- In dose escalation across a range of dose regimens, tumor volume reduction was observed in 23% of evaluable participants despite heavily pretreated, advanced solid malignancies -

- Monotherapy expansion cohorts with multiple tumor types are planned -

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 oral presentation of results from the dose-escalation portion of NEON-1 (NCT04186637), a first-in-human, dose-escalation and expansion study of davoceticept monotherapy in participants with advanced malignancies, at the 2022 Annual Meeting of the American Association for Cancer Research (AACR).

Highlights from the presentation include:

• Despite a highly heterogeneous, heavily pretreated, advanced solid tumor population – the majority classically considered to be unresponsive to immunotherapy – 11 (23%) of 48 evaluable participants demonstrated tumor volume reduction; 26 (54%) achieved clinical benefit as defined as a best response of stable disease or better; Three (6%) remained on treatment beyond 6 months. Two partial responses were observed in colorectal and renal cell carcinoma.
• Davoceticept was well-tolerated with no reported events of cytokine release syndrome. Adverse events of interest included immune-related adverse events and infusion-related reactions, the majority of which were grades 1-2. A single dose-limiting toxicity of gastritis was observed at 3 mg/kg, but a maximum tolerated dose was not reached.
• Immunophenotyping demonstrated favorable increases in activated and central memory T cells, as well as reductions in regulatory T cells. Overall, pharmacodynamic analyses suggest 1 or 3 mg/kg every 3 weeks as the optimal biological dose.
• Monotherapy expansion cohorts in metastatic cutaneous melanoma, renal cell carcinoma, and PD-L1-positive tumors are planned.

“These results indicate that it is indeed feasible to engage CD28 for cancer immunotherapy, and further suggest that this approach may be clinically advantageous, even for heavily pretreated cancers,” remarked Stanford Peng, MD PhD, Alpine’s President and Head of Research and Development. “We eagerly look forward to advancing to expansion cohorts as soon as possible.”

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

About NEON-1

NEON-1 is a first-in-human dose escalation and expansion study of davoceticept monotherapy in advanced malignancies. Dose escalation enrolled adults with advanced solid tumors refractory or resistant to standard therapy, exploring 0.001-10 mg/kg every 1 and/or 3 weeks. Expansion cohorts are planned to include cutaneous melanoma, renal cell carcinoma, or PD-L1-positive tumors at 1 or 3 mg/kg every 3 weeks. Preliminary results were previously reported at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting. More information is available at www.clinicaltrials.gov (NCT04186637).

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. NEON-1 (NCT04186637), a Phase 1 monotherapy dose escalation and expansion trial in advanced malignancies, was initiated in June 2020 and is progressing to expansion cohorts. 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 preclinical development activities; clinical and regulatory objectives and the timing thereof; the potential efficacy, safety profile, future development plans, addressable market, regulatory success, and commercial potential of our product candidates; the efficacy of our clinical trial designs; anticipated enrollment in our clinical trials and the timing thereof; 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: clinical trials may not demonstrate safety and efficacy of any of our product candidates; efforts to have the partial clinical hold on our NEON-2 trial lifted may be prolonged or ultimately unsuccessful; 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; 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; 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.

“NEON-1,” “NEON-2,” "Synergy," and the Alpine logo are registered trademarks or trademarks of Alpine Immune Sciences, Inc. in various jurisdictions.

ALPN-202, NEON-2 study is being conducted in collaboration with Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA

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