Benitec Scale-Up Success with Insect-Based Tech Ahead of IND Filing

Benitec Biopharma says it has successfully scaled-up its investigational oculopharyngeal muscular dystrophy (OPMD) gene therapy using a baculovirus-based expression system.

Benitec Biopharma’s lead candidate BB-301 is a gene therapy for the treatment of oculopharyngeal muscular dystrophy (OPMD), a disease caused by a mutation of the poly(A)-binding protein nuclear 1 (PABPN1) gene.

The candidate received orphan drug status from the US Food and Drug Administration (FDA) in January this year, and the firm hopes to bring it into the clinic by the end of the year.

And during a Q3 financial briefing last week, the firm said it is one step closer having successfully scaled-up production.

“We’ve completed manufacturing of high titer and highly active supplies of BB-301 at a 50L scale to support the ongoing toxicology studies,” said CEO Greg West. “And we are completing a face-to-face meeting with our world-class group of leaders in swallowing and the treatment of OPMD to finalize the plans for the first clinical study with BB-301.”

‘Exceptionally Scalable Quantities’

The ability to produce the drug in sufficient quantities is key to supporting clinical trials, CSO David Suhy added

“For BB-301, we produce the material in a baculovirus-based system which is a suspension manufacturing system that allows for the manufacturer of viral-based products in exceptionally scalable quantities.”

Traditionally, gene therapy products using adeno-associated viruses such as AAV-9 have not been readily produced using baculovirus, expressed in insect cells. However, he continued, Benitec modified the AAV-9 capsid to produce highly active materials that have high titers.


Read More: ‘Insect Cell Culture and the Baculovirus Expression Vector System: Challenges of Scale-Up and Development’


Three separate lots of BB-301 at the 50 L scale have so far been produced in excess of 1e14 vector genomes per liter, which “is excellent for this process,” Suhy said.

“The recovery yields in the final product range from 30% to 40% which is also quite outstanding for these types of processes.”

Benitec is using an undisclosed contract manufacturing organization (CMO) to make clinical-grade material, and is looking to move to the 250 L scale.

“If we assume scalability of this process is maintained, we’ll anticipate being able to produce upwards of 1e16 vector genome protocols within the 250 liters, which is far enough to support all of the patients in the Phase I/II study, as well as have a large excess of vector to spare.”

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