What Drug Hunters Wish They’d Known When Starting Out
There is an adage credited to the Greek philosopher Epictetus that Dennis Koester wishes his younger self had learned: "We have two ears and one mouth so that we can listen twice as much as we speak."
"I talk a lot," said Dennis, now a Director of Medicinal Chemistry at FibroGen. "I should listen more. I definitely need to work on that."
Dennis's blunt admission arose during a Drug Hunter Flash Talk webinar. While presenting on drug discovery strategies to optimize unbound brain concentrations in CNS infectious diseases, Dennis Hu asked Koester what lessons he'd learned professionally that he wished he could have understood earlier in his career.
Dennis Hu asks this question of all guests who take part in Drug Hunter's ongoing video series. Their responses vary in topic, but when combined they serve as a masterclass for anyone interested in becoming a more effective and more impactful drug hunter.
Your Time is Valuable
Kaid Harper has spent nearly eight years as a scientist at AbbVie and currently is a Principal Scientist. He spoke about the innovative implementation of photoredox chemistry at scale developed by chemists and engineers at AbbVie.
Kaid started at AbbVie after working as a postdoctoral researcher at Harvard. When he made that professional transition, he developed a new appreciation for time — and how he should spend it.
"Value your time," Kaid said. "The way we train chemists in academia, their time is not as valuable as it is in actuality."
He thinks that “the thing of the greatest value you have" is time, and suggests that young scientists make the transition away from the academic view of time as quickly as possible in their careers.
Andrew Parsons agreed.
Andrew, a Director of Process Development at Amgen, spoke about the development of a commercial manufacturing process for sotorasib, a first-in-class KRASG12C inhibitor. Andrew learned to value his time more during his postdoc at the Massachusetts Institute of Technology, but he wished he developed that appreciation sooner.
"When I was In graduate school, I would say I was a pretty serious student who didn't necessarily pause to enjoy the environment and the people around me," he said. When he became a postdoc, he tried to spend more time developing relationships with his labmates. As a result, he made lifelong friendships.
Mistakes aren't necessarily setbacks if you learn from them
Oliver Ju is Chairman and CEO of Porton Pharma Solutions, a contract development and manufacturing organization. Ju founded the company in 2005 and in 2022, it had 127% revenue growth with more than $1 billion in revenue.
Oliver learned a number of lessons as the company grew, but one he wished he could go back and tell himself at the start was to be wary of something that feels too good to be true.
"I'm a very optimistic person," Oliver said. "Don't be over-optimistic. As a business, there are a lot of risks. When I was young, I would always see opportunity. You have to see the risks."
Dennis Koester also thinks it’s important to understand that in life — and particularly in drug discovery — mistakes happen. The key is to learn from those mistakes.
"Don't get personally upset by your setbacks," he said. "In grad school, we all have lots of failed reactions. As a medicinal chemist, it gets even more complicated.”
He found that early in his career, he’d take mistakes personally. "I try not to do that these days. I try to see failure as an opportunity to embrace negative data and try to design a positive spin on it."
Katrina (Kate) Jackson wished she had developed that same mindset early on. Kate is Senior Director of Chemistry at C4 Therapeutics, where she's worked since 2018. Prior to that, she was a research scientist at Vertex Pharmaceuticals.
When she first made the transition from academia to industry, there were challenges that, in hindsight, she wished she handled differently.
"At first I was overwhelmed that I didn't understand every piece of data I was seeing right up front," Kate said. "But drug discovery learning takes time - I think you have to go through some project cycles to really start to understand the way the process works, and even still, it changes every time. You just have to be patient with it."
On a more tactical level, she suggests that new scientists entering industry should wait a moment before jumping into courses like the Drew University ResMed one. “It’s a fascinating place to learn; I just wish I had waited about six months to a year before going so I had more context to absorb the information being presented.”
Start Thinking About Translation Sooner
Prof. Richard (Rick) Silverman discovered pregabalin, which was acquired by Pfizer and sold under the name Lyrica to treat epilepsy, fibromyalgia, and neuropathic pain. Although his work has had a vast impact on the field, he realized he probably could have started earlier to develop drugs for underserved diseases.
"Unfortunately, early in my career, I really wasn't focused on discovering drugs," Rick said. "I was just doing academic science and fell into (drug discovery) when I realized that we can use this basic science in developing drugs."
In 2019, Rick founded AKAVA Therapeutics, a company focused on addressing unmet medical needs in neurodegeneration and oncology. If he could do things over again, Rick said he would have started the company earlier in his career.
"I've had compounds licensed to companies that have gone a certain distance and shown they're pretty good, but then the company runs out of money (or) changes direction," he said. "Those drugs could have really helped people, and they're sitting on a shelf." If he had started his company earlier, perhaps some of those molecules could already be further in development.
Prof. Andrew Wilks, the discoverer of the JAK enzyme family and founder of Cytopia, the developer of recently approved momelotinib (Ojjaara), echoes the sentiment. “I was the most snooty and self-indulgent academic for the longest time. Very much poo-pooed this notion of translation,” he chuckles. “I regret now having had that stance. I wish I’d become more translational… I arrived quite late at the idea that you could actually make a difference with a translational mindset.”
Seek Out People From Different Backgrounds
Chris Burns, Andrew Wilks’ chemistry collaborator on the discovery of momelitinib and CEO and Managing Director of Amplia Therapeutics, says “always seek out and work with people from different backgrounds. I worked on a company developing biosensor technology which is definitely out of the normal training for a medicinal chemist. But I learned an awful lot from that program that I’ve been able to call on in drug discovery, working at the interface of chemistry and biology. I would’ve liked to have done more of that in the early phase of my career.”
Don’t Try to Change What You Can’t Control
Christian Gampe said it is easy for anyone, not just drug hunters, to get frustrated or confused over business decisions or changes they might not agree with. He frequently found himself having those feelings early in his career. Now, though, as a Senior Principal Scientist at Genentech, he said he's shifted his perspective and wishes he’d done so years ago.
"Decisions are being made strategically above your paygrade and outside of your realm of influence, but (they impact) your daily life.” Christian said while discussing strategies to extend the duration of action for oral and inhaled drugs at a recent Drug Hunters webinar. "What I had to learn the hard way over the years was to focus on what you can influence and not get derailed by things that are beyond your control."
Celebrate the Small Things and Enjoy the Ride
Dafydd Owen, Senior Scientific Director at Pfizer and one of the inventors of Paxlovid, says he’s heard “a lot of people say I’m joining industry to work on a drug.” On reflection, he never said that with good reason, because that’s a lot to live up to. “On average, your average medicinal chemist will work on zero drugs in their career. But that’s no indictment of them as a scientist. Don’t measure yourself by that very binary one or zero because it’s likely to be zero, you’d be lucky if it’s one, and it’d be amazing if it was two,” Dafydd says. “Celebrate the small things along the way - celebrate a molecule that’s safe enough to go through toxicology and be administered to a human being. What an amazing responsibility that is, to think of something like that.”
What an amazing responsibility and opportunity indeed.
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