BERKELEY, California, United States – May 8, 2026
Azalea Therapeutics announced groundbreaking late-breaking data at the upcoming American Society of Gene & Cell Therapy (ASGCT) 2026 Annual Meeting demonstrating the first successful in vivo generation of genomic site-specific TRAC-CAR T cells in non-human primates following a single intravenous administration. The company’s novel dual-vector platform generated engineered CAR T cells directly inside the body without requiring lymphodepletion or ex vivo cell manufacturing, representing a potentially transformative advancement in the field of genomic medicine and cell therapy.
According to the presented preclinical findings, all six rhesus macaques treated in the study experienced deep B cell depletion exceeding 90% in peripheral blood by Day 10, while potent B cell clearance was also observed across lymph nodes and bone marrow. The therapy was generally well tolerated, with no deaths, no neurotoxicity, and no detectable off-target CAR expression or integration in non-T cells. The results position Azalea Therapeutics among the emerging biotechnology companies developing next-generation in vivo engineered cell therapies aimed at simplifying manufacturing, improving scalability, and expanding access to advanced genomic medicines for cancer, autoimmune diseases, and genetic disorders.
In Vivo CAR T Engineering Demonstrates Precise Genomic Integration
The presented study marks what Azalea believes to be the first demonstration of site-specific genomic integration in T cells directly inside a living primate model, a major milestone for the rapidly evolving field of in vivo cell engineering. The company’s proprietary platform combines CD3-targeted Enveloped Delivery Vehicles (EDVs) carrying transient Cas9 complexes with a T cell-tropic adeno-associated viral vector (AAV-T) containing a promoterless CAR gene flanked by TRAC homology arms. This dual-vector system enables highly selective insertion of the CAR construct into the TRAC genomic locus, allowing CAR expression to remain under the control of the endogenous T cell promoter for more physiologic regulation and potentially improved durability.
In the study, six immune-competent rhesus macaques received a single intravenous administration of the platform at varying dose levels without prior lymphodepletion. Investigators observed TRAC-CAR T cells reaching as high as 41% of all peripheral T cells by Day 11, demonstrating efficient in vivo engineering and expansion. The company stated that this genomic locus-specific approach could become foundational for improving the safety, durability, and precision of future in vivo CAR T cell therapies while potentially eliminating the complexity and cost associated with individualized ex vivo manufacturing workflows currently used in commercial CAR T programs.
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Potent B Cell Depletion and Favorable Safety Profile Observed
The study generated strong pharmacodynamic activity across multiple tissue compartments, supporting the translational potential of Azalea’s genome editing platform. All six treated animals demonstrated profound B cell aplasia in peripheral blood, while five of six animals treated at the highest dose level achieved greater than 90% B cell depletion within lymph nodes and bone marrow within two weeks of treatment. Researchers highlighted that the therapy achieved these results without preconditioning chemotherapy or lymphodepletion, which are commonly required in traditional CAR T treatment protocols and often contribute to significant toxicity risks. Importantly, the therapy showed a favorable safety profile throughout the study.
According to the company, no deaths, neurotoxicity events, or major safety concerns were reported during treatment and follow-up evaluations. Molecular analyses further confirmed the absence of detectable off-target CAR integration or expression in non-T cells circulating in the blood, supporting the precision and selectivity of the delivery platform. Azalea leadership emphasized that the ability to selectively engineer immune cells in vivo while avoiding unintended genomic integration could represent a critical advancement for the long-term clinical development of programmable cell therapies targeting oncology, autoimmune disease, and inherited genetic conditions.
ASGCT 2026 Data Highlight Growing Momentum in In Vivo Cell Therapy
Azalea Therapeutics’ late-breaking ASGCT presentation reflects growing industry momentum toward in vivo engineered cell therapies, an emerging field seeking to overcome the manufacturing limitations, logistical complexity, and high costs associated with conventional ex vivo CAR T therapies. Traditional CAR T treatments require patient cell harvesting, laboratory engineering, expansion, and reinfusion, creating substantial barriers to scalability and global accessibility. In contrast, Azalea’s approach aims to engineer therapeutic immune cells directly inside the patient through targeted genomic delivery systems.
Industry observers increasingly view in vivo engineering as a potentially disruptive next-generation platform capable of expanding CAR T applications beyond hematologic malignancies into solid tumors, autoimmune diseases, and broader immune-mediated disorders. The company believes its proprietary EDV and AAV-T technologies may provide the foundation for a new class of programmable genomic medicines capable of delivering durable therapeutic effects through a single administration. As precision genomic medicine continues advancing rapidly, the first-in-primate demonstration of site-specific in vivo TRAC-CAR T cell engineering may become an important milestone in the broader evolution of gene editing-based immunotherapies and next-generation cellular medicine.
Source: Azalea Therapeutics press release
