Innovations in closed-ended DNA (ceDNA) and cell-targeted lipid nanoparticle (ctLNP) production processes generated peak mean of 205% normal human factor VIII expression in mice


  • Innovations in closed-ended DNA (ceDNA) and cell-targeted lipid nanoparticle (ctLNP) production processes generated peak mean of 205% normal human factor VIII expression in mice


  • Non-human primates (NHPs) demonstrated up to 2% normal human factor VIII expression, and higher-than-expected variability within and between studies


  • Company is using insights from preclinical studies to advance additional novel proprietary ctLNPs to improve species translation to meet target profile for a development candidate

CAMBRIDGE, MASS., Dec. 14, 2021 (GLOBE NEWSWIRE) — Generation Bio Co. (NASDAQ:GBIO), a biotechnology company innovating genetic medicines for people living with rare and prevalent diseases, today provided an update on factor VIII expression from a series of mouse and companion non-human primate (NHP) studies in hemophilia A, as well as an update on the development of its non-viral genetic medicine platform. Generation Bio's proprietary genetic medicine technology comprises a closed-ended DNA (ceDNA) delivered via a novel, cell-targeted lipid nanoparticle (ctLNP). In July 2021 the company announced that it would incorporate its novel, proprietary rapid enzymatic synthesis (RES) for ceDNA production into its pipeline programs. RES has improved ceDNA purity to 99%.

In mouse studies, RES-derived ceDNA delivered by ctLNP generated peak mean human factor VIII expression of 205% of normal at 2.0 mg/kg. This is compared to peak mean human factor VIII expression of 23% of normal at 2.0 mg/kg using ceDNA produced by the company's prior Sf9-based manufacturing process. In addition to the increased potency attributed to the RES-produced ceDNA and to ctLNP production process innovations, the company observed lower variability of factor VIII expression and of tolerability within and between mouse studies. Findings from companion studies in NHPs demonstrated human factor VIII expression of up to 2% of normal at 2.0 mg/kg, with higher-than-expected variability in both factor VIII expression and tolerability within and across studies. Additional optimization is needed to translate the improvement in potency and reduction in variability observed in mice to NHP, and to support nomination of a development candidate for the company's hemophilia A program.

"Over the course of the year, we have made significant progress in the development of our platform," said Matthew Stanton, Ph.D., chief scientific officer. "We have demonstrated that RES produces highly pure ceDNA across a variety of manufacturing scales and we have developed new production processes that have similarly enabled substantial improvements in the control and consistency of our ctLNPs. We are working to translate the improved potency and decreased variability that we have observed in mice to NHPs. By applying novel analytical methods to these preclinical studies in both species, we have gained important insights that we believe will allow us to advance additional novel proprietary ctLNPs to meet our target profile for a hemophilia A development candidate."

"At Generation Bio, we are innovating genetic medicines intended to exceed the limits of conventional gene therapies and to impact the lives of millions of people," added Geoff McDonough, M.D., chief executive officer. "Since our founding, we have been leading the frontier of systemic DNA delivery to build an entirely new non-viral genetic medicine platform to realize this vision. While we still have work to do, we believe the creativity and rigor of our science will unlock the full potential of genetic medicine. We have a terrific team and strong balance sheet to pursue this work and look forward to further progress in the next year."

The company expects to announce updates from its pipeline programs in 2022 and to provide timing for its first IND submission in the future.