A bioengineered probiotic for resetting immune function in rheumatoid arthritis

The National Institute of Arthritis and Musculoskeletal and Skin Diseases awarded Virtici LLC $306,341 on August 26, 2026, under the Arthritis, Musculoskeletal and Skin Diseases Research program (CFDA 93.846) to develop VTC-B35, a bioengineered oral probiotic therapy for rheumatoid arthritis.

The award funds commercialization of VTC-B35, designed to induce long-term disease remission in rheumatoid arthritis patients by stimulating regulatory T cells and B cells to produce immune tolerance rather than inflammation. The therapeutic approach aims to redirect auto-antigen specific immune responses to provide disease-specific tolerance, potentially allowing patients to achieve sustained remission without the immunosuppressive side effects associated with existing biologic therapies. Current standard-of-care biologics fail to achieve sustained remission in more than half of rheumatoid arthritis patients and carry risks including serious infections, cancer, and neurological complications.

Virtici LLC, a Seattle-based for-profit biomedical research and development company, is the recipient. Performance occurs in Seattle, Washington. The period of performance runs through July 31, 2027. This is a Project Grant, the assistance type for NIAMS-supported research awards.

Abstract

Our goal is to commercialize VTC-B35 as a novel, orally administered therapy for long-term disease remission of rheumatoid arthritis (RA). RA is a chronic, systemic inflammatory disorder affecting up to 1% of the US POPULATION1-3. While many organs are affected, the main targets of RA are synovial joints. As the disease progresses, approximately half of RA patients become DISABLED6. RA patients also face higher unemployment and double the risk of depression of the general POPULATION9. Treatment of RA remains a significant unmet medical need. Despite the advent of a number of effective but costly biologic therapies, less than half of RA patients achieve sustained remission, with many non-responsive or experiencing RELAPSE10 . Further, tolerability of biologics is limited by immunosuppressive side effects, such as increased risk of serious infections, cancer and, in rare instances, neurological COMPLICATIONS11-14 therapies that redirect immune responses to produce immune tolerance instead of inflammation have potential to treat the cause rather than the symptoms of disease, and so represent superior treatments for RA. For these reasons, we are developing an oral immunotherapeutic that regulates auto-antigen specific regulatory T cells (TREGS) and B cells (BREGS) to provide disease-specific tolerance. This approach has the potential to 1) "switch off" the immune response against the patient's own tissues specific to RA in an enduring manner, and; 2) maximally balance the relationships between effector cells of different lineages to prevent relapses of inflammation. As such, our approach will provide patients long-term remission and increased safety without systemic immunosuppression. Our team recently demonstrated that oral administration of a probiotic bacterial strain expressing the cytokine IL-35 effectively induced treg cells, reduced disease severity, and generated a tolerogenic response in the mouse model of CIA22. Building from this initial work, we have engineered a clinical strain of the probiotic yeast S. Boulardii (termed VTC-B35) that expresses human IL-35 from a genome-integrated operon. The use of S. Boulardii allows US to leverage a well-accepted, gras (generally regarded as safe) probiotic strain with unique immune regulation, protein expression, and protein processing attributes. This application is designed to advance VTC-B35 towards the clinic by establishing its manufacturing, therapeutic activity, and animal safety. Successful commercialization of VTC-B35 will ultimately provide a profound front-line medical advancement in the treatment of RA, and potentially other autoimmune diseases as well.