Alpine Immune Sciences Presents ALPN-101 Program Data Demonstrating Potent Preclinical Activity in Arthritis and Inflammation

--Poster to be Presented at 2017 ACR/ARHP Annual Meeting--

Alpine Immune Sciences, Inc. ALPN, a leading immunotherapy company focused on developing treatments for autoimmune diseases and cancer, today announced results from preclinical studies evaluating ALPN-101 program dual ICOS/CD28 antagonists generated by the company's variant immunoglobulin (Ig) domain (vIgD) platform. The ICOSL vIgD-Fc fusion proteins demonstrated potent activity in an animal model of inflammatory arthritis and in a humanized model of graft vs. host disease (GvHD). Findings suggest molecules from the company's vIgD platform could potentially have clinical therapeutic utility in multiple inflammatory diseases. The data were presented today in a poster session titled "Rheumatoid Arthritis – Animal Models Poster II" [#1328] at the 2017 American College of Rheumatology/Association of Rheumatology Health Professionals (ACR/ARHP) Annual Meeting in San Diego, CA.

"These preclinical studies suggest our ALPN-101 program vIgDs can potently reduce pathogenic T cell activation, inflammatory cytokines, and disease activity in multiple inflammatory diseases," said Stanford Peng, M.D., Ph.D., Executive Vice President of Research and Development and Chief Medical Officer of Alpine.

Background

The immunoglobulin superfamily (IgSF) is a large, diverse family of proteins expressed on immune cells and collectively plays critical roles 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 have employed monoclonal antibodies binding to a single target.

In contrast, Alpine's vIgD platform 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-Fcs bind and inhibit both ICOS and CD28 co-stimulatory pathways.

Evaluations included a mouse model of inflammatory arthritis and 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, and abatacept, approved by the FDA to treat rheumatoid, psoriatic, and juvenile idiopathic arthritis, were used as comparators.

Preclinical Study Results

Presented data from the ICOSL vIgD-Fcs:

• Inhibited multiple parameters of disease in inflammatory arthritis including reducing paw swelling, inflammatory cell infiltrates, circulating inflammatory cytokines, anti-collagen autoantibodies, and lymph node follicular helper T cells, B cells, and activated T cells.
• Prolonged survival and reduced disease activity in GvHD.
• Appeared superior to abatacept in arthritis based on clinical scores and histology, and to belatacept in GvHD based on disease activity scores and survival.

"We are encouraged by the preclinical data generated to date. The vIgD platform can produce novel, potent IgSF-based immuno-modulators whose efficacy has the potential to exceed existing approved therapies," said Mitchell H. Gold, M.D., Executive Chairman and Chief Executive Officer of Alpine.

About Alpine Immune Sciences, Inc.

Alpine Immune Sciences, Inc. is focused on developing novel protein-based immunotherapies using its proprietary variant Ig Domain (vIgD) platform technology. The vIgD platform is designed to interact with multiple targets including many present in the immune synapse. Alpine's vIgDs are developed using a process known as directed evolution, which produces proteins capable of either enhancing or diminishing an immune response and thereby may potentially apply therapeutically to cancer, autoimmune and inflammatory diseases. Alpine has also developed Transmembrane Immunomodulatory Protein (TIP) technology, based on the vIgD platform, to potentially enhance engineered cellular therapies. For more information, visit www.alpineimmunesciences.com.

Forward-Looking Statements

This release contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, Section 21E of the Securities Exchange Act of 1934 and the Private Securities Litigation Reform Act of 1995. These forward-looking statements are not based on historical fact, and include statements regarding Alpine's platform technology, potential therapies and the potential efficacy of such therapies. Forward-looking statements generally include statements that are predictive in nature and depend upon or refer to future events or conditions, and include words such as "may," "will," "should," "would," "expect," "plan," "intend," and other similar expressions among others. These forward-looking statements are based on current assumptions that involve risks, uncertainties and other factors that may cause actual results, events or developments to be materially different from those expressed or implied by such forward-looking statements. These risks and uncertainties, many of which are beyond our control, include, but are not limited to: Alpine's discovery-stage and pre-clinical programs may not advance into the clinic or result in approved products on a timely or cost-effective basis or at all; Alpine may not achieve additional milestone payments pursuant to its collaborations; the impact of competition; adverse conditions in the general domestic and global economic markets; as well as the other risks identified in Alpine's filings with the Securities and Exchange Commission. These forward-looking statements speak only as of the date hereof and Alpine undertakes no obligation to update forward-looking statements, and readers are cautioned not to place undue reliance on such forward-looking statements.

"Transmembrane Immunomodulatory Protein," "TIP," "Variant Ig Domain," "vIgD," and the Alpine logo are registered trademarks or trademarks of Alpine Immune Sciences, Inc. in various jurisdictions.

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