- ALPN-303 uniquely binds BAFF and APRIL with high affinity, differentiating from related inhibitors including wild-type TACI-Fc’s -

- Ongoing phase 1 study demonstrates highly encouraging preliminary pharmacodynamic reductions in circulating immunoglobulins -

Alpine Immune Sciences, Inc. (NASDAQ:ALPN), a leading clinical-stage immunotherapy company focused on developing innovative treatments for cancer and autoimmune and inflammatory diseases, today announced the presentation of novel preclinical and clinical data in a poster titled “ALPN-303, an Engineered Dual BAFF/APRIL Antagonist, Potently Inhibits Pathogenic Autoantibodies in Preclinical Models, with Corresponding Pharmacodynamic Activity in Humans,” at the European Alliance of Associations for Rheumatology (EULAR) European Congress of Rheumatology. ALPN-303 is being developed for systemic lupus erythematosus and other B cell-mediated inflammatory and autoimmune diseases.

ALPN-303 is an Fc fusion of an engineered TACI domain that has significantly improved affinity against the B cell cytokines BAFF and APRIL -- particularly the latter, which wild-type TACI-Fc binds inferiorly. Correspondingly superior pharmacokinetics were observed in animals, as well as pharmacological activity in mouse models of immunization and lupus. Preliminary findings in early single dose cohorts of adult healthy volunteers demonstrate dose-dependent reductions in circulating immunoglobulins (IgA, IgG, IgM).

“The preliminary, emerging clinical findings are particularly encouraging,” said Stanford Peng, MD, PhD, Alpine’s President and Head of Research and Development, “because they are highly consistent with our nonclinical data which predict that ALPN-303 may be a more potent yet conveniently-dosed therapeutic. This is of particular importance as we endeavor to surmount challenging target diseases such as lupus and other B-cell related inflammatory diseases.”

A copy of the poster presentation is available on the Scientific Publications page of Alpine’s website.

About ALPN-303

ALPN-303 is a dual B cell cytokine antagonist being developed for multiple autoimmune and/or inflammatory diseases. Engineered by directed evolution, ALPN-303 potently inhibits the pleiotropic B cell cytokines B cell activating factor/B lymphocyte stimulator (BAFF, BLyS) and a proliferation inducing ligand (APRIL), which play key roles in B cell development, differentiation, and survival, and together contribute to the pathogenesis of multiple autoimmune diseases like systemic lupus erythematosus (SLE) and many other autoantibody-related inflammatory diseases. By simultaneously blocking these two cytokines, ALPN-303 has the potential to improve outcomes in patients suffering from severe autoimmune and/or inflammatory diseases. Initiation of a phase 2 study in systemic lupus erythematosus (SLE) and at least one basket study in renal, hematologic, and/or dermatologic indications are planned by the end of 2022.

About the Phase 1 Study

The Phase 1, randomized, placebo-controlled study in healthy adult volunteers is designed to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of intravenously and subcutaneously administered ALPN-303, a dual BAFF/APRIL antagonist. More information on this study can be found at clinicaltrials.gov (study identifier ID NCT05034484)

About Alpine Immune Sciences

Alpine Immune Sciences is committed to leading a new wave of immune therapeutics. With world-class research and development capabilities, a highly productive scientific platform, and a proven management team, Alpine is seeking to create first- or best-in-class multifunctional immunotherapies via unique protein engineering technologies to improve patients’ lives. Alpine has entered into strategic collaborations with leading global biopharmaceutical companies and has a diverse pipeline of clinical and preclinical candidates in development. For more information, visit www.alpineimmunesciences.com. Follow @AlpineImmuneSci on Twitter and LinkedIn.

Forward-Looking Statements

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