Exothera SA has entered a collaboration with LogicBio Therapeutics and Polyplus-transfection SA for the development of a highly scalable AAV manufacturing platform with a capacity from 200 L to 2,000 L.

Adeno-associated viruses (AAV) are non-enveloped, non-pathogenic viruses largely used as drug delivery vectors for biotherapeutics, like gene therapies and vaccines. Although the application of AAV is spreading rapidly, the industry is struggling to find cost-effective manufacturing strategies to reach clinical and commercial scales.

The collaboration among Exothera, LogicBio and Polyplus aims to focus on the scale-up of a transient transfection-based AAV serotype 8 (AAV8) manufactured in suspension cell culture. The consortium selected the Allegro stirred tank Single-Use Bioreactor (from Pall) as a suspension culture device due to its scalability and single-use features. The project aims to assess reproducibility and comparability between the different scales of suspension bioreactors, up to 2,000 L bioreactor scale.

Exothera will provide state-of-the-art production space, process development expertise and access to the latest enabling technologies. LogicBio will support the initiative with its mAAVRx plasmid technology and its AAV expertise. Polyplus will provide transfection reagent expertise with FectoVIR-AAV for a smooth scaled-up GMP-eligible process development.  

“Exothera’s team is proud to work with the experienced teams at biotech companies like LogicBio and Polyplus,” said Hanna Lesch, chief technology officer, Exothera. “The success of AAV-based therapeutics requires a change in the manufacturing paradigm and through this collaboration, we aim to enable a new approach to consistently scale AAV manufacturing.”

Matthias Hebben, global vice president, technology development, LogicBio, said, “We are excited to collaborate with Exothera, an emerging leader in the CDMO industry and with Polyplus, a long-time transfection partner, for implementing an AAV manufacturing process at 200L scale and above. We believe our proprietary mAAVRx plasmid technology could dramatically help to improve manufacturing yields and consequently reduce AAV manufacturing costs. We are hopeful that the work done under this collaboration will be an important step forward in making gene therapy products accessible for a greater number of patients.”

Roel Gordijn, chief commercial officer, Polyplus, said, “We are delighted to scale up AAV Viral vector Manufacturing processes to larger bioreactor volumes with innovators in the industry like Exothera and LogicBio. At Polyplus we aim to improve gene-therapy viral vector manufacturing economics by increasing titers in the upstream processes using novel transfection reagents like FectoVIR-AAV. The collaboration will use a combination of state-of-the-art manufacturing technologies, innovative plasmid technologies and scalable transfection reagents which will make gene-therapy viral vector therapies affordable.”

Exothera specializes in the industrialization of vaccine and gene therapy processes. It has recently performed successful viral vector manufacturing scale-up studies in adherent and suspension cell systems helping its clients to reach the clinical trial scale. Additionally, the team is operating and continuously improving its own GMP manufacturing platform, exoREADY, for viral vector-based gene therapies and vaccine production.