--Povetacicept Superior to Wild-Type TACI-Fc and B-cell Depletion in a Preclinical Model of Lupus--

-- Initiation of Phase 2 SLE Study Planned for 2H 2024 --

Alpine Immune Sciences, Inc. (NASDAQ: ALPN), a leading clinical-stage immunotherapy company focused on developing innovative treatments for autoimmune and inflammatory diseases, announced today that the Company presented new translational data for povetacicept (ALPN-303) in systemic lupus erythematosus (SLE) at the American College of Rheumatology Convergence 2023, November 10-15, 2023.

Povetacicept Presentation Highlights Include:

• In SLE patients, BAFF- and APRIL-related genes (i.e., BAFF, APRIL, TACI, and BCMA) are increased in myeloid lineage cells and B cells compared to healthy adults.
• Povetacicept, as compared to single BAFF or APRIL pathway inhibitors, more potently downregulates genes associated with activation in B cells.
• Povetacicept significantly reduces multiple disease parameters in a mouse model of lupus, more effectively than WT TACI-Fc or conventional B cell depletion.

“SLE is a serious, potentially fatal disease with few approved and effective treatment options,” said Stanford Peng, M.D., Ph.D., President and Head of Research and Development at Alpine. “BAFF and APRIL have been heavily implicated in its pathogenesis, and these data indicate that potent inhibition of both may be required to achieve optimal efficacy. Along with the encouraging clinical data we presented earlier this week with povetacicept in glomerulonephritis, particularly IgA nephropathy, we look forward to advancing povetacicept into a phase 2 clinical study in SLE next year.”

American College of Rheumatology Convergence 2023

Date/Time: Tuesday, November 14, 2023, 9:00 am – 11:00 am PT

Poster Title: Upregulation of Both APRIL and BAFF in Systemic Lupus Erythematosus Suggests Non-Redundant Roles, Further Revealed by Dual Inhibition with Povetacicept (ALPN-303)

Abstract ID: 1553950

Session Name: SLE – Treatment Poster III

Location: Exhibit Hall, San Diego Convention Center, San Diego, CA

Presenter: Tiffany Blair, Ph.D., Alpine Immune Sciences

Link to Poster: https://bit.ly/3ssynXM

About Povetacicept (ALPN-303)

Povetacicept (ALPN-303) is a dual antagonist of the BAFF (B cell activating factor) and APRIL (a proliferation inducing ligand) cytokines, which play key roles in pathogenesis of multiple autoimmune diseases via their roles in the activation, differentiation and/or survival of B cells, particularly antibody-secreting cells, as well as T cells and innate immune cells. Based upon an engineered TACI (transmembrane activator and CAML interactor) domain, povetacicept has exhibited greater potency in preclinical studies versus wild-type TACI-based comparators, as well as other inhibitors of BAFF and/or APRIL alone and B cell depletion. Povetacicept is in development for multiple autoimmune diseases, including systemic lupus erythematosus, IgA nephropathy and other autoimmune kidney diseases, and autoimmune cytopenias.

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 X and LinkedIn.

Forward-Looking Statements

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