Great. Good morning, everyone. My name's Jess Fye. I'm a biotech analyst at J.P. Morgan, and we're continuing our 44th annual healthcare conference this morning with Mirum. First, you're going to hear a presentation from the company, and then we're going to go into a Q&A session. So for all of you in the room, if you do have a question, just raise your hand so someone can bring you a microphone for the webcast. And if you're listening online, you can submit questions to the portal, and I can read them off up here. But with that, let me pass it over to Mirum's CEO, Chris Peetz.
Thanks, Jess, and thanks, everyone, for your interest in Mirum today. Quick update that I'll be making forward-looking disclosures to refer you to our SEC statements for a more complete discussion of risk factors. In particular, I know we're going to be talking about the proposed acquisition of BlueJay Therapeutics, which has not yet closed, but really excited to give an update on Mirum, one of my favorite topics to talk about. We are a rare disease company focused on delivering life-changing medicines to rare disease patients and heading into what I see as a pivotal year for the company, so excited about much of what's going on across the business, and we find ourselves finishing 2025 with really strong commercial performance.
So at the start of the week, we announced that we sold an estimated $520 million of total product revenue for the year and gave guidance for 2026 of $630-$650 million. So a track record of really strong commercial performance across our three approved medicines. And that sets us up nicely for a slate of readouts of high-impact clinical stage programs in the pipeline, namely four potentially pivotal programs reading out in the next 18 months. So a really exciting time for our pipeline as we head into the next 18 months. And behind that is substantial potential for future revenue. So across our current commercial and pipeline programs, we see over $4 billion of potential across the Mirum portfolio. I'll use this pipeline chart as a bit of a table of contents of what we'll cover here. We'll spend some time talking about Livmarli.
This is our lead program that was our first commercialization, now approved for two indications in Alagille syndrome: pruritus and Alagille syndrome and pruritus in PFIC. A third indication with a pivotal readout later this year. We have just accelerated the timelines for the EXPAND study, which we will touch on in a bit more detail, expecting top-line data in Q4, so label expansion opportunity for next year. Chenodal and Cholbam are approved ultra-rare medicines that continue to grow nicely. Volixibat is kind of the next big catalyst that's up with top-line data from the VISTAS PSC study expected next quarter and potential NDA filing in the second half of the year. A follow-on indication in PBC with the VANTAGE study tracking towards completing enrollment later this year with top-line data in the first half of next year. Fragile X program in phase 2 behind that.
We'll touch on the exciting addition to the portfolio, the announced acquisition of BlueJay Therapeutics. The key program there that fits quite well with the Mirum adult hepatology program is Brilovatug for hepatitis delta. Great synergy across all of our call points, not only for Livmarli currently, but for the anticipated expansion for Volixibat into adult GI and hepatology, which we'll touch on in a bit more detail. We are set up and commercializing directly across North America and Western Europe. All of these products fit nicely into a focused commercial team across these geographies. I've seen really great success using partnerships and distributors to expand to smaller countries, leveraging our team to geographies where it's not able to have a direct presence in smaller countries.
As mentioned, the track record on the commercial side has been strong with an expectation of $630-$650 million in net product revenue this year. And breaking out some of the potential of the pipeline here at the bottom of the page, with Livmarli having a billion-plus potential opportunity, Volixibat and MRM-3379, also billion-dollar potential brands, and the latest addition of Brilovatug, we see as at least a $750 million opportunity. So let's go into a bit more detail on Livmarli. Livmarli is an oral, minimally absorbed IBAT inhibitor, and its mechanism of action reduces the over-accumulation of bile acids that's relevant across a number of different cholestatic settings.
In particular, this has been a game-changing medicine in Alagille syndrome and PFIC, where we see from the clinical programs rapid and dramatic reductions in serum bile acid levels and the associated symptomatic burden of disease with pruritus and fatigue improvements, and over long-term comparisons, seeing an impact on the transplant rate in these pediatric settings. And it's been a strong growth driver for the company. So Livmarli in 2025 hit $359 million in net product revenue. You can see there's been a nice acceleration of growth over the past year. What's underneath these numbers is a steady pattern of growth from the Alagille syndrome indication, where we've now been in market for four years. And we've seen a continued accumulation of patients, largely driven by pediatric patient starts that then has a quite high persistence rate given the symptomatic benefit of the medicine.
And over time, these patients starting out with pediatric weight-based dosing do increase their dose over time. In 2024, we had a label expansion into PFIC, and this has been a really interesting acceleration of that pattern of the background growth from Alagille syndrome. In particular, a dynamic where we're finding that PFIC, in particular in adult settings, is underdiagnosed. So we've been focused on building awareness of genetic testing in adult hepatology clinics, where it has not been a standard practice to run genetics on a number of their cholestatic and pruritic patients. And we're finding this having an impact not only for Livmarli's growth, but also having a new option for treatment of these cholestatic and pruritic patients. And all of these trends that we've seen throughout the year, we see them as durable into 2026 as well.
So a lot of that driving the guidance that we're quite excited about for the year. Beyond Alagille syndrome and PFIC, the EXPAND indication is another substantial expansion for the opportunity for Livmarli. We see this sized as at least the size of PFIC, potentially the size of Alagille syndrome in terms of its underlying epidemiology. A quick comment on the balance of the commercial portfolio, the bile acid replacement products, Cholbam and Chenodal, these are relevant across a number of different ultra-rare genetic synthesis disorders to replace one of the missing bile acids that is disrupted by a mutation in the cascade for biosynthesis. We acquired these programs in late 2023 and have had a focus on bending the curve in diagnosis, in particular for CTX patients.
We achieved a formal approval of Chenodal for CTX last year and have seen an increase in diagnosis and treatment of patients driving this nice increase in the growth curve. We also see this as a durable trend moving into 2026. Some comments on the pipeline, and I'll start with Livmarli's EXPAND study. The EXPAND study is a basket design that really was informed by a surprising amount of interest for compassionate use across a number of very, very rare cholestatic settings for patients that presented with cholestatic pruritus as a result of some other background indication. Given the overwhelming interest, we designed a basket protocol to look at ultra-rare settings of cholestasis in the EXPAND study. EXPAND looks at 45 patients for Livmarli twice-daily dosing versus placebo.
This is a 20-week study focused on pruritus, oriented for a label expansion into other cholestatic pruritic indications. The study's nearing completion of enrollment. We've been able to accelerate that timeline to a Q4 top-line readout, and really interesting mix of different settings here and a lot of unmet need that we think that EXPAND will help address. Worth noting that a sizable portion of these patients, maybe just a bit less than half, are biliary atresia patients that can have a persistent cholestasis after a successful Kasai procedure, so excited about what this can mean for an additional treatment option for those patients. Moving into Volixibat, similar to Livmarli, is an oral, minimally absorbed ileal bile acid transport inhibitor, and we are studying Volixibat in both PSC and PBC. These are larger adult settings of cholestasis where pruritus burden can be a substantial unmet need.
So two programs ongoing for Volixibat in these settings for PSC with the VISTAS study and PBC with the VANTAGE study. In PSC, orienting on some of the U.S. epidemiology numbers, we see that there's likely about 30,000 patients, and about two-thirds of them deal with pruritus as an aspect of their disease burden. It is hard to overstate what this can mean for a patient's day-to-day life to deal with the persistent pruritus and itching that is related to the elevated bile acid levels of the disease. Fatigue is also a big component of this, and we've seen across the clinical studies improvements in both itch and fatigue with IBAT in these cholestatic settings. So this means that we're orienting around at around 20,000 patients as the target launch population for Volixibat and PSC of those patients with PSC and related pruritus.
There's strong evidence behind IBAT driving an improvement in pruritus in prior studies and compassionate use experience for Livmarli and patients with PSC. This is data on the page here of the CAMEO study, which looked at Livmarli at lower doses on patients with PSC. You can see there's a nice improvement in itch in those that had itch at baseline and reduction in bile acids. We took this observation as well as some of the compassionate use experience and designed and are running the VISTAS study. VISTAS is an adaptive phase 2b study, now fully enrolled, that had an interim analysis in 2024. It's worth spending a moment on that interim analysis and design because it really informs how we see the readout coming up next quarter.
The study was designed to have a blinded interim analysis where a data monitoring committee reviewed the data in detail and had a minimum threshold that had to be met for the study to continue blinded. That is the case. The study remained blinded. We're excited about what this can mean in terms of the outcome next quarter and expect to file an NDA in the second half of the year based on that top-line data. Next big readout for the Mirum portfolio coming up soon. Follow-on indication for PSC with Volixibat is PBC, and quite a bit in common between these two settings in terms of the cholestatic disease burden. PBC patients also suffer from elevated bile acid levels and pruritus.
There's a bit more of a segmentation of the market because there have been recently new medicines approved in a second-line setting where patients may not have biochemical control. So the recent approvals of two PPARs in this setting have been a nice advance for PBC patients, but leaves unaddressed a large number of those patients in the front-line setting who do not have a treatment for their pruritus. And that's a big part of what we're focusing on here with Volixibat, is going after those 31,000 patients in the front line that have elevated bile acids and pruritus, but may be controlled on their alkaline phosphatase. And the VANTAGE study, similar to VISTAS, is an adaptive phase 2b study, but we're targeting a larger population with VANTAGE.
We were able to conduct an unblinded interim analysis and present some of those data at AASLD and EASL at prior meetings. It's quite striking results that I'll skip to here from the interim analysis. You can see here the two doses of Volixibat having a dramatic reduction in the pruritus levels versus placebo, a clear treatment effect that sets in early and is durable over the treatment time period. We've chosen the 20-milligram twice-daily dose to take forward in both the VANTAGE and the VISTAS study. We do see read-through across these settings. The dosing of IBAT inhibitors, as we've looked across all of the different settings where we've studied cholestatic pruritus with an IBAT inhibitor, if you get to a sufficient dose level, you can drive a similar response across different settings.
I'm excited about what these interim results mean, what these interim results mean for both the VANTAGE PBC study and also the VISTAS PSC study working together as a program. I'll talk for a quick moment about 3379 and the Fragile X program before moving on to the acquisition of BlueJ. The Fragile X program that we've designed with MRM-3379 is targeting males with a full mutation of Fragile X, which is estimated to be about 50,000 patients across the U.S. and Europe. This is kind of where the most need is in this setting across the males with the full mutation. MRM-3379 is a PDE4D inhibitor that helps boost cyclic AMP levels. One of the key features of Fragile X as an indication is depressed cyclic AMP levels and the impact that that has on neurodevelopment and cognition.
And there's actually been a really compelling phase 2 dataset with another PDE4D inhibitor that inspired our program. And what attracted us to 3379 as a program is that it is highly CNS penetrant. And so we think we can have an improvement in what's been seen in a prior phase 2 study by having more CNS exposure and driving an effect on cognitive scores in Fragile X patients. We've seen this play out in animal models of Fragile X. So recently presented animal data confirms that we can get to comparable levels of activity to another competing PDE4D program with a fraction of the dose. And we've taken that into the BLOOM phase 2 study. BLOOM is a dose-ranging study that just recently randomized its first patients on track for data in 2027, looking at the NIH Toolbox cognitive score domains.
We've had an interaction with the FDA supporting this program and the use of this endpoint with validation for a potential approval in a subsequent phase 3 study. So excited about getting this towards data next year. Now we'll finish the pipeline discussion with an overview of Brilovatug in HDV. And first, for a little bit of context on the acquisition of BlueJay Therapeutics, which we see as a unique fit with the Mirum pipeline and team. So hepatitis delta is a rare disease that's treated primarily in GI and hepatology clinics. A lot of the same call points that are already prescribing Livmarli and will be target prescribers for Volixibat. So high synergy to be able to bring this into the pipeline as we're moving into the Volixibat launch. Hepatitis delta is a rare co-infection with HBV.
We think there's about 15,000 diagnosed and insured patients in the U.S. So that's our target launch population, though prevalence rates are much higher in certain other countries. So in the U.S., we see this as a rare disease launch that fits really well with our commercial team. In the phase 2 data to date, Brilovatug is very compelling. At AASLD last year, an update for a dose-ranging phase 2 study was presented where Brilovatug achieved 100% virologic response, so a two log or greater reduction in hepatitis delta levels. And more importantly, on the right side of the page, the FDA's approval endpoint for this setting of virologic response with ALT normalization, you see a 65-82% response rate on the approval endpoint. So really compelling results here and a safety profile with a single agent regimen that is really compelling.
Minimal rates of flu-like symptoms, which has been a real issue with interferon and some of the legacy treatments in this setting, and a clean, fully humanized antibody profile beyond that. And taking this forward, the AZURE phase 3 program is currently enrolling, and I'd say enrolling rapidly. So AZURE 1 and 4 are the registration studies for the U.S. These are placebo-controlled evaluations of Brilovatug at either 300 milligrams weekly or 900 milligrams monthly, looking at that composite endpoint of virologic response with ALT normalization. We expect top-line data from the AZURE 1 and 4 programs in the second half of this year. That is the planned submission package for FDA. And worth noting that in Q2, we'll have an interim look at AZURE 1. So the first 50 patients in AZURE 1 will be evaluated in an interim analysis right around the corner.
EMA, because there is another approved agent in Europe with Hepcludex, has the AZURE 3 and 2 studies as the basis for approval there, where you look at either a head-to-head or a switch of Brilovatug versus Hepcludex. So slightly longer timelines to get to those EMA endpoints. And so pulling it all together, Mirum is in a really strong position with a track record of compelling commercial performance, guiding towards $630 million-$650 million of revenue this year. Our expanding pipeline has a lot of exciting readouts on the page here. And in addition to all of the readouts that we're heading into, these four pivotals really of note with the VISTAS PSC top-line next quarter, the Brilovatug AZURE program the second half of this year, the EXPAND Livmarli study in Q4, and PBC data for Volixibat in the first half of next year.
It is just a pivotal stretch for the Mirum pipeline, and pulling this together with the financial performance, that's compelling as well. Well-financed balance sheet and expect to be cash flow positive in 2027 with all of this investment across the pipeline, and so with that, I'll pause and turn to questions from Jess.
Thanks. Just as a reminder for everyone in the room, if you want to ask a question, just raise your hand. So someone can bring you a microphone. You started out talking about Livmarli and the growth that you've seen. So when we think about the growth that you're looking for in 2026, what are the major sources of that growth? And just how are those sources of growth evolving, right?
So the growth patterns for Livmarli are largely consistent in 2026. I think there's a couple of things to note. And some of this just one thing I noticed, the seasonality for international. The tail end of the year tends to be a little bit stronger. So we expect to see that going into this year as well, where the international markets, in particular with some of our distributors, have bigger orders in the back half of the year. But other than that seasonality, we do expect international to continue to grow. Our partner Takeda had a bit of inventory buildup in 2025. But other than that, all geographies, we expect continued growth. So Takeda, we do expect to be a little bit lighter into 2026. On the U.S. side, clear line of sight that the trends are continuing.
Alagille syndrome now for many quarters has had a steady accumulation of patients. You see some weight-based adjustments for the patients on therapy longer term. The adult PFIC phenomenon and supporting patient finding in PFIC is a big driver of patient starts throughout 2025. We expect that throughout all of 2026.
A couple of audience questions.
Couple of audience questions here. So sticking with Livmarli, can you say how many patients are being treated for Alagille and for PFIC?
We haven't broken out patient numbers. What I would say is that our U.S. revenue number is direct sales. So there is no inventory in the U.S. number. So you can get a sense of patient numbers pretty directly by looking at the net revenue for the U.S. market. We have some of that broken out in our supplemental materials in the back of our corporate deck. So invite you to go take a look at that. And in terms of we also get asked about indication breakdown between the two, between Alagille syndrome and PFIC. Alagille syndrome to date is the larger component of that revenue. But PFIC really is the bigger growth driver over recent quarters. One of the ways to put some perspective around it over the long term is we talk about Livmarli being a billion-plus brand.
We see these trends taking Livmarli to that level, and there's probably roughly equivalent size between the three indications, between Alagille syndrome, PFIC, and EXPAND when you extrapolate out to that peak revenue number.
Another audience question here. Can you talk about the latest pricing for Livmarli in those two indications between Alagille and PFIC?
Alagille syndrome on a net basis for the average patient, you have to keep in mind this is weight-based dosing. There are patients that are well below the average and also patients above the average. But on a net basis, the average Alagille patient is in the mid-$400,000 to $500,000 per year. PFIC has a higher dose. The average price in PFIC can be as much as two times that. The EXPAND population has yet another dose level that's kind of in between the two. You think of that as the range of net price for Livmarli.
Great. And then another question here. Where are you on IP for Livmarli?
Livmarli's IP, the guiding assumption we look at is the 2040 family of patents, many of them Orange Book listed. Those are directed at the unique dose response pattern in general for IBAT and very specific to Livmarli and the data that we've generated. Those are a 2040 expiring family, though there are many supportive families at other time points as well in addition to that. Note, going all the way out to 2043 is our longer dated IP for the tablet formulation of Livmarli. Kind of didn't talk about that on the revenue page, but the tablet has been a big part of this growth story that we've seen, in particular for the older patients, teenagers and adults having a preference for that tablet formulation, which has the 2043 IP timeframe.
Great. Maybe turning to EXPAND, where it looks like we could hear an update on that before the end of this year, right? You mentioned that up to half of those patients are biliary atresia. And there was some development history with Livmarli in biliary atresia. Can you just kind of recap what the backstory was in that setting and kind of how this development approach makes sense?
Yeah. I'll give a little perspective on the disease setting as well as part of answering that question, because this has been a learning over the time on developing Livmarli. So in biliary atresia, these children are born with a disruption and really no connectivity of the biliary tree to the GI tract. And so standard of care is to urgently, upon diagnosis, to complete a Kasai procedure, which establishes bile flow from the liver to the GI tract. So that's a lifesaving procedure, really important for these patients. And there are two different ways that IBAT has been studied after that procedure. One is, which we looked at in a phase 2 study, looking at the chance to improve outcomes after that Kasai procedure, which is different from what the EXPAND study is looking at, which is improving pruritus much later than the Kasai procedure.
And what we've learned from these studies and from the compassionate use experience is that that Kasai procedure really determines the outcome near term. So the Kasai procedure surgically reestablishes bile flow when it works. These patients have a very nice response on their liver parameters, their bilirubin. And when it works, it tends to work quite well. They stabilize nicely, at least in the near term. When it doesn't work, they move very rapidly to liver transplant, because it can be fatal if they do not get sufficient flow of bile into the GI tract. So in those earlier patients, which we studied in the EMBARK study, if they didn't do well, they went right to a transplant. And those that did well saw really no need for therapy in that acute setting.
But what we see is over time, they can start to develop more of a slower progressing cholestasis, and the pruritic burden can be quite substantial. And think of these children as kind of starting in the two- to three-year-old range all the way out to as old as a teenager when they start to develop that profile.
Okay. Maybe switching to Volixibat with the PSC readout coming up in the second quarter, can you just expand on what specifically gives you confidence in a positive outcome, and maybe also to the extent, what are the risks for that trial?
Yeah. Many layers of evidence that we look at here for the VISTAS PSC study, and really starting with what we know about the class. IBAT, as a treatment, when you're dosing at a high enough level, drives a very consistent reduction in bile acids and improvement in cholestatic pruritus, so we've seen now across all these different settings, when IBAT is dosed sufficiently, you can drive a response on pruritus. Specific to PSC, we actually have IBAT data in the indication, so we know we have case studies and analysis of responders from other studies, where you can see that there's an improvement in itch that those that have pruritus, that baseline, and then kind of the third and probably the most direct evidence we have really comes from the study itself, so the VISTAS study had the first portion where two doses of Volixibat were evaluated versus placebo.
And the data monitoring committee had a dose selection algorithm as part of that. And for them to select a dose and leave the study blinded means that the treatment effect exceeded the minimum threshold for the study to continue. We wanted to be able to unblind the study and evaluate what needed to be changed if that wasn't the case. However, the study remained blinded. So we know that the data monitoring committee saw something, selected a dose, and rolled the study forward to part two.
Does your conviction in the likelihood of success in PSC differ from PBC, and if so, why?
Not at all is how I would answer that. I mean, across all of these settings, in particular when you look at the PBC interim data, which we think informs what could be happening in that blinded PSC data, it is a highly active dose. So really confident that Volixibat is a relevant medicine for both of these settings, where while the underlying disease may differ, the commonality is that there is a restriction in bile flow causing cholestasis. They have elevated bile acids and pruritus. And I think that another element to add on top of that conviction is the screening criteria, how we've enrolled these studies, is common across the two. So we're screening for baseline pruritus due to cholestasis, similar profile for entry criteria between the two studies.
This is a sort of a different version, but similar question. So if we see positive data for PSC, should we read that across positively to the PBC study?
I do think that there is reason to extrapolate between these indications. We'll be excited to share that data when we get to it and share any findings that might be unique or change that view. But overall, IBAT in these settings has a really consistent response.
What do you see as kind of the market opportunity for Volixibat in PSC and PBC, and kind of how much of each market could Volixibat capture?
Yeah. There's a very unique market opportunity that is different between the two. And I spend a little more time maybe talking about PSC, because it is just a lot easier to get your head around. In PSC, there are no approved therapies. There is a desperate need for new medication. And pruritus is a burden across most of these patients. We think that the pruritus is likely underreported. When you talk with patients and some of the advanced practitioner team versus physicians, it comes up to be as high as 90% of patients talk about pruritus as an element of their disease. So getting a new therapy out there will be high impact. And Volixibat is really the only agent we see on the horizon with a near-term approval potential. Endpoints have been really challenging for PSC.
This is quite different than the PBC setting, where FDA and industry have not come up with adequate surrogate markers to use for approval in PSC, so the path kind of points towards a much longer outcomes approach, which is daunting, and with the VISTAS study, we found an alternate path, so we've been able to use itch as the outcome in a reasonable amount of time to get a new medicine approved for PSC patients, so it's a really unique positioning for how we're approaching it and bringing it forward, and that plays through for a market opportunity that there's 20,000 estimated addressable patients in the U.S., Volixibat being the only approved therapy, we think there's a really high potential for Volixibat in that setting. PBC is a little more competitive, so there's some nuance in patient segmentation.
We talk about breaking up the PBC market into kind of a first and second line setting. First line setting are patients that start UDCA and have control or a lowering of their biochemical measures, namely alkaline phosphatase, so an alkaline phosphatase level of normal or normal to 1.67 times upper limit of normal tends to be how the first line setting is defined. There are no other therapies approved in that setting other than UDCA, and UDCA has not been shown to address pruritus, so that's one of the treatment opportunities for IBAT inhibition. The second line setting, PPARs have been recently approved there. They can really target and address some of the biochemical disruption. They have reported some effect on itch as well, but frankly, at lower rates than what we see from the IBAT studies.
So we see the evolution of the second line market really being patient-by-patient consideration on how the PPARs in an IBAT might get sequenced or used, depending on an individual patient's disease burden, symptomatic burden, and some of the decisions they're making with their physician.
Assuming positive data in PSC, how are you preparing for commercialization?
So a lot of what we already have in place overlaps with where we're going for Volixibat. Namely, last year, we already expanded our field medical team to cover the expansion into adult hepatology and GI. For Livmarli, we're already targeting some of the kind of the top adult hepatologists as well. So that overlaps substantially with the KOLs and some of the prescribers for Volixibat. We are planning to have a field expansion to get to more of the community physicians and GI physicians that see a large number of PSC and PBC patients and hepatitis delta. So it's really an expansion for all three of these indications for the two medicines in the pipeline. Current planning is probably about another 30-40 people in the U.S. field force.
We'll have kind of similar plans on a scale-up across some of our direct Western European markets, where it would be smaller numbers, but kind of a similar scale of expansion.
On the slide, it looks like both the VISTAS data and the AZURE 1 interim are coming in Q2. Which comes first?
At this point, I haven't clarified which comes first, but we'll have two great announcements on what I think are going to be really compelling data sets.
Maybe while we're on it, we can just expand a little bit on what specifically makes you confident in positive phase three results for the BlueJ asset.
For the Brilovatug program, the phase 2 data are just so striking. And so with that 100% virologic response, we do expect that to replicate across other settings and some of the aspects of the design of the phase 2 program, and frankly, of a competing program, which also has a hep B surface antigen antibody in it, where you're seeing consistent response on HDV viral load and ALT normalization. So we've seen this across multiple sequential cohorts with Brilovatug itself in the phase 2 program, so kind of replicating in independent cohorts, as well as seeing in the Tobevibart program that's been presented as well, showing another HB surface antigen that has driven some virologic response. So we know this is an active and relevant mechanism. Really confident in the dosing regimen for Brilovatug that was chosen in the phase 3 program.
That's what was shown to be so active in the phase 2. And really, as an antiviral, you see these data sets replicate quite well in most cases. So confident that we're tracking towards bringing Brilovatug to hepatitis delta patients.
What is the addressable market for hepatitis delta in the U.S. and then Europe and then elsewhere?
Yeah. In the U.S., we talk about these 15,000 diagnosed insured patients that we've analyzed from claims data. The prevalence is actually much larger than that. We think it's probably 40,000. But the diagnosis is really insufficient for hepatitis delta. It's a co-infection with HBV. And to date, there has not been kind of automatic reflex testing to test for delta if you are diagnosed with HBV. And we think that's an important step in guidelines to help bring better diagnosis to these patients. And there's actually been recent experience in Europe that has shown that can change diagnosis rates, moving from what to date is more of a risk-based hepatitis delta testing paradigm to one that's reflex, where you get a hep B diagnosis, you automatically test for delta.
So working towards doing that in the U.S., we think can expand from that 15,000 patients to more diagnosed and more brought to care. As you get into other geographies, the prevalence actually can be substantially higher. Some of our direct markets in Southern Europe, we think, are going to be higher prevalence countries. And then as you get into Eastern Europe and parts of Asia, there are some very high prevalence countries as well. But in terms of our direct markets, North America, the U.S. numbers is what we're going after with the AZURE One and Four program in the second half of this year. Subsequent studies will expand into those other settings.
Okay. Looks like we're about out of time. So we'll stop there. So thank you.
Excellent. Thanks for the interest.