Generation Bio Announces Breakthrough in its Non-Viral Genetic Medicine Platform with Novel “Immune-Quiet” DNA - Seite 2

Systemic dosing in mouse and NHP studies demonstrates that iqDNA delivered via LNP evades detection by the key innate immune pathways that are reactive to DNA. Figure 1 below shows a comparison of IL-6 levels, representative of all cytokines measured, in a cohort of NHPs that received an infusion of ceDNA, iqDNA, or mRNA, each delivered using the same LNP at 1 mg/kg and containing luciferase as a reporter gene.

Figure 1: IV infusion 1 mg/kg

Importantly, companion mouse studies demonstrate that iqDNA conserves the key features of ceDNA that afford therapeutic benefit, including expression.

Due to the superior tolerability profile of iqDNA, Generation Bio is discontinuing development of prior ceDNA constructs and is advancing iqDNA as the cargo for its lead program in hemophilia A as well as for all other programs. Scaling of iqDNA factor VIII for NHP testing is underway, leveraging existing RES systems and processes.

“The identification of iqDNA is the culmination of six years of work at Generation Bio to address the central challenge of immune activation for DNA-based genetic medicines,” said Geoff McDonough, M.D., chief executive officer of Generation Bio. “We expect that iqDNA will significantly enhance the tolerability profile of our lead program in hemophilia A allowing us to leverage our broad portfolio of LNPs to advance this and our other programs.”

Dr. McDonough continued: “In parallel with cargo optimization, we have made substantial investments in the translation of our ctLNP delivery system from mice to NHPs, initially motivated by avoiding the innate immune stimulation caused by off-target delivery of ceDNA to immune cells. This led to the development of our stealth LNP plus targeting technology, which unlocks the potential for reaching non-liver cell types and tissues. Our collaboration with Moderna aims to create highly specific in vivo delivery to T cells and other immune cell types with both iqDNA and mRNA cargos. We are excited to share updates on our iqDNA and ctLNP platforms as we make progress across our liver and non-liver programs.”

Cash runway extended into 2026

Generation Bio believes it has sufficient cash to extend the funding of its operations into 2026 based on income from the Moderna collaboration, including the initial upfront payment, as well as interest income and expense control. Concurrent with extending its cash runway, the company is increasing investment in its iqDNA and ctLNP platforms.