• In vivo proof-of-concept achieved in humanized mice and non-human primates (NHPs) using Gene Writers encapsulated in proprietary lipid nanoparticles (LNPs) targeting long-term hematopoietic stem cells (LT-HSCs) to rewrite the hemoglobin subunit beta (HBB) gene, the genetic locus associated with sickle cell disease (SCD)
• Single intravenous infusion of Gene Writer formulated in proprietary LNP generated chimeric antigen receptor (CAR)-T cells in a tumor-bearing xenograft mouse model that expanded in vivo and cleared tumor
• In a separate in vivo mouse model containing resting human T cells, an average of 30% CAR writing was achieved, with complete B cell depletion observed, highlighting its therapeutic potential in autoimmune diseases

SOMERVILLE, Mass., Dec. 09, 2024 (GLOBE NEWSWIRE) -- Tessera Therapeutics, a biotechnology company pioneering a new approach to genome engineering through the development of its Gene Writing™ and delivery platforms, is presenting preclinical updates from its in vivo programs in sickle cell disease (SCD) and T cell therapies respectively. Data were presented highlighting delivery advances across hematopoietic stem cells (HSCs) and T cells, enabling efficient in vivo HSC rewriting in humanized mice and NHP, and tumor clearance and B cell depletion in mouse models with in vivo generated CAR-T cells. These new data were shared in one oral presentation and two poster presentations at the 66^th American Society of Hematology (ASH) Annual Meeting taking place in San Diego, California, December 7 – 10, 2024.

“We are excited by the totality of preclinical data presented at ASH, which underscores the ongoing progress of our Gene Writing and delivery platforms,” said Michael Severino, M.D., CEO of Tessera Therapeutics. “In our sickle cell disease program, we have shown in vivo editing of HBB in mouse models that surpass that of asymptomatic carriers of the sickle mutation, and for the first time in NHP, editing efficiencies that reach anticipated therapeutic levels. Additionally, we have achieved proof-of-concept for generating functional CAR-T cells across multiple mouse models, all with a single dose of an LNP-RNA composition, without toxic chemotherapy conditioning or lymphodepletion. Our focus on advancing groundbreaking in vivo treatments for sickle cell disease and novel T cell therapies remains steadfast.”

In Vivo SCD Data

• Gene Writer formulated in a proprietary LNP for delivery to LT-HSCs achieved an average of 62% rewriting of the HBB gene, the locus responsible for SCD, in LT-HSCs of humanized mice after a single intravenous administration
• Early proof-of-concept study of Gene Writer formulated in a LNP achieved an average of 24% of HBB rewriting in LT-HSCs in NHP, reaching anticipated therapeutic levels established by human mixed-donor chimerism studies that demonstrate 20% chimerism can reverse the sickle phenotype in patients following allogeneic hematopoietic stem cell transplant¹
• Proof-of-principle study demonstrated that in vivo rewriting in LT-HSCs with high efficiency is achievable using a single dose of Gene Writer with a surrogate reagent targeting beta-2 microglobulin (B2M). Rewriting efficiency of 76% was achieved in NHP, with stable editing out to day 84. B2M rewriting was observed across multi-lineages in peripheral blood, providing evidence that edited HSCs were functionally contributing to hematopoiesis and gave rise to edited blood cells
• Tessera’s non-viral delivery platform is critical to enabling these in vivo results, as well as successfully developing an in vivo therapeutic for SCD. Using a proprietary LNP developed for delivery to HSCs, both liver de-targeting and enhanced bone marrow delivery was achieved, resulting in 11-fold lower liver delivery and 52-fold higher bone marrow delivery of green fluorescent protein (GFP) as compared to a liver-tropic LNP in mice
  

Advances Towards In Vivo T-Cell Therapies

• Gene Writers formulated in LNPs can integrate CAR transgenes targeting CD20 in resting NHP T cells, achieving an average of 60% CAR writing in vitro
• LNP delivery of Gene Writer and CAR template RNAs targeting B-cell maturation antigen (BCMA) to activated or resting T cells in vitro generated functional CAR-T cells that efficiently killed tumor cells in vitro and in vivo in tumor-bearing xenograft mice
• Proof-of-concept studies in oncology demonstrated that with a single intravenous infusion of Gene Writer formulated in a proprietary LNP to tumor-bearing xenograft mice generated functional CD19-targeted CAR-T cells in vivo that were able to expand and eradicate tumor burden
• LNP delivery of Gene Writer and CAR template RNAs targeting CD20 resulted in an average of 30% CAR writing in vivo in a naïve humanized mouse model containing resting T cells, which led to the elimination of human B cells in the blood compared to control, highlighting its therapeutic potential in autoimmune diseases

¹Blood. 2017;130(17):1946-1948

About Tessera Therapeutics

Tessera Therapeutics is pioneering a new approach to genome engineering through the development of its Gene Writing™ and delivery platforms, with the aim to unlock broad new therapeutic frontiers. Our Gene Writing platform is designed to write therapeutic messages into the genome by efficiently changing single or multiple DNA base pairs, precisely correcting insertions or deletions, or adding exon-length sequences and whole genes. Our proprietary lipid nanoparticle delivery platform is designed to enable the in vivo delivery of RNA to targeted cell types. We believe our Gene Writing and delivery platforms will enable transformative genetic medicines to not only cure diseases that arise from errors in a single gene, but also modify inherited risk factors for common diseases and create engineered cells to treat cancer and potentially autoimmune and other diseases. Tessera Therapeutics was founded in 2018 by Flagship Pioneering, a life sciences innovation enterprise that conceives, creates, resources, and develops first-in-category bioplatform companies to transform human health and sustainability.

For more information about Tessera, please visit www.tesseratherapeutics.com.

Contact

Kristin Politi, PhD
LifeSci Communications, LLC
kpoliti@lifescicomms.com