This interview comes shortly after Novartis became the first company to get a gene therapy approved in the United States, the CAR-T cell therapy, Kymriah®. The historic event demonstrates to investors, the public and funding providers alike that cell therapy is a sector that has emerged, no longer one that is evolving in the future. There are close to 40 companies developing redirected T cells or NK cells for therapeutic use. There are also 800+ cell therapy clinical trials underway around the world, and a considerable amount of research and preclinical work taking place across the cell therapy sector.
In the light of the recent, but still to-be-confirmed, Gilead takeover of Kite Pharma for $11 billion, the cellular immunotherapy sector is in focus among both investors and oncology and non-oncology companies. The search for the “next Kite” has begun!
Glycostem is a 10-year old clinical stage cellular immunotherapy company based in The Netherlands. The uniqueness around Glycostem, beyond that it is a privately funded company with strong phase I safety clinical trial data, is that it may become the first company with an allogeneic off-the- shelf product (oNKord®). This would potentially position NK cell technology to leapfrog CAR-T cell products, due to a safer profile, lower production costs, off-the- shelf status and positive clinical trial data.
Troels Jordansen, Chairman and CEO of Glycostem is an unusual interviewee, because he does not come from a clinical nor scientific background. However, he does have an abundance of industry sector experience. He was one of the first Genzyme Tissue Repair recruits in Europe and ended up overlooking 14 consecutive quarters with revenue expansion with Genzyme’s Epicel and Carticel pioneering products.
Since those early days, Troels has been involved in 5 cellular therapy companies and guided three of them into clinical trials, GMP manufacturing and product approvals. Being part of various management teams, Troels also raised around $150 million for these 5 companies. I am excited to share his insights with you today.
Interview with Troels Jordansen, Glycostem Chairman & CEO
Cade Hildreth: How and when was Glycostem founded?
Troels Jordansen: Over 10 years ago, the stem cell expansion and NK cell differentiation technology caught the interest at the German Cancer Institute in Heidelberg. Three years later, the technology was spun into Radboud University Medical Centre and under the scientific stewardship of Dr Jan Spanholtz Glycostem set-up a closed system manufacturing operation expanding NK cells from umbilical cord blood. The development work concluded in a 10-patient phase I clinical trial which was published in CCR March 2017. In the meantime, Glycostem left Radboud and set-up its own R&D laboratories in a science park in The Netherlands, where our work is continuing.
Cade Hildreth: How did you become involved in Glycostem?
Troels Jordansen: Back in 2013, I was approached by one of the investors in Glycostem and asked if I would be interested in becoming Chairman. After a closer look at the technology, publications and speaking to friends within the industry, my response was an easy but solid “yes”. The NK cell technology, the scientific work of Dr Jan Spanholtz, and the people within the company holds so much promise and expertise, that this was an opportunity not to be missed.
Cade Hildreth: What excited you most about the company’s potential?
Troels Jordansen: NK cells are perfect for the job of killing abnormal cells, such as cancer cells. Glycostem is positioned to potentially generate the 1st off-the-shelf cellular immunotherapy, which is possible with oNKord®, as we utilise the mismatched principle. This means that we can culture cells and store them frozen and thaw them at bedside. Due to the allogenic nature of oNKord®, there are no logistical hassles and the production costs are a fraction of CAR-T cells with a much better safer profile.
Cade Hildreth: Your phase I clinical trial data is very interesting and I am surprised that it is not more talked about. Can you please give a brief summary?
Troels Jordansen: The main focus of our trial was to establish safety in a dose escalation study and we met that milestone very convincingly, with no dose related side effects at all. We got to treat 10 fragile and elderly AML patients who were otherwise given 6+ months to live (usually 30% survive 12+ months) and for whom transplant was not possible. Our year one data shows 80% survival and today 50% of the patients are still alive with 48 months median follow-up. We also observed oNKord® to enter the bone marrow and survive in the body for more than a week, being cytotoxic against the remaining AML blasts.
Over the last 9-12 months there has been an increase in NK cell news from MD Anderson and several companies. Personally I feel that the safe profile of NK cells combined with fatalities in the CAR T cell trials is expanding the immunotherapy field to also include NK cells and not just CAR T cells.
Cade Hildreth: What did you learn from this study and what is your clinical focus?
Troels Jordansen: There were a few learning points. First, in our next study, we want to treat all patients with 3 transfusions 4 weeks apart, because we believe this will improve the survival. Second, we will in our next trial include newly diagnosed AML patients, as well as relapsed/refractory AML patients, so we can cover more AML stages.
We will initiate our pivotal phase I/II trials early 2019 in Europe. We plan on treating 31 patients in each of the two indications and will aim to have trial completed mid 2021 with product approval around 6 months later. It is a very aggressive timeline, but with our orphan drug designation in Europe and the USA, we feel it is entirely possible.
We are also investigating whether oNKord® can reduce the risk of secondary cancers following cancer surgery. We have convincing pre-clinical data to indicate this. But we are also interested in other blood cancers, such as MM and the like. There is plenty to explore.
Cade Hildreth: What is the main focus for Glycostem right now?
Troels Jordansen: Right now, the whole organisation is focused on setting up a GMP manufacturing facility at our current location. Over the last 5-7 years, there has been so much progress in technology, materials, and processes that we are aiming to set up a 100% closed and automated system that will significantly increase the cell yield. We have a very experienced Executive Management Team with entrepreneurial background and several GMP approvals behind them.
After consultation, we have been told that cell expansion in a class D laboratory with open processes taking place in an isolator placed in class D laboratory is according to the guidelines. We have seen several European authorities moving in this direction and we understand the EU is considering these movements to support innovation, as long as the procedures are validated. This move will greatly support cost reductions, simpler operations procedures and a larger selection of laboratory space for future expansion.
Cade Hildreth: What research areas is Glycostem exploring?
Troels Jordansen: At Glycostem, we are so fortunate to have 6 patent families covering our platform technology. This allows us to explore many different directions. For now, we are focused on in-house CAR NK cell research and have already achieved some interesting and early successes. The combination with antibodies is another interesting field.
We are currently co-developing a CAR NK product with a third party partner and we expect that we will see more of these collaboration over the coming years. We are very interested in seeing how our NK cells can support better clinical outcome with other companies’ technology.
Cade Hildreth: Do you have a message for our readers?
Troels Jordansen: There has been so much hype around CAR T cells that the CAR T sector is now pretty close to “patented up to the hilt”. This will automatically force academic researchers/developers, hospitals, clinicians and companies to look elsewhere. NK cells have been around for a long time and are universally understood as being safe and efficient. We hope that your readers will see Glycostem as a world leader in production in this parallel universe.
Cade Hildreth: Thank you for allowing BioInformant to publish this unique story about Glycostem. With your market disruptive technology, you are most definitely a company to keep an eye on and I wish you good luck.
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