Generation Bio Announces Demonstration Of Highly Selective T Cell Transduction In Vivo With CellTargeted LNP Platform
- 70% of circulating T cells and splenocytes are positive for mRNA expression in humanized mice, with less than 8% reaching non-target immune cells.
- The latent properties of the cell-specific liposomal nanoparticle (ctLNP) platform were validated in primates, demonstrating sustained turnover and <0.1% release in the liver and spleen.
- These data provide initial proof of concept for in vivo delivery to T cells and the applicability of the ctLNP platform to extrahepatic tissues and cell types.
- The company will speak at the 30th ESGCT Annual Meeting today , and will host an in-depth research and development webcast on November 1.
CAMBRIDGE, MA, Oct. 26, 2023 (GLOBE NEWSWIRE) -- Generation Bio Co. (Nasdaq: GBIO), a biotechnology company developing genetic medicines for people with rare and advanced diseases, announced that it has achieved two major breakthroughs in its in vivo studies, including a collaboration with Moderna, Inc. First, Generation Bio demonstrated highly selective in vivo T cell targeting using a cell-specific LNP (ctLNP) platform in a humanized mouse model. In addition, the company tested the latent properties of its ctLNP platform in nonhuman primates (NHPs). Generation Bio will present the data today at 16:40 CET at the 30th Annual Congress of the European Society of Gene and Cell Therapy (ESGCT) in Brussels, Belgium. Presentation slides will be available on the Generation Bio website after the presentation.
Generation Bio's ctLNP platform delivers RNA and DNA cargo to hard-to-reach tissues and cell types, avoids off-target clearance by the liver and spleen, and uses conjugated targeting ligands for selective receptor-mediated uptake. The ctLNP platform supports immune cell targeting programs through the Generation Bio and Moderna collaboration, which aims to provide in vivo DNA therapies to select immune cell types, including T cells, using ctLNP.
“The data we have collected for our ctLNP platform demonstrates the unique ability to target tissues and cell types outside the liver, giving us confidence in developing genetic medicines to treat non-liver diseases, representing an exciting new milestone in the field and in this area,” said Matt Stanton. Ph.D., Chief Scientist at Generation Bio.
As part of the company's collaboration with Moderna, Generation Bio demonstrated that its T cell ctLNPs successfully controlled highly selective receptor uptake and mRNA expression in humanized mice during systemic administration, as shown in Figure 1. Additionally, uptake and expression upon T cell delivery into cells, the number of non-target cell types increased in a dose-dependent manner, as shown in Figure 1. Figure 2.
Figure 1: T cell ctLNP mRNA expression in a humanized mouse model.
Figure 2: Dose-response of ctLNP T cells in a humanized mouse model.
In a separate NHP study, the company confirmed the properties of stealth LDL, including a long circulation half-life and very low off-target delivery to the liver and spleen, as shown in Figures 3a and 3b.
Figure 3a: Latent half-life of LNP in NHP and mice.
Figure 3b: Biodistribution of latent LDL in NNP.
“The mRNA expression data demonstrates the ability of ctLNP to target the liver and spleen and reach specific extrahepatic cell types via a targeting ligand,” said Philip Samayava, Ph.D., chief strategy officer, Generation Bio. “In addition, the latent LNP delivery methods underlying our ctLNP platform are very encouraging as we continue to advance our work in cell targeting. We have made significant progress in bioconjugation and optimization of ligands, which we use to develop ctLNPs for new applications.”
In addition to today's presentation at ESGCT, the company will host an in-depth research and development session and an online Q&A session on Wednesday, November 1st. In this presentation, you will learn more about Generation Bio's ctLNP and iqDNA platforms and their RES production. Registration information for the detailed research and development webcast can be found on the event page on the Generation Bio investor website.
About biogeneration
Génération Bio is driving innovation in genomic medicine to provide sustainable, reproducible treatments for people with rare and common diseases. The company's nonviral genomic medicine platform includes a novel immune suppressive DNA construct called iqDNA; Unique cellular liposome or ctLNP delivery system; A large-scale capsid-free manufacturing process that uses cell-free rapid enzymatic synthesis (RES) to produce iqDNA. This approach is designed to provide multi-year duration of action with a single dose, deliver large genetic loads including multiple genes to specific tissues and cell types, and titrate and repeat the dose to adjust or increase expression levels in each patient. RES has the ability to scale Generation Bio's production to hundreds of millions of doses to support its mission of bringing genomic medicine to more people with more diseases around the world.
For more information, visit www.générationbio.com .
Forward-Looking Statements
All statements contained in this press release regarding the Company's future expectations, plans and prospects, including statements regarding the Company's strategic plans and objectives, cash resources, technology platform, clinical research and development plans, and the terms of the research collaboration between Moderna and Generation. Personal biography. Development of new DNA-based therapies, including the ability to target immune cells with different DNA content and the liver for gene replacement, targets to be developed through the collaboration, and potential benefits and results that may be obtained from other preclinical and other data. , which contain the words “believes,” “expects,” “plans,” “expects” and similar expressions constitute forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Actual results may vary materially. Forward-looking statements may differ from those contained in these forward-looking statements due to various important factors, including: the expected benefits from working with Moderna may not be realized within the expected time frame, if at all; Such data may not support further development of treatments offered in collaboration with Moderna due to safety, efficacy or other reasons. uncertainties associated with the identification and development of product candidates, including the conduct of research activities, initiation and completion of preclinical studies and clinical trials, and clinical development of the Company's product candidates; uncertainties regarding the availability and timing of preclinical studies and clinical trial results; uncertainties associated with our new technologies; Will the results of previous preclinical studies predict the results of subsequent preclinical and clinical studies; uncertainties associated with the renewable energy generation process; problems in the production of genetic medicine products; whether the Company's cash resources are sufficient to finance the Company's operating expenses and capital investment requirements for the planned period; The impact of the COVID-19 pandemic on the Company's business and operations; and other risks and uncertainties discussed in the “Risk Factors” section of our most recent annual report on Form 10-K and quarterly report on Form 10-Q filed with the Securities and Exchange Commission and subsequent filings that the Company may file with the Securities and Exchange Commission. Security and Exchange Commission. In addition, the forward-looking statements contained in this press release reflect the Company's views as of the date of this press release. The Company expects that subsequent events and developments will cause the Company to change its view. Although the Company may elect to update these forward-looking statements at some point in the future, the Company disclaims any obligation to do so. These forward-looking statements should not be relied upon as representing the views of the Company as of any date subsequent to the date on which they were made.
Contacts with investors and media
Marin Killaki
Organic generation
mkillackey@generationbio.com
857-371-4638
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