Jazz and Zymeworks enter exclusive zanidatamab agreement

Jazz Pharmaceuticals and Zymeworks, Inc. have announced that Jazz and Zymeworks BC, Inc. (a Zymeworks subsidiary) have entered into a licensing agreement, under which Jazz is to acquire the exclusive development and commercialisation rights to Zymeworks’ zanidatamab across all indications in the US, Europe, Japan, and all other territories – except for those Asia Pacific territories previously licensed by Zymeworks.

In what is a further expansion of Jazz’s oncology portfolio – following a $1.3 billion licensing agreement with Werewolf Therapeutics earlier this year to acquire its first immuno-oncology candidate – Zymeworks will receive $50 million as an upfront payment, with a second payment of $325 million to follow at Jazz’s option, as well as further potential regulatory and commercial milestones for total potential payments of up to $1.76 billion (plus royalties on net sales).

These include up to a $525 million eligible payment to Zymeworks upon the achievement of certain regulatory milestones and up to $862.5 million in potential commercial milestone payments. And, pending approval, Zymeworks is eligible to receive tiered royalties between 10% and 20% on Jazz’s net sales.

Zanidatamab is an HER2-targeted bispecific antibody with multiple novel mechanisms of action that has demonstrated ‘compelling’ anti-tumour activity in several HER2-expressing cancers, operating both as a monotherapy and in combination with chemotherapy and other agents.

Currently in pivotal trials as a second-line treatment for HER2-expressing biliary tract cancer (BTC) and as a first-line treatment for HER2-positive gastroesophageal adenocarcinoma (GEA), the FDA has granted zanidatamab Breakthrough Therapy designation for BTC (for which no HER2-targeted therapies are currently approved) in those patients who have previously been treated for HER2 gene-amplified BTC. The FDA has granted Fast Track designations for zanidatamab as a single agent for refractory BTC, and as a combination with standard of care chemotherapy for first-line GEA.

Zanidatamab is based on Zymeworks’ Azymetric platform. It can simultaneously bind two non-overlapping epitopes of HER2 (known as ‘biparatopic binding’) and result in such novel mechanisms of action as dual HER2 signal blockade and removal of HER2 protein from the cell surface – this potent effector function leading to encouraging anti-tumour activity in patients.

Top-line clinical data for zanidatamab in BTC (HERIZON-BTC-01) is expected by the end of this year and is hoped to provide a foundational HER2-targeted therapy for patients with difficult-to-treat cancers who currently have limited treatment options.

MD, MSCE, and executive vice president, global head of research and development at Jazz Pharmaceuticals, Rob Ionnone, said: “Zanidatamab is a novel HER2-targeted bispecific antibody with biparatopic binding and the potential to transform the current standard of care in multiple HER2 expressing cancers. This agreement reflects Jazz’s strategic focus on opportunities where we cannot only apply advanced technologies to address critical unmet patient needs, but where we can also leverage Jazz’s existing integrated capabilities and global infrastructure to commercialise efficiently.”

Under ‘Vision 2025’, Jazz aims to deliver at minimum five novel therapies to patients by the end of the decade.

Kenneth Galbraith, chair and CEO of Zymeworks, said: “In partnering with Jazz, we are thrilled to be working with a leading global biopharmaceutical team that brings a wealth of development and commercial experience in oncology and shares our vision and passion for working hard every day to improve outcomes for cancer patients around the world.”

Closing of the agreement is subject to expiration or termination of the waiting period under the Hart-Scott-Rodino Act of 1976. The transaction is expected to close within the 2022 calendar year.

The move comes close on the heels of news of Gilead Sciences’ $60 million upfront payment for licensing of a bispecific antibody from MacroGenics (MGD024), in development as a treatment for CD123-positive blood cancers, including acute myeloid leukaemia (AML) and myelodysplastic syndromes (MDS).