- Novel approach to CD28 to enhance activation of T cells and anti-tumor activity -

- Crystallography demonstrates critical interaction between davoceticept’s CD80 domain and PD-L1 -

- Data further encourage ongoing davoceticept development, including NEON-1 monotherapy and NEON-2 pembrolizumab combination trials -

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 a publication in Nature Communications on the preclinical development of davoceticept, Alpine’s lead immuno-oncology therapeutic candidate uniquely designed to combine PD-L1-dependent CD28 costimulation with dual PD-L1 and CTLA-4 checkpoint inhibition. CD28 is a critical T cell receptor recognized as a principal target of immune checkpoints like PD-1 and CTLA-4.

“Lack of sufficient CD28 costimulation in the tumor microenvironment may underlie checkpoint inhibitor resistance and, therefore, CD28-directed treatments hold much promise. Davoceticept is an exciting first-in-class CD28-targeting drug that is distinct among others in this space for its triplicate mechanism and structural elegance,” said Rafi Ahmed, PhD, Professor of Microbiology and Immunology and Vaccine Center Director at Emory University, and member of Alpine’s scientific advisory board.

“This achievement is the culmination of years of our scientists’ efforts to target CD28 in a highly differentiated fashion,” remarked Stanford Peng, MD PhD, President and Head of R&D at Alpine. “It distinctively illustrates the unique yet powerful approach of our discovery platform, and further encourages us to continue to pursue clinical development of davoceticept with vigor.”

Davoceticept is being studied in two clinical trials, NEON-1 as monotherapy, and NEON-2 in combination with pembrolizumab, in adults with advanced malignancies. Data from NEON-1 will be presented at the upcoming American Association for Cancer Research (AACR) Annual Meeting in New Orleans on April 12.

About Davoceticept (ALPN-202)

Davoceticept (ALPN-202) is a first-in-class, conditional CD28 costimulator and dual checkpoint inhibitor intended for the treatment of cancer. Preclinical studies of davoceticept have successfully demonstrated superior efficacy in tumor models compared to checkpoint inhibition alone. Completion of dose escalation and initiation of expansion cohorts of NEON-1 (NCT04186637), a Phase 1 monotherapy dose escalation and expansion trial in patients with advanced malignancies, is anticipated in the first half of 2022. NEON-2 (NCT04920383), a combination study of davoceticept (ALPN-202) and pembrolizumab was initiated in June 2021 and is currently on partial clinical hold.

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

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 our platform technology and potential therapies; the timing of and results from clinical trials; and the potential efficacy, safety profile, future development plans and regulatory success of our product candidates. 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: the impact of the COVID-19 pandemic on our business, research and clinical development plans and timelines and results of operations, including the impact on our clinical trial sites, collaborators, and contractors who act for or on our behalf, may be more severe and prolonged than currently anticipated; clinical trials may not demonstrate safety and efficacy of any of our product candidates; the partial clinical hold on our NEON-2 study may not be lifted in a timely manner or at all; our ongoing discovery and preclinical efforts may not yield additional product candidates; our discovery-stage and preclinical programs may not advance into the clinic or result in approved products; any of our product candidates may fail in development, may not receive required regulatory approvals, or may be delayed to a point where they are not commercially viable; we may not achieve additional milestones in our proprietary or partnered programs; the impact of competition; adverse conditions in the general domestic and global economic markets; as well as the other risks identified in our filings with the Securities and Exchange Commission. These forward-looking statements speak only as of the date hereof and we undertake no obligation to update forward-looking statements, and readers are cautioned not to place undue reliance on such forward-looking statements.

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