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spk07: Good afternoon and welcome to the Ananta Pharmaceuticals Fiscal First 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.
spk04: Thank you, Operator, and thanks to everyone for joining us this afternoon. The news release with our fiscal first quarter 2022 financial results was issued this afternoon and is available on our website. On the call today are Dr. Jay Lulli, President and Chief Executive Officer, Paul Mellott, our Chief Financial Officer, and other members of the NANTA'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. Anantha 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?
spk11: Thank you, Jennifer, and good afternoon, everyone. Anantha had a very productive fiscal first quarter of 2022, as we made significant progress in our RSV and COVID-19 programs. building a strong foundation for important inflection points to come this year. Today, I'll update you on our clinical development programs for respiratory syncytial virus, SARS-CoV-2, and hepatitis B virus, all of which have the goal of providing safe and effective oral antiviral treatments for viral diseases infecting broad patient populations. I will additionally comment on our ongoing discovery efforts and progress in human metapneumovirus. Ananta has a successful and proven history of discovering and developing antiviral treatments, as demonstrated by Glicaprovir, the HCV protease inhibitor component, and Maverick, a leading treatment for chronic hepatitis C virus. We have expanded and leveraged this long and deep experience in virology to discover small molecule therapeutics for multiple viruses, recently expanding our respiratory virology pipeline by developing a coronavirus protease inhibitor for SARS-CoV-2 and an L inhibitor for RSV. The pandemic has made it clear that viruses can cause serious disease, which makes our work especially significant. With that backdrop, today I will start by detailing progress in our respiratory virology programs, where we continue to build an industry-leading treatment portfolio. Our most advanced RSV program is our in-protein inhibitor, EDP938, which has fast-track designation and is currently in three Phase II studies in multiple patient populations. Additionally, we continue our leadership in RSV with the announcement of a clinical candidate in our RSV-L inhibitor program, EDP323. As a reminder, RSV is a severe respiratory infection associated with significant morbidity and mortality. The virus can cause serious disease in children, the elderly, and the immune compromised, and there are no treatments or vaccines available for the virus, which was first characterized in 1956. We were excited by the potential of EDP938, which is a potent inhibitor of the RSVN protein that has shown robust clinical data in a Phase IIa challenge study, where it was not only safe and well tolerated, but also demonstrated significant effects on viral load and reduced symptoms of infection. In this human challenge study of EDP938, we met the primary endpoint of viral load reduction and also a key secondary endpoint of total symptom score. In order to confirm our findings outside of a challenge study setting, we conducted the RSVP study to evaluate EDP938 in an adult outpatient population infected with community-acquired RSV, and to provide us additional information on symptom alleviation and viral load decline. Following a period of decreased RSV transmission due to social distancing measures, late last year there was an uptick in RSV activity in various regions of the world, including parts of the United States and Europe, which allowed us to complete enrollment beyond our initial target of 70 patients. We are on track to report top-line data from RSVP next quarter. Our broad clinical development program includes two key Phase II studies of EDP938, evaluating its safety and efficacy in young children and hematopoietic cell transplant recipients with RSV infections. Our clinical trial named RSVP is a Phase II study in pediatric RSV patients, and the trial RSV-TX is a Phase IIb study in adult hematopoietic cell transplant recipients with RSV. Data from these two studies will confirm the doses to be used in subsequent pivotal studies in these populations. These studies, which were initiated after RSVP, are expected to extend at least into 2023. We are monitoring RSV globally and will be providing further updates as the incidence rates evolve. This quarter, we are pleased to announce that we broadened our footprint in RSV by introducing ADP323, a potent RSV-L inhibitor. ADP323 targets the RSV-L protein, which is a viral polymerase that contains multiple enzyme activities required for RSV replication. Preclinical data demonstrate nanomolar potency across the major RSV subtypes, RSV-A and RSV-B, and good absorption and plasma exposure across multiple different species. We envision EDP-323 as a standalone treatment or for use in combination with other agents such as EDP-938 to potentially broaden the treatment window or expand the addressable RSV patient population. We expect to initiate a phase one study of EDP-323 in the second half of this year. I'm proud of the work we have done thus far in RSV, and I'm excited by the potential of our broad development program, allowing us to extend our leadership in the development of treatment for respiratory viruses. Turning to SARS-CoV-2, we're also excited by the promise of EDP-235, our oral coronavirus 3CL protease inhibitor, also known as a main protease inhibitor, specifically designed for the treatment of COVID-19. EDP-235 is on track to begin dosing subjects this month. This first-in-human, single and multiple ascending dose ranging study will determine the safety, tolerability, and pharmacokinetics of EDP-235 in healthy participants. In preclinical studies, EDP-235 demonstrated highly potent antiviral activity against SARS-CoV-2 and pharmacokinetic properties supporting a once-daily oral dosing regimen without the need for a boosting agent, such as ritonavir, all which indicate the potential of EDP-235 as a best-in-class compound. Specifically, EDP-235 potently blocks the replication of SARS-CoV-2 in multiple cellular models, including primary human airway epithelial cells with an EC90 of 33 nanomoles. Importantly, ADP235 has shown potent antiviral activity in vitro across a range of currently circulating SARS-CoV-2 variants, including Omicron and Delta, giving it pangenotypic potential. Furthermore, ADP235 has potent activity against other human coronaviruses, enabling the potential for a pan-coronavirus treatment including possibly coronaviruses that may infect human populations in the future. EDP-235 has also shown excellent exposure after oral administration without ritonavir abusing and favorable distribution into key target tissues, including lung and preclinical models. This positions EDP-235 among the most potent direct-acting antivirals currently in development for SARS-CoV-2 infection, with the potential for convenient once-daily dosing. With our phase one study starting this month, assuming supportive data, we would advance ADP235 to the next stage of clinical development in the second half of 2022. We also continue to pursue our respiratory virus discovery program in human metapneumovirus, or HMPV, a virus that was first identified 20 years ago and now circulates worldwide with nearly universal infection by age five. Like with RSV, there are a number of vulnerable populations, including children, 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 our vision of developing a combination regimen to deliver a functional cure for chronic HPV patients. EDP514, our HPV core inhibitor with fast-track designation, has been evaluated in two Phase 1B studies in different chronic HPV patient populations. Those who have a 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 suppress patients. Last year, we presented data demonstrating that EDP514 has clear clinical evidence of a good safety profile alone and in combination with a nuke and displays significant antiviral activity over 28 days with a pharmacokinetic profile consistently supportive of once daily dosing orally putting EDP514 among the best core inhibitors currently in development. We remain focused on evaluating internal and external opportunities for additional compounds 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 reiterating our upcoming milestones. We expect multiple catalysts, including the start of dosing in our phase one study of our oral 3CL protease inhibitor, EDP-235, this month. If supported by phase one results, we plan to advance EDP-235 to the next stage of clinical development for the treatment of COVID in the second half of this year. We plan to report top line data from the RSVP study of EDP938 next quarter. Finally, we look forward to initiating a phase one study for EDP323, our RSVL inhibitor, and nominating a human metapneumovirus clinical candidate in the second half of this year. With that, I'll stop here and turn the call over to Paul to discuss the financials. Paul?
spk12: 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 first fiscal quarter ended December 31, 2021. For the quarter, total revenue was $27.6 million and consisted entirely of royalty revenue earned on AbbVie's global HCV product sales of $427 million. This compares to total revenue of $31.7 million for the same period in 2020. As reported by AbbVie, treated patient volumes remain suppressed compared to pre-COVID levels. Royalty revenue was calculated on 50% of Maverick sales at a blended royalty rate for the quarter of 13% and on approximately 30% of the Carer sales at a royalty rate of 10% after adjustments for certain contractual discounts rebates, and set-offs, which are now approximately 2.7% of Abbey's total reported HCV product sales. As a reminder, our royalties are calculated on a calendar year basis. Therefore, royalties for our fiscal first quarter ending December 31st are 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 2021 Form 10-K. Recently, Abbey reported their global HCV sales were $1.7 billion in calendar 2021 and guided to $1.7 billion for global HCV sales in calendar 2022. Moving on to our expenses, for the three months ended December 31, 2021, Research and development expenses totaled $48.5 million compared to $36.7 million for the same period in 2020. The increase was primarily due to the timing of manufacturing in support of the company's clinical studies in our virology programs. General administrative expense for the quarter was $9.5 million compared to $7.4 million for the same period in 2020. This increase was primarily due to increased headcount in compensation expense. An answer recorded a minor income tax benefit related to the release of a state tax reserve for the three months ended December 31, 2021, compared to an income tax benefit of 3.3 million for the same period in 2020. An answer recorded a larger income tax benefit in 2020 than in 2021 due to the provisions of the CARES Act of 2020, which enabled us to carry back our prior year tax loss 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 December 31, 2021 was 30.1 million or a loss of $1.48 per diluted common share compared to a net loss of 8.3 million or a loss of 41 cents per diluted common share for the corresponding period in 2020. Anantha ended the quarter with $347.7 million in cash and marketable securities. Anantha expects that its current cash, cash equivalents, and marketable securities, as well as 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 release 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?
spk07: Thank you. As a reminder, to ask a question, you will need to press star 1 on your telephone. To withdraw your question, press the pound key. Again, that's star 1 on your telephone to ask a question. Please stand by while we compile the Q&A roster. Our first question. comes from the line of Brian Abrahams of RBC Capital. I'm sorry, RBC Capital Markets. Your line is open.
spk09: Hey, good evening. Thanks so much for taking my questions. I guess just a couple on 235. I'm curious, with some of the latest developments on the progress with other protease inhibitors in the space, I'm wondering how you're thinking about the overall competitive opportunity for 235. Would you be thinking about maybe focusing initially on patients who may not be able to take ritonavir, which Paxlovid is boosted by, or are there other subpopulations you might initially focus on? And then I'm just kind of curious, it sounds like the healthy volunteer study is on track to start this month. What are your plans for how you might reveal the safety and PK data, which, of course, given the in vitro potency, is going to be very important in gauging what the ultimate opportunity and probability of success of the drug could be. Thanks so much.
spk11: Thanks, Brian. Hi, this is Jay. The phase one in health use is about to begin via standard SAD and MAD. And we plan to harvest that data here in the first half. And as with all of our other studies, once we've got that data in hand, we'll find the appropriate mechanism and venue to put it out. Regarding the field and protease, I would describe it as very early yet. There are a few entrants in the space, but as we, not only in virals, but in lots of other disease areas, it's not necessarily the first one in. It's the high quality molecules that ultimately stand the test of time. So again, I think we've built some advantages into EDP 235 from a potency standpoint, from a PK standpoint, from a tissue targeting standpoint. And overall, we think the profile is a strong one that should compete very well over a longer timeframe. Regarding trials, you know, beyond the phase one healthy study, of course, we'll be getting into key patient populations. You know, there's the standard risk, high risk, post exposure, prophylaxis, et cetera. And we would anticipate, you know, tapping into all of those opportunities. Thank you.
spk09: Great. Thanks, and congrats on all the continued progress. You're welcome.
spk07: Thank you. Our next question comes from Eric Joseph of J.P. Morgan. Your question, please.
spk14: Hi. Good afternoon. This is Hannah on for Eric. Thanks for taking the questions just to see from us. So first, just wanted to get your thoughts on the severity of RSV symptoms in patients and how they might compare this season versus prior seasons, given the lapse in seasonal emergence. Just wondering if there's any reason to think we might see more severe symptoms in patients this year. And then also based on any unblinded looks at patient baselines entering the RSVP study, how should we be thinking about median age entering the study? Are there any pre-specified subgroup analyses by age or other risk factors? Thank you.
spk11: You know, maybe I'll let Natalie comment on some of these, but, you know, again, I don't think there's necessarily anything special about this RSV season versus prior ones. But I'll let Natalie chime in.
spk02: Thank you, Jay. So your question, I think, was about if the sentence of the RSV infection was worse than before. We, I mean, obviously, you know, even though we don't have access to unblinded data, but we can monitor, you know, safety in our current ongoing studies, and even the study that was completed, and we have not observed any worsening in the symptoms the way the patients presented themselves to the clinic, as far as we can tell.
spk14: All right, and so we don't have any data on median age entering the study at this current time?
spk02: Sorry, I'm not sure you understood the question about age.
spk11: Median age.
spk02: Median age. The median age. We haven't, you know, we haven't logged the database yet that are being, you know, collecting. So I don't have the median age. But if you look at the criteria of eligibility, it's from 18 to 75 years old. And so, you know, we would expect something. I would say, you know, if I have to guess, I would say something along the line of the 50s.
spk14: Okay. And I'm just wondering, based on or assuming success in the RSVP trial, could you describe what next steps would look like would look like toward the federal program? Specifically, how would a program and general adults be prioritized relative to pediatric and transplant population? And would either of these trials be getting factors to end the phase two discussions at the FDA?
spk11: So we're going to, we're going to focus post RSVP on high risk patient populations. Um, you know, and they, they fall mainly into three buckets, the peds, um, transplant, and then, um, you know, other adult populations that are at higher risk. So those will be the, uh, the basic, um, you know, patient populations that we'll be targeting. Two of the three of which we've got ongoing now.
spk14: Okay, great. Thanks for taking the questions.
spk11: You're welcome.
spk07: Thank you. Our next question comes from Yasmeen Rahimi of Piper Sandler. Please go ahead.
spk06: Hi, Steve. Thank you so much for the update. Two questions for you. A frequent question from a lot of our clients are just to understand how big the RSVP outpatient population is, adult population is. So can you maybe share with me some of the market research that Inanta has done? How big is this addressable market? And then the second question I have is in regards to the L protein inhibitor entering the clinic into the second half of 2022. What is the strategy there? Like which patient population would you be prioritizing Are you going to go into the P or immunocompromised or would you try adult population? So, thanks for, you know, answering my question.
spk11: You're welcome. So, yes, the, you know, again, the RSVP, you know, so-called the RSVP patient populations, otherwise healthy, otherwise healthy adults. which is probably not where the, you know, it's a great sort of staging trial and it's a great bridge from our challenge study into other patient populations, adult NPs, but it's not the main patient population that we would be focused on instead, you know, going after the three high risk ones that I had mentioned. That's not to say that of course, an otherwise healthy adult that's presenting with RSV couldn't be addressed by our drug. It's just that on the route to approval and looking at the critical markets to address on the registration pathway, it's really going to be in the PEDS transplant and higher risk adult populations. In terms of the L protein, we're going out in RSV, I think, in a very significant way. There aren't any approved therapeutics out there. We hope to be the first or certainly among a small number of drugs that could be approved in RSV over a reasonable timeframe. And we just, as you know, we've been working on human respiratory viruses long before the pandemic because we saw it as a major unmet medical need from a therapeutic standpoint. So when we size up a situation like that, we usually, you know, are doubling down on our strengths. And so I think, you know, having an inhibitor like 938 is great, has high barrier effects. It's very potent. It's once daily dosing. We've already demonstrated strong antiviral effects. So it should be fine along the way as a single agent. But we also are looking at other direct acting antiviral mechanisms, too. And, you know, L-protein and polymerase is another very interesting target from a replication perspective. So exactly how we tuck that in, could it be pursued principally as another single agent in, say, maybe a different patient population? Perhaps you could think about different ways to position these things if you had multiple of them. Or mightn't we put the two of them together in certain patient populations that might be very advanced in their infection, otherwise very hard to treat, maybe severely immune-compromised patients that would just struggle with anything? And or might we use it to explore, you know, could we widen the treatment window versus any single agent alone? We all know that in these... and these infections, viral infections, there's a ticking clock. You have a defined window, you know, based on what virus it is and what mechanism you're pursuing. And whatever that window is for one mechanism, you know, by putting two drugs together, hitting it harder earlier, you know, might you be able to, or hitting it harder, might you be able to, you know, postpone treatment a little bit longer before, therapy is is uh is administered and and so doing you would obviously be uh increasing the addressable patient population which you know would grow the market opportunity significantly so it's just various different ways once you have um a couple tools that you could exploit them and uh we'll be we'll be looking into that as we evolve it but uh 323 is a very strong looking molecule um very potent um great pk again we'll have it in the clinic in the second half and uh and we'll be you know tracking you know hopefully a very uh successful other pathway uh using our in protein and and uh and edp 938. um thank you jane if i may ask a follow-up question to the remarks you had so i think that question from a lot of investors will come in
spk06: How do we take the RSVP study and understand its translation in the more vulnerable population? So have you been able to provide some clarity how this first study could really de-risk, you know, RSVPs and RSVTX?
spk11: It's a stepwise de-risking. I think actually one of the most significant de-risking events for ADP938 happened in phase one healthies. when we established that a really potent molecule with a high barrier to resistance could be administered safely and could deliver, you know, very nice drug exposures. So that gave us great confidence going into, you know, our first RSV infection study, the so-called challenge model, where, as you know, it performed incredibly well. All of that said, you know, that was a virus that had been administered to patients, volunteers under a controlled setting. But it was still, you know, a real virus and real patient population. So to demonstrate, you know, good viral kinetics and good safety in that setting was further de-risking. Now we're taking it one step further and doing it with real-world virus. um a real world infection i should say so that people are you know catching uh the strain that's going around uh presenting in a very uh natural way to a treater and then we uh and then we treat them so i think it's um you know it's yet another de-risking step along in evolution rarely in in clinical medicine or clinical investigations do you have such checkpoints to be able to establish that your drug is actually doing what you had hoped for it to do. And granted that every patient population is slightly different and we'll explore those as we do. But again, I think the profile of the drug, the fact that it's a really potent antiviral and it appears to be working in every setting that we've put it in, you know, bodes well.
spk06: Thank you so much.
spk07: You're welcome. Thank you. Our next question comes from Roy Buchanan of GMP Securities. Please go ahead.
spk01: Hey, great. Thanks for taking the questions. I guess I'll start on EDP-235. It sounds like, you know, the next trial is going to be after the Phase 1 is going to be treating patients in the second half of the year, maybe a Phase 2, 3. Just curious... If you guys plan to run multiple phase ones in addition to the one that you're going to start this month, and if so, what those might be?
spk11: Well, I mean, you're always doing other kinds of ancillary studies along the way in development, you know, such as DDI studies. Is that what you were thinking of?
spk00: Anything.
spk11: Those types of studies. Yeah. No, I think those are the main ones. Once you have SAD, MAD, you understand your exposure and tolerability. you kind of know what your dosing parameters are for phase two. So you don't want to be slowing that down phase two, three. And so, but there's always other studies that you're doing in parallel in terms of BBI, et cetera, et cetera. Those will help, you know, down the road with special patient population.
spk01: Okay, great. And then I had one on 514. I guess just curious, maybe if you can speculate if that could be back into the clinic this year? And what about, I guess, how are you guys thinking about the combos? You know, maybe there are some less ideal agents out there that you could partner with just to get more data on the compound. You know, what about running maybe a longer combination trial with just a nuke? Some KLOs have mentioned to us that might be something worth exploring. Anything like that? Thanks.
spk11: No, those are... You know, all good questions. I think to answer your first and probably direct question about, you know, is it likely to be in the clinic this year? I won't say that it couldn't be under any circumstance, but what I would say is, you know, we're really focused on, you know, we have 514. It plays well with nukes. We've done it in a one-month study with making up a two-drug combo. We saw, you know, very nice behavior in terms of the two drugs playing well together, good safety profile in the combination. We observed good antiviral effects, you know, et cetera, et cetera. So it's the two-drug foundation now is just waiting for an ideal third ingredient to be added. And, again, you know, we thought we had that one lined up before. Turns out we don't now. And so again, we're looking sort of both internally and externally for what I think, you know, will hopefully be, you know, a great next combo ingredient. I don't know. I don't really necessarily want to be pursuing, you know, the lesser ideal ones. To me, that's, you know, maybe just not a, not a good use of capital. But, you know, as it pertains to, for a longer nuke study, I think was your other question, you know, could you do a core and a nuke for a really long time? I mean, that's probably not super high up on our list, but it is something that I know KOLs think could work, you know, over time. You just have to be patient enough to run those kinds of studies and sort of, uh, launch that satellite, um, and, and, uh, and then hope that it reports, uh, you know, data back after a significant period of time. So those are, those are interesting studies that maybe should be done in some fashion someday. But again, our, our principal focus right now is, um, looking for something that would make for a great third agent, to add such that we could get to a functional cure and hopefully in a more reasonable amount of time.
spk01: Okay. Thanks for taking the questions.
spk07: You're welcome. Thank you. Our next question comes from Zegre Jala of Roth Capital. Your question, please.
spk13: Good afternoon. Thanks for taking my questions and really helpful updates. I think we just have a few. The first one is in the Phase II ARSB study, you had symptom improvement that was being evaluated as a secondary endpoint, and you did show some impressive reduction in nasal mucus. But I think I was just kind of curious about symptom improvement being a primary endpoint for the Phase IIb study. And if you're going to be looking at nasal mucus, how important is that endpoint to patients, and is it likely that you'll be looking at some additional symptom measures for the Phase 2b study?
spk11: Yeah, so good question, Zegba. So yeah, in the Phase 2a study, the so-called challenge study, you know, we did, I think virology was the primary and symptom score was, you know, the secondary, and you can look at all kinds of but I have to say one of the most curious endpoints I've encountered in my career was, you know, mucus weight, which turned out to be actually a very interesting endpoint to look at, and it actually mirrored other data quite well. That said, you know, the going as you advance, viral loads in later stage trials will be interesting, but symptom scoring is gonna be more important on the path to registration. And so there will be a number of different symptoms that are observed in that capacity that will add up to the overall score. It was one thing to do the the mucus secretion in the challenge study setting because these patients were domiciled, they were inpatient, and it's very easy to collect all the Kleenexes and weigh them. In an outpatient setting, that's just not practical. So from RSVP onward, that's a tough one. We'll have plenty of others to look at. Yep.
spk13: Thanks. And then I'm sure you get this one a lot, but just kind of curious about the five-day treatment period for the RSVP study. I know you used the same treatment period in a prior study, but I was just wondering, is that really long enough or based on the MOA of the N inhibitor, it's likely that no additional benefits could be gained from treating longer?
spk11: Well, I guess you could never really know the answer to that without doing the study, but what we did find in this patient population, an RSVP, we think it'll substantially mirror the challenge setting. We think that should be adequate. When you get into the immune compromised setting RSV-TX, you know, the hematopoietic cell transplant recipients are highly immune suppressed in the first year post-transplant. And for these individuals who don't have a competent full immune system helping them, we are dosing longer, 21 days, in fact, in that study. So there may be certain pockets or patient populations where you want to have the latitude to be able to dose longer. But ultimately the goal is, you know, to try to find a convenient dose and regimen that's, you know, that is adequate and quite effective. And, you know, generally speaking, the shorter you can make that, the higher you're going to have compliance and the better the product profile is overall.
spk13: Got it. Was thinking that, yeah, it was probably related to also being cautious of the burden to patients. And then the last one here is, It's just about the combo strategy. So if you were to do a combo with the N and L, do you start with the N inhibitor and then follow with the L, and do you just onboard both of them at the same time? And then I'm just going to squeeze in a question here from Paul regarding maverick revenues. 2021 revenues came in lower than what AbbVie guided to at the beginning of the year, which was $2 billion. and I think it came in at 1.7, and they've guided modestly for 2022 at about that 1.7. So I was just wondering, how should we be thinking about, you know, the cadence of revenues beyond 2022 and how that has factored into your projections where I think you set a runway for the next two years?
spk12: Well, regarding what happens after 2022, it's really all up to the COVID pandemic situation. You're correct, ADVI has got it again for fiscal, for calendar 2022 at 1.7. So they're expecting a flat year to 2021 with no relief, I guess, from the COVID suppression impact. What happens after that is really going to be up to, you know, are we through with variants? Is there going to be a fall on Omicron? It's unknown at this point in time. And I would say that the two-year guidance we gave on cash was based upon our existing cash balances, our R&D and G&A guidance for fiscal 22, and obviously our ATV royalties for the next fiscal year. So, we look at that whole picture, and we feel comfortable that we've got at least a two-year run rate on cash.
spk11: And to answer your other question, Zagba, you know, if we were doing a combination study, we would add the drugs together at the same time.
spk13: Thanks, guys, and thanks for the clarification, Paul.
spk07: You're welcome. Thank you. Our next question comes from Jay Olson of Oppenheimer. Your line is open.
spk10: Oh, hey, thank you for the update, and congrats on the progress. I think there's been some discussion about using Merck's Momupiravir together with other antivirals in a combination approach to treat COVID. Is that something you would consider with EDP-235? And if so, which drugs would you consider combining it with? And then if I could ask a financial question, assuming AbbVie's guidance of $1.7 billion in 2022 sales indicates that Maveritt is stabilizing. Would that support a level of royalties that could continue to support Enanti's operating expenses for the foreseeable future?
spk11: I think as Paul sort of just outlined, the 1.7 that the guiding for the year is pretty much where they came in now, and that's what's built into our forecast. We model based on their guidance, and we do see that as propelling the cash runway for that two-year, at least the two-year period based on current cash and anticipated royalty revenue. Regarding your question about combos, there's no indication right now that you need combos. You know, it is an acute viral infection. You know, we have potent antivirals. It appears to be, you know, from what we can see with, you know, antiviral drugs going after COVID, the five-day treatments, are sort of the norm, much like we had already established, you know, in our RSV study. So I, you know, I would say that, you know, there could be the need for combinations down the road, but we don't see that need yet. But nonetheless, we're anticipating that having more mechanisms rather than fewer down the road you know, could be a valuable thing. So, you know, we're not just working on produce in-house here. When the pandemic started, we started multiple different programs, and we're hoping to harvest, you know, other agents of other mechanisms over time. So stay tuned on that front. But in any event, to your direct question, I don't see the – you know, the need at this time to be doing those combination studies. I'm not sure what you'd be trying to establish.
spk10: Okay. Thanks for taking the question.
spk11: You're welcome.
spk07: Thank you. Our next question comes from Brian Scorny of Baird. Please go ahead.
spk08: Hi. This is Luke Herman on for Brian. Thanks for taking my question. And thinking about RSV development strategy, from earlier questions, it seems like you're leaning towards the higher risk RSV populations for the initial registrational path. In a situation that RSVP reads out positively, do you think the RSVPs and RSVTX studies might serve as pivotal for those indications? And otherwise, what can we expect a pivotal program to look like? And would you choose to move it forward yourself? Thank you.
spk11: Yeah, so, again, I think, you know, once you have the data for RSVP, you know, we'll have that information and, of course, we'll have that discussion with the agency. That could inform how, you know, the future of the development program looks like on the path of registration, but at this time, we are not currently expecting that those two studies are necessarily registration studies. Does that help, Paul?
spk08: Yep, thank you.
spk11: I'm sorry, did you have another question?
spk08: It was just other, if those weren't, what would pivotal development look like if you could speculate at all?
spk11: Yeah, I think the FDA, I mean, I think the FDA and the EMA, you know, both want to, I think, focus on high risk as the expedient path to approval. So I think that's what we need to do.
spk08: All right, thanks.
spk11: Yep, you're welcome.
spk07: Thank you. Our next question comes from Rana Riz of SVB Lorinc. Your line is open.
spk05: Great, thanks. So I wanted to circle back to your COVID asset. So for 235, do you have any thoughts on what percentage of patients out of the total eligible patient pool for antivirals might be really fully unable to take an antiviral that has ritonavir boosting, maybe possibly due to drug-drug interactions or things like that?
spk11: Yeah, it's hard to get your hands on that exact number now. Maybe that is more of a Pfizer question. I think the... But what I will say is there's a very substantial amount of the pharmacopoeia that is influenced by ritonavir dosing. So you just need to understand what other concomitant meds patients are on and understand what potential impact ritonavir would have. Do you need to take people off certain meds, do you need to dial them down or dose adjust? In some instances, ritonavir can reduce exposure of other medicines. Might you need to dose elevate other drugs to compensate for that? So there's just different things going on that you need to be able to understand. And I think any time a patient's on concomitant meds, it's a question that physicians will need to understand and explain to patients and then set up whatever plan of attack that you would need to set up to make sure everyone is safely medicated. Our hope is to just sidestep that issue entirely.
spk05: Yep, makes sense. And then a quick one for your RSV programs. I was curious, for the phase two studies in pediatric and transplant patients, are there any other strategies or levers that you can pull to further accelerate the enrollment of those trials? And what are you tracking to help you make that kind of decision if you want to apply those additional strategies?
spk11: Yeah, so we're looking at new strategies, you know, all the time. The other thing you do is, you know, improve your catchment in terms of trial sites, etc, etc. I think it's, it's just a question of how you adapt protocols to make it friendly for, not friendly is maybe the wrong word, but make it convenient for parents of peds to enhance enrollment, you know, not having extensive barriers there, extensive blood draws, other kinds of things that might, you know, slow things down a little bit or put people on the fence in terms of coming in and participating in the trial. Like one of the other things, you know, just during a pandemic, the transplant recipients are probably among the the most cautious people, right, because they're immune suppressed, they have to be have to be incredibly careful post transplant, because of COVID. And, you know, so that that raises other, you know, special challenges during a pandemic, but we're just going to have to just like with RSVP, you know, we had to, it was, as you know, was compromised by the pandemic for a while. And we just needed to be ready with sites, you know, and all the appropriate spots for when things opened up a little bit and then take advantage of harvesting the trial enrollment. So I don't know that there's any special tricks. We're just always trying to optimize enrollment in which way we can without jeopardizing the study, of course.
spk05: Yep, that makes sense. Very helpful. Thanks a lot.
spk07: You're welcome. Thank you. Again, to ask a question, please press star 1 on your touchtone telephone. Again, that's star 1 on your touchtone telephone to ask a question. Our next question comes from Lisa Baco of Evercore ISI. Your line is open.
spk03: Hi, thanks for taking the question. Just wanted to get a sense, so you'll have one data for the COVID program, you know, looks like in the second quarter. Is that going to come before or after, do you think, the RSV data? And then how quickly would you be able and prepared to go into phase two slash three with your COVID program from, you know, wrapping up the phase one?
spk11: Yeah. I can't really, I guess, speak to which data, you know, would come first. We haven't, you know, we're going to begin dosing 235 soon. And, you know, we'll get into that study and get it, you know, get it and get the various cohorts progressed. So, you know, depending upon how many doses we have, et cetera, et cetera, it's safe to say they're, They're probably both Q2, but exactly, you know, which one's first, I can't really speak to today. And then your other question, you know, obviously we'll be preparing for, you know, the steps in phase two, three after the phase one is to get into that as quickly as we can. you know, making sure drug supply and sites, et cetera, et cetera, lined up. And so we'll be doing it as quickly as possible and starting in the second half. So stay tuned on that front.
spk03: Okay. And is that part of your assumption in your guidance? And I'm just looking at R&D because you came in at around 49 million this year. I feel like you have a lot going on in your pipeline. You're going to 168, sorry, 150 to 170. Where, like, how do we kind of make the math work with all these studies going on? Is there something I'm not, I know a couple things are probably wrapped up in the fourth quarter, maybe are wrapping up, you know, in the first quarter. But given you might be starting, what do we think about it?
spk11: Sure. No, there's wind down, you know, costs and so forth associated with, you You know, some of the, the Nash studies, et cetera, et cetera, they won't be obviously carried through through the rest of the year. Um, we're, um, but you know, I, I think the plan is, is, uh, still intact, um, and, and encompasses, uh, you know, what we're, what we're aiming to do with these, uh, these various programs.
spk03: Okay. And then just one or two questions on RSVP. The strain that you used in the challenge study, is that, like, pretty representative of kind of how the different, you know, viruses out there? And it just came to my attention because you talked about, you know, the strains going around right now. How similar or divergent can strains be for RSV compared to what you looked at in the challenge study? Because as I recall, yours was one of the more seems like I don't know if the right word is virulent or whatever, but you had one of the higher viral loads. You know, as I was kind of looking across other challenge studies, so it looked like you had a, you know, a pretty serious, you know, virus that you were now using. Yeah, I think it's a standard.
spk11: Yeah, no, sorry to, sorry to interrupt Lisa, but I, I think it's a standard virus that has been used as the Memphis strains and used in multiple challenge studies. I think It may differ a little bit in terms of when people elected to dose. We waited to dose once the viral load had reached a certain threshold, not a certain number of days post-inoculation. So we inoculated people in that challenge study with the virus, waited for the viral load. We checked people twice a day by RT-PCR. waited for the viral loads to start to climb up and, you know, waited until they got up to about three logs as I recall. And then, and then we started dosing. So, um, you know, obviously if you go sooner than that, you'll be doing some with a lower viral load. Um, so that's probably the variable there. You know, I think ultimately it's, you know, it's, it's a real virus. We, But you do need to ultimately get out into the real world where you're going to run into slightly different strains. You might have RSV-A. You might have RSV-B. There might be various subtypes along the way. But this is why we did a lot of work on clinical isolates before embarking on this study. We weren't using just lab strains of things, et cetera, et cetera. We got geographically dispersed studies. live virus samples from different patients in different seasons, et cetera. And we tested our drug against them. And the drug performed uniformly very well against the clinical onset. So it is a variable, but that's the real world, right? That's real world infection. And that's among the things that RSVP will be, looking at. But I think we've tried to fence in as much as we could possibly fence in from a, you know, de-risking prior to doing this.
spk03: Okay. And then just final question for me. So you mentioned you dosed around three logs, and I see from your graph your child said that makes sense. It's when you started dosing. How does it relate to, like, symptoms and when patients start feeling symptoms and present, because I think that's what we're, you know, a lot of people are trying to figure out is like that window of opportunity you have. I know it has to be within two days of symptoms, but you started dosing on day three here. How does, sorry, not on day three, at three logs of viral loads, how does that relate to kind of the onset of symptoms and that kind of stuff?
spk11: Well, if you, and we've got these slides in our corporate deck on our, on our website, it's probably what you're looking at, but I, I, If you look at the symptoms, by the time people were three logs in the challenge study, and this is the trial we're talking about, it's the challenge study, by the time people were three logs, they were also starting to express at least one symptom. And so they were becoming symptomatic. So then if you translate that into the real world study now, and say in RSVP, you know, what is the window? What is the window that we could possibly be dosing patients in? You're not going to get people to come into your study or into the doctor's office period within 24 hours of symptoms, right? Nobody sort of does that. They languish a little bit before they pick up the phone. And so the earliest you might reasonably expect to catch a patient in a real-world setting is within 48 hours. And that's obviously what we were able to do in RSVP. That was one of the parts of the study we were just doing, just to make sure we could catch RSV patients within 48 hours of symptom onset. And that indeed was the case. That's the requirement for flu. If you want a flu drug to work, you've got to catch people in the first 48 hours or maybe 72 hours of symptoms if you want that drug to work. We don't know what the window is for RSV. It's probably more forgivable, forgiving, I should say, than flu, where it's a real tight window. We're starting to get experience now in the community with RSV, with regards to COVID, right? It appears that you can, maybe there's a five-day treatment window for COVID. Where does RSV lie? These are among the things that we'll, you know, ultimately be sorting out in various studies. But just for the very specific RSVP trial, we did put that 48-hour constraint on there just recently. because we didn't have a basis to necessarily make it much longer. We just said, well, let's assume it's like flu, and then we can always go longer. You don't want to make the wrong guess at the beginning of your development life. So I think that's where it is. You can't practically do it. shorter than 48 hours, and we saw no reason necessarily to go longer than 48 hours. So I think it's a good sweet spot.
spk04: Okay. Thank you.
spk11: Does that make sense? Yep. Good.
spk07: Thank you. At this time, I'd like to turn the call back over to Jennifer Vieira for any closing remarks. Ma'am?
spk04: Thank you to everyone for joining us today. If you have additional questions, feel free to reach out and contact us by email or give us a call at the office. Thanks so much. Have a good night. Bye-bye.
spk07: This concludes today's conference call. Thank you for participating. You may now disconnect.
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