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spk08: Good afternoon and welcome to Enanta Pharmaceuticals Fiscal Third Quarter 2021 Financial Results Conference Call. At this time, all participants are in listen-only mode. There will be a question and answer session at the end of the prepared remarks. Please be advised that this call is being recorded. I would now like to turn the call over to Jennifer Vieira, Investor Relations. Please go ahead.
spk01: Thank you, Operator, and thanks to everyone for joining us this afternoon. The news release with our fiscal third quarter financial results was issued this afternoon and is available on our website. On the call today is Dr. Jay Lulli, President and Chief Executive Officer, Paul Mellott, our Chief Financial Officer, and other members of Enanta's senior management team. Before we begin with our formal remarks, we want to remind you that we will be making forward-looking statements, which may include our plans and expectations with respect to our research and development pipeline and financial projections, all of which involve certain assumptions and risks beyond our control that could cause our actual developments and results to differ materially from those statements. A description of these risks is in our most recent Form 10-Q, and other periodic reports filed with the SEC. And ANSA does not undertake any obligation to update any forward-looking statements made during this call. With that, I'd now like to turn the call over to Dr. Jay Lui. Jay?
spk12: Jay Lui Thank you, Jennifer, and good afternoon, everyone. Our fiscal third quarter was marked by the achievement of several important milestones and continued progress across our clinical portfolio. Starting with COVID-19, we are pleased to announce that we have identified a clinical development candidate, EDB235, an oral protease inhibitor specifically designed to treat SARS-CoV-2 infection and potentially other coronavirus infections. We are eager to progress this program into the clinic and are on track to initiate a phase one study of EDB235 early next year. In hepatitis B, we are excited by the progress we've made with EDP514 and EDP721, which we are developing as part of an all-oral combination regimen to achieve a functional cure. We expect to begin dosing in our Phase I study of EDP721, a novel oral HPV RNA destabilizer, this month. Additionally, this quarter, we announced positive Phase Ib 28-day data for our core inhibitor, EDP514, in two important patient populations, chronic HPV patients who have a high viral load, whom we refer to as viremic patients, and chronic HPV patients who are on a treatment with a nucleoside reverse transcriptase inhibitor, whom we refer to as nuke-suppressed patients. The significant progress we've made across our HPV program brings us closer to our goal of developing an all-oral functional cure for patients. Moving to the rest of our pipeline, we have three ongoing Phase II clinical studies investigating 938 for respiratory syncytial virus, or RSV, and two ongoing clinical studies for candidates to treat non-alcoholic steatohepatitis, or NASH. In addition to our clinical programs, we continue to progress our respiratory virus discovery initiatives to identify an L inhibitor for RSV, and an inhibitor for human metapneumovirus, or HMPV. With that, I'd like to dive deeper into each of the programs that make up our robust pipeline, beginning with SARS-CoV-2. We are pleased to have selected EDP-235, a direct acting antiviral oral protease inhibitor, as our clinical development candidate for SARS-CoV-2 and plan to initiate a clinical study early next year. As SARS-CoV-2 continues to mutate and new variants arise, we believe there remains a need for a potent oral treatment that is specifically designed to inhibit replication of this virus and are excited to progress this program. While vaccines and antibody therapeutics in development today target the viral spike protein, EDP235 has been specifically designed to target a conserved region in the active site of an enzyme essential for SARS-CoV-2 replication, so we do not expect mutations in the spike protein to significantly affect the activity of our candidate. Further, EDP235 potently and selectively inhibits SARS-CoV-2 replication in multiple cellular models including primary human airway epithelial cells, where it demonstrated an EC90 of 33 nanomolar. Importantly, activity is retained against currently circulating SARS-CoV-2 variants, and a high barrier to resistance has been observed. Additionally, EDP235 demonstrates preclinical properties supportive of once-daily oral dosing. If we are successful, our vision is for an early diagnosis of COVID-19 followed by outpatient treatment with a highly potent and targeted oral therapy. Shifting gears to HPV, we recently announced preliminary data from the first two dose cohorts of our Phase 1b study of EDP514 in viremic chronic HPV patients, which further demonstrated the compound's safety and tolerability, as well as its ability to reduce HPV DNA levels significantly over the 28-day dosing period. To briefly recap the data, 16 patients were randomized to receive daily doses of either 200 milligrams or 400 milligrams of BDP514 or placebo for 28 days. Mean reductions in HPV DNA of 2.9, 3.3, and 0.2 logs were observed in the 200 milligram, 400 milligram, and placebo groups respectively. with a maximum reduction of 4.2 logs in the 400 milligram group versus 0.5 log in the placebo group. More patients receiving EDP514 had HPV DNA below the lower level of quantitation compared to none who received placebo. Additionally, mean reductions in HPV RNA of 2.9, 2.4, and 0.3 logs were observed in the 200 milligram, 400 milligram, and placebo groups, respectively, with a maximum reduction of 4.8 logs with EDP514 versus 1.9 logs with placebo. HPV RNA was undetectable at day 28, and eight patients in the 514 group was compared to none in placebo. Further, EDP514 was shown to be safe and well-tolerated in this patient population. This study provides important clinical evidence of EDP514's safety profile, as well as kinetics of viral inhibition when used as a single agent over 28 days, and is a significant advance in our efforts to deliver an all-oral functional cure for hepatitis B. Building on that success, we also recently reported positive 28-day data from the first two cohorts, 200 and 400 milligrams, of our Phase 1b study of EDP514 in nuke-suppressed chronic HPV patients. Importantly, these 28-day data demonstrate that EDP514, when combined with a nuke, is safe and well-tolerated. Additionally, EDP-514 demonstrated reductions in HPV RNA, along with a pharmacokinetic profile supported of once-daily dosing. Together, these data support development of EDP-514 in combination with a nuke as a two-drug foundation on which to add other agents, such as EDP-721. Such an all-oral combination therapy is a differentiated approach that could potentially lead to a functional cure for patients with chronic HPV. To that end, we expect to begin dosing in the Phase I study of EDP721, our oral HPV RNA destabilizer, this month. Our enthusiasm for the development of EDP721 is based in part on the preclinical data we presented at EESL in June. In vitro, EDP721 potently reduced HPV surface antigen with pangenotypic HPV activity through its selective inhibition of PAPD5 and PAPD7. Moreover, EDP721 showed additive to synergistic antiviral activity in vitro when combined with nukes or HPV core inhibitors such as EDP514. Oral administration of EDP721 and the AAV HPV mouse model also demonstrated favorable efficacy characteristics, inducing up to a three-log drop in the HPV surface antigen. These preclinical data are particularly exciting because effective reduction of HPV surface antigen has presented a substantial challenge to achieving long-term HPV viral clearance. Moving to RSV, EDP938, the only N inhibitor in advanced clinical development today, is currently being evaluated in three ongoing Phase II studies. As a reminder, RSV is a severe respiratory infection associated with significant morbidity and mortality, not only in infants, but in the elderly and in immune-compromised adults as well. There is no safe and effective treatment for this viral infection. So we previously mentioned RSV, like flu, did not emerge during the most recent northern and southern hemisphere seasons due to COVID-19 mitigation measures. However, where social distancing measures have subsided, RSV has begun to reemerge and has already been observed with recent spikes of pediatric RSV cases in Australia and parts of the United States. In fact, in June, the Centers for Disease Control and Prevention issued a health advisory to notify clinicians and caregivers about increased inter-seasonal RSV activity across parts of the Southern United States. With this in mind, we've continued to establish additional trial sites in North America, Europe, Asia Pacific, and the Southern Hemisphere. These efforts will be key to our recruitment in our RSV clinical program, which includes RSVP, our Phase IIb study evaluating EDP938 in adults with a community-acquired infection, RSVTx, a Phase IIb study evaluating 938 in adult hematopoietic cell transplant recipients, and RSVPs, a Phase II study in pediatric RSV patients. Given that the recent reemergence of RSV is not following any normal seasonal pattern, it's very difficult to predict how significant or sustained the new incidence of RSV will be moving forward. Nonetheless, we are more hopeful that we will be able to complete enrollment in the RSVP study during the northern hemisphere winter season, as long as there are no renewed social distancing trends. Assuming this enrollment occurs, we would expect the data in the first half of 2022. As for RSVTX and RSVPs, which were initiated more recently than RSVP, we will continue to monitor the situation and update as appropriate. Beyond EDP938, our other two respiratory virus discovery initiatives targeting RSV and human metapneumovirus are also showing promise during lead optimization. RSVL inhibitors are another drug class that block viral replication and could potentially be used alone or in combination with other agents such as 938 to possibly broaden the treatment window or addressable patient population. As for HMPV, we believe this initiative is a natural adjacency for us as the virus is very similar to RSV. HMPV has been shown to have worldwide circulation with nearly universal infection by age five. Adults at highest risk include elderly, adults with underlying pulmonary disease, and those who are immune compromised. By year end, we hope to nominate another clinical candidate from either our HMPV or RSV-L inhibitor initiatives. Finally, I'll end with a summary of our work in NASH, a liver disease with a significant unmet need, where we are conducting clinical studies of two FXR agonists, EDP-305 and EDP-297. Recruitment and dosing in Argon-2, our Phase IIb study of EDP-305 in patients with biopsy-proven NASH with fibrosis, is progressing. Later this quarter, we'll have a planned internal interim analysis based on 12 weeks of treatment and a subset of patients from this study. Also later this quarter, we expect to report data from a Phase I first in human study of our follow-on FXR agonist candidate, EDP297. We anticipate that the combined data from this Phase I study and the EDP305 internal interim analysis will enable us to determine next steps, such as potential partnering and combination approaches for our NASH program. Before moving to our financials, I'd like to highlight our upcoming milestones, which we believe position us for a strong remainder of the year. For COVID-19, we've nominated EDP-235 as our lead oral protease inhibitor and expect to initiate a clinical study in early 2022. In HPV, we plan to dose the first patient in the Phase I clinical study of EDP721 this month. In NASH, we look forward to preliminary data from the Phase I study of EDP297 later this quarter and determination of next steps for our NASH program following an internal interim analysis of Argonne2. Finally, we continue to be excited about the early prospects coming out of our two other respiratory virology discovery initiatives and are eager to name a new clinical development candidate for RSV or human metapneumovirus by year end. We'd also like to take a moment to thank Dr. Natalie Otta, Senior Vice President and Chief Medical Officer for her dedication to the company over the last six years. during which she built and led the clinical development and regulatory team and helped advance our pipeline candidates. As announced, her retirement is planned for February, and we wish her the best. We're thankful that she is staying with us in a consulting capacity thereafter. With that, I'll stop here and turn the call over to Paul to discuss her financials for the quarter. Paul?
spk10: Thank you, Jay. I'd like to remind everyone that Ananta reports on a September 30th fiscal year schedule. Today, we are reporting results for our third quarter ended June 30th, 2021. For the quarter, total revenue was $21.6 million and consisted of royalty revenue earned on AVI's global Maverick net product sales. This compared to total revenue was $18.7 million for the same period in 2020. The increase in royalty revenue compared to the same period last year was driven by higher HCV product sales as treated patient volumes have increased compared to the third quarter of last year when the COVID-19 pandemic began. HCV product sales continue to remain below pre-COVID levels as a residual impact from the pandemic continues. Royalty revenue is calculated on 50% of Maverick sales at a royalty rate for the quarter of 10% after adjustments for certain contractual discounts, rebates, and set-offs, which are now approximately 2% of AbbVie's total reported HCV product sales. You can review our royalty tier schedule in our 2020 Form 10-K. Moving on to our expenses, for the three months into June 30th, 2021, research and development expenses totaled $47 million, compared to $34.7 million for the same period in 2020. The increase was primarily due to the timing of our clinical trials year over year. General and administrative expense for the quarter was $8.4 million, compared to $6.8 million for the same period in 2020. The increase was due to an increase in headcount in compensation expense. Anenta recorded an income tax benefit of $9.4 million for the three months ended June 30th, 2021, compared to an income tax benefit of $7.1 million for the same period of 2020. These income tax benefits were due to the provisions of the CARES Act of 2020, which enables the company through fiscal 2021 to carry back its projected current year tax loss to offset taxable income in prior years. Net loss for the three months ended June 30th, 2021 was 24 million or a loss of $1.19 per diluted common share. compared to a net loss of $14.3 million or a loss of $0.71 per diluted common share for the corresponding period in 2020. Ananta ended the quarter with approximately $373 million in cash and marketable securities. We expect that our current cash, cash equivalents, and short-term and long-term marketable securities as well as our ongoing royalty revenue, will continue to be sufficient to meet the anticipated cash requirements of our existing business and development programs for at least the next two years. Further financial details are available in our press release and will be available in our quarterly report on Form 10-K when filed. I'd now like to turn the call back to the operator and open up the lines for questions. Operator?
spk08: We will now begin our Q&A session. To ask a question, you will need to press star one on your telephone. To withdraw your question, press the pound key. Your first question will come from Brian Scorkney with Baird. Please proceed.
spk03: Hey, good afternoon, guys. Thank you so much for taking the question. So I really wanted to talk about EDP938 and was wondering if you could kind of give us some compare and contrast on the potency of this protease inhibitor with remdesivir and maybe Pfizer's PI. And can you do effective serial passage studies with SARS-CoV-2 models? And can you comment at all on what sort of resistance you can induce? And then just on the safety front, what sort of room do you have on selectivity index before you start hitting some of the human proteases and seeing cytotoxin? That's it.
spk12: Hi, Brian. This is Jay. So I think you meant EDP-235, not EDP-938. Oh, sorry. So anyway, EDP-235, the SARS-CoV-2 protease inhibitor that we announced today, you know, serial passenger, I mean, we don't have the live SARS-CoV-2 virus in-house, so we rely on external providers for some of those kinds of studies, but we do do, you know, extensive work looking at resistance in-house, but we use model coronas for that work. And so to that end, you know, the profile that we've generated so far internally looks, it's very, very nice. And so we were excited by, you know, not only that That attribute, but obviously also the potency that we have there. I think, you know, when you look at a candidate, at least the way we look at a candidate versus others that are out there, just even, you know, where we put the mark on the map for what we're trying to hit. You know, we obviously want to drill down on potency and look at that lots of different ways. You know, we've reported good data in primary human airway epithelial cells, which is a great way to look. We also look at activity against variants, and we're pleased with the profile that we've seen there. Talked about the serial passages that we've done. And then getting on to I think we've, you know, we look, we do, you know, sort of extensive safety work prior to taking any of our candidates that we feel very comfortable with the safety package that we've put together for this candidate. So I, given the potency and the wide windows, we don't expect any, you know, sort of complications going into our clinical studies with this molecule. But looking beyond that, these are sort of the meat and potato things, but we pushed it and looked at even further. As you know, we're always looking at tissue targeting and tissue distribution, whether it's with our FSR, whether it's with our hepatitis drugs. And SARS-CoV-2 is no exception. We saw very good tissue distribution and looked at lung levels in rodents, very pleased with that profile. And also having surveyed PK across multiple different species, we feel pretty confident that this is a QD dose and drug. So it's really the aggregate of all these things put together. You can put a punch list together and you know, check nine of the 10, but you know, we, we weren't done until we checked every, every box we were aiming to do, uh, in this, uh, in this candidate. I think the other sort of exciting aspect of this is we have, uh, seen activity against other coronaviruses, uh, with this as well. So there's the, the possibility that we could go beyond SARS-CoV-2 here and think about, uh, readiness for other pandemic viruses or other coronaviruses. So all in, it's a very exciting candidate. And, you know, as we've mentioned, we're on track to initiate clinical studies early next year.
spk03: Great. Thanks for taking the question, Jeff.
spk12: You're welcome.
spk08: Your next question will come from Yasmeen Rahimi with Piper Sandler. Please proceed.
spk00: Hi. Good evening. This is Swapnil on Forgas. A couple of questions. First is for 721, should we expect to see the 800 milligram cohort data at ASLD? And then based upon your internal PKPD modeling work, how much additional HPV DNA bent knockdown benefit do you expect to see over the reported 200 and 400 milligram doses?
spk12: I think you've got a count on number. Mixed up, too. I think you said EDP-721, and I think you were referring to EDP-514. Yeah, that's right. Sorry. Yeah, I know we have a lot of molecules to keep track of here. So with regards to 514, you know, the 200 and 400 milligram doses, you know, whether we were looking in nuke suppress patients or viremic patients, Both of them showed very good performance, not only in terms of safety and PK, which is one of the main things we were looking for, but also in the case of the nuke suppressed, we wanted to make sure that our molecule behaved well with a nuke, right, because we wanted to set the foundation of a two-drug combo on which to add the other molecule you mentioned, 7-2-1, to make an oral triple. So I think we got, you know, based on the virology that we saw at the 200 and 400, whether you looked at DNA or RNA, whether you looked at one fish population, For the other, we saw good safety and good virology as we would have expected in each of those different patient populations. And it definitely sets the stage for moving ahead. I think the 800, you know, what will we see there on top of that? We saw such significant exposure at 200 and 400. You know, it's not clear that any more exposure will give you any more benefit. But, of course, we'll pull that data in and see it. And we'll put it out at, you know, whatever the next appropriate, you know, sort of major scientific conference is to do that at. So stay tuned on that front. But, again, I think we've seen what we need to see already to know that 514 has a great antiviral effect, a great safety and tolerability profile to see today in HPV patients up to 28 days. and a good T drug foundation with the loop to set the stage for a triple with the ET721.
spk00: OK, great. I had one follow-up question. So for 235, what gating factors are remaining? Where are you guys in terms of regulatory pathway before you initiate the phase 1 trial in 2022?
spk12: Yeah, I'd say that, you know, I mean, all the IND enabling studies are done. So we're packaging, you know, that sort of stuff up. We're procuring drug supply. We're doing all those kinds of things in terms of readiness as we prepare for the, you know, the phase one study. That's just sort of routine stuff at this point.
spk00: Great. Thank you for taking our questions.
spk08: Your next question will come from Brian Abrams with RBC Capital Markets. Please proceed.
spk11: Hey, guys. Congrats on the progress. Thanks for taking my questions and my congratulations and best of luck to Dr. Otto on his retirement. First question on 235, maybe a bigger picture question. I was wondering if you could maybe talk about how you're thinking about, you know, next steps here in phase one and beyond for the program. what you think the clinical path might look like. And is this something where you might expect a PI alone to be adequate, or do you think this could be more akin to, you know, HIV or Hep C, where you'd want to combine this with other classes of direct acting antivirals like nukes?
spk12: Well, you know, it's a good question, Brian. The answer is nobody really knows, but that said, we're talking about an acute infection here. So I think we're pretty encouraged that a single agent could be enough. Now, obviously, when we set up this program at the beginning of the pandemic, we didn't work just on this mechanism. We have been continuing to be working on other mechanisms. just because you never know what could happen here down the road with regards to variants or anything else. But from what we see, I think we would be very encouraged to take a protease in and see an impact on hopefully viral loads and symptoms very quickly. These mechanisms are or sort of trying true DAA mechanisms. And we certainly don't know yet that we would need to go in with combination therapy, as you might expect to do in hepatitis C or certainly in hepatitis B. So as you know, with RSV, we're looking at short-term treatment with our RSV drug as a mono agent. But, again, for that program, just like with SARS-CoV-2, you know, we're going to take multiple approaches just because at the end, you know, if we can come up with an even better approach down the line, that would be great. If combinations are needed down the line, you know, we want to be in the position to, you know, have potentially multiple quality assets. That's why we continue, you know, exploring in RSV, you know, in multiple areas. these three studies with a very promising agent. Can it help us, for example, get into different patient populations that you might not otherwise be able to get into? Could it allow us to treat more severe patients or broaden the treatment window? These are all questions that we can ask and do course. But one of the things, just from a paradigm in general, that we thought about RSV You know, sort of the holy grail here is early diagnosis and rapid treatment. You've heard me talk about that concept now for multiple years in connection with RSV. We believe it applies in human metanemovirus, where we were talking about that just before the pandemic launched and now with SARS-CoV-2. we think that possibly checks in there as well. So, you know, again, this is, we've been stating this sort of approach and goal for a long time now with different viruses. And I think a lot of people now that the sort of the vaccine visibility has run a course for a while now, people are starting to think about and wonder about and worry about the lack of therapeutics. And to that end, I think a lot of people are thinking it would be wonderful to have something that if you, you know, are, you know, symptomatic, you go to CVS, you get a swab, you're positive, and you get treated as an outpatient, you know, with a easy-to-use, safe oral drug that you just go home, knock that viral load down, stop the shedding, get back to work. So, yeah, That's among the things that we're thinking about. I hope that helps.
spk11: Yeah, no, that's really helpful, Jay. Thanks. And then maybe one more on 938. I know you've been continuing to expand and mobilize your sites. I'm curious to what degree you've been able to take advantage of the recent off-cycle RSV spikes. Is there, I guess, how much consistency is there regionally with where these spikes are and where your trial sites are? And is there any Are there any changes in the way you might screen or even monitor patients in an off-season RSV surge versus the normal seasonal uptick?
spk12: Yeah, we're pretty spread out geographically in the U.S. and globally. You are correct, and I saw your note earlier this week, and we've been pointing it out too, that first starting in the southern hemisphere, once Summer rolled around in the summer. While we were in winter, it was becoming summer in the southern hemisphere, and the masks started to drop a little bit in Australia. And they saw this huge pediatric spike, interseasonal spike. And then we were quietly thinking, well, that could well happen here. And guess what? It did happen. It did start to happen. A few weeks ago, the CDC said there's been this big uptick on interseasonal RSV in some spots. It's been in certain southern parts of the United States where these things sort of pop up. So we've got sites all over the place. And so we have seen some upticks, and that's why we are cautiously optimistic that if if trends continue and we go into the winter season here, that we should be able to, uh, to wrap up, uh, you know, the, uh, RSVP study, uh, this season. And if that's the case, then, uh, you know, we would have data in the first half of next year. But what I think we really need to see is, you know, are these little interseasonal spikes just going to, you know, tamp down? Are they, um, Are they going to camp down and then come roaring back in the fall and the winter months when RIC is normally prevalent? I mean, there's every expectation that you start to hear about it on the news. You know, the other, you know, yet another respiratory virus that people should have on their minds that we don't have enough to think about with COVID. But we're starting to hear more and more that awareness for RSVs coming back, the testings coming back. The CDC has recommended that just because somebody has something, don't assume that they have SARS, and if they're SARS-CoV-2 negative, you know, get tested for RSV anyway. So this is where we're going to start to figure out, you know, where these real patterns are. But we've got our catcher's mitt on, and we've got lots of sites around, and so as patients come in, we'll be, you know, ready to grab them. Great, thanks again. You're welcome.
spk08: Your next question will come from Roy Buchanan with JMP Securities. Please proceed.
spk09: Hi, great. Thanks for taking the questions. Had a couple on 235, I guess. So, you know, the structure of Pfizer's lead oral inhibitor is out there. I'm just curious if you guys did any side-by-side comparisons, you know, in view of potential differences between assays and if you have a side-by-side comparison of the potency. And then can you tell us if 235 is covalent? Is it reversible?
spk12: And a follow-up. Yeah, no, I know exactly the kinds of questions you're asking. It's not the kinds of questions I usually answer until we're ready to answer them. But it's fair to assume that we do extensive benchmarking across all kinds of parameters with every molecule that we can lay our hands on. And we've done that with 235. Okay.
spk09: And then kind of along the same lines, are you going to present or publish either preclinical or chemical data before the phase one results? Or are the phase one results going to be the first we're going to see data?
spk12: So there might be a, you know, we'll see. You're talking about putting out preclinical data of some sort.
spk09: Right, like a poster or a paper.
spk12: Yeah, we're working on that strategy internally. I think, you know, on the one hand, it's exciting to put these kinds of bits of information out in various public fora, but we're really focused on mobilizing and pushing ahead to get ourselves into the clinic and then ultimately get into... later stage clinical studies as fast as we can. But the data will come out in due course.
spk09: Okay, got it. And I had a few on 721. I was looking at the clinicaltrials.gov record. I see the one site in New Zealand. I guess there are going to be additional sites added. And I didn't see any breakdown of the number of patients in the viremic and the nuke-suppressed groups. Can you give us a sense of what the target breakdown is, if there is one? Um, and then I have a few more questions.
spk12: Yeah. So, um, you know, right now we're, as we, uh, as we sort of had in our prepared remarks and in the release, um, you know, the 71 study has been initiated. We're screening now. We're, uh, expecting to dose, uh, you know, this month. So, um, you know, let us, uh, let us do the, uh, this study, and we'll report more details on our clinical trial design on how we're going to put this triple combo together, et cetera, et cetera. We'll have more details on that at a later time.
spk09: OK, fair enough. So you probably won't answer my other questions either, but I didn't see you have the combo with 514 already in the trial design, so that's exciting. All right, I guess I'll ask one last question on a different topic. So, Nash, not the current programs, but you guys have talked about a novel mechanism for some time. I'm just curious, you know, when you might disclose the target or the pathway, just any news there. Thanks.
spk12: Yeah, so we obviously haven't prepared to disclose that target yet. and program this quarter. But I think it's fair to say, you know, we've just got a lot in Nash all coming together here in the next, you know, little bit. And I think this quarter will be really interesting for us as we're pulling in, you know, our internal interim read on Argonne 2. We'll have phase one data on our other FSR agonist, EP297. You know, with the Argonne 2, by A, you know, our hope is to figure out, you know, what are the appropriate doses that we can peel off then and entertain combination studies with, perhaps in the context of a partnership, you know, et cetera, et cetera. So suffice it to say, we're thinking about this quarter in Nash in a big picture sort of way. And even if we were thinking of, you know, ultimately teaming up in some sort of a partnership? Would we do that even with our earlier stage program? These are questions that we haven't completely sorted out, but we're thinking through right now. But with regards to your very specific question about what is the target, we're not
spk07: talk a little bit about as we prepare for RSVP, you know, what specifically we should be looking for, you know, in the data to make an assessment?
spk12: Sure. Maybe I'll, you know, pull this question over to Natalie to comment on further, but, you know, maybe I just will preface it by saying, you know, you recall our our human challenge study where, you know, human volunteers were infected with the virus. You know, you wait around, you constantly monitor their viral loads, and once the viral load puts a certain threshold, you begin dosing. And when the people began to receive drugs, they were also symptomatic with at least, you know, a symptom of sorts. What we saw was, number one, a very nice set of viral kinetics as one of the key things we were looking for in that study. Very different than placebo. As soon as he started dosing drugs, the course of the infection completely changed. People with placebo continued to get worse, and people on drugs got better. You could look at that in the form of viral loads. You could look at it in parallel with the same time course with people's symptoms. I think in the outpatient setting, we're not able to get the same frequency of viral loads. I think we were doing, in the challenge study, you're able to take swabs twice a day. I think we were doing over the course of the whole study. That's just not feasible in an outpatient study. So that's not to say that we won't get any virology, but what we are tracking is symptoms. So we'll have symptoms and we'll have virology as a set of readouts. But Natalie, do you want to comment any further?
spk05: sure hi lisa uh thank you for your question so um maybe just to what to what jay was saying i think there's um you know i would like you know a few a few additions to that uh obviously you know we want to confirm uh the selected dose um the 800 milligrams that was assessed in the challenge study, you know, there were 600 milligrams, but through the BA, we had to increase it. So I think it's going to be important, you know, to at least have a good assessment and confirm that our selected dose is the one for the patient setting. That's one thing. And we'll confirm them through important primary endpoint, which is, you know, the sample score. We want obviously to get out of that study understanding that the translation from the challenge study in a more, I would say, you know, artificial setting is confirmed in an outpatient setting. And we want to show that as you treat patients within a very short window, that we can allow the patient to not progress to a more severe disease and that would be translating into more symptoms. This is why it's going to be important to look at our primary endpoint. We have well-powered our study to be able to do that without. We believe that the effect size that was assess for the core of the study is appropriate. And then we benchmark that to the challenge study, but we were very conservative for our study. So I think we will be able to confirm the translation from the challenge to the allocation.
spk07: Okay, great. And then, Jay, if you could talk a little bit about kind of your different, I guess, potential paths you could take with the NASH program and what you're looking for in the data kind of go down those different paths. Maybe you can summarize how you're thinking about it ahead of data coming out. Thanks.
spk12: Yeah, well, you know, we've always, you know, for years now, I think actually we've We've said that with regards to NASH, we don't aspire to be a commercial stage NASH company. We don't aspire to be a phase three NASH company. Instead, we want to do phase two work, get appropriate phase two data points, and then team up with another party. And so I think that's really how we're thinking about it, the focus on that. I think ultimately FXR in the right doses can still make a big impact, I think, in the form of combinations. And so we'll be, again, that's why the IA that we're going to be getting here soon is really appropriate. You recall from our Argonne 1 study, we looked at 1 milligram and 2.5 milligrams. We saw unacceptable pruritus at 2.5. It's sort of like an intercept. We looked at 10 and 25. We looked at 1 and 2.5. And so Argon-2 now, as you know, and I know we've had discussions on this in the past, Argon-2 has gone down between those two doses just to see is there another dose other than the one milligram where we did see significant target engagement. So even at one milligram we saw it, but we felt like we could be leaving some efficacy on the table. So can we tweak it a little further to see you know, extract more efficacy without, um, pushing on a pruritus, uh, button, whatever mysterious button that is. Um, and so, uh, that's what we'll get. We're going to, we're going to get that data. Again, we already know the one milligram, we know the two and a half, we're looking at data in between those points. And then that will give us dose and information again, for which we can, uh, peel off and do, um, you know, seek certain combination possibilities. So, and we would aim to do that in the context of a partnership.
spk07: Okay, great. Thank you.
spk12: You're welcome.
spk08: Again, as a reminder, to ask a question, you will need to press star one on your telephone. Your next question will come from Jay Olson with Oppenheimer. Please proceed.
spk02: Hi, this is Matt on for Jay. Thanks for taking our questions. The first thing I wanted to ask was, since HPV is a large global opportunity, what are your thoughts for a potential partnership there, especially XUS? And also, since a potential partner would be likely to seek a role in clinical development, at what point would you consider potentially identifying a potential partner in HPV? Thanks.
spk12: Sure, those are great questions. Well, since actually we just talked about partnering and at nash um i've also spoken about you know partnering in hbv and um now there it's a little bit different than nash and it's and that in turn is a little bit different than our human you know respiratory uh program but let's let's talk about hbv um and i'll contrast it to hcv you know when we did our hcv deal with Abbott, which became AbbVie several years ago, you know, we had a protease inhibitor and they had other assets, but neither of us had, you know, the combination that we needed to put together to create the all oral cure. This is a little different. You know, we do have, possibly anyway, we're assembling the agents that we hope to be sufficient for an all-oral cure, right? We have nips as a standard of care. Everybody sort of gets a nuke for free. We've got our core inhibitor. We've now put out two good data sets on that, including a T-drug combination with a nuke. And now we've got 721, you know, getting ready to be dosed here, you know, very soon, which will be the third part of that process. potential all-oral triple. So I think what we're going to ask is, you know, is that enough? We'll be doing the experiments, clinical trials that will help us sort out, you know, whether or not that is enough. We're very excited by the possibility because if we do, it's a highly differentiated product profile with an all-oral therapy, all-oral therapy. will always win out over a mixture of, uh, injectable and oral therapies, all things being equal. And so, um, you know, with, uh, now with the advent of 71, which we announced, you know, just this year, we announced it in the context of a candidate and a short runway into the clinic, uh, and a potent effect on antigen reduction. We think we may have all those bits and pieces. So, um, So that's the nearer term, right? We'll hopefully be in an all-oral triple trial next year. And if that data looks good, you can start to think about, well, what are the steps beyond that? And that's where you start to think about HPV being such a big global infection. If you look at The US, if you look at the EU5, if you look at Japan, you add them all up, it's a very large market. But it's only a fraction of the worldwide unmet need for treating and curing hepatitis B patients who are chronically infected. And so for global reach and scale, If you follow the dots, it's highly likely that we'll have a global commercialization partner. Would we retain co-commercialization opportunity in certain territories? Yes. At least the option to do that. We had that option with two different drugs in our hepatitis C program with AbbVie. We elected not to do co-commercialization. At the time, we needed to do that. We were In one instance, we were a private company. In another instance, maybe even both times, we might have been a private company. There's no way we could have even contemplated that. Fast forward in thinking a few years into the future, if we have an all-oral triple, it could be a different set of circumstances for us. And we'll see where we are at that time. But I do believe we'll still, independent of that, we'll still want to have another partner to help us to maximize this to patients worldwide.
spk02: Is that helpful? Okay, got it. Yeah, that's awesome. Really helpful. Thank you. And then the last question we had was just on EDP 938. And so for the pediatrics and adult studies that you recently initiated, just curious what you're hoping to see in the data there, also when we could expect to see data, and kind of how you're thinking about the market opportunities for each. That would be great. Thank you.
spk12: Yeah. Well, PEDS is the biggest. I'll tell you that. You know, the PEDS is a very large market. Transplants, a very important market also. I mean, these folks who are immune compromised, if they get an RSV infection, it can just be catastrophic. And so it's a really important to other patient population. But PEDS is definitely a larger population. The transplant study we just got going at the end of last year and the PEDS study we just got going in March. And also I'll remind you too in the PEDS study, the first part of it is really safety and PK. And then the second part of it is when we'll get into other aspects of the RSD infection. So those are necessarily tracking behind a a study RSVP, which we already had ongoing and partially enrolled. So it's a bit early for us to give any sense of timing on those two studies, other than they're going to be, you know, further out. I think this upcoming season will be very telling in each of them. Allow us, you know, once we get this next season under our belts, I think we'll have a much better idea of where we stand.
spk02: Okay, got it. That makes sense. Really helpful. Thanks again for taking the questions. You're welcome.
spk08: Your next question will come from Zeg Bajala with Roth Capital Markets. Please proceed.
spk06: Hi, thanks for taking my question. Just had a quick one really about your COVID program. We're just wondering if you're considering any unique treatment strategies in light of, you know, other, you know, COVID drugs being approved or vaccines being approved. I know this is, you know, quite different as a treatment, but we're just wondering because, you know, Regeneron did also get their drug approved as a prophylactic after exposure. So we're just wondering if you're thinking about anything unique in terms of, you know, when treatment will be delivered?
spk12: Yeah, well, you know, there's, you know, treatment of any sort would be a major milestone, but I do believe you could also consider prophylaxis in certain settings. So that's among the things that we're thinking about and chewing on. But straightforward treatment is clearly where... where the most urgent need is right now. So let's assume that we'll do that. And it's true there. I mean, the antibodies, I think, that are out there played an important role, particularly early in the pandemic and prior to vaccines. Vaccines have kind of, you know, helped an enormous amount. It could obviously be helping even more. But I think ultimately, The missing piece here and the piece that will be durable long term are going to be the small molecule, antiviral molecule, direct acting antiviral, of which obviously 235 is. And there will be multiple generations. We're going to assume that people are going to be out there doing it. I mean, when we were going into Hep C, you know, Enanta wasn't the first protease inhibitor, but we were the best, you know, so, and even our first protease inhibitor, even though it was better than the prior ones that had been looked at, we came up with an even better one than that later on, which ultimately did become best in class with the capovir. So I think 235 is a very strong entrant. We feel very good about it, and we'll let the data speak
spk06: Shannon, just a quick follow-up in terms of the dosing. What's the dosing regimen, or what are you hoping to achieve with that?
spk12: Well, we think we can, again, we always aim for QD dosing. One scale is always best, and we pretty much always have hit that mark. Our preclinical studies suggest that that's likely to be the case here. I mean, we usually hit that mark in the clinic because we're very good at modeling that pre-clinically across multiple different species. And so spend a lot of time, you know, sort of engineering that attribute as well. And I think people who know this landscape know that it's not necessarily a given that you can achieve that. So again, we'll have to prove that in the clinic, but we feel very good about you know, the kinetics that we've seen preclinically. And then beyond that, again, it's an acute infection. We would expect in normal people who are generally competent immune systems, we could do a short-term dosing. You know, probably, I mean, it wouldn't be unreasonable to assume it's something like a five-day dosing regimen, just like you do in RSV. But, you know, we'll see. Could be going to be short um relatively uh speaking to you know some protracted days engagement thanks jay looking forward to hearing more about the program you're welcome and at this time there are no further questions i would now like to turn the call back over to jennifer vieira for closing remarks
spk01: Thank you everyone for joining us today. If you have any additional questions, please feel free to contact us by email or call us in the office. Thanks and have a good night.
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