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spk05: Good afternoon and welcome to Enantez Pharmaceuticals Fiscal Fourth Quarter and Full Year Ended September 30th, 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'll now like to hand the call over to Jennifer Vieira, Investor Relations. Please go ahead.
spk12: Thank you, Operator, and thanks to everyone for joining us this afternoon. The news release with our fiscal fourth quarter and full year 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 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?
spk08: Thank you, Jennifer, and good afternoon, everyone. At Enanta, we are leveraging our expertise in medicinal chemistry, virology, and preclinical sciences to discover new compounds that can be developed into groundbreaking medicines. Our fiscal fourth quarter, as well as 2022 overall, was a year of progress toward this effort. With multiple ongoing and planned clinical studies across our pipeline, we are poised to execute on our vision to transform the lives of patients with curative therapies, building on our prior success in hepatitis C. Today, I'll start by detailing our recent advances in the development of EDP-235, our once daily orally dosed inhibitor of coronavirus 3CL protease, which is in clinical development for the treatment of COVID-19. I will then comment on our RSV and human metapneumovirus pipeline progress since our last call, as well as our work in hepatitis B. Starting with COVID-19, we are pleased with the recent advancement of EDP-235 into the next stage of clinical development with the initiation of SPRINT, a Phase II clinical trial in COVID-19 patients. This randomized double-blind placebo-controlled study will enroll approximately 200 non-hospitalized symptomatic patients with mild to moderate COVID-19 who are not at increased risk for developing severe disease. Patients will receive 200 milligrams or 400 milligrams of EDP-235 or placebo orally once daily with food for five days and will be followed for 28 days thereafter. Patients will be eligible to participate if they have had symptoms for not more than five days and have not received a SARS-CoV-2 vaccine or been infected with SARS-CoV-2 within 90 days of enrollment. Primary objective of the study is safety and tolerability, and key secondary objectives include pharmacokinetics and multiple virologic measures to guide our dose selection for subsequent trials. In other studies of protease inhibitors, the viral load decline has been similar between high and standard risk populations. Thus, we believe enrolling from a larger pool of standard risk patients will be a more efficient way to collect this information. We are aiming to report results from SPRINT in the first half of 2023. As previously reported, data from the Phase 1 study of EDP-235 demonstrated it was generally safe and well-tolerated up to 400 milligrams for seven days with strong exposure multiples over the EC90, which is a measure of potency. Specifically, it is a concentration of the drug that results in 90 percent inhibition of viral replication in vitro. Adverse events were generally mild and infrequent. Two hundred milligrams of EDP-235 taken once daily resulted in mean trough plasma levels at steady state that were threefold and sevenfold over the plasma protein-adjusted EC90 for the Alpha variant and Omicron variant, respectively. while 400 milligrams resulted in levels that were six-fold and 13-fold over the plasma protein-adjusted EC90 for the respective variants. Importantly, these target exposure multiples were achieved without the need for ritonavir boosting and its associated drug-drug interactions. Based on preclinical studies, EDP235 is projected to have four times higher drug levels in lung tissue compared to plasma, which would be expected to drive up to a 28-fold multiple for the Omicron variant at even the 200 milligram human dose. As COVID-19 persists and new variants arise that can circumvent immunity from vaccination, previous infection, or monoclonal antibody treatments, we are committed to developing EDP-235 as a convenient and easily prescribed antiviral which continues to show strong activity against all COVID-19 variants tested to date. Beyond COVID-19, we are also encouraged by the progress we have made in our Respiratory Syncytial Virus, or RSV program. RSV is a virus that represents a significant unmet need as it can result in a severe respiratory infection and is associated with significant morbidity and mortality in children, the elderly, and other high-risk populations. While RSV was mitigated for some time due to social distancing measures during the pandemic, RSV infections are now on the rise in the U.S., and the need for a treatment remains high, as there are no targeted therapeutics currently available. We are pursuing a robust RSV program, which includes EDP938, the most advanced N-protein inhibitor in clinical development today, as well as EDP323, a novel oral therapeutic targeting the RSVL protein RNA polymerase. We're currently evaluating EDP938 in high-risk populations, including pediatric patients, adult hematopoietic cell transplant recipients, and other high-risk adults, all of which have a significant unmet need. Last month, we initiated RSVHR, a Phase IIb study in adults with acute RSV infection who are at high risk of complications, including those over 65 years of age and or those with congestive heart failure, COPD, or asthma. The study is a randomized, double-blind, placebo-controlled, multicenter global study designed to evaluate the effect of EDP938 compared with placebo on the progression of RSV infection. Approximately 180 patients will be treated with 800 milligrams of EDP-938 or placebo for five days and then evaluated over the next 28 days. The primary endpoint for the study is time to resolution of RSV lower respiratory tract disease symptoms through day 33. Our other studies of EDP-938, namely RSV-PEDS, a phase two study in pediatric RSV patients, and RSV-TX, a Phase IIb study in adult hematopoietic cell transplant recipients with RSV, are ongoing. We believe EDP938 has the potential to deliver a potent oral antiviral treatment for all populations at high risk from RSV infection. We'll continue to monitor the RSV trends during this northern hemisphere season to enable us to better evaluate timing for data. This quarter, we also began dosing in our phase one randomized double-blind placebo-controlled study of EDP323 in healthy adult subjects. The study will evaluate the safety, tolerability, and pharmacokinetics of orally administered single and multiple doses of EDP323, our novel oral therapeutic targeting the RSVL protein RNA polymerase. EDP323 is supported by promising preclinical data presented this quarter at the 12th International RSV Symposium, which showed that EDP323 inhibited polymerase activity in vitro and also inhibited the virus-induced cytopathic effect of both RSV-A and RSV-B strains. In a rodent RSV infection model, treatment with EDP323 was associated with improved lung histopathology and dose-dependent reductions in pro-inflammatory cytokines. We believe EDP-323 could serve as a standalone treatment or may be used in combination with other agents such as EDP-938, potentially broadening the treatment window or addressable patient populations for RSV. Moving on to our respiratory discovery program in human metapneumovirus, or HMPV, which is a virus that is similar to RSV and impact several vulnerable populations, including the elderly, adults with underlying pulmonary disease, and those who are immune compromised. This quarter, we presented preclinical data at the 12th Annual RSV Symposium, highlighting advancements in HMPV detection, quantification, and growth methods for the generation of an improved toolkit for the in vitro characterization of multiple HMPV strains. Our goal is to select a development candidate for HMPV next year. Turning to hepatitis B, our goal remains to develop a functional cure for chronic HPV patients. We continue to evaluate internal and external opportunities for additional candidates to develop in combination with EDP514, as we believe the ultimate cure for this infection will involve combination therapy. Our commitment is based on the continued high unmet need for this disease which is a global public health threat and the world's most common serious liver infection, making it the primary cause of liver cancer, also known as hepatocellular carcinoma, or HCC, the second leading cause of cancer deaths in the world. We believe that a core inhibitor such as EDP514 could ultimately be an integral component of a successful combination regimen. Finally, I'd like to wrap up by highlighting our near-term clinical milestones for the first half of next year. We look to progress SPRINT as quickly as we can through Phase 2 and to report data in the first half of 2023. Further, we expect to have data from our Phase 1 study of EDP323, our RSVL inhibitor, also in the first half of 2023. With that, I'll turn the call over to Paul to discuss their financials.
spk07: 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 full year-ended September 30th, 2022. For the quarter, total revenue was $20.3 million and consisted of royalty revenue earned on AVI's global Maverick net product sales. This compares to total revenue of $23.6 million for the same period in 2021. The decrease compared to the prior year was due to a decline in AVI sales of Maveritt. Royalty revenue was calculated on 50 percent of Maveritt sales at a royalty rate for the quarter of approximately 10 percent, after adjustments for certain contractual discounts, rebates, and set-offs, which are now approximately 2 percent of AVI's total reported HCV product sales. You can review our royalty tier schedule in our 2021 Form 10-K. Moving on to our expenses, for the three months ended September 30, 2022, research and development expenses totaled $34.8 million compared to $48.9 million for the same period in 2021. The decrease was primarily due to the timing and scope of the company's clinical trials. General and administrative expense for the quarter was $12.6 million, compared to $8.4 million for the same period in 2021. The increase was due to additional headcount and stock compensation expense. An ANTA recorded an income tax expense of $0.01 million for the three months ended September 30, 2022, and an income tax benefit of $0.4 million for the 12 months ended September 30, 2022, which are due primarily to the release of state tax reserves. Ananta recorded an income tax benefit of $8.8 million and $28.6 million for the three and 12 months ended September 30th, 2021, respectively, due primarily to a federal net loss carryback available in fiscal 2021 under the CARES Act of 2020. Ananta is still due a refund of $28.7 million for the tax losses carried back in 2021 to offset taxable income in prior years. Net loss for the three months ended September 30th, 2022 was $26.3 million or a loss of $1.27 per diluted common share compared to a net loss of $24.6 million or a loss of $1.22 per diluted common share for the corresponding period in 2021. and at the end of the quarter with approximately $278.5 million in cash and marketable securities. We expect that our current cash, cash equivalents in short-term and long-term marketable securities, as well as our ongoing royalty revenue, will continue to be sufficient to meet the anticipated cash requirements of our existing business and development programs into the fourth quarter of our fiscal 2024. Regarding guidance of fiscal 2023, we expect our research and development expense to be between $210 million to $230 million, and our general and administrative expense to be between $46 million to $52 million. Further financial details are included 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 open up the lines for questions. Operator?
spk05: Thank you, sir. As a reminder, to ask a question, you would need to press star 1-1 on your telephone. Please stand by while we compile the Q&A roster. And I show our first question comes from the line of Brian Abrahams from RBC Capital Markets. Please go ahead.
spk06: Hey, good afternoon, and thanks so much for taking my questions. Congrats on the continued progress across all the programs. Maybe just starting on the COVID, on the 235 study, the SPRINT program, I'm wondering if you could maybe talk a little bit more about some of the key virological measures that you're going to be looking at in order to help guide dose selection going forward, and I guess how much are you going to be also looking at symptoms as well and is there, I guess, how might you account for the potential for patient-to-patient variability just based on intrinsic immune differences, vaccination status, prior exposure status in terms of elimination of virus in order to make sure you have kind of a standardized look at the different doses relative to placebo?
spk08: Sure. So thanks, Brian, for the question. So in terms of looking at the you know, quote, standardized population. I think we're trying to control at least for some of the variables that we can. One of them is vaccination status. By now, so many people are vaccinated, but we're asking for people to be enrolled who have had a vaccine in the last three months. And the same is true with COVID within the last 90 days. That's when immunity tends to wane and, you know, you're not taking fresh COVID patients or people who have been freshly vaccinated. So that's one of the factors. And then going back to, you know, the study design, you know, we're focusing, you know, primarily for safety and tolerability as a primary endpoint. And then in a you know, gather enough information as possible in the shortest, smallest possible study that we could conduct that would be phase three enabling. We're going to look at other parameters, you know, virologically, you know, the things that you can measure are going to, you know, predominantly be viral load. Again, as you know, COVID Drugs in general don't show hugely profound changes on viral loads. In fact, remdesivir doesn't show any change on viral loads. So the protease inhibitors, though, have shown small sort of modest changes in viral load reduction. So we'll certainly be looking at that. We'll look at AUC, time to undetectable, things like that. Regarding clinical symptoms and outcomes, again, in a small study like this, they're more exploratory than anything, I think, in a small study that's sized in this way. You're not really, and in this patient population particularly, you're not really going to be expecting to see too much in the way of that, but we'll be looking for We'll definitely be looking for trends and things that we can possibly measure and focus on as it relates to later stage studies. So hopefully putting all that together in a small study, we'll have enough information from there to select our dose between the 200 milligram dose and the 400 milligram dose, and then go forward on to the next step.
spk06: Got it. No, that makes a lot of sense. And then we've obviously seen a wave of RSV across the country and the globe of late. To what extent have you been able to, I guess, take advantage of that with regards to patient enrollment in the ongoing 938 studies? Or are there any changes or adjustments you might make to this site onboarding, number of sites, overall protocols? to be able to optimize enrollment in light of the spike we're seeing?
spk08: Yeah, so, well, as you know, we have three high-risk patient trials going on. We have a pediatric study, and we have an immune-suppressed patient population who are bone marrow transplant recipients. And then the third study, which we just announced and has just got up, is – the high-risk adult studies. So these are adults who are 65 years and older and or have some other things going on, either asthma, COPD, congestive heart failure, things like that. So things that are putting them at high risk. And so, as you know, from the past, there was definitely a drought in RSV during the heart of the pandemic. And it's clear that some of that's come, you know, unwound now that patients, various people's immunities have, you know, waned over the period of time. There's also seems to be a very early season of RSV this year. You know, we'll wait and see. For the very least, it's early. We'll see, you know, how severe it is over time and how protracted it is over time. So we need to... basically watch this northern hemisphere season, which is definitely cranking up, and then see where we stand with all of our sites around the globe on these various studies at the end of the northern hemisphere season, I should say. And then we'll have a better sense of where we stand in each of those studies.
spk06: Got it. I'll hop back in the queue. Thanks again.
spk08: You're welcome.
spk06: Thank you.
spk05: One moment while we compile our next question. And I show our next question comes from the line of Yasmin Rahimi from Piper Sandler. Please go ahead.
spk13: Good afternoon, team. Congrats on all of the updates and your thoughtful remarks as usual. I guess the question for you team is, you know, like fast forward to Sprint data coming out in the first half of 2023. Thank you for telling us of what's the bar and what do you want to see in the study, but what would the next steps be? You know, where are we in terms of regulatory approval of COVID therapeutics? What's the bar? So just give us some framework on what are elements of the next steps post-SPRINT that are determined and what are maybe unknowns that would be really helpful, and then I have a quick follow-up.
spk08: Sure. So, well, SPRINT is a Phase II study. Again, we're aiming to have it be Phase III enabling and then also, you know, a dose-selecting trial that we would So, the next step would be, you know, phase three. The specifics of that trial design, you know, we'll continue to plan internally and also have interactions with the agency with regards to the exact, you know, trial design. So, it's going to be some more interactions along the way, hopefully with the hands having good data in our hands. during those discussions. So a little bit early to focus on what that design will look like. But again, we're hoping to wrap up this study as quickly as we can, have data in the first half, and then aim for phase three in the back half of the year.
spk13: Thank you, Jay. And then in question about 323, It seems after we see the phase one data, is the strategy, like what is the type of data that you would want to see that would support moving it forward in monotherapy versus in combination? So maybe if you could walk us through what the data scenarios could be for both optionalities, that could be helpful for us. And then we'll jump back into the queue.
spk08: Sure, so as you know, Our first molecule in the clinic, 938, is a direct acting antiviral. So it's a replication inhibitor in contrast to other approaches that have been tried in the past and in the present, I guess, in terms of entry inhibitors. So we're focusing on replication inhibitors. Again, we believe that that's the fastest, best way to shut down you know, an active replicating virus in a patient who's presenting. And so to that end, we didn't want to just have one such class in hand. We're very committed to RSV over time, and we want to have, you know, multiple different approaches over time. Someday you might think about combining them. Again, there's no reason a priori to believe that in the overwhelming majority of patients, you would need to have a combination strategy. But we would like to have that possibility for a few different reasons that I can articulate in just a second. But 323 is another replication inhibitor. It goes after the polymerase enzyme. And what we do in any of our candidate discovery programs, you know, we're always focused on finding very potent molecules with good safety and good pharmacokinetics and good biodistribution. And so 323, you know, checks all of those boxes preclinically. And so phase one, as is our usual approach, is really just hopefully recapitulating all of those kinds of bits of data in a human phase one setting. So we'll be looking for, of course, good safety. We'll be looking for good PK. All of our, again, preclinical predictions support that it should have good oral PK once daily dosing, something we also are always aiming for here. And then, you know, we know that the molecule has extraordinarily good virology. It's very, very potent. It's a picomolar inhibitor of this polymerase. Preclinically, we believe, you know, it's a good standalone molecule on its own right. It's a, it's potentially a good combination partner, you know, down the road. Again, thinking about different patient populations, ones that might need an extra little, you know, support in terms of drug pressure on the virus, maybe in highly immune suppressed patients, for example. and or just reeling in a more normal patient by maybe able to reach a little bit later in the stage of infection by using two agents rather than one and translating that into patient value. It's potentially widening the treatment window that you might have to come after a patient a person, you know, once they present with the infection. So, you know, however many days of a window, treatment window you might have with one drug, you know, maybe two drugs would just widen up that opportunity, you know, therefore increasing the addressable patient population. So these are the kinds of things that we're looking for. Again, it's always better to have multiple different approaches on any area or any disease indication that you feel very strongly about. And as you know, we've been championing RSV for, you know, quite a number of years, starting with the earliest of discovery efforts a long time ago. And I think now through the pandemic, the attention is very high on human respiratory viral treatments. And, you know, we're very pleased to have a second molecule now in the clinic. So next steps, we'll get the phase one data. We'll look at it. And then we'll think about, you know, our next steps carefully once we have that data in hand. And you could go a couple different routes. You could go into a challenge study or you could go directly into a patient population. And we're obviously thinking about that sort of thing right now. And we'll have more details at a future time.
spk05: Thank you. And I show up. Our next question comes from the line of Brian Scorny from Baird. Please go ahead.
spk04: Hey, good afternoon, everyone. Thanks for taking my questions. I had a few quick ones on the 235 Sprint study. I guess to start, since you're at 7 and 13 full BC90s for the Omicron variant, are you expecting any dose response on viral load? I mean, it seems like it would be overkill in terms of shutting down the virus. I'm just wondering what, if anything, you're expecting in terms of differences between the dose. And then I noticed on clinical trials you have a couple different measures of viral load. Can you just discuss how you're measuring RNA viral load versus infectious viral load? And then finally, how do you think of the number of days of symptoms you're enrolling patients? I think five days is where you're cutting off. Is that too many to sort of catch a separation of the curve compared to placebo? Just trying to think through the time course of viral load evolution here and if there's a risk that you're catching a lot of patients in the decline phase. Thanks.
spk08: Sure. Maybe I'll let Tara comment on the, you know, the viral readouts. But what I would say is on the 200 and 400 milligram doses, you know, we may or may not see, we may see, well, there's all kinds of possibilities, right, when you look at two doses. But it's possible that given the strong multiples we have that either of those two doses does what we need it to do. Or there is still a possible that you might see some dose range or dose response in something. But, you know, these are the two reasonable doses that we chose to evaluate this, and it's exactly why we're running the study, just to see if we can differentiate. Is there any differentiating to be done here? The five-day piece. You know, Shinogi and Pfizer have shown good viral load drop in various patient populations with the five-day treatment window. You can obviously stratify people, you know, depending upon what their actual window was, you know, but it won't be more than five days. So that's what I would say about that. And then, Tara, do you want to comment on the viral readouts?
spk03: Sure, Jay. Hi, this is Tara Bryan. So we'll be looking at the viral load, the RNA, and that'll be done by PCR. And that's, you know, primarily what a lot of other companies have read out on their programs. We'll also be looking at infectious virus, and that'll be done through culture. So this is actually looking at, you know, live infectious virus that is still in the samples. So we'll be looking at both of those readouts.
spk04: And those are both just nasal swabs?
spk03: Correct.
spk04: Thank you.
spk09: Thank you.
spk05: Thank you. One moment while we compile our next question. And our next question comes from the line of Lisa Baco from Evercore ISI. Please go ahead.
spk11: Yeah, I think most of my questions have been answered, but maybe just on the COVID study that you announced, can you explain sort of, I guess, the overall goal here, and do you you know, when you're trying to learn from the study and in terms of, you know, enrolling the more, you know, kind of lower risk patients, are you concerned at all that you have a similar outcome, you know, than you did in RSV where you kind of don't see any, you know, necessary, you know, kind of, you know, separation in terms of resolution of symptoms or or any outcomes just given that you're not focusing or enriching the study for sort of that higher risk group. So, could you comment on what your objectives are of the study in light of the focus there on the low risk patient population? Thanks.
spk08: Sure. Thanks for the question, Lisa. So, you know, one of the key reads that we'll be, you know, watching for on the virologic side of the table is viral load. And one of the things that we know is standard risk patients and high risk patients have very similar viral loads. What happens after that to those various patient populations differs. But this is why if you're looking at symptoms or outcomes, some of those things, those would be harder to measure in this so-called standard risk patient population. um but again when bringing it back to looking at the virus trying to figure out which dose you're going to use looking at safety and tolerability those are the kinds of things that you should be able to do quite adequately in this in this patient population and then once we've got our dose based on all those parameters again going into phase three you can you can broaden out and look at many different outcomes and we'll have, you know, obviously larger powered studies to, you know, to look at those kinds of things. So, yeah, so Pfizer's shown that it's the viral loads are very similar in standard risk or high risk. And, you know, she and I saw viral load effects in that standard risk population.
spk13: Thank you.
spk08: You're welcome.
spk05: Thank you. One moment while we compile our next question. And our next question comes from the line of Eric Joseph from JP Morgan. Please go ahead.
spk10: Good evening. Thanks for taking the questions. I was just thinking about this phenomenon of viral rebound seen with Pfizer's Paxlovid. I'm just wondering sort of what your understanding is behind that phenomenon and whether Sprint offers the opportunity to kind of look at a similar phenomenon, at least assess for it in the post-treatment follow-up period. Are you looking at viral load beyond, let's say, two weeks? And then as it relates to RSV and the potential for, you know, kind of thinking through potential combinations with 938 and 323, I guess practically speaking, when would be sort of the first opportunity to really explore that potential? Is there a useful pre-clinical model that would kind of inform the potential for additive benefit through combinations? Thanks.
spk08: Yeah. Two good questions. So the rebound thing, you know, is interesting. I mean, it does seem to be certainly a real phenomenon, although, you know, you can get rebound even in people who don't take Paxlovid. It's just part of the natural course in patients. Some will resolve, you think you're better, and then you rebound. But that phenomenon has definitely been observed, you know, in protease-treated patients to date. And part of the You know, the thing that we've been wondering about is, you know, well, why is that? And clearly there must be some little pocket of virus that's not fully taken care of. You know, ideally you want to beat the virus down to a low enough level in whatever tissue you need to beat it down in and then get it down to sufficiently low levels that the immune system can kind of come in and mop things up and help you out. So our speculation is that among the possibilities, there could be a little reservoir a virus hiding somewhere and that you need to further extinguish it. And so do you do that by treating for longer days? I think that's one parameter that will be sorted out over time. But the other intriguing possibility is one that potentially EDP-235 could have an advantage on, and that is higher tissue uptake in terms of uptake into key target organs such as lung tissue. where we've demonstrated at least preclinically, you know, drug concentration, you know, out of the plasma and into the tissue in a, at least in lung tissue, you know, a four to one concentration. So that wasn't observed with another protease inhibitor that's out there. And so we've looked not only at lung tissue, but we've looked at many other tissues as well that are potential reservoirs for virus. And some of our concentration goes up even higher than that. So we'll have more data on that topic coming up this year. But, you know, we're hoping that 235, owing to its really good potency, really good, you know, drug exposures after QD administration has, you know, Brian Scorney mentioned we've got very nice multiples at either of our doses against the Omicron variant. And then you add on top of that the potential of having good tissue uptake where the virus might be hiding out and a little harder to treat. So we're hoping that that could all add up to having some impact on rebound. And we will certainly be looking at that in our study because we'll be dosing for five days and then we have a 28-day So, we'll have a chance to watch these people out to day 33. So, that's an intriguing hypothesis that we'll be testing. The other question that you had, I think, was about RSV. You know, we have 938, obviously, advancing in three high-risk patient trials right now. We have 323. proceeding nicely in a phase one study, it'll be ready to look at in virally infected people hopefully soon enough. And you asked, I think, the specific question of how could you look at that as a combination. And one of the possibilities that could be thought about is doing that in a challenge study. We already have fantastic challenge study data with 938 You know, one could do a challenge study with 323 and also look at the combination of the two to see what parameters one might be able to improve. So you asked what would be the earliest way that you could look at that. That is probably the earliest, quickest way to get interesting data about combinations.
spk10: Okay, great, great. I appreciate you taking that question. Thanks.
spk08: Thank you.
spk05: Thank you. And I show our next question comes from the line of Rona Ruiz from SVB Securities. Please go ahead.
spk02: Great, thanks. Afternoon, everyone. So a quick question on the SPRINT trial. I was curious on the clinical symptoms secondary analysis. Specifically, are you going to focus in on a key set of symptoms similar to what we saw with Shinogi's late stage trial data? Or will you plan to be a bit more broad in your exploration of different symptoms of COVID?
spk08: Tara, you want to handle that?
spk03: Sure. Hi, Ruana. It's Tara. So, we'll certainly look at all the symptoms in our trial, and then we'll have the ability to do analyses of specific subsets. So, to your point, you know, looking at those five symptoms that Shinogi was able to show an effect on. So, we'll be able to do both, and we'll also be able to learn this way with the comprehensive data set, you know, how best to move into later studies as well.
spk02: Got it. Makes sense. Yep, that helps. And for, I want to ask about 938. For the RSV-HR study, do you expect to see a good balance of different high-risk patients being enrolled, like across COPD, asthma, etc.? ? And I'm not sure if I missed this, but do you have any input on what you think the sequence of readouts might be between your different RSV trials, like the RSV-PEDS, RSV-TX, and RSV-HR?
spk08: Yeah, so the readouts on those, you know, we'll just need more data through, you know, season of RSV to really tell, you know, they're such different patient populations. You know, peds are, they're just three very different patient populations. And so I think we just need more information to know, you know, what we'll pull ahead. With regards to your question about, you know, are we worried about too much enrichment of one patient population or another? Is that what you asked? I mean, for example, we are capping, you know, You know, those older age 65 and asthma at 20%, this will help enrich for the more high-risk COPD and congestive heart failure patients. It won't be just completely filled up with asthmatics, if that is what you're getting at in your question. Is that helpful?
spk02: Yep, that's helpful. Thanks a lot.
spk05: Good. Thank you. Thank you. And I show our next question comes from the line of Jay Olson from Oppenheimer. Please go ahead.
spk09: Oh, hey, congrats on the progress and thanks for taking the questions. At a very high level, how long do you anticipate it will take to get regulatory approval for 235? So are we talking about a couple of years or is it going to be several years? And how will COVID treatment dynamics evolve over that timeframe? And then what are your latest thoughts about a potential partnership for the development and commercialization of 235? And then I had a follow-up question on 514, if I could, please. Thank you.
spk08: Sure. So those are some big questions, actually, the future of the pandemic and, you know, you know, how that'll play out over time is one that's continued to vex the vaccine. Clearly, we're, at least for now, you know, we seem to be getting into an endemic phase. You know, maybe we're at the, you know, the beginning of the end of the pandemic phase, shifting toward endemic, but even that's going to, you know, be probably several years away before it's truly in the endemic phase. I think the trends, you know, in terms of regulatory pathway that's available, I think that's also going to be something that will be, you know, looked at carefully as we progress through development. You know, there's different assumptions depending upon what variants that might emerge. But right now, you know, our focus is on finishing up SPRINT and having data in the first half, moving into a phase three study in the back half of the year, and conducting that as expeditiously as we can. I think, you know, EUA is still an option as far as we are aware, at least in certain patient populations. But, you know, will that be the case, you know, later? You know, you really need to let it play out in terms of the timing of the program, juxtapose the backdrop of the, you know, the environment that's going on. You know, one of the interesting things about the variants is they're changing, you know, all the time. It was not that long ago that we were talking about BA.4 and BA.5. Within the last few weeks, you know, BQ1 and 1.1 have all but taken over. And, you know, mercifully, the, you know, they don't seem to be as lethal as certainly some of the earlier variants, which is good. But, you know, these things can switch all around. You know, we'll just be watching the landscape and that's going to dictate a lot of, you know, how our phase three enrolls and what patient population, what regulatory pathways are available to us at that time. There's still an unmet, huge unmet need for antivirals. You know, the vaccination rates have probably stabilized to a great degree. and there's some vaccination fatigue out there. The antibodies also continue to be losing efficacy and many of them, as you know, have dropped off in terms of being effective so far. And there really aren't that many therapeutics that are, you know, mechanism-based and well understood that are going forward. So this is a really large market opportunity. It's going to be one, you know, pretty much, going forward, and one in which there aren't, you know, I would submit that the, you know, the optimal therapies are not yet approved. We look at 235, it's having a very strong profile in that regard. So that part, I think the need for therapeutics will be very high. Fits in extraordinarily well, too, as you know, with our respiratory portfolio, not just in COVID, but obviously the breath, all the RSV stuff that we just have been talking about this evening, as well as human metanuma. Again, human metanuma is something you're going to continue to hear more and more about as these things are being under the spotlight increasingly. Partnering is still the plan. Again, this is... you know, going after a pandemic virus on a global scale is bigger than we are. And it's our goal to really maximize 235 globally to the greatest patient base we could possibly serve. And in order to achieve that, we will be seeking a global partner in our efforts here.
spk09: Great. Thank you. That's super helpful. And then on 514, can you talk about what sort of mechanisms you plan to combine with 514? And will it be an existing antiviral treatment or something in clinical or preclinical development? And will it be something in your own pipeline or something external? And what are your latest thoughts on seeking a partner for 514?
spk08: Yeah, so the right combination, you know, Hep B is important. it's a slow story to play out in terms of combination therapy. I mean, combination, you know, when we were working on Hep C, you know, combination therapy, even though all combination therapy takes a while, combination therapy was fairly straightforward by comparison. And as much as, you know, the trials were much shorter, you had things that you could measure very quickly. You had profound changes in viral loads and, those seem to correlate with getting to basically a cure. And all of those rules are slightly different in HPV. And so I think we're still at the stage where the right combo is not yet known yet. We know that nukes and core inhibitors do useful things in terms of reducing viral load, not only the DNA, that nukes do well but you can also with the core inhibitor reduce dna and rna so i think we're going to need something that will you know adequately address the s antigen reduction component of this might you need an immune modulator in the mix i mean these are all things that other people are starting to do combinations on and and get data readouts on but it's not You know, it's not perfectly clear yet what that best asset class would be. And so we're being a little bit patient here. We're thinking and doing a little bit internally, and we're looking externally as well. And ultimately, you know, we'll pool the right assets. I hope that we'll be able to do that. you know, at some point to really get back on the triple combination horse that we really want to be on. But in the meantime, you know, the spend on clinical trials, you know, isn't going to happen until we're clear on that.
spk09: Okay. Understood. Is that helpful? That's super helpful. Thanks for all the cover. Appreciate you taking the questions. Thank you, Jay. You're welcome.
spk05: Thank you. As a reminder, to ask a question, you would need to press star 11 on your telephone. And I show our next question. It comes from the line of Roy Buchanan from JMP Securities. Please go ahead.
spk01: Hey, thanks for taking the question. I had a follow-up on the 235 comment around the higher tissue uptake. Jay, you said you're going to have more data on that topic this year. Is that going to be a publication? or a meeting presentation, and then kind of relatedly for 938, any near-term plans to publish the RSVP results?
spk08: So the RSVP results, I'm not sure what the timing is on that, you know, quite perfectly honest. I'm not sure what that timing is. It's an important study to have conducted. It's not the most important thing we're doing right now in terms of execution. The 235 data, though, that I referred to in tissue distribution, as you know, some of it's been out there. And, you know, other abstracts are being written and submitted. So, you know, stay tuned on that front. We will, you know, report once, you know, we've been accepted and announced a confirmed venue for that.
spk01: Okay. But we'll see that data before the end of this year?
spk08: Before the end of 22? Yes.
spk01: That's what I heard you say. No?
spk08: I don't believe I said that. If I did, I didn't mean it. Okay. I didn't mean to say that. Not sure what data you're talking about. Are you talking about 235 tissue uptake data? Yeah. Is that what you... Exactly. No, not this year. Not anymore this year.
spk01: Okay. Fair enough. All right. And then maybe you kind of answered this with the partnering question, but how are you thinking about funding the phase three for 235? Your expense guidance for R&D is going up quite a bit. Are you... Does that bake in... Starting a phase three for two, three, five, possibly start up for RSV phase three.
spk08: Yeah, so the the guidance is our fiscal year guidance that will go out through the quarter ending 930. And so, again, we're aiming to to have, you know, the sprint data in the first calendar half. And so any phase three, I mean, we've been doing preparations for phase three for quite some time. You know, the CMC, drug supply, you know, all the rest, you don't wait until the last minute. So we've been, if you will, incurring certain, you know, phase three related costs uh you know right now um and we would expect those to you know to continue during the uh you know up through the quarter of 9 30 and those are in um included in that but in that uh in that number okay great thank you yep so it's a conservative thing you know and if there were a partnering change then obviously that changes you know bunches of things but uh But anyway, so conservatively, we've modeled it that way.
spk05: Thank you. I'm sure no further questions in the queue. This concludes our Q&A session. At this time, I'd like to turn the conference back over to Jennifer Vieira for closing remarks.
spk12: Thank you, everyone, for joining us today. If you have additional questions, please feel free to contact us by email or call the office. Have a great evening.
spk05: Thank you. This concludes the conference. You may now disconnect.
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