Merck Expands Multispecific Antibody Collaboration with Zymeworks in $900M Deal

Compiled by Keke

Recently, Zymeworks Inc., a Canadian clinical-stage biopharmaceutical company, announced that it has signed a new licensing agreement worth over $900 million with its long-term partner Merck Sharp & Dohme (MSD), granting the latter the rights to use its Azymetric™ and EFECT™ platforms to develop multispecific antibody therapeutic candidates.

Under the new agreement terms, Zymeworks will grant MSD a global, royalty-bearing license to research, develop, and commercialize three novel multispecific antibodies tailored to MSD’s therapeutic targets. In return, Zymeworks will receive an undisclosed upfront payment and, if all three investigational programs gain approval, will be eligible for $411 million in option exercise fees, clinical development and regulatory approval milestone payments, as well as $480 million in commercial milestone payments and tiered royalties on global sales.

Zymeworks and MSD have collaborated since 2011, expanding their partnership in 2014 to include the development of bispecific antibodies. Dr. Scott Lesley, Vice President of Discovery Biology at Merck Research Laboratories, stated, “Zymeworks’ technology plays a critical role in our efforts to identify and develop multispecific antibody therapies. We are pleased to continue collaborating with the Zymeworks team.”

As indicated on the Zymeworks website, the Azymetric™ platform converts monospecific antibodies into bispecific and multispecific antibodies, enabling simultaneous binding to multiple distinct targets and facilitating the development of multifunctional therapeutics. Unlike many other bispecific platforms, Azymetric™ generates fully IgG-like antibodies and is compatible with other target-binding formats (such as Fab, scFv, and VHH) as well as antibody-drug conjugates (see figure below). The EFECT™ platform is a library of engineered antibody Fc modifications designed to activate or inhibit antibody-mediated immune responses. This platform is compatible with both conventional monoclonal antibodies and Azymetric™ bispecific antibodies, further enabling the customization and optimization of therapeutic responses for various diseases.

Zymeworks’ pipeline is dedicated to the development of next-generation multifunctional biotherapeutics. Its lead clinical candidate, ZW25 (zanidatamab), is a HER2-targeted bispecific antibody developed using the Azymetric™ platform. ZW25 simultaneously binds to two distinct epitopes on HER2, a unique design that results in multiple mechanisms of action, including dual HER2 signaling blockade, enhanced antibody binding, receptor clustering, and removal of HER2 from the cell surface with potential effector functions. ZW25 is currently being evaluated in multiple Phase 1, Phase 2, and registration-enabling clinical trials worldwide for the treatment of patients with HER2-expressing cancers, including biliary tract cancer, gastroesophageal adenocarcinoma, breast cancer, and other tumor types. It has received Fast Track designation for two indications: previously treated or recurrent HER2-positive biliary tract cancer, and first-line treatment of gastroesophageal adenocarcinoma in combination with standard-of-care chemotherapy. Additionally, it has been granted Orphan Drug designation for the treatment of biliary tract cancer, gastric cancer, and ovarian cancer.

Another key clinical candidate, ZW49, is a HER2-targeted bispecific antibody-drug conjugate currently in Phase 1 clinical development for the treatment of patients with locally advanced or metastatic HER2-expressing cancers who have progressed after existing therapies, including HER2-targeted agents. The candidate combines the unique design and antibody framework of ZW25 with a linker-cytotoxin from the ZymeLink™ platform, leveraging ZW25’s enhanced antibody-mediated internalization into HER2 to deliver a novel cytotoxic compound, auristatin, to tumor cells.

Both ZW25 and ZW49 have commercialization collaborations with BeiGene, which holds the rights to these two drugs in China, South Korea, Australia, New Zealand, and other East Asian countries (including Japan). In addition, Zymeworks is advancing the development of multiple preclinical candidates in oncology (including immuno-oncology agents) and other therapeutic areas, and has collaborations with Eli Lilly, Celgene, GlaxoSmithKline, and Daiichi Sankyo.

Reference Sources:

1、Merck expands scope of Zymeworks antibody alliance, adding close to $900M in milestones

2、Zymeworks Announces New Multispecific Antibody Collaboration with Merck