Alpine Immune Sciences Reports FDA Partial Clinical Hold on NEON-2 Trial of Davoceticept (ALPN-202) in Combination with Pembrolizumab

Rhea-AI Summary

Alpine Immune Sciences announced a partial clinical hold on its NEON-2 trial evaluating davoceticept (ALPN-202) in combination with pembrolizumab after a Grade 5 serious adverse event, resulting in patient death. The incident was linked to potential immune-mediated myocarditis. Despite this setback, the ongoing NEON-1 trial of davoceticept as a monotherapy remains unaffected. The company emphasizes patient safety and expects to work with the FDA and partners to resume the NEON-2 trial with safety precautions after review.

Positive

• The NEON-1 trial of davoceticept as a monotherapy remains unaffected by the NEON-2 trial's hold.
• Company expresses strong commitment to patient safety.
• Scientific rationale for davoceticept and pembrolizumab combination remains strong.

Negative

• Partial clinical hold on NEON-2 trial due to a patient death related to treatment.
• Potential delays in resuming the NEON-2 trial could impact future development timelines.

-NEON-1 Study of ALPN-202 as a Monotherapy is Unaffected-

SEATTLE--(BUSINESS WIRE)-- 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 that the U.S. Food and Drug Administration (FDA) has placed a partial clinical hold on its NEON-2 trial evaluating davoceticept (ALPN-202) in combination with pembrolizumab in adults with advanced malignancies.

The partial clinical hold was prompted by Alpine’s report of a Grade 5 serious adverse event (patient death) in the NEON-2 trial. The participant had choroidal melanoma previously treated with nivolumab and ipilimumab, and had received a single dose each of davoceticept and pembrolizumab. The participant’s death was attributed to cardiogenic shock, considered by the treating physicians as likely related to immune-mediated myocarditis, or possibly infection.

“Patient safety remains, as always, our top priority,” said Mitchell H. Gold, Executive Chairman and Chief Executive Officer of Alpine. “We appreciate the dialogue with FDA and look forward to working diligently with FDA, Merck, the study Safety Monitoring Committee, and the study investigators to further understand this unfortunate event. Given the strong scientific rationale for the combination of davoceticept and pembrolizumab to benefit treatment-refractory patients, we are hopeful that the study will soon be resumed after appropriate safety review, and with appropriate safety precautions in place.”

Patients currently enrolled in the NEON-2 trial may continue to receive davoceticept and pembrolizumab, although no additional patients may be enrolled until the partial clinical hold is resolved. The partial clinical hold does not affect the ongoing NEON-1 clinical trial of davoceticept as monotherapy (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. 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 as described above.

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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Investor Relations

Alex Sharif

Director, Investor Relations and Corporate Development

Alpine Immune Sciences, Inc

206-788-4545

ir@alpineimmunesciences.com

Media Relations

Kelli Perkins

Red House

kelli@redhousecomms.com

Source: Alpine Immune Sciences, Inc.

FAQ

What caused the partial clinical hold on ALPN-202's NEON-2 trial?

The FDA placed a partial clinical hold on the NEON-2 trial after a Grade 5 serious adverse event, which was a patient death attributed to possible immune-mediated myocarditis.

Is the NEON-1 trial of davoceticept affected by the NEON-2 trial's hold?

No, the NEON-1 trial of davoceticept as a monotherapy is unaffected by the NEON-2 trial's partial clinical hold.

What is the status of the NEON-2 trial for ALPN-202?

The NEON-2 trial is currently on partial clinical hold until further review and safety measures are established.

What measures is Alpine Immune Sciences taking after the NEON-2 trial's hold?

Alpine is working diligently with the FDA, study Safety Monitoring Committee, and investigators to review the situation and implement safety precautions.