Mast cells (MCs) are key players in many allergic and inflammatory diseases. Briquilimab is a monoclonal antibody that binds to c-Kit, blocking stem cell factor from binding and activating c-Kit, leading to MC apoptosis and depletion. Pharmacokinetic and pharmacodynamic evaluation of briquilimab in non-human primates and in murine disease models of asthma and dermatitis suggest that briquilimab-mediated depletion of MCs is well-tolerated, protects against MC activation from various stimuli, and significantly reduces tissue inflammation.

Obexelimab is a CD19 x FcgRIIb bifunctional monoclonal antibody resulting in an inhibitory effect, rather than depletion, across B cell lineage (pro-B cells, pre-B cells, B cells, plasmablasts and CD19-expressing plasma cells). It mimics natural antigen-antibody complex for inhibition of B cells. It is being developed for multiple I&I indications for autoimmune diseases. Clinical data from obexelimab-treated patients and relevant mechanisms of action will be discussed.

InduPro leverages inherent and induced proximity of cell surface proteins to discover novel biology and enable therapeutic development. We demonstrate that re- location of immunomodulatory proteins into or out of the immune synapse using select bi-specific antibodies can alter T cell activation. Application of this approach to dampen T cell signaling for the treatment of autoimmune disease will be presented.

Oxidative stress occurs in many autoimmune diseases which give rise to oxidative post translationally modified (oxPTM) neoepitopes that are recognized by the immune system as ‘non-self’. The detection of autoantibodies against oxPTM neoepitopes, might improve early diagnosis and monitoring of disease activity. Importantly, oxPTM neoepitopes accumulating in the diseased tissue can be exploited for targeting therapeutic specifically to diseased tissue. Studies on musculoskeletal diseases and type 1 diabetes will be reviewed.

DNTH103 is an investigational, fully human, half-life extended, potent monoclonal antibody engineered to selectively target the classical pathway by inhibiting only the active form of the C1s protein, to enable a more convenient subcutaneous, self-administered injection dosed as infrequently as once every two weeks. Additionally, selective inhibition of the classical complement pathway may lower patient risk of infection from encapsulated bacteria by preserving immune activity of the lectin and alternative pathways. DNTH103 is in development for Myasthenia Gravis, CIDP and MMN.

Regulatory T cells (Tregs) are naturally occurring immune cells that modulate immune responses and promote tissue homeostasis. Treg dysfunction is characteristic of many chronic autoimmune and inflammatory diseases. Sonoma Biotherapeutics genetically engineers and expands patients’ Tregs as a “living therapy” with antigen receptors that target diseased tissue to regulate inappropriate immune responses, reducing inflammation and facilitating tissue repair without compromising host defense.