CG01 is CombiGene's gene therapy for the treatment of drug-resistant focal epilepsy.
The newly released GMP plasmids were produced by Cobra in the early part of this year. It said the material had to be quality assured through a variety of analyses, a process that is now finalized.
The plasmid production itself was very successful and generated so much material that, according to current estimates, it will be enough for more productions of CG01 than originally planned, according to the parties.
“The release of the plasmids produced by Cobra means that we will be able to start GMP production of CG01 later this year. In doing so, we are taking another important step towards the first in human study that we plan to start in 2022,” said Jan Nilsson, CEO of CombiGene.
Milestone
When asked why this production of plasmids is considered a landmark moment, and whether it was thought that the process was going to be more challenging than it turned out to be, Tony Hitchcock, technical director, Cobra, told BioPharma-Reporter:
“This is a critical milestone for CombiGene as it provides the starting materials for the production of their clinical CGO1 therapy for the treatment of epilepsy. Cobra Biologics has been producing plasmid DNA for its customers for over 20 years, however the production of key plasmids for the production of AAV vectors such as CG01 can produce some challenges due to sequence elements and the size of the plasmids. There was a requirement to optimize processes to overcome these issues to generate plasmids of the required quality, and quantity, to support CombiGene’s planned manufacturing campaigns.”
Unlike many gene therapies, which are developed for the treatment of rare diseases, CG01 caters to a large population of patients, said CombiGene.
Epilepsy is a major global problem. Every year, approximately 47,000 drug-resistant patients with focal epilepsy are estimated to be added in the US, EU4, UK, Japan and China. CombiGene believes that it is realistic that 10-20% of these patients could be treated with the drug candidate, CG01.
Assuming, for example, that the therapy cost per patient is somewhere between $134,000 and $200,000, it provides sales between $750-$1,500 million annually, it added.
Viral vectors
Cobra anticipates that there will be a long-term requirement to supply plasmid DNA to support the production of viral vectors, including AAV and Lenti viral vectors, for advanced therapy products, he added.
“Whilst some manufacturers may adopt the use of stable cell lines for the production of certain vectors such as Lenti, it is likely that transfection approaches will be retained for some vectors such as AAV, where the generation of stable cell lines is more challenging,” remarked Hitchcock.
What is next in terms of goals, both short term and long term, for Cobra Biologics?
“Like many plasmid suppliers, Cobra is working to expand is plasmid production capabilities, both in terms of throughput and the numbers of High Quality (HQ) and GMP grade plasmid batches it can produce, whilst also scaling up its production processes to meet the needs for products entering later phase and commercial supply.
“Furthermore, with Cobra Biologics becoming a Charles River company, alongside Cognate BioServices, and Vigene BioSciences, the goal is to continue to grow and develop our offering in the cell and gene therapy space, offering supply chain simplification and an end-to-end service offering for development, testing, and manufacturing, providing clients with an integrated solution from basic research and discovery through GMP production.”