Good afternoon, everyone. Welcome back from lunch. I'm Brian Skorney. I'm one of Baird's senior biotech analysts. I'm really happy to have with us the management team from Enanta Pharmaceuticals next. It's a company that I've followed for a long time. They have a number of pipeline programs that I think are really interesting and exciting to talk about. I'm going to have Jay Luly, the CEO, come up here and give a little bit of an intro talk to the company, and then we'll sit down and go through some questions. Thanks, Jay. Great. Thank you. The slides up. Here we go. Before I begin, I want to remind you that I'll be making some forward-looking statements. For a summary of the risks associated with these statements, please see our filings on our website and sec.gov. So Enanta historically has been a virology company. You'll see in a little bit we've evolved further into immunology. We started a long time ago, actually, in hepatitis C and built up a number of different programs in hepatitis C from the very discovery stages all the way through development, and then ultimately commercialization with our partner AbbVie. Mavyret is the only eight-week cure for hepatitis C. It's also the only hepatitis C cure that's indicated for not only chronic hep C, but also now recently acute hepatitis C. We've worked in other liver viruses, namely hepatitis B, and then we marched into respiratory viruses. This was pre-pandemic, recognizing that Respiratory Syncytial Virus was a really important unmet need. The virus was first characterized in around 1956, but until very recently, there were no vaccines for that virus. In fact, there are now a couple that are used for adults. There was a monoclonal antibody called Synagis that was used prophylactically in children. That was replaced by now a couple of monoclonal antibodies fairly recently. But to this day, there's no treatment for an active RSV infection. And so we aim to change that. We have two different programs. One is an N-protein inhibitor. One is an L-protein inhibitor, otherwise known as the viral polymerase. And what distinguishes these two targets from many other approaches that have been done, other programs historically have really focused on viral entry using the F protein as a target. We reckoned that viral entry is an interesting step. It's maybe best used in a prophylactic setting. It's great to be able to stop viral entry in a prophylactic mode, but once you have an active infection, you've got serious ongoing replication, and you really need to shut down viral replication. So we've only worked on replication approaches, and that's what these two are about. So we'll get into RSV in some detail today. We couldn't not work on the pandemic virus when it happened. In fact, Brian called me very early in the pandemic and asked me if we were going to do anything about this virus, and so we set about. We were working on protease inhibitors historically in other viruses, and we came up with a very good 3CL protease inhibitor called EDP-235 and have a phase two data set. We're ultimately hoping that the regulatory landscape will clarify in a way that other protease inhibitor or other drugs for treatment of SARS-CoV-2 will have a straightforward development pathway, and then a partner would be the goal there. Having worked through respiratory viruses and liver viruses fairly extensively, we were looking for areas to expand. A lot of the skill sets in the company were amenable to shifting into the immunology space. We early last year announced that we had been working in this space and that our first program was going after kit and mast cell-driven diseases such as chronic spontaneous urticaria. Late last year, we revealed our second program with some really exciting work in STAT6. This is going after an oral molecule that would effectively be an oral Dupixent. That's the goal for there. Then later this year, we expect to announce a third program in immunology. It's an area of growth and evolution for the company. Let's talk about the high-risk adult study that we're doing in Zelicapavir. If I go back a slide, I think I can go back a slide. I just want to remind you that with Zelicapavir, it's the N-protein inhibitor. We reported pediatric data at the end of last year. I want to highlight that there are two main high-risk patient populations that we're trying to address with Zelicapavir, and they're at each end of the age spectrum. The first is in pediatrics. Children are born with no immunity to the RSV infection, and so they will get repeated RSV infections throughout childhood until they start to build up some sort of an immunity on their own. So any of the prophylactic approaches for peds or for that matter for adults will only prevent you from getting infected in any given year, but that protection is not durable. And so children must get multiple RSV infections throughout childhood. They will get them, and again, there's no effective treatment. So that data set has already been reported. We did dose ranging. It was a first in ped study. We wanted to demonstrate that the drug, especially in pediatric populations, was incredibly safe, well tolerated, that the doses that were targeted were chosen properly, and that we saw an antiviral effect. And we checked all of those boxes in that clinical study. Now we're looking at the other end of the age spectrum, namely high-risk adults. These are adults who by definition are older than 65, although we've skewed the patient population to the higher end of the age category because we capped the 65 to 74-year-olds along with just plain asthmatic patients who are also at high risk. We capped those two groups to be a total of 20% of the trial population. That left 80% of the trial population to be 75 years or older to have COPD or congestive heart failure. We slightly over-enrolled the study. We were targeting 180 patients, but when the pandemic started to ease and RSV came back, we didn't want to not recruit as many patients as we could. So we wrapped up the study at the end of this year's RSV season, and we expect to announce data later this month. I would also point out that among the things we targeted in this study was to get patients into the study within 72 hours of symptom onset. Anytime you're treating a viral infection, the earlier you can treat, the better, and that's a practical inclusion criteria for a trial of this sort. So everybody is within 72 hours of symptom onset. And then quite simply, we're going to be looking at a shortening of the time for the resolution of those symptoms. That's something that is a clinically meaningful thing to do. It's a registration type of endpoint that you could use in a registration study. You can't use just simply viral load reduction. You need to put something on top of that. During the pandemic and COVID, you could use in the early days, you could use hospitalization and death as an endpoint. That's really no longer feasible given the numbers of those events have dramatically decreased, so you have to rely on symptomatic types of endpoints, and so for that, we're using a patient-reported outcome tool called the RIIQ, and you can read the types of symptoms that we'll be looking for. So what kind of an improvement might one expect? And so there aren't any registration studies really to point to in high-risk adults for RSV, but you can look at other acute respiratory viral infections, namely flu and SARS-CoV-2, and here are some of the key data from registration studies that were performed by various sponsors on oseltamivir, otherwise known as Tamiflu, also another flu drug called baloxavir, otherwise known as Xofluza, and a SARS-CoV-2 drug called ensitrelvir, which was approved in Japan on a phase 3 symptom outcome study. And in each case, what's striking here is that whether it's influenza or it's SARS-CoV-2 or whether it's one influenza drug versus another, that in each instance, the clinically meaningful result was about one day shortening of symptom duration. And so we might expect that RSV could fit into this same sort of paradigm. Again, these were the trials that led to registration for the respective drugs. And so we're targeting roughly that same sort of result, about a day. You can also see at the bottom of the slide the N's here. There are about 500 to 700 patients, more or less, in the phase three registration studies where these results were each shown to be statistically significant. Our study is a proof of concept study. It's the first study we've done in this high-risk adult population. As a phase two, it's sized about 180 patients, roughly. So it's around a third or so of the registration type of study that you would do. But we're basically looking for a symptom duration reduction of about a day. In addition, we'll be looking at a number of different secondary endpoints. We'll be looking at all sorts of symptoms high and low in the respiratory tracts. We'll be looking at virology and a number of other measures that we can look at, and some of which are predefined, so as to be able to enable the best design for a registration study that we could. And then ultimately, having determined the effect size here, we would aim to show that again with statistical significance in a larger phase three study. So that's the trial in a nutshell. Again, data is expected later this month, and we look forward to reporting that in the future. We also have, as I mentioned, some efforts now expanding into immunology. This is just one slide on our KIT program where, again, we're going after mast cell diseases. So KIT is an important target that leads or maintains the survival of mast cells. So inhibition of it leads to mast cell apoptosis and also downregulation of activity of mast cells if they're not apoptosed. And so what we've done is created a very strong development candidate. It's very, very potent. Importantly, for kinases, you want to have high selectivity so that you can limit off-target side effects. We're always optimizing ADME properties in our drug candidates to match what type of dosing we would expect to need to do. And so basically, we're doing the IND enabling activities, finishing those up, scaling up drug for clinical trials, and hope to be in the clinic as early next year as possible. The other is STAT6 program. So STAT6 is a transcription-driven process where you're shutting down basically the signaling pathway downstream from the targets that are impacted by Dupixent. So you have IL-4, IL-13. These signaling pathways go down and coalesce at STAT6. So we're aiming at a very specific target in that signaling pathway. Once again, we've got a high degree of selectivity for STAT6 versus others, super good potency and good in vivo model work that is being demonstrated with a bunch of our advanced molecules in-house. We've got a stable of strong chemical matter, and we're very, very much on track to having our development candidate in the second half of this year that we'll be pointing toward the clinic next year. So exciting program. Again, I think having the opportunity to have an orally dosed Dupixent would be a really, really important choice for patients. And then just to wrap, so KIT is, again, we're doing scale-up IND enabling activity wrap-up, STAT6 on track for the candidate second half. We aim to have a third program announcement in immunology, and we have RSV data set, a key phase 2b data set that, if positive, should be phase 3 enabling. We're also considering the partnering of one or more RSV assets at this time. I mean, we learned the wisdom of doing that at the right time, right place, with the right partner in Hepatitis C. And given the opportunity to have the first drug to market in a new category like RSV and have a global launch, we're going to be evaluating potential global partners. So with that, I think I'll wrap up my presentation. We get into Q&A. All right. Great. Thanks, Jay. Give him a second to sit down here. But maybe on the Zelicapavir program first, one of the slides that jumped out at me was just looking at sort of the high-risk flu data versus sort of the younger group data, and there was a much longer placebo side for respiratory symptoms. So I guess in the context of it, and I know we've discussed previously the historical all-comers RSV seasonal study versus the high-risk study, what's sort of the expectation for what the duration of symptoms would be for placebo in a high-risk RSV study? Would it be similarly like a seven and a half day or eight and a half day, I think, in flu, or do you think that would be a much shorter duration? It's probably, again, we haven't seen data, so it's harder to give you that with specificity. But I think generally speaking, it's in the boundaries of something on this page, is my guess. Flu, again, it depends. You can see sort of in the younger category, they tend to, the placebos will tend to resolve things quickly. Flu comes on hard, hits hard, and blows out reasonably fast. As you get into age, I'm sorry, more elderly people, you can see that the symptoms are protracted. So that's a general truism that we have in these respiratory viruses. The older you are, the more immune compromised you are, either because you're immune naive as a child or you have immune senescence as an elderly person, the longer those symptoms are going to persist. And so that's the whole idea of going after high-risk patient populations to begin with. If you're otherwise healthy, and we did that study, right? We did a standard risk study in otherwise healthy adults right after we did our challenge before we could get into our high-risk studies. And even though we got into patients within 48 hours, those people were already on the mend, and viral loads were coming down, symptoms were coming down. So we just couldn't get in there. It's impossible to get in there. You have to get in there prophylactically early in that patient population. So lesson learned, standard risk is not in need of treatment and probably couldn't benefit from treatment. But the high-risk patient populations, and the most exaggerated of that would be in the truly immunocompromised where they can't battle it at all, right? So you might even want to take two mechanisms at those patients and dose for a longer time to really take down that virus. And then just when we think about sort of the secondary endpoints and what's important there, I mean, how important is sort of virology here, obviously, in respiratory viruses or any virus you would want to sort of see symptoms kind of correlating with virology and reduction? Yeah. I think symptoms, obviously, is the path forward for registration, but virology is very important. The quicker you knock down the virus, the quicker the symptoms will resolve. So they are correlated, and it certainly is supportive. This is a proof of concept study, as Jay said. So we're looking at a whole host of secondary endpoints in addition to the primary endpoint on lower respiratory tract symptoms. We'll look at other symptoms, we'll look at virology, and all that data will be supportive for us to be able to look at that kind of totality of the data package to give us the confidence to move forward. Can you discuss anything just in terms of sort of a blinded data set that you have so far in terms of enrollment of the various subgroups of like COPD, 65 plus, and I guess it goes back to the question, do you know overall what the number of days of symptoms are in the study? No. We don't right now. Sitting here today, we do not. But I think we do know that we capped, that we got the cap in place because if you weren't careful, you could just be enrolling a lot of healthy 65-year-olds, and that's not what the study should be about, and so we know we hit the cap, so we know by definition that 80% of the participants are in those higher, higher risk categories, and so the placebo should be longer. Great. And then you mentioned sort of partnering at the right time. No one went to partner at the right time. I guess it's sort of a broad context question. We have a pretty powerful person in HHS who has a preconceived bias against vaccines. I'm just wondering, has this sort of catalyzed discussions around an actual antiviral and a treatment? It would seem that the administration is maybe more predisposed to targeting through an antiviral than a preventative vaccine. Yeah, so I mean, the vaccines are interesting because even pre-politics around this, pre, I think there was just a lot of vaccine hesitancy as a result of the pandemic. People who were taking vaccines took almost all the vaccines they could have possibly taken. At some point, they kind of get tired of doing that, and RSV uptake with the vaccines that are available for RSV, and GSK has one, Pfizer has one, the adoption has never been really super optimal. I mean, they've been hitting around, I think, not even 20% of the potential target population there, and so politics aside, it's just the uptake hasn't been super high. Even if there is vaccination in play, it's going to be there's still a fair amount of breakthrough infection and other kinds of things, and the majority of patients are not vaccinated, so they're going to get the virus. Right, and you also have an earlier stage RSV therapeutic in development, and you said you consider partnering one or both of them. Just how do you think about the differentiation and role of each of them in treating RSV? Well, one of them is more advanced. So we always like more advanced. And so Zelli is sort of blazing the way and has now been in two high-risk adult studies. Before that, the gatekeeper for going forward is the human challenge study. And I would call that a trial that's necessary but not sufficient, right? You have to pass that hurdle. And the good news about 323, our follow-on molecule, is that it passed that hurdle with flying colors. In fact, the challenge study data is just truly extraordinary. We were hoping it would be, quote, at least as good as Zelli, but it was amazing. Within 12 hours after the first dose, the viral loads are gone as measured by culture. So you're actually looking at live virus gone after 12 hours, one dose. So it's incredibly fast acting, and that could be an advantage in any situation, but could be used as a follow-on or a next gen. Great. And then maybe talking about the INI programs for a second here. I mean, STAT6 seems to be a very hot area of development right now. Could you sort of characterize direct inhibitor STAT6 versus the opportunity for degraders? It's a question I get about the relative value of each. Sure. I think ultimately we'll have to wait to see what clinical data looks like for both. I mean, they're both mechanisms to try to inhibit or reduce the amount of STAT6 and blocking that signaling pathway. Certainly, Enanta has a history of small molecules and expertise in small molecule chemistry and preclinical development. Clear translation from preclinical studies into clinical development in terms of metabolism, PK/PD translation. So we're very familiar with that modality. Degraders are a novel modality, nothing approved to date, so we'll have to wait for some clinical data to see ultimately how things pan out. Great. And then maybe on the KIT program, just thoughts about differentiation versus other KIT assets in development and what kind of drives the choice of the initial indication to target? So we like KIT as a target for a couple of reasons that Jay had mentioned initially, that you're actually reducing the number of mast cells that we know drive the pathology in chronic spontaneous urticaria. So that was kind of an obvious indication, but really any disease that's driven by mast cells, you could contemplate for this type of a mechanism. And so there's many of those that we're looking at. There is an antibody that is targeting KIT. It's currently in phase three studies in CSU, but they're also looking at other indications as well. So we're sort of obviously learning from that data. I think they have a readout in prurigo nodularis. They had some initial data that looked good there, so that's another potential indication. But the data from that antibody has been some of the best in disease that we've seen for CSU. And so if we're able to deliver an oral version or an oral molecule treatment against that target, I think that would be significant for patients. There are others developing oral small molecule inhibitors of kit as well. I think Blueprint has one that showed some data in phase one, so we're watching that carefully. But our molecule, as Jay kind of went over, shows really good potency. We've seen good selectivity, which is really important. So we're looking forward to getting into the clinic. Great. And then from your COVID-19 efforts, obviously you have a treatment that seems pretty robust, but I think there's a little background litigation that's occurred between you and Pfizer to develop the first COVID therapeutic. Can you give us any update on where that stands right now in the U.S.? And I think there was a recent update in Europe. Sure. I mean, there's a limited amount I can actually discuss, but we have intellectual property in the U.S. and in the EU now that covers the SARS-CoV-2 protease called nirmatrelvir, which is the active component in Paxlovid. We filed suit in the U.S. in June of 2022. That case currently sits at the U.S. Court of Appeals for the Federal Circuit. More recently, what we have is now a filing of a suit in the EU. And we use the UPC over there, a Unified Patent Court, which covers 18 member countries. And what's interesting about that court is that they have sort of a program timeline of 12 months. So they work generally to have a hearing within a 12-month period of the filing, which was last month in August. And then they render their decision a few weeks later. One of the interesting aspects of that court, unlike the U.S., is that the panel of judges that hear the case tend to be very skilled in patent law and in the science of what's going on. So I think that'll be an interesting venue to have our case heard. Great. Well, thanks for being here today. I'm really looking forward to the Zelicapavir phase two study. I was hoping you'd announce it here. Maybe tomorrow. Jay, thank you so much for being here. Thank you.