Cline: Newsletter September 2022 - A strong start to the fall
As communicated last week, Cline has finished up the first series of testing of StemCART with human cartilage tissue and showed encouraging results across the three primary goals of the project. More than 20 experiments have been carried out since February 2022.
The project had three primary sub-goals:
1. Show that the method differentiates induced pluripotent stem cells (iPSC) into functional cartilage cells (chondrocytes)
2. Test the cells' regenerative ability in damaged cartilage tissue, and
3. Evaluate the ability of the matrix to support the cells in place.
Goal 1 - Characterize the differentiation of IPSCs to cartilage cells
The first key step of the StemCART method is to transform iPS cells into chondrocytes. Cline quantifiably showed that specific chondrocyte markers increased and pluripotency markers decreases, measured with a method called qPCR. This verifies that the cells have differentiated in the correct targeted lineage toward chondrocytes and showed a similar phenotype to the native chondrocytes. Additionally, Cline confirmed our method provides an excellent environment during activation on Cline's unique surface as cell viability was shown be high.
These results are important as they contribute to the safety and quality of the cells produced. Additionally, Cline now has robust QC methods to measure these factors consistently in future studies as well as in a production setting.
During a recent interview with Analyst Group (https://www.analystgroup.se/kommentarer/kommentar-pa-cline-scientific-positiva-ex-vivo-tester-inom-stemcart/) VP of R&D, Dr Hanne Evenbratt elaborated on the importance of cell viability for safety and functionality -
"When a cell therapy is approved by pharmaceutical authorities, they look at various aspects of safety, for example, the presence of dead cells that can lead to uncontrolled cell death in the surrounding tissue, and effectiveness, for example, how durable the newly formed tissue is. The viability of the cells is about how healthy the cells are, which is crucial for the cells' potential to develop and function as they should, as opposed to die or initiate a rejection reaction. When we see that the cells are doing well and are vital after they are grown on our surfaces, we know that we can safely proceed to the next step in the production process with a large cell count of living and healthy cells."
Read the full interview/commentary (https://www.analystgroup.se/kommentarer/kommentar-pa-cline-scientific-positiva-ex-vivo-tester-inom-stemcart/), their recent analysis of the Cline share (https://mfn.se/a/analyst-group/aktieanalys-pa-cline-scientific-starkt-position-genom-starka-patent) and video interview with CEO Patrik Sundh (https://www.youtube.com/watch?v=SpndrojlvnE) on their website. (https://www.analystgroup.se/bolag/cline-scientific/)
Goal 2 - Testing cells' ability to repair tissue
The second aim was to study the cells' regenerative ability in induced cartilage injuries. This testing is done by first sourcing patient cartilage tissue from our partner hospital, creating an artificial injury to each sample, implanting the cells together with the matrix, and observing what occurs over 2-4 weeks.
The team observed that the implanted cells interact with the cartilage tissue and cells grow attached to the injury site, which is exactly the intended purpose of StemCART. This is encouraging as this is a central part of how StemCART will repair injured cartilage in patients.
When asked if Cline has quantified this repair, VP of R&D Dr Hanne Evenbratt explains -
"An interaction between our cells and the surrounding tissue shows that regeneration has begun. The extent to which this happens depends, for example, on how many cells are in contact with the tissue, which means that the size of the damage also affects how long regeneration h takes. In this first series of tests, the goal was to demonstrate an interaction between StemCART cells and cartilage, which was clearly achieved. In the future, we aim to optimize the number of cells needed for a certain type of injury and study healing time, durability, and similar parameters. Once this is done, we can start quantifying how StemCART works in different situations."
Goal 3 - Evaluation of support matrix
The final aim was the evaluation of the matrix material which Cline uses to support the cells in place during implantation which is an important part of the product and its success in patients. The matrix has been developed with material and pharmaceutical formulation expertise from Chalmers University of Technology as well as input from our orthopedic surgeon advisors.
Earlier in the project, the matrix demonstrated functionality and we have elaborated in more detail in the April 2022 Newsletter.
VP of R&D Dr Hanne Evenbratt reflects on the lessons learnt over this project -
"A large part of the lessons learned in this first series of trials has been about manageability and technical feasibility when it comes to implanting the cells in an injury model together with the matrix we developed and studying the results. An important part is to determine what an optimal test set-up should look like to be as comparable to reality as possible. We have learned a lot which will be crucial for us to be able to show and document for regulatory purposes how our product works and, in the extension, can be used on patients."
Now that Cline has shown these encouraging results, the team will continue with further optimization and testing of the StemCART product. Several exciting follow-ons steps from these results are planned. This includes:
1. Further investigation into the final process stage where the cells condense together, produce an extracellular matrix, and form cartilage-like material. This stage allows the cells to become more similar to native cartilage and have longer-lasting restorative effects as functional cartilage.
2. Work on optimizing tissue repair in "real-world" conditions. Examples of this are increasing the number of cells implanted and adapting methods to produce larger batches of the cells to be made. This step will also be important when transitioning the project into a manufacturing development stage.
StemCART patent update
The patent application covering the StemCART method has recently entered the national phase. This means that Cline has now designated the countries and territories to seek protection that Cline sees as an important market. National patent applications have now been submitted to the USA, Japan, South Korea, China and Australia, in addition to the original EU application that is ongoing. Read more about the original patent (https://www.clinescientific.com/news/cline-scientific-seeks-to-patent-new-method-for-stem-cell-therapy) and the national phase (https://www.clinescientific.com/news/cline-submits-patent-application-for-stemcart-product-in-usa-japan-south-korea-and-australia).
We look forward to continuing to share further updates and more Cline's journey in future newsletters!
The Cline Team
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