Q&A: Lilly’s top scientists on genetic medicine ambitions, and how they’re not just for rare diseases

The company is betting those drugs will be key to its future, such as a gene-silencing RNA called lepodisiran to be tested in a 12,000-person trial, to see if shutting down production of lipoprotein(a) can reduce the risk of heart attacks and strokes.

At the center’s opening, Endpoints News spoke with Skovronsky and Andrew Adams, co-director of the Lilly Institute for Genetic Medicine, about the company’s ambitions. The conversation has been substantially edited for length and clarity.

Ryan Cross: I wanted to start with the statistic that you mentioned, that nearly one-third of Lilly’s pipeline is genetic medicines. Last summer, it was about a quarter.

Dan Skovronsky: The pipeline is not shrinking.

Cross: Do you think people really appreciate how invested Lilly is in genetic medicines?

Andrew Adams: It’s a little bit under the radar, but mainly because we chose not to talk about it so much in the early days. With things like lepodisiran now in Phase 3, we feel very confident talking about siRNA. And within the company, there’s been a huge amount of excitement over the last few years.

Skovronsky: To get to a third, it’s mostly in the early stages.

Cross: Dan, last fall, you told me it’s important for Lilly to plan for a future beyond Alzheimer’s and obesity. So how important will genetic medicines be to the company?

Skovronsky: I hope it’ll be important. Of course, this is a humbling business, and there are lots of failures along the way. It’s hard to predict what will work and what won’t work. But I just don’t see why this won’t be a major way that we cure diseases. Nearly everything important in our body starts out as something in the genetic code, and therefore almost every disease has its roots in the genetic code — setting aside injuries.

Second, you can make a great medicine, but it only helps people if they take it. And sometimes we don’t take our medicines. So when it comes to some of the common diseases, genetic medicines have the potential for one-a-year or once-in-a-lifetime therapies. I don’t see a clear path to that with small molecules or biologics.

Cross: During my tour of your new labs today, much of the focus was on neuroscience. I was surprised to not hear about work on diabetes, obesity and cardiometabolic diseases. Is there a genetic medicine future in those conditions?

Adams: Absolutely. In my mind, the two biggest therapeutic areas for near-term success would be neuroscience, and then diabetes and obesity.

In places where we already have great medicines like Mounjaro and Zepbound, it’s really important to use tools like genetic medicines to make those medicines even better, to address comorbidities that are still not fully solved, or to accentuate some of the benefits and minimize some of the other aspects of those medicines, and to help patients stay on them longer and get closer to their targets. There’s still more work to do. And we think that genetic medicine can be a part of helping that happen.

Skovronsky: I’ll just add that Lilly is a global company, and we care about global health. At first blush, you might say, “Genetic medicines, aren’t those expensive, limited distribution kind of drugs?” No. Actually, a genetic medicine — the Covid vaccine — is probably one of the most well-distributed drugs in the world ever. So genetic medicines can be made in a way that actually fits into healthcare systems around the world better than other classes of medicine. So that’s also a focus of ours.

Cross: So is this as simple as making a once-annual or once-in-a-lifetime version of a GLP-1 drug? Or are you looking at other biology, other targets?

Skovronsky: I’m not sure that a constitutively active GLP-1 is the best idea. These are drugs that require titration. People need to change their metabolism over time. People need to get pregnant. You need to gain weight. I would just say that we’re not ready to think about ideas like that yet. And so once-in-a-lifetime kind of ideas are more suitable to targets where we really understand that there’s a gene abnormality that you’re born with and that we can correct.

Adams: It’s probably going to be one of these multimodal, complicated molecules, where we can sort of turn it on and off at will. But we’re a little bit away from that. We can barely do the “get-it-in-there-and-make-it-do-what-we-want” flavors.

Cross: I’m almost surprised there hasn’t been a flood of companies trying to do mRNA or gene therapy versions of a GLP-1 drug.

Skovronsky: I don’t see that as a competitive threat, or a competitive imperative to work on that next.

Cross: Julia Vitarello and neuroscientist Timothy Yu, who spearheaded the development of a truly individualized medicine for Vitarello’s daughter, spoke at your opening ceremony today. I wasn’t expecting to see them here. Is Lilly working on N-of-1 therapies? Is there a place for that in pharma?

Adams: I’ve known of Julia since I started the genetic medicine work at Lilly. One of the reasons that I got into this space was reading about her story and the work that Tim was doing, and trying to imagine the potential of that to help millions of people one day.

My hope is that not only do some of these patients with rare and terrible diseases get a great medicine, but it also teaches us how to make those medicines for patients with things like Alzheimer’s or cardiovascular disease.

Cross: I wanted to ask about the emphasis on neuroscience. You have a big, brain-shaped conference room.

Skovronsky: We’re surprised to see that too.

Cross: Are you working on the second, third or fourth generation of Alzheimer’s drugs here? And what does that look like?

Skovronsky: Two big ideas that we’re pursuing now. One is neurodegenerative targets other than amyloid. There are so many other targets and diseases, and often patients have more than one neurodegenerative disease or pathology in their brain. So we’re going after all of the other usual suspects beyond amyloid in the brain.

And then the second idea, which isn’t necessarily a genetic medicine play, although may someday be, is preventing Alzheimer’s disease. Just getting in there early requires early diagnosis and early intervention. That could be with antibodies. We’ve got a trial ongoing with donanemab and are super-excited about that.

Cross: Thank you both for your time.

Skovronsky: Thank you.

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