Tolerance Immunotherapies

Autoimmunity and other inflammatory diseases can arise due to an imbalance in the immune system.

Inflammatory diseases including autoimmunity, allergies, and transplant rejection are characterized by an inappropriate or overactive immune response caused by an immune system imbalance. T effector (Teff) cells that normally fight infections and cancer inappropriately attack the body and overwhelm the regulatory T (Treg) cells that are meant to prevent inflammation.

Need for improved therapies

Conventional treatments are broadly immunosuppressive and do not directly target the specific T cells underlying the disease process. Broad immunosuppression, particularly with chronic steroid use, can be associated with severe side effects and often provides only temporary relief . Target-specific (e.g., anti-TNF-alpha antibody and B cell depletion) therapies have emerged as effective tools for modifying and often delaying disease progression , however, such therapies are associated with increased infection risk and are not believed to be curative. Therefore, there remains a need for more targeted and potentially curative therapies that directly address the T cell (Treg/Teff) imbalance underlying inflammatory diseases.

Antigens as targets for treatment

Improved understanding of the cause of inflammatory diseases is allowing the identification of the specific antigens that Teff cells are attacking. In autoimmunity, Teff cells recognize and attack tissues harboring self-antigens, such as pancreatic beta islet cell associated antigens in type-1 diabetes . Knowledge of the problematic antigens that the Teff cells are responding to allows for the development of highly specific treatments that only target the T cells involved in the disease.

Our approach to treatment

Barinthus Bio aims to directly address the disease process underlying autoimmunity and other inflammatory diseases by developing antigen-specific immune tolerance therapies based on our proprietary SNAP-TI technology platform. Our approach is to use SNAP-TI to provide the immune system with problematic antigens within an appropriate tolerogenic context that promotes a reduction in Teff cells and increase in Treg cells, aiming to restore the natural state of immune tolerance and control over disease.

Our approach to indication and antigen selection

While many inflammatory diseases may be amenable to treatment with antigen-specific immune tolerance therapies, Barinthus Bio is prioritizing the research and development of candidates for treating inflammatory diseases that are at least in part driven by Teff cells and preferably have a known human leukocyte antigen (HLA) association. This focus allows us to select indications and patients who are most likely to benefit from therapy with SNAP-TI.

For each indication, we undertake a rigorous antigen selection process to identify key antigens that are recognized by Teff cells involved in disease pathology or present in disease tissue that may be helpful for inducing bystander Tregs. Our pipeline integrates clinical precedent, in silico bioinformatics and ex vivo screening of candidate antigens with patient derived Teff cells. The result of this screening process is the selection of antigens to include in SNAP-TI with the aim of inducing antigen-specific immune tolerance tailored to the specific disease indication.