SAIL-0804 shows rapid and deep B cell depletion along with repopulation by mostly immature phenotypes in preclinical models, supporting its advancement into IND-enabling studies

CAMBRIDGE, Mass. --(BUSINESS WIRE)

Sail Biomedicines, a Flagship Pioneering company and leader in RNA-based programmable medicines, today announced the presentation of preclinical data on its in vivo CAR-T product candidate, SAIL-0804, at the 28th Annual Meeting of the American Society of Gene & Cell Therapy (ASGCT 2025). The poster presentation highlights Sail’s differentiated approach to treating autoimmune diseases through transient, non-integrative T cell reprogramming using its Endless RNA™ (eRNA™) platform and targeted lipid nanoparticles (tLNPs). The data support Sail’s nomination of SAIL-0804 as its first development candidate and advancement into IND-enabling studies.

“SAIL-0804 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, Sail Biomedicines and Managing Partner Emeritus, Flagship Pioneering. “This program underscores the power of Sail’s new class of medicines to enable programmable, targeted RNA therapies with potentially transformative impact. We look forward to continuing to advance SAIL-0804 towards the clinic.”

Current approaches to deplete B cells in autoimmune diseases, including monoclonal antibodies like belimumab, rituximab, or more recently obinutuzumab, have demonstrated limited efficacy. Recent breakthroughs with autologous lentiviral CAR-T therapies have shown transformative efficacy but present significant barriers to access, safety, and scalability. In contrast, the presented data support the potential of SAIL-0804 to combine the deep B-cell depletion efficacy of lentiviral CAR-T with the convenience and safety profile of an outpatient-administered therapeutic.

ASGCT 2025 Poster Highlights:

  • Broad and deep B cell depletion: SAIL-0804 demonstrated complete B cell ablation in humanized mouse models across blood, spleen, lymph nodes, and bone marrow—including pro-B and pre-B progenitor cells.
  • Efficient T cell reprogramming in vivo: Sail’s targeted LNPs achieved 50–80% transfection of CD4+ and CD8+ T cells across species (rodents, NHPs, and human T cells). In humanized mice, 2,000–5,000 CAR molecules were detected per T cell – levels which are above the threshold for effective killing.
  • Durable expression with eRNA: The eRNA-encoded CD19 CAR was expressed over multiple days post-dosing, providing a transient but therapeutically potent window of cytotoxic activity without the need for genome integration or conditioning regimens.
  • Immune reset: Repopulating B cells after depletion exhibited a largely immature phenotype, indicative of effective reset of the B cell compartment and potential for long-term remission without sustained immunosuppression.

Sail Biomedicines will present these 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.” The presentation will take place Tuesday, May 13, from 6:00pm to 7:30pm CT.

In addition to the poster, Sail Biomedicines’ Chief Platform Officer Kerry Benenato, Ph.D., will give a presentation, titled, “Pioneering the Design and Deployment of Fully Programmable RNA Medicines,” on Friday, May 16 at 1:45pm CT in the Scientific Session: Targeted Nanosystems for Gene Transfer and Editing: Beyond Delivery to the Liver.

Her presentation explores how Sail’s eRNA™ and programmable nanoparticle (NP) platforms are engineered to enable durable, cell-specific RNA expression beyond the liver. Through the integration of high-throughput data generation, natural chemistry-enabled nanoparticles, and machine learning-driven design, Sail is building a modular system to systematically engineer fully programmable RNA medicines. SAIL-0804 is the first development candidate to emerge from this platform, demonstrating its potential to enable selective, transient in vivo reprogramming of immune cells.

About SAIL-0804

SAIL-0804, an investigational in vivo CAR-T development candidate, combines Sail’s proprietary Endless RNA™ (eRNA™), a circular RNA technology optimized for enhanced stability and expression, with targeted lipid nanoparticles (tLNPs) engineered for selective delivery to T cells. Designed for intravenous administration without the need for lymphodepletion or cell harvesting, SAIL-0804 enables transient, non-integrative expression of an anti-CD19 chimeric antigen receptor (CAR) in vivo. The approach aims to emulate the therapeutic impact of conventional CAR-T therapies while offering a more accessible and scalable modality. Sail Biomedicines is currently preparing to advance SAIL-0804 towards IND-enabling studies to support future clinical evaluation in autoimmune diseases.

About Sail Biomedicines

Sail Biomedicines is pioneering the integrative design and deployment of fully programmable medicines to transform patient care. Sail’s platform combines first-in-class programmable circular RNA technology (Endless RNA™ or eRNA), and an industry-leading platform of programmable nanoparticles, to unlock comprehensive programming of medicines for the first time. By leveraging cutting-edge eRNA and nanoparticle deployment technology, Sail is building a wealth of data, enabling unparalleled use of generative AI techniques to identify and design fully programmable medicines that are potent, targeted, versatile, and tunable. Sail was founded by Flagship Pioneering. For more, visit www.sail.bio and follow us on X (@SailBiomeds) and LinkedIn.

Copyright Business Wire 2025

Information contained on this page is provided by an independent third-party content provider. XPRMedia and this Site make no warranties or representations in connection therewith. If you are affiliated with this page and would like it removed please contact [email protected]