Alpine and Merck Study Checkpoint, Anti-PD-1 Cancer Combo in Collab Study


Clinical-stage immunotherapy company Alpine Immune Sciences has entered into a collaboration agreement with Merck to evaluate the efficacy and safety of Alpine’s checkpoint in combination with Merk’s anti-PD-1 therapy in cancer.

The new clinical trial collaboration and supply agreement will evaluate Alpine’s dual checkpoint inhibitor and first-in-class conditional CD28 costimulator, ALPN-202, with Merck’s anti-PD-1 therapy KEYTRUDA® (pembrolizumab) in the NEON-2 trial. The study, which swiftly follows NEON-1, started its dosing phase in June.

According to Alpine’s President and Head of R&D, Stanford Peng, M.D., Ph.D., the study “will provide insights across a broad spectrum of cancers and lines of therapy.” Dr. Peng added that “prior preclinical studies demonstrated that the combination of ALPN-202 and a PD-1 inhibitor can be particularly advantageous, and this collaboration will greatly enable our ability to pursue this opportunity in the clinic.”

Yesterday, Merck announced the European Commission (EC) approved KEYTRUDA in combination with platinum- and fluoropyrimidine-based chemotherapy as an initial therapy regimen for locally advanced unresectable or metastatic carcinoma of the esophagus or human epidermal growth factor receptor 2-negative gastroesophageal junction adenocarcinoma in patients with tumors expressing PD-L1.

The Phase III KEYNOTE-590 trial, which showed the combination therapy significantly improved survival in these patients, formed the basis of the EC approval of KEYTRUDA. The approval now allows the KEYTRUDA combination to be marketed in all 27 European Union member states, in addition to Lichtenstein, Iceland, Norway and Northern Ireland.

In addition to Alpine’s focus on cancer, the Seattle-based company has also been centering its research efforts on lupus. Last week, the company announced it dosed its first patient in the Phase II ALPN-101 clinical trial, a study focused on patients with Systemic Lupus Erythematosus (SLE).

Alpine said in the ALPN-101 announcement that the company had also achieved $45 million in pre-option exercise development milestones, which was part of an Option and License Agreement with AbbVie set in 2020. The two companies inked an $865 million deal in June 2020 to license a drug for lupus, in addition to other inflammatory diseases.

Under terms of the deal with AbbVie, Alpine received an upfront payment of $60 million and became eligible for a $805 million in option- and success-based development, regulatory and commercial milestones. The company was also made eligible to receive tiered royalties on net sales of the lupus drug, once approved.

“AbbVie is an ideal partner for ALPN-101, with the therapeutic area expertise, R&D commitment, and global resources needed to maximize ALPN-101’s potential for patients suffering from autoimmune diseases,” said Alpine’s executive chairman and chief executive officer, Mitchell H. Gold, in a statement on the deal. “Today’s agreement validates our unique Directed Evolution platform that has yielded multiple product candidates, including ALPN-101.”

A poster presented at last year’s European League Against Rheumatism (EULAR) E-Congress by the company showed ALPN-101 was safe and demonstrated desirable dose dependence in healthy adults.

Alpine’s first-in-class, conditional CD28 costimulator and dual checkpoint inhibitor, ALPN-202, also demonstrated an ability to overcome T-cell suppression and improve the durability of engineered T-cell anti-tumor responses, according to a poster presentation presented at last year’s AACR Virtual Annual Meeting. Updated data presented at the 2021 ASCO Virtual Annual Meeting showed many patients with tumors non-responsive to immunotherapies derived clinical benefit with ALPN-202.

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