On November 10, 2017 Alpine Immune Sciences, Inc. (NASDAQ:ALPN), a leading immunotherapy company focused on developing treatments for autoimmune/inflammatory diseases and cancer, reported immuno-oncology preclinical data characterizing the functional activity of molecules Alpine successfully generated from its variant immunoglobulin domain (vIgD) platform (Press release, Alpine Immune Sciences, NOV 10, 2017, View Source [SID1234521920]). Several novel immuno-oncology molecules were functionally active via multiple mechanisms of action, including the demonstration of tumor suppression in an animal model. The findings will be presented on Friday, November 10, in a poster session titled "Immune Modulation, Cytokines, and Antibodies" [#P343] at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s (SITC) (Free SITC Whitepaper) 32nd Annual Meeting in National Harbor, MD.
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"Our unique vIgD platform is capable of producing first-in-class immuno-oncology biologics with potentially unique mechanisms of action," said Stanford Peng, M.D., Ph.D., Executive Vice President of Research and Development and Chief Medical Officer of Alpine. "This promising data highlights the versatility of the platform, showing vIgDs may be implemented in multiple therapeutic formats and may be tailored to modulate multiple molecular pathways according to the desired therapeutic application."
Preclinical Study Design and Results
Alpine scientists used the vIgD directed evolution platform to engineer a number of vIgDs with unique binding profiles to proteins relevant to the immune synapse, including PD-1, PD-L1, CTLA-4, TIGIT, CD155, CD28, and/or ICOS. The poster describes the vIgD domains in multiple therapeutic formats, including tumor-localized Fc fusion proteins, multi-checkpoint inhibitors, and vIgDs fused with tumor-specific monoclonal antibodies (V-mAbs). Various in vitro and in vivo tests characterized the functional activity of these potentially novel therapeutics. Data include:
Tri-specific vIgDs for treating cancer with a single domain capable of interacting with three different B7 family members. Depending on formatting, tri-specific vIgDs are potentially capable of agonizing CD28, blocking PD-L1, blocking CTLA-4, and/or depleting tumor cells and/or regulatory T cells. Initial formats investigated in an animal model of cancer demonstrated activity with tumor growth suppression.
A dual ICOS/CD28 costimulatory vIgD fused with the HER2-targeting monoclonal antibody trastuzumab to provide immune stimulation in the tumor microenvironment. These V-mAbs demonstrated in vitro proof of principle for immune cell stimulation and proliferation in response to HER2-positive tumor cells.
Multiple vIgD Fc fusions capable of targeting TIGIT and PD-1 while sparing CD226. These multi-checkpoint inhibitory molecules blocked checkpoint activity and improved IFN-γ production by "exhausted" T cells.
"The SITC (Free SITC Whitepaper) data suggest the versatile vIgD platform has the potential to contribute to the next generation of immuno-oncology therapeutics. Based on these and other encouraging preclinical data, we are continuing to identify and develop appropriate candidates from our vIgD platform for clinical trials for both oncology and inflammation," said Mitchell H. Gold, M.D., Executive Chairman and Chief Executive Officer of Alpine.