Enanta Pharmaceuticals, Inc 2026 Global Healthcare Conference

Sure. Before I begin, I want to remind you I'll be making some forward-looking statements, and for a summary of the risks associated with these statements, please see our filings on sec.gov and on our website. In terms of Enanta, core competencies have always been in drug discovery and development, and discovering the drugs we develop ultimately. Our entire pipeline is filled with homegrown assets and wholly owned assets, except for, I would say, the hepatitis space. As you pointed out, we started out in virology and more particularly liver virology. Then we moved not out of that, but beyond that. We still have, obviously the Hepatitis C stuff that have these cells as in the form of Mavyret, which gives us good royalty revenue.

We moved beyond liver virology and got into respiratory virology before the pandemic and chose RSV as one of the major unmet needs in pretty much all of virology in terms of its sort of universal attack on humankind starting from birth right away. We took that on as a problem. The pandemic broke out. We got involved in that. Increasingly, after liver virology and respiratory virology, we had a harder and harder time finding interesting things to really sink our teeth in and build the company on. We picked up on some of the adjacencies in the company from people who had trained. Many of our virologists actually trained in immunology and became virologists later. Given some of the skill set overlaps, it was sort of an easy migration into that area. We took that on. My background, I worked in immunology for a couple of decades, probably earlier in my career.

Coming back and going down even JAK-STAT pathways were things I worked on several decades ago. Now that some of these things are more druggable and we will get into that, there is just lots of interesting opportunities. We view the I&I space as sort of an expanding universe of opportunities and again, building on our strength in virology. That is where we were and how we got here.

Yep. Zelicapavir is a replication inhibitor, and I will contrast that with entry inhibitors that many other people took on earlier in the RSV era. Pretty much all those replication or entry inhibitors have fallen to the wayside, whereas we concentrated on replication inhibitors in both of our programs. Zeli was the first discovered as an N-protein inhibitor. As you pointed out, we have taken it into many clinical studies, first in the human challenge, well, phase I healthy stuff. Great PK, good safety. We have been in over 700 patients now with a very good safety record, so there is a good database there. We demonstrated really good activity, antiviral activity, and symptom effects in a human challenge study, and then moved into various real-world settings. The first study, one probably in retrospect probably wouldn't have run, was in otherwise healthy patients who contracted RSV.

It turns out you cannot get to those patients fast enough. They self-resolve very quickly on their own. The teaching from that is you focus on the high-risk patient populations, and they are at opposite ends of the age spectrum. High-risk adults. Let me start with the younger. You are born with no natural immunity. You have to acquire it. Newborns onwards are incredibly vulnerable until they have had repeated RSV infections in childhood. Then you go through sort of the otherwise healthy period, and then you get into a period of immunosenescence as you get older. The immunity starts to wane. You have either end of the age spectrum and also people in the in-between that maybe they are otherwise healthy, but if you have any sort of a respiratory or cardiovascular complication, it can be very serious. COPD, congestive heart failure severe asthma.

These things predispose you to poor outcomes with an RSV infection. We have focused on opposite ends of the high-risk adults, high-risk peds, and peds in general are high risk just because they have no immunity. To go to your question about LOTUS. LOTUS is a pediatric study. We are running it in Thailand right now, where the RSV season has already begun. The idea there is to look at about 150 children age 4 weeks to 3 years, so very young children in some instances, who have RSV and can come into the clinic within 72 hours of symptom onset. In that study, we are aiming to use our proprietary observer-reported outcome. These peds can't self-report, not in any cogent way, so we have to use an observer-reported outcome tool.

We have been developing that literally for the last few years in connection with caregivers, physicians, and also groups that create these tools, and regulatory bodies in the U.S. and in Europe. Got a lot of input into building this tool, which we hope to be able to use as a tool for registration studies. You may recall in our first ped study, we got it in at the very end of that study. We didn't have the tool ready in time, but we do now, and it will be used as our primary endpoint in this study.

I think the learnings is earlier is always better, and that's why we selected this 3 days from symptom onset. We saw about a little over a log. I think it's about 1.2 log reduction, which doesn't sound like much if you are thinking about Hepatitis C. But in a study, it's very similar to what people saw, for example, in COVID, about a log reduction. In fact, the only other study that we had to compare it to was one of those entry inhibitors in a study that was run in China. They saw about a 0.6 log, so we about doubled that. We will be looking at other, but you don't get approved on virology. It's supportive. We will be looking at other clinical measures as well. But the primary would be on symptoms. That's what we would aim to get approved on.

Yeah. In some ways, the common denominator is they are high-risk categories, right? Standard risk as I mentioned before, you really do not need treatment. But in the high-risk categories, we focused on some of the ones that were number 1 in the FDA guidance for RSV, but also ones that were deemed to be high risk, for example, in COVID. Predisposing factors are age over 65. We ratcheted that down because we found that 75 and older is even higher risk. So we are picking 75 and older, or people with COPD, or people with congestive heart failure. That is the so-called HR3 population that we identified in our prior study, and where we saw a very meaningful reduction in time to resolution of symptoms. Again, symptom endpoints. We will be looking at other stuff. We also saw a very pronounced reduction in hospitalization rate in that patient population.