Flu fighter

By Prasanthi Vasanthakumar

In 1987, Les Tari was playing in an intramural hockey game at UM when he met his soon-to-be PhD supervisor. The second-year chemistry student didn’t know who Professor Anthony Secco was at the time, but after the game the pair got to chatting about structural biology.

Secco invited Tari to his lab to learn more about his work on X-ray crystallography, a method that shows the three-dimensional structure of matter.

“It blew my mind,” says Tari [BSc/89, PhD/95]. “I thought, ‘Wow, that is amazing. I want to understand that more.’” He went on to do his honours project and PhD with Secco. For Tari, it was “a life-changing connection.”

That was nearly 40 years ago. Today, Tari is spearheading life-changing drug discoveries. As Chief Scientific Officer at San Diego-based biotechnology company Cidara Therapeutics, his latest drug development is a flu antiviral. The flu kills up to 650,000 people worldwide each year. In Canada alone, influenza is linked to an estimated 3,500 deaths and 15,000 hospitalizations annually. But many brush it off as a seasonal nuisance.

“People acknowledge that [the flu] sucks, but I don’t think people realize just how dangerous [it is],” says Tari.

Vaccines are the best defence against many infectious diseases, but in the case of the flu, they are an imperfect science. That’s because the flu virus is a shapeshifter: it mutates rapidly, making it hard for vaccines to keep up. As researchers use influenza strains circulating in the southern hemisphere’s flu season to predict which variants will dominate ours in six months—predictions that inform the vaccine’s formulation—the flu virus has time to change.

“You might see protective efficacy ranging from 30 to 60 per cent … so the vaccine, it’s really a crapshoot as to whether it’s going to be matched to the strains that are circulating [in our flu season],” explains Tari. Still, health experts encourage Canadians to get their annual flu shots because they help prevent severe outcomes. But the vaccine’s gaps inspired Tari and his team to find a better solution.

What they came up with is an antiviral that binds to a specific spot of the flu virus that does not morph over time—its “Achilles heel,” as Tari puts it. The drug then blocks the virus from infecting other cells, despite the strain. Because it doesn’t rely on the immune system, the antiviral should theoretically be effective in everyone, including higher-risk populations like the elderly. All it should take is one dose per flu season for six months of protection.

Seeing the drug’s potential, pharmaceutical giant Merck acquired Cidara Therapeutics earlier this year in a $9.2-billion deal. The U.S. government is also betting big on the preventive treatment: it has already allocated $339 million to the project as a part of its pandemic preparedness. As Merck takes the drug across the finish line, it could become widely available in the next few years.

This flu antiviral isn’t Tari’s first success story. Over the past 25 years, he has had a hand in developing antibacterial agents and a drug for Type 2 diabetes, among others. But even today, he connects his success back to UM. “I credit [Professor Secco] with teaching me scientific rigour, work ethic, persistence and getting me on to some exciting research that led me here.”

This mentorship is something Tari, who grew up in Winnipeg, values in Canadian academia. Like him, many of his friends and colleagues were drawn into graduate school by professors they met as undergraduates. “There’s a lot more of that [mentorship] in the Canadian system,” he says. “I love … [that] you have these high-quality universities in your hometown.”

Tari himself had a brief stint in academia as a professor at the University of Calgary. He says academic research is crucial because it underpins many drug discoveries, especially for rare diseases that draw little investor interest: “You have complete freedom to pursue what you want to pursue.” 

But he was always drawn to the applied side of the discipline and the opportunity to make new therapies that could change lives—something that takes a “ton of money.” After unknowingly scooping a competitor in California with a paper he published while at the U of Calgary, Tari got an invite from said competitor, Duncan McRee, of the Scripps Research institute, to join the pharmaceutical firm he was building in 2001. Tari packed his bags for sunny San Diego.

California’s biotech sector is buzzing. In 2024, the San Diego region’s life science industry contributed US$54.1 billion in total economic output. “There’s just so much opportunity and money flowing into San Diego for startup biotech companies,” says Tari, who had an equity stake in Cidara, which is standard practice in the field to incentivize employees.

Cidara Therapeutics is the fourth company Tari has been a part of since his move south.

“Making a drug takes a village,” he says. “It’s exciting to be with people who have the same vision and the same goal to do these big, risky, exciting undertakings that can transform human health.”

While drug discovery can be euphoric, it is not without challenges. In Tari’s experience, biotech is risky business, where job security is non-existent, team cohesion is essential and failure is inevitable. Choosing the right drugs to pursue is half the battle because an idea must have the potential to be profitable. Even when companies drum up investor interest, time and money can run out. In this respect, every company Tari has worked at has had its ups and downs.

“You have to be persistent,” Tari says. “Don’t dwell on the failures, because they will happen. And don’t lack self-confidence. If you don’t do it, who will?”