Benzinga | Jan 4, 2021 06:31AM EST

Generation Bio Announces Two Non-Viral Gene Therapy Milestone Achievements: Target Levels of Factor VIII Expression in Hemophilia A Mice and Translation of Expression from Mice to Non-Human Primates

Data confirm delivery of closed-ended DNA to the liver via novel, cell-targeted lipid nanoparticles

Well tolerated at all dose levels in mice and non-human primates

Company on track to select development candidate for hemophilia A and begin IND-enabling studies this year, submit IND in 2022

Webcast and conference call to be held today at 8:00 a.m. EST

CAMBRIDGE, Mass., Jan. 04, 2021 (GLOBE NEWSWIRE) -- Generation Bio Co. (NASDAQ:GBIO), an innovative genetic medicines company creating a new class of non-viral gene therapy, announced data today from a study achieving tolerability and targeted factor VIII expression levels in hemophilia A mice with a single dose of closed-ended DNA (ceDNA) delivered via the company's novel, cell-targeted lipid nanoparticle (ctLNP) system. In this study, conducted with a ceDNA development construct, a dose response was observed across three cohorts, with the highest dose of 2.0 mg/kg yielding a mean human factor VIII expression of 23% of normal.

The company also announced data from studies conducted with a ceDNA research construct delivered via ctLNP demonstrating approximately 2:1 species translation from mice to non-human primates (NHPs). All doses in mice and NHPs were well-tolerated up to the highest dose of 2.0 mg/kg. These data confirm delivery of ceDNA to the liver via ctLNPs in higher species.

"Non-viral gene therapy has been an elusive goal for scientists for more than 40 years. Today's data are a significant step toward reaching that objective for the first time," said Matthew Stanton, Ph.D., chief scientific officer of Generation Bio. "Lipid nanoparticles have demonstrated remarkably predictable species translation from NHPs to patients across modalities such as RNAi and mRNA. We believe the high levels of factor VIII expression in mice using our ceDNA development construct and the demonstrated translation of expression from mice to NHP for our ctLNP delivery system are important proof points for our platform."

Generation Bio has previously demonstrated in immunocompetent mice that its ceDNA constructs with human factor IX achieved durable expression for months and that expression increased proportionately with redosing.

"These data are significant milestones as we create a new class of genetic medicine to overcome the limitations of viral gene therapy," said Geoff McDonough, M.D., president and chief executive officer of Generation Bio. "We have now demonstrated in preclinical studies the key features of our platform, including durability, titration and redosing and, importantly, translation of our novel, liver-directed ctLNPs. With predictable species translation and potent murine expression levels in line with our target product profile, we are on track to initiate IND-enabling studies for our hemophilia A program this year."

In parallel with hemophilia A, Generation Bio plans to advance programs in phenylketonuria (PKU) as well as in additional rare and prevalent diseases that are addressable using the company's liver-specific ctLNP delivery system and established, capsid-free manufacturing.