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spk03: Good afternoon and welcome to the Enanta Pharmaceuticals Fiscal Fourth Quarter and Year-End 2020 Financial Results Call. At this time, all participants are on 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, Senior Director, Investor Relations. Please go ahead.
spk02: Thank you, Operator, and thanks to everyone for joining us this afternoon. The news release with our fiscal fourth quarter and 2020 year-end 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 Mellett, 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. Ananta does not undertake any obligation to update any forward-looking statements made during this call. I'd now like to turn the call over to Dr. Jay Lulli, President and CEO. Jay?
spk07: Thank you, Jennifer, and good afternoon, everyone. Throughout 2020, we made meaningful advances across our pipeline. Today, I'm excited to review this progress and to share our plans for multiple catalysts in 2021. Looking ahead, we believe that we are in a unique position to leverage our years of drug discovery experience to deliver new medicines to patients. Not only do we have a robust and growing internal portfolio, which I'll review momentarily, but our efforts are informed by our previous successes, including the discovery of two products which are currently marketed by AbbVie as part of its leading treatment for chronic HCV infections. In the beginning of the year, we announced our program for human metapneumovirus, or HMPV, and in March, we began working to find a treatment for COVID-19. I'm proud and appreciative of my colleagues for their efforts in rapidly responding to the pandemic and for the nimble and creative thinking they applied to translate our extensive experience in virology, notably respiratory virology, to fight this global challenge. Taking a step back, By focusing on these two respiratory viruses, combined with our work in respiratory syncytial virus, we're establishing our position as one of only a few biotechnology companies explicitly developing a broad portfolio of respiratory virus treatments. We also advanced our hepatitis B compound, EDP514, a novel core inhibitor that displays potent anti-HPV activity in vitro at multiple steps in the HPV life cycle. In February, we announced positive results from Part 1 of our Phase 1A-1B clinical study of BDP514 in healthy subjects, which supported further evaluation of once-daily dosing in Part 2 of the study and chronic HPV patients treated with marketed nucleoside reverse transcriptase inhibitors, which we refer to as new suppressed patients, as well as in chronic HPV-infected patients with high viral load, not currently on treatment, which we refer to as viremic patients. Moving to our NASH programs, the past quarter was also marked by the initiation of two clinical studies. Argon-2, our Phase IIb study evaluating our first FXR agonist, EDP305, in subjects with liver biopsy-proven NASH, and a first in human study of EDP297, a highly potent and targeted FXR agonist that is their follow-on FXR candidate. As we move forward toward the remainder of 2020 and beginning of 2021, we look forward to initiating two new Phase II trials, for our program in respiratory syncytial virus, or RSV. Now let's look at our portfolio programs in a bit more detail. I'll begin with our virology-focused programs, more specifically our respiratory virus programs, RSV, HMPV, and SARS-CoV-2. I'll start with RSV, where we are developing EDP938, a potent non-fusion inhibitor of RSV-A and RSV-B. RSV is a severe respiratory infection associated with significant morbidity and mortality in infants, the elderly, and immune-compromised adults, in a condition for which there is currently no safe and effective therapy. In an average year in the U.S., RSV infections lead to around 2 million outpatient visits among children younger than 5 years old and hospitalizations of more than 57,000 children under age 5 and about 177,000 older adults. Our Phase IIb double-blind placebo-controlled study of EDP938 is designed to enroll approximately 70 subjects up to the age of 75 years randomized to receive either 800 milligrams of EDP-938 or placebo for five days. Starting in the southern hemisphere, recruitment in this study has been affected by the ongoing COVID-19 pandemic and related shutdown and social distancing measures which have reduced the incidence of flu and RSV. Thus, as we've previously said, we are hopeful that the 2021 Northern Hemisphere RSV season will allow us to finish enrollment in RSVP, but that will be dependent on RSV being as prevalent as in a normal season. To that end, we are reactivating close to 50 of our existing RSVP clinical sites in North America. These sites are prepared with RT-PCR machines to diagnose patients' RSV and and to rule out flu and COVID in the same day, which should make enrollment as efficient as possible. In addition, we're working to set up about an equal number of sites in six different European countries by year-end, and are also planning to add sites in select Asia-Pacific territories in 2021. As we know, COVID-19 is unpredictable, and the rate of enrollment in this trial will continue to depend on the prevalence of RSV infections, and the precautions that people are taking for COVID-19 as the winter progresses in the Northern Hemisphere. Considering that respiratory viruses often have hotspots, we are prepared with many geographically dispersed sites to identify and enroll as many patients as possible in this RSV season. Assuming we can complete enrollment in the second quarter of 2021, our goal remains to report data in the third quarter of 2021. We also plan to initiate two additional Phase II studies with EDP938, one in adult transplant patients by the end of 2020, and another in pediatric patients in the first quarter of 2021. The adult transplant study named RSV-TX is a Phase IIb randomized double-blind placebo-controlled study to evaluate the effect of EDP938 in adult hematopoietic cell transplant recipients and acute RSV infection of the upper respiratory tract. The pediatric trial named RSVPs will be a phase two randomized double-blind placebo dose ranging study to evaluate EDP938 regimens in hospitalized or non-hospitalized infants and children aged 28 days to 24 months who test positive for RSV based on an approved diagnostic assay. Our goal for both of these studies to enroll during 2021 and 2022, subject to the potential impact of COVID-19 on the incidence of RSV infections and activities at trial sites. Turning to our other two respiratory virus treatments and development, HMPV, a virus that causes respiratory infection with symptoms similar to RSV, and SARS-CoV-2, We have discovered several potent molecules. For SARS-CoV-2, we are leveraging our expertise in direct acting antiviral mechanisms to discover new compounds to treat COVID-19 using a combination of drug target screening and drug design. The advantage of this discovery approach is that you can make potent purpose-built inhibitors against multiple different targets. While we are encouraged that the vaccine could be available soon, we still see a need for an oral treatment for those in various patient populations who are nonetheless infected with COVID-19. Regarding HMPV, since announcing our new drug discovery effort in January, we've been optimizing nanomolar inhibitor leads against this virus. We are hoping to finalize a clinical candidate selection for each program next year. Let's move on to our hepatitis B program with EDP514, our lead core inhibitor currently being tested in chronic HPV patients who are nuke-suppressed and in viremic HPV patients. In February, we announced positive results from Part 1 of the Phase 1A, 1B clinical study of EDP514 in healthy subjects, which allowed us to initiate Part 2 in chronic nuke-suppressed HPV patients. These encouraging data, which highlighted positive safety and tolerability, as well as pharmacokinetics suitable for once-daily dosing, were presented in a poster presentation in August at the Digital International Liver Conference, sponsored by the European Association for the Study of Liver, or EASL. Part 2 of the Phase 1a1b study, which is now ongoing, is designed to evaluate the safety, tolerability, pharmacokinetics, and any viral activity of orally administered multiple ascending doses of EDP514 versus placebo in up to 24 randomized nuke-suppressed patients over a 28-day period. Barring any further significant COVID-19 disruptions, we plan to have preliminary data from Part 2 in the second quarter of 2021. Also in our HPV program, in July we initiated a Phase 1B clinical trial in viremic HPV patients. This randomized, double-blind, placebo-controlled Phase 1B study in viremic chronic HPV patients not currently on therapy has a similar design to the one in nuke-suppressed HPV patients. We plan to enroll 24 subjects at our clinical trial sites in Hong Kong and Taiwan. which are both areas with large unmet need for HPV treatment. We expect preliminary data from this trial in the second quarter of 2021. And finally, we continue our HPV efforts in search of a novel oral agent against a different HPV mechanism that could be combined with EDP514 and a NUC to create an all-oral triple regimen. Progress against that has been strong this year, We'll have further details around this new program and our oral HPV triple strategy early next year. Shifting gears to our work in non-viral liver disease, we are currently focused on NASH, where we are conducting clinical trials on EDP305, our first FXR agonist. Based on data from Argon1, which was highlighted in an oral presentation at EASL in August, We initiated recruitment in Argonne 2 in July. Argonne 2 is a Phase IIb randomized, double-blind, placebo-controlled, 72-week study in approximately 340 subjects with biopsy-proven NASH with fibrosis. The primary endpoint of Argonne 2 is improvement of fibrosis without worsening of NASH and or NASH resolution without worsening of fibrosis. We're using EDP-305 doses of 1.5 milligrams and 2.0 milligrams, which we believe will favorably balance strong efficacious target engagement with tolerability. We're additionally developing EDP-297, our follow-on FXR candidate for NASH, with potentially best-in-class potency and targeted effects. At EASL, we presented two posters which demonstrated the treatment with EDP-297 demonstrated significantly reduced fibrosis progression and improved liver function in a rat model match. We were encouraged by EDP-297's preclinical profile, which shows high target tissue distribution in the liver and intestine versus plasma and skin. In September, we announced the initiation of a Phase I randomized, double-blind, placebo-controlled, first-in-human study designed to assess the safety, tolerability, and pharmacokinetics, including the effect of food intake, of orally administered ADP297 in approximately 74 healthy adult subjects. The study includes two phases, a single ascending dose phase enrolling six cohorts, including a two-part food effect cohort and a multiple ascending dose phase enrolling three cohorts. We look forward to reporting clinical data in the second quarter of 2021. By mid-year 2021, we expect to have important new insights for both EDP-305 and EDP-297, which will inform next steps across our NASH programs. We will know whether the tissue targeting and potency design elements we introduced in 297 will allow us to better leverage FXR agonists without encountering tolerability challenges. And at approximately the same time, we expect that Argon2 will provide us an interim analysis at 12 weeks of treatment on a subset of patients to enhance our ability to prioritize our FXR agonist compounds and seek opportunities more quickly for development of one or both of them in combinations with other mechanisms for NASH. We are encouraged by the efficacy demonstrated by FXR agonists for NASH with fibrosis, a disease with high unmet need, and believe that this mechanism has promise as a potential therapeutic. We've accomplished all of this while we're still managing the impact of COVID-19 on our lives and business. I'm continually impressed by the team we have built and their ability to maneuver around the challenges with which we have been presented. I want to thank our very talented and committed employees who have worked tirelessly during the pandemic. Their dedication is evidenced by the progress we've been able to make this year. I'd like to conclude my remarks by emphasizing a few key points. We made significant progress during our fiscal year despite the multitude of challenges presented by the COVID pandemic, including the initiation of four new clinical trials, two for our HPV program and two for our NASH program, concurrent with conducting our ongoing Phase IIb program for RSV. Further, we are on schedule to initiate RSV-TX in adult transplant patients later this quarter, and RSVP in pediatric patients in the first quarter of 2021. We were also successful in moving our HPV trial and viremic patients forward as well as in progressing our phase 1b trial and HPV patients who are new suppressed with preliminary data expected for both these studies in the second quarter of 2021. And finally we look forward to advancing our candidates in NASH with the Argonne 2 trial of EDP 305 and the Phase 1 study of EDP 297. Looking toward 2021, we are poised for an exciting year with multiple data readouts anticipated across our pipeline. I'll stop here and turn the call over to Paul to discuss the financials for the quarter. Paul?
spk09: Thank you, Jay. I'd like to remind everyone that Enanta reports on a September 30th fiscal year schedule. Today we are reporting results for our fourth quarter in fiscal year ended September 30th, 2020. For the quarter, total revenue was 23.6 million and consisted entirely of royalty revenue earned on AbbVie's global HCV product sales of 414 million. This compares to total revenue of 51.3 million for the same period in 2019. The decrease in our royalty revenue was due to lower global HCV product sales, as reported by AbbVie, as treated patient volumes have remained below pre-COVID levels. AbbVie now expects total HCV sales of approximately $1.9 billion for the calendar 2020, as treatments remain below pre-COVID levels. Our royalty revenue was calculated on 50% of Maverick sales at a blend of our first and second royalty tiers of 10% and 12%, respectively, and on approximately 30% of Vaquera sales at a royalty rate of 10% after adjustments for certain contractual discounts, rebates, and set-offs, which are now just over 2% of Abby's total reported HCV sales. Our royalties are calculated on a calendar year basis. Therefore, royalties in our fiscal first quarter ending December 31 will be calculated at the highest royalty rate for the year, and royalties for our fiscal quarter ending March 31st will be calculated at 10%, our lowest royalty rate tier in our fiscal year. You can review our royalty tier schedule in our 2019 Form 10-K. Moving on to our expenses, For the three months ended September 30th, 2020, research and development expenses totaled $36.7 million compared to $38.7 million for the same period in 2019. This decrease was primarily due to the timing of our clinical studies year over year and COVID-19 related delays in two clinical studies that are now ongoing. General and administrative expense for the quarter was $6.7 million compared to $6.2 million for the same period in 2019. An answer recorded income tax expense of $10.7 million for the three months ended September 30, 2020, compared to an income tax benefit of $.5 million for the same period in 2019. The income tax expense in 2020 was driven by a non-cash valuation allowance recorded against our deferred tax assets of approximately $18 million, which was partially offset by $7.3 million of NOL carrybacks in R&D tax credits. For the 12 months ended September 30, 2020, and ANTA's effective tax benefit was approximately 3%, compared to an effective tax rate of approximately 2% for the 12 months ended September 30th, 2019. I'd like to note that the drivers of the decrease in the effective tax rate are covered in the press release. Net loss for the three months ended September 30th, 2020 was $29.3 million or a loss of $1.46 per diluted common share. compared to net income of $9.2 million, or $0.44 per diluted common share, for the corresponding period in 2019. The net loss for 2020 was due to the decrease in HCV royalties earned under our AVI agreement, which were adversely affected by the COVID-19 pandemic. And at the end of the quarter, with approximately $419 million in cash and marketable securities, an increase of approximately $19 million from our 2019 fiscal year-end balance of $400 million. Notwithstanding our current level of operating losses, our existing cash balances together with our ongoing royalties are expected to be sufficient to fund our operations for the foreseeable future. Regarding guidance for fiscal 2021, we expect our research and development expense to be between $145 and $165 million, and our general and administrative expense to be between $27 and $33 million. Further financial details are available in our press release and will be available in our annual report on Form 10-K when filed. I'd now like to turn the call back to the operator, and he'll line up the lines for questions. Operator?
spk06: And at this time, I would like to inform everyone, in order to ask a question, you will need to press star 1 on your telephone. To withdraw your question, press the pound or hash key. Please stand by while we compile the Q&A roster. Your first question comes from the line of Roy Buchanan from J&P Securities. Please go ahead.
spk10: Hi, great. Thanks for taking the questions. Had a few on the RSV program. So for RSVP, it sounds like you're more set versus the last quarter in terms of adding Asian sites in 2021. Does the northern Asian season largely mimic that in North America, and can you provide any specifics on a potential Asian site, is China included?
spk07: Hi, this is Jay. So in terms of Asia, different countries have slightly different season. Some are actually almost year-round. So in the broader perspective, when we look at the northern hemisphere, the U.S. and Canada, and we look at Europe, we think if we can build on Asia, that we'll be getting coverage at least somewhere for, you know, maybe nine or so months out of the year. Um, so I think, um, you know, specifically we'll, we'll come back later with, uh, you know, other Asian countries in particular that we're, that we're picking up, but that's, uh, the plan is to continue to add some of those 2021 timeframe. Of course, in the meantime, we'll have, um, Lots of North American sites on board. You recall we were poised with dozens of them previously. So we'll have approaching 50 North American sites and hopefully at least that many more in the EU by the end of the year. So really trying to pull the stocks out for many, many sites.
spk10: So are any of the North American sites yet open? Do you have any feedback from those sites?
spk07: It's just coming up, you know, but what we can tell is, you know, if you recall last year, the season came early. And so this year versus last year, it's a little quiet so far this year. And, you know, we'll just have to keep an eye on that. We've started to screen. But in general, the rates, you know, as tracked by CDC are, you know, pretty quiet right now. We'll just have to wait and see as the season progresses and with the backdrop of COVID and social distancing and the like, you know, what the season will provide.
spk10: Okay, great. And I had a couple on the new phase two trials, if you don't mind. So for RSVPED, how many patients are you planning? And the endpoint is progression to lower respiratory tract infection. And then for that trial, do you have investigators lined up? And I guess maybe kind of similar to the last question, just how are they viewing the current situation and the feasibility of starting the trial?
spk07: I'm sorry, are you talking about the PEDS study?
spk10: Yeah, right, RSV-PEDS PEDS.
spk07: Yep. Yeah, so the, you know, on the PEDS front, you know, we're aiming to start in next quarter. We're aiming for about 90 patients total. And, yeah, so I think those are the, You know, the main points in terms of the PEAD study itself, you know, part one is going to be safety and PK. And then we'll have a part two where we'll be looking at the actual virus. So change in RSV shedding is one of the things that we look at. So PEADs will be given 938 or placebo for five days. And, you know, we'll be looking at cohorts. up to 24 months of age.
spk10: Okay, great. Then one last one on the transplant trials we don't mind. So how many sites are you planning for that one? Are you also including Europe? And is there any information on the current RSV rates in the transplant setting, either in the U.S. or elsewhere? Thanks.
spk07: I don't think so. The sites, you know, will come online. We'll you know, get numerous sites up. There'll be a global study that will have, you know, sites in all the obvious sort of territories. They'll be looking at 938 versus placebo for 21 days. And, you know, it goes a little bit longer because the patients are obviously immune compromised. There aren't a lot of statistics on this specification population, so we just get set up in a lot of the centers during the normal season and recruiters as they come.
spk06: Your next question comes from the line of Brian Scorney from Barrett. Please go ahead.
spk11: Hi, thank you. This is Jack Donahan for Brian. Thanks for taking our questions. We have one quick one. We're wondering about if you had any updated thoughts with regard to the HBV opportunity for core inhibitors in light of the disappointing news from Assembly and their core plus nuke regimen and the sustained viral response data we saw there. I know you're looking at the triple combination internally as well, but we're just wondering what your thoughts were in light of that news. Thank you.
spk07: Yeah, so it's an interesting data set. You might have to hand it to them for doing that study. The study was looking at a core inhibitor plus a nuke plus time. So the question is, could a core plus a nuke plus time get you to a functional cure? And again, nobody knew the answer to that question. They looked at different time points. over the course of their investigations, three months, six months, a year, and so forth. And, you know, the results that were produced in this initial study weren't particularly positive. You know, there could be a lot of different reasons. It's either a nuke plus a core plus more time, you know, although they went for 12 to 18 months, so it's a good chunk of time. It's possible that their first generation core inhibitor wasn't potent enough. I think that's one of the reasons why they're working on other generations. EDP514, our core inhibitor, is roughly 10 times more potent than than the one that you're referring to in that, in that study. And then another possibility of course, is that a core plus a nuke plus, um, a third agent can actually, um, you know, be the, the one in strategy to, to get you there, you know, just applying enough pressure on the virus and from different angles and from different stages of, uh, mechanistic intervention. And so, um, All along, we've been working on multiple different mechanisms. So we'd have something in addition to a nuke plus a core inhibitor. And we're making pretty good progress on that front. So I think earlier next year, we'll have more to sort of discuss around our progress on that front and also on our strategy of coming up with a potential triple. I think for us, we're highly focused on all oral treatments. As you know, some of the, well, historically people have used interferon as an injectable, you know, with or without a nuke, but it's sort of a poorly tolerated treatment that leads to very, very low cure rates. Other folks have been using some RNA approaches to add injectables to oral agents. And, you know, that's an interesting approach that some others are taking. We're highly focused and committed to, if we can, come up with an all-oral regimen. We think in the end, having all oral therapies that potentially could be put together as a fixed-dose combination and that could be, you know, disseminated to, you know, to the millions of people, hundreds of millions of people globally that suffer from this infection, that that would offer, you know, significant advantages overall. So highly focused on all oral agents and hopefully with the addition of a nuke and all oral triplets.
spk06: And your next question comes from the line of Akash Tiwari from Wolf Research. Please go ahead.
spk05: Hi, this is Amy Lee on for Akash. Thanks so much for taking our questions. We just had several on RSV and then one on HPV. So starting with your phase 2b and stem cell transplant, do you have any data supporting the safety of longer term dosing with EDP938? And then why did you set the symptom onset cutoff to be three days instead of two days like you did for outpatient adults? And then on the RSV outpatient trial, how many patients are currently enrolled in this trial? And is there any way to modify it into a phase two, three registrational trial? Additionally, how are you ensuring that patients will be dosed within the right time window? And then one last one on HBV. One hypothesis why assembly's core inhibitor failed is that the drug doesn't completely stop the formation of new CCC DNA. And we were just wondering what the in vitro or in vitro potency of EDP 514 is to specifically inhibit CCC DNA formulations? Thank you.
spk07: Well, let's start with the first one. So three days versus two days in terms of the transplant, I think it's in the range we're looking at You know, 48 hours was the inclusion criteria for RSVP. There was nothing special about that other than we believe that, you know, sooner is always likely to be better. You know, flu drugs are often within two days or three days. And so 48, 72 hours in there is, are probably pretty reasonable time frames to be looking at. We certainly have all the talks as you asked to support this type of study progressing forward. So what were some of your other questions? Couldn't write them down fast enough. Would you go offline?
spk05: Hello, can you hear me?
spk07: I can now.
spk05: Okay, great. I apologize for that. Yeah, so for the RSV outpatient trial.
spk04: How about one at a time?
spk05: Yeah, for sure. Yeah, so outpatient trial, how many patients are currently enrolled, and is there a potential to modify it into some sort of a Phase 2, 3 registrational trial?
spk07: Yeah, I think this is really a Phase 2 study, you know, that we're using to capture the initial results data in that patient population. So our plan is for it to be a phase two. We don't really discuss recruitment on ongoing trials other than to set targets for where we are, where we expect to have data. But then again, to be clear, RSVP is not a registrational study, but instead to be supportive of the entire program overall to better assess the feasibility of the window, et cetera. And so we, again, are able to get people to arrive with symptoms within the 48-hour timeline. And so, again, I think the bigger wild card is, you know, what will the season be? in the presence of COVID and social distancing and potential lockdowns. That's something that, you know, no one has any idea. We'll just have to go into and sort out.
spk05: Okay, great. Thank you. And then our last question on hepatitis B. Just wanted to know what the in vitro and in vivo potency of EDP514 is specifically on inhibiting CCC DNA formation?
spk07: In terms of CCC DNA formation, as I recall, it's in the nanomolar range. I want to say it was around 30 nanomolar or so. Again, this is something that you determine in vitro at the time of infection. So 30 nanomolar sticks in my mind.
spk05: Great. Thank you so much.
spk07: You're welcome.
spk06: Your next question comes from the line of Yasmeen Rahimi from Piper Sandler. Please go ahead.
spk13: Hi, team. I have two questions. Maybe the first question is, what do we know about the viral kinetics? Obviously, if ROC is different between, you know, a hospitalized patient versus a pediatric patient versus immunocompromised? And how do we really capture this efficacy in the next stage of development? So I think commenting on that would be helpful. And then the second one question is, recently at the meeting, we saw data from another FXR agonist that had very encouraging biomarker data, but failed to achieve histological benefits. So how do we think about sort of the myths of correlation, especially as we think about, you know, data for the first generation and second generation X-ray agonist. And we're taking our questions.
spk07: Sure. So starting with the second question first, I think trope effector is the effector you're referring to, correct? It was in a 48 We studied, and they did see a lot of the markers moving in a lot of the right directions. They did see pruritus, but they didn't see – I don't think they had stats said on fibrosis improvement. And I think one of the key differences, you know, people generally view intercepts results as – being sort of the benchmark ones to be looking at as leadership in the class. And I think one of the big differences was they didn't go 72 weeks. So that's obviously what we've built into our Argonne 2 study. Again, many people have looked at shorter duration wines and various levels of success in terms of trying to demonstrate an effect on fibrosis. So we just looked to Intercept's Flint study, the phase three work, and designed Argon 2, you know, accordingly. So I think the other thing is the Novartis study, you know, wasn't, I don't believe it was, hugely power in terms of numbers of uh subjects also so i would question i guess um you know the uh the powering in order to get a difference from a placebo and also the uh the shorter duration of the of the study that they did i think some of these fibrosis improvement endpoints are just necessarily going to be once one needs to be more patient um You know, in peds, you know, peds usually present, you know, with the upper airway infection. They have a high viral load in the upper respiratory tract initially. And, you know, the key, whether it's immune compromised or not, is to, you know, make sure, try to prevent, try to catch the infection when it's an upper airway infection. prevent it from the virus from sort of going down the elevator shaft into the lower airways, which is where you start to have as much of an inflammatory disease going on as you do a viral disease. I think symptoms can be assessed on a specific outcome scale. In transplant, you know, we'll be looking for patients that have initially upper airway disease and try to, you know, have the prevention of the lower airway complications. It's a – I'm not specifically – able to point to at least right now anyway i'm not my team can um on the uh you know the differences in terms of how that viral course plays out in the compromised one but i do believe um you know longer treatment duration is is warranted in that patient population thank you so much jay for answering my questions
spk06: Your next question comes from the line. Your next question comes from the line of Jake Vigel from Rock Capital Partners. Please go ahead.
spk04: Hi. Thanks for taking my question. I have two quick ones for you. I think the first one is I've seen that you've been really busy with multiple studies, and I'm just curious about the Planned RSV study. Do you think that they could hamper the enrollment of the ongoing face-to-face study? Also, what are some of the risks? that you think could, you know, pause or delay the studies since Paul did mention increased costs associated with some studies being slowed or delayed due to COVID?
spk07: So what was the first part of the question? Were they competing for one another, the studies?
spk04: Yeah, just competing for enrollment, or do you not expect that to be a problem?
spk07: Among our studies or between our studies and other studies?
spk04: between your studies?
spk07: Yeah, no, I think they're, you know, they each requires, you know, significant internal resource, but, you know, they're very different and diverse patient populations, so I don't expect any real challenges there. The question on COVID, though, is a question. I mean, we do know, you know, people have been, as we As we were setting up for the southern hemisphere, you know, in the late spring, no one really knew what the wintertime would look like in the southern hemisphere. And it turns out, due to a lot of the mitigation strategies that places like New Zealand were right on top of, you know, they were able to stem the tide of COVID significantly. But with that, due to travel bans and lockdowns and social distancing and closing things up, they did pretty much prevent many other respiratory viruses from really occurring. And to that end, you can look at flu as one of the major symptoms for that, and RSV as well. So there was very little with regards to some of the other respiratory infections due to COVID mitigation strategies. And now we're rolling into what looks like a pretty nasty COVID situation emerging in the Northern Hemisphere, particularly in the U.S. and the U. And so we'll just have to see. The most we can do is have sites set up everywhere. Again, we'll have approximately 100 sites in the U.S., EU, and ultimately in parts of Asia to try to capture a total of 70 patients. But it is going to be, in some measure, COVID-dependent, I think. Hopefully we won't have some of the specific trial impacts that we had in the earlier COVID waves in North America. But no one can rule those sorts of things out. And we'll just have to see what some of the social distancing and other sorts of things plays out in terms of rates of diagnosed RSV and flu and other kinds of things. So take the season we're rolling into, but we'll just have to watch.
spk04: Makes sense. Thanks, Shannon. Just a quick follow-up here about the NASH data expected in May 2021. How much data do you expect or would you actually like to have at the time of readout? And then based on the enrollment that you're seeing now, I'll call it and argue that you'll be able to achieve that.
spk07: So are you talking about 305? Yeah. I suppose both, but more 305 since you said some cohorts. Yeah, okay. Yeah, so, you know, we're on track. I mean, today's guidance that we gave, we have two bids in NASH. In fact, we have a lot of catalysts coming in sort of the first half of the year. We'll have two in HPV in the second quarter. We're also expecting to have data from our follow-on FSR 297 in the second quarter, and in our Phase 2B study of EDP305, the so-called Argon-2 study, we're hoping to have enough patients hit the target for the interim analysis threshold that we can then have that inform decision-making around the whole the whole NASH program. So, again, we'll have all kinds of data, you know, to look at in that timeframe. Right now, things are running along and going generally smoothly. So anything can happen between now and the middle of next year with regards to COVID, but it will be something that we're not currently seeing. So we're on track for those, you know, targets to be guided to tonight.
spk04: looking forward to the multiple updates.
spk07: Yeah, thank you.
spk06: Your next question comes from the line of Eric Joseph from JP Morgan. Please go ahead.
spk01: Hi, good evening. Thanks for taking the questions. From our recent interactions with KOLs, there's a lot of interest in pursuing FXRs as a combination regimen, and you talked about exploring some non-FXR regimens. um, modalities in Nash. What's your latest thinking on the, um, what would be an attractive, uh, mechanism to partner with either 305 and 297? And do you have a sense of whether development of a combo regimen to novel agents would be feasible as an initial registration strategy? Thanks.
spk07: Um, no, thanks, Eric. So, you know, I think, um, FXR combos are really interesting, you know, because there's some elements of FXR. I mean, FXR is a little bit of a sort of a utility hitter. I mean, it goes after some of the pro-fibrotic mechanisms. It's got some anti-inflammatory components, and there's also, you know, effects metabolically. And so these are some of the the hallmarks of the, uh, of the, of the disease. Um, so as such, it could really tuck in with, you know, many of the different, um, mechanisms that are, um, you know, under study and, um, you know, there are a bunch of them out there. So I, um, I think, um, There's a reasonably solid rationale to tuck an FXR in with virtually any of the other classes. Ultimately, in terms of combination strategies, I think clearly some people are... thinking of fixed-dose combinations in there. Some people are thinking of maybe taking single agents forward so that they can be mixed and matched. I think both of those are possibilities, but in the end, you know you're going to need likely to have a combination. So our plan is to generate interesting, in the case of 305, interesting phase two combinations data set that would enable us, you know, even through having checked at the interim analysis at 12 weeks next year, to then think about peeling off a dose that could then be used in combination with another agent from somewhere else. So that's the plan there. I think as the field matures, this is very likely to end up in combinations that if they're oral, you know, could be potentially, uh, fixed those combinations. I know that was, you know, one of the approaches that Gilead was clearly taking at the beginning when they were looking at, uh, their multiple single mechanisms and doing combinations. It's, it's almost, you know, reminiscent of the days of, uh, of Hep C, um, And so that's following it down further on, but if combination studies show promise of one sort or another, I would imagine that people will go forward with combinations for approval.
spk01: Okay, great. And just a follow-up on HPV, if I could. Just picking up on your comments about the potential for an all oral triple regimen, any light you can share on what the third leg of that stool might look like? And I guess, is there a protease component to the ACV life cycle that could be adapted here? And I guess, when you're able to say more about what that mechanism might be, would we be surprised on its identity relative to some of the other points in the life cycle that are being pursued so far for either HPV or HCV. Thanks.
spk07: Yeah, thanks for the question. We're not quite ready tonight to, you know, to sort of unfurl that, but we expect that we will be by early next year. So, you know, on that front, stay tuned. But, you know, we've been sort of grinding away for a long time in the background on other Hep C stuff. I mean, we've sort of hinted at that over time, and I think we're getting to the point now where some of this is hopefully getting pretty close. And, again, our plan is to try to go for all oral, but stay tuned. That's what I'll say tonight.
spk01: Thanks for taking the question. Thank you.
spk06: Your next question comes from the line of Brian Abrams from RBC Capital Markets. Please go ahead.
spk12: Hey, Jay. Hey, Paul. Hey, team. Thanks for taking my questions. Starting on NASH, I was wondering if you could speak broadly about your views on the evolving regulatory landscape there and how you might incorporate that into the development program. For instance, are there additional non-invasive tests you may explore to ensure easily translatable methods for identification of patients that where benefit-risk of an FXR is optimal? Do you have any views on what the accelerated approval endpoints are and whether those might evolve? Thanks.
spk07: Yeah, no, thanks for the question. As you know, everybody is focused on, you know, trying to get rid of biopsies. It's not only, you know, an endpoint that is one that, important for approval but um but also in terms of more robustly um you know looking for a non-invasive test that could stratify patients you know in a better way and um and also um you know perhaps give you a more informed and reliable readout than histologic uh endpoints so um you know we're um We'll be working along with the scientific community to explore this within our programs. We hope that the landscape will change before our registration study, and there's a chance that it could. There's a chance that it may not. But nonetheless, the field is moving very solidly in that direction. There's a lot of you know, encouraging signs, you know, even coming out of ASLD, you know, on that front, it's probably not quite right there, but, um, uh, you know, but for now we're still including histologic readouts, obviously in our, our study, because that is the, uh, you know, the, you know, the, the best, uh, at this time, at least in terms of, um, you know, targeting, you know, approvable impact. But I suspect that landscape will change, and it could change by the time, you know, one is ready for Phase 3.
spk12: Got it. And then on the earlier stage respiratory programs, human metanemovirus and SARS-CoV-2, I was wondering if you could talk about the potential timelines for development there once you select lead candidates and What's the, how did the recent success of vaccines for COVID-19 impact your prioritization of development among those early stage programs? Is there a role you would still potentially see for a COVID-19 therapy, for instance, in stockpiling? Thanks.
spk07: Yeah, so absolutely. I think, you know, the last few weeks, including, I guess, in part today, there's been a lot of news on the vaccine front, and much of it's, you know, quite encouraging. I think there's sort of the things we know and the things we don't know. Number one, we don't know what the, you know, the efficacy rates are going to be, you know, broadly across all sorts of different patient populations. That's number one. Or do we, you know, fully know yet, although there's some encouraging signs that durability may be in a good direction. But, you know, you just really need a lot more information to, you know, understand how fully efficacious vaccines are and further, you know, how much they do or don't obviate the need for therapy. So I think, you know, there's questions about even long-term safety. There's questions about compliance in terms of getting vaccinated. And so, you know, for the foreseeable future, I think there are going to be people for one reason or another who turn up testing positive for COVID-19. And to that end, particularly in people who are asymptomatic or otherwise fairly early in their stage of their their infections, this is where it makes fantastic sense, you know, to have a therapeutic. So we'll, um, you know, we'll continue, um, down this path with the, with the full expectation that there will be, um, the need in some form for, um, therapeutics. Um, with regards to that and human metanemo, which is a virus for which there's, you know, no current vaccine, same with RSV, um, Coming back to human metanemo and our SARS-CoV-2 program, I'd say they're tracking pretty similarly right now, even though we announced our human metanemo program in January with some early leads, and then we announced the start of this beginning to look at SARS-CoV-2, in the March time frame, but the scientists have made really good progress. I'd say we've got potent molecules, very potent molecules from against both of those viruses. And we're now turning, you know, potent molecules, selection of potent molecules into, you know, the finalist candidates for clinical development. So we're targeting to have, you know, hopefully one from each of those programs as a candidate for next year. And then, you know, from the time, I think part of your question was from the time of your candidate selection or how long until you get it in the clinic. You know, there you've just got to finish a lot of IND enabling things. But, you know, typically, you know, nine, ten months, something like that is often achievable instant on hand by the criteria that we use to, you know, nominate our candidates. So, um, again, we're hopeful to try to harvest the candidates for each of those viruses next year, which would really begin to round out, um, you know, as our goal is really building out sort of the leading human respiratory virus, uh, portfolio, you know, with the slide share of RSV, um, you know, um, In just weeks, we expect that we'll have three different phase twos going on. Just FYI, we haven't stopped working on RSV research. We're still exploring other mechanisms there to consider. Again, not because we don't have tremendous faith in 938, but we just want to continue to establish a leadership position there looking at you know, any reasonable mechanism, start comparing them. Even looking, we don't think we need combinations for a reason, but maybe there is a certain patient population that would profit from having a combination. And if that's the case, we would love to have that for an off-the-shelf asset that we have and have 100% ownership of. So, That's going in an RSV. Again, hopefully soon we'll be supplementing that with a human metanumo agent, human metanumo, second leading cause of pretty much everything RSV causes. And then, you know, COVID therapeutics, too. We've got a watchful eye on how vaccines are going to play there. But, again, I think there's no one who wouldn't want to have an effective COVID-19 vaccine SARS-CoV-2 agent available to them, something that was safe and oral and that could be administered at early stages, you know, from the first sign of a positive test and without, you know, needing to head into an infusion center, either for a monoclonal antibody or an agent that's injectable. So, you know, this remains a strong goal. And I think in the aggregate, It really builds out an interesting sort of portfolio of human respiratory viral assays.
spk12: Great. Thanks so much.
spk07: You're welcome.
spk06: Your last question comes from the line of Jay Olson from Oppenheimer. Please go ahead.
spk08: Oh, hey, guys. Thanks for taking our questions. We have two of them. The first question is about GSK's RSV vaccine, which, they announced today was moving into a phase three study. If that vaccine is eventually successful, would it have any long-term impact on your view of the market opportunity for an RSV therapeutic? And then we have another question about NASH.
spk07: Yeah. You know, maternal, this is a maternal vaccine. Is that right?
spk08: Yes, that's correct.
spk07: Yeah. I mean, that approach has been tried before and has had promising results in Phase 2, only not to hold up in Phase 3 studies. I think there's just a fair number of questions around that strategy, not least of which is the degree of penetration and compliance in terms of doing you know, mandatory or not mandatory, but, uh, doing real broad, um, vaccinations of, um, of, of pregnant women, uh, for something that, um, you know, may, may or not, um, end up being a, you know, a, a big issue. There's, I think there's other questions that are, um, reimbursement questions, how are these things getting paid? Will people really reimburse for something that, again, is just a question of the dollar value per benefit garnered there? Some of these vaccines may not be that durable, and you're ultimately just maybe postponing the inevitable. I mean, children reliably get RSV infections, and they usually rely on a few years of successive RSV infections to sort of build up a certain immunity to it. But if there's a break in that and it's not sort of a durable one, we're going to be prone to getting these infections anyway. So I think there's big questions around the efficacy piece of that approach. And once again, one in which I think you would want to still have, even under any vaccine scenario, a robust armamentarium of small molecule therapeutics. I think there's been safety hurdles in that area.
spk08: Okay. Great. Thank you. And then our second question is about NASH, and we're wondering if the CRL that Intercept received and then the subsequent work they're doing to resubmit their NDA have any impact on your own development plans for an FXR agonist in NASH, and specifically if you would consider targeting a narrower NASH patient population with advanced fibrosis?
spk07: I think we just need to fully understand the situation. I'm not sure anybody really knows you know, all the details around that CRL. You know, for us and for our immediate next steps, they're on a certain path that we've, you know, outlined and defined again today. And they're not, you know, so there's literally no impact of that based on our current ongoing activities. I think You know, we as a Nash company in part and all other Nash companies, you know, should be watching, you know, what that CRL meant just to fully understand it. But until we have a lot more granular detail around it, I'm hesitant to, you know, sort of recommend course changes at this time.
spk08: Okay, great. Thanks for taking the questions, and have a happy Thanksgiving.
spk07: You too.
spk08: Thank you.
spk06: I will now turn the call back over to Jennifer Vieira for closing remarks.
spk02: Thank you, everyone, for joining us today. If you have any additional questions, please feel free to give us a call or send me an email. Thanks so much. Have a good night. Bye-bye.
spk06: Ladies and gentlemen, this concludes today's conference call. Thank you for participating. You may now disconnect.
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