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What is the Cymerus™ technology and how could it potentially assist in the battle against Coronavirus cases on a global basis? Cymerus™ is a stem cell manufacturing platform being developed by Cynata Therapeutics Limited (ASX: CYP), an Australian regenerative medicine company.
The proprietary technology utilizes induced pluripotent stem cells (iPSCs) originating from an adult donor as the starting material for generating mesenchymoangioblasts (MCAs). It then differentiates these cells into mesenchymal stem cells (MSCs).
In short, its Cymerus™ platform is a scalable manufacturing solution to produce iPSC-derived MSCs—a cell type which a produced favorable responses in seven COVID-19 patients in a recent clinical trial in China.
Specifically, the Chinese study evaluated the clinical outcomes of seven patients treated with allogenic MSC therapy at Beijing You’an Hospital over a two week period. The researchers noted that MSCs substantially improved the “functional outcomes” of the patients without observed adverse effects.
Following this news and the growing recognition that MSCs may represent an intriguing tool in the battle against Coronavirus, Cynata is engaging in explorative talks with international pharma companies and other collaborators for the use its Cymerus™ platform as a way to manufacture MSCs at scale.
In cases of COVID-19 that produce serious complications, such as acute respiratory distress syndrome, sepsis or cytokine release syndrome, Cynata’s Cymerus™ derived MSCs may be positioned to fill the void. This is because the company’s iPSC-derived MSCs have demonstrated improvements for these indications in preclinical studies.
Of course, numerous other developers are also positioning their stem cell products for use in the war against Coronavirus. As examples, Mesoblast’s Remestemcel-L has proved itself to be effective in treating advanced respiratory distress. Athersys has reported positive outcomes in other studies using MSCs in treating respiratory disease. Pluristem Therapeutics is exploring its PLX cell product candidate for treating respiratory and inflammatory complications caused by Coronavirus infection.
Exploring MSCs as a Tool Against Coronavirus
Currently, there the 29 stem cell clinical trials reported both by WHO International Clinical Trial Registry Platform and ClinicalTrials.gov, 23 of which are active and 19 of which use MSCs.
As mentioned above, the first reported study using MSCs was the collaborative project led by researchers from Shanghai University and Peking Union Medical College (PUMC) and Chinese Academy of Medical Sciences (CAMS) investigating the potential of using mesenchymal stem cells (MSCs) to reduce the severity of COVID-19.
With 7 out of 7 patients responding favorably to MSC infusions within this study, researchers are encouraged by the findings. This research was published in the peer-reviewed journal Aging and Disease.
Cynata’s Cymerus™ Technology
Although MSCs are being explored in more than 1,000 clinical trials worldwide, robust technologies for scaling and standardizing the manufacture of MSCs are scarce. Because Cynata is using iPSCs as starting material for manufacturing therapeutic MSCs, it has the potential to solve a bottleneck in therapeutic use of MSCs.
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. This makes the Cymerus™ technology is a needed solution to traditional stem cell manufacturing challenges.
The importance of the Cymerus™ technology is that it overcomes major roadblocks that have traditionally limited 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.
Who Invested the the Cymerus™ Technology?
As background, one of the key inventors of Cynata’s Cymerus™ technology is Igor Slukvin, M.D., Ph.D., a world-renowned researcher 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 works at the University of Wisconsin-Madison, a global leader in stem cell research. 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).
Unsurprisingly, the cost-savings advantages, consistent cellular product, and unlimited production capacity of the Cymerus technology position Cynata as an attractive manufacturing partner for biopharmaceutical companies pursuing MSC clinical trials related to Coronavirus.
This is because a consistent cellular product is essential to establishing consistent clinical findings. It is also critical to scaling up the manufacturing process.
With more than 318,000 confirmed cases of Coronavirus worldwide (and an exponential growth rate), any viable therapy against Coronavirus needs to be prepared to treat an unprecedented number of patients.
What are the Key Advantages of the Cymerus™ Technology?
In my opinion, there are five advantages of Cynata’s proprietary Cymerus™ MSC manufacturing platform that make it novel. These advantages are:
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, the Cymerus™ technology gets around the loss of potency with the unlimited iPS 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, 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)
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.
Potency is a final advantage of Cymerus™ produced MSCs. This was demonstrated in Cynata’s Phase 1 trial in GvHD wherein patients showed an excellent clinical response following two doses of its CYP-001 product. It requires 8-12 doses of a bone marrow derived MSC product to achieve a similar outcome (see TEMCELL® information).
Future of MSCs in the Battle Against Coronavirus
Another company utilizing iPSC-derived MSCs in the battle against COVID-19 emerged on April 1, 2020. On this date, Citius Pharmaceuticals signed an exclusive six-month option agreement to in-license a stem-cell therapy for acute respiratory distress syndrome (ARDS) from a subsidiary of Novellus, Inc.
Novellus’s patented process is slightly different than Cynata’s, in that it uses non-immunogenic synthetic mRNA molecules to create iPSCs that are turned into MSCs. However, the end outcome is similar, in that its iPSC-derived MSCs have the potential to support a larger supply, faster scale-up, and a more consistent cellular product than traditional primary adult, donor-derived MSCs.
To learn more, view the market report, “Coronavirus (COVID-19)—Global Market Conditions, Vaccines, Trials & Potential Treatments.”
What are your thoughts on using iPSC-derived MSCs in the battle against Coronavirus? Share them in the comments below.
*Feature Image Source: Center for Disease Control (CDC).