On December 9, 2017 Alpine Immune Sciences, Inc. (NASDAQ:ALPN), a leading immunotherapy company focused on developing treatments for autoimmune/inflammatory diseases and cancer, reported results from a preclinical study of the company’s ALPN-101 program in a humanized model of graft vs. host disease (GvHD) (Press release, Alpine Immune Sciences, DEC 9, 2017, View Source [SID1234522455]). Results showed Alpine’s ICOSL vIgD-Fc fusion proteins demonstrated therapeutic efficacy, including suppressing an allogeneic immune response in vitro, improving survival, and reducing GvHD disease activity. The data were presented in a poster session, titled "Experimental Transplantation: Basic Biology, Pre-Clinical Models: Poster I" (poster #1892) during the 59th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting & Exposition in Atlanta.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"These preclinical data showing activity with novel ICOS/CD28 dual antagonists from our vIgD platform in a humanized model of GvHD are encouraging because of the ongoing unmet medical need in GvHD," said Stanford Peng, M.D., Ph.D., Executive Vice President of Research and Development and Chief Medical Officer of Alpine. "These preclinical findings suggest our platform can generate novel immuno-oncology molecules with potential broad clinical therapeutic utility."

GvHD, a complication that can occur after stem cell or bone marrow transplants, has a major impact on survival following transplantation. Transplant-related mortality is as high as 92 percent in grade IV acute GvHD. Approximately 30 to 50 percent of bone marrow transplant patients will develop clinically significant GvHD – or 2,500 to 4,200 patients per year in the United States.

Background on Alpine’s ICOSL vIgD-Fc Fusion Proteins

The immunoglobulin superfamily (IgSF) is a large, diverse family of proteins expressed on immune cells collectively playing a critical role in immune regulation. Well-known IgSF proteins include PD-1, PD-L1, CTLA-4, CD28, CD80/CD86 (B7-1/2), inducible T cell costimulator (ICOS), and TIGIT. Most therapeutic strategies targeting this family of proteins for the treatment of cancers and autoimmune/inflammatory diseases have employed monoclonal antibodies binding to a single target.

Alpine’s vIgD platform, in contrast, transforms natural IgSF proteins into multifunctional protein domains. CD28 and ICOS are expressed on T cells, interacting with CD80/CD86 and ICOS ligand (ICOSL), respectively, and play critical roles in T cell activation. Alpine’s ICOSL vIgD-Fc bind and inhibit both ICOS and CD28 co-stimulatory pathways.

Preclinical Study Design and Results

The preclinical study presented at ASH (Free ASH Whitepaper) 2017 evaluated the function of Alpine’s ICOSL vIgD-Fcs both in vitro and in a humanized mouse model of GvHD. Belatacept, an immunosuppressive T cell co-stimulation blocker approved by the U.S. Food and Drug Administration (FDA) to prevent kidney transplant rejection, was used as a comparator.

Results showed Alpine’s ICOSL-vIgD-Fc:

Demonstrated superior efficacy to belatacept in vitro in inhibiting T cell proliferation (CD4 and CD8 T cells) and cytokine production, including interferon gamma and tumor necrosis factor alpha, two key cytokines induced in a GvHD response
Significantly protected against GvHD at levels comparable to or better than belatacept in the humanized model
Significantly prolonged survival and greatly reduced GvHD disease activity in the humanized model as assessed by a disease activity score and weight loss compared with saline and wild-type ICOSL-Fc