I began the interview by asking Dr. Macdonald to provide us with a little background on why mesenchymal stem cells are so attractive for Cell Therapy applications. He explained that the literature is clear in this area, mesenchymal cells provide profound immunomodulatory and immunocoordination function in the body. He then provided some examples of their role in coordinating immune functions and their demonstrated success in several clinical studies.
Next, I asked about the key criteria for successful mesenchymal stem cell manufacturing and Dr. Macdonald said that really it is the same as any pharmaceutical product. The product must be safe, effective and it must be able to be manufactured consistently and reproducibly. If any of those elements are absent, then you don’t have a commercial product. This is especially true with products that have a large unmet need. He went on to describe how the real Achilles heel of trying to commercialize MSCs as therapeutics has been the reliance on multiple donors and then need for massive expansion of these cells to meet therapeutic demand. He said that the current process has allowed the industry to get to where we are today and has enabled a great deal of medical understanding, however to really capitalize on the clinical potential, we must be able to meet all the manufacturing criteria at commercial scale. In particular, it is difficult to use multiple donors for mesenchymal stem cell manufacturing because every donor is different, their cells are different, and their cells are even different at different times of collection. This makes consistent manufacturing a real challenge.
I then asked Dr. Macdonald if he could share some background on Cynata Therapeutics and the science behind their Cymerus technology platform. He said that Cynata’s roots were based at the University of Wisconsin in the labs of Dr. Igor Slukvin and Dr. James Thompson. The Cymerus technology was first developed at the University of Wisconsin and was transferred to Cynata Therapeutics where they have moved forward with the development of this technology for potential therapeutics. The science behind the Cymerus technology platform emerged from Dr. Slukvin’s work identifying the biological steps in moving from pluripotent precursor cells to MSCs. Dr. Macdonald said that since we have the biological pathway from pluripotency to lineage specific development from Dr. Slukvin’s work we can use the mesenchymal lineage to define media and processes which allow us to produce MSCs from pluripotent precursors.
Next we discussed the difference between Cynata’s Cymerus technology and first-generation methods of mesenchymal stem cell manufacturing. Dr. Macdonald said it’s really about an evolution in the technology. The first generation method employed the use of donor derived tissues and the scarcity of MSCs in those tissues along with the process of expansion and then purification made manufacturing in this method difficult.
The Cymerus technology uses IPSCs as a starting material instead of donor tissue. Using IPSCs eliminated the problem of multiple donors and provided an unlimited quantity of identical starting material. The IPSCs are differentiated into MSCs using a proprietary method to create the final product. The result is robust and consistent mesenchymal stem cell manufacturing at a reasonable cost. The identical starting material enables no variability or senescence in the final product.
I then wanted to find out the status of Cynata’s Phase 1 trial of CYP-001 in graft vs. host disease. Dr. Macdonald explained that they were granted regulatory approval to begin a trial in 2017 with a total of 16 patients. The first cohort of 8 patients has been completed and was reviewed by a data safety monitoring board who found no safety concerns regarding moving on to the second cohort which is now underway and is set to wrap up in the next few months.
In addition to the positive safety outcomes, they saw indications of efficacy. At day 100, they saw an overall response rate of 100% with response being defined as improvement by at least one grade compared to baseline. This is quite impressive as these are patients that typically don’t improve and the disease is progressive. Complete response was 50%, with complete response being defined as showing no signs or symptoms of the disease. While Dr. Macdonald cautioned that it is still early, these results are very promising.
Next, I asked about Cynata Therapeutics’ partnership with FujiFilm and Dr. Macdonald explained that Fujifilm is a corporate partner for this product and has a global license option. They have agreed to fund further product development and commercialization of the product as well.
I asked Dr. Macdonald about the status of his interactions with the FDA and he said that they have had productive interactions both formally and informally. While they have already begun their studies in the UK and Australia, in the US additional studies were required, which they were expecting. The additional requested studies are underway and they are expected to wrap up soon when they will reengage with the FDA.
My last question was about Cynata Therapeutics’ earlier-stage programs and research collaborations. Dr. Macdonald described how Cynata Therapeutics has a strategy of engaging with academic centers around the world with expertise of studying the utility of MSCs in different clinical models. They have worked with several different groups exploring the following indications: asthma, respiratory distress syndrome, repairing cardiac tissue after heart attack, and therapeutic use in cancer, particularly glioblastoma.
We closed with Dr. Macdonald sharing that it is clear that MSCs have a profound biological function that can be deployed in a variety of indications and that this is an exciting time in Cell Therapy and an exciting space to watch. Successful mesenchymal stem cell manufacturing is a key component for successful commercialization of MSCs as a therapeutic to address many important indications.
Update: On May 24, 2018, Cynata announced that the final patient has been treated in Cohort B of its Phase 1 clinical trial of CYP-001 in steroid-resistant acute graft-versus-host disease. Data analysis will commence at 28 and 100 days post treatment.
For more information on Cynata, please visit www.Cynata.com