Fighting pandemics in a post-vaccine world

But for Dr. Ravi Shankar Singh (PhD’11), senior director of clinical pharmacology & early clinical development with Pfizer, there’s a world beyond vaccines that can expand our available defensive tools against COVID-19 and further protect everyone’s health and wellness.

“We had a very effective vaccine,” Singh said. “But we also needed some therapeutic options so that, if someone is infected, it can be treated. As drug development scientists, we see the suffering all around us and that was a motivation to find a solution.”

Singh has worked with Pfizer since September 2016, and his current position sees him helping to guide the process of drug development — not creating new pharmaceuticals directly, but studying the effects those products have on the human body and vice versa. The result, he says, is a clearer understanding of whether the material is safe for the general public and what dosage is most appropriate during use.

Most recently, Singh was among those at Pfizer who oversaw clinical development of the groundbreaking Paxlovid oral antiviral treatment for COVID-19.

As the first oral antiviral treatment approved by Health Canada for use against COVID-19, Paxlovid — which is actually two co-packaged oral medications named nirmatrelvir and ritonavir — works by preventing the invading virus protein from replicating within the human body. In the process, the treatment buys the immune system more time to fight back early on in the infection.

“It stops the virus by inhibiting an essential enzyme necessary for replication, “ Singh said. “By preventing that replication, it reduces the viral burden.”

Describing this breakthrough medication as an “exciting molecule” even in his early estimation, Singh and associated Pfizer personnel got to work testing the ways in which the antiviral would react if and when it was introduced to human participants.

“We need to understand what the drug does to the body when it is taken by humans,” he said. “You have to understand if it is safe to be given and what the overall level of drug is in humans. That is evaluated in the healthy volunteers, and then we take that data and understand the characteristics of the molecule body before testing in patients.”

Singh’s experience working on COVID-19 may be particularly unique, given the virus’ ongoing influence on global events, but his time at the University of Saskatchewan shows he’s no stranger to research on key issues of the modern age.

Working under his supervisors, Singh’s PhD program at the USask saw him testing the boundaries at the forefront of anti-cancer research.

“Obviously, when you've got a new anti-cancer agent, you can't start poking this into patients and there's a great deal of preliminary work,” said Dr. Jonathan Dimmock (PhD), professor emeritus with the USask College of Pharmacy and Nutrition and one of Singh’s co-supervisors. He describes Singh’s role as similar to what he would later take on with Pfizer — finding out what would happen once a new compound was introduced into experimental contexts.

“What was happening to it? Was it remaining unchanged in the body? Or is it breaking down to bioactive metabolites and so forth?”

Dimmock speaks of Singh in glowing terms, expressing no surprise that his former student would go on to work on prominent projects after transitioning into his professional career.

“He was a luminary from Day 1,” Dimmock said. “He was an exemplary graduate student picking up ideas very quickly. I thought wherever he went he would distinguish himself.

“He's a person of unusual ability.”

Dr. Jane Alcorn (DVM, PhD), professor and dean USask's College of Pharmacy and Nutrition, was similarly impressed by Singh — even taking notice of his merit long before meeting him based on the wealth of experience on the curriculum vitae that accompanied his application for PhD study.

“He was a potentially strong student,” Alcorn said of Singh’s experience, which even before his application was submitted and included work with research institutes in India and hands-on preclinical experience in the pharmaceutical industry.

“There were things he still had yet to develop, but the skills within the lab itself were things that I think he had already pre-developed when he came to Saskatoon.”

Key to Alcorn’s positive impression of Singh was the way he handled himself in the research environment, building on his prior academic and professional accomplishments to pick up new concepts and maintain an easy autonomy with only essential oversight.

“He had a lot of experiences to draw upon and a number of skills that spoke to his ability to be independent within the lab study,” Alcorn said. “You might nudge him in a certain direction, but then he takes it and you don't need to provide much more support because he figures it out.”

This feeling of liberty is one that Singh recalls fondly from his time at USask, counting his mentors’ trust and the opportunity they afforded him among the foremost influences on his development through to this day.

“Everyone was very encouraging, and the independence that you get — not trying to handhold, but really helping you to become an independent researcher and giving you the freedom of thinking and coming up with your own ideas,” Singh said. “Those are important aspects of my growth as a person and as a researcher.”

Singh’s interest in medicine stretches back to his youth in India, where an education in pharmacy would lead him to discover the ways in which lab-based study can influence the world of health care.

“Out of pharmacy, I saw that we were developing some things which would help people,” Singh said. “I saw myself as developing tools that help doctors to deal with deadly diseases, and in that way we are also helping the patients.”

Being a part of the team developing much-needed medication in the fight against a global pandemic is a reality that Singh doesn’t take lightly, remembering the emotional moment when he learned Paxlovid would make its introduction to the world at large.

“We had been putting everything into this drug and it could have failed, but we were fortunate that it was effective,” he said. “I’m not sure I’ll have a chance to repeat this in my future — and I hope that I don’t have to repeat it, that this pandemic ends and that nothing else comes that makes us do the same things — but this was very exciting.”

“This is a lifetime achievement for me.”