Originally announced in January 2014, a global strategic collaboration between Eli Lilly and Company and Zymeworks Inc. focused on the development of an undisclosed number of novel bi-specific antibody therapeutics using Zymeworks’ proprietary Azymetric™ platform.

The Zymeworks’ Azymetric™ platform is an IgG1-based heterodimeric antibody scaffold that consist of two different heavy chains engineered to exclusively assemble into a single molecule. This allows bi-specific binding to two different antigens or drug targets.

Azymetric was developed by engineering proprietary amino acid changes in the CH3 region of the constant Fc domain of a native IgG1 class antibody. Aside from bi-specificity, the advantages of the Azymetric™ Scaffold include tailored effector function and optimized serum half-life.

Bi-specific antibodies have the potential to provide improved outcomes for patients by simultaneously targeting two proteins resulting in additive or synergistic responses. This approach is especially interesting in the development of anti-cancer drug because bi-specific antibody therapeutics potentially scientists to combine two existing cytotoxic drugs used as a cocktail into one therapeutic.

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Based on the new agreement, Lilly expand the collaboration by up to potentially US $375 million in milestones and other payments, plus tiered sales royalties based on country-by-country intellectual property, and sales to include development of several immuno-modulatory bi-specific antibodies against multiple targets.

Zymeworks receives an initial up-front payment in the form of an equity investment, which will strengthen the strategic relationship between the two companies. The majority of financial terms consist of potential milestone payments contingent on the achievement of certain development and commercial milestone events predominantly focused on the United States, Japan and global sales.

“We are pleased to expand our collaboration with Zymeworks to develop potential immunotherapies for those fighting cancer around the world. There are many targets involved in the controlled activation and redirection of the immune system and we know that immunotherapies will not be a one-size-fits-all treatment,” explained Sue Mahony, senior vice president and president, Lilly Oncology. “In addition to immunotherapy programs, Lilly has a robust oncology pipeline that includes both small molecules and monoclonal antibodies, which are being studied to treat a wide range of cancers.”

“Lilly is a global pharmaceutical company and we are delighted to expand our collaboration to develop novel bi-specific immunotherapies. This expansion of our strategic collaboration speaks to the robustness of our Azymetric™ platform for the development of innovative biologics,” said Ali Tehrani, president and CEO of Zymeworks. “Lilly’s investment in Zymeworks also highlights the strength and promise of our oncology-focused pipeline candidates in helping patients with significant unmet medical needs.”

This collaboration with Zymeworks adds to Lilly’s bi-specific antibody and immunotherapy research portfolio. In July 2014, Lilly also announced an agreement to co-discover and co-develop novel cancer therapies with Immunocore, a privately owned, clinical-stage, UK-based biotechnology company, focused on the discovery and development of novel T-cell receptor-based drugs to treat cancer and viral disease.

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