- ALPN-303 demonstrates superior immunomodulatory activity and efficacy in preclinical models -

- Phase 1 study to begin Q4 2021 -

Alpine Immune Sciences, Inc. (NASDAQ: ALPN), a leading clinical-stage immunotherapy company, today announced a presentation in a Plenary session of the American College of Rheumatology (ACR) Convergence 2021 Annual Meeting. The oral presentation will highlight the preclinical development of ALPN-303, an engineered dual BAFF/APRIL inhibitor being developed for B cell-related diseases such as systemic lupus erythematosus.

The presentation will highlight preclinical data that suggest a best-in-class profile compared to wild-type TACI-Fc:

• ALPN-303 inhibits the activity of the B cell cytokines APRIL and BAFF with greater than 5-fold greater potency in vitro;
• In mice, ALPN-303 exhibits superior pharmacodynamics, including greater suppression of T-dependent antibody production and reduction of B cell populations, such as follicular B cells;
• In cynomolgus monkeys, ALPN-303 is well tolerated and exhibits nearly 3-fold greater serum exposure, accompanied by a greater than 2.5X maximal percent reduction from baseline in serum immunoglobulins (IgG, IgM, IgA); and
• In a mouse model of lupus, ALPN-303 treatment significantly suppresses anti-double stranded DNA antibody titers, inflammation in the kidneys (glomerulonephritis), while preserving renal function and improving survival.

“These findings reinforce the data we presented earlier this year at EULAR, and continue to suggest that ALPN-303 may prove to be a superior therapy for many severe diseases like lupus,” noted Stanford Peng, M.D., Ph.D., President and Head of R&D at Alpine. “We look forward to initiating enrollment in its first-in-human study in adult healthy volunteers later this quarter, and thereby enable rapid advancement of this novel, potentially best-in-class therapy in multiple indications.”

The abstract titled “ALPN-303, an Enhanced, Potent Dual BAFF/APRIL Antagonist Engineered by Directed Evolution for the Treatment of Systemic Lupus Erythematosus (SLE) and Other B Cell-Related Diseases”, can be found here. A copy of the presentation will be available on the “Scientific Publications” page of the Alpine 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 (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.

About the Phase 1 Study

The Phase 1, randomized, placebo-controlled study in healthy adult participants 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

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 preclinical development activities, clinical and regulatory objectives and the timing thereof, expectations regarding the sufficiency of cash combined with the $45 million in achieved and the potential additional $30 million in pre-option exercise milestones payable under our option and license agreement with AbbVie to fund operations through 2023, the potential efficacy, safety profile, future development plans, addressable market, regulatory success, and commercial potential of our product candidates, our ability to achieve additional milestones in our collaboration with AbbVie, the progress and potential of our other ongoing development programs, the timing of our public presentations and potential publication of future clinical data, the efficacy of our clinical trial designs, anticipated enrollment in our clinical trials and the timing thereof, expectations regarding our ongoing collaborations, and our ability to successfully develop and achieve milestones in our development programs. 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; 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.

“SIP” and “TIP,” and the Alpine logo are registered trademarks or trademarks of Alpine Immune Sciences, Inc. in various jurisdictions.

Alpine Immune Sciences, Inc.

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