Antibody-based therapeutics have come to dominate modern medicine in recent years, and according to the Financial Post, six of the top 10 most innovative drugs globally in 2016 were antibody-related molecules. The Canadian biomedical sector hosts a number of companies advancing the field, and a notable example is the Vancouver-based group Zymeworks.
Zymeworks is a clinical-stage biopharmaceutical group developing multifunctional therapies for a variety of cancer types. New therapies are developed through their three proprietary drug development platforms, which have different modes of action against cancer cells. The group’s suite of complementary platforms provides engineers with the freedom to design highly differentiated drug candidates in a speedy and cost-effective manner.
Antibodies are proteins made by the immune system that bind to specific markers on cells or other tissues and can help the body fight all sorts of diseases including cancer.
One of Zymeworks’ biggest selling points is their Azymetric platform, which enables scientists to transform monospecific antibodies, which only bind to one target, into bispecific and multispecific antibodies. These modified antibodies can simultaneously bind to multiple different disease targets, and that could pave the way for treatments that block multiple signalling pathways found in a range of conditions.
“It is an exciting time for the field of bispecific and multispecific therapeutics with candidates like ZW25 (Zymeworks’ flagship drug candidate) demonstrating great promise in clinical trials,” said President and CEO Ali Tehrani to Business Wire.
Zymeworks is now one of the biggest and fastest-growing biotechnology companies in Canada, with a market capitalization exceeding $1 billion. They are part of a growing sector in the Canadian economy and are contributing towards establishing the country as a hub for biomedical innovation.
Lead drug candidate ZW25 is in clinical trials
Zymeworks’ lead drug candidate is ZW25, a novel Azymetric bispecific antibody that is currently undergoing both Phase 1 and Phase 2 clinical trials in different locations around the world. Scientists are evaluating its use for patients with HER2-overexpressing cancers like biliary tract, gastroesophageal adenocarcinomas, breast, and other tumours.
The job of the HER2 gene (human epidermal growth factor receptor 2) is to control a protein on the surface of cells that stimulates growth. If there are changes to the HER2 gene, it can aid the development of cancer, and approximately 1-in-5 breast cancer cases involve the overexpression of HER2.
ZW25 is designed to attach to two different parts of the HER2 protein with the goal of removing the protein from cancer cells, which would in turn boost the immune system’s capacity to destroy these cells and slow the growth of cancer.
In the US, the FDA granted ZW25 a Breakthrough Therapy designation for biliary tract cancer as well as a Fast Track designation for first-line gastroesophageal adenocarcinoma packaged with chemotherapy as a dual treatment. Phase 2 trials for ZW25 are currently underway.
A HER-2 drug for when existing treatments fail
ADCs are a class of anti-cancer drugs in which an antibody is chemically connected to a small molecule drug. They precisely target tumour cells and avoid the dangerous toxicities associated with cancer therapies while also improving their efficacy. ADCs contain three main components: the antibody that targets specific cells, the cytotoxin (cell killer), and a linker that connects the two.
ZW49 was created using ZymeLink, an ADC platform containing a library of proprietary cytotoxins, stable linkers, and conjugation technologies. It builds upon the design and antibody framework of ZW25 coupled to a proprietary cytotoxin via cleavable linker, meaning the ADC has a specific release mechanism for the toxic payload when it reaches the target site.
The release mechanism is activated when the linker comes into contact with a specific protease, a naturally occurring enzyme in our body that breaks down other proteins and helps with recycling. Proteases can distribute throughout the body in a non-uniform fashion, and because of this, the linker only breaks in the areas of the body where this particular protease is abundant.
ZW49 is currently under Phase 1 evaluation as a treatment for patients with locally advanced HER2-related cancers that have progressed in spite of treatment with existing therapies.
Lastly, the EFECT platform manages the immunogenic adverse effects (a negative response from the patient’s immune system, which could range from a mild, itchy rash to something serious like anaphylaxis) of the bi- and multispecific antibodies. The platform features a library of modifications to the constant region of the antibody not involved in binding called the Fc region; these modifications are designed to activate or suppress the antibody-mediated immune response.
Zymeworks has a deep pipeline of preclinical candidates and discovery-stage programs in therapeutic areas like immuno-oncology. The suite of platforms has been further capitalized on through multiple strategic partnerships with leading international biopharmaceutical companies. Zymeworks’ list of corporate partners includes 9 pharmaceutical companies investigating over 46 potential therapeutics.
Canada as a hub for biomedical innovation
The Canadian biomedical sector is experiencing a boom and presents lucrative opportunities for investors. To discuss the state of the industry and the exciting potential, the Globe and Mail invited industry leaders including Tehrani to a virtual summit in November 2020.
At the summit, Tehrani expressed his commitment to developing a competitive biotech ecosystem in Canada that would keep skilled talent at home and inspire emigrants to return. This would create jobs, hone future leaders, and create more opportunities for biotech spinoffs, he added.
Brian Bloom, CEO of the investment bank Bloom Burton & Co, noted that investment in Canadian biotech is up 75% compared to 2019 and that companies raised a total of $3.2 billion in 2020. While Canada is not leading the global charge in biotech, we are excelling in subfields like regenerative medicine, immunotherapy, and targeted therapies.
For Tehrani and his team, they’ve come a long way since Zymeworks was founded in 2003: “We are a case study in tenacity. When we started, it was the world of a thousand ‘no’s,’” said Tehrani to BDC. “Now that we have close to $8 billion in potential pharma deals and two wholly-owned drugs undergoing clinical trials, it is easier for everyone to care.”