Alpine Immune Sciences Announces Preclinical Data Showing Novel Immuno-Oncology Costimulatory Molecules Generated from vIgD Platform Fused with Trastuzumab Enhanced Immune Responses Against HER2-Positive Tumor Cells

-- Data Presented at 2017 San Antonio Breast Cancer Symposium --

Alpine Immune Sciences, Inc. ALPN, a leading immunotherapy company focused on developing treatments for autoimmune/inflammatory diseases and cancer, today announced results of a preclinical study of novel immuno-oncology molecules derived from the company's variant immunoglobulin (Ig) domain (vIgD) platform. Alpine scientists fused these novel molecules with trastuzumab with the goal of activating T cells against HER2-positive tumors in the tumor microenvironment. Results showed these trastuzumab-ICOSL "V-mAbs" promoted T cell proliferation and cytokine secretion and enhanced killing of tumor cells. The data were presented in a poster session, titled "Treatment: Novel Targets and Targeted Agents (abstract # P1-09-10)," during the 40^th Annual San Antonio Breast Cancer Symposium (SABCS).

Trastuzumab, known by its brand name Herceptin®, is a U.S. Food and Drug Administration-approved monoclonal antibody against HER2. It has been shown to improve survival in HER2-overexpressing cancers, including metastatic breast and gastric cancer, and when administered during adjuvant treatment for breast cancer.

"These preclinical data clearly indicate that the V-mAb format for our unique vIgD platform can yield novel HER2-targeted, T cell-activating immunotherapies," said Stanford Peng, M.D., Ph.D., Executive Vice President of Research and Development and Chief Medical Officer of Alpine. "With these findings, we are encouraged that the V-mAb format more broadly will be able to enable target- or tumor-specific immune modulation by our vIgDs for this and many other therapeutic applications."

Preclinical Study Design and Results

Alpine scientists previously used the company's directed evolution vIgD platform to engineer a dual ICOS/CD28 agonist (ICOSL vIgD) capable of providing a costimulatory signal when localized to targeted cells.

In patients with HER2-positive breast cancer, the presence of tumor infiltrating lymphocytes (TILs) is associated with an improved prognosis. To promote anti-tumor activity of TILs in HER2-positive tumors, Alpine fused ICOSL vIgDs to trastuzumab, generating trastuzumab-ICOSL V-mAbs. Alpine used various in vitro and in vivo tests to characterize the functional activity of these V-mAbs. Results showed they:

• Retained binding to CD28, ICOS, and HER2.
• Demonstrated in vitro proof of principle for T cell stimulation and proliferation in response to HER2-positive tumor cells – i.e., they enhanced interferon-gamma production, promoted CD4 T cell and CD8 T cell proliferation, and promoted cell lysis (tumor killing).

"These preclinical results add to the growing body of data suggesting our versatile vIgD platform has the unique potential to create the next generation of immuno-oncology therapeutics with novel mechanisms of action when fused with already-approved monoclonal antibodies," said Mitchell H. Gold, M.D., Executive Chairman and Chief Executive Officer of Alpine. "We continue to identify, develop, and evaluate candidates from our vIgD platform for oncology and inflammatory indications."

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 and potential 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. Herceptin® is a registered trademark of Genentech, Inc.

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