A Paradigm Shift in Therapeutic Research

Zymeworks president Ali Tehrani explains the company’s role in changing the way drugs are designed

Although Ali Tehrani has a master’s degree in biochemistry and a PhD in microbiology and immunology, he realized that conducting research was not for him. “I realized my strength was in being the voice for the scientists doing the research,” he explains. “In the world of innovation, you need the innovator as well as the person who is promoting and finding funding for the research. That was where I belonged.”

In 2004, Tehrani cofounded Zymeworks (the “Zyme” comes from “enzyme”) in Vancouver, British Columbia. “After I got my PhD, I was deciding what to do next,” he says. “Investors asked me to look at some projects. But I could see there was a bigger opportunity—an opportunity to develop a rational, more intelligent drug design process.” Tehrani describes Zymeworks as a leader and top innovator in protein modeling and protein engineering. The company initially focused on industrial biotechnology applications in areas such as paper pulp and food—for example, using enzyme-based bleaching of paper pulp versus chemical bleaching.

But the company’s leadership could see that Zymeworks would never have its own products; it would always be part of a process. As a result, the focus shifted to protein-based therapeutic applications. “We’re modifying the functionality of proteins,” Tehrani explains. “We look at the top players in the human immune system, such as antibodies, and make them more specific, more effective, in order to develop medications that meet the unmet needs of patients.”

Zymeworks now focuses on immuno-oncology, using the immune system to fight cancer. “Antibodies are the soldiers of the immune system. They typically work on a 1:1 basis—one antibody to one foreign entity,” he says. “With our Azymetric platform, we can engineer it so that one antibody can recognize two different foreign entities or antigens. That makes it more specific—and more powerful in protecting a person. And we can engineer the Azymetric antibodies so that they’re tailored to recognize cancer cells.”

Tehrani explains that cancer cells are typically “cloaked,” so antibodies can’t find them and cause their destruction. Azymetric antibodies can, in essence, uncloak the cancer cells, making the antibodies more intelligent and powerful. Zymeworks is also using AlbuCORE technology to help albumin proteins do their job more effectively so they too can be used to defeat cancer cells.

Zymeworks is part of a paradigm shift in therapeutics research. As an analogy, Tehrani explains that in the past a builder would construct a building brick by brick and hope it would last for years. Then a hurricane would come along, and the building would collapse. Nowadays, buildings are designed by computers and heavily tested before construction begins. Likewise, in the old days, drug development was rather scattershot. When new drugs were in development, researchers had to guess which compounds seemed most likely to work and then would test those in the lab. It was a flawed system that often ended up wasting many resources. Today, the world is demanding more intelligent drug design.

“We combine high-tech and drug design,” he notes, explaining Zymeworks’ digitization of the drug development process. “We take large numbers of permutations in drug development and narrow them down to those with the best probabilities, then we test only those in the lab. Our goal is to develop a product that is better through a process that is cheaper—and to get the products to market faster. Through our ZymeCAD technology, we develop a better understanding of a target disease, a drug, and how they interact. By being able to visualize it and study it, we’re able to manipulate it.”

Tehrani notes that in the past it would take eight to fifteen years to get a drug to patients. They’re cutting that by one-third, or even one-half. “Intelligent drug design benefits patients and the community,” he adds.

The company’s lead drug under development, ZW25, is used to treat breast cancer. It is in adaptive Phase l clinical trials, and if all goes as expected, the drug should be available to the public in 2021.

Tehrani describes the corporate culture at Zymeworks as “lead, follow, or get out of the way.” He feels a leader is someone who paves a path, inspires others, and makes others look good when a job is accomplished. “We try to create a culture of leaders here,” he says. “It’s better to do it right rather than to do it faster. People’s lives depend on how we do our jobs.” He describes his role as president of the company as being the visionary and strategist who ensures that the company is relevant, exciting, and is generating shareholder value for investors. He says his management strategy is different from most. “I surround myself with very smart specialists, to generate a strategy that takes into account many different points of view,” he says. “I’m on the front lines surrounded by my generals. We execute as a team.”

Zymeworks is currently collaborating with big pharma, and the company’s work has been heavily validated externally. “We have signed deals with Merck, GSK, Eli Lilly, and Celgene,” Tehrani says. “They’re using our technology and capabilities to build next-generation therapeutics. That is rare for a biotech firm. That puts us in the top 10 percent of biotech firms.”

Tehrani knows that work isn’t the only place to find true rewards. Outside of his job, his three passions are being a husband (“my wife is my best friend”), being a dad to his wonderful son, and training with CrossFit. But at the office, he says that the most rewarding aspect of his job is getting to work with some of the smartest people on the planet who are doing what they love—as well as having a positive impact on patients’ lives.

“I read once that you have to look to help people who can never thank you and will never know you,” he says. “That had a big impact on me. Here at Zymeworks, it’s not about the paycheck or the accolades. It’s about making a positive difference and utilizing the time we have on this planet the best way possible.”