For years, it has been clear that mesenchymal stem cells (MSCs) are a leading type of stem cell being investigated for therapeutic applications, as they have the potential to treat a wide range of acute and degenerative diseases. In addition to secreting factors that can stimulate tissue repair, MSCs can substantially alter their microenvironment, exerting effects that are both anti-inflammatory and anti-fibrotic.
MSCs are also advantageous over other stem cells types, because they avoid the ethical issues that surround embryonic stem cell research and appear to be immuno-privileged. Importantly, MSCs also well-suited for use in the exponential growth area of 3D printing, because of their unusual capacity to form structural tissues.
There have been more than 30,000 scientific publications published about the cell type. What’s more, there are now nearly 500 MSC clinical trials underway worldwide, with East Asia, Europe, and the United States representing hot-spots for clinical trial activity. Clearly, MSCs represent an extremely active area of cell therapy development.
However, there are also major roadblocks that have impeded the therapeutic use of MSCs, which are donor-to-donor variability and the sky-high costs of manufacturing MSC products that rely upon multiple stem cell donors.
To date, the only approved MSC product is Mesoblast’s Prochymal, a mesenchymal stem cell treatment approved in Canada and New Zealand. Prochymal is produced by purifying MSCs from the bone marrow of screened donors, then culturing and packaging the cells. Prochymal addresses graft-versus-host disease (GvHD), a dangerous complication that can occur after a stem cell transplant when the transplanted donor cells identify the patient’s body as “foreign” and attack it. A related product, “Temcell,” has recently been approved in Japan. This product is also for GvHD.
Unfortunately, current approaches to manufacturing MSCs involve using multiple donors. This process drives up cost and risk by introducing batch-to-batch (donor-to-donor) variability.
A recent article titled “Sky-high price of new stem cell therapies is a growing concern” highlighted this problem, citing that Prochymal can cost as much as $200K. Temcell’s indicated price is US$113,000 to US$170,000.
Cynata to Revolutionize MSC Manufacturing – Unlimited Quantities, Uniform Batches, Single Donor, and Low Cost
Perhaps, however, good news is in sight. Cynata Therapeutics recently burst onto the regenerative medicine scene with a revolutionary new approach to MSC manufacturing. The company’s breakthrough is multi-faceted: it can produce MSCs in unlimited quantities, in uniform batches, from a single donor, and at low cost.
Cynata Therapeutics Limited (ASX: CYP) is an Australian stem cell and regenerative medicine company that is developing a therapeutic stem cell platform technology, Cymerus™, originating from the University of Wisconsin-Madison, a world leader in stem cell research.
Cynata’s Cymerus™ technology utilizes iPSCs originating from an adult donor as the starting material for generating mesenchymoangioblast (MCAs), and subsequently, for differentiating the cells into MSCs.
One of the key inventors of the approach is Igor Slukvin, who has released more than 70 publications about stem cell topics, including the landmark article in Cell describing the now patented Cymerus technique. Dr. Slukvin’s co-inventor is James Thomson, the first person to isolate an embryonic stem cell (ESC) and one of the first people to create a human-induced, pluripotent stem cell (hiPSC).
Interestingly, a handful of other innovative companies, such as Accellta and RoosterBio, have begun to explore methods of rapidly growing stem cells in large quantities at low cost, although their approach has been to use 3D bioreactors. These companies also represent an exciting new category of stem cell manufacturing companies, because they are introducing a new level of expertise to stem cell culture.
While this approach dramatically improves the time, volume, and cost of manufacturing stem cell populations, it does not provide Cynata’s key benefits of batch-to-batch uniformity and essentially infinite production. Additionally, both Accellta and RoosterBio are targeting the research products marketplace and have not yet expanded into producing clinical-grade products for companies executing clinical trials.
Most importantly, Cynata is the only company using induced pluripotent stem cells (iPSCs) as starting material for manufacturing therapeutic MSCs.
Cynata is also positioned to be the very first company to use iPSC-derived MSCs within human patients, as it announced on November 5, 2015, that mesenchymal stem cells produced using its Cymerus™ manufacturing platform will be utilized in a Phase 1 clinical study involving patients with steroid-refractory GvHD. The company also announced on January 12, 2016, that it had published positive findings from a preclinical study that utilized Cymerus™ -derived MSCs in the treatment of critical limb ischaemia (CLI).
Additionally, Cynata has strong patent protection in the area of iPSC-derived MSC manufacturing. The University of Wisconsin (Wisconsin Alumni Research Foundation) owns the technology for producing iPSC-derived MSCs, and has granted Cynata has an exclusive license to it in all major markets, including the United States, Japan, Australia, and other key regions worldwide.
Cynata is well-positioned to profit from its stem cell manufacturing solution, because its technique is simple, elegant, and cost-effective. These powerful attributes give it both a strategic advantage and a powerful differentiator within the marketplace.
It also puts the company in a high-reward, low-risk position, because its cost-savings advantages and consistent cellular product make it an attractive manufacturing partner for biopharmaceutical companies pursuing MSC clinical trials.
Furthermore, Cynata is not dependent on the outcome of any one clinical trial, because it could be a preferred manufacturing solution to a wide range of therapeutic companies. Each of these partnerships would potentially be worth multi-mullions, in the form of up-front payments, milestones for meeting specific objectives, and royalty payments for products that are granted regulatory approval.
For the first time in history, MSCs can be manufactured in unlimited quantities, in uniform batches, from a single donor, and at low cost – a powerful combination of advantages.
Key Advantages of Cynata’s Proprietary Cymerus™ MSC Manufacturing Platform
The four key advantages of Cynata’s proprietary Cymerus™ MSC manufacturing platform, as described below.
1. Unlimited Quantities
Cynata’s Cymerus™ technology utilizes iPSCs originating from an adult donor as the starting material for generating mesenchymoangioblasts (MCAs), and subsequently, for manufacturing clinical-grade MSCs. According to Cynata’s Executive Chairman Stewart Washer who was recently interviewed by The Life Sciences Report, “The Cymerus technology gets around the loss of potency with the unlimited iPS cell—or induced pluripotent stem cell—which is basically immortal.”
2. Uniform Batches
Because the proprietary Cymerus™ technology allows nearly unlimited production of MSCs from a single iPSC donor, there is batch-to-batch uniformity. Utilizing a consistent starting material allows for a standardized cell manufacturing process and a consistent cell therapy product.
3. Single Donor
As described previously, Cynata’s Cymerus technology creates iPSC-derived mesenchymoangioblasts (MCAs), which are differentiated into MSCs. Unlike other companies involved with MSC manufacturing, Cynata does not require a constant stream of new donors in order to source fresh stem cells for its cell manufacturing process, nor does it require the massive expansion of MSCs necessitated by reliance on freshly isolated donations.
4. Economic Manufacture at Commercial Scale (Low Cost)
Finally, Cynata has achieved a cost-savings advantage through its unique approach to MSC manufacturing. Its proprietary Cymerus technology addresses a critical shortcoming in existing methods of production of MSCs for therapeutic use, which is the ability to achieve economic manufacture at commercial scale.
Evidence of Favorable Competitive Positioning for Clinical Trial Partnerships
The four advantages described above will likely position Cynata as a preferred manufacturing solution for biopharmaceutical companies that are undertaking MSC clinical trials.
As evidence, Cynata recently announced that it had signed a Letter of Intent (LOI) with the German company, apceth GmbH & Co. KG regarding a future option and license agreement. apceth is a leading company using modified MSCs to treat cancer. It now has a trial underway using modified MSCs to address gastrointestinal cancer. As with Mesoblast’s Prochymal, apceth has struggled with the high costs of MSC manufacturing, which is where Cynata can provide a solution. While the terms of the agreement have not yet been released, it is clear that apceth is looking to utilize Cynata’s Cymerus MSC manufacturing technology for its anticancer program.
This is a significant announcement for Cynata, because apceth GmbH & Co. KG is an extremely well-funded group. Their major shareholders are the Strungmann family, which previously owned Hexal, one of the largest manufacturers of generic pharmaceuticals in Europe. While apceth GmbH & Co. KG is not widely known within the United States, it is a major force within the European Union (EU) biotech market. Therefore, this partnership could represent a major manufacturing contract for Cynata, with the potential for future milestone payments or royalties.
Cynata also announced on November 5, 2015, that MSCs produced using its Cymerus™ manufacturing platform will be utilized in a Phase 1 clinical study involving patients with steroid-refractory graft-versus-host disease (GvHD) and followed that announcement on January 28, 2016, with a statement that it had received favorable advice from the UK regulatory authority to proceed with the Phase 1 clinical trial for GvHD disease.
To learn more about Cynata’s novel Cymerus™ technology and near-term market potential, visit www.Cynata.com.
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To learn more about MSCs, view the global strategic report “Mesenchymal Stem Cells – Advances & Applications.”