Awesome. I think we can probably kick it off at this point. So, good afternoon-or good morning, everyone-and, welcome back to our Global Biopharma Conference. I'm Nik Gasic. I'm a Vice President, Equity Research, at Leerink, working with Senior Analyst Roanna Ruiz, covering infectious disease, endocrine, and cardiovascular disorders. Very pleased, to introduce Dr. Jay Luly, President and CEO of Enanta Pharmaceuticals, as well as Dr. Tara Kieffer, Chief Product Strategy Officer, who are joining us today to discuss the company, and its multiple clinical development programs. So I guess with that, I'll start off with a bigger question, maybe for you, Jay. Just for investors who are newer to the story, could you give us, you know, a sense or an overview of the company, you know, your different antiviral programs, and, you know, how-how you're expanding your focus into, into, immunology?
Sure. So, 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. Yeah, Enanta, for those of you less familiar, we're—we've historically been a virology company, sort of a pure-play virology company, starting, for many years in hepatitis C. We did, you know, multiple deals in hep C, teamed up when it made sense to team up, and worked with AbbVie to help bring two cures for hepatitis C across the finish line. The most recent one is called MAVYRET, the first and really only eight-week cure for hepatitis C. So we're pleased to have had that as, as part of our legacy, where we've cured well over 1 million patients worldwide with chronic hepatitis C.
So we, we parlayed that strength into lots of other areas and approaches in hep C, but ultimately broadened into other areas of virology, first going into another liver virus, hepatitis B, and then ultimately thinking that we really needed to branch out of the liver compartment, because hep C and hep B were the really big ones there, and we already had a footprint. So we got into respiratory viruses, and the one that was just calling out dramatically for, you know, some success in a therapeutic was RSV. So there are no approved drugs for RSV treatment. And we really wanted to try to be the first there. So we carved that out. We got going with our first approach, which is an N-protein inhibitor, called EDP-938, or otherwise known as zelicapavir. I'm sure we'll talk about that a lot today.
And then we got another program going, a polymerase inhibitor, which is another direct-acting antiviral. It's a replication inhibitor. It shuts down viral replication, called EDP-323. And we have some data coming on that one, too, this year. And then the pandemic broke out, and doing what we do in not only virology but respiratory virology, we couldn't not work in COVID. So we jumped into that fray. We had deep experience in protease inhibitors from our hepatitis C days. And so, not surprisingly, we went after SARS-CoV-2 protease and came up with an interesting molecule there. But at some point we looked at human metapneumovirus a little bit. It's not as big of an opportunity as RSV, but a good adjacency.
So we began to feel like we had sort of started to cover many of the major unmet needs in human respiratory viruses. So we had to start to think about, well, what next? And, you know, we did a little bit of boiling of the ocean in terms of thinking of all the white space we could get into. But fairly quickly, we zeroed in on immunology, just in part because of the unmet needs that still exist there, the opportunities that are present clearly today, and where benefit could still be gathered, and also because of the adjacency to virology in certain ways, where it allowed us to make a sort of a seamless transition into that area. So we started diving into that, well, certainly more than a year ago, you know, quietly working and bringing up some new things.
So I think, you know, going forward, we've looked at virology extensively. It's not to say that there aren't other things that could be done in virology, but we're, you know, looking at that as a, you know, as a trade to going into immunology, where there could be yet other many other things that we could work on, so.
All right. Lots going on.
Yep.
I guess looking ahead, later this year, you know, what are some of your clinical regulatory priorities for the year? You know, what catalysts would you highlight for investors, to look forward to or focus on later this year?
Yeah, well, clearly two big ones in virology are RSV data readouts. So we have a data readout coming for each of two RSV drugs. So the N-protein inhibitor, again, our more advanced asset, we're targeted to have a phase II readout in our pediatric study in Q3. And then also, our polymerase inhibitor is in a phase II challenge study right now. And we should also have data for that molecule from a human challenge study in Q3. So I'd say those are the two major clinical ones. We obviously have other clinical things going on. We've got a study in high-risk adult patients with RSV. That's going to continue down into the Southern Hemisphere. They're beginning to head into winter. So RSV just never sleeps. It just keeps moving around.
So it's time for the Southern Hemisphere to light up. And we have sites in Brazil and Argentina and South Africa, Australia, New Zealand. And so we'll continue to recruit that study down there and see what that season brings to us. On the immunology front, it's not a clinical catalyst per se this year, necessarily, but we have a, you know, a goal of establishing a KIT inhibitor development candidate this year. And the goal would be to have a very polished molecule with a good data set and have it ready to move fairly quickly into the clinic with that package. So that's on our radar as well. And then also, we're aiming to, you know, sort of roll out publicly another immunology program later this year.
Interesting. Lots to look forward to then.
Yeah.
Maybe, zeroing in on RSV a little bit.
Yep.
You mentioned, you know, you're going to have the top-line data from the phase II pediatric study for EDP-938 or zelicapavir in the third quarter. You know, how should investors think about, you know, how to gauge efficacy, safety in that trial? You know, what are you hoping to see there? And, you know, how might it, you know, inform future design of a possible registration program?
Okay. Maybe I'll let Tara.
Sure. So the RSVPED study is a first-in-pediatric study. So we have to think about it a little bit differently, because we do need to do some dose finding and selected dose. That's going to be done. That has been done in part one of the study, where we're looking primarily at safety and PK at two different age cohorts. So the goal there is really to show good safety, which obviously is important for any drug, but especially in this young patient population. We're dosing patients down to 28 days, up to three years. We're looking at the PK as well to select an optimal dose for the different age cohorts. And then that dose then moves into part two, where we're looking primarily at virology. So we'll look at a number of virology endpoints.
We will also look at clinical endpoints like symptoms as well, although the study's not powered on that. The goal of the study was to run an efficient study about 90 patients that gave us some data that would build confidence in the antiviral activity, have some directional data and trends that would allow us to move into a larger, more powered, phase III study. So we'll be interrogating the data as it comes in, here in Q3 and looking at that to then help design what that phase III program would look like.
Got it. That's helpful. And we've gotten this question from investors quite a bit. It's, you know, what read-through do you see from the pediatric trial, RSVPEDs, to, you know, the higher-risk adult, older adult trial? You know, is there any potential read-through there? How should we think about that?
So I don't think that there's limited read-through in my mind because the patient populations are quite different. So pediatrics are at high risk for RSV because they have no immunity built up. All children will have exposure to RSV by the time that they're two. And they probably need multiple infections to really build a robust immunity that would be similar to what a, you know, a young, otherwise healthy adult would have. Whereas in the adult high-risk patient population, you have a couple of different risk factors. So we're enrolling patients that are 65 and older. So, you know, as these older folks get into those age ranges, their immunity begins to wane, and they have, you know, less immune response towards RSV.
We are also enrolling patients that have asthma, COPD, congestive heart failure, so other comorbidities that put them at high risk for RSV. It's a little bit more of a heterogeneous population. We've tried to focus on the most severe of those patients. So we've capped patients that are 65-75 and those that are asthmatic at 20%, so really trying to enrich for the most severe patients. Study designs are a little bit different between the two studies. We talked about RSVPEDs, but the RSVHR study is a little bit bigger. It's about 180 patients. We'll be primarily looking at symptoms in that study. Obviously, a positive result in RSVPEDs is promising for RSVHR. But, you know, we'll be looking at both studies separately.
Got it. And in terms of enrollment for the RSVHR study, you know, you mentioned it is a larger program. How is that, you know, progressing this year, across the, you know, Northern Hemisphere? And, you know, what are your, I guess, future plans for enrollment there and timelines for that data there?
Yeah. Well, as I indicated, I mean, we used to get questions all the time about, you know, which one was going to come first. And for, you know, a period of time, you know, we couldn't call it. We did call it, you know, fairly recently this year because it became clear that PEDs, again, given that it's about half the size of this study and that we did have, you know, a fairly normal season this year, it's still ongoing in the Northern Hemisphere. It became clear that the PEDs study just was going to get across the finish line first. So that necessarily takes you down to the Southern Hemisphere. We'll just have to see, you know, hopefully they're going to have a fairly normal season again.
Hopefully, the Northern Hemisphere here was sort of a harbinger of what, you know, that we're back on the tracks in a, I don't want to say a post-COVID world, but in a post-crazy COVID world where, you know, it completely obliterated RSV. And then when it came back, it messed around with the seasonality and made it very challenging to recruit. But I feel like we're on a more even trajectory. So we'll just see how the Southern Hemisphere plays out as the year evolves. And then we'll give continual updates on guiding where that stands.
Got it. I mean, maybe switching gears a little bit, just given, you know, the availability of maternal vaccines for RSV and, you know, older adult vaccines, where do you see, you know, an oral antiviral like EDP-938 or zelicapavir, you know, fitting into the treatment landscape? You know, how large could a, you know, the market opportunity ultimately be for an oral in this space?
Sure. So we still see a vast opportunity for treatments. There aren't any treatments at the moment for RSV. Despite you know progress in vaccines, which I think is an important part of the solution, we still think treatment is needed. So we look at the adult population. There have been two vaccines recently approved there. What we know for this first season is that about 11% of the eligible population has been vaccinated, leaving you know the vast majority of almost 90% of patients still vulnerable. We do know that patients that even get vaccinated can have breakthrough infections. So we'd be looking to treat those patients. On the pediatric side, there's sort of two strategies there because vaccines, true vaccines for pediatrics have yet to be developed. So one strategy is to vaccinate the pregnant mother.
Then obviously, the antibodies transfer to the infant. So key to success there is vaccinating as late in pregnancy as possible so that those antibodies have as much time as possible in the infant. So the challenge with that program has been a little bit around safety. GSK had a program that was terminated. Pfizer's vaccine has been approved, although they did see a numerical imbalance in the number of preterm births in that study. So I think we'll see ultimately what the uptake will be there. The other strategy is a monoclonal antibody that would be given at birth for the pediatric population. Both of those strategies are passive immunity. So once the antibodies leave the baby's system, which is, you know, generally four to six months, they become completely susceptible to RSV.
And so these strategies are essentially just going to push the first RSV infection to a slightly older age range. And again, in this setting, even with these prophylaxis options, there is breakthrough that we see. And so ultimately, looking to treat all of those patients as well.
Got it. I think you mentioned, another antiviral in development that you have, EDP-323.
Yep.
Currently in a challenge study. You know, how should we think about that molecule? You know, how is it differentiated from EDP-938 as far as the mechanism goes? You know, where do you see it fitting in the treatment paradigm relative to EDP- 938? Do you see potential for combination use of the two?
Yep. So they're both, you know, one of the things that sort of differentiates our approach from historical approaches. Historical approaches predominantly were fusion inhibitor targeted. So they were trying to block viral entry into cells. But what we reasoned early on was that by the time a patient presents, you know, they can have a very serious infection ongoing. The viral load is, you know, dramatically ramping up as the virus expands and is under a high rate of replication. And entry inhibitors can only try to block entry into new uninfected cells. And so the drug basically has to try to catch a number of arrows. We decided it would be more efficient to get in there, just like we'd done in hep C and lots of other viruses have, you know, obvious precedent for working on shutting down viral replication.
So those are the only approaches we took with our molecules. So both of ours are replication inhibitors. One goes after the N protein. One goes after the L protein. So the one that you're referring to, our second one, goes after L, which is the viral polymerase. So they're just slightly different mechanisms. Now, we've got a great challenge study on EDP-938. It's published in the New England Journal for people who haven't seen those data. But it's a high bar, you know, that we've already set with our first one. And so we're hoping that the data from our second molecule should, you know, hopefully at least replicate that early success we had with zelicapavir. EDP-323 is a very, very potent molecule. And it's a picomolar inhibitor of the polymerase. It's safe and well tolerated in phase I studies.
And so we have that expectation for the challenge as well. It has a great PK after a single dose, single daily dose of what will ultimately be, well, is in the challenge, five days of dosing. And then the trough concentration at the 24-hour time point, even after a single dose, gives huge multiples over the protein-adjusted EC90. So these are all sort of harbingers of efficacy, if you will. And, you know, we're hoping to see that. Now, the next question is, well, how do you position those two? So the good news is we'll be getting, you know, phase II data in PEDs roughly around the same time that we should be getting the challenge study. And so we'll have a couple of data sets to look at. You asked the question, could they be used in combination?
You know, we're hopeful that, for the majority of patients, that a single agent would be adequate. Again, the proof is in the pudding. You ultimately have to show that. But it's an acute viral infection. The molecules, both of them have good barriers to resistance. EDP-938's extraordinary when it comes to its resistance barrier. So you shouldn't need to do a combination to sort of thwart the possibility of viral resistance, which, by the way, has always been an issue with fusion inhibitors, the other class that we didn't go near it. That was another reason we didn't go there is, you know, even after dosing fusion inhibitors for two to three days, you can see the emergence of resistance mutations. And that's never a good thing, in the area of virology.
So, we don't know that we need them in the ordinary case of a patient population. But mightn't there be different ways to position one drug in one population, another, and another, or create a combination for those particularly challenging to treat cases, where, you know, you might be able to, for example, catch somebody a little bit later in their stage of infection, but much more aggressively, reel them back in with two drugs rather than one? The net effect of that would be to widen the treatment window potential, which would obviously increase your addressable patient population. So these are all kinds of things under consideration.
You know, when we went out at the beginning of this, it was really to scope out and to chart a leadership position in this area, you know, try to be first to market if we can, try to have the broadest footprint. If anybody's going to come up with an agent in one of these other classes, we would rather be us rather than someone else. It just gives us a lot of optionality in the future.
Got it. That's helpful. Maybe a bigger picture question, in RSV, just, you know, how are you, how are you thinking about partnership opportunities in the space? Is this something, you know, you're looking to advance, and commercialize on your own? You know, when, you know, when would you expect to share more around possible partnerships in the RSV space?
Yeah. Well, we're, you know, there, we're always receptive to entertaining, you know, discussions along the lines. I, I think one of the things, you know, I would contrast RSV a little bit, versus COVID, where in COVID, we've indicated, you know, we're only going to go forward in COVID in the context of a collaboration, right? It's a, you know, sort of a, a world pandemic situation, or at least a very large global footprint that, some of the existing COVID drugs have on the marketplace out there. And I think, it's one of the things where we would want to have line of sight into a, a commercial partner before we, advanced it. And ideally, we would have, you know, the, the, strategic partner, you know, carrying that load from an operational standpoint and from a funding standpoint. I would say RSV is a little bit different.
I mean, you know, our plan is to, you know, seamlessly keep moving forward. And then obviously, we, you know, could or would entertain discussions along the way. But that's not, I don't view that to be the same sort of imperative as in COVID, that we could, you know, well go, you know, into phase III ourselves and beyond.
Helpful. Maybe switching gears a little bit. I want to make sure we have enough time to cover your chronic spontaneous urticaria work.
Yep.
I guess what data or evidence motivated you to sort of look at the space and develop a therapeutic in the space? I guess relative to other immunology indications, what kind of pushed you into that direction?
Sure. So I think we were very excited by the data that Celldex generated with their antibody against KIT, which is barzolvolimab. They have recently given a lot more details around their phase II study that look very promising, efficacy that seems to be best in disease from what we can tell, with a good safety profile. And so our objective here was to go after the same target with an oral molecule, small molecule. And so, you know, I think that the clinical path for CSU is very straightforward, clear regulatory endpoints, and early biomarkers that can give you a sense of activity, early on in the program, that being serum tryptase.
So I think one nice thing about this is that immediately when you move into the clinic in a phase I dose-ranging in healthy volunteers, you can take a look at this biomarker and get a good sense of activity of your compound. There's a lot of data generated that is able to correlate tryptase to downstream clinical outcomes ultimately. So we like that about the program. High unmet need, this affects anywhere between 0.5% and 1% of the population. It's a very severe disease. Patients get hives, you know, across their body, and it's quite itchy. It's also, you know, affecting multiple other, you know, sleep, patients develop anxiety, depression. So it's quite a severe disease. And the standard of care is antihistamines, which really only works in about half of the patients.
There is still a lot of need for better improved efficacy for these patients.
Got it. No, that's very helpful. I think you mentioned plans to select, you know, a KIT inhibitor candidate to advance by the end of the year. In terms of, you know, what's left to do ahead of that, you know, decision, you know, what are you looking for in a potential candidate that you're hoping to advance and, you know?
Yeah. So we, you know, we initiated, you know, sort of the hardcore drug discovery and non-clinical development activities in this program a while back and, you know, have generated a lot of chemical matter, as you might expect. And I mean, and that's among the things that Enanta does incredibly well. And, you know, we're zeroing in on a lot of the things we would for any program. You know, you're looking for potency, selectivity, safety, good PK, biodistribution, you know, compartments to try to get into, compartments to try to avoid getting into, et cetera, et cetera. So, it's a little bit, you know, we always, at any given time, we've always got a good molecule in hand that we're trying to knock off its pedestal with a better molecule. And, you know, I think, there just becomes a point where you say, good enough.
It's a good molecule. We could always keep going on and iterating. But I think we're doing well in this in terms of achieving our goal for a candidate this year. And the further goal would be to have a candidate that has you know a lot of preclinical characterization in it so that it's you know could be moved fairly quickly into the clinic.
Got it. You mentioned, you know, possibly announcing a second immunology program towards the end of the year. Could you help contextualize, you know, what possible disease areas you could look at or, you know, how maybe in terms of, you know, how large the market opportunity could be or unmet need in the, in the space?
Yeah. Well, I mean, we wouldn't get into something that it didn't make commercial sense. I mean, one of the things that we do as a very early cross-check in any of our programs is we're testing the commercial feasibility, looking broadly across the landscape. You know, obviously in immunology, there are a lot of antibody approaches to things. We're, at least right now, we're zeroing in predominantly on small molecule approaches where a small molecule might have a different treatment modality, a benefit in that market, or at least be able to capture a good chunk of it. Ideally, we're looking for things that have really strong scientific rationale and good mechanisms. If you can have clinical proof of concept already in the area, that's wonderful.
I would expect that over time, we'll have a blend of those kinds of things where there may be clinical proof, there may not be, there's pros and cons to those kinds of things. Yeah, so we're working on multiple different things internally right now. And again, it's a vetting process. We used to do that in virology too. Not everything that we worked on, you know, ultimately, you know, went forward. And we pushed some things off to the side. So I think in any next target approach that we announce next program, we want to make sure, again, the commercial boxes check, the biology is up, assays are developed, chemistry is underway. We're on the boards with molecules, intellectual properties being built, you know, just a really solid program.
You know, again, we believe that that will, that card will turn over later this year.
Got it. Looking forward to it. Maybe in the last minute or so, just taking a look at the balance sheet, you know, how should we think, you know, how, how should we think about the cash runway outlook? And maybe how are you planning to prioritize the R&D across antivirals, antiviral programs, and then your immunology program as well?
Yeah. I mean, we've got a sort of a holistic view on it. We finished the last quarter with just under $340 million in cash. We're due a tax refund as well, a rather sizable one, that would be on top of that. We have cash currently through fiscal Q4 of 2027. It contemplates, you know, moving all programs except for COVID forward ourselves. Obviously, having monetized a bit over half of our hep C royalty, you know, topped off our tank, we still get cash flow from the other not quite half. It's all in a pretty good balance, I think, you know, for right now.
Got it.
Yep.
I think we're just about at time here, but it was a pleasure having you here. Thank you, Jay. Tara, thank you.
Thank you.