“The first patient treated with a CAR-T based product manufactured using the Cocoon platform represents a significant milestone on our way to producing cell and gene therapies faster and on a much larger scale,” Eytan Abraham, head of personalized medicine, Lonza, told BioPharma-Reporter.
The Sheba collaboration aims to demonstrate the Cocoon platform can successfully manufacture cell therapies such as CAR-T, in a clinical setting, and at the point-of-care, he said.
Lonza’s Cocoon platform is a closed automated cell therapy manufacturing platform enabling decentralized process development. A transportable cassette that internalizes all of the media, agents, and consumables used in the process is attached inside and the Cocoon closes and begins processing.
Installed at the Sheba Medical Center in Tel HaShomer, Israel, since early last year, the automated system is now being used in a clinical trial of chimeric antigen receptor (CAR) T-cell therapies against B-cell malignancies. The first patient treated with Sheba’s CAR-T from the Cocoon has diffuse large B cell lymphoma (DLBCL).
Sheba and Lonza said the plan is now to treat additional patients under the same CD19 CAR-T cell immunotherapy protocol using the Cocoon platform.
In early 2019, the contract development and manufacturing organization (CDMO) established a clinical collaboration with Sheba Medical Center, the largest hospital in the Middle East and rated as one of the top ten hospitals in the world.
The center had an ongoing clinical trial utilizing cell therapies, treating patients “quite successfully, with very good clinical data,” according to Lonza and it was looking for a way to increase the ability to treat more patients.
The scientists at Sheba had a deficiency in the number of ‘hands’ available. So Lonza believed the Cocoon could assist on that, as, by closing and automating the process, fewer ‘hands’ and considerably less space is required.
Lonza said it worked closely with Sheba to complete process development, tech transfer, training and a full clinical comparability study requiring regulatory approval before the first patient could be treated.
The ultimate goal of cell and gene therapies is to treat large patient populations, and the only way to truly scale cell therapy manufacturing is automation, commented Abraham.
“Patients that can be treated with CAR-T cell therapies often have to wait for months to get treated. This is often caused by current manufacturing practices, as manual processes need highly skilled manpower and sufficient manufacturing capacity.”
The Cocoon platform addresses such bottlenecks, he said. “Each cassette produces a product to treat one patient. This process can be streamlined, and up to 10 individual processes can be run simultaneously on only 1 meter squared. In addition, point of care/decentralized manufacturing eliminates the back and forth shipping of cells, thus reducing turnaround and costs.”
Others such as GE Healthcare are also developing more-automated systems to speed up CAR-T manufacturing and to cut costs linked to more hands-on methods. So how does the Cocoon platform stack up against those?
There are several partially automated solutions currently available and various advantages of the Cocoon platform compared with these, said Abraham, including superior efficiency of clean room space usage, and incorporation of most or all unit operations into one automated system.
He also mentioned the flexibility of the single-use cassette in the Cocoon platform that can accommodate various cell therapy processes, as well as the platform’s “enhanced in-process analytics, electronic batch record, the inclusion of 4c incubation for reagents, ease of use and simplified tech-transfer, integration of electroporation into the process, and more.”
The Lonza system, he continued, primarily lowers cost of goods (COGs) through minimizing the required process touch points, and potentially allowing Cocoon placement in lower cleanroom classifications.
“The Cocoon Tree, a multiplexing solution, allows us to utilize clean room space much more efficiently. We are also working with suppliers to help drive down the costs of raw materials. The process is mostly automated, eliminating around 80% of manual steps. In addition, automation and enhanced analytics allow for reduced manufacturing deviations, which may result is manufacturing failures.
“Furthermore, we are working with numerous analytical companies to help make the manufacturing process more efficient. Our goal is to bring production costs down significantly with the Cocoon Platform over the next few years,” said the personalized medicine lead.
Centralized or decentralized manufacturing
The CDMO is already working with multiple partners on extending the use of the Cocoon Platform for clinical manufacturing of additional cell therapies.
"Some of these have been publicly announced including Triumvira Therapeutics, Stanford University School of Medicine, the Fred Hutchinson Cancer Research Center, the Parker Institute for Cancer Immunotherapy and Noga Therapeutics.
“We expect many more additional partnerships and clients to use the Cocoon platform, which will be available to customers for use in a centralized or decentralized manufacturing model. Customers can purchase the system for their own internal use as they see fit or come to Lonza for full CDMO services.”