will be published this year. We plan to begin the Phase III registration, randomized controlled studies of NiCord®, around mid-next year.
We have already reached agreement with both the FDA and EMA regarding the design of the studies. We are now finalizing the last aspects of the clinical protocol. We also plan to begin another study with NiCord® next year in pediatric patients with refractory leukemia. This is again an orphan indication with significant clinical needs and sad patient outcomes. One of the aspects we are hoping to evaluate in this patient population is the specific anti-tumor effects and anti-leukemia effects of NiCord®. So, this is another study which will begin in the second half of next year.
For our registration phase III study, which is the critical path obviously, we will recruit patients across approximately 15 clinical sites within the United States and Europe. The follow-up will be for one year, meaning that readout will be available in 2019.
We also have another program going, with a product called CordIn™ for hematopoietic stem cell transplantation in non-malignant diseases. We are now recruiting patients with sickle-cell disease or thalassemia. We also plan to begin another study in patients with aplastic anemia, which would be the first indication among bone marrow failure syndromes.
The product CordIn™ has potential not only to address hemoglobinopathies such as sickle cell disease and thalassemia, but also genetic metabolic diseases, bone marrow failure syndrome and eventually also refractory autoimmune disease.
Last but not least, later this year we plan to begin the first clinical study with our NK cell product. It will be an investigator initiated study.
Cade Hildreth: Interesting. What are the advantages of NiCord® relative to other transplantation approaches that seek to address the limited cell dose in cord blood, including double cord blood transplantation, Wagner’s exploration of SR1 at the University of Minnesota, and similar?
Dr. Yael Margolin: The big problem with cord blood transplantation is the limiting number of stem and progenitor cells in an unmanipulated cord blood unit. This limited cell dose is associated with delayed engraftment, and delayed engraftment correlates with increased morbidity and mortality. There is a lot of literature around this.
The approach of using a two blood cord units does not significantly improve time to engraftment. So, time to engraftment with single or double cord blood is still between to 23 to 27 days, compared to approximately 14 days with peripheral blood.
With NiCord®, we’re seeing engraftment after only 10 to 11 days. The rapid engraftment is associated with reduced morbidity. Because NiCord® is based on cord blood it can obviously be available to practically all patients, unlike peripheral blood.
Clinicians that have experienced NiCord® with their patients in our clinical trials are saying that NiCord™ represents a “paradigm shift in transplantation”.
The reason is that NiCord® can be available to practically all patients and the clinical outcomes seems to be at least as good as peripheral blood, which is the gold standard.
Therefore, what we are actually offering here, the proposition of NiCord®, is a graft solution with clinical outcomes that are comparable to peripheral blood, and that can be available to all patients, while peripheral blood is only available to 40 to 50% of patients.
Peripheral blood, like bone marrow, requires full tissue matching between the patient and the donor. When you look at the patient population, there are approximately 70,000 patients each year with a high risk leukemia or lymphoma who are indicated for a donor-derived (allogeneic) hematopoietic stem cell transplantation.
Of these 70,000 patients, approximately 20% (14,000) have a family-related matched donor and the other 80% (56,000) start a search for a matched unrelated donor through the public registry. But in the end, only an additional 20% of those searching through the public registry will find a matched donor (another 14,000).
Also, you have to consider that the search itself takes time, and during this time, the disease may deteriorate or relapse. Sometimes patients cannot be transplanted anymore, because it’s too late. The median time of the search is between 3 to 4 months.
Then, there are the additional 10% of patients who get transplanted with some type of investigational graft, for instance, a haplo donor or unmanipulated cord blood.
The bottom-line is that the pie chart of 70,000 patients is divided up into 20% matched-related donor, 20% matched unrelated donor, 10% investigational products, and 50% that never get a transplant, which is the unmet need in transplantation.
Therefore, the big advantage of NiCord® being an umbilical cord blood product is that in addition to cord blood being readily available through public cord blood banks, you do not need full tissue matching with the patient. Partial tissue matching is good enough.
Therefore, all of these tens of thousands of patientswho do not have a matched donor will have at least one unit of cord blood that matches them well enough.
Most patients will actually have more than one unit that matches them. So, theoretically, cord blood could solve the unmeet needs in transplantation.
However, currently, the use of cold blood is limited to largely to the pediatric population, because of the limiting cell dose.
You need a minimal cell dose, which is calculated per kilogram body weight of the patient. Therefore for patients with small body weight, say 30 to 40 kilograms, you can usually find a unit of cord blood with enough cells for transplantation.
But, for the adult population or the adolescent, it becomes almost impossible to find a unit of cord blood with enough cells. Therefore the use of cord blood in the adult patient population is more limited at this time, and NiCord® will solve that problem.
Cade Hildreth: I like your visual of the pie chart divided into sections of 20%, 20%, 10%, and 50%.
To summarize, NiCord® can provide a transplant solution for the 50% (35,000) of patients each year that never get transplanted. It could also serve the additional 10% of patients that are getting investigational grafts, as well as those patients who cannot wait to search for an unrelated matched donor. Is this correct?
Dr. Yael Margolin: Right. NiCord® can definitely solve the problem for the 50% that are not getting transplanted and the 10% that are getting investigational products with clinical outcomes that are not very good. However, it would also benefit the 20% of patients that spend 3 or 4 months searching for a matched unrelated donor. These patients may prefer a faster transplant with NiCord®, because the clinical outcomes are comparable, based on the clinical data we have so far. Therefore, the market potential is very significant.
Cade Hildreth: So, NiCord® would be a better alternative for 60-80% of the patient population requiring a donor-derived hematopoietic stem cell (HSC) transplant.
Meaning, it would be a preferred outcome for everyone except the 20% of patients who receive a family-related matched donor each year.
Dr. Yael Margolin: Exactly, because the matched related donor is available immediately. It is usually a sibling.
Cade Hildreth: Excellent. What are your 5 to 10 year goals for Gamida Cell?
Dr. Yael Margolin: The biggest goal is to bring NiCord® to market. It is a life saving product, so it is our company mission to bring this product to the market.
Additionally, we are a leader in developing technology for the expansion of functional cells, so we want to maintain and expand our scientific and clinical leadership in this area. The next step is for us to bring additional products to market and to develop new applications for the NAM platform technology, because it has substantial growth potential that we want to explore.
Cade Hildreth: With the NAM platform technology having such a wide range of applications, how did you initially decide which target markets to go after?
Dr. Yael Margolin: The reason why we targeted bone marrow transplantation first with the NAM technology is because there is huge unmeet clinical need in this area.
Also, when you think about cell therapies, most of them are not currently being used in clinical practice. For instance, if you think about the use of mesenchymal stem cells to treat cardiology indications, this is not yet in clinical practice.
Therefore, to introduce this approach, you would need to educate clinicians to use cells and to handle cells for their patients. Bone marrow transplantation is the only cell therapy that has been in clinical practice for more than 40 years.
We aim to leverage the clinical practices that already exist, and at the same time, provide a solution for huge unmet clinical needs.
Cade Hildreth: Gamida Cell has had some major partners and investors involved with the company, including relationships with TEVA Pharmaceutics and Novartis, among others. What has been the importance of these partnerships?
Dr. Yael Margolin: Both our partnership with TEVA Pharmaceuticals and Novartis have been important. TEVA was important for the development of StemEx™, because Gamida Cell was then a young a company with less experience.
Today, Novartis is a shareholder in the company but does not have strategic rights to any of our products. Gamida Cell owns the worldwide rights to all of its products and technologies.
However, Novartis is a major player in the field of cell therapy and respected as a high quality pharmaceutical company, so they are very valuable as partners.
Cade Hildreth: Do you anticipate any future partnerships?
Dr. Yael Margolin: Once we begin the Phase III study of NiCord® we will look into potential partnerships to commercialize the product. We are not active in that direction right now, but it is something that we will be considering once we move into the Phase III study. Gamida Cell is well financed at this stage.
We definitely have enough money to begin the Phase III study, but we will be looking to raise more money in 2016.
Cade Hildreth: Excellent, will you be targeting investors in Israel, the United States, or worldwide? And, are there specific types of investors that you are seeking?
Dr. Yael Margolin: We will be looking primarily, but not only in the United States.
Cade Hildreth: Do you know what amounts you are seeking at this point?
Dr. Yael Margolin: Several tens of millions.
Cade Hildreth: Thank you for this enlightening conversation and the honor of doing this interview. Congratulations on your successes so far with NiCord® and the NAM technology platform. I look forward to following Gamida Cell’s progress through 2016 and beyond.
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To learn more, view the “Complete 2015-16 Global Cord Blood Banking Industry Report.”