SAN DIEGO — For savvy dealmaking, Vertex’s 2001 acquisition of Aurora Biosciences is near the top of the list.
Vertex bought the San Diego biotech for $592 million in stock. The site eventually developed the suite of cystic fibrosis drugs that transformed the devastating lung disease and became the cornerstone of the biotech’s business, bringing in nearly $10 billion last year. Vertex is now valued at $122 billion, with its stock price setting new all-time highs earlier this month.
Paul Negulescu joined Aurora as employee No. 5 in 1996 and led the San Diego site from 2003 to 2022. For their cystic fibrosis work, Negulescu and two other Vertex colleagues won the $3 million Breakthrough Prize in Life Sciences last year.
Now, Negulescu is leading Vertex’s pain research, one of the biotech’s most advanced and closely-watched efforts. As the biotech is close to finishing its FDA approval filing for its non-opioid pain pill, Wall Street analysts debate its commercial future. Many project blockbuster sales, but others wonder how it will fare against generic opioids that cost pennies per pill.
Endpoints News sat down with Negulescu earlier this month at his San Diego laboratory to get his perspective on the future of pain research, what made the Vertex-Aurora tie-up an M&A success, and his views on AI in biology.
This conversation has been edited for length and clarity.
Andrew Dunn: What do you think made Aurora a successful merger?
Paul Negulescu: Whenever there’s an acquisition, there’s a business process, but it’s also just people getting to know each other and trust each other. There’s no formula for success there.
The site-based model that Vertex continues to have — sites in San Diego, Boston, the UK, and we’ll see what we do with the new Seattle group — they all have their own focus, but also work together and follow certain common principles.
Vertex wasn’t so big that they had this, ‘You must do things this way.’ What Josh [Boger] appreciated — and Vicki [Sato] and Matt Emmens — was we were pretty early in our overall evolution. They sent one of their top chemists, Roger Tung, to help establish the chemistry group. People came to help build the site not necessarily in their image but to celebrate the differences.
Dunn: What are the common pitfalls you see in pharma acquiring companies?
Negulescu: Most acquisitions don’t start with an expectation it’s going to take 10 years to get a return on your investment. Sometimes you have to be patient to figure out where the value is in the thing you acquired. Some of the stories I know externally, the time horizons for doing those things are just not there. They’re too short. They need to see a certain outcome in a certain amount of time, or they’re just willing to walk away.
Dunn: We’re talking about the importance of developing tools and assays in the early days of Aurora. To shift to AI in drug discovery, how useful is the work in areas like protein structure? Do you see a parallel with AI?
Negulescu: AI is another tool. It’s going to open up new ways of thinking and new ways of discovering drugs. If we apply it correctly, it will open up possibilities. There’s no question in my mind, just like the voltage sensitive dye opened up the ability to study CFTR.
Can I predict today how it will affect our ability to design drugs? It can’t do it yet.
Dunn: Vertex is fairly unique in typically filing just one or two INDs per year. Far fewer than most companies of Vertex’s size. What do you make of the ambition in AI to make drug design less artisanal and more like engineering? Will there always be a role for human expertise?
Negulescu: AI is not going to tell you what disease to work on tomorrow. When you’re going into new areas, or trying to solve something that hasn’t been solved before, that’s where the human shines. If you’re repeating something over and over with minor variations, you can automate that and you can engineer a process.
People are strong when they’re making connections between things that haven’t been connected before. AI can do that too, but it’ll make some connections that are irrelevant. It still takes a person’s judgment.
Dunn: In leading pain research, what’s the latest on Vertex’s programs?
Negulescu: We’ve just announced we’re filing with the FDA for approval in moderate-to-severe acute pain for the first selective pain signal inhibitor. Suzetrigine has the potential to be a drug that will change the way we think about treating pain.
Dunn: This is a Nav1.8 inhibitor. What else is in the works?
Negulescu: Nav1.7 is still in research, not yet in the clinic. There’s a next generation 1.8, called VX-993, that is going into Phase 2 this year. That’s part of our serial strategy to see if we can find a compound that’s even better than suzetrigine.
Dunn: Is there a biomarker you can use to compare?
Negulescu: Pain. I wish there was a better one than just, “How do you feel on a scale of 0 to 10?”
Dunn: There’s no biological marker?
Negulescu: We have not, as a field, figured out how to quantitatively measure pain signals. I don’t know if it’s just too hard, or if we’re just not smart enough.
But this whole notion we’re putting forward — that there are signals in the periphery that go to the brain that are specifically for pain — I think we’re going to figure out how to measure them electrically in the body.
As new technologies become available for sensitive detection, maybe we’ll be able to tease that out. Maybe an AI algorithm will be able to tease out a little signal from all our electrical activity. It might be a pattern so subtle it would take a lot of data and some computational iteration.
Dunn: How do you see the field evolving?
Negulescu: At the moment, we’re focused on the sodium channels. There’s enough validation of them alone to work on each of them.
Dunn: Would you expect a potential combination of blocking Nav1.7 and 1.8 to be better?
Negulescu: There is a rationale that a combination could be better, but you need both compounds to prove that. The clinical data suggests that we may want to see more efficacy than we’re seeing with the 1.8 compound alone. We’re seeing good efficacy. We’d like to be able to take people who are at an eight or nine in their pain to maybe a three or four. We’re not seeing that yet.
Dunn: What are you seeing now?
Negulescu: Two, three points reduction. Is it, in one fell swoop, going to solve the pain problem? Maybe not. That’s why we’re thinking about what we can do beyond that, just like in CF. The first generation of the double combination stopped the disease. We wanted to see if we can further improve, and we could.
It’s definitely a journey, but it’s an important first step. For the last 20 years, everyone’s been trying to take this first step. I think we’re going to be the ones.