Atea Pharmaceuticals Inc (AVIR) 2023 Q1 法說會逐字稿

Good afternoon, ladies and gentlemen. Welcome to the Atea Pharmaceuticals First Quarter 2023 Financial Results and Business Update Conference Call. (Operator Instructions)

I would now like to turn the call over to Jonae Barnes, Senior Vice President of Investor Relations and Corporate Communications at Atea Pharmaceuticals. Ms. Barnes, please proceed.

Thank you, operator. Good afternoon, everyone, and welcome to Atea Pharmaceuticals First Quarter 2023 Financial Results and Business Update Conference Call. Earlier today, we issued a press release, which outlines the topics we plan to discuss. You can access the press release as well as the slides that we'll be reviewing today by going to the Investors section of our website at ir.ateapharma.com.

With me today from Atea are Chief Executive Officer and Founder Dr. Jean-Pierre Sommadossi; Chief Development Officer, Dr. Janet Hammond; Chief Medical Officer, Dr. Arantxa Horga; Chief Financial Officer & Executive Vice President of Legal, Andrea Corcoran; and our Chief Commercial Officer, John Vavricka. They will all be available for the Q&A portion of today's call.

Before we begin the call, and as outlined on Slide 2, I would like to remind you that today's discussion will contain forward-looking statements that involve risks and uncertainties. These risks and uncertainties are outlined in today's press release and in the company's recent filings with the Securities and Exchange Commission, which we encourage you to read. Our actual results may differ materially from what is discussed on today's call.

With that, I'll now turn the call over to Jean-Pierre.

Thank you, Jonae. Good afternoon, everyone, and thank you for joining us. As you will see on Slide 3, we have had a busy start of the year with progress across our COVID-19 and HCV program. I will begin with a few highlights from our COVID-19 program.

First, we remain laser-focused on the execution on our global SUNRISE-3 study, where I am pleased to report that as of today, we have a broad geographic footprint with regulatory approvals in over 50% of the targeted countries.

Just last month, we were excited to receive from the U.S. FDA a Fast Track designation for bemnifosbuvir for treatment of COVID-19, which has the potential to expedite the development of bemnifosbuvir.

We presented multiple data sets at scientific meetings, including CROI, ICAR and ECCMID, each of which highlighted bemnifosbuvir's clinical efficacy and favorable safety profile, including a compelling drug interaction profile. Finally, we continue to make progress advancing our second-generation protease inhibitors.

Turning to HCV. We remain on target for the first patient to be dosed in our Phase 2 combination trial this quarter, and we continue to expect initial results from our first cohort of 60 patients by year-end. Data recently presented at ICAR support our combination profile and new in vitro results indicate a highly compelling antiviral profile compared to the current standard of care.

Moving to Slide 4. As I mentioned, we have a large presence at the major antiviral medical meetings during the first quarter. Some of the key highlights of our COVID program include the full results in the MORNINGSKY trial, we presented showing a 71% reduction in risk of hospitalization with bemnifosbuvir as compared to placebo in the MORNINGSKY trial with a subset showing 82% reduction in risk in patients over 40 years old. Low risk of drug-drug interaction with commonly prescribed medicine for COVID-19 in HCV, which we believe is a key feature of the drug.

Slide 5, outlines the data presented at medical meetings beyond our COVID-19 program. At ICAR, we presented HCV combination data showing the bemnifosbuvir and ruzasvir are potent in vitro synergistic antiviral activity and in vivo preclinical safety without adverse interactions In addition, we presented data at ECCMID 2023 on the AT-752 for dengue. While, as you know, we deprioritized our dengue program and the development of AT-752 in February 2023, we are exploring opportunistic ways to continue to move this program forward.

Moving now to Slide 6. AT-511, the free base of bemnifosbuvir has been shown to be a potent inhibitor of SARS-CoV-2 in vitro. New results demonstrated AT-511 also as potent antiviral activity against the SARS-CoV-2 Omicron sub variant XBB. This is consistent with the previously demonstrated in vitro potent antiviral activity against other variants of concern and of interest, including Alpha, Beta, Gamma, Epsilon, Delta and various Omicron sub variants BA.1, BA.2, BA.4 and BA.5 and now the XBB.

I will now turn the call over to Janet.

Thank you. Turning to Slide 8. The COVID market dynamics continue to shift and the U.S. COVID-19 public health emergency expect to expire this week. Last Friday, the World Health Organization declared the end to the global health emergency. They also went on to say that COVID as a virus is here to stay, which is highlighted by the fact that globally, nearly 2.8 million new cases and over 17,000 deaths were reported in the last 28 days. Once that remains, there is still a large unmet medical need for the treatment of COVID-19.

We're experiencing waning immunity with both vaccines and natural infection exacerbated by the low booster uptick with only approximately 17% of the U.S. population having received the booster. And in some patient populations, there is also a failure to mount any immune response to vaccines.

Moreover, the limitations with currently available oral antiviral are considerable due to safety concerns and drug-drug interactions with commonly prescribed medications such as seizure medications, antipsychotics, anticoagulants and more. This significantly limits the use of these drugs in high-risk elderly and immunocompromised patients who are the most vulnerable and most likely to have the most severe cases of COVID. As a result of this remaining unmet medical need, an emergency use authorization is still available if certain criteria for issuance are met.

Turning to Slide 9. As Jean-Pierre mentioned earlier, we are seeing strong operational execution from our clinical team. The global SUNRISE-3 geographical footprint now has regulatory approvals in over 50% of the targeted countries and patient enrollment continues.

COVID-19 continues to evolve with new variants and ways, such as what we are experiencing with the Omicron subvariant XBB 1.16, the Arcturus variant, where we've shown, again, good in vitro potency with bemnifosbuvir. Our goal is to enroll patients from circulating waves by being well positioned with our extensive global footprint as new variants and waves of infection emerge.

SUNRISE-3 is focusing on high-risk patients that are at the greatest risk for disease progression to severe COVID-19, leading to hospitalization or mortality. Its primary endpoint is all-cause hospitalization or death through day 29 in at least 1,300 patients from the monotherapy cohort.

I'll now hand the call back to Jean-Pierre to review our HCV program.

Thank you, Janet. Moving now to our Hepatitis C program of a fixed dose combination of bemnifosbuvir and ruzasvir. We believe that our combination has the potential to improve upon the current standard of care by offering a protease-inhibitor free shorter-duration option for HCV patients with and without cirrhosis. Bemnifosbuvir is a highly potent pan-genotypic with demonstrated clinical antiviral activity. In addition, ruzasvir, a potent NS5A inhibitor has shown broad genotypic in vitro antiviral activity with EC50 lower than 10 picomolar against all genotypes with demonstrated clinical antiviral activity.

Naturally occurring NS5A resistant variants have emerged and can impact the effectiveness of currently available HCV treatments. We recently profiled the antiviral activity of both bemnifosbuvir and ruzasvir against a panel of previous NS5A resistant associated variants selected in vitro or identifying HCV patients who have fair treatment with the current standard of care. We are pleased to share this data with you now, supporting that we have the potential for a best-in-class regimen.

As outlined on Slide 11, recent data shows that bemnifosbuvir retained high potency in vitro, being at least 10x more potent than sofosbuvir against all HCV genotype 1a and genotype 3a, NS5A resistance associated variants that we call RAVs.

In addition, as you will see on Slide 12, ruzasvir is also a potent NS5A inhibitor. In the [Replicon] side, ruzasvir has demonstrated a more favorable in vitro potency profile as compared to velpatasvir and similar antiviral activity to pibrentasvir, which is the most potent NS5A inhibitor currently approved.

In fact, and as outlined on Slide 13, in the same transient replicon assay ruzasvir was shown to be 5 to 10-fold more potent than velpatasvir against RAV HCV genotype 1a and the difficult-to-treat genotype, genotype 3a.

Turning to Slide 14. In summary, the combination of bemnifosbuvir and ruzasvir is very important and has the potential to be the best-in-class regimen based on its Pan-genotypic antiviral potency, low risk for drug-drug interaction, absence of food effect and potential for short treatment duration. Indeed, we are targeting 8 weeks of therapy with the potential for even a shorter duration. This profile, along with the totality of the preclinical data give us greater confidence in the potential of this combination to become the new standard of care.

As you will see on Slide 15, newly diagnosed HCV cases in the U.S. increased 400% between 2010 and 2020. And as just mentioned, this is an area where we believe that bemnifosbuvir and ruzasvir combination can be especially effective given its potential for short treatment duration with a highly compelling profile. According to the WHO, 58 million people globally have chronic HCV infection, and there are approximately 1.5 million new infections occurring every year.

We lose nearly 300,000 people to HCV-related liver disease each year. And this has become such a problem, even in the U.S. that the U.S. government has recently proposed an HCV program with the goal to eliminate HCV. This is important because it recognizes this resurgence and acknowledges the need for new effective treatment options.

On Slide 16, we outlined our Phase 2 open-label study of bemnifosbuvir and ruzasvir in HCV patients. This study will enroll approximately 280 HCV-infected direct-acting antiviral naive patients across all genotypes, including a leading cohort of approximately 60 patients. Patients who will be administered 550-milligram bemnifosbuvir in combination with 180 milligram ruzasvir once daily for 8 weeks.

The primary endpoint of the study is safety and sustained biological response as we are at week 12 post-treatment. Other biologic endpoints include Virologic failure, SVR24 post-treatment and resistance. Regulatory submissions for the initiation of this global trial are ongoing and dosing of patients in this clinical trial is expected to begin this quarter. Initial data from the leading cohort of approximately 60 patients is anticipated around the end of the year.

With that, I will now turn the call over to our CFO, Andrea Corcoran to review our financial update.

Thank you, Jean-Pierre. As Janet mentioned in her introductory remarks, earlier today, we issued a press release containing our financial results for the first quarter of 2023. The statement of operations and balance sheet can be found on Slides 18 and 19. For the first quarter of 2023, each of R&D and G&A expenses remained relatively consistent with the first quarter of 2022. As we further our clinical development of both our COVID-19 and HCV clinical programs in 2023, we do anticipate that R&D expenses will increase in a measured way as these programs advance.

We are exercising focused financial discipline and manage spend as we invest in these programs. At the end of the first quarter of 2023, our cash, cash equivalent and marketable security balance was $620.5 million. Based on our current plans, we are reiterating our cash guidance with a runway into 2026.

I'll now turn the call back over to Jean-Pierre for closing remarks.

In -- thank you, Andrea. In conclusion, we have already made a notable clinical and operational progress across our COVID-19 and HCV program so far this year. We also presented significant, scientific and clinical evidence in support of the potential of our clinical programs among an audience of a leading virologists and infectious disease specialists at several scientific conferences.

We believe that this data continues to validate our approach and will enhance our development efforts as we advance our global clinical trials. We look forward to reporting our continued progress throughout the year. As always, we thank you for your continued interest and support of Atea as together, we strive to address the unmet medical needs of patients with serious viral infections.

With that, operator, we will now open the call up to your questions.

(Operator Instructions) Our first question comes from Eric Joseph with JPMorgan.

It's Billy on for Eric. We just had one question. We recently heard from Pfizer about -- that antiviral which doesn't need return of variants, just wondering what are your thoughts on this in terms of the competitive landscape?

Well, we have not seen any data at a scientific conference. We -- as everyone got only a feedback from the earnings call. So it's clear that -- it looks quite interesting, but it's clear that we will need a lot more data to address really the potency, the safety and what we expect with this new generation.

Our next question comes from Maxwell Skor with Morgan Stanley.

Are you -- I just want to ask, are you on track to report interim analysis from the SUNRISE-3 study in the second half of '23? And also, I believe you stated on a prior call that you've not committed to reporting on the primary and secondary endpoints for this trial. But could you give any additional details regarding what we can expect after the interim?

Janet, do you want to address the question?

Yes. So with regards to whether we're still on track, I think our guidance has not changed. And then with regard to the interim analysis, it will provide us the opportunity to re-estimate the sample size and increase our population if that is being necessary in order to achieve the primary endpoint. And the primary endpoint is the all post-hospitalization and mortality in the patient population. And currently, for the statistical analysis, we're projecting that ultimately we'll need 1,300 patients in the standard care monotherapy arm.

And the remainder of the patients of the 1,500 would be incorporated into the combination with a current total estimate of 1,500 patients. But the primary endpoint is really just for the monotherapy patients. And at the present time, that is the anticipated population we would need. But that's what the interim analysis is designed to help us with, just to be sure that we upsize the study as necessary depending on hospitalization.

Our next question comes from the line of Jon Miller with Evercore ISI.

Two quick ones from me. One, obviously, the state of emergency is scheduled to lapse, but you seem very confident that EUAs will still be available. Can you talk a little bit more about how the regulatory environment and how EUAs will be around if there isn't a state of emergency to support those?

And then secondly, on that interim data analysis from SUNRISE and the sizing of the primary endpoint, how will the high likely percent of seropositive patients at baseline impact placebo rate of hospitalization?

Obviously, we just saw this afternoon another company stumble on efficacy for their COVID treatment because placebo patients did better than expected due to baseline seropositivity. So I'm wondering where you're getting your estimate of baseline of placebo arm hospitalization rates and weather in a higher number of seropositive patients at baseline might impact those estimates?

Janet, maybe you want to start with the second question first, and then we'll go to the first one. Go ahead, Janet.

It's an interesting question. I think that where we are is that -- obviously, we're going to have to see what the overall hospitalization rate is. And our -- and this is -- one of the points for the interim analysis is to determine what the hospitalization rate is and whether we need to upsize the study in order to have a sufficient greater hospitalization, not unblinding that but just understanding what that hospitalization rate is. And so that's the idea behind the adaptive design.

I think with regard to seropositivity, it's an interesting but I think a moving target in that we know that for the most part, almost everybody has seen COVID at this time and that what is likely to be seropositive. We believe that in the more vulnerable patient population that antibody effectiveness probably wanes over time more quickly than for others.

And I think there have been some interesting articles actually in the last week or 2, again, looking at the efficacy of the Omicron booster and that sort of thing, and we're again, I think demonstrating that there is very rapid waning immunity to the vaccine as well as to natural infection. And I think as the virus continues to evolve with new strains coming through, it's likely that, that immune evasion is likely to continue, but it's impossible, obviously, to predict with any certainty what the hospitalization rate is likely to be as a result.

And that's really the basis for why we have designed the study in that way, I think, firstly, from the point of the population, which is the most vulnerable to hospitalization. So I think it's likely to be higher in that patient population. And then secondly, so that we can adapt the study numbers if necessary to accommodate a lower hospitalization rate.

On the first question, as we have already indicated, we're not targeting an NDA. And if the data EUAs -- the data will be sufficient for an EUA, that would be wonderful. But let's not forget that what we're targeting is the NDA as we have indicated also that the FDA had indicating writing that this trial SUNRISE-3 will be sufficient for an NDA filing. Janet, do you want to add anything?

No, I think you've covered it well.

Our next question comes from the line of Tim Lugo with William Blair.

Maybe I'll switch to HCV. Jean, you mentioned the ability to reduce days of dosing for bemnifosbuvir. What kind of dosing regimen do you think you can achieve? Is the ongoing Phase 2 going to inform that?

Look, that's a great question, Tim. We will have a better view with the clinical data on the leading court. We have a collaboration with Alan Paulson, as you know, who is the guru on viral kinetics and that will -- the analysis of those viral kinetics will really help us in determining how short we can go in terms of treatment duration.

But you should do that at the end of this Phase 2?

Yes. Basically, what we'll do is -- we obviously feel that we have a very good profile with 8 weeks, protease free better than the standard of care, as you know the current standard of care with Epclusa, great safety. Especially you see the difference when we are talking now with the NS5A variance, the field, as I'm sure you look in the publication it's very different now than 6 or 7 years ago when those NS5A variant were not as extensive as they are today. And we believe that this is going to play a major role in the differentiation of our combination, a lot more potent against any of those variants as compared to Epclusa, for example. So -- and we'll see, as soon as we have the viral kinetics out even shorter we can go than 8 weeks.

(Operator Instructions) Our next question comes from Roanna Ruiz with SVB Securities.

This is Rosa Chen on for Roanna Ruiz. A couple from us on bemnifosbuvir for COVID. So congrats on getting Fast Track designation for bemnifosbuvir. First, we understand its implications for potential NDA, but does the Fast Track designation provide advantages for potential EUA submission?

And secondly, what proportion of the monotherapy population in SUNRISE-3 do you expect will be coming from the U.S.? And is that representative of the full enrollment? So interim and full?

Janet?

So I think that the Fast Track designation ought to allow us to have a close and collaborative data exchange and discussion with FDA as we proceed with the clinical trial and our submission. So I think there's a possibility that it will allow things to go more rapidly than otherwise. And certainly, I think, obviously, familiarity with the data might help in FDA's determination of whether the data are worthy of an emergency use authorization. But that's obviously some time down the road, and we'll have to see, and it's obviously at FDA's discretion.

And then with regard to the proportion of patients receiving monotherapy in the U.S. and in comparison to elsewhere, I think it's early days to comment on what that's going to look like. But certainly, I think the population that we're studying in our trial is a population that is particularly vulnerable to COVID. And I think for that reason, interestingly, often ineligible for the currently available treatments within the U.S. and elsewhere. And so we continue to see a good representation of patients requiring monotherapy, both here and abroad.

That concludes today's question-and-answer session. I'd like to turn the call back to Jean-Pierre Sommadossi for closing remarks.

Thank you again for joining us today.

This concludes today's conference call. Thank you for participating. You may now disconnect.