Alpine Immune Sciences Presents Preclinical Data on Novel Dual BAFF/APRIL Inhibitory Domains for B cell Mediated Autoimmune Diseases at the European Congress of Rheumatology E-Congress 2020
First presentation of Alpine’s Variant Tumor Necrosis Factor (TNF) Receptor Domain (vTD) Program demonstrating expanded applicability of its directed evolution platform
The poster, entitled “B Cell Modulatory Variant TNF Receptor Domains (vTDs) Identified by Directed Evolution to Inhibit BAFF and APRIL, Alone or Combined with Variant Ig Domains (vIgD™) that Inhibit T Cell Costimulation, for the Treatment of Systemic Lupus Erythematosus and Other Severe Autoimmune Diseases”, was presented during the
BAFF and APRIL are tumor necrosis factor (TNF) superfamily cytokines which play key roles in B cell development, differentiation, and survival, contributing to the pathogenesis of B cell-related autoimmune diseases like systemic lupus erythematosus (SLE). Alpine’s proprietary directed evolution platform was used to identify vTDs, derived from the TNF superfamily receptors TACI or BCMA, exhibiting enhanced affinity for BAFF and APRIL. When developed as Fc fusion proteins, such vTDs dramatically reduced B cell function, including antibody production, sometimes more effectively if the vTDs were also fused with CTLA-4 variant immunoglobulin domains (vIgDs) inhibiting the CD80/CD86 T cell costimulatory molecules. Both the vTD-Fc and vIgD-vTD-Fc fusion variants effectively inhibited T-dependent antibody production in keyhole limpet hemocyanin (KLH)-immunized mice and significantly reduced both anti-DNA antibodies and renal disease (nephritis) in a NZB/WF1 mouse lupus model.
“This work is particularly important to us since it demonstrates the expanded applicability of our directed evolution platform to protein families beyond the immunoglobulin superfamily, the protein family Alpine initially focused upon when founded,” remarked
A copy of this poster is available in the “Scientific Publications” section of Alpine’s website at alpineimmunesciences.com.
Chief Financial Officer