This conference call transcript was computer generated and almost certianly contains errors. This transcript is provided for information purposes only.EarningsCall, LLC makes no representation about the accuracy of the aforementioned transcript, and you are cautioned not to place undue reliance on the information provided by the transcript.
spk11: Good afternoon and welcome to Enanta Pharmaceuticals Fiscal Second Quarter 2021 Financial Results Conference Call. At this time, all participants are in a 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.
spk13: Thank you, Operator, and thanks to everyone for joining us this afternoon. The news release with our fiscal second 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 development and results to differ materially from those statements. A description of these risks is in our most recent form 10Q 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. I'd now like to turn it over to Dr. Jay Lulli, President and CEO. Jay?
spk10: Jay Lulli Thank you, Jennifer, and good afternoon, everyone. Our fiscal second quarter marks another productive quarter for the company. as we continue to work towards several upcoming catalysts across our pipeline in the remainder of the year. We currently have three active clinical programs across our portfolio in virology and liver diseases, in which we are conducting seven clinical trials. Starting with hepatitis B, we are excited to report preliminary data from one of the two ongoing Phase 1B studies of our core inhibitor, EDP514, which I will discuss in more detail shortly. Our HPV program also includes EDP721, our oral HPV RNA destabilizer, which is set to enter the clinic in the middle of this year. Additionally, we have three ongoing studies investigating EDP938 for respiratory syncytial virus, or RSV, and two ongoing clinical studies for two candidates to treat non-alcoholic steatohepatitis, or NASH. Further, we continue to progress our viral respiratory discovery initiatives to identify an L inhibitor for RSV and an inhibitor for human metapneumovirus, or HMPV. Finally, we are particularly enthusiastic about the prospects for an oral protease inhibitor specifically designed to target SARS-CoV-2. With that, I'd like to turn to our robust pipeline, beginning with our HPV program, where we are pleased to be able to report today positive data from the first two dose cohorts of part two of our ongoing phase 1B study of EDP514 in chronic HPV patients treated with a nucleoside reverse transcriptase inhibitor, who we refer to as NUC-suppressed. The data announced today provide critical support for our approach to developing an all oral functional cure for patients with chronic HPV. Based on preliminary results of the phase 1B study, EDP514 was safe and well tolerated and nuke suppressed patients for up to 28 days. And the pharmacokinetic profile of once daily dosing consistent with what was observed in part one in healthy subjects. Going a bit deeper into the data, a total of 16 patients, the majority of whom were e-antigen negative, were randomized to receive 200 milligrams of EDP-514, 400 milligrams of EDP-514, or placebo, for four weeks. There were no grade three or serious adverse events, and the majority of the treatment emergent adverse events were mild. One patient in the 200-milligram arm had a grade II adverse event that led to study drug discontinuation. There were no liver enzyme elevations or other laboratory abnormalities. EDP514 exposure increased linearly with trough concentrations up to 18% of the protein-adjusted ET50, supporting once-daily dosing. As expected, the HPV DNA assessment did not show any change from baseline because these patients already had suppressed DNA levels from their new therapy. Additionally, no virologic failure or breakthrough was observed. Exploratory viral endpoints were also evaluated in this study, and a mean reduction of one log in HPV RNA was observed in patients receiving ADP514 compared to 0.3 log reduction in placebo consistent with data reported for other core inhibitors after four weeks of treatment. Further, maximum reductions of 2.3 logs in the e-antigen negative group and 2.8 logs in the e-antigen positive group were observed in patients receiving EDP514 versus a 1.2 log maximum reduction in the placebo group. The study is ongoing, and we will obtain data on the highest dose group, 800 milligrams, and report final results at a future scientific conference. Later this quarter, we are also expecting preliminary results from our Phase 1B study of chronic HPV-infected patients with high viral load who are not currently on treatment, whom we refer to as viremic patients. Then the NUXA PRESS study, preliminary data in viremic patients will include safety, tolerability, and pharmacokinetics, And importantly, the viremic study will give the first indication of EDP514's effects on viral kinetics when used as a single agent over a 28-day period. In addition, we're developing EDP721, our newest HPV compound, for use in combination with other mechanisms such as nukes and or EDP514 with a goal of creating an all-oral functional cure for chronic HPV infections. Nukes are the current standard of care for HPV patients and suppress HPV DNA. Core inhibitors, such as VDP514, also suppress HPV DNA. In addition, affect several other stages of HPV replication, including uncoating and nuclear import of the virus, capsid assembly, and recycling. However, high levels of HPVS antigen remain a challenge to achieving a functional cure. EDP721 is an oral agent that destabilizes HPV viral RNAs, potentially leading to a reduction in HPV S antigen, as well as other viral proteins in patients. We are encouraged by compelling data showing a three-log reduction in S antigen levels with EDP721 in a mouse model, which demonstrated equal or superior efficacy to SI RNA-based agents and antisense oligo-based agents tested in the same model. We look forward to presenting data on the discovery and characteristics of BDP721 in a poster presentation at this year's International Literate Congress sponsored by EASL in June. And we are eager to start our phase one trial of BDP721 in mid-year with initial results expected in the first half of 2022. Moving to RSV, EDP938, our lead product candidate and the only inhibitor in clinical development today, is currently being evaluated in three ongoing studies. RSV is a severe respiratory infection associated with significant morbidity and mortality in infants, the elderly, and immune-compromised adults, and a condition for which there is currently no safe and effective therapy. Leveraging our expertise in virology, we designed EDP938 to uniquely target the end protein and block the replication machinery of the virus rather than blocking viral entry. As we've mentioned previously, RSV, like flu, did not emerge during the usual late fall and winter RSV season in the northern hemisphere in the past year due to the continuing COVID-19 mitigation measures. However, once social distancing measures subside, likely that RSV will reemerge, as has already been observed in the recent spike of pediatric cases in Australia. With this in mind, we continue our preparedness efforts to ensure we are ready when RSV reemerges globally, including establishing trial sites in North America, Europe, the Asia-Pacific region, and the Southern Hemisphere. These efforts will be Key to recruitment in our clinical trial program, which includes RSVP, our phase 2B study evaluating EDP938 in adults with community-acquired infection. RSVTX, a phase 2 study evaluating EDP938 in adult hematopoietic cell transplant recipients with acute RSV infection and symptoms of upper respiratory tract infection. and RSV-PEDS, a Phase II randomized double-blind placebo-controlled dose-ranging study of EDP938 in pediatric RSV patients. The primary objective of the first part of RSV-PEDS, which we initiated in March, is to evaluate the safety and pharmacokinetics of EDP938 in multiple ascending doses While the primary objective of the second part of the study will be to evaluate the antiviral activity of EDP938. Once RSV becomes prevalent again, we will provide updated guidance for these ongoing clinical studies. Beyond EDP938, our lead optimization efforts in our RSV-L protein inhibitor and human metapneumovirus inhibitor discovery initiatives continue to progress. RSVL inhibitors are another drug class that block replication and can potentially be used alone or in combination with other agents, such as CDP938, to possibly broaden the addressable treatment window or patient population. For HMPV, we are making progress with lead optimization of potent molecules, and our most advanced discovery initiative for respiratory viruses is SARS-CoV-2, where our current efforts to develop an oral, direct-acting antiviral are focused on protease inhibitors and polymerase inhibitors. Building on our virology expertise and success in hepatitis C, we are designing compounds that prevent replication of the virus in human cells versus blocking viral entry, and we expect our approach will be effective against emerging spike protein variants. We plan to initiate IND-enabling studies with our lead oral protease inhibitor later this quarter, and if all progresses positively, we could have a candidate in phase one clinical study in early 2022. I'll end my pipeline review with a summary of our work in NASH, a liver disease with a significant unmet medical need, where we are conducting clinical studies of FXR agonists, EDP305 and EDP297. Recruitment and dosing in Argon-2, our Phase 2b study of EDP305, approximately 340 patients with biopsy-preven NASH with fibrosis, is ongoing. Due to the impact and resurgence of COVID-19 rates in Europe and in South America on some of our global clinical sites, our internal interim analysis based on 12 weeks of treatment on a subset of patients will now be in the third calendar quarter of 2021 rather than in mid-year. Recruitment and dosing are also ongoing in our phase one first human study on our follow-on FXR candidate, EDP297, and we expect to report data from that study in mid-year to build upon compelling preclinical data suggesting differentiated high-potency and tissue-targeting characteristics compared to other FXR agonists and developments. In aggregate, we anticipate that EDP297 data and the EDP305 internal interim analysis will enable us to determine next steps, such as potential combination approaches for our NASH program. Before moving to the financials, I'd like to reiterate our upcoming milestones. In HPB, we expect preliminary results of the Phase 1b study of EDP514 and viremic HPV patients later this quarter, and we look toward the initiation of a clinical trial for SARS-CoV-2-1, our oral HPV RNA destabilizer, in mid-year. For COVID-19, we expect to begin IMD-enabling studies later this quarter for our lead oral protease inhibitor fully designed to target SARS-CoV-2. For NASH, we look forward to reporting preliminary data from the Phase I study of our FXR agonist, EDP297, in the mid-year, followed by an interim analysis of Argon-2 and determination of next steps for this program. Finally, we are excited by the early prospects coming out of our respiratory virology discovery initiatives and are eager to identify two clinical development candidates out of our COVID-19 RSV, and human metapneumovirus programs by year end. With that, I'll stop here and turn the call over to Paul to discuss our financials for the quarter. Paul?
spk09: Thank you, Jay. I would like to remind everyone that Enanta reports on a September 30th fiscal year schedule. Today, we are reporting results for our second quarter ended March 31st, 2021. For the quarter, total revenue was $20.1 million and consisted primarily of royalty revenue earned on AbbVie's global Maverick product sales of $415 million. This compares to total revenue of $27.6 million for the same period in 2020. The decrease in royalty revenue compared to the same period last year was driven by lower HCV product sales as treated patient volumes have remained below pre-COVID levels, as reported by AbbVie. Royalty revenue was calculated on 50% of Maverick sales at a royalty rate for the quarter of 10%, and on approximately 30% of Vicaris sales at a royalty rate 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. As a reminder, our royalties are calculated on a calendar year basis. Therefore, royalties for our fiscal first quarter ending December 31 were calculated at the highest royalty rate for the year. And royalties for our fiscal quarter ending March 31 are calculated at 10% our lowest royalty rate tier. You can review our royalty tier schedule in our 2020 Form 10-K. Moving on to our expenses, for the three months ended March 31, 2021, research and development expenses totaled $41.5 million, compared to $32.6 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 $8.3 million, compared to $6.9 million for the same period in 2020. The increase was due to additional headcount and related compensation expense. AnANA recorded an income tax benefit of $7.1 million for the three months ended March 31, 2021, compared to an income tax benefit of $3.9 million for the same period in 2020. The income tax benefit in the current period was due to the company's pre-tax loss which can be carried back under the CARES Act of 2020. Net loss for the three months ended March 31, 2021 was $22 million or a loss of $1.09 per diluted common share compared to a net loss of $6 million or a loss of $0.30 per diluted common share for the corresponding period in 2020. And then at the end of the quarter was approximately $400 million in cash and marketable securities. Further financial details are available in our press release and will be available in our quarterly report on Form 10Q when filed. I'd now like to turn the call back to the operator and open up the lines for questions. Operator?
spk02: We will now begin our question and answer session. To ask a question, you will need to press star 1 in your telephone. To withdraw your question, press the pound key. Please stand by while we compile the Q&A roster. Our first question will come from Brian Abrams with RBC Capital Markets. Please proceed with your question.
spk08: Hey there. Thank you for taking my questions and nice to see all the progress across the pipeline. First question is on 514. Can you provide a little bit more granularity on maybe some of the differences in RNA declines, as well as lowest trough concentration that you observed across the two doses, and I guess what you're looking to optimize in this particular study with the higher 800 milligram dose?
spk10: Yeah. Hi, Brian. This is Jay. Thanks for the question. You know, regarding the trough levels, so the trough levels, you know, are basically measured at the 24-hour time point after a given dose. And we're just really, really pleased to see the high trough levels. As you know, we bank on those kinds of attributes with all the product candidates that we make, whether it's RSV or any of the other viruses. And It's just a very helpful confidence builder when you see that you have such heavy pressure on the virus at the lowest concentrations that you'll see during the day. So we saw not only very good trough levels at the 400-dose group, which were about 18x the protein-adjusted EC50, But we also saw very high trough levels at 200 as well. So we'll get all that data out once we put it together with the third and final arm of the study, 800. But I can say so far, based on what we're seeing with even the two lower doses, we have very, very good exposures at trough concentrations. And then, you know, regarding the viral load reductions, you know, again, in a new suppressed study such as this, you know, we've guided all along that this study isn't so much about virology as it is, you know, looking at safety and tolerability and these PK levels. you know, confirming that we see the same, you know, good safety and tolerability and exposure that we saw in healthy volunteers. And we've done that with these doses. But importantly, it was on top of a nuke and HPV patients and going out for, you know, for 28 days. So all in, it's a very strong package. The Again, the DNA is already suppressed from the mucus, so you're not going to see much there. RNAs are generally lower effects than you see when you see it. It really kind of depends on the exact patient population you have and what their starting RNA levels were, how far they were also may or may not have been suppressed. But what we saw was... you know, what's been typical of a strong RNA response from core inhibitors at, and I want to underscore it, at a four-week time period. So, which is a, you know, short time period in the grand scheme of some longer trials that will ultimately be run. We're looking forward to the partner study of this, which I'd call the Viremic study. So, there, you know, the patients will have, uh, coming into study will have high viral loads. Um, so their DNA will be elevated and there you have a chance to see a single agent without a nuke, uh, coming along, um, to, uh, to see what, you know, 514 does in a dose related manner as a, uh, as a single agent. So, um, again, um, So far, so good. The virology is very strong preclinically, as you know. Very potent molecule. It's pan-genotypic. It works incredibly well in animal models. Now we've got our first inpatient data that we're very excited about. Looking forward to the next installment, which will be viremic data, which we expect to get later this quarter.
spk08: Got it. And did you guys look for any potential changes in tenofovir concentration? And I know the adverse events appeared pretty mild, but I'm just curious, did any of those grade one and two side effects, were any of them consistent with potential tenofovir-related AEs?
spk10: You know, I'd have to check on that. I don't believe so. I think it was... Again, we'll put all the information out at a conference when we have the final cohort in, but the AEs observed were mild.
spk08: Got it. One more from me, then I'll hop back in the queue. What are your latest views on what you'd be looking for in the coming months to determine a potential path forward in NASH, and what might those paths forward look like strategically? Thanks.
spk10: Well, you know, again, we have two ongoing studies. We have two different compounds. We have EDP-297, which is our follow-on FXR. Obviously, that's a super-potent molecule. It looks like it's the most potent FXR in clinical development today. So that's one attribute that we observed certainly pre-clinically. The other is the tissue targeting of that. So I think we've laid out the hypothesis of why and how that could you know build to a a a better index if you will from a from a efficacy and target engagement versus tolerability profile and so we'll let that study run to its conclusion we're expecting data on that as we just said mid-year and then also we're going to have To share alongside with that, or to see alongside with that internally, we're going to have an internal look at an interim analysis on a subset of patients in EDP-305 Argon-2 study. And as you know, we've looked at the goalpost doses previously in Argon-1, and we're looking at interim doses now. So we'll have a very good calibration point to look at, again, it's all about target engagement slash efficacy versus tolerability, whether it's, you know, molecule A or molecule B. We had hoped to have that data on Argonne 2 mid-year, but as we just stated, COVID attracted some of our sites in Europe and in South America, and that's, we had hoped to have that around our early August earnings in mid-year, but it looks like that's not going to happen, but it should be in Q3. So we'll look at the aggregate of all that data, see what makes the most sense. I mean, in particular, we're looking for doses of drugs that could be very interesting in terms of their target engagement and tolerability profile and that could be used in combination. The goal here is to identify as early as we can this year dose or doses on either or both molecules that could be used in combination and then seek about looking for combination opportunities up here, including possible business development opportunities. So stay tuned on that front, but that's the plan.
spk08: Makes sense. Thanks so much, Jay. You're welcome.
spk02: Your next question will come from Yasmeen Rahimi with Piper Sandler. Please proceed with your question.
spk03: Hi, team. Congrats on the continued progress and updates. Two questions for you. Maybe the first one is Can you help us understand if there were any serological tests done at week two? I guess what I'm trying to get at is, you know, sort of the time-dependent change in viral load reduction. And then also, like, you know, was there a dose separation difference between the 250 and 400, and I recognize that the number of patients are really small. That's sort of part one. And then part two, was that one AE that led to discontinuation, was that deemed to be drug-related? You know, and this occurred at the 200-milligram dose group. And thank you for taking my question.
spk10: Yeah, answering the second question first, I guess, the AE was possibly drug-related. It was scored as possibly, so that's kind of all you know. It's not definitive, but it was stated as possibly related and at date 12, I believe. With regards to looking at viral loads or kinetics, that's not really what this study was designed to do, so there wasn't... that sort of data at two weeks. And then we'll give, you know, we'll put out the data. You're right that it's a small study. Again, it's a small but yet informative study to help us think about combinations, how we build them going forward. And again, looking into the future, This trial was to set the table, if you will, for the ultimate of adding a third agent to the combination so that we would have a nuke, we would have a core inhibitor, and then we would have our BDP721, which is our RNA destabilizer, which should be an oral agent to target as antigen. And so that's... That's what we're shooting for, obviously. That's why this is an incredibly important study, even though it isn't laden with virology. But that will come in due course and as early as the next study that we'll report out later this quarter.
spk03: Thank you so much. And then maybe one last question. I apologize. As we head into easel, we're very much looking forward on the preclinical data from 721. Should we be expecting some preclinical models where you have done combination studies with 514?
spk10: So I won't comment on an actual presentation until it's finalized. But what we have said is we have looked at combinations. We've looked at 721 plus core inhibitors and seen additivity to synergistic behavior, and we've also added 721 to nuke and observed the same. So we have done those experiments. What shows up at easel in its final form will be to be finalized. But we're pleased to be able to have the opportunity to present that.
spk03: Thank you so much.
spk10: You're welcome.
spk02: Your next question will come from Eric Joseph with JPMorgan. Please proceed with your question.
spk06: Thanks for taking the question. Maybe just a follow-up on 514 and safety. Can you talk a little bit about the time of onset of OBs, albeit low grade, and how they resolve. I'm just curious to know whether, as you continue to dose Escalate, or potentially look to explore longer course of the treatment, how you think the taking profile might vary. And then in terms of thinking about next steps with the HPV program, what we hear from KOLs is that there's going to be a multimodal approach, three to four mechanisms perhaps, being what it will take to get patients to a functional cure. Similarly, I guess, are you strategically thinking, or how are you strategically thinking about um you know combinations with 514 outside of your internal portfolio perhaps with an oligo approach i'm sorry could you repeat the last part of that last question you drifted up how are we thinking strategically about about what uh evaluating 514 combinations uh with uh agents outside of your portfolio potentially with an oligo Like an SRNA or an ASO or with immunotherapy.
spk10: Got it. So, and again, with regards to any AEs, again, which were all mild except for the one that we noted, you know, they're just scattered throughout the study in different areas. doses over different periods of times and so on and so forth so there's just nothing to really uh point out at this time it looked very um you know sort of just like any any sort of study like this whether it's a phase one study or any study like this when you see unremarkable safety findings uh they're just sort of uh scattered so we'll have again a summary of all of that but there was nothing uh concerning with regards to how we're looking at anything going forward. This is actually a very unremarkable profile with no real pattern. With regards to the strategy, so, you know, it wasn't so long ago that people in the community were wondering, you know, could a core inhibitor plus a nuke lead to a functional cure? And I guess, in theory, we really still know the answer to that, although some of the work that others have done suggests that that may not be enough. Even though we had a core inhibitor, we've had a core inhibitor for many years now, and we're obviously planning for this study for a long time that we just announced today, which was the first such combination of a nuke plus a core. We were never assuming that that would be enough. If it were to be enough, we would be delighted, because 514 is amongst the finest core inhibitors, we believe. But we were – that would be an exciting upside, but we were always planning for the future, assuming that that wouldn't be the case. So now what you now know is 721 – Our molecule that is oral and goes after S-antigen is the result of our, you know, continued pursuit down the line of, you know, we will keep going until we know we have enough agents. And ideally, we're going to try to harvest all those agents in-house. I see right now we've shown comparative data of 721. you know, versus SIRNAs and antisynthalgas. You know, we've had a slight comparison of that in the same animal model that's been reported. And 721 stands up, you know, very well against them. You know, so could that be a third agent, 721 plus our core inhibitor 514 plus a nuke? Could that be enough? It certainly gives you a stronger chance than a nuke plus a core alone. We're hopeful that it could be, but it might or it might not. We'll find that out as we propel down into next year and hopefully get triple combinations going. But suffice it to say, we hope that it could be, but we won't rest in terms of looking at other kinds of things, thinking about other mechanisms. until we're sure we give a functional cure, and hopefully one that's an all-oral one. Could we find an asset outside that we could combine with on top of R-triple? Possibly could we generate something in-house that could be combinable on top of R-triple, if you count the nuke again? I think that's another possibility. But our strategy, to be clear, is to keep aggregating as many mechanisms as we need to provide the same, ideally the same quality cure that we've been able to offer hepatitis C patients. That's our goal and our dream. Thanks for taking the question.
spk05: You're welcome. Thank you.
spk02: Your next question will come from Roy Buchanan with JMP Securities. Please proceed with your question.
spk01: Thanks for taking the questions. And congrats on the Phase 1 results for 514. First question on that, can you just remind us, it sounds like you're stopping at 800 milligrams, how you chose that cutoff?
spk10: Yeah. So we, you know, we modeled all of these doses were just modeled based on, you know, Phase 1 work we had done in HealthEase. You know, to that end, we pay particular attention to pharmacokinetics, you know, the exposure overall, but importantly, you know, sort of the C24 concentrations, you know, make sure we have good pressure on the virus. And so it's really a combination of PK, PD, safety information that we get from Phase I patients A, the healthy portion, to help establish the doses that we did. And, you know, it's played out quite well. I think, again, 200 and 400 both give very, very nice exposures. And to mind everyone, we did put out the study in Healthy Volunteers.
spk01: um at easel um you know back at the virtual easel meeting last year that's the reference too okay great and then the for the sars cove 2 inhibitor i mean you guys are clear that it's specific for sars cove 2. i'm just curious if you have any sense of the pan coronavirus potential have you specifically looked at it um and then do you think that your polymerase inhibitor might be close behind in development such that you might have a potential combination treatment option in the not too distant future?
spk10: Well, so starting, so the polymerase program is not as far along as the protease. So I, you know, and the way science goes, you know, some things catch up, other things, you know, lag behind. But, you know, the goal ultimately will be to press down on both of these mechanisms, bring them forward, and hopefully the, you know, the two paths are able to cross if we need them to cross, you know, to ultimately build combinations. So let's all hope for the world, you know, one agent will be enough. And then with regards SARS-CoV-2, I mean, we, you know, we designed protease inhibitors to target it. We do look at other coronaviruses as well. So I think, you know, we'll have more to say on that ultimately, but there is the possibility that, you know, whereas we didn't want something... Well, let me back up. As you know, earlier in our process, we did scan through libraries of compounds and so on and so forth just to see if there couldn't be an expedient start by catching a lead earlier. And whereas we did find molecules that had activity against the virus, we weren't satisfied with the degree of potency and other characteristics that we saw with them. So in parallel, and I'm leaving nothing to chance, you know, we were doing more of a design approach. And we did look and we have paneled against multiple different coronaviruses, including SARS-CoV-2. But to be clear, this was very targeted to make sure more than anything that we had molecules that worked really well against SARS-CoV-2. I do believe now we're building up a stable environment. of molecules with multiple different chemical classes and other kinds of properties that will be able to hit multiple different coronas. And that'll put us in a great position to the extent there's ever, God forbid, another such beast as SARS-CoV-2 to be in a position to really harvest a much more targeted library that we know hits coronaviruses versus what we had prior to our efforts here.
spk01: Okay, great. And then one last one. Actually, on Maverick, I know you guys are not marketing that drug yourself, but AbbVie sales came in quite a bit lower than we were expecting. And I understand the first quarter seasonality dynamics, but was there anything else that you guys can communicate that That has impacted the sales in the first quarter. Thanks.
spk10: Yeah, no, I would take your input from Abby on that. And Lisa and what, you know, what Gilead has also noted, there's still a COVID impact. Okay. Thank you. You're welcome.
spk02: Your next question will come from Brian Scorny with Baird. Please proceed with your question.
spk07: Hey, good afternoon, guys. Thanks for taking my question. Let's start on EDP721. I mean, it sounds like you either have or are just about to submit an IND. So I was just wondering how we should kind of think about the clinical development program here. I mean, you know, can you kind of start with traditional, sad, mad, and healthy, and then how early can you get into patients, and what's sort of the goal in terms of initial proof-of-concept data? I mean, obviously it's not an antiviral, so it wouldn't be necessarily for DNA testing, or RNA impact. So, I mean, is the comps here really kind of the RNAi-based therapeutics where, you know, what's important is to look at the assay antigen reductions or what other sort of biomarkers should be kind of considering here for proof of concept?
spk10: Yeah, I think it'll be, you know, somewhat similar to the path of 514. You know, first we'll do sad, mad, healthy, as you point out. Then we'll get into HPV. you know, patients. And, you know, we might, you know, be able to look at viremic and nuke patients for a period of time. But clearly with this one, we're going to be also looking at S antigen levels, right? So that will be one of the key reads in addition to obviously DNA and RNA, which a number of other mechanisms will take care of. So, you know, hopefully being able to get as early a read as we can on that in HPV patients will be clearly one of our aims and getting the triple together as expeditiously as we can. So stay tuned on that front. I think we'll have more to say As we take that into healthies, again, we're aiming to do that mid-year, have the results from that in the first half of next year, but also be getting on to other programs other studies as quickly as we can, kind of like 514, meaning with 514 we had the healthy stuff done, we saw the dose information, and then we were on to the next studies because we saw what we knew we had to see in order to propel it. So I think as we get the healthy data and we're embarking upon the patient studies, we'll have a very detailed outline to share in terms of how we're going to prosecute them.
spk07: Great. And on the SARS-CoV-2 Protease Inhibitor Program, I mean, I don't know if you'd be comfortable sharing specific data on your lead or just want to talk kind of generally about what we know about the potential selection pressure and potential conservation of important binding pockets for protease inhibitors and the ability to drive resistance. I think there's a bit of, I guess, remorse for the... utilization of MAB monotherapy and potential selection pressure. I guess, are regulators hesitant at all about sort of use of an antiviral monotherapy without a really well-characterized barrier to resistance? And think about that in the context of a protease inhibitor.
spk10: Yeah, well, you know, the good news is we're talking about a, you know, a hopefully short period of treatment duration, right? you know, a correlate that one might think about is looking at our RSV program and thinking about, you know, drug dosing durations of maybe five days or something like that. So that's number one thing that's good. The other is that, you know, we're not going after spike protein. Instead, we're going after highly you know, conserve targets with conserved binding pockets that are key for the survival of the virus. So, um, I think the, the opportunity to go in and go in and, um, and, uh, inhibit these, you know, sort of conserved regions of conserved targets, um, would be, uh, about the best strategy you could take if you're trying to minimize these sorts of challenges. So I think that's what we're on the mark for. And, you know, so far so good. Again, we're excited to be pushing our first protease inhibitor against this target into IND-enabled studies soon. And if those go well, We hope to be in our phase one study early next year.
spk07: Great. Thanks, Jeff.
spk10: You're welcome.
spk02: Your next question will come from Akash Tiwari with Wolf Research. Please proceed with your question.
spk05: Hi. This is Leo for Akash. Thank you for taking our questions. Starting with 514, I think the first question we have is, We noticed you mentioned that the treatment lead to one log reduction of RNA. Did you notice any like dose response between the 200 mg versus 400 mg in reducing the RNA level? And the second, the COVID program, previously you mentioned about both protease inhibitor as well as polymerase inhibitor being a very interesting target for COVID. So now you have moved forward the protease inhibitor. So I wonder, is there any pros and cons in comparing these two different targets, both in terms of efficacy as well as safety? And do you plan to test both molecules of different MOAs in the clinic? I think the last question is more related to the RSV regulatory pathway.
spk10: Maybe we'll just pause there with the questions so we can keep up with it. I think, I mean, this was a very small study in 514. And we, again, the dose response, I'm not sure we, Natalie, do you want to comment on any dose response?
spk04: Sure. Hello. So I think just to complete maybe what Jay was starting to say, obviously, as you have noticed, we have a small number of patients in each of our dose groups. It is not totally clear that we can see a dose response, but I don't think you would have expected that clearly in the new surprise patients. Now, if we look at E-plus versus EMEK patients, um you know we could maybe say that the 400 milligram may have a little bit more decrease in the rna but again you know we're talking with a very small sample size uh you deal with the ability of the sa and variability of your small sample size so i think once we get all the very new data and we compile all the data together across the three doses we'll have a better sense
spk10: And so, um, and again, I think the viremic data, you know, we'll probably be dealing with a much more elevated, uh, DNA to, to start with obviously greater opportunity to see responses. Again, we've only got two of the doses then not the third. And, um, the changes that you're going to see when this new suppressed population are going to be a very small RNA changes if you see them typically and usually they're larger than e-antigen positive patients and they were the minority of patients in this study. Some other studies have selected to get the e-antigen positive patients selected. We didn't do that so we have e-mig and e-pos. Regarding your question about PI and polymerase, we're prosecuting both targets. And was your question, if we're successful there, would we take them into the clinic? Did I understand your question right?
spk05: Yes. And also, just in high level, is there any, do you think, pros and cons in terms of both efficacy and safety between these two targets?
spk10: Yeah. I think no one knows. pros and cons yet. There's just no data really to speak of broadly across these different classes other than to say, you know, either or both has a compelling rationale to work. You know, within protease inhibitors versus polymerases, with polymerases you can have either nukes or non-nukes. Sometimes nukes can have safety challenges over non-nukes, but, you know, it really just depends, comes down to an individual molecule. So again, I think both, we wouldn't be working on both mechanisms if we didn't think that they were compelling ones to try. That said, you know, we need to let the field mature a little bit, get these molecules with some clinical data sets that are, you know, you know, that are analyzable so that people will understand what these therapeutics can do. We're obviously very bullish on the need to have these beyond vaccines for obvious reasons.
spk05: Got it. Thank you. I think my last question is about the RSV regulatory pathway. I wonder, based on your discussion with FDA, do you have any thoughts on the design for the pivotal trials specifically on the endpoint selections, any specific outcome selection? For example, it could be percentage of progression to lower spread of infection, or maybe time to hospitalization.
spk10: Yeah, so I think we need to finalize our Phase 2b program, then we'll have these discussions with the agency over registration endpoints. It's, you know, it's not appropriate to comment on that until you've had that discussion.
spk05: Got it. Thank you very much.
spk10: You're welcome.
spk02: Your next question will come from Zegbay Jalla with Roth Capital Partners. Please proceed with your question.
spk12: Hey guys, thanks for taking my question and congrats on all the progress. I just have a few quick ones for you. I think the first, Jay, is just trying to clarify if you will not be moving forward towards approval if you don't have something that could perhaps reduce a cure with your HBV program. Even if you get your triple E and you don't have a cure, you're not going to move forward with that.
spk10: No, did I? So I don't believe I said that. You have to keep, I think what I was trying to say was, if two mechanisms isn't enough, you add a third, and if a third isn't enough, you know, maybe you need to add a fourth, or maybe you need a longer duration of treatment, or um you know what have you maybe there's certain patient populations that you need to explore uh further so um no i i think um you know it's uh it's really premature to know what a triple uh therapy uh will look like uh in this especially given one that hits so many different cylinders i i think we're you know for us um you know, core inhibitors do a lot of things in addition to pushing on DNA like nukes do, but they have a number of other points of mechanistic interest against the virus. But what a nuke and a core or nuke plus, you know, a lot of other mechanisms don't have is the ability to robustly affect S-antigen. And that's something that we We really are anxious to get brought into this mechanism. It can affect the S-antigen, which obviously, among other things, is sort of a foil to the immune systems being able to fully take on the virus. If you can knock that down, along with the other mechanisms that we're adding, we're quite hopeful that we'll be able to you know, have a major impact. Um, but like I said, it's more of a, a, uh, we're not going to, we're not going to say we're finished until we're done. Um, if we need ultimately to add another mechanism, whether it's immune stimulation mechanism or something else, um, we'll continue to explore that. And if we can, we want to try to keep on our, um, on our track of having an all oral regimen. Because right now, the three agents that we're talking about for our triple do represent an all oral opportunity, which is fairly rare in the landscape of HPV treatment. So I think what we want to do is we can continue to build on that. Obviously, there could be other things out there that could give you an immune boost. I mean, an easy thing to look at, and others are doing it too, is to tack on an interferon arm to see what it could do. So there's easy ways to build a quad if you want to do that in part of your arms. We're obviously thinking about all kinds of things right now. But to be very clear, I think we're very bullish going into this. you know, the possibility of having our oral triple.
spk12: Thanks, Jim. Just to follow up to that, just kind of wondering, and this is a difficult one, but just kind of wondering what it is that we should be looking for, especially with the vermic data coming up, you know, in terms of signals as to perhaps, you know, combining this with your other agents could perhaps, you know, lead to that care with perhaps longer duration of treatment or whatnot. But just, you know, what should investors and analysts be looking towards? Is it the long difference or, you know, what should we keep our eyes on?
spk10: I would say, you know, it's the you know so we've looked at safety tolerability and pharmacokinetics and healthy we've looked at safety um tolerability and pharmacokinetics now in hbd patients and on top of a nuke and now we're in this next study we're going to just back out the nuke these will be patients that have higher viral loads particularly on the dna side and so what um What we want to see is just a very solid, you know, reduction in viral DNA and probably, again, to a lesser extent, you should hopefully see some effect on RNA. You know, the RNA changes are never as much as the DNA changes that you can usually see in these types of studies. So, you know, a good couple solid logs of viral load reduction in good trough levels at 28 days. good safety and tolerability, these will all be things that give us green light, green light, green light in terms of moving ahead into more advanced studies with 514. It's really helpful to, again, help define the optimal dose in terms of dose selection for future studies. So that's what we would be looking for. I think, you know, today's just sort of a good prequel in terms of the kinds of information we get. I think just in addition, we should be able to get information on HPPD. You're not going to see effects on antigens, you know, in a 28-day period.
spk12: understandable. I think people are just getting excited, me included, with the teaser from the HPV. But moving on to the eyes, we program, you know, DSK similar like you, they noted, you know, finding it really difficult to find regions where there are high RSV cases. But I'm just wondering, you know, even when those cases do return with, you know, Sanofi talking about perhaps filing their drug for pediatric use, you know, sometime in 2022. I'm just wondering for your later studies, for pediatric at least, you know, how you're thinking that may affect it.
spk10: Yeah, I think, well, I mean, people, they're looking for a more potent version of Synergist, you know, which is a which is a monoclonal antibody that historically has been used prophylactically in high-risk premature births and which, when used therapeutically, did not work. Got a longer-acting, you know, version of that. And so you just have to wait and see, you know, how, you know, A, how it might work, and then B, you know, to the extent it... has efficacy in the target patient population. You know, one of the things I think you're going to see then is children get RSV. They need to get RSV repeatedly when they're children to sort of build up a, you know, sort of a partial natural immunity to it. And if they're not... If they're not getting exposed to the virus, in some ways you're kicking the can down the road. So I suspect if these antibodies go on and start treating younger children, especially in their first year of life, the first season that they're exposed, would otherwise be exposed to them, they're and they're being treated prophylactically with a monoclonal antibody, you're just setting them up to get their first RSV infection in the next season that they're not on a prophylactic antibody, right? So I think it's just a question of what age group of people our drug is going to ultimately treat. But there will be a lot of pediatric RSV out there.
spk12: Thanks, Jim. Just the last one here for me. Regarding the NASH program, again, don't want to put words in your mouth, but just wanted clarification on whether or not you'll be looking at 305 as a single agent. or as combo use when you do get the data and you're thinking about moving forward. And then the last bit here, I thought the data for 305 and 297 would be coming at the same time, but it seems like 305 might be a little delayed. I don't know about 207, but I was just wondering if you're going to wait to have both of those data sets in hand before making a decision to move forward.
spk10: Yeah, I think the answer, I mean, we can't make a decision relating to 305 until we have the data on 305. So I think we will need to wait to look at that data to put it into the mix clearly. But I think ultimately I see FXRs and drug classes against NASH. All of them, the ones that have efficacy anyway, are going to do something, right? But they're not going to be treating patients optimally. And I do believe that optimal treatment for patients is only going to come by way of combos. And I think the sooner you get on with the combos and start running combo trials, you know, I think the better just because you'll be getting – more relevant data sets that have a higher chance of higher impact. And again, as we've stated previously, our ultimate goal here is to partner up and find a partner for our FXR program, certainly before phase three. And any time as soon as a data supports, data set supports doing a combination potentially. So that's what we're thinking about. But we just need to harvest the data.
spk12: I was just wondering if you're waiting for the data from 305 before making a decision on 297. But it doesn't sound like that's the case. And then your last comment sounds like, you know, 297 is definitely up for consideration also as a combo.
spk10: I think all the FXRs will be up for consideration in combo. Again, I think we won't be able to make a complete analysis on our FXR program and strategy, which includes two different molecules, until we see the totality of the data.
spk12: Perfect. Thanks, Jay. I appreciate it. You're welcome.
spk02: At this time, we will do one final call for questions. If you would like to ask a question, please press star 1 in your telephone keypad. And at this time, there appears to be no further questions in queue. I would now like to turn the call back over to Jennifer Vieira for closing remarks at this time.
spk13: Thank you everyone for joining us this afternoon. If you have additional questions, please do not hesitate to reach out to us. Thanks so much. Bye-bye.
spk02: This concludes today's conference call. Thank you for participating. You may now disconnect.
Disclaimer