The trademark Cymerus refers to the patented process of generating cell-based products from intermediate cells, known as mesenchymoangioblasts (MCAs), which in turn are derived from induced pluripotent stem cells (iPSCs). This technology was originally developed at the University of Wisconsin-Madison (UWM), a world-renowned leader in stem cell research.
The means of producing MCAs from pluripotent precursors, and the defining pattern of MCA cell surface markers, are the subjects of US patent 7,615,374, and a number of other patent applications in process around the world, licensed to or owned by Cynata.
At present, Cynata is focussed on the production of mesenchymal stem cell (MSC)-based products using the Cymerus technology.
First generation methods of MSC production rely on isolation of MSCs from tissue donations, for example bone marrow or fat. This approach is associated with a number of important limitations, including:
Conversely, since iPSCs can proliferate indefinitely, and MCAs themselves can expand into extremely large quantities of MSCs, Cynata expects to be able to manufacture all of the cells that it will ever need from a single Master Cell Bank of iPSCs – derived from a single donor.
Consequently, the 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 without requiring multiple donors or excessive culture expansion of the derived MSCs. This opens up a wide range of therapeutic and manufacturing possibilities for the Company.
The Cymerus technology has several characteristics which makes it ideal for the commercial development of cell-based therapeutics. Most critically, the Cymerus manufacturing process ensures that cells for therapeutic use can be produced in virtually limitless quantities from a single donor. This means that Cynata will not have to constantly seek out fresh donors to meet its manufacturing demands. This has the potential to create a new standard in the emergent arena of regenerative medicine and stem cell therapeutics and provides Cynata with both a unique differentiator and an important competitive position.
The Cymerus technology utilises induced pluripotent stem cells (iPSC) and a recently identified precursor cell, known as a mesenchymoangioblast (MCA), to achieve economic manufacture of cell therapy products, including mesenchymal stem cells (MSCs), at commercial scale.
MCAs were first identified by Professor Igor Slukvin (one of Cynata’s founders) and his team, working at the University of Wisconsin-Madison. MCAs are an extremely important class of early clonal mesoendodermal precursor cells, meaning that they are the common precursor for both MSCs and endothelial cells (an important component of blood vessels). The capacity for these MCA cells to develop into multiple cell types makes them the ideal starting material for the development of stem cell therapies.
The Cymerus process utilises iPSCs as the starting material, due to their ability to proliferate indefinitely and create an essentially infinite amount of MCAs that can then expand into extremely large quantities of MSCs. Due to these qualities, Cynata can manufacture all of the MSCs that it will ever need from a single Master Cell Bank of iPSCs – derived from a single donor, in just one blood donation.
MCAs can be used to make a range of cell types, each of which has different properties and may be suited to the treatment of different diseases. In the first instance, Cynata is using MCAs as the basis for producing commercially relevant quantities of very pure and well characterised mesenchymal stem cells (MSCs) that are being used in preclinical and clinical trials.
As cells mature, they become less and less “expandable”. Therefore, MSCs derived from primary tissue sources have a limited expansion capacity, meaning that manufacturers constantly need to be identifying and screening new cell donors. This is an expensive and time-consuming process. Cynata manufactures its MCAs – and in turn MSCs – using induced pluripotent cells (iPSCs) as a starting material. Pluripotent cells are immortal – effectively, meaning that they have infinite expansion capacity. Consequently, Cynata expects to be able to source all of the cells it will ever need from a single donor. Furthermore, it means that Cynata does not need to excessively expand MSCs in culture in order to produce large numbers of doses. This is important, as excessive culture expansion has been shown to result in changes in the functionality of MSCs.
Because Cynata is developing its products from a pluripotent cell source, it is able to eliminate the need to repeatedly source, screen and qualify new donors. This will substantially reduce the costs and complexity of manufacturing. In addition, Cynata expects to have far fewer batch-to-batch variability issues, since all of its cellular material will be sourced from a single donor.
It is well-established in the scientific literature that batches of MSCs produced from different donors have substantially different properties, which is likely to result in unpredictable and inconsistent clinical efficacy. Conversely, the Cymerus process achieves batch-to-batch consistency, which is expected to increase the predictability of clinical outcomes.
MSCs are immunoprivileged, meaning that they can generally be infused or injected into recipients without provoking a dramatic immune response. However, antibodies to injected cells have been detected in some clinical trials. One reason for this may be the presence of non-immunoprivileged contaminating cells, left over from the process of extracting and purifying cells from donor tissue, which contains a wide variety of different cell types. Cynata’s cells are manufactured from iPSCs, rather than being purified from primary tissue sources such as bone marrow and adipose tissue. Consequently, the level of purity of Cynata’s cell products is high, which translates into a lower likelihood of stimulating an immune response in the recipient.