Drug discovery partnership leads to lucrative agreement

November 01, 2012 — Ottawa, Ontario

"NRC’s data helped us convince Merck that we had a viable platform. Without that data, the deal would not have happened."

David Tucker,
COO, Zymeworks Inc.

A young Canadian biotech company has landed a lucrative agreement with a pharmaceutical giant, for a therapeutics platform developed using its "virtual" drug development technology.

Using a unique approach based on computer modelling — and backed by a large and experienced team of NRC researchers — Vancouver-based Zymeworks Inc. has developed a novel antibody platform technology that produces "bi-specific" or Azymetric™ antibodies capable of binding to two disease targets at once.

These new antibodies could be used to treat a range of conditions including cancer, inflammation and autoimmune diseases.

Last year, the company announced a strategic collaboration with the global pharmaceutical company Merck & Co., worth up to US$187 million. Zymeworks’ Chief Operating Officer David Tucker says the company’s relationship with NRC was instrumental in reaching an agreement with Merck.

"NRC’s data helped us convince Merck that we had a viable platform," says Tucker. "Without that data, the deal would not have happened."

NRC has been helping Zymeworks by producing, purifying and testing its antibodies, and playing a key role in proof-of-concept studies needed to validate the company’s approach.

In 2009, the company asked NRC to validate the results of its "virtual" protein engineering platform in a laboratory setting. Zymeworks takes a protein — an antibody for example — looks at its structure with a computer model and then predicts the impact of mutations such as how well the altered protein will bind to another molecule.

Zymeworks gives NRC the DNA sequence for the protein, which NRC produces. NRC then verifies the impact of the designed changes by testing and analyzing the new protein’s characteristics such as its binding affinity and stability.

"NRC has a very diverse set of capabilities necessary for the testing and development of therapeutic proteins, together with knowledgeable and professional staff. This makes them an ideal partner to complement our computational protein engineering capabilities."

David Tucker
COO, Zymeworks Inc.

"So far, we’ve done this for a large number of protein variants," says Dr. Maureen O’Connor, the NRC scientific lead. "This represents thousands of hours in laboratory and technical staff time, and the handling of enormous quantities of data."

NRC is also now conducting manufacturing studies and examining the "pharmacokinetics" of these molecules (how they behave in a living body). This work has allowed NRC to demonstrate the viability of Zymeworks’ design platforms and help it foster additional strategic collaborations.

One of Zymeworks’ four main products is a bi-specific antibody platform, which "allows our partners to put two different ‘warheads’ on a single antibody," says Tucker. While traditional antibodies can only target one antigen at a time, the dual "warheads" could simultaneously target two different disease antigens – representing a new way to treat patients. Alternatively, Zymeworks’ bi-specific antibodies can bind to two "epitopes" or handles on a single molecule, thereby improving the binding capability of the antibody to its target.

NRC and Zymeworks plan to continue working together. For example, the partners are developing new therapeutic candidates and working to combine NRC’s proprietary ‘warheads’ with Zymeworks’ antibody platform. "If this yields commercially promising results, then we plan to explore co-developing drug candidates from this research," says NRC business development officer, April Luong.

"Zymeworks’ Azymetric™ platform allows our partners to put two different disease ‘warheads’ on a single antibody."

David Tucker
COO, Zymeworks Inc.

Bi-specific antibodies and antigens

Normal human antibodies are Y-shaped proteins with two identical arms that are used by the immune system to identify and neutralize objects that have invaded the body. The antibody works by recognizing and binding to a unique part of the invader (known as an antigen). Each tip of the "Y" of an antibody contains a structure that locks on to the antigen target, binding the two molecules together.

Using its Azymetric™ technology platform, Zymeworks produces stable antibodies with two different "Y" arms engineered into a single antibody molecule that can bind to two different antigens or drug targets. These antibodies could be used to combat a range of conditions including cancer, inflammation and autoimmune diseases.

More information

Did you know?
NRC provides a "one stop shop" of facilities, services and expertise to help biotech companies develop new diagnostic and therapeutic products. We can generate customized antibodies or identify new therapeutic targets. We also offer efficient proprietary protein expression systems; bioprocess development and scale up services to help increase product yields; and systems biology research to provide critical pre-clinical assessment data.

Talk with an expert today about a customized, complex R&D solution for your biotechnology business:

Eileen Raymond
Email: Eileen Raymond
Telephone: 514-496-6349

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