Generation Bio to Present Preclinical Data on iqDNA and ctLNP at ASGCT 27th Annual Meeting

Generation Bio Co., a biotechnology company listed on NASDAQ under the ticker GBIO, is spearheading advancements in genetic medicine. The company recently showcased its innovative platforms involving immune-quiet DNA (iqDNA) and cell-targeted lipid nanoparticles (ctLNP) at the American Society of Gene and Cell Therapy (ASGCT) 27th Annual Meeting. They presented five posters detailing their progress and will further elaborate on these technologies in an upcoming oral presentation.

Dr. Matt Stanton, the Chief Scientific Officer of Generation Bio, emphasized the potential of their novel platforms to address fundamental challenges in genetic medicine. According to Stanton, the iqDNA cargo and targeted LNP delivery systems are pivotal for unlocking the potential of non-viral genetic treatments, particularly for conditions involving T cells, hematopoietic stem cells, and hepatocytes.

The iqDNA, as described in the presentations, consists of a modified and partially single-stranded DNA structure, which helps it evade the body's innate immune responses while remaining transcriptionally active within cells. Mouse studies revealed that iqDNA manages to bypass key innate immune pathways, such as the cGAS-STING pathway, known for its lower binding affinity for single-stranded DNA compared to double-stranded DNA. This non-immunogenic nature of iqDNA is seen as a breakthrough for developing DNA-based genetic therapies with a broad therapeutic index, overcoming a significant hurdle in the field.

Generation Bio's iqDNA is produced using a proprietary rapid enzymatic synthesis (RES) process. This cell-free method allows for precise chemical and structural modifications, enhancing the DNA’s functionality. Unlike traditional biologic methods, which are complex and time-consuming, RES can produce 99% pure material within a week. This approach not only streamlines production but also scales efficiently to meet clinical and commercial needs.

In their continuous efforts to refine the iqDNA platform, Generation Bio has optimized various structural and chemical elements through RES. New data presented at ASGCT showed that the second generation of iqDNA achieved higher luciferase expression compared to the first generation. The company is also experimenting with formulations of this second-generation iqDNA encoding Factor VIII, indicating ongoing improvements and potential applications.

The ctLNP platform, designed to deliver therapeutic transgenes with high specificity, targets a wide range of cell types and tissues. The presented data at ASGCT highlighted the foundational work on the "stealth" lipid nanoparticle, developed by modifying the ionizable lipid components. This selective targeting is enhanced by optimizing ligand selection and linker chemistry. The company plans to discuss further details regarding the in vivo delivery of therapeutic transgenes to T cells via ctLNP in their upcoming oral presentation.

Generation Bio aims to extend the reach of genetic medicine by advancing these platforms, with a focus on creating durable and redosable treatments for various diseases. Their approach leverages non-viral genetic medicines to potentially transform the treatment landscape for patients with rare and common diseases globally.