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spk01: Good afternoon, and welcome to Enanta Pharmaceuticals Fiscal Second Quarter 2022 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.
spk07: Thank you, Operator, and thanks to everyone for joining us this afternoon. The news release with our fiscal second quarter 2022 financial results was issued this afternoon and is available on our website. On the call today are Dr. Jay Lulai, President and Chief Executive Officer, Paul Mellott, our Chief Financial Officer, and other members of Enanta's senior management team. Before we begin with our formal remarks, we want to remind you that we will be making forward-looking statements. which may include our plans and expectations with respect to our research and development pipeline and financial projections, all of which involve certain assumptions and risks beyond our control that could cause our actual developments and results to differ materially from those statements. A description of these risks is in our most recent Form 10-Q and other periodic reports filed with the SEC. Ananta does not undertake any obligation to update any forward-looking statements made during this call. With that, I'd now like to turn the call over to Dr. Jay Lulai, President and CEO. Jay?
spk16: Jay Lulai Thank you, Jennifer, and good afternoon, everyone. Last quarter was an important one for Ananta during which we made progress in our pipeline and advanced our mission of developing therapeutics for life-threatening viral infections. This progress comes at an important time. as we are soon approaching meaningful inflection points in our pipeline. Today, I'll start by detailing our most advanced programs in respiratory virology, where we continue to build an industry-leading treatment portfolio. Respiratory syncytial virus, or RSV, can result in a severe respiratory infection and is associated with significant morbidity and mortality. The virus can cause serious disease in children, the elderly, and the immune-compromised and there are no targeted treatments or vaccines available. Our robust RSV program includes EDP938, the most advanced N-protein inhibitor in clinical development today, as well as our newest clinical candidate, EDP323, a potent L-protein inhibitor. We're excited by the potential of EDP938, which currently is in three Phase II studies in different patient populations. EDP938 is an oral, potent molecule that has shown robust clinical data in a Phase II challenge study where it was safe and well-tolerated and resulted in a significant decline in viral load and reduced symptoms of infection. Our leadership in RSV is further highlighted by the recent publication of the results of the challenge study in the New England Journal of Medicine. Our most advanced study of EDP938 is RSVP, a Phase IIb trial and otherwise healthy adults with community-acquired RSV infection. The study was designed to confirm in a community-acquired setting the positive results of our Phase IIa challenge study and to further characterize efficacy by measuring symptom alleviation and viral load decline. Enrollment in RSVP is now complete. We are on track to report top-line data from this study later this quarter. Our two other ongoing studies are RSV-PEDS, a Phase II study in pediatric RSV patients, and RSV-TX, a Phase IIb study in adult hematopoietic cell transplant recipients with RSV. Both are expected to recruit into 2023. Moving forward, our broad clinical development pipeline for EDP938 will focus on evaluating its potential in populations with greatest unmet need. namely those who are at high risk for severe disease. This includes children, the elderly, adults with other high-risk conditions, and the immune compromised. To that end, we are also planning to initiate another Phase IIb study in high-risk adults, including the elderly and those who have asthma, COPD, or congestive heart failure. We expect to initiate this study in the fourth quarter of this year. We're excited to add this study to our clinical development program as we believe EDP938 has potential to deliver a potent oral antiviral treatment for all high-risk populations. Indeed, we believe these high-risk patients would benefit the most from antiviral treatment with EDP938. They represent populations in which an even greater benefit is likely to be observed since they have suboptimal RSV immunity, and manifest much greater RSV disease severity and mortality, allowing demonstration of the full potential of EDP938. Adding to our robust RSV portfolio, in February, we introduced EDP323, a novel oral antiviral therapeutic targeting the RSVL protein RNA polymerase. Preclinical data have shown that EDP323 has sub-nanomolar in vitro potency against major subtypes of RSV, RSV-A and RSV-B, and is not expected to have cross-resistance to other classes of inhibitors. Additionally, in preclinical studies, EDP-323 has shown strong oral absorption and good plasma exposure across different species. We believe EDP-323 could serve as a standalone treatment or may be used in combination with other agents, such as EDP938, to potentially broaden the treatment window or addressable RSV patient populations. And we plan to initiate a Phase I study of EDP323 in the second half of this year. Turning to SARS-CoV-2, we're making strong progress with EDP235, our oral inhibitor of the 3CL protease, also referred to as the main protease, or MPRO. EDP-235 is specifically designed to be a once daily oral treatment for COVID-19 without the requirement for ritonavir boosting. Novel variants of SARS-CoV-2 are continuing to emerge, causing new waves of COVID-19 cases globally. This highlights the need for conveniently dosed oral therapeutics, especially given the suboptimal vaccination rates decreased protection against new variants, and waning immunity observed to date with the current boosters. We believe EDP-235 has the potential to be a best-in-class treatment for COVID-19 based on the preclinical data demonstrated to date, which positions it amongst the most potent direct-acting antivirals currently in development for SARS-CoV-2 infection. In March, the FDA granted fast track designation for EDP235, further highlighting the potential for EDP235 and emphasizing the urgent unmet need that exists for COVID-19 treatments. Last month, we presented data on EDP235 in vitro pharmacology and molecular mechanism of action at the annual meeting of the American Society for Biochemistry and Molecular Biology. These preclinical data demonstrated that EDP-235 is a potent inhibitor of SARS-CoV-2 3CL-pro with nanomolar antiviral activity against SARS-CoV-2 variants of concern, including the Delta and Omicron variants. EDP-235 also showed potent antiviral activity against most other pathogenic human coronaviruses, potentially making it a pan-coronavirus therapy. We are on schedule to report preliminary data from our phase one study of EDP235 later this quarter. This first in human single and multiple ascending dose ranging study is evaluating the safety, tolerability, and pharmacokinetics of EDP235 in healthy volunteers after once daily dosing without ritonavir. If supported by phase one results, we plan to advance EDP235 to the next stage of clinical development in the second half of this year. We also continue to pursue our respiratory discovery program in human metapneumovirus, or HMPV, a virus that is similar to RSV and impacts a number of vulnerable populations, including the elderly, adults with underlying pulmonary disease, and those who are immune compromised. We are nearing completion of lead optimization of potent nanomolar HMPV inhibitors and plan to select a clinical candidate in the second half of this year. Moving to hepatitis B, we remain committed to developing a combination regimen as a functional cure for chronic HPV patients. EDP514, our core HPV core inhibitor with fast-track designation, has demonstrated safe and potent antiviral activity in two Phase I studies in different chronic HPV patient populations. those who have high viral load, whom we refer to as viremic patients, and those who are on a treatment with a nucleoside reverse transcriptase inhibitor, whom we refer to as nuke-suppressed patients. These data suggest EDP514 has the potential to be a best-in-class core inhibitor for HPV. We remain focused on evaluating internal and external opportunities for additional components with alternative mechanisms to develop in combination with EDP514, as we believe that a core inhibitor such as EDP514 will ultimately be an important component of a successful combination regimen. Before moving to the financials, I'd like to wrap up by highlighting our near-term milestones. We plan to report data from RSVP this quarter and look forward to initiating a new Phase II RSV study in high-risk adults by year-end. We expect to report preliminary Phase I data for EDP235, our oral antiviral specifically designed for the treatment of COVID-19, later this quarter. If indicated by Phase I results, we plan to advance EDP235 to the next stage of clinical development in the second half of this year. We also look forward to initiating a Phase I study for EDP323, our RSVL inhibitor, as well as nominating a clinical candidate for human metapneumovirus in the second half of this year. With that, I'll turn the call over to Paul to discuss our financials. Paul?
spk15: 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 second fiscal quarter ended March 31, 2022. For the quarter, total revenue was $18.7 million and consisted entirely of royalty revenue earned on AbbVie's global HCV product sales of 380 million. This compares to total revenue of 20.1 million for the same period in 2021. This decrease is due to treated patient volumes continuing to remain suppressed compared to pre-COVID levels. AbbVie has guided to 1.7 billion for global HCV sales in calendar 2022. As a reminder, Our royalties are calculated on a calendar year basis. Therefore, 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 2021 Form 10-K. Moving on to our expenses, for the three months ended March 31, 2022, research and development expenses totaled $42.1 million, compared to $41.5 million for the same period in 2021. The increase was driven by the timing of manufacturing and clinical trial costs associated with the company's virology and liver disease programs. General and administrative expense for the quarter was $10.5 million, compared to $8.3 million for the same period in 2021. This increase was primarily due to increased headcount and stock-related compensation expense. Enanta recorded no income tax expense for the three months ended March 31, 2022, compared to an income tax benefit of $7.1 million for the same period in 2021. Enanta recorded an income tax benefit in 2021 due to the provision of the CARES Act of 2020, which enabled the company to carry back its tax loss in the 2021 period to offset taxable income in prior years. This provision does not apply to periods ending after September 30th, 2021. Net loss for the three months ended March 31, 2022 was $33.6 million, or a loss of $1.63 per diluted common share, compared to a net loss of $22 million, or a loss of $1.09 per diluted common share for the corresponding period in 2021. Enanta ended the quarter with $322.5 million in cash and marketable securities. Enanta expects that its current cash, cash equivalents, and marketable securities, as well as its continuing royalty revenue, will be sufficient to meet the anticipated cash requirements of its existing business and development programs for at least the next two years. Further financial details are available in our press releases and will be available in our quarterly report on Form 10-Q when filed. I'd now like to turn the call back to the operator and open up the lines for questions. Operator?
spk04: Thank you. Ladies and gentlemen, if you'd like to ask a question at this time, you will need to press the start and the one key on your touch-tone telephone. Please stand by while we compile the Q&A roster. Now, first question coming from the line of Brian Scorney with Baird. Your line is open.
spk13: Hi, this is Lou Kerman on for Brian. Thanks for taking the questions. Just if you're on COVID, could you discuss your current stance regarding potential for an evasive mutation of the main protease to reduce the antiviral impact of the existing PIs or EDP-235? And then is there anything specific about the healthy volunteer data you think could be particularly informative about a potential advantage over the competition at this point? Thanks.
spk16: Hi, thanks. This is Jay speaking. So with regards to resistance, you know, we wouldn't expect to see much in an acute infection like, you know, COVID or even in some instances perhaps RSV. If you have, you know, a good robust molecule going after the drug and it's only, or going after the virus, it's only five days of treatment, um i think that that helps minimize things a lot i don't think pfizer has has reported anything at this uh as of now um with regards to the healthy volunteer study absolutely you know so we'll be we'll be looking at um we'll be looking at safety of course first and foremost uh you know demonstrating good safety profile uh we'll also learn a lot from pharmacokinetics um I think, again, the goal here really in this COVID protease space is to try to come up with something that's very convenient, not only for the patient, but also for the healthcare provider treating the patient. And to that end, something that's once daily dosing and once daily dosing without ritonavir boosting. As you know, ritonavir adds a lot of complexity to the patient care. So, Those are the main points I think we'll be trying to assess in our healthy volunteer study.
spk13: Great. And if I could just ask one more, could you just provide any color on what a Phase II design might look like at this point, or is that to be announced?
spk16: Well, certainly it'll be to be announced in the future. We haven't We're sifting through all of that right now and in the context of the changing landscape and ultimately it's common to go in and take a look at antiviral activity. So I suspect there's a good chance we'll be doing some of that, assessing that antiviral activity and then having discussions with regulators to finalize the path.
spk13: Gotcha. Thanks a lot. Back in queue.
spk04: And our next question coming from the lineup, Brian Abrahams with RBC Capital Markets. Your line is open.
spk09: Hi. Good afternoon. Thanks for taking my questions. Two from me. I guess first off on 938, what's the right way that we should be thinking about the potential translatability from the RSVP data to a higher risk population that you're going to be testing subsequently. I'm just wondering, I guess, if there's differences in immune impairment that might change the impact that 938 might have on viral load or on symptoms between the two populations. And then my second question is on 235. There's been some, I guess, anecdotal reports on rebound from Paxlovid and also some recent prophylactic data that didn't quite hit statistical significance. So I'm curious if those evolving data points, I guess, how those shape the way you might think about a development or regulatory path for 235 with respect to the doses, durations, and populations you might study to best elicit its potential differentiation. Thanks.
spk16: Sure, so addressing 938 on the translation. Again, as you know, we're coming on the heels of some very strong data in the human challenge study, which of course was in healthy volunteers who were infected with virus, all infected with the same strain, the same level of inoculum, and then ultimately treated. And what we saw was a dramatic reduction In symptoms, we saw a dramatic reduction in viral load. And so RSVP, you know, steps into the real world. We're dealing with a not terribly dissimilar patient population. They're otherwise healthy volunteers or adults. And, you know, the big difference is, you know, how did they contract the virus? You know, what was the strain? What was the degree of inoculum? And so on and so forth. But one of the gating items is the emergence of symptoms. So that's sort of a grand unifier in the patient population is when did symptoms emerge and then getting people dosed and treated within the first 48 hours post-symptom onset. So it's a great translational study going from the challenge study to the real world. um it's a slightly different patient population than others in the real world so obviously we have a transplant study going on where people are immune compromised we have um you know pediatric study uh and young children um you know many of whom haven't you know been exposed before and um and are now being exposed uh you know later this year we're going to have a study in high-risk adults, adults who are elderly or have another issue going on that puts them at high risk in an RSV infection setting. So each one of them is a little bit different, but I think, you know, you're going to be firmly grounded on the fundamentals, you know, the fact that the drug has very strong PK, very good exposures, half-life, C-mans, it's a very potent drug, has a high barrier to resistance. So all of the things, all the boxes that you could check along the way are in place. I think, you know, these are tremendous confidence-building steps. And, you know, you mentioned, you know, could there be a – I would say the most different patient population is perhaps the immune-compromised. where obviously you don't have the helping hand of a competent immune system working alongside the antiviral. But to that end, we're mitigating some of that by dosing for 21 days, a longer duration. And ultimately, in severe immune compromise, maybe that will, in a rare instance, spawn the need for you know, a combo with a molecule, for example, like EDP323. So, you know, it's about as good of an interesting translational confidence-building step as you could do, but, you know, in these high-risk patient populations, I'll remind you that they're at high risk. It sort of goes without saying, but often the viral loads are higher and often the duration of infection is longer, and often the consequences along the way are more substantial. So it will, I think, be an ideal backdrop for a strong antiviral to really showcase, you know, an effect in that high-risk patient population. So steady as she goes. We had a question, a couple on Paxlovid. I think one was about... It's fairly rare, I think it is, sort of rebound of symptoms in patients. You know, so one can think about different durations. I think, you know, a duration of five days was what Pfizer used. You know, I think there was some discussion in the Pfizer arena and some recent discussions from, you know, regulators recently. around the context of, you know, well, if you see such a thing, should you be dosing with another five-day course? I think that was recommended against, at least, you know, for now, that it should be fine dosing with the first course, and then in the rare instance where something appears, you know, a bit later, it's probably not enough of a deal to really focus on any further treatment. So, obviously, we'll be progressing our molecule, you know, with our eyes wide open in terms of the, you know, the latest and greatest on that front. But I think that's the state of play on that. Did you have one other question on Paxlovid?
spk09: Well, I think you kind of covered it, but I was just getting at, you know, some of the possible shortcomings that are beginning to emerge and maybe some slightly disappointing data on the prophylactic side, if that sort of changes how you might gear 235 for future development to most differentiate it and maybe take advantage of some of the potential advantageous properties like potency.
spk16: Got it. I think in the sort of standard risk, lower risk patient population, I think people are still trying to sort through what are the best endpoints to be looking at there. I think Pfizer had their run at it with some fairly stringent endpoints. And the question is, you know, what will that set of endpoints look like in the patient population as the virus continues to, you know, evolve? You know, we'll be paying close attention to that. The same is true with post-exposure prophylaxis. Again, some of the first trial information is – starting to come out, but I think figuring out the dynamics of how and when to get that drug on board to make a difference in that patient population, these are all things to sort out. But having one that is more accessible and easier to use without limitations based on ritonavir with other drugs. You know, it's one thing if you're trying to treat a single patient who's infected. It's another to prophylax and then bring it into a broader swath of family members or other close contacts where each of them, you know, might have different circumstances that are confounded by ritonavir. So each one of those things would need to be carefully thought through and sorted through. And meanwhile, the clock is ticking. So, you know, You know, you want to try to mitigate that by getting people on drugs as soon as possible. And that's why we're really focused on things that are easy to use and hopefully without rotameter boosting.
spk09: Makes sense. Thanks so much, Jay.
spk16: You're welcome.
spk04: Our next question coming from the line of Yasmeen Rahimi with Piper Sandler. Your line is open.
spk14: Hi, this is for Yasmeen. A couple of questions for us. So we have, we have been like speaking with experts and KOLs and protease inhibitors who suggested that the return on boosting might be a critical component to maintain efficacy, especially in light of growing variants. So do you like how confident, like what gives you confidence that 235 and not really need a return on boost and could have a similar efficacy? And then the second question is like, at what junction do you plan on partnering this asset? And like, if you could walk us through the, through the decision tree of, of like when that, that could happen. Thanks for taking our questions.
spk16: Sure. So I mean, we're ton of areas is, um, I mean, we know, um, what the drug did without return of beer. Uh, uh, the, the specter was, I believe it was, um, it was, um, three times a day dosing and over a gram dosing and so forth. And I think someone made the call that in the grand scheme of things, it would be better to do ritonavir boosting in order to get adequate drug exposure that a BID regimen would be acceptable. And so there's no magic about it. I mean, it's an HIV drug. It's a non-boosting agent and boosts lots of drugs. And that's both the benefit and the confounding element of ritonavir boosting. So if you can demonstrate, you know, similar or better PK and you don't need ritonavir, then there's no reason to use it. And so that's the angle that we're exploring. Obviously, that product profile tests very well. And we're in the process of sorting that out even as we speak. With regards to partnering, I've said previously that our expectation is we will team up. This is a global pandemic. you know, it's bigger than we are, so to speak. And I think, you know, to that end, much like we did in the area of hepatitis C, to take on a really global problem like that just made a tremendous amount of sense to, you know, to team up. So we, you know, our plan is to do that. And our plan is to do that, you know, really in enough time such that, you you know, when it comes time for global supply chain and global launch that we're well partnered at. You know, in terms of supply chain for clinical trial supply through registration, we've got all of that under control. We're thinking about the fees, you know, after that. And that's where given the timing and often compressed timelines you find in COVID, we'd be looking to do that sooner than we might otherwise. But it's definitely in the plan.
spk04: Our next question coming from the lineup. Akash Tiwari with Jefferies. Your line is open.
spk11: Hey, guys. So, given the RSVP study completed sometime in January, is the C-suite fully blinded to the data at this time? And if that's the case, what gives you the confidence to initiate the high-risk study before getting a chance to look at the RSVP data? Additionally, I noticed on the press release today, you mentioned RSVP was run in a low-risk and otherwise healthy population. Is it fair to say the chances of outright success for this trial are low given the background patient dynamics? Thank you.
spk16: Yeah, so there, thanks for the question. I mean, it brings up, you know, again, an interesting point that, you know, these, the progression beyond RSVP is sort of independent as we look at these high-risk patient populations. You know, of course, we're looking to you know, demonstrate safety in that patient population and also hopefully, you know, symptom reduction and viral load changes. But, you know, when you look at high-risk patient populations, as I mentioned before, you know, you've got a bigger dynamic window. Maybe this is getting at your question about the – the low risk, uh, difference in low risk and high risk. And in the COVID, uh, case, um, you know, people demonstrated efficacy and high risk patient populations without yet doing it in, in lower risk. I think in part, um, it has to do, um, with the dynamic range and the end points that you're able to work with. So, um, again, I, I think it's an interesting, uh, translational study. Um, But, you know, I view them independently.
spk04: And our next question coming from the lineup, Roy Buchanan with JMP Securities. Your line is now open.
spk10: Thanks for taking the question. Just a couple quick ones for me. On the RSVP study, Jay, I think you've said it's designed to show a 40% benefit. Just want to check, that's at 80% or 90% powering? It's an 80% powering to show a 55% effect.
spk16: Okay. Okay. And the... So... But the minimal separation or effect size that you can detect with the sample size is 40% reduction. So as long as the final results show a 40% reduction, the study will be positive.
spk10: Okay, great. And then for the EDP-235, the phase one, later this quarter, you said preliminary data. I just want to check, are we going to get both the single ascending and multiple ascending data? results this quarter, or is it just a single ascending?
spk16: So we should have most cohorts from SAD and MAD. You know, we'll see if we have all, but we should have most of them.
spk10: Okay, great. I'm going to throw in one more. I guess the RSVP study, is it stratifying between hospitalized and non? And I didn't, clinical trials, I don't see a specification between upper and lower respiratory tract infections. Is it stratifying by that? And then I guess is it safe to assume that the hospitalization would imply a lower respiratory tract infection? Thanks.
spk16: Actually, I'll let Natalie answer this one. The hospitalization part is in part because, again, this is the first study in peds, and you're going to do it in a very careful environment. So that's the nature of the hospitalization. But, Natalie, do you want to comment on any stratification?
spk12: Yeah, sure. Thank you, Jay. I can just complement the answer. So there's no stratification, you know, first in pediatric study. There was many a requirement from regulatory because of safety purposes, and that was necessary just for the first cohort. So it doesn't mean necessary that the kids will come with an LRTI.
spk16: Got it. Thank you.
spk12: You're welcome.
spk16: You're welcome.
spk04: Our next question coming from the lineup, Eric Joseph with JP Morgan. Your line is open.
spk02: Hi, this is Hannah on for Eric. Thanks for taking the questions. So first, just can you talk a little bit about some of the gating items to reporting data from the RSVP study? Enrollment's been complete since the end of last year. Just wondering if there's any work left to complete prior to announcing that data. And then also, you're planning to initiate the RSVP study or the RSV study in older adults at high risk by the end of the year. Just wondering, from a sense of timelines, Would you be anticipating being able to complete the study within one RSV season? And which data sets from which studies would you need to have in hand prior to designing or initiating a phase three pivotal study? Thank you.
spk16: Sure. So with regards to the high-risk patient, it's a study, again, we'll get started in the second half of this year. Historically, it's been almost impossible for anyone to recruit a study in one season, certainly in one North American season. As you know, you start in the Northern Hemisphere and you get to the Southern Hemisphere. It's really just going to depend on what RSV rates look like in terms of the speed to enrollment. So we get into the actual season first. It's really hard to provide granular guidance. The good news is as we roll through this study, we have a pretty good sense as we go. This study should enable a Phase III registration study, but this is something that we'll discuss with the agency as we go. you know, have an end to phase two meeting. So, um, I think the, what was your, the other question about RSVP, um, the study did enroll, finish enrollment, um, late last year. And I think, uh, you know, one of the, the gating items was pulling in all of the, uh, the viral logic data samples from a, um, from from an outside vendor who is doing the clinical virology so it's really related to that but we're you know we're on track to report out top on this quarter so just to follow up on just pivotal thinking about the pivotal design for rsv so with each phase two study do you then plan to evaluate
spk02: a pivotal opportunity in that setting, or would you wait until all three studies have completed? Well, I guess all four studies now have completed.
spk16: No, we wouldn't wait. We would definitely not wait. Okay, it makes sense. Thank you. You're welcome.
spk04: And our next question coming from the line of Jay Olson with Oppenheimer. Your line is open.
spk17: Oh, hey, thanks for the update, and thanks for taking the questions. For RSV, how are you thinking about the monotherapy versus combination opportunities in various different patient populations? And what's the best strategy to advance both 938 and 323? Sure.
spk16: Actually, I'm going to dish this one over to Tara Kiefer to chat a little bit about that strategy.
spk05: Sure, no problem. Hi, Jay. This is Tara. So we're certainly looking at 3T3s that advances into the clinic, and we'll be looking at that in a typical phase one study, and then understanding a little bit more about the characteristics in antiviral activity on its own, and then thinking about potential combinations down the road with 938. And that would be either to look at different patient populations or potentially expanding the treatment window you know, the opportunity of when we're able to treat patients after symptom onset. And so we'll be, you know, we'll be thinking about how best to bring both of those compounds forward alone and which settings we might try in combination. But certainly both compounds have the ability and the profile to, you know, move forward as a monotherapy and there may be settings where we, you know, want to look in combination.
spk17: Great, thank you. And if I could ask a follow-up on 235. Do you expect 235 to benefit from an emergency use authorization? And also, will future studies of 235 require an active control line?
spk16: So, there's... In terms of a control arm, I think we don't know. This is going to have to ultimately be discussed with the agency. With regards to EUA, again, that's sort of facts and circumstances on the ground at the time in terms of the agency decides what gets emergency use authorization. In some instances, as you've known, they've given it and then they've pulled it back depending upon you know, the evolution of the virus and the severity. Right now, you know, there is a thought that EUA could possibly be available in high-risk patient populations, but needs to be confirmed ultimately, obviously, through discussions with the agency.
spk17: Great. Super helpful. Thank you both very much. You're welcome.
spk04: Our next question coming from the line of with Roth Capital. Your line is open.
spk03: Hello. Thanks for taking questions. I do have a few here. The first one is just about your 235 program relative to Paxil. We've been looking at the chemical structure and we've just been wondering, you know, what you did to kind of optimize your molecule relative to theirs. and then how do you expect these programs to be differentiated in the clinic?
spk16: Well, much as I could or much as I would love to, we won't get into chemical structures this evening. But suffice it to say, you know, this is what we do at Enanta. Among the things we do at Enanta is just very good at drug candidate optimization. So it's... It's a process that we know well. We've done many times on protease inhibitors and have ultimately got to market with two protease inhibitors. So this process is no different. It's been a very strong drug discovery effort, and now we're going to supplement that with a very strong development effort. I'm sorry, the second part of your question?
spk03: I was just wondering how you expect the molecule to be differentiated in the clinic, yeah, efficacy-wise or safety-wise.
spk16: Yeah, sure. A lot of people can, you know, it's very easy to make, well, I shouldn't trivialize it. It's easy to make a really potent molecule sometimes, but having all the other drug candidate characteristics that you would like to have on top of that can often erode the potency gains that you have. So getting everything put together in one package is the art and the challenge here. And so we just spent a lot of time focused on DMP characteristics of the molecule, making sure that the molecule had really good oral absorption, had really good half-lives, a very good trough drug concentrations, a very good distribution into important target organs, in this case lung tissue. And so it was an iterative process, you know, working through lots of different molecules, lots of different chemical classes, and then ultimately refining all the various attributes, including lots of virology, into a single molecule to take forward. So I think, you know, so far the preclinical safety has been very good and moving in the clinic soon we'll have the clinical correlate of that in terms of safety and importantly PK. So I think those are ways that you can differentiate starting in phase one. We certainly have differentiated already preclinically.
spk03: Thanks. And then the follow-up here is just about another catalyst, the ISB program. I think everyone's been trying to figure out, you know, how would this translate to the high-risk patient population? And so I just kind of wanted to follow up one of the questions regarding which patient population do you think will be more difficult or easier to kind of show a treatment benefit? I know you are doing the high-risk because it's a more addressable patient population, but in terms of translating the the data from the less severe patients to the more high-risk patients, you know, which patient population is it more difficult to show a benefit in?
spk16: That's a very good question, but a very hard one to answer. It's because they're all unique. You know, in PEDS, you've got... you know, you have kids that, you know, even from a DMPK standpoint, kids are different. They're not just little adults. Then you have a slightly different clinical presentation in high-risk elderly populations. Sometimes they have other comorbidities and that can be confounding. The immune-suppressed obviously have very different things going on. So, you know, to look at three very different patient populations and say which is going to be the hardest. Very hard to do that from where we sit today. That said, it is fairly easy to understand how each of those patient populations, you know, could benefit from an antiviral versus not getting one. And that's, in the end, what we need to show. And as long as we can show a good clinical benefit, we will have moved the ball down the field where no one's done it.
spk03: Thanks, Jen. And the last one here is a combo question. The first part is just about, you know, plans or more detailed specifics about the human metapneumovirus program. I think one of the things we liked about the pipeline initially was the multiple shots on goal. And so I think people are just really interested in kind of understanding what you know, where you are with your next development candidate. And then the second part here is for Paul. Can you talk a little bit about, you know, capital allocation towards these different efforts, including early stage development efforts, and then whether or not the expenses associated with the NASH program have all fallen off? Thanks again.
spk16: Yeah, so Human Meta Pneumo, again, as I said in my opening remarks, um, programs looking very exciting. Um, you know, we've made a lot of drug candidates at Ananta and, um, you know, we're, we're taking it down to finalist molecules right now for human metanuma to remind, um, some of you who don't remember the, uh, human metanuma virus is, uh, sort of the second leading cause of, uh, of everything that RSV does, and then basically the same patient population. So the young, the elderly, high risk, the immune compromised. And so it's a very nice complement to RSV. We've got two candidates moving forward. And RSV, obviously, human metanuma, and COVID, of course, will really round it out. But from a capital allocation perspective, you know, we fund them as needed. You know, and it's all stage dependent. You go through sometimes, you know, you get into safety studies. That becomes very expensive for the preclinical side of things. And then you get into phase one. It's all charted out basically in terms of how we're laying out the pipeline evolution and the timing of all the things that we've got going on. But that allocation changes quickly. around a little bit. What I will say is you are correct. You know, the clinical trials and NASH, you know, we're wound down. We do have a discovery program that's, you know, quite interesting that we'll be presenting at EASL that is just sort of the last phase of the internal NASH activities. So we, you know, really the focus there is now that we have two FXRs where we've defined doses for future combination, it would ultimately reside in potential combinations down the road through business development activities. But those would be activities that would be conducted by the partner. Okay. Thank you.
spk04: Our next question coming from the line of from SBP Securities. Your line is open.
spk08: Great. Afternoon. So a question on your new adult RSV study. Could you talk a bit more about the rationale behind selecting high-risk patients that have asthma, chronic obstructive pulmonary disease, or congestive heart failure over other possible comorbidities that could have conferred high risk? I know it's still in the works, but are you considering doing anything to help balance enrollment across these subgroups in the future trial, or are you thinking about other levers that you can pull here?
spk16: Sure. Why don't I ask Natalie to take that one in terms of the other subpatient populations chosen and more.
spk12: So maybe just simply answering that one of the patient population that we are defining at higher risk of developing severe progression of RSV disease are well established, not only in their regulatory guidance, but also, you know, from a clinical standpoint. So patients with high risk are defined as being age of more than 65 years old, so they will be part of our next study for adults with high risk outpatient study. And typically, the ones that have BPCO, that have congestive heart failure and asthma, are also candidates to develop progression to severe disease with RSV. So it is important, obviously, to look at the patient population to better understand, once you use an antiviral treatment, how you change the course of the progression of the disease. So those are mainly the justification of why we are defining our adult high-risk patient this way. Did I answer your question?
spk08: Yep, and I was curious if you would do anything to balance enrollment across the different subgroups?
spk12: There's no particular need to stratify within this group, but there would be certainly, once the study is As you know, we always look at different subpopulations if we need to, but there's no need to stratify for now. And again, I think Jay has mentioned earlier that we will give a little bit more color on the protocol design as we are getting closer to disclose it after discussion with our regulatory.
spk08: Got it. And one more RSV question from me. Do you have any updates on how recruitment is going for the RSVPs and RSVTX studies? Have you noticed any seasonal trends or unusual seasonal trends, et cetera, across your different sites?
spk16: Yeah, so you might have seen the RSV kind of spiked up and then trailed back down, and so it's actually very low rates you know, presently. So I think, you know, like, like before, we'll be looking for spikes in the southern hemisphere followed by ultimately spikes in the northern hemisphere and in the fall and early months.
spk08: Okay, great. Thanks. You're welcome.
spk04: Thank you, and I will now turn the call back over to Jennifer Vieira.
spk06: Thank you, everyone, for joining us today. If you have any additional questions, feel free to contact us by email or call the office. Thanks, and have a good night.
spk04: Ladies and gentlemen, that does end our conference for today. Thank you for your participation. You may now disconnect.
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