Cymerus Platform Technology

Limitations in conventional methods of MSC production include the dependence upon donors, the variability between donors, the relative scarcity of MSCs in adult tissue, and the low proliferative capacity of adult stem cells compared to pluripotent stem cells.

Cynata believes that the Cymerus™ technology may address all of these issues, and the Company’s development of the Cymerus™ technology are aimed at achieving that.

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 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). It has also been shown that MCAs have potential to differentiate into pericytes and smooth muscle cells.

The commercial potential of MCAs was identified by Cynata, following a process which sought to identify the ideal “next generation” stem cell technology. Cynata seeks to address the limitations inherent in current adult stem cell technologies, specifically:

  • donor dependence and variability;
  • contamination with non-target cells;
  • and limited scalability.

Cynata’s Cymerus™ technology, which incorporates MCA-derived MSCs, has the potential to address these issues, and in addition, has the possibility of being able to derive multiple cell therapeutic platforms.

The capacity for these MCA cells to develop into multiple cell types means that they are ideally suited for the development of therapeutic cell platforms.

Since iPSCs can proliferate indefinitely, and MCAs themselves can expand into extremely large quantities of MSCs, Cynata should be able to manufacture all of the MCAs that it will ever need from a single Master Cell Bank of iPSCs – derived from a single donor.  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 Cynata.

Key Features of the Cymerus™ Technology:

Versatility

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). Cynata believes that it can produce cells much more efficiently than companies using first generation MSC manufacturing technology.

Manufacturing scalability

As cells mature, they become less and less “expandable”. So, MSCs derived from adult tissues have a limited expansion capacity, meaning that manufacturers constantly need to be identifying, qualify 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.

Manufacturing costs and complexity

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.

Clinical predictability

Inevitably, batches of cells produced from different donors will have different properties. Cynata’s expected reduced batch-to-batch variability may increase the predictability of clinical outcomes.

This will need to be confirmed in clinical trials.

Safety

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 adult donors.

Cynata’s cells are manufactured from iPSCs, rather than being purified from primary tissue sources such as bone marrow and adipose tissue. Consequently, it is expected that the level of purity of Cynata’s cell products will be extremely high, which may translate into a lower likelihood of stimulating an immune response in the recipient.

This will need to be confirmed in clinical trials.