There is our forward-looking statement, and further information can be found in our most recent regulatory filing. We are very pleased to have the following KOL expert with us today: Dr. Jordan Feld from the University of Toronto, Toronto General Hospital in Canada, Dr. Eric Lawitz from the Texas Liver Institute, the University of Texas Health San Antonio, Dr. Anthony Martinez from the University of Buffalo in Erie County Medical Center, and Nancy Rowe from Rush University Medical Center in Chicago. Also with us today from Atea: John Vavricka, our Chief Commercial Officer, who will review the HCV commercial market opportunity. Dr. Janet Hammond, our Chief Development Officer, Dr. Arantxa Horga, our Chief Medical Officer, who will review the profile of our regimen and the ongoing phase III program. Janet and Arantxa will also moderate the fireside chat with our distinguished panel.
At the end of today's event, there will be a Q&A session. Now let's initiate the meeting with Janet and Arantxa. Janet?
Thank you, JP. Good morning, everyone. On slide five, let's now turn to our global phase III program, which is the first head-to-head phase III program for chronic hepatitis C, comparing our regimen with the current global standard of care: sofosbuvir and velpatasvir, which is marketed as Epclusa. Our regimen includes bemnifosbuvir, the most potent nucleotide inhibitor, and ruzasvir, a highly potent NS5A inhibitor. Data support from our regimen as a potential best-in-class treatment option for patients infected with hepatitis C, with a differentiated profile featuring a short duration of treatment, a low risk for drug-drug interactions, and convenience with no food effect. I'd like to highlight that we have a new study result demonstrating no risk of drug-drug interactions with proton pump inhibitors, which are estimated to be taken by at least 35% of patients with hepatitis C. These results will be presented at an upcoming scientific meeting.
We view this as a key differentiator since proton pump inhibitors can substantially decrease the effectiveness of current approved DAA therapies for hepatitis C. Our phase III program is designed to confirm the efficacy, safety, and tolerability demonstrated in our robust phase II study, where we achieved a 98% sustained virologic response at 12 weeks post-treatment, or SVR12. These phase II results gave us confidence to move to our current phase III stage program. Slide six. I'm pleased to share with you that a few days ago we presented multiple data sets at the liver meeting. These data sets further demonstrate the antiviral potency with our short treatment duration of our regimen for hepatitis C. In an oral presentation, multi-scale modeling results predicted that our combination regimen inhibits both intracellular replication of hepatitis C as well as viral assembly and secretion of new hepatitis C variants into the bloodstream.
The model predicted a cure time of approximately seven to eight weeks. Because the regimen suppresses the virus at multiple critical stages, the data reinforced the potential of the combination regimen as a potent, short-duration therapy for chronic hepatitis C. We also presented two posters. The first poster was identified as a poster of distinction, and it highlighted a resistance analysis from the phase II study of our regimen, demonstrating that SVR12 rates were not impacted by NS5A-resistant variants at baseline. Viral kinetics and pharmacokinetic analyses indicated that most of the viral failures were due to treatment non-adherence and not to viral resistance. The second poster reviewed the results from a phase I study in healthy participants, which demonstrated the high relative bioviability of bemnifosbuvir and ruzasvir commercial formulation for the fixed-dose combination.
These data also support dosing of the fixed-dose combination with or without food and with famotidine, an H2 blocker, which can substantially diminish the effectiveness of oral antivirals. The fixed-dose combination commercial formulation is being used in the ongoing phase III program. Slide seven. As mentioned, bemnifosbuvir is a nucleotide NS5B polymerase inhibitor with an established mechanism of action of inhibiting hepatitis C RNA through chain termination, thus blocking viral production and replication inside the cell. Our collaborators at Los Alamos National Laboratories have conducted hepatitis C viral kinetic modeling using data from the phase I bemnifosbuvir monotherapy trial. The new modeling suggested that bemnifosbuvir might have an additional mechanism of action inhibiting hepatitis C viral assembly or secretion and the secretion of new hepatitis C variants into the bloodstream, significantly reducing extracellular hepatitis C RNA, a mechanism previously only associated with NS5A inhibitors such as ruzasvir and velpatasvir.
New in vitro results confirmed that extracellular hepatitis C viral RNA levels were comparable with exposure of bemnifosbuvir or velpatasvir, demonstrating that bemnifosbuvir also inhibits hepatitis C viral secretion and assembly, in addition to inhibiting viral replication. Slide nine. Slide eight. I think this graphic on the slide visually illustrates on the left side the hepatitis C viral life cycle, and then to the right, the dual mechanism of action of bemnifosbuvir, showing how bemnifosbuvir blocks the virus from making copies inside the cell, and it also blocks new virus from entering the bloodstream. In conclusion, on slide nine, these new data demonstrate that bemnifosbuvir is a potent and differentiated nucleotide product with a unique dual mechanism of action, which may explain the high potency of bemnifosbuvir as compared to sofosbuvir in vitro.
Importantly, even in the presence of NS5A resistance, bemnifosbuvir would continue to block viral assembly and secretion due to its dual mechanism of action. Lastly, these new results further highlight the differentiation and the potency of the bemnifosbuvir and ruzasvir regimen for the treatment of hepatitis C. I'll now hand the call over to Dr. Arantxa Horga, who will review the phase III program. Arantxa?
Good morning, everyone. Moving to slide 11, the global phase III program is composed of two pivotal trials: CBEYOND, which is enrolling across approximately 120 sites in the U.S. and Canada, and CFORG, which includes another 120 sites across 16 countries outside of North America. Combined, these studies are expected to enroll approximately 1,760 patients. Both trials are open label and randomized one-to-one against the active comparator, and they are stratified by cirrhosis status and genotype, including HIV co-infected patients. In non-cirrhotic patients, treatment duration is eight weeks compared to 12 weeks with the standard of care. For patients with compensated cirrhosis, patients receive 12 weeks of either regimen. The primary endpoint for both studies is SVR12, which is recognized as the definitive measure of HCV cure. Excuse me. Slide 12.
I am pleased to confirm that enrollment in the North America CBEYOND trial is on track for completion next month, with top-line results anticipated mid-2026. For CFORG, which has a broader global geographic footprint, enrollment completion is expected mid-2026, followed by top-line results by year-end 2026. I would like now to hand the meeting over to John Vavricka, our Chief Commercial Officer. John?
Good morning, everyone. On slide 14, following the phase II clinical results, we conducted a quantitative market research study of high US DAA prescribers. IQVIA selected the study participants and conducted the market research. 153 top US DAA prescribers reviewed the BEM-RZR profile, including the phase II results, on their own prior to assessing their likelihood of prescribing. The study revealed high preference for BEM-RZR, with 76% extremely likely to prescribe our regimen. When asked about the percentage of the patients they would likely prescribe BEM-RZR to, the study showed that BEM-RZR would be used in approximately half their patients. The results were similar for both non-cirrhotic and compensated cirrhotic patients. Moving on to slide 15, I'd like to highlight that these latest quantitative market research results conducted following the BEM-RZR phase II results are consistent with the previous quantitative market research conducted over the past two years.
The three market research studies consistently show significant preference for BEM-RZR with high US DAA prescribers. Now let's move on to the KOL panel discussion that will be moderated by Janet Hammond and Arantxa Horga.
Thanks, John. Thank you, and again, welcome to our panelists. We're delighted to have you with us today. Just coming off the heels of the AASLD meeting, and I think also a number of other events this year which have been highlighting the epidemiology of hepatitis C and the crisis that we face in terms of this epidemic and our failure to eradicate it. I thought it would be useful to start perhaps off with you, Jordan, talking a little bit about the epidemiology and the current HCV patient population. Perhaps starting off with how you see the patient population to have evolved since direct-acting antivirals really became mainstream about 10 years ago. What about their age? Are they the same? Comorbidities, risk factors, et cetera. What are you seeing in terms of these patients? Why do you think this continues to be such a problem for them?
Thanks, Janet. It's nice to be here this morning. I think things have changed a lot over the last number of years. When we started treating, we were primarily treating baby boomers, middle-aged folks, many of whom had already been diagnosed, many of whom already had advanced liver disease. Fortunately, we were able to cure those with the available regimens over time. Most of those people, fortunately, now have either been cured of their infection.
It has really changed quite dramatically in the last number of years, but also somewhat disconcertingly, when you look at the latest numbers from the CDC, we see that actually the number of people living with chronic hepatitis C in the U.S. has not diminished significantly over the period of time that we've had DAAs, which is quite remarkable when you think about how effective these therapies are, that we're continuing to see new infections almost keep pace with cures, which really is a major challenge for us. This reflects the ongoing opioid epidemic that we've seen throughout North America. This has really shifted the population in pretty dramatic ways. We are seeing younger people infected, reflecting the epidemiology of those who use and inject drugs. This means a number of things. One is it means that the population has many challenges that are not liver-related.
Unlike seeing patients with advanced liver disease, we're now seeing people with complicated lives related to injection drug use and many of the social determinants of health, poverty, and other challenges. We're also seeing very few with cirrhosis. The typical people we see now being diagnosed with hepatitis C are younger people without advanced liver disease, often with many significant social rather than medical comorbidities. This means that we've had to shift our practice and figure out models of care that work well for these populations. The key there is really focusing on very simplified regimens that can be taken by these populations that may have a lot going on in their lives, but also recognizing that, fortunately, advanced liver disease has become less of an issue.
That is why much of the treatment has moved, particularly out of hepatology practice and more into infectious disease, addiction specialists, and even primary care.
I could go on, but I think I don't know whether others want to join in there and talk about this at all or whether we should move on. Arantxa, would you like to perhaps follow on to the next question? I don't know.
Yes, I think maybe we can move on to the next question, which is related to innovations in screening and diagnosis, really with a focus on the test and treat strategy. I am going to direct this question to Dr. Anthony Martinez. For example, we looked at the recent meeting with the CDC, and they emphasized the importance of same-day diagnosis and treatment. Dr. Martinez, from your perspective, what is still needed to achieve that goal of same-day test and treat as standard of care?
Yeah, we've moved very close to that to achieve that right now. In some spots in the United States, my clinic being one of them, we've actually reached that point where we're utilizing newly FDA-approved point-of-care testing machines. We've had these machines now for about a year and a half where we can deliver a diagnosis in under an hour. The next step there is obviously to have rapid access to medications, ideally providing the full supply of those medications. To deploy a test and treat model, you need a couple of key things. You need a medication regimen that's simple, that's fast, obviously efficacious and safe, and that has minimal drug-drug interactions. You want to take as many things off the table as you can so that it can literally get down to poking a patient's finger, getting a result, and then giving the course of medication.
I think that anything that can minimize some of these drug-drug interactions, Jordan highlighted exactly what we're seeing in the U.S. It's a younger patient population. We know that under age 45, almost 98% of these patients do not have advanced fibrosis. That even raises the question, do you even need some of these additional labs? You probably don't. With the point-of-care testing, I think that if we have a regimen that can deliver a high SVR rate, that eliminates a lot of these drug-drug interactions, because even though these patients are young, they're on multiple concomitant medications, but these tend to be in the psychiatric disciplines. They're on mood stabilizers or antidepressants, anti-anxiolytics. They still are on multiple medications. Any regimen that can eliminate those potential drug-drug interactions becomes important.
I think this is uniquely suited to get us even closer to a true test and treat model of care.
Thank you, Dr. Martinez. We have a question related to this somehow. Do you differentiate in that context of test and treat, do you differentiate acute versus chronic patients?
You know, we stopped doing that a couple of years ago in my own practice. You have to understand that we were able to do that because the state that I'm in, in New York, we eliminated all the barriers and restrictions. There was no need to differentiate. That said, that's not the case throughout the United States. The new guidelines have moved toward eliminating these characterizations, and they've kind of moved toward just defining a patient as being viremic. That said, a lot of states have not yet caught up to that. A lot of payers have not yet caught up to that. That still remains a bit of a barrier. We now have one of the two regimens that's on the market that's indicated for the treatment of acute hep C.
As the guidelines catch up with the payers, I think that that becomes less of an issue. The short answer is no, I don't differentiate between acute and chronic anymore. We've moved completely toward viremic.
Thank you. Janet, would you like to go to the next?
My next question I was going to address to Dr. Rowe. Sort of looking at the policy and system-level changes in the cost of not treating hepatitis C patients, in spite of the available DAAs, the infections, as Jordan mentioned, have continued to increase in the U.S. and worldwide. In your opinion, where is the failure of the system that is allowing this to happen?
Yeah, I think that the United States is very heterogeneous, and we've lacked national policy, which we're hoping to fix now that the government is open. Senator Cassidy's bill for working towards hepatitis C elimination has bipartisan support, and we're really hoping that that motivates states to work towards elimination in these local networks. It is going to be an opt-in, so it's not going to be mandatory. States can still misbehave. I think that's really going to be where those grades, you can look to see how your state's doing on hepatitis C elimination efforts. They're all given grades. If you're an F state, then you have pretty low hanging fruit in order to be better. If you're a B-plus state, it's going to be a little bit harder for you.
I think that national policy, that national investment is going to be really important because we just don't have the resources to make hepatitis C treatment a priority when there's so many other priorities at state and local levels.
Are there any changes that would improve the efficiency of healthcare, do you think, in your practice, I mean, in delivering care to people?
Yeah, I mean, anything that's automated is certainly better. There are a lot of programs that have been shown to be effective where the EMR flags individuals that have either been tested positive for hepatitis C but not treated. I think that we've been discussing, but if you look at young people who lack insurance, about one out of six of them do not get treatment. You know that there are people that are identified out there that are still not cured of their hepatitis, and that's low hanging fruit. Your EMR can find those people for you, especially if they're still connected in your system. I also think that we get alert fatigue, but identifying individuals, especially if you're focusing on a young, higher-risk cohort or that have not yet been tested for hepatitis C, and then focusing your efforts.
No one wants to talk about microelimination because we want to have macroelimination. There are places where they are enriched with hepatitis C. Look at your incarcerated individuals, recent incarceration. I mean, again, these are easy places that local and states can start with because they're going to be enriched in hepatitis C. No one wants to screen 10,000 people to find three people with hepatitis C. You want to screen a small population that is enriched with individuals that need treatment. That's going to be unique to the location that the people are at.
What is the cost of not treating people with hepatitis C?
Yeah, the cost is significant. We don't want to forget that hepatitis C is an immune modulatory virus. It has an increase in all-cause mortality independent of liver-related mortality and morbidity. Delay until someone has cirrhosis or advanced disease increases the risk of developing liver cancer or requiring liver transplantation even after a cure. Delaying in treatment also increases the risk of transmission. You now have to treat a lot more individuals than you would have if you had treated someone earlier in their infection when they are more likely to transmit to the people around them. There are lots of mathematic models demonstrating that engaging someone who is newly diagnosed with hepatitis C is incredibly cost-effective. A delay from diagnosis to treatment is incrementally more expensive independent of just waiting for advanced liver disease.
It's really an easy sell to demonstrate how cost-effective early treatment is.
Yeah. And then looking at it from the perspective of the payers, what might changes to coverage policies, including Medicaid and Medicare, how might they impact success to getting therapies and advancing eradication efforts? Do you see a blockage there or not really?
I mean, I think there are blockages everywhere. Even when you remove a blockage, sometimes there's another speed bump a little bit farther down the road. Take Illinois, for example. We got rid of fibrosis restrictions. We got rid of restrictions based on substance abuse. Then we ended up having a restriction that was on provider type, which is kind of hard. I mean, it's difficult to demonstrate if you have completed a module that allows you to be a trained hepatitis C provider. And so there just ended up being a speed bump a little bit farther down the road. I believe that Senator Cassidy's bill is looking at something like a subscription model where Medicare, Medicaid, these groups can get discounted drug in a way that makes it affordable, that cost is shared over a period of time.
I think this is going to be really important. Now, will a state opt in? I don't know why they wouldn't. That's why it's got bipartisan support. I think that we do much better if we understand what's in our budget. If you can take the cost of treating your population with hepatitis C and divide it over a period of time so that it's predictable how much you're going to pay in each cycle, that should really get rid of some of the hesitancy in rolling out these much more inclusive elimination projects.
Yeah. And I mean, just to give you some of the raw numbers, just by having hep C, it costs the system on average about $20,000 per person per year. If that patient goes on to develop cirrhosis, the cost goes up to about $40,000 per person per year. If they decompensate, develop liver cancer, it's around $70,000 per person per year. The difference between making an early diagnosis and getting someone started on treatment, there's about a 58% higher mean annual cost for somebody who gets treated in a delayed system. On average, it's about $21,000 versus $8,000 when you look at those incremental costs. All of that downstream is completely avoidable if you get people diagnosed and treated early. There's one other statistic that's really important in this young cohort.
We know that if you're specifically talking about people who inject drugs, which is where the base of this epidemic is, one person who's actively injecting will potentially infect up to 20 other people within the first three years of their diagnosis. Do the math on that. With the numbers that I just gave you, there's tons of cost savings here. I mean, this only makes sense. When you deploy a test and treat model of care, you're eliminating missed visits, which are billable, redundant laboratory testing, which happens a lot. You're really streamlining this, and you're making it much more cost-effective. This makes a lot of sense. It makes so much sense that that's why there's this federal elimination plan, because when we look at this, I mean, the cost savings are in the tens of billions of dollars.
This makes sense to a lot of people. I think it's hard for the states because these downstream cost savings tend to occur 10, 15, 20 years down the line, and you have to answer to a more here-and-now world. You have to look at the cost savings and the cost benefits in, say, three years and five years in addition to the downstream.
For the patients who have insurance, is navigating the insurance reimbursement and payment system, is that a hurdle to getting timely treatment? I mean, what happens there?
It can be. This is, again, very state-specific. Again, here in New York, no, there's no hurdle. I'm able to stock the medications on the shelf, poke your finger, give you the full supply of medication, no barriers. We're a robust Medicaid state. Now, if you go some places in the South or out West, that's not the case. There are insurance hurdles. Nancy was pointing out some of the restrictions, whether it was prescriber-type, sobriety, need for a prior authorization. These are all just unnecessary barriers that are in place that inhibit elimination. Those things would go away with this federal elimination plan. It's really state-specific when you're looking at what some of these barriers are. Some places are very easy, some places not so easy.
Arantxa?
Yes, I think the next section really ties very nicely with this one. It is also about the integration of other public health initiatives and elimination goals. I am going to direct a couple of questions to Dr. Lawitz. In terms of a regimen like this that we are developing right now, which is an optimized kind of a next-generation regimen, how would that help and enable broader uptake of care and accelerate the progress towards the hepatitis C elimination in the U.S.?
Yeah, thanks for the opportunity to be here. You know, one of the facts that I like to think about is when we think about the number of treaters in the U.S., there's about 7,000 different treaters. How many overall treaters in the U.S. is about 700,000. It's actually fairly amazing that only less than 1% of the treaters in the U.S. actually are treating hepatitis C today. When you mirror that with the 33% undiagnosed, it's no wonder we're not doing so well on our efforts of eradication. Ultimately, what would be the goals would be to enhance screening and finding those undiagnosed, but probably more importantly, enlarging the treater base. We think we have a lot of treaters now, but I was actually interested when I went back and looked, it's actually still 1% of the treaters in the U.S.
If we're able to even enlarge that by a handful of %, the multiplier effect on getting treatment across the U.S. is going to be exponential. That raises the question, how do we enlarge the treater base? We have a regimen that is uncomplicated and easy to use and one that people, the providers, are not afraid of per se or worried about and feel like they need to refer their patient for treatment.
The things that you've already laid out nicely earlier in the call, the simple, safe, highly effective, low pill count, agnostic to genotype, agnostic to fibrosis stage, really some of the attributes that have been demonstrated in bemnifosbuvir and ruzasvir in phase II, if they're reproduced in phase III, I think are going to bring us towards the next step of enlarging the treater database and ultimately bringing us much closer than we are today to more fully treating patients. It's absolutely amazing that we have as many patients infected despite all the treatments we've done. In San Antonio, I always thought I've treated the whole city twice or three times, but ultimately, we still have a consistent couple hundred we treat a year. Actually, that number has not decreased or increased.
Our flow of hepatitis C referrals over the last 10 years has really been very, very consistent without really a significant rise or fall. We have a very broad population that see us. We have some of the rural areas in South Texas and the more sophisticated patients. Ultimately, it's amazing how people have still, despite all the information around hepatitis C, how many people are still 50s, 60s, 70s. Yesterday in clinic, I saw a 72-year-old gentleman who never knew he had hepatitis C, and we're going to treat him, and he's had it for probably a couple of decades. Despite all the aggressiveness, we need to continue to further our education, both to patients and providers.
I think as we think about the possibilities with adding a new regimen that has a short duration, limited drug interaction profile, and will have the lowest pill count in the field is important because, as Tony and Jordan and Nancy alluded to, these patients can have challenges, socioeconomic challenges, psychologic challenges. Having a limited number of pills and an ability to get people cured while they're interested in the topic and kind of it's in the front of their mind, I think is going to be very useful. Ultimately, with the phase II data showing the non-cirrhotics having 180 out of 181 patients cured, as long as phase III reproduces our phase II studies, we can see that this is going to be a highly, highly effective therapy. The other nice thing about the regimen is it's second-generation antivirals.
We have a different resistance profile, more potency than the first-generation antivirals that have been on the market now for more than a decade, which are more potent and actually have activity against some of the resistance-associated substitutions of the first generation. I think it all kind of rounds out to really show how the community should be receptive to this. The hope is that we can increase screening and probably more importantly, increase the treater base.
Great points. Thank you. Janet, would you like to move on?
Yeah. Back to you a little bit, if I may, Dr. Martinez, just to comment a little bit on practice challenges. I think Eric already perhaps highlighted some of these. How does the fact that many of your patients are on multiple medications, some that you know about and some that you do not, influence your prescribing decisions? What are the most common medications that you see your patients actually taking that could lead to drug-drug interaction issues?
Yeah. So I mean, the most commonly considered medications, obviously the statins, the PPIs, some of the antipsychotics, I think those are the big groups. In the younger population, especially the antipsychotics, medications used for medically assisted therapy for opiate use disorder, so things like buprenorphine or methadone, those are probably the most common medications. Some of these other variables, I mean, I think everybody's pointed it out. With these patients, speed is the key. That's true even right now with the regimens that we have available. The shorter the duration of the regimen and the closer to SVR, the better. Shorter is better. It's just a simple fact. If you have shorter, less pill burden, no food effect, minimal DDIs, you're perfectly aligned with a rapid start model, a true test and treat model of care.
It almost takes a lot of the thinking off the table. I don't need to worry about these DDIs. I know that if they get through the eight weeks, they're going to get cured. I don't need to worry if they're eating with the medications. All of these things become a factor when you're trying to do this in a very quick way. You may not have these patients for long, so the quicker you can initiate them and get them through that treatment journey, the better.
I was just going to stress, I fully agree with everything Tony said. He mentioned the food effect, but I would actually highlight that that is actually not a trivial consideration when you're treating folks that are really in a rough spot. People experiencing homelessness or people that are actively using and really living pretty chaotic lives, that when they're eating their next meal and reliably eating is not always something that you can count on. Having to sort of just take that out of the picture with an eight-week regimen is actually, I think, quite impactful for the populations that we're treating now.
Yeah. Arantxa?
We want to talk a little bit about drug forgiveness in the context of these populations that you are describing. This question is for Dr. Rowe. Why would it be important to have a regimen that is forgiving to missing doses?
Yeah, I think there is lots and lots of data showing that adherence, even when people want to be adherent, is difficult. You want to make sure that missing doses or short treatment disruptions, especially in an unstable population, is going to be able to have wiggle room within the therapy and still result in a cure. There are great examples where there are heat maps of individuals who have missed multiple doses and still end up with curative outcomes. We need to make sure that you do not slide back from that. Obviously, we encourage all of our patients to take all of their medications, but life happens. We want to make sure that if you cannot be cured, that the resistance or the outcome for retreatment opportunity are marginal.
If you are missing things, we want to make sure that there's enough wiggle room in there that this regimen would not be inferior to another therapy where there is more wiggle room.
Janet?
Oh, sorry.
Oh, sorry.
No, go ahead.
Yeah, in fairness to the patients, I just want to make this point because it comes up in every single discussion about Hep C for the history of hepatitis C. Adherence is an everybody problem. It's a people who use drugs problem. It's a people who don't use drugs problem. I'm a 50-year-old physician, and I have Z-Paks left over from five years ago. Adherence is an every single human problem. People who use drugs, people who live with Hep C right now, they inherently know how to follow a regimen. They do well with meds. Do they miss dosages? Yeah, they'll make an eight-week regimen, nine or ten weeks. To Nancy's point, yes, it is very important that we don't slide back, that we have that forgiveness there because, yeah, they will miss dosages. I just don't want the perception to be that they're wildly adherent.
We often talk, we're talking about them as though they have these chaotic lives. You have to understand that with this patient group, I have a chaotic life. Nancy has a chaotic life. We all have a chaotic life in our own way. This patient population, it's all about perception. Their chaotic life is very normal to them. They do perfectly fine. They do even better when they have a short, easy-to-take regimen. As long as we have that forgiveness there, I think it only amplifies why this regimen has such potential.
I did not mean to limit my adherence discussion to individuals that had engaged in high-risk behaviors. The heat maps are present from all of the clinical trials. We became more and more brave with who we treated as we got to understand exactly how safe and effective these therapies were. Even the most well-chosen patients for these clinical trials still occasionally miss doses. I have three children because I'm not always adherent in my chaotic lifestyle. You can take that wherever you want. Just like Tony, even in the best of circumstances, doing everything perfectly is challenging.
Yeah. Great points.
I'll add in, when you talk about compliance, the duration really matters because I was thinking about three months of an antifungal for onychomycosis and how many people actually can't get through that three-month period. You do really well for the first month or maybe two, and then that last month trickles off. People say eight versus 12 weeks, maybe not that big of a deal, but actually probably is because the intent and the focus on a shorter duration is very, very important. I'm equally bad as it gets longer in a duration of trying to take a pill a day. I find the pills in my pocket occasionally that I was supposed to take and are not. Not only is short important, but packaging is important too to help patients adhere.
If we have an eight-week regimen that has a very specific packaging and we can ensure that the patients know if they took it, because the worst thing in the world is to say, "Did I take my pill today or not? Was that yesterday? Was that tomorrow?" I think it's a combination of short duration and helping the patient succeed with the way the product is packaged will really go a long way to ensuring compliance.
Thank you very much for that. Just adding to that, really just one last question around the absence of a protease inhibitor in an eight-week regimen. How do you see that affecting simplification of care and ease of use? Dr. Lawitz?
Sorry, I had to find the unmute button. Protease inhibitors obviously helped us in some ways originally, right? They brought the duration down, but they also carry the baggage of drug-drug interactions because they're metabolized in the liver. They also concentrate in the liver as you get worse and worse liver disease, thus some cautionary tales and increasing levels of cirrhosis. Also, some complications on the drug-drug interaction. We all, as hepatitis C treaters, we've all understood the estrogen and a number of drug-drug interactions. The University of Liverpool app has been very popular, particularly people using protease inhibitors because it allows them to quickly try to figure out if their patient's at risk based on their concurrent medication.
Albeit the protease inhibitor has decreased the duration from nucleoside polymerase inhibitor and NS5A from 12 to eight weeks, it hasn't decreased the complications of caring for patients. It's only taken care of part of the problem, which is shorter duration is always better, but it hasn't got rid of the complexity. Ultimately, if we want more people to treat, we can't have this long list of yellow, red, and green stoplights on the Liverpool app to figure out which medications are okay, which I can continue, which I need to change, which I need to hold. As we move to simpler, both decreased drug-drug interactions and decreased duration of treatment are very important. Ultimately, that's why we tend to use the nucleoside NS5A, sulfosphorylated valprotosphere, and anybody that's got a decent medical list, right?
If they have a bunch of, if they're the usual internal medicine patient with 15 medications, I'm always going to turn to the nucleoside NS5A inhibitor because I know my risk of drug-drug interactions is significantly less. If I have a young person on no medications, then speed is better. If they don't have advanced liver disease, I can get away with the eight-week protease-based therapy. It would be nice to have one solution that fits everybody, regardless if you're young and no medicines or middle age or older with more medicines as I get older. Older is starting to be older and older. I think we need this opportunity to have a short duration with minimal drug-drug interactions is going to be very popular for treaters and patients. Hopefully, we'll put less people on the Liverpool app for a shorter duration of time.
Thank you. Arantxa.
Yes. I'm going to turn it to Dr. Feld. Maybe you can also give us a little bit of the XUS experience. In terms of patient identification and engagement, how could screening and care coordination approaches be improved to ensure that all patients have equitable access to diagnostics and treatments?
I think we've touched on a number of the things that will allow us to try to really expedite the cascade of care in every part of it. It really does start with testing and diagnosis. Outside of the U.S., healthcare systems are different. Obviously, I'm in Canada where we've got, it's good that everyone has health insurance and coverage for their healthcare, but it still varies by provinces. It's still complicated probably everywhere you go. I think what we've been focusing on and what I think many of the countries, particularly with national healthcare systems, have been able to do is to develop national strategies for addressing hepatitis C to really improve screening, get people diagnosed and into care.
As Tony and Nancy nicely discussed about the importance of removing barriers, we have been very effective at that in Canada of taking away some of those barriers to make getting people onto same-day starts, for example, very easy. Now we have good access to point-of-care HCV RNA testing, like Tony described, and we are able to start people on therapy immediately because of the lack of need for pre-authorization. Some of those barriers, as Nancy mentioned, we used to have provider barriers. Those have been taken away. Fibrosis barriers, sobriety barriers went away a long time ago. This allows us to really get people into care.
What we've found is that if we can get them onto their first dose of medication, our success rate of getting people to complete treatment is incredibly high, even with imperfect adherence, as you've heard from all of us that affects everybody. Our cure rates are really remarkably high in the real world, just as they were in the clinical trials. I think the experience we've had in Canada is pretty similar to what's seen in Europe, where the healthcare systems are much more similar to ours and a little bit less fragmented than the U.S. system, where we have a little bit more unified access to care, universal access to care, which I think streamlines really all of the HCV care, particularly for more marginalized populations.
I think we've had a problem in the U.S. with a reliance for too long on a patient readiness model of care. That's kind of how we've always operated, is the patient ready? I don't know how you determine readiness. I can tell you in my own clinic, it's that you're sitting in front of me. If we're going to achieve elimination, we have to move to a provider readiness model of care. I think as these regimens come into play like this, where it's even easier, even safer, even less complicated, you start to shift that mindset to a provider readiness model where we just accept the fact that this is how the patients live. To treat Hep C in 2025 with the patient base that's most affected, you have to make a truce with a reality that's not necessarily your own.
You have to step one foot into their world, recognize this is how they live. It's perfectly fine. You have to come to the readiness point. They may never be abstinent from drugs enough. They may never be stably housed enough. They may never be psychiatrically compensated enough. While you're waiting, they're spreading. The quicker that we can get to a regimen where it takes all these kind of other variables off the table, it just makes it that much easier. As we upscale our deployment of point-of-care viral-first testing, especially in high-risk and high-prevalent areas, that goes a long way to getting to those diagnoses. If we can deploy a regimen like this, it makes things even easier. Short-duration, like Eric was saying, is the key. Shorter is better. Speed and simplicity is the name of the game.
Thank you so much. I think that's a wonderful summary. If we can, I'm going to turn it back now, I think, to the operator, and we're going to have some questions. I believe there are a couple of people who are dying to get a question in quickly. Jonae, can I perhaps hand it over to you to help facilitate that?
Yeah, Janet. Yeah, I'll take it from here. We have a question from Andy Hsieh at William Blair. Please go ahead, Andy.
Actually, two questions, if you don't mind. One has to do with maybe adherence. Upon commercialization, do you expect patients to receive the full regimen? Meaning two bottles or two months' worth of supply just to ensure that the compliance is really, really optimal there. That's question number one. Question number two has to do with the cost or healthcare economics analysis. I think I appreciate the Fireside Chat kind of alluded to that before, but I'm sitting back here looking at the kind of Madrigal's Ristifra, which is positioned to prevent the advancement into the cirrhotic stage. That's a chronic treatment versus this is a fixed dose combination, right? It has a fixed duration of treatment. I guess the health economic argument is very strong here, preventing with a cure that prevents a lot of different adverse outcomes for patients, including cirrhosis.
Maybe, John, you can comment on some of the health economics analysis that you've done, particularly looking at that as well. Thank you.
I'll answer the first question with regard to what amount of drug product is provided at the time. That is really provider-driven and what their rules are, or in this case, if you have test and treat, what the rules are there to what is provided. It does not come down to the manufacturer. From that standpoint, obviously, our company would support what is in the best interest of the payer. At the end of the day, it is a patient, but at the end of the day, it is in the eyes of the payer and in the test-to-treat models about how they conduct their business.
That said, it would be a very good strategic move if the manufacturer were able to package the full eight weeks on a single dispense. That would be a game changer. That is something that the other companies on the market now have been trying to achieve. There is a role for whoever commercializes this to take that into consideration. You did raise an important point in that this is not chronic disease management. This is the cost of cure. There is a big differentiator there. You are absolutely right. I mean, this makes a ton of economic sense.
Yeah, we do see the merits in obviously providing everything in the cure. I guess we can further look into that and explore payers' preferences and what they want to pay for.
Great. Thank you so much.
I think perhaps if there are any other questions from outside, [Arantxa] .
Yes. Hi, this is Jonae. Yes, there is a question from Maxwell Score at Morgan Stanley. Maxwell would like to know what proportion of patients present with cirrhosis.
Jordan, you touched on that, I think, quite nicely at the beginning. Do you want to recapitulate what you said there?
Sure. It's really changed dramatically. It depends a little bit on where you look. We did some work with some colleagues around the U.S. last year looking at fibrosis assessment. What we looked at, it really depends on the practice type. In a specialized hepatology practice, you still might see up to 15-20% of people with cirrhosis. These are older data. I actually think from our own practice, that's gone down dramatically. It's probably closer to around 5-7%. If you go into a primary care setting, it's under 5%. That's consistent really across any primary care setting that the proportion that have cirrhosis has really, really diminished.
I think as Tony nicely highlighted, there are now a number of models that show that if you take a population certainly under 35 and maybe even extending that out to 45 without significant other risk factors for advanced liver disease, so not heavy alcohol use disorder or major risk factors for advanced NASH, the risk of cirrhosis is extremely low, which gives us confidence that you could actually move to either very simplified fibrosis testing with FibroScan or other sort of point-of-care technologies or FIB4, very simple serologic tests, or to forgo it altogether when you're doing sort of field deployment of test and treat models when you're doing like a needle syringe program or something like that where you're actually doing outreach work, identifying people and treating them. Very clearly, the best harm reduction approach to cirrhosis and all of the complications is to treat people.
If you actually get it wrong and you inadvertently misrecognize cirrhosis, first of all, the treatment efficacy is still very high, even if you gave someone an eight-week course. Secondly, the risk of long-term complications, the biggest risk, the biggest way to reduce the risk of long-term complications, most importantly, cancer, is to get their Hep C cured, not to get them into a surveillance program. Fortunately, it's much less of a problem than it used to be.
Yeah. And you're not going to hurt them. I mean, that's one of the key things that you're, by treating them, even if you've missed the cirrhosis, you're addressing and eliminating the underlying hepatic insult. So the only thing you're going to do is help them.
I think that's probably a nice way to conclude.
Thank you. In closing, first, I would like to thank our KOL participant for the time, interest, and really very interesting view. They have a daily view, unfortunately, and are making a really difficult decision and very rapidly in a very rapid time matter. We hope that our regimen, if approved, would provide an additional important option for the prescriber and the patients infected with hepatitis C. We believe that our regimen may represent a potential best-in-class profile, as some of you have discussed. We look forward to hopefully play an important role in the eradication of this serious chronic viral disease. Thank you all for joining the Atea HCV KOL panel today. Thank you again.