that he doesn’t want to be pigeonholed, or for people to think he’s merely running a contract shop for the Whitehouse Station, NJ-based pharma giant. The alliance is structured as a non-exclusive deal, so that Zymeworks owns the protein engineering technology, and Merck has the right to use it to develop a certain number of drugs against a certain number of targets. As part of the $11 million financing, Zymeworks will invest in its own internal cancer drug candidate that it hopes to drive into clinical trials by late 2014, Tehrani says. And the company expects to announce “more Merck-type deals” that provide access to the technology for specific drug development uses, but with more lucrative financial terms for Zymeworks because of the progress the technology has made, he says.
“The Merck deal wasn’t a fluke or a one-off,” Tehrani says. “If you have a best-in-class technology, others should want to come to the table.” He adds that because of the value placed on trusting relationships in biotech, it’s possible to get a single partnership on a relationship and chalk it up to luck. Getting a second partnership provides further validation. Getting a third, he says, should prove that “in terms of structure guided protein engineering, we are one of the best.”
Without going too deep into the science, here’s the basic gist of what Zymeworks is attempting to do. Most companies seeking to make bispecific antibodies start with the DNA sequence for making a conventional Y-shaped antibody that can hit one target, and use a chemical linker to attach another molecular binder. That technique is what’s known as a homodimeric approach, Tehrani says.
Zymeworks, by contrast, is seeking to make engineered antibodies a different way, through a heterodimeric process. This technique essentially creates a single Y-shaped antibody in which each half can bind with a distinct molecular target, without the need to attach any other molecule. That means the heterodimeric bispecifics should behave in the body more like conventional antibodies, and should be easy to scale up and manufacture for similar cost, Tehrani says. A homodimeric antibody, he says, is analogous to having a third arm added to a person’s back, which might be useful for grabbing things, but which also would throw off a person’s gait, and make it harder to sleep. A heterodimeric antibody would be a little more like keeping both arms intact, but engineering in some new skill for both the left and right hands.
Since this is still science in the early stages, plenty is still unknown and plenty can go wrong. Tehrani acknowledges all the risk, but he was also brimming with optimism when we met yesterday morning in Seattle, discussing how far Zymeworks has come in the past year.
“We have the IP (intellectual property), we have a pharmaceutical collaboration, we have money,” Tehrani says. “We have the main ingredients to move forward.”
