The challenges in drug discovery and development run deep. With an average of at least 10 years and $2.6 billion to reach the market and a less than 12% chance of success after a drug enters clinical trials, the process requires patience, persistence and many great minds working together.
Bristol Myers Squibb just celebrated the first U.S. approval of its first-in-class psoriasis pill Sotyktu in September. The drug is the first TYK2 inhibitor to reach the market — TYK2 is a target that puts Sotyktu among a class called JAK inhibitors, though it has been thought to have a better safety profile. Past predictions have shown Sotyktu could bring in as much as $4 billion in yearly sales.
And while the drug plays a pivotal role in the company's strategic direction, one person who might have been celebrating the approval the most is Ryan Moslin — who helped bring Sotyktu into the world at its initial discovery.
Now a senior principal scientist at BMS, Moslin talked to PharmaVoice about how a discovery team sifts through molecules to find the right one, how the pharma giant approaches the discovery process, his own experience as a psoriasis patient and what makes a good science leader at a Big Pharma.
This interview has been edited for style and brevity.
PHARMAVOICE: Can you talk about the process of bringing Sotyktu through the very beginning of the development process?
RYAN MOSLIN: You need to bear in mind that this, of course, is not the first molecule we looked at, and it probably wasn't even the thousandth molecule. We started much earlier with a structure that looks nothing like Sotyktu. And that's where I began my career, with this very small screen looking at trying to inhibit something in a different way. And it wasn't the precedent — it wasn't established, so a lot of what we were doing was, maybe this is real, maybe it isn't. And so what we did from there is try to build the molecule up to the point where it's good enough that you can test it — trying to make it more selective, more stable, more permeable, adding a number of other properties. And as you start testing each molecule more, you find out more problems and then you go back to the drawing board. So that's how these things move forward. It's iterative. Two steps forward and two steps back over and over again with a lot of people, a lot of frustration, a lot of challenges and a lot of setbacks.
One of the beautiful things about the way our teams were set up is you had so many different types of chemists working on it, and they all had a vested interest in different types of molecules. So there were no punches pulled.
"Let's try and rewrite the rules. I love rewriting rules. It's my favorite thing."
Ryan Moslin
BMS senior principal scientist
How do you recognize what you have when so many early programs don't make it through?
It's tough. In hindsight, you can say 'I just knew,' but I don't think you know when something is special. Usually when you think it's special is when it addresses whatever your issue of the day is — what is the thing that's hardest for me right now? And when the molecule fixes that, that's when you think it's special. And sometimes it is, but in this field, remember the failure rate is astronomical on a per-compound basis. So most of the time, you end up being wrong.
Does Bristol Myers have an approach to early science that might stand apart from its peers in the industry?
We had this incredible leadership at every level, and the leaders were universally regarded with respect and admiration at every level from the highest down to my supervisor, one over a new hire. These people were viewed as the best in the field. Something that made me enjoy coming to work each day [was] not just that my boss was somebody that I admired, but his boss and all the way up, the people that earned their jobs by being the best at their jobs.
What we do differently is you want to have people on your team that disagree not just with you but with each other. You want to have a diverse approach to the science. These problems are so hard that if everyone uses the same types of tools or thinks the same way, you're going to find yourself in local minima, and you see this throughout the industry. But if you have five or six people who you respect, admire, who are talented at what they do, and they're pulling toward the same goal via different directions, you can avoid that sort of tunnel vision. Having someone who likes computer-aided drug design, someone who likes to make it because you can, someone who likes data analysis, someone who likes just looking at the structures, all the different approaches you use in drug discovery and chemistry — all of those on a team with a leader who's willing to embrace strategies that he or she may not use themselves was what set us apart and allowed us to make this molecule.
The immunology market is a very crowded space and sales are subject to a lot of factors. How do market dynamics inform what you pursue on the science side?
Market factors of course play a role, but they just reflect the patient need. So if patients don't need a medicine, the market is going to tell you they don't need a medicine. I prefer to think of it as we're responding to unmet needs. And that's what guides our decision making. In psoriasis, an oral treatment option is something that is going to be appreciated by a lot of people. It's not always obvious what the unmet needs are, but we look for them and we make sure we understand what they are. So it's more than the market.
You also happen to be a psoriasis patient. How has that formed your perspective as a researcher in this space?
When I first started this program, it was exciting — it was a groundbreaking scientific endeavor and I was just coming from academia. So I would have done this program if it was to treat a disease I'd never heard of. And it wasn't until later that it became involved in my disease. To be honest, it's so much bigger than me. If it affected me in any way, it made sure that to me, the speed wasn't the most important thing. Rigor was the most important thing if I'm going to take this. Do I really want to cut any corners on the way there? The answer is no, I don't. So that's how it informed me personally.
Now I have a larger role in determining what types of projects and diseases are targeted. That perspective as a patient taking this medicine has carried over. I don't like working to rushed timelines. I don't think being a month faster with a worse compound is better. So that's how it's influenced me is to take the time to do it right, take the time to do what's transformational, take the time to break ground.
"Two steps forward and two steps back over and over again with a lot of people, a lot of frustration, a lot of challenges and a lot of setbacks."
Ryan Moslin
BMS senior principal scientist
You mentioned academia. I know this industry is especially tied into what's happening there, and vice versa. If they could be more like one another in any way, what do you think that could be?
I do believe they are getting closer. A lot of professors have companies now. A lot of professors have come up with some groundbreaking ideas. I think the current relationship is good. I don't think that they want to become each other. A lot of how I guide myself is with diversity — you want different approaches. And I think it's really important that academia doesn't try too hard to be industry, and that industry doesn't try too hard to be academia. We can complement each other much better if we work together via different perspectives. I think that has worked so far, and I think it's going to continue to work.
What are you working on right now?
I'm not working on Sotyktu, but I'm really excited about what I'm working on. I can't tell you what it is, unfortunately. It's more of the same in terms of, let's do something that hasn't been done. Let's try and rewrite the rules. I love rewriting rules. It's my favorite thing.
We've got a really rich commitment to the immunology pipeline. In various stages, we're trying to tackle these diseases because these are critical diseases. The body's immune system is at the center of so many different disease areas. We've got a lot going on there. Even if you look at Sotyktu, there are a lot of indications that we're pursuing there as well.
What can leadership at any company do more to support drug discovery programs?
Trust your scientists. We are passionate, we are committed. We're going as quickly as we can and we're as invested as anyone in providing what is being asked of us. Trust in science and the scientists — we will do everything we can to create the medicines that people need.
