Sail Biomedicines Advances Novel In Vivo eRNA CAR-T Therapy for Autoimmune Diseases
核心洞察
Sail Biomedicines (搜索) presented promising preclinical data for SAIL-0804 (搜索), an innovative in vivo CAR-T candidate that achieved complete B cell ablation in humanized mouse models without requiring cell harvesting or lymphodepletion.
The therapy combines Sail's proprietary Endless RNA™ technology with targeted lipid nanoparticles, enabling transient T cell reprogramming that could offer CAR-T efficacy with outpatient convenience for autoimmune disease treatment.
SAIL-0804 (搜索) demonstrated 50-80% T cell transfection efficiency across species and produced an immune reset with repopulating B cells showing mostly immature phenotypes, supporting advancement to IND-enabling studies.
Sail Biomedicines (搜索) has unveiled promising preclinical data for its novel in vivo CAR-T product candidate, SAIL-0804 (搜索), at the 28th Annual Meeting of the American Society of Gene & Cell Therapy (ASGCT 2025). The data showcase a potentially transformative approach to treating autoimmune diseases (搜索) through non-integrative T cell reprogramming using the company's proprietary Endless RNA™ (eRNA™) platform and targeted lipid nanoparticles.
The preclinical results support SAIL-0804 (搜索)'s nomination as Sail's first development candidate and its advancement into IND-enabling studies, potentially offering a more accessible alternative to conventional CAR-T therapies for autoimmune conditions.
"SAIL-0804 (搜索) represents a paradigm shift in autoimmune disease treatment, bringing the precision of CAR-T to a broader patient population through a non-integrating, off-the-shelf RNA therapeutic," said Stephen Berenson, Executive Chairman of Sail Biomedicines (搜索) and Managing Partner Emeritus at Flagship Pioneering (搜索).
Novel Approach Addresses Limitations of Current Therapies
Current B cell depletion approaches for autoimmune diseases (搜索) rely primarily on monoclonal antibodies such as belimumab, rituximab, and obinutuzumab, which have shown limited efficacy. While recent autologous lentiviral CAR-T therapies have demonstrated transformative results, they face significant barriers in terms of access, safety, and scalability.
SAIL-0804 (搜索) aims to bridge this gap by combining the deep B-cell depletion efficacy of lentiviral CAR-T with the convenience and safety profile of an outpatient-administered therapeutic. The therapy utilizes Sail's circular RNA technology optimized for enhanced stability and expression, delivered via targeted lipid nanoparticles engineered for selective T cell delivery.
Key Preclinical Findings
The poster presentation at ASGCT 2025 highlighted several significant achievements:
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Complete B cell ablation: SAIL-0804 (搜索) demonstrated thorough B cell depletion in humanized mouse models across blood, spleen, lymph nodes, and bone marrow—including pro-B and pre-B progenitor cells.
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Efficient T cell reprogramming: Sail's targeted LNPs achieved 50-80% transfection of CD4+ and CD8+ T cells across multiple species, including rodents, non-human primates, and human T cells. In humanized mice, 2,000-5,000 CAR molecules were detected per T cell—exceeding the threshold required for effective killing.
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Durable expression without genomic integration: The eRNA-encoded CD19 (搜索) CAR maintained expression over multiple days post-dosing, providing a transient but therapeutically potent window of cytotoxic activity without requiring genome integration or conditioning regimens.
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Immune reset potential: After depletion, repopulating B cells exhibited a largely immature phenotype, suggesting an effective reset of the B cell compartment and potential for long-term remission without sustained immunosuppression.
Platform Technology Enables Programmable RNA Medicines
In addition to the poster presentation, Sail's Chief Platform Officer Kerry Benenato, Ph.D., will deliver a presentation titled "Pioneering the Design and Deployment of Fully Programmable RNA Medicines" on May 16. Her talk will explore how Sail's eRNA™ and programmable nanoparticle platforms enable durable, cell-specific RNA expression beyond the liver.
The company's approach integrates high-throughput data generation, natural chemistry-enabled nanoparticles, and machine learning-driven design to build a modular system for engineering programmable RNA medicines. SAIL-0804 (搜索) represents the first development candidate to emerge from this platform.
Mechanism and Administration
SAIL-0804 (搜索) is designed for intravenous administration without the need for lymphodepletion or cell harvesting—two major limitations of conventional CAR-T therapies. The candidate enables transient, non-integrative expression of an anti-CD19 (搜索) chimeric antigen receptor in T cells in vivo.
This approach aims to emulate the therapeutic impact of conventional CAR-T therapies while offering a more accessible and scalable treatment modality. If successful in clinical trials, it could significantly expand access to CAR-T-like therapies for patients with autoimmune diseases (搜索).
Next Steps
Sail Biomedicines (搜索) is currently preparing to advance SAIL-0804 (搜索) towards IND-enabling studies to support future clinical evaluation in autoimmune diseases (搜索). The company will present detailed findings in Poster #774, titled "In Vivo Transient Programming of T Cells with SAIL's Targeted Nanoparticles Encapsulating eRNA™-encoded hCD19 CAR Achieves Deep Depletion of B cells in Blood and Lymphoid Tissues in a B-cell Repopulating Humanized Mouse Model" on May 13.
Founded by Flagship Pioneering (搜索), Sail Biomedicines (搜索) is focused on pioneering the integrative design and deployment of fully programmable medicines to transform patient care. The company's platform combines programmable circular RNA technology with an industry-leading platform of programmable nanoparticles to enable comprehensive programming of medicines.