For being here this afternoon. We've got a lot of Atea management here. JP, thank you. Wonderful to see you again. Dr. John, great to have you here in Miami. Before we get into the nitty-gritty, JP, please, why don't you give us the lay of the land as we head into 2024? Sure. What are you excited about? Thank you, John and Umar, for very kind invitation, and the opportunity to share the latest at Atea Pharmaceuticals. 2024 has been a very busy year for us, with great progress in clinical and operational targets that we had with both our clinical programs in COVID and hepatitis C. This put us in a good position to have the opportunity to deliver to shareholder what we believe are really important milestones for early 2024 and during the entire year. As you know, we target viral diseases with multibillion dollars commercial opportunities. We believe that our clinical candidate, our product candidates can really have a significant impact, either with safer, better tolerability, and the lack of drug-drug interaction in COVID. We believe that for our combination of bemnifosbuvir with ruzasvir, we'll have also a new way, in terms of a new standard of care, where you're going to see short-term, eight weeks pangenotypic, and also without protease inhibitor. So protease inhibitor-free, which obviously allow us to decrease tremendously the potential risk for drug-drug interaction as well. So, we are very excited where we stand today, we continue to enroll in the COVID program, our phase III SUNRISE-3. We anticipate next year, we'll have two interim analysis, and then top-line data. Unfortunately, COVID is here to stay, and it's going to stay for a long time. You know that, it is estimated today to be around the $10 billion market. And we don't see it going down in terms of a slower slowing down, or have a lower market. Actually, quite the opposite. And when we see—I've been, as you know, a long time in viral diseases, and I've been shocked to see that you have constant mutations with COVID at the rate that is 2-3x any other endemic RNA viruses, like flu and hepatitis C. So- JP, do you think we're fully endemic with COVID now? Do you think this is a steady state- Yeah. -mutational rate? Yeah, we are fully endemic now, and it's clear that we need new oral therapeutics for the most vulnerable patients, immunosuppressed, elderly. Today, we do not have the standard of care that we believe should lead to the use of millions of patients. So, for HCV, as I said, why do we need another treatment? And we are inside. What's interesting, and you may have seen the New York Times just a few days ago, we still are a long way from eradication in the United States. So what probably we don't know is that this market is about $3.5 billion net sales. But more importantly, when we look at the market, the patient population, we have a tremendous underserved patient population in the United States, even with two options. And this is growing with the opiate crisis, with the injection drug abuse, and reinfection, about 25% of reinfection here. And what we think with our combinations, which will be extremely convenient, very potent, obviously, but pangenotypic, short-term, 8 weeks, we are... Then Arantxa can share, we had quite a bit of interaction with care when I'm prescribed them. And it's a big difference for this kind of underserved patient population, when we're talking eight weeks and 12 weeks. And lastly, especially in these days, we are well-capitalized. We reported $595 million at the end of September, and we definitely have the cash and the runway to go all the way with our clinical programs. Thank you. Now- Excellent. Uh- Excellent. I think you've answered all our questions. Thank you, JP. JP, can I start by asking, I feel like if you had asked the audience at this conference last year, no one would have guessed that Paxlovid would still do 5 million courses this year, which, at the market pricing, still implies at least a $5 billion market in US, and the equivalent of a $7-$8 billion worldwide market. Again, I'm going off of end-user demand, not based on contracting revenues, because those are irrelevant. They go up and down. In that backdrop, what that means to us is- If your phase III makes it over the line, the market is very much existent, and it's one- to two-player type of market. Could you remind us? 'Cause I know folks were paying a lot of attention to Atea three years ago and paying much less attention, right? Could you remind us, what was the initial phase III plan, what changes were made, and what's the new phase III with the interim coming up? 'Cause I feel like let's start there, and we can get more specific on- Sure. We have, our Chief Medical Officer, Arantxa- Yes. We've got with us, and why don't you summarize? Yeah, and this, I ask this because Gilead dropped one of their hospitalizations studies. Yep. Could you just remind us of that? Yep. Mm-hmm. We know. Please, Arantxa. So I think, about a year and a half ago now, we got excellent results from the MORNING SKY trial, which is a trial that basically has the size of a robust phase II, and there we saw a decrease in hospitalization of 70%, in the seventies- This is a Roche phase II you're referring? It was really a phase III trial, but because we stopped the partnership with Roche, that was dissolved, we decided to take a look at the data, and the data came out, and it was quite good, like 70% in the overall population, which included vaccinated patients. And if you look actually at even the higher risk, like patients above 40, we were in the 80s in terms of efficacy in preventing hospitalization in MORNING SKY. Of course, these results came out after the dissolution of the partnership, so they. You know, Roche wasn't aware of these results. So based on that, we designed what we call the SUNRISE- 3 trial, the phase III trial that we have right now ongoing. What's very interesting about this trial is that it's on top of standard of care, which is something that is a requirement from the FDA. So that's globally. It's on top of standard of care, so if the standard of care is nothing, I mean Tylenol, then the patient's basically given monotherapy. And what we are finding is that globally, but also in the United States, there is a lot of patients that don't receive Paxlovid, and this is because they don't qualify because they have drug interactions. A lot of the patients also, you know, don't want to take Paxlovid because of the potential for GI adverse events or the rebound or whatever. For whatever reason, quite a lot of patients are receiving monotherapy with bemnifosbuvir in SUNRISE. And that is a difference because Gilead, in their trial, they were not in the United States in high risk, but we are using this mechanism of doing it on top of standard of care. So far, we have about 50% are enrolled in the United States. Yeah, we got quite a- Wait, wait, I'm sorry. Yeah. There was two very important disclosures. They're all, like, real drivers of the trial. Yeah. Mm. One, you said, you guys are 50% of the patients are in the US? Are enrolled in the U.S. Enrolling, yeah. So far in the trials, 50% have been enrolled in the US. 50% of patients are in the U.S. for your trial, and what did you say about Gilead, conversely? The same trial that you mentioned, they were not in the United States. They were- For the high-risk trial. For the hospitalization trial. With, for the high-risk patients. Exactly, which is equivalent sort of to the trial. Yeah. Okay, that's number one. Okay. The other one is, remind me, you said quite a lot of patients in your trial are not on standard of care, meaning- No, they're on standard of care, but- They're not on Paxlovid. Exactly. Is it fair to say three-fourths of the trial is not on Paxlovid? Right now, I think we have said- Most ... We have said that 90% on the global basis have been enrolled as a monotherapy. Oh, wow! Yeah. 90% of the global- ... 50%. An active arm. Correct. Okay, so that's important. Third thing is, remind me, and I'm getting this confused in my head. You guys never went down the direction of a symptom trial- No ... phase III. No. No. You only want to do hospitalization. Well, that's the challenge. Look, you know, we have to be aware, and we follow what the CDC recommendations are, which is, you know, I don't wish anyone to get COVID and to be sick, but, so far, we have enrolled based on the infection rates on a global basis. We anticipate, based on the CDC, that 50% of the respiratory infection in the U.S. will be COVID with an increased rate of hospitalization for the winter wave, and that's what we are looking. If we do not have a winter wave, if we do not have what the CDC is expecting and is sharing with the population, well, then after, we'll see where we are when- Just to be clear, you're... How far enrolled are you guys right now? Isn't... if the first interim is in 1Q24... The first- Presumably you're over half enrolled at that point. The first interim analysis is after 650 patients, which will occur in the first quarter, and then the second will be at 1,250. And again, as I said a moment with Arantxa, you know, we are following the news, and if we do not have COVID as expected, well, it will be a different situation. If hospitalization rate, if hospitalization rate median expectation is what now? 5%? So you have- No, no, no, no, no. So that's what we have to—we have had an amendment in the summer. Initially, it was between 4% and 6%, and we amended so that we can still have sufficient power with a hospitalization rate of 2%-3%. As long as we have 2%-3% with the target patient number that I just shared with you. And that was coincident with an increase in the loosening of the enrollment criteria. I'm sorry? That was coincident with the loosening of the enrollment criteria. Yeah. Yeah. Yeah, you have to find a balance between- Yeah ... you know, how tight your population is, so you are able to enroll it comfortably, and a population that remains at risk. And the, I think that the criteria that we have right now are doing both, you know, allowing us to enroll the trial while having a high-risk population. 2,500 patients, 2-3 you're aiming for 100 events by the final analysis. Correct. On the first analysis, I think you said it's 650 patients, so- But the first interim analysis is the futility and safety. You've said there, there'll be no look at efficacy in either of the first two intervals? None. It's a futility analysis. Of both? It's so you look at safety, and they look at some of the, events as well, and the- Yeah ... the DSMB decides to continue, and that's what the outcome that we see. But you won't have any visibility on- No, it's a criteria that the DSMB- There'll be no communication. Exactly. And regarding your point, Umar, you were very quick to calculate in your head the number of events. I'm very impressed, but I don't think that we are committing right now to exactly the statistical number of events as a company. Got it. So- So but just to be clear, the second interim also has no efficacy look? It's a futility again, you know? Again. Mm-hmm. I guess, said differently, if you have 30 events at the time of second look, okay, and that's split up as 25 versus 5, if I'm FDA, it could form the basis of early stoppage, no? I'm not going to speculate. So you will look at that? That's all. Is there a- The DSMB. The DSMB will look at it. Yes. The DSMB can do it. Yes. Is there a mechanism for the DSMB stopping the trial early for efficacy? Well, any trial, as you know, can be stopped if the efficacy is so overwhelming that the... as compared to the placebo, that- Okay ... it becomes unethical to continue enrolling. So, yeah. So the First is futility, second is technically futility, but it could potentially have overwhelming efficacy. In any trial, that's the possibility. Mm. Do you have visibility on what the blinded event rate's tracking at right now? No, no, we're completely blinded. So you don't know- No, we don't ... it's 2%, 3%, no? No, impossible. Completely, completely blind. No, we have no idea. JP, why wait on spring or winter COVID season, when there was a pretty intense COVID season? I know half my team was- Well, why? First of all, it's not really seasonal, although, you know, obviously, when you have more people inside, well, you have more risk, right, of being infected if someone has COVID. You know, let's see what the risk is, the next wave after Thanksgiving. Actually, we're talking with Arantxa. So it looked like so far, like last year, first we had the flu, and then after the RSV. First, RSV, then flu- And then COVID. ... and then COVID again. And then COVID. Right. So- So a peak- So we will know where we are. Mm ... where we stand in January, February, March. Got it. That's- I guess, JP, I'm And then I'm sorry, just to interrupt you. Yeah. Just to make sure that we have now almost 250, our target is 300 clinical sites, 30 countries. So you can imagine if there is a wave, we can really catch the wave and move very fast. Got it. That's the whole idea. Now, we've only got a handful of minutes left. Yeah. Oh. I wanna make sure we talk about- Well, nice to be. Go ahead. ... a couple of other programs. Yeah. First, on the novel PI, which you've talked about. Well, look, on the novel PI, you know, I think what the next phase for PI, we have learned that after Tamiflu with Xofluza, right, is you want one pill as a treatment. Mm-hmm. Okay? So if, and again, and that program is very likely dependent on, you know, in term of how we are going to move, and there have been quite a bit of interaction with the FDA and the NIH, is really clinical endpoints. And right now, one of the challenge, as you know, is clinical endpoints. So for us, the PI means new generation, means single dose, single pill, and obviously, no drug-drug interaction and potentially limited drug resistance. Okay. Makes sense. Now, you've talked about providing an update to that program, first half 2024. I think you've given us a little bit of a preview of what we could expect there in terms of what the differentiating features are for a novel PI. On the what? On the novel PI. The novel PI is quite simple. If you were to take a single pill instead of five days, it's quite- Yeah ... it's quite different, right? That would be differentiating. The same thinking as part of a combination, you don't have to deal with any drug-drug interaction as well. So, we are... Look, we are one, we are one mutation away to have no drug at all, as all therapeutics. You have a mutation, the 166 with Paxlovid, that's it. And I'm sure, I don't know, I didn't see the data, but I feel quite confident that all, any other PI are cross-resistant. All right. Well, let's move to HCV- Yeah ... in the last couple of minutes here. It's a very exciting program because we are going to be able to share data in January with the HCV. Excellent. So, I'm sure, as you alluded to in your opening statement, one of investors' top questions is: What's the need here? What's the market opportunity? So for your HCV program, how do you evaluate the space for it to exist, and how do you evaluate the market size? John, do you want to- Sure. So I think from a profile perspective, I think we could be the best in class in terms of combining the best of both worlds for the two products that are out there. You know, obviously, short duration and obviously other characteristics that providers are looking for. But as far as for the market goes, it's just a unusually large market. You're talking a $ multi-billion market at net sales. There are 2 million patients in the United States who have HCV. 75% of the patients who are diagnosed are not treated, and it's just... You know, and if you look at the number of patients that we do cure here in this country, it's roughly 100,000, and we also have roughly 100,000 patients that get hepatitis C in the United States each year. The market is there, and being able to compete effectively in a multi-billion-dollar market with three products, I think is a very good proposition for our company. We have to do something in this country. When you see that Egypt has been able to eradicate almost HCV, when they're the 3%-4% of the population, I'm shocked to have 75% of diagnosed individual not being treated in the United States. And you have seen maybe just a couple of days in the Wall Street Journal in the New York Times, eradication will cost the country $20 billion. We believe that we have with the combination of ruzasvir and bemnifosbuvir, the answer to it, which is a very convenient, short, pangenotypic, protease inhibitor free, and be ready to attack this new phase of eradication. JP, and just as we wrap up- Fair to say then, that you would expect to compete on price as well, relative to the existing products? I think the market price is set right now, and I think you have two players right now that play quite nicely, and the market pricing has stabilized, and for a multi-billion-dollar market, can easily support three products. Got it. Yeah, but just before we wrap up, I was just thinking about something off top. What are the currently communicated timelines for the phase III trial? Have you guys only guided to the 1 Q-2024 first interim, but not much more beyond? Yeah. Look, we are going to start end of the year 2024, and the reason is that, so we are going to share the data in January on the SVR4. We will immediately- Oh, sorry, I was talking about the COVID trial. Huh? I was talking about the COVID trial, sorry. Oh, I'm sorry. I thought that we were talking about HCV. No, no, no, no. Sorry, I was just going back to COVID. Timeline, timeline for the COVID trial, we are talking about the top line mid-year and filing the NDA end of the year, 2024. Okay. I'm just going down this thought chain. Five, we know about 50 million Americans took a COVID vaccine over the last cycle, meaning they're kind of protected fairly well against hospitalizations. We also know... and against even catching it. We also know about 5 million Americans took, Paxlovid, assuming a treatment rate of anywhere between 10% and 20%. That implies maybe another 25-50 million Americans have had COVID, meaning the natural immunity in the population, maybe it's between 75 and 100 million people at least- Mm-hmm ... through next summer. Which makes me wonder, my odds of winter spike are probably low, so the event rate is probably gonna accrue next fall. So, have you guys baked in the scenario where timelines might have to slip into 2025, just given the amount of treatment? Again, it's, yeah, it's reading the crystal ball now, okay? Mm. We will know better where we are end of March, early April, and then we'll let you know about the timelines. Okay. Makes sense. Makes sense. Excellent. Well, thank you so much for joining us. Thank you so much for joining us. Thank you so much for having us. Thank you for hosting us. Excellent. We're still hopeful for the second interim.