Hello, everyone, and welcome to Oppenheimer's 34th Annual Healthcare Conference. I'm Jay Olson, one of the biotech analysts here at Oppenheimer, and I wanna thank you all for joining us. It's my pleasure to welcome Enanta Pharmaceuticals to our conference, and it's an honor to introduce Tara Kieffer, the SVP of New Product Strategy and Development, and Jay Luly, President and CEO. If you have any questions during our discussion, please feel free to submit them using the Q&A function, and with that, we'll get started. Thank you for joining us, Jay and Tara. Jay, I'll turn it over to you for any opening remarks you'd like to make for those who may not be familiar with the Enanta story.
Sure. So thanks, thanks for having us to the conference. Before I begin, I wanna remind you that 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, so for those of you who are less familiar with Enanta, we are a virology and immunology company. Probably our foundation is in virology, and we'll talk about that, and our transition as we move beyond just virology. But started working in hepatitis and came up with a couple of cures for hepatitis C with AbbVie, the only 8-week cure for hepatitis C patients.
It's gratifying to be able to have been a part of that discovery and development, and commercialization, process, where we've cured over 1 million patients with chronic hepatitis C. Then we moved on to other viruses, got heavily involved in respiratory viruses. RSV became a major focus for the company, and we were getting along in that area when the pandemic broke out, another respiratory virus some of you may have heard about. So we strapped that virus on the pipeline as well, and went back to our roots in protease inhibition, and came up with a protease inhibitor for COVID.
So we have a strong concentration in respiratory viruses, but we've also, you know, run out of huge viral opportunities, viral opportunities where we think there's a massive unmet medical need, and where there's a commercial opportunity for the company, and where we think we can innovate. And so, beyond respiratory viruses, we decided to transition into other areas of interest, and immunology rose very high up on our priority list. You know, there's some adjacent skills that are applicable from the team. In fact, some of our virologists actually trained in immunology first.
And so we've been building that up, you know, quietly, I would say, for the last couple of years, and now more visibly as we rolled out with our first immunology program earlier this year. So, I'm sure we'll get into a lot of that as we discuss today, but that's sort of the backdrop of where we were and where we are.
Excellent. Thank you so much for that overview. It's super helpful, and I know a lot of investors are very excited about your recent expansion into immunology, so maybe we'll start there. Can you just give us a background to some of the key achievements last year, and then what, I guess, kind of drove you into immunology? You gave a little bit of background there, but what kind of drove you into immunology?
Yeah. So again, I think, you know, one of the things we wanted to do is just focus on, you know, what are our core strengths, right? We have very strong drug discovery engine, you know, very good development capabilities. And so that's when you're presented with that, you could go in lots of different directions, maybe too many. So we started focusing. Well, we started looking, you know, broadly and then narrowing things down, you know, ultimately into immunology. I think part of it was, again, the some of the adjacent skills that were already built in-house. I mean, a lot of people, some people had actually focused on immunology in their past. I used to do it. I mean, most of my pharma career actually was in immunology, and my first biotech was in immunology.
But I think there's just tremendous unmet need there. You know, we have lots of diseases where biologics have sort of come into a prominent and deserved presence in immunology, but there's still, we're largely a small molecule discovery and development company. So we think there are some unique opportunities where small molecules could provide other modalities that would be of interest to patients in this arena. So we're focused on looking at a lot of different diseases with high unmet medical need, ones where we really understand.
You know, the underlying pathology of the disease so that we can get at the root cause, and come up with, you know, hopefully interesting targets where, again, small molecules can deftly do their work and provide, again, good alternatives. And also indications where maybe there's, you know, well-defined development pathways, where there's interesting opportunities perhaps for biomarkers to give you early signs of efficacy. For example, there's a biomarker in CSU that you can use. And so it's along those lines. So I would say that, you know, again, we got into it, we've been working on multiple different things.
I think we're still triaging some other opportunities internally, and I expect, you know, we'll roll out another program publicly later this year.
Great, thank you for that. And we are getting, some additional questions on immunology coming in from the audience. I wanna encourage you to keep those questions coming. We'll come back to immunology in a, in a moment, but I think more near term, just a few questions on RSV. Since you are expecting top-line data from the phase 2 RSV ped study with zelicapavir in the third quarter this year, can you just talk about how the recruitment's going across the phase 2 studies, and the infection rates in the Northern Hemisphere, and, I guess any expectations you'd like to set for this year in RSV?
Yeah, well, you hate to say you're happy that a virus is back and behaving in a normal, you know, world epidemic fashion, but, but it, it kind of is. You know, when prior to COVID, there was a very, you know, clear seasonality with RSV within, you know, some season- like anything, some seasons are a little earlier, some are a little later, some are a little bit more severe. But for the most part, you know, you could set your watch by RSV coming in in, you know, sort of late October, picking up some steam in November and December, and usually peaking in Q1, and then, you know, tailing into Q2. So it's the pandemic, I think, really messed with that.
It pushed the rates down, and then it moved seasonality around, and then it caused some severe early spikes and disappearances of the virus, and so forth. So it made recruitment and studies, you know, pretty challenging, to say the least. But I think, you know, we were pleased to see, as pleased as we could be, see a virus showing up in late October, and really allowed us to recruit in both those studies, you know, at the tail end of 2023 and into 2024. So we're hopeful that with this, you know, somewhat normal, as it appears so far anyway, Northern Hemisphere season, that if it continues on that track, we should be able to wrap up. Before we were saying, you know, it'd be one or the other, it's.
And then as we got more information, we'd be able to make a call. I think, on our earnings call recently, we did make the call. We think it's gonna be peds, which is a smaller study than our adult high-risk study. It's about half the size. And so, you know, if things stay on that track, you know, my expectation is we would wrap up recruitment in Q2 and announce data in Q3. Yeah, and then the high-risk adult study, you know, we'll continue to recruit, but I expect that'll go down to the Southern Hemisphere, and then we'll just see how the seasonality is working for us or against us down there. So we'll-
Okay, great [crosstalk]
as the year progresses. Yep.
We'll certainly look forward to those readouts. And with regards to RSV ped, can you just help set investor expectations in terms of where's the internal bar for go, no-go decision for the study results there? What should investors be looking for?
Well, we're certainly looking for trends in virology, right? So this is a first in peds study, so you know, we're doing things like dose ranging. We're doing age ranging too. We're down into children as young as 28 days, all the way up to three years of age. And so there's a few different things going on in terms of the dose finding, which was in Part 1. Part 2 is all about virology. And we're you know, finishing up Part 2 now. So with the virology, unfortunately, you know, there's just not a lot. We're in sort of a front position in peds studies right now, and there isn't a lot of data out there.
I'd say the only other data set that's been out there that one could begin to look at is one by a Chinese biotech called ArkBio. They're looking at an entry inhibitor, which is in contrast to our mechanisms. And they did a ped study, a phase 3 ped study in China. And they reported out about a, I think it was a, about a 0.6 log reduction in that phase 3 ped study. And so I guess that's some sort of a benchmark that we'll be, you know, keeping our eye on in our study.
But generally, we're looking for that, you know, viral load drop, directional trend that will give us, you know, the confidence to go to the regulators, map out the final phase three design, and then get into registration studies.
Okay, great. And then since you have both hospitalized and non-hospitalized children in the, in that study, can you just talk about the split of those two populations and, and how they might be different? And is that a pre-specified stratification factor when you look at the results?
Yeah. Maybe I'll let Tara dive in on the, on that one in terms of peds.
Absolutely. So yeah, Jay, as you said, the study will include both outpatients and inpatients, and we've been actively enrolling both of those populations into the study. In terms of the differences, you know, the outpatient population tends to present a little bit earlier, and so, you know, we'll be looking to the data from these patients that may give us a signal on what the treatment window could look like. And then in the inpatient population, those patients obviously are a little bit sicker and could give us some insight into harder clinical endpoints, you know, looking at things like ICU admission or requirement for oxygen. We don't have a stratification factor in this study, but we'll certainly analyze both populations.
Okay. That sounds good. We'll look forward to that. And then, I guess, if the study is positive, and you commented on this a little bit, Jay, how soon can you get a phase 3 study started?
Well, you know, that depends on, That depends on discussions with regulators and getting, you know, everything defined in terms of protocols and endpoints. But we've already begun, you know, a certain amount of preparations and readiness to put us in a position to be able to move as quickly as we're able to do so.
Okay, great. And then, is there any read-across from RSV ped to RSV HR?
You know, they're very different patient populations. Again, we're looking at children down to 28 days of age. And even within children, you know, you've got differences as kids get a little bit older. You know, the youngest of them, or maybe it depends on, you know, the pandemic has sort of changed around the age at which you know, some kids are getting infected. But suffice it to say, it's an incredibly immune-naive patient population. These children have either never seen RSV before, or maybe they've seen it once. And so that's one consideration.
Kids also tend to spike higher viral loads than adults, probably for the, you know, in part because of that reason of the immune system not being completely, accustomed to seeing RSV. At the other end of the spectrum, we're looking at, elderly people who are either over 65 or over 75, adults who may have some other comorbidity that puts them at high risk: congestive heart failure, asthma, COPD. So these are all different kinds of, patient populations, but at the, at the elderly end of that spectrum, you have the immune system sort of going in the opposite direction. People are starting to lose the immunity that they've, built up over, their lifetime.
There's a bit of an immune senescence, and so they're immune-compromised a little bit on both ends of the spectrum, but they're very different kinds of patient populations. So we're just gonna, you know, we'll look at the data in each trial as an individual trial. Obviously, a good readout in peds is, you know, gives. That encouragement would translate over to the next study.
Okay, that sounds good. And then, I guess, can you just talk about how you plan to leverage your lessons learned from zelicapavir to EDP-323, and how you're thinking about monotherapy versus combination therapy for RSV, and whether or not you'd make a, a fixed-dose combination?
Well, we've certainly learned a lot on the way with zelicapavir. You know, we took it from infancy, you know, into, I guess, the first rite of passage for an antiviral, and for RSV is the human challenge study, right? So, I think we learned a lot doing our first challenge study with EDP-938. We got on the boards. We showed a very strong antiviral effect. We showed an effect on symptoms. A nd it's in a controlled sort of way. Obviously, you're taking healthy volunteers, and you're infecting them with the virus under a sort of a hospitalized setting. And so you're able to look at viral load measurements twice a day.
You're looking at symptoms three times a day, gathering all this information to prepare you to go out into the real world. I think with zelicapavir too, we learned you don't want to go after standard risk patients. Standard risk in RSV, you know, does not need treatment. So we learned that in one of our studies, which we certainly won't do again with our potent L inhibitor. Beyond that, we just learned a lot. There's tricks about how you set up clinical trials and how you write protocols in this arena that we've learned over time, and that can only you know, help benefit you know, another molecule from our stable going down that development path.
It also represents, you know, a little bit of a barrier to entry for other players, although there aren't. The good news is we, you know, we're sort of running ahead ourselves, with probably the main competitor is Pfizer with their entry inhibitor. And then with regards to combination—well, so 323, we're gonna. We got a very nice phase 1 package on 323 last year. And phase 1 is often sort of an unsung hero data set, but it's ever so important. You can't get to phase 2 if you don't have good phase 1 data. But more importantly, in virology, if you have good exposures and you can deliver good exposures safely, you know, you're kind of on your way to having a pretty good shot at efficacy.
So, you know, we demonstrated a 30x multiple, I think, of the protein-adjusted EC90 for 323 at trough concentrations after a single dose. So, you know, we took that positive data set into a human challenge study for 323. As I mentioned, we've got a great benchmark challenge study in zelicapavir that we've already got, and we should be able to read that study out in Q3 also. So, you know, it'll be nice to have, you know, antiviral data information on each of our molecules coming in Q3. Your question about combos, you know, we're cautiously optimistic that combos may not be required. In fact, I think it's likely that they won't be required in the majority of patients.
I guess you could ask yourself the question, you know, which is better, N-protein inhibition or L-protein inhibition? Maybe the challenge study will give us some insights into that. You could also ask the question, well, is there a time and a place to do combos? And that's a slightly different question. There may be an opportunity to do that in certain settings.
So, certain high-risk patient populations, say, who are really immunosuppressed, that might be able to, you know, deliver the extra punch that's required to truly eradicate a virus or to take it down as quickly as possible in an otherwise immunosuppressed patient, so that, you know, mutations don't start occurring, and so that you can, you know, give it the most antiviral punch without the help of the human immune system, which is usually critical for mopping up little bits. The other thing you might think of combinations for is potentially widening a treatment window. You know, if you get to a patient later, can you reel them back in if you hit it with two drugs rather than one?
I mean, that's one concept that could be thought about in terms of, you know, broadening the addressable treatment population. These are all options that we'll have, given multiple tools in our pipeline to be able to answer some of those kinds of questions, but they're all interesting questions. I don't think we would go about doing fixed-dose combinations until we thought of that right combination opportunity, and then it would make a tremendous amount of sense to do a fixed-dose combination.
Okay, great. And then, I know that our audience is eager to get to your immunology program, so we'll jump ahead to that. I guess, can you just talk about for the oral KIT inhibitor, how did you choose to pursue CSU as your first indication, and what other, I guess, mast cell-driven diseases are you thinking about?
Yeah. Tara, you want to take that one?
Sure. Yeah, I think we primarily focused on CSU as a primary indication. It's clearly driven, a disease that's driven by mast cells, so it gives us confidence in the target of KIT. There are good biomarkers available for early signs of efficacy, so we can look at serum tryptase, even in the phase 1 healthy population. And that really can de-risk the program early on. We know there's a defined and accessible larger patient population to address, and the clinical trials are fairly straightforward with clear endpoints. You know, for example, a POC, you can look at endpoints within 12 weeks. But we certainly are looking at a number of opportunities to expand into with this program.
So we know mast cells have been implicated in a number of diseases, so looking at things like chronic inducible urticaria, eosinophilic esophagitis, PN, there's a number of, you know, potentially asthma, a number of other opportunities we would consider as well, as we broaden, you know, with this mechanism.
Okay, great. And any initial thoughts on how you would compare the potential efficacy of an oral KIT versus an antibody?
I think, I mean, it's hard to compare at this point 'cause there's limited data on the oral KIT inhibitors. The only one that has gone into the clinic was from Third, a company called Third Harmonic, where they did do a phase I study. It's since been stopped due to off-target toxicity, but they did show good activity, at least in reducing serum tryptase. And so I think that bodes well, and you know, the optimization around potency and selectivity is gonna be key in these oral inhibitors for KIT. But, you know, our goal is really to provide that efficacy that has been seen with the antibodies, and just doing it via an oral mechanism.
Okay. Got it. Makes sense. And then, I guess, can you just talk about where you are in terms of optimizing the features of that drug, and how soon do you think you can move into clinical studies?
Yeah, so we showed some data on a prototype molecule, you know, earlier this year. So it's a highly optimized prototype. You know, we sort of waited to reveal the program until we were sort of at that stage. But we've got a lot of effort, you know, people trying to knock any prototype we have. Somebody's always internally trying to knock it off the mountain and come up with something better. So we're gonna give ourselves a little bit more time to, you know, to continue to see what other optimization things we can do, either from a potency or a selectivity or the, you know, ADME properties, looking at tissue localization and PK, and a bunch of different things.
So, you know, sort of in the Enanta fashion of highly optimizing drug candidates before we move them ahead. So our goal is to have the finalist this year. And then, you know, that finalist would come with a lot of safety information, too. So we would be poised, I think, to move into the clinic fairly quickly thereafter.
Okay, we'll look forward to that. And then I know you mentioned earlier that you might have another program in immunology. Is there any additional color you can share with us around what we should be looking for there?
Not a lot of color at this time, other than the broad strokes of, you know, how we're thinking about the world, which I sort of, you know, got into. I mean, looking at unmet need and looking for ways that small molecules could really add benefit, looking at development pathway, you know, ideally, quick ways to demonstrate efficacy, you know, things where biomarkers are available. So we're, we're triaging, you know, multiple different kinds of things, and, and I think, you know, some will move forward and some won't. But one way or the other, I, I suspect that there will be another, another program to talk about later this year.
Okay, got it. And then another burning question from the audience: Would you be open to partnering your immunology programs early on, or do you prefer to wait until you have some additional data?
Well, we're certainly, we're certainly poised to move it ahead, but we, we always, entertain any business discussions at any stage. I mean, I think-- yeah, I mean, the hepatitis C stuff, we, we partnered well before we even had a candidate, selected internally, But in other instances, you know, we've had molecules that were, in moving into the clinic or in a clinic. So I, I think, I think we're open-minded ultimately, but we're, we're poised and financed to, to move our entire pipeline, through the end of, fiscal 2027.
Okay, understood. And, you've mentioned a couple of really important catalysts, RSV Ped later this year, moving your oral KIT into the clinic. That'll be exciting. Any other catalysts we should be looking out for this year?
Again, the human challenge study on 323. We're really interested in seeing that come out because it's a super, super potent L inhibitor that has, you know, great characteristics. And so, having multiple RSV shots on goal and potentially multiple RSV molecules to position is an interesting situation to be in.
All right. Well, it's an exciting year ahead, and we look forward to future updates. Thank you so much for joining us here today, Jay and Tara. Really appreciate your getting us educated on all the impressive progress you're making at Enanta.
Great! Well, thanks a lot-
Thanks, Jay [crosstalk]
... for the opportunity.
Yes, our pleasure. Thanks for joining us, and thanks everyone.
Thank you.