Enanta Pharmaceuticals (ENTA) Q1 2022 Earnings Call Transcript

Enanta Pharmaceuticals (ENTA -2.16%)
Q1 2022 Earnings Call
Feb 08, 2022, 4:30 p.m. ET

Contents:

• Prepared Remarks
• Questions and Answers
• Call Participants

Prepared Remarks:

Operator

Good afternoon, and welcome to the Enanta Pharmaceuticals fiscal first quarter 2022 financial results conference call. [Operator instructions]. Please be advised that this call is being recorded. I would now like to turn the call over to Jennifer Viera, investor relations.

Please go ahead.

Jennifer Viera -- Investor Relations

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 Luly, president and chief executive officer; Paul Mellett, our chief financial officer; and other members of Enanta's senior management team.

Before we begin with our formal remarks, we want to remind you that we will be making forward-looking statements, which may include our plans and expectations with respect to our research and development pipeline and financial projections, all of which involve certain assumptions and risks beyond our control that could cause our actual developments and results to differ materially from those statements. A description of these risks is in our most recent Form 10-Q and other periodic reports filed with the SEC. Enanta 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 Luly, president and CEO. Jay?

Jay Luly -- President and Chief Executive Officer

Thank you, Jennifer, and good afternoon, everyone. Enanta 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 impacting broad patient population. I will additionally comment on our ongoing discovery efforts and progress in human metapneumovirus.

Enanta has a successful and proven history of discovering and developing antiviral treatment, as demonstrated by glecaprevir, the HCV protease inhibitor component and MAVYRET, a leading treatment for chronic hepatitis C virus. We have expanded and leveraged this long and deep experience in virology, we 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 N-protein inhibitor, EDP-938, which has fast track designation and is currently in three phase 2 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, EDP-323. 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 immunocompromise, and there are no treatments or vaccines available for the virus, which was first characterized in 1956.

We are excited by the potential of EDP-938, which is a potent inhibitor of the RSV N-protein that has shown robust clinical data in a phase 2a 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-challenged study of EDP-938, 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 the challenged study setting, we conducted the RSVP study to evaluate EDP-938 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 RSP next quarter. Our broad clinical development program includes two key phase 2 studies of EDP-938, evaluating its safety and efficacy in young children and hematopoietic cell transplant recipients with RSV infections. Our clinical trial named RSVP is a phase 2 study in pediatric RSV patients, and the trial RSVTx is a phase 2b 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 this population.

These studies, which were initiated after RSVP, are expected to extend at least end of 2023. We are monitoring RSVP globally and will be providing further updates as the incidents rates evolve. This quarter, we are pleased to announce that we broadened our footprint in RSP by introducing EDP-323, a potent RSV L-inhibitor. EDP-323 targets the RSV L protein, which is a viral polymerase that contains multiple enzyme activities required for RSV replication.

Preclinical data demonstrated 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 stand-alone 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 I study of EDP-323 on the second half of this year. We're 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 range in 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-a-daily oral dosing regimen without the need for a boosting agent, such as ritonavir, all which indicates 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 [Inaudible] 33 nanomole. Importantly, EDP-235 has shown potent antiviral activity in vitro across a range of currently circulating SARS-CoV-2 variants, including omicron and delta giving that pangenotypic potential. Furthermore, EDP-235 has potent activity against other human coronaviruses, enabling the potential for a pan-coronavirus treatment, including possibly coronavirus that may infect human populations in the future.

EDP-235 has also shown excellent exposure after oral administration without ritonavir boosting and favorable distribution into key target tissues, including lung in 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 1 study starting this month, assuming supportive data, we would advance EDP-235 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 lever a functional cure for chronic HBV patients.

EDP-514, our HBV core inhibitor with fast track designation, has been evaluated in two phase 1b studies in different chronic HBV patient population. 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 nuc-suppressed patients. Last year, we presented data demonstrating that EDP-514 has clear clinical evidence of a good safety profile alone and in combination with the nuke and displays significant antiviral activity over 28 days with a pharmacokinetic profile consistently supportive of once-daily dosing orally, putting EDP-514 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 EDP-514 as we believe that a core inhibitor such as EDP-514 will ultimately be an important component of the 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 1 study of our oral 3CL protease inhibitor, EDP-235 this month. If supported by phase 1 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 EDP-938 next quarter.

Finally, we look forward to initiating a phase 1 study for EDP-323, our RSV L-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?

Paul Mellett -- Chief Financial Officer

Thank you, Jay. I'd like to remind everyone that Enanta reports on a September 30 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 MAVYRET sales at a royalty rate for the quarter of 13% and on approximately 30% of the care sales at a royalty rate of 10% after adjustments for certain contractual discounts, rebates, and set-offs, which are now approximately 2.7% of AbbVie's total reported HCV product sales. As a reminder, our royalties are calculated on a calendar year basis.

Therefore, royalties for our fiscal first quarter ending December 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, AbbVie reported their global HCV sales were 1.7 billion in calendar 2021 and guided to 1.87 billion for global HCV sales in calendar year 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 and 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 head count in compensation expense.

Enanta recorded a minor income tax benefit related to the release of the 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. Enanta recorded a larger income tax benefit in 2020 than in 2021 due to the revision in 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 30, 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 $0.41 per diluted common for the course running period in 2020.

Enanta ended of the quarter with 347.7 million in cash and marketable securities. A net expects that as 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?

Questions & Answers:

Operator

Thank you. [Operator instructions]. Our first question come the line of Brian Abrahams of RBC Capital -- I'm sorry, RBC Capital Markets. Your line is open.

Brian Abrahams -- RBC Capital Markets -- Analyst

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, 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 [Inaudible] is boosted by? 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 and engaging what the ultimate opportunity, probability success of drug to be? Thanks so much.

Jay Luly -- President and Chief Executive Officer

Thanks, Brian. Hi. This is Jay. So yes, so the phase 1 in healthy is about to begin, be it 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 in proteus, I would describe it as very early yet. There are a few entrants in the space, but as we -- not only in viral, 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.

And 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 in the longer time frame. Regarding trials, beyond the phase 1 healthy study, of course, we'll be getting into key patient populations, there is standard risk, high risk postexposure prophylaxis, etc., and we would anticipate tapping into all of those opportunities. So thank you.

Brian Abrahams -- RBC Capital Markets -- Analyst

Great. Thanks, and congrats on all the continued progress.

Jay Luly -- President and Chief Executive Officer

You are welcome.

Operator

Thank you. Our next question comes from Eric Joseph of JPMorgan. Your question, please.

Unknown Analyst

Hi. Good afternoon. This is Hannah on for Eric. Thanks for taking the questions.

Just a few from us. So first, I just wanted to get your thoughts on the severity of RSV symptoms and patients and how do they compare this season versus prior season given the lots in seasonal mergence? Just wondering if there's any reason to think we might see more severe symptoms in patients this year. And then also to based on any unblinded look at patient baselines entering the RSVP study, how should we be thinking about medium age entering the study? Are there any prespecified subgroup analyses by age or other risk factors? Thank you.

Jay Luly -- President and Chief Executive Officer

Maybe I'll let Natalie comment on some of these. But again, I don't think there's necessarily anything special about this RSV season versus prior ones. But I'll probably let Nathalie chime in.

Nathalie Adda -- Senior Vice President and Chief Medical Officer

Thank you, Jay. So your question, I think, was about the symptoms of the RSV inflection was worse than before. We -- I mean, obviously, we now don't have access to unblinded data, but we can monitor on going studies. The study that's just completed and we have not observed any horsing in the center, the way the patient is given himself to the clinic as far as we can send.

Unknown Analyst

All right. And so we don't have any data on median age entering the study at this time?

Nathalie Adda -- Senior Vice President and Chief Medical Officer

Sorry. I'm not sure I understood the question. On what age?

Jay Luly -- President and Chief Executive Officer

Median age.

Unknown Analyst

Median age.

Nathalie Adda -- Senior Vice President and Chief Medical Officer

The median age. We haven't looked the database yet that are being 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 we would expect something, I would say -- and if I have to guess, I would say something along the line of the [Inaudible].

Unknown Analyst

OK. And just wondering based on -- or assuming success on RSVP trial, could you describe what next steps would look like toward the pivotal program, specifically how would a program and general adults be prioritized relative to pediatric and transplant population? And would either be trial be gating factors to end of phase 2 discussion to the FDA?

Jay Luly -- President and Chief Executive Officer

So we're going to focus post RSVP on high-risk patient populations. They fall mainly on two, three buckets to peds, transplant, and then other adult populations that are at higher risk. So those will be the basic patient populations that will be targeting two of the three on which we've got ongoing now.

Unknown Analyst

OK. Great. Thanks for taking the question.

Jay Luly -- President and Chief Executive Officer

You are welcome.

Operator

Thank you. Our next question comes from Yasmeen Rahimi of Piper Sandler. Please go ahead.

Yasmeen Rahimi -- Piper Sandler -- Analyst

Hi, team. 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 Enanta 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 then? Are you going to go into the pedes or immunocompromised or would you target all population? So thanks for answering my questions.

Jay Luly -- President and Chief Executive Officer

You are welcome. So yes, the -- now again, the RSVP -- so called RSVP patient population is otherwise healthy adults, which is probably not where the -- it's a great sort of staging trial, and it's a great bridge from our challenge study into other patient populations, adult, and peds. But it's not the main patient population that instead going after the three high risk ones that I had mentioned. It'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 road to approval 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 just see -- we're going out in RSV, I think, in a very significant way. [Inaudible] 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 time frame. And we just -- as you know, we've been working on human respiratory virus along before the pandemic. Because we saw it as a major unmet medical need from a therapeutic standpoint. So when we sized up a situation like that, we usually -- we don't know, doubling down on our strength.

And so I think having an inhibitor like 938 is great, has high barrier. It's very potent. It's once daily dosing. We've already demonstrated strong antiviral effect.

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 L-protein commemorates. There's another very interesting target from a replication perspective. It's exactly how we tuck that in.

Could it be pursued principally as another single agent in, say, it may be a different patient population, perhaps you could think about different ways to position this things if you had multiple of them, or might we put the two of them together in certain patient populations that might be clear advanced in their infection. Otherwise, very hard to treat maybe severely immunocompromised patients that would just struggle with anything, and or might we use it to explore, could we widen the treatment window of any -- versus any single agent alone. We all know that in these infections, viral infections, there was a ticking clock. You have a defined window based on what virus it is and what mechanism you're pursuing.

And whatever that window is for one mechanism by putting two drugs together, hitting it harder earlier, might you be able to -- or hitting it harder, might you be able to postpone treatment a little bit longer before the therapy is administered. And so doing you would obviously be increasing the addressable patient population, which would grow the market opportunity significantly. So it's just various different ways once you have a couple of tools that you could exploit them, and we'll be looking into that as we evolve. But 323 is a very strong looking molecule, very potent, great PK.

Again, we'll have it in the clinic in the second half, and we'll be tracking hopefully, a very successful other pathway using our N protein and EDP-928.

Yasmeen Rahimi -- Piper Sandler -- Analyst

Thank you, Jay. May I ask Paul a question to the remarks you had? So I think a question from lot of investors who are commanding, how do we take the RSVP study and understand translation in the more vulnerable population. So have you been able to provide some clarity how this first study could really derisk RSVP and RSVTx?

Jay Luly -- President and Chief Executive Officer

It's a step-wise derisking. I think actually one of the most significant derisking events for EDP-938 happened in phase 1 healthy when we established that a really potent molecule with a high barrier to resistance could be administered safely and could deliver very nice drug exposures. So that gave us great confidence going into our first RSV infection study, the so-called challenge model, where as you know it performed incredible well. All of that said, that wasn't a virus that had been administered to patients, volunteers under a controlled setting, but it was still real virus and real patient population.

But -- so to demonstrate good viral kinetics and good safety, and that setting was further derisking, now we're taking one step further and doing it with real-world virus or real-world infection, I should say, so that people are catching the stream that's going around, presenting in a very natural way to a treater and then we treat them. So I think it's yet another derisking step along in evolution, rarely 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 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 really putting any viral and it appears to be working in every study that we put it in, it bods well.

Yasmeen Rahimi -- Piper Sandler -- Analyst

Thank you so much.

Jay Luly -- President and Chief Executive Officer

You are welcome.

Operator

Thank you. Our next question comes from Roy Buchanan of JMP Securities. Please go ahead.

Roy Buchanan -- JMP Securities -- Analyst

Great. Thanks for taking the questions. I guess start on EDP-235, it sounds like the next trial is going to be after the phase 1, is going to be treating patients and the second half of the year, maybe a phase 2,3. Just curious if you guys plan to run multiple phase 1s in addition to the one that you're going to start this month? And if so, what those might be?

Jay Luly -- President and Chief Executive Officer

Well, I mean, you're always doing other kinds of ancillary studies along the way in development, such as DDI studies. Is that what you were thinking of, those types of studies?

Roy Buchanan -- JMP Securities -- Analyst

Yes. Anything. Sure.

Jay Luly -- President and Chief Executive Officer

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 2, so you don't want be sowing that down phase 2 or 3, and so -- but there's always other studies that we're doing in parallel in terms of DDI, etc., etc. This will help down the road with special patient population.

Roy Buchanan -- JMP Securities -- Analyst

OK. Great. And then I had one on 514. I guess just curious, maybe if you can just speculate that could be back into the clinic this year? And what about -- I guess, how are you guys thinking about the combos maybe there are some less ideal agents out there that you could partner with just to get more data on the compound? What about running maybe a longer combination trial with just NUCs.

Some KOLs mention to us that might be something worth exploring, anything like that? Thanks.

Jay Luly -- President and Chief Executive Officer

No, those are all good questions. I think to answer your first probably direct question about 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 we're really focused on -- we have 514. We -- it plays well with NUCs.

We've done it on a one-month study with a two -- making up a two-drug combo. We saw a very nice behavior in terms of the two drugs playing well together, good safety profile and the combination. We have observed good antiviral effects, etc., etc. So it's the two drug foundation now is just like waiting for an ideal third ingredient to be added.

And again, we thought we had that one lined up before it turns out, we don't now. And so again, we're looking sort of both internally and externally for what I think will hopefully be a great next combo ingredient. I don't know, I don't really necessarily want to be pursuing the lesser ideal ones. To me, that's maybe not a great use of capital but as it pertains to -- for a longer NUC study, I think, was your other question.

Could you do a core and a NUC 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 overtime, you just have to be patient and have to run those kinds of studies and sort of launch that satellite over and then hope that it reports data back after a significant period of time. So those are interesting studies that maybe should be done in some fashion and some day, but again our principle focus right now is 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.

Roy Buchanan -- JMP Securities -- Analyst

Great. Thanks for taking the questions.

Jay Luly -- President and Chief Executive Officer

You are welcome.

Operator

Thank you. Our next question comes from Zegbeh Jallah of ROTH Capital. Your question, please.

Zegbeh Jallah -- ROTH Capital Partners -- Analyst

Good afternoon. Thanks for taking my question. I think we just have a few. The first one is in the phase 2a RSV study, you had a symptom improvement that was being evaluated as a secondary endpoint, and you did show some impressible document in nasal mucus.

But I think I was just kind of curious about symptom improvement being a primary endpoint for the phase 2b 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?

Jay Luly -- President and Chief Executive Officer

Yes. So good question, Zegbeh. So yes, in the phase 2a study, this is so-called challenge study, we did I think virology was the primary and symptom score was the secondary, and you can look at all kinds of things. But I have to say one of the most curious endpoints I've encountered in my career was mucus way, which you -- which turned out to be actually very interesting endpoint to look at and it actually mirrored other data quite well.

That said, the going as you advance viral loads on later-stage trials will be interesting, but symptom scoring is going to 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. One thing to do the mucus secretion in the challenge study studying because these patients were domicile, they were inpatients. And it's very easy to collect all the clean xs and weigh them. In an outpatient study, that's just not practical, right? So from RSVP onward, that's a tough one.

We got plenty of other symptoms to look at. Yes.

Zegbeh Jallah -- ROTH Capital Partners -- Analyst

And then I'm sure you get this one a lot, but just kind of curious about the five-day treatment period with 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.

Jay Luly -- President and Chief Executive Officer

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 that with RSVP, we think it will substantially mirror the challenge study, that should be -- we think that should be adequate. When you get into the immune compromised setting RSVTx, the hematopoietic cell transplant recipients or how really means suppressed in the first year post transplant. And for these individuals who don't have a confident 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 go longer.

But ultimately, the goal is to try to find a convenient dosing regimen that is adequate and quite effective. And generally speaking, the shorter you can make that, the higher you're going to have compliance and the better the product profile is overall.

Zegbeh Jallah -- ROTH Capital Partners -- Analyst

Got it. I was thinking that, yes, it was probably related to also being cautious of the burden to patients. And then the last one here is just about the combo strategy. So if you want to do a combo with the N and L, do you start with the N-inhibitor and then follow with the L or do you just onboard both of them at the same time? And then I'm just going to squeeze in a question here for Paul regarding MAVYRET revenues.

2021, our revenues came in lower than what AbbVie guided 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 the cadence of revenues beyond 2022? And how that has factored into your projections why I think you set a run rate for the next two years?

Paul Mellett -- Chief Financial Officer

Regarding what happens after 2022, it's really all up to the COVID pandemic situation. You're correct AbbVie as guided 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 with variants, it's gonna 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 AbbVie HCV 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.

Jay Luly -- President and Chief Executive Officer

And to answer your other question, so if we were doing a combination study, we would add the drugs together at the same time.

Zegbeh Jallah -- ROTH Capital Partners -- Analyst

Thanks, guys. And thanks for the clarification, Paul.

Paul Mellett -- Chief Financial Officer

You are welcome.

Operator

Thank you. Our next question comes from Jay Olson of Oppenheimer. Your line is open.

Jay Olson -- Oppenheimer and Company -- Analyst

Thank you for the update, and congrats on the progress. I think there's been some discussion about using Merck's molnupiravir 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 MAVYRET is stabilizing, would that support a level of royalties that could continue to support Enanta's operating expenses for the foreseeable future?

Jay Luly -- President and Chief Executive Officer

Right. 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 years or 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. It is an acute viral infection. We have potent antivirals that appears to be, from what we can see with antiviral drugs going after COVID, the five-day treatment are sort of the norm much like we had already established in our RSV study. So I would say that 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 could be a valuable thing. So we're not just working on protease in-house cure. When the pandemic started, we started multiple different programs, and we're hoping to harvest 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 need at this time to be doing those combination studies. I'm not sure what you'd be trying to establish.

Jay Olson -- Oppenheimer and Company -- Analyst

OK. Thanks for taking the questions.

Operator

Thank you. Our next question comes from Brian Skorney of Baird. Please go ahead.

Luke Herrmann -- Baird -- Analyst

This is Luke Herrmann on for Brian. And thinking about RSV development strategy, from earlier questions, it seems like you're leaning toward 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 the pivotal program to look like? And would you choose to move it forward yourself? Thank you.

Jay Luly -- President and Chief Executive Officer

Yes. So again, I think once you have the data for RSVP, we'll have that information and of course, to have that discussion with the agency, that could inform how the future of the development program looks like on the path to registration. But at this time, we are not currently expecting that those two studies are necessarily registration studies. Is that helpful?

Luke Herrmann -- Baird -- Analyst

Yes. Thank you.

Jay Luly -- President and Chief Executive Officer

I'm sorry, did you have another question?

Luke Herrmann -- Baird -- Analyst

It was just other -- if those weren't registrational, what would pivotal development look like, if you could speculate at all?

Jay Luly -- President and Chief Executive Officer

Yes. I think the FDA -- I mean, I think the FDA and the EMA, 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.

Luke Herrmann -- Baird -- Analyst

All right. Thanks.

Jay Luly -- President and Chief Executive Officer

Sure. You are welcome.

Operator

Thank you. Our next question comes from Roanna Ruiz of SVB Leerink. Your line is open.

Roanna Ruiz -- SVB Leerink Partners -- Analyst

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 against a viral that has ritonavir boosting, maybe possibly due to drug-drug interactions or things like that?

Jay Luly -- President and Chief Executive Officer

Yes. It's hard to get your hands on that exact number now. Maybe that is -- it's more of a Pfizer question. I think the -- but what I will say is there's a very substantial amount of the pharmacopeia 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 the patients 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.

Roanna Ruiz -- SVB Leerink Partners -- Analyst

Yes, makes sense. And then a quick one for your RSV programs. I was curious for the phase 2 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 when are you -- what are you tracking to help you make that kind of decision if you want to apply those additional strategies?

Jay Luly -- President and Chief Executive Officer

Yes. So we're looking at new strategies all the time. The other thing you do is improve your catchment in terms of trial sites, etc., etc. I think it's just a question of how you adapt protocols to make it friendly for not friendly, it's maybe the wrong word, but make it convenient for parents of peds to enhance enrollment, not having extensive barriers or extensive blood draws, other kinds of things that might slow things down a little bit or put people on the fence in terms of coming in and participating in the trial.

I think one of the other things just during the pandemic, the transplant recipients are probably among the most cautious people, right, because they are immune suppressed. They have to be incredibly careful post transplant because of COVID. And so that releases other special challenges during the pandemic, but we're just going to have to -- just like with RSV, we had to -- that was compromised by the pandemic for a while, and we just needed to be ready with sites 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 but just always trying to optimize enrollment in which way we can out jeopardizing the study, of course.

Roanna Ruiz -- SVB Leerink Partners -- Analyst

Yes. That makes sense. Very helpful. Thanks a lot.

Jay Luly -- President and Chief Executive Officer

You are welcome.

Operator

Thank you. [Operator instructions]. Our next question comes from Liisa Bayko of Evercore ISI. Your line is open.

Liisa Bayko -- Evercore ISI -- Analyst

Hi. Thanks for taking my question. Just wanted to get a sense, so you'll have phase 1 data for the COVID program 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 2/3 with your COVID program from wrapping up the phase 1?

Jay Luly -- President and Chief Executive Officer

Yes. So I can't really, I guess, speak to which data would come first. We haven't -- we're going to begin dosing 235 soon, and we'll get into that study and get the various cohorts progressed. So depending upon how many doses we have, etc., etc., like it's safe to say they're probably both Q2, but exactly which ones first, I can't really speak to today.

And then your other question, obviously, we'll be preparing for the steps in phase 2, 3 after the phase 1 is to get into that as quickly as we can, making sure drug supply and sites, etc., etc., lined up. And so we'll be doing it as quickly as possible starting in the second half. So stay tuned on that front.

Liisa Bayko -- Evercore ISI -- Analyst

OK. 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 guiding 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 of things have probably wrapped up from the fourth quarter, maybe are wrapping up in the first quarter. But given that year-end. So what do we think about that?

Jay Luly -- President and Chief Executive Officer

Sure. No, there's wind down costs and so forth associated with some of the NASH studies, etc., etc., that won't be obviously carried through the rest of the year. We're -- but I think the plan is still intact and encompasses what we're aiming to do with these various programs.

Liisa Bayko -- Evercore ISI -- Analyst

OK. 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 virus out there, and it just came to my attention because you talked about the strains going around right now. How similar or divergent constraints be for RSV from -- and compared to what you looked at in the challenge study? Because as I recall yours was one of the more, it seems like, I don't know if the right word is Verlinde or whatever, but you had one of the higher viral loads as I was kind of looking across other challenge studies, it looked like you had a pretty serious virus that you were using in the challenge study.

Jay Luly -- President and Chief Executive Officer

Yes. No, I think it's a standard -- Yes. No, sorry to interrupt, Liisa. But I think it's a standard virus that has been used, some different 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 check people twice a day by RT-PCR, waited for the viral loads to start to climb up and waited until they got up to about three logs as I recall, and then we started dosing.

So obviously, if you dose sooner than that, you'll be dosing with a lower viral load. So that's probably the variable there. I think ultimately, it's a real virus, but you do need to ultimately get out into the real world where you're going to run into different slightly different strains. You might have RSV-A, you might have RSV-B, it might be various subtypes along the way.

But this is why we did a lot of work on clinical isolates before embarking on the study. We weren't using just lab streams of things, etc., etc. We've had geographically dispersed by virus samples from different patients and different seasons, etc., and we tested our drug against them and the drug performed uniformly very well against the clinical aspects. 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 derisking prior to doing this.

Liisa Bayko -- Evercore ISI -- Analyst

OK. 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 where 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, at three logs of viral loads. So what that relates to kind of the onset of symptoms and that kind of stuff?

Jay Luly -- President and Chief Executive Officer

Well, if you -- when we've got these slides in our corporate deck on our website, it's probably what you're looking at. But 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 a challenge study, at 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 RSV, 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 a factor as 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. You have -- 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 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 will ultimately be sorting out in various studies. But just for the very specific RSVP trial, we did put that 48-hour to the street on there just 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.

Liisa Bayko -- Evercore ISI -- Analyst

OK. Thank you.

Operator

Thank you. At this time, I'd like to turn the call back over to Jennifer Viera for any closing remarks. Ma'am?

Jennifer Viera -- Investor Relations

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 much. Have a good night.

Bye-bye.

Operator

[Operator signoff]

Duration: 65 minutes

Call participants:

Jennifer Viera -- Investor Relations

Jay Luly -- President and Chief Executive Officer

Paul Mellett -- Chief Financial Officer

Brian Abrahams -- RBC Capital Markets -- Analyst

Unknown Analyst

Nathalie Adda -- Senior Vice President and Chief Medical Officer

Yasmeen Rahimi -- Piper Sandler -- Analyst

Roy Buchanan -- JMP Securities -- Analyst

Zegbeh Jallah -- ROTH Capital Partners -- Analyst

Jay Olson -- Oppenheimer and Company -- Analyst

Luke Herrmann -- Baird -- Analyst

Roanna Ruiz -- SVB Leerink Partners -- Analyst

Liisa Bayko -- Evercore ISI -- Analyst

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