Alpine Immune Sciences, Inc. (NASDAQ: ALPN), a leading clinical-stage immunotherapy company focused on developing innovative treatments for cancer and autoimmune/inflammatory diseases, today presented a new preclinical program targeting B cell diseases in a poster session at the European Congress of Rheumatology (EULAR) E-Congress 2020.
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 EULAR virtual meeting during the poster session titled “New perspectives: Mechanisms driving SLE, Sjögren's and APS”.
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 Mitchell Gold, MD, Alpine’s Executive Chairman and Chief Executive Officer. “Furthermore, this preclinical work suggests these domains may be superior to approved and/or clinical-stage therapeutics like belimumab, abatacept or telitacicept – suggesting they have the potential to be best-in-class clinical candidates for a number of B cell autoimmune diseases like lupus or other connective tissue diseases. We look forward to advancing one or more of these product candidates towards the clinic in the near future.”
A copy of this poster is available in the “Scientific Publications” section of Alpine’s website at alpineimmunesciences.com.
About Alpine Immune Sciences, Inc.
Alpine Immune Sciences, Inc. is committed to leading a new wave of immune therapeutics, creating potentially powerful multifunctional immunotherapies to improve patients’ lives via unique protein engineering technologies. Alpine has two programs in clinical development. The first, ALPN-101 for autoimmune/inflammatory diseases, is a selective dual T cell costimulation antagonist engineered to reduce pathogenic T and B cell immune responses by inhibiting ICOS and CD28. ALPN-101 has recently completed enrollment of a phase 1 healthy volunteer study, and BALANCE, a phase 1b/2 study in acute GVHD, has recently been initiated. The second, ALPN-202 for cancer, is a conditional CD28 costimulator and dual checkpoint inhibitor, and enrollment is open in NEON-1, a phase 1 study in advanced malignancies. Alpine is backed by world-class research and development capabilities, a highly productive scientific platform, and a proven management team. For more information, visit www.alpineimmunesciences.com.
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Alpine Immune Sciences, Inc.
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