Breakthrough in mitochondria therapy: CSEM and cellvie automate isolation process for clinical use

cellvie, a pioneer in leveraging the therapeutic potential of mitochondria—the energy-producing structures within cells—is developing a novel treatment for ischemia-reperfusion injury, which could benefit > 3 million patients in Europe and the USA every year. A main bottleneck for clinical translation and particularly scaling, has been the automation of the manufacturing process. In the framework of an Innosuisse project, cellvie and CSEM joined forces to design a new automated solution to streamline and standardize the manufacturing process.

Ischemia-reperfusion injury (IRI) is one of the world’s leading causes of death. It arises when blood supply returns to a tissue after a period of restricted flow and is associated with a wide variety of medical conditions, including heart attacks, strokes, organ transplantation and long surgical procedures. Today, there is no specific cure, with treatments focusing on minimizing damage through rapid intervention and supportive care. cellvie is pioneering Therapeutic Mitochondria Transplantation (TMT) as a novel treatment modality for addressing ischemia-reperfusion injury. The approach involves the delivery of active mitochondria, which were derived and purified from a human cell source, during or after reperfusion, to reinvigorate the cell energy metabolism to save cells, which would otherwise die. cellvie is pursuing kidney transplantation as first indication but has cultivated a pipeline within the context of IRI and established the potential of using mitochondria for the delivery of gene therapies in and ex vivo.

In 2023, cellvie, together with the Swiss technology innovation center CSEM, received an Innosuisse grant of more than CHF 700,000 to advance cellvie's mitochondrial isolation process with the goal of enabling scalable, consistent, and cost-effective manufacturing of its therapy.

Enabling GMP-Grade Mitochondria Isolation

The original mitochondria isolation protocol conceived by cellvie’s co-founder Dr. McCully required several manual steps and open manipulation, which could introduce operator variability and did not lend itself well to scaling, particularly under conditions of Good Manufacturing Practice (GMP). Within the Innosuisse project, the teams were able to revise the process and develop a closed, automated solution for mitochondria isolation in a single workflow. "Establishing a robust and scalable system for mitochondria isolation is essential to ensure bioenergetic functionality and safety and paves the way to bringing revolutionary mitochondrial therapies one step closer to the clinic", said Charlotte Fonta, Senior R&D Engineer at CSEM

"The system was designed with Good Manufacturing Practice in mind and will allow mitochondria-preparations at high volumes and very reasonable costs", added Dr. Martijn Brugman, COO at cellvie.

Next Steps

With the isolation and preparation process redesigned, optimized and tested, the next step will be to transfer it to an external partner for the manufacturing of the clinical and ultimately commercial supply of cellvie’s product. "This will be a major puzzle piece in the clinical translation, and thanks to the Innosuisse project and the teams’ relentless efforts, we have a solid starting point", said Dr. Alexander Schueller, Founder and CEO of cellvie.