All right. Good morning. I'm Eric Joseph, Senior Biotech Analyst with J.P. Morgan. Our next presenting company this morning is Enanta Pharmaceuticals, and presenting on behalf of the company is CEO Jay Luly. There's a Q&A after the presentation. Just raise your hand, and we'll bring a mic to you for folks who have a question. And for those tuning in via the webcast, questions can also be submitted via the portal. So with that, Jay, thanks for joining us.
Thanks, Eric. Before I begin, I want to remind you that we'll be making some forward-looking statements. For a summary of the risks associated with these statements, please see our filings on SEC.gov and on our website. For those of you who are less familiar with Enanta, we are a virology and immunology company. It's very strong in drug discovery and early development. We have multiple phase II programs that are delivering data in respiratory virology. And more recently, we've been branching out into immunology, where we've got a couple of very exciting earlier-stage programs that are coming up. We've been in virology for a long time and have a couple of drugs that have come through Enanta and made it to patients in the marketplace. AbbVie is our partner in hepatitis C, and our current product with them is a drug called glecaprevir.
It's one of the two parts in the drug sold as Mavyrin, so it's been a very exciting journey from the discovery through development, and then with AbbVie development and commercialization to get this drug to patients, and well over a million patients have been cured by Mavyrin. We have a strong balance sheet and ongoing royalties to fund our efforts. We finished the last quarter with $248 million in cash. In addition, we have a $30 million refund due to us from the IRS, and we have an ongoing royalty stream, so let's dive into the pipeline a little bit. You can see at the top is sort of our legacy work in liver viruses. In the middle portion is the very rich concentration of respiratory virology programs. We have two drugs for RSV. One is known as zelecapavir, formerly known as EDP-938.
We just finished a pediatric study that I'll talk about in a bit. And we have a second high-risk patient population in high-risk adults that's ongoing and due to wrap up this year. Next, we have an L-protein inhibitor. The L-protein is the so-called viral polymerase, a very well-understood mechanism in the field of virology. We'll talk about that. That's successfully completed late last year, a human challenge study in RSV. And during the pandemic, we were very intensely focused on COVID-19. We were already working on respiratory viruses, and SARS-CoV-2 was a big problem, to say the least. We focused on protease there and came up with a once-daily dosing very interesting 3CL protease inhibitor, akin to what is sold by Pfizer as Paxlovid. A year ago, we announced something that we had already had underway for a while, and that was the broadening into immunology.
A year ago at this conference, we revealed that we were working in immunology. We disclosed our first program, KIT, with the promise of disclosing a second program later in the year, which we did late last year as STAT6. We'll talk about both of those programs today as well. Let's start with respiratory virology. RSV is a big problem. There are no approved therapeutics for this. People have heard about some of the opportunities in prophylaxis. There are a couple of approved vaccines and monoclonal antibody for children that helps at least get them through their first year of infection. But they don't really provide long-term durable immunity. A couple of problems with prophylaxis overall is, number one, as we know, not everybody gets vaccinated.
In fact, the uptake for RSV vaccines is really suboptimal in terms of the number of patients that are eligible. And with the pediatric antibody, again, you develop no durable immunity. So the child will still need to get repeated infections during the course of childhood to give them somewhat of an immune response so that they can advance into later adulthood without the same vulnerabilities to RSV. So despite good efforts in prophylaxis, there's still needs to be a highly effective treatment for this virus. And again, the most vulnerable patient populations are the high-risk category shown on the left of this slide. Pediatrics are at high risk because they have no immune system to really fight it, no built-up immunity to fight it. High-risk adults, elderly, people over 65 or over 75, or people who have other things that put them at high risk, like COPD, for example.
Then the immunocompromised, whatever age they are, they have difficulty mounting a response against this virus. So it's a very open opportunity, and we're hoping that we'll have assets that can be first to market. Okay, let's talk a little bit about zelecapavir. There are a few different mechanisms you could approach in terms of stopping viral replication, which is what we do. Some of the earlier attempts in the field have been trying to block viral entry through the so-called fusion protein shown in the top of this cartoon. We instead focus on replication, shutting down replication, because we assume that at the time of presentation of a patient, they already have a lot of viral entry that's occurred, and ongoing replication is the problem that you need to really shut down and extinguish the flame. So zelecapavir is the first of two replication inhibitors we have.
Again, it's potent. It goes after both major types of the virus. It has a very high barrier to resistance, which is something that fusion inhibitors lack, and we've taken it now through well over 500 patients, and it's consistently shown a favorable safety profile, once-daily dosing, and we'll talk about some of the work in patients. At the bottom of the slide, you can see it successfully passed a human challenge study, which is sort of a rite of passage for RSV antivirals. Healthy volunteers are infected with the virus, and then when the virus starts to build up, you can then come in and treat them with the drug, so we've demonstrated very strong activity in that human challenge model, both in terms of virology and clinical symptoms, so these are the two high-risk patient populations.
We want to focus on them because, number one, they're the most at risk. They're the ones in FDA guidance that are shown to be the target populations for pathways to approval, and more importantly, too, there's a longer disease window in these patients. Otherwise, healthy adults resolve infection very quickly, and it's hard to show a drug effect, but in pediatrics or elderly, where maybe immune senescence has begun to step in, they have less robust immunity to fight this infection, and so you'll see a larger disease window, if you will, for the drug to work. Okay, RSV-HR. This is the high-risk adult study. It's in about 180 patients. It's ongoing right now. We migrated the study from the Southern Hemisphere, where in our summer, it was their winter, and so we were doing patient recruitment down there.
It's now in the northern hemisphere, and we're hoping to wrap up recruitment in this study during this current northern hemisphere season. We have sites throughout the United States and Europe and parts of Asia, and we're well along our way, so it's a nice study because it's sized well. It's 180 patients. That's a five-day treatment. We bring people in to study within three days of symptom onset, which is an advantage. Always bringing people in as soon as possible is a good thing to do, and we do have a symptom endpoint in this study. It's called RiiQ. We'll be looking at the time to resolution of RSV, lower respiratory tract disease symptoms, so seeing if we can shorten the time to resolution, so as I mentioned, that study is ongoing. I'll have more on the timing of that at the end of the presentation.
The study that we reported out just in December, a few weeks ago, was the PED study. This is a specifically designed small study. It's a first-in-PED study. You have to be very careful when you're embarking upon a journey and doing drug studies in pediatrics. As you can see from the slide, we're dosing infants down to as young as 28 days of age. It's very, very important that you've established a good safety profile coming into such a study, and you dose very cautiously as you're examining this vulnerable pediatric population in the first study. Part one of the study was really to look at safety in PK and establish a dose.
We looked at a couple of different doses, and the punchline is, as it turns out, it was safe and well tolerated in part one of the study as we were looking at it. And the PK also showed that even our low dose that we were looking at was predicted to have a therapeutic level of drug. And we had modeled that by looking at our successful challenge study in adults. So there were two main dose or age cohorts: 28 days to six months, six months to 36 months. Part one of the study, again, was the safety in PK. And then part two of the study was to explore the antiviral effect in these infected children who were either hospitalized or outpatient. And the results of the study were very encouraging. The drug, as I mentioned, was well tolerated and had a favorable safety profile.
I can't emphasize enough how important this is when you're going into a pediatric indication. In fact, I think there have been other RSV agents that simply just didn't have the safety profile necessary to get into children, which is a very large portion of the market opportunity. The antiviral effect was observed for primary and secondary virology endpoints in the overall population. Then as we drilled down into part two, which was the one that was taking the selected dose and looking at virology in particular, we saw over a log drop. Another interesting aspect of this study was when we had some pre-specified sub-analyses. We always believe that getting to people, children or adults earlier in an infection is better. We demonstrated when we got within three days of symptom onset a 1.2 log viral load drop.
So it was a very good study overall. Again, we hit the overall endpoint. We hit the part one safety and PK endpoint. We hit the antiviral activity endpoint in part two. And we had some other exploratory endpoints because going down in later stage development, we want to be able to focus not only on virology, but also on symptoms. And so in that context, we had a couple of symptom tools that were used. One ReSViNET was established, but it's known, but it's probably not one that regulators would allow for an approval because it really wasn't designed to look at changes in virology over time. But it was really the only tool that was out there. And when we started the study, we thought we would look at it just to see what information we could glean from it.
There was no difference in signs or symptoms between groups using this tool. Again, the study wasn't powered in any way for looking at symptoms or even virology for that matter, but what we had been doing in parallel was designing a tool called RESOLVE-P , and this is an observer-reported outcome tool that we have been designing with the help of people and organizations that specifically design these patient-reported outcome tools. We've been working with input from physicians and caregivers, input from FDA, input from ex-US regulators to build a tool that could ultimately be used to measure symptoms in this pediatric type of trial in a go-forward basis, so we were able to have that tool finalized in a way that we could introduce it into the study.
Unfortunately, it was very late in our study, and we only got data on 15 patients, but it was an encouraging trend there. So RESOLVE-P is something that we're very interested in maturing for later stage studies. We'll talk more about that in a bit. So anyway, in the aggregate, the data support advancement. This is a slide that shows the MITT3, which is the patients who were dosed within three days of symptom onset. And you see a very nice, roughly 1.2 log drop at day five. And that's roughly twice what had been seen in terms of a viral load drop in a patient population like this in a Chinese phase III study that had been done on a fusion inhibitor. So it's a very, and I'll remind you that even Paxlovid for COVID gives about a 0.8 or a one log drop.
This was good virology for certain. Okay, our other protein or molecules in L-protein inhibitor. Again, I mentioned it's a viral polymerase. Very, very potent. It's a picomolar inhibitor. We took it into phase I, and it had a good safety profile, wonderful PK profile after single dosing. Even at the 24-hour trough concentrations after a single dose, you could see multiples, at least 30x multiples of the EC90 necessary to take out the virus. So it's a very, very strong PK and virology profile for the molecule. This is just a summary of the challenge study results we saw. Very strong viral load reduction of, in the mid-80% reduction. When we looked in cell culture, which is infectious virus, it was a very, very high % reduction in viral active virus.
And in fact, 12 hours after a single dose, all but one patient had demonstrated no live culture in their viral samples. We also saw good symptom improvement in that human challenge study. So in total, it's probably the best challenge study data that's ever been seen. And this is just one of the panels. We've given a full presentation on this data, but it just shows how quickly, when the drug is on board within one day, the viral loads have dramatically climbed down, and placebos continue to get worse over time. And green. Okay, let's talk a little bit about immunology. As I mentioned a year ago, we sort of unveiled our first program going after KIT. It's a mast cell targeting mechanism that targets mast cells and inflammation. And there are a number of different disease indications that you could go after.
One of the ones that's talked a lot about in this area is chronic spontaneous urticaria. Later in the year, we announced our STAT6 program. And in total, we believe that these two mechanisms offer us a wide, wide variety of opportunities to go after many, many different indications in the inflammatory and immunology disease space. It's no secret that these are very large market opportunities. Urticaria alone is estimated at $5 billion. Atopic dermatitis around $30 billion. And there's room for growth in, again, lots of these different areas that we're talking about. So very wide opportunities that we're talking about here. So let's get into the KIT inhibitor briefly. As I mentioned, it's a mast cell targeting mechanism. KIT is responsible.
If you inhibit KIT, you're blocking the cell survival signal, so you can actually cause mast cells to apoptose and reduce the numbers of mast cells in mast cell-driven disease, which is a powerful thing. You can also dial it back a little bit and modulate mast cell activity. So it's a really interesting target, and it's a target that actually has proof of concept with monoclonal antibodies. Companies like Celldex, for example, have demonstrated probably best in disease efficacy in chronic spontaneous urticaria, for example. The disease, if you're less familiar with it, can be really debilitating: itch, hives, erythema. You can have angioedema in various soft tissues. And one of the surprising things, at least to me, was that it affects about up to 1% of the global population. So this is a lot of folks.
Most people would think in these instances you would just pile on antihistamines for the itch. And even high-dose antihistamines only control about 50% of the patients. There's one biologic that's indicated in this indication, and it treats a minority of patients with this condition. So big opportunity for an oral agent to come in. We selected a candidate, another one of our goals for last year called 1421. It's a nanomolar potency , has lots of different properties that you would like, including a high degree of selectivity for KIT, which is as a kinase, you want to make sure you have very good selectivity. And again, one of the things Enanta does very well is optimize ADME properties for any agent that it goes after to try to match good ADME with the appropriate need for the disease. This is just some data.
The data on the left is in vitro data looking at binding and cellular activity, and it demonstrates that it's certainly potent in the nanomolar range, sort of in the 2-11 nanomolar range. And the data on the right is new data that we haven't disclosed previously, but it's an in vivo model in which you have a KIT ligand. It's a cytokine called stem cell factor or SCF. And what this data demonstrates is that you can very effectively block SCF-stimulated mast cell activation and histamine release. And so you see a very nice dose response and an EC50 in this animal model of 0.25 nanomolar. So it's quite, quite, quite potent. So another thing, as I mentioned, is selectivity. You want to make sure that you're selective going after KIT versus the world of kinases, and we've demonstrated good selectivity in that regard.
You also want to demonstrate that you have good selectivity against more related kinases to KIT, and these would be so-called KIT family members like CSF1 receptor and the like, and you can see that we've demonstrated very large selectivity windows over related kinases. Okay, just a bit on STAT6 to sort of wrap up. This is our newly announced program. We've been working on it for a while here, but basically, in a nutshell, we're viewing STAT6 inhibitors as an opportunity to develop an oral DUPIXENT, so DUPIXENT is a monoclonal antibody that targets the IL-4, IL-13 receptor complex, and instead, what we're going to do is just downstream, you can see where STAT6 is. It's a transcription factor that's phosphorylated by JAK, then it undergoes a homodimerization.
It undergoes a nuclear translocation, and then it turns on and off various genes so it can transactivate a number of different pro-inflammatory gene phenotypes. So in that regard, we should be able to recapitulate a lot of the biology of DUPIXENT, but with an oral agent, which is our ultimate goal here. And I think most people are highly familiar with, for example, atopic dermatitis. It's a very substantial market. It's Th2-driven, affects a huge number of adults. And whereas DUPIXENT dominates the market, now I think there's a great opportunity for an oral agent. Oral JAKs were thought to be one of those, but they're less used because of some of the safety implications of JAK inhibition. So we're very excited about STAT6. So where are we? So we have, again, a very concentrated effort going on at Enanta on STAT6.
We've demonstrated we can potently inhibit STAT6 biochemically and in cells. Important to have high selectivity. If there's something called STAT6, one might imagine there are other STATs that you have to be thinking about. And we've really started to unravel how you build a really selective profile there and gone further in terms of in vivo work that we'll describe in the future. So with that said, I just will close now by talking about some key catalysts for 2025. On the KIT program, we indicated we picked EPS-1421 late last year. This year, we're performing scale-up of drug for all the preclinical and final drug supply for clinical trials. We're completing IND-enabling activities this year. And STAT6, our goal is to select the development candidate for STAT6 in the second half of this year.
And then lastly, in immunology, much like last year, where we indicated that we would try to have a candidate for the target in question, we would also aim to have another program. So much like last year, where we added our second program, this year we plan to add a third program in immunology. In virology, the really key things for us to do are to go to regulators, talk to them about trial design for what does the registration trial pathway look like? and next steps in RSV in pediatrics. In parallel, we're working on completion of the high-risk adult study. Our plan is to finish recruitment of that next quarter and to report data in Q3. And then finally, from a business development perspective, our goal is to pursue partnerships for Zelli and/or EDP-323.
I think it's time to explore those in earnest so that we can scale this in a way that will help fulfill our vision of bringing forward the first-ever treatment for RSV infection. So with that, I'll pause and thank you.
Well, great. We have time for a few questions. So for the phase two high-risk study, just when looking at symptomology, you're using the RiiQ, patient-reported outcome scale. Can you just talk about sort of how that endpoint, the extent to which it's how well it's validated and the extent to which it's intended for utilization in a potential registration-directed study?
Sure. So the RiiQ.
Sorry, I apologize. This is Dr. Tara Kieffer, our head of product strategy at Enanta.
Thanks, Jay. So the RiiQ is a patient-reported outcome tool used to assess symptoms and impacts of respiratory infection in adults. And so it's been in a number of clinical trials for RSV previously. So there's generally good evidence for the content validity. And we'll be generating our own data as well through the phase II study, RSV-HR. It is certainly something that we could use as an endpoint in a registrational trial.
Okay, got it. And just also picking up on the results from the RSV-PEDS trial that recently read out, your plan is to sort of explore RESOLVE-P a little bit more to kind of enhance that as a symptomatology measure. I guess, can you talk about sort of any other studies that are underway, either internally or externally, that could serve to better validate that scale?
Sure. So we do have an observational study that's ongoing with RESOLVE-P that's in children that have community-acquired RSV infection. We obviously have some of the data from the RSV-PED study, and we'll be continuing to generate more data in new studies going forward.
As you've kind of noted, Jay, in wrapping up the presentation, you're kind of coming to a decision point here in choosing between either zelecapavir or 323. I guess, what are the aspects of L-protein inhibition that might differentiate from N-protein inhibition? How do the different mechanisms perhaps lead to better potency or different outcomes?
Yeah, well, we're not necessarily choosing between them. I think, and this is particularly why at a point a partner could really help propel the thing, because I think we have Zelli, which is a bit further along. It's a replication inhibitor. It's shown what we intended it to show along the way. It has the chance to be probably the faster product to market.
That said, I guess we're blessed with having another agent, which one might have originally thought, well, maybe it's a backup in case Zelli doesn't work, or it's always good to have a different mechanism and see what happens. Maybe you want to have a combination in certain rare patient not rare, but instances, for example, with a highly, highly immune-suppressed patient, maybe they would benefit from two drugs rather than one with orthogonal mechanisms. But they're both very strong replication inhibitors. It's just what's so interesting about 323 is just how rapidly it attacks the virus, and Zelli set a pretty high bar with regards to that.
But 323, again, that first day, when you look at the slope of how quickly the viral loads come down and how quickly it extinguishes live virus, even 12 hours after one dose, you can't help but wonder, maybe if the goal here is to get to a patient as soon as possible and get the drug on board, the only way you could make that even better is if the drug were even more rapidly acting. So is that something that could be exploited with time to create the best-in-class profile for a second molecule? So these are things that could be sorted over time, but right now, we think they're both very strong.
Okay. And maybe just a final question on the STAT6 inhibitor program. Can you just talk a little bit more about the mechanism by which you're engaging the target there? Obviously, there are different approaches that are being pursued in the competitive landscape: protein degraders, SH2 domain binders. I guess, talk a little bit about your approach here and sort of the level of inhibition, the readouts basically that you're using to assess that depth and potency of inhibition?
Sure, yeah. So Enanta is going about it using a small molecule inhibitor. There are other approaches such as degraders, as you mentioned. Both of these modalities, the goal essentially is to block the signaling for an IL-4/13 pathway, either through inhibiting the protein, STAT6, or degrading it. For a small molecule inhibitor, if you can get exposure, drug exposure in the right tissue at levels that are multiples above your EC90, you should be able to get complete inhibition of the protein. So our goal at Enanta is to optimize around potency.
We'll use a number of different cellular assays and animal models to achieve that potency. And then that, coupled with also optimizing around DMPK profile, drug metabolism, drug distribution, pharmacokinetics preclinically, those things can help guide dose selection for the human trials. I think for a degrader, Kymera is testing this currently in a phase one study. And so that will be very informative in terms of the safety and the PK translation into humans, as well as other biomarkers for STAT6 degrader.
Okay, great. I think we'll leave it there for time. So thanks very much, Jay and Tara, for joining us today. And thanks to everybody for tuning into the session.