Good afternoon, and welcome to Mirum Pharmaceuticals Third Quarter 2026 Earnings Conference Call. My name is Joel, and I will be your operator today. All lines are currently in a listen-only mode, and there will be an opportunity for Q&A after management's prepared remarks. I would now like to hand the conference over to Andrew McKibben, SVP of Strategic Finance and Investor Relations. Please go ahead.
Thank you, Joel, and good afternoon, everyone. I'd like to welcome you to Mirum Pharmaceuticals Third Quarter 2026 Conference Call. I am joined today by our Chief Executive Officer, Chris Peetz, our President and Chief Operating Officer, Peter Radovich, our Chief Medical Officer, Rob Myers, and our Chief Financial Officer, Eric Bjerkholt. Earlier today, Mirum issued a press release announcing the company's results for the third quarter of 2026. Copies of the press release and our SEC filings are available on the Investors section of our website. Before we start, I'd like to remind you that during the course of this conference call, we will be making certain forward-looking statements based on management's current expectations, including statements regarding Mirum's programs and market opportunities for its approved medicines and product candidates, and financial guidance.
These statements represent our judgment and knowledge of events as of today and inherently involve risks and uncertainties that may cause actual results to differ materially from the results discussed. We are under no duty to update these statements. Please refer to the risk factors in our latest Form 10-Q and subsequent SEC filings for more information about these risks and uncertainties. With that, I'd like to turn the call over to Chris. Chris?
Thanks, Andrew. Third quarter was another strong period for Mirum, both commercially and across our clinical programs. We generated $186 million in third quarter net product sales, and we are increasing our full year net product sales guidance to $715 million-$720 million. We have also had great progress across the portfolio since our last earnings call.
Positive phase III AZURE-1 data for brelovitug, positive EXPAND data for LIVMARLI, the approval and launch of ATEBRIOZ, and another positive ATEBRIOZ readout in younger patients. Our recent progress feels quite meaningful as Mirum approaches its eighth anniversary. It is remarkable to think about what this team has accomplished in eight years. We started Mirum around a simple idea, that by identifying important opportunities in rare diseases and combining great medicines with relentless execution, we could have a meaningful impact for patients and build an enduring company.
Eight years later, we now have four approved medicines, a commercial business approaching three-quarters of a billion dollars in annual net product sales, and a late-stage pipeline with multiple opportunities to drive our next phase of growth. Coming up, we have two more potentially registrational readouts approaching, with the brelovitug AZURE-4 study in HDV expected this quarter and the volixibat VANTAGE study in PBC expected in the first quarter of next year. Together, these are part of five potential approvals and label expansions ahead of us as we work towards realizing the greater than $4 billion peak revenue potential of the Mirum portfolio. Eight years in, we're entering our next phase from a position of real strength, and we're excited to touch on some highlights and updates today. With that, I'll turn the call over to Peter. Peter?
Thanks, Chris. The third quarter was another excellent quarter for Mirum's commercial business, with $186 million in net product sales. LIVMARLI continues to be the primary growth driver, with third quarter net product sales of $133 million, including $100 million in the U.S. Our bile acid medicines also provided steady growth, generating $52 million in net product sales for the quarter. Continued growth across LIVMARLI and our bile acid medicines has allowed us to increase that outlook throughout the year, and based on our performance through the first nine months, we are increasing full-year guidance today to $715 million-$720 million.
This is a testament to our high-impact medicines and the high-performing team dedicated to getting them to patients. For a little more color on LIVMARLI, in Alagille syndrome, uptake remains steady and durable, supported by new patient starts, persistence on therapy, and weight-based dose increases.
PFIC continues to be an important driver, particularly among adults, where we believe there are at least 2,000 addressable patients in the U.S., though the substantial majority of these patients remain undiagnosed. Greater awareness of later-onset PFIC and increasing use of genetic testing will continue to help improve diagnosis rates, and we are expanding our commercial efforts on this front, which should lay a strong foundation for 2027. This expansion will also enable our other upcoming potential launches for LIVMARLI, volixibat, and brelovitug. I'm also happy to say that our fourth medicine, ATEBRIOZ, was approved in September for adults and pediatric FOP patients ages 12 and older, and our U.S. launch commenced in October. ATEBRIOZ is a natural addition to our rare genetic disease business.
The FOP community is uniquely engaged, and the response to the approval to date reinforces our belief that ATEBRIOZ can address a significant unmet need for patients and families living with FOP, with the convenience of oral dosing and a mechanism designed to address the underlying cause of the disease. Our near-term focus is on patient identification and access, and we're encouraged by the strong early engagement from patients, caregivers, and healthcare professionals. Overall, I'm very happy with the progress we made this quarter. We are growing our existing medicines, launching our fourth medicine, and laying a strong foundation for multiple new potential indications and launches in 2027 and beyond. With that, I'll turn it over to Rob. Rob?
Thanks, Peter. It's been an exciting couple of months for Mirum, with significant clinical progress across rare liver and rare genetic diseases. We are now working towards five potential regulatory submissions across the portfolio: NDAs for volixibat in PSC and PBC, a BLA for brelovitug in hepatitis delta, a label expansion for ATEBRIOZ in FOP, and an sNDA for LIVMARLI based on the EXPAND study. Starting with volixibat in PSC, we continue to make progress toward our planned NDA submission in the first half of 2027. We remain confident in the strength of the VISTAS results and the potential for volixibat to address an important unmet need for patients with PSC and pruritus. We look forward to submitting our NDA and will provide an update if there's any material change in our plans or an FDA's prior feedback.
We've also recently reported positive results from three important studies across the portfolio. In FOP, cohort two of the pivotal PROGRESS study extended the encouraging ATEBRIOZ results into children ages six to under 12. The results were consistent with cohort one, with reductions in heterotopic ossification, encouraging improvements in joint mobility, and a safety profile consistent with that observed in older patients. The mobility findings are particularly encouraging in a progressive disease like FOP, where preserving function by intervening early is especially important.
Our next step is the planned sNDA submission in the first half of 2027 to potentially expand ATEBRIOZ to children ages six to under 12. Cohort three, evaluating zilurgisertib in even younger children, continues to enroll. Now, turning to the liver portfolio, EXPAND was another positive phase III study for LIVMARLI, meeting its primary endpoint and all pre-specified secondary endpoints, with particularly encouraging results in biliary atresia.
These findings further strengthen the body of evidence supporting IBAT inhibition for pruritus across a range of underlying cholestatic liver diseases. In hepatitis delta, the positive phase III AZURE-1 results provide important validation for brelovitug, demonstrating meaningful improvements across key measures of virologic and liver disease activity. We'll build on this momentum at AASLD later this week, where we'll present new data across our rare liver disease portfolio, including the full AZURE-1 results and longer-term brelovitug data, as well as additional analyses from VISTAS and LIVMARLI data in rare cholestatic liver disease.
Without getting ahead of these presentations, we're particularly excited by the growing body of evidence with brelovitug, showing deepening virologic suppression and continued improvements in ALT normalization and liver stiffness with longer treatment, including in patients with cirrhosis, a population with particularly urgent unmet medical needs.
Looking beyond AASLD, we expect the AZURE full readout this quarter, an important next milestone for the brelovitug program and our planned BLA submission in the first half of 2027. Overall, these recent clinical successes, together with the regulatory milestones ahead, give us strong confidence in the potential for our portfolio to deliver meaningful new treatment options for patients. With that, I'll turn it over to Eric to discuss the financials. Eric?
Thanks, Rob, and good afternoon, everyone. Our third quarter financial performance reflects our ongoing operating priorities, continued top-line growth with focused investment in bringing our late-stage programs through several potential approvals and launches. As Peter mentioned, net product sales for the third quarter were approximately $186 million, compared with $133 million in the third quarter last year. Through the first nine months of the year, net product sales were approximately $522 million, which I am excited to point out already equals full-year 2025 revenues. In the third quarter, the cash contribution margin from our commercial business was in the high 50s percent of sales, and cash used in operations was approximately $4 million.
Total operating expenses for the quarter were approximately $245 million, cost of sales of approximately $28 million, SG&A expense of approximately $70 million, R&D expense of approximately $94 million, all on a cash basis, in-process research and development of $13 million, and stock-based compensation, depreciation, and amortization expense of $40 million. Our investment in R&D reflects the breadth of activity across our expanded late-stage pipeline, as well as the planned manufacturing expenses for our HDV program. On a cash basis, R&D was approximately 50% of revenues, as expected. We expect this level of R&D spend to continue for approximately two more quarters. In total, revenues this quarter exceeded expectations, while expenses are on plan. We also took steps this quarter to improve our capital structure.
In September, we repurchased $20 million in aggregate principal amount of our 2029 convertible notes for approximately $62 million in cash, thus further reducing both future dilution and ongoing interest expense. This follows the financing we completed in the second quarter when we issued $690 million of zero-coupon convertible notes due in 2032 and settled 75% of the outstanding 2029 notes. Together, these transactions have reduced the outstanding balance of our 2029 notes by over 80% while preserving substantial financial flexibility. As of September, cash equivalents, and investments were approximately $500 million. Our commercial business continues to scale, and our balance sheet gives us the resources to support our upcoming launches and late-stage clinical programs. With that, I will turn the call back to Chris.
Thanks, Eric. Taking stock of where we are today, Mirum is at a strong inflection point. Commercial business continues to outperform, driving an increase in our full-year guidance. We have launched ATEBRIOZ as a fourth commercial medicine, and including the ATEBRIOZ supplemental NDA for younger patients, we have five upcoming approval opportunities to further accelerate the commercial business. The strong performance commercially, paired with our pipeline advancements, positions us to be cash flow positive next year. As we wrap up our prepared remarks, I want to direct attention again to the upcoming brelovitug datasets being presented at AASLD this weekend. With data maturity now out to two years from the early program, we will be able to share more of a complete picture of what brelovitug can achieve for patients with hepatitis delta.
As we approach our eighth anniversary, I am incredibly proud of what this team has built, but even more excited about what is ahead as we enter a unique period of commercial growth, multiple launch opportunities, and strong financial performance. Finally, as always, I want to thank the entire Mirum team for their exceptional execution, the patients, families, and physicians whose partnership keeps us focused on what matters most. We have a lot to look forward to. With that, operator, please open the call for questions.
We will now begin the question-and-answer session. If you would like to ask a question, please press star one to raise your hand. To withdraw your question, press star one again. We ask that you pick up your handset when asking a question to allow for optimum sound quality. If you are muted locally, please remember to unmute your device. Please stand by while we compile the Q&A roster. Your first question is from Josh Schimmer with Cantor Fitzgerald. Your line is now open. Please go ahead.
Great. Thanks for taking the questions. Just a couple of quick ones. First, were there any Takeda purchases of LIVMARLI this quarter or expected in the next quarter as part of the revised guidance? Then second, for the [inaudible] and or the CHOLBAM and CTEXLI franchise, at least combined, you are starting to get to levels that I think historically you have suggested might attract generic interest or competition, not necessarily breaking out the relative contribution of each, but how should we be thinking about modeling the exclusivity of that franchise?
Josh, thanks for the questions. First, I can hit on the bile acid franchise, and we are really excited with how these have grown. Just as a quick reminder on the backdrop on exclusivity, for CHOLBAM, that is now beyond its orphan exclusivity time period. But CTEXLI does have orphan protection. They are both contributors here, and for both of them, we actually, we have not seen an entrant. That is really all we have visibility to at this point, to speak to. So, see the trends we are seeing for the near term, in any case, to roll forward. I will ask Eric to maybe speak to Takeda dynamics.
Yes. Thanks, Chris. We had very minimal revenues from Takeda this past quarter, and we do not really expect any new orders in Q4.
Got it. Thank you.
Next question.
Your next question is from Kalpit Patel with Wolfe Research. Your line is now open. Please go ahead. Hi there, Kalpit. Your line is now open. Please go ahead with your question. We will move on to the next question. Your next question is from Brian Skorney with Baird. Your line is now open. Please go ahead.
Hi, team. Could you provide a little more color on your confidence in the timing of the planned PSC submission? What is the next regulatory touchstone we should be looking for here? This is Luke, by the way. Thank you.
Hi, Luke. Thanks for the question. On the PSC situation, for the time being, really nothing changed in what we can speak to and the status of the program. Strategy is underway, and as we spoke about previously, multiple different touch points as we work towards a potential submission in the first half of next year. I would say we are really confident in the datasets. Rob called out some of the abstracts at AASLD that touch on IBD safety, for example, some of that work coming out of our prep for that NDA submission. Just kind of come back to, we feel really confident in our guidance to submit an NDA in the first half of next year. Beyond that, no material updates to what we have seen or heard.
Great. On ATEBRIOZ, I guess, has there been any difference in the early launch experience as far as compared to your expectations going into it?
Yeah, it is early days. I will hand over to Peter to get some color.
Yeah, Luke, as Chris mentioned, early days, just launched in October, so we are a couple weeks in. But really positive feedback from patients, caregivers, physicians. I think high receptivity to the value proposition we see with ATEBRIOZ, so we are really excited, but obviously early days to get to any more detail than that.
All right. Thanks, team.
Your next question is from Gavin Clark-Gartner with Evercore ISI. Your line is now open. Please go ahead.
Hi, this is Yesha on for Gavin. We were just wondering if ahead of the Q1 VANTAGE readout for PBC, there were any blinded baseline or trial conduct metrics you are expecting to share, in particular maybe like baseline itch severity, background therapies, discontinuation rates, anything along that realm. Thank you.
Thanks, Yesha, for the question. I think maybe Rob can speak to a little bit of the trial design, but probably not too much on the actual data to speak to at this point.
Yeah, really not much to report at this point, and we're still tracking towards reporting the data in the first quarter of next year, and I think premature to talk about baseline characteristics and aspects of study conduct at this point.
Thanks so much.
Your next question is from Kalpit Patel with Wolfe Research. Your line is now open. Please go ahead.
Yeah. Hey, good afternoon, and thanks for taking the questions. Two from us. For the guidance raise, is most of that related to the adult PFIC patients that are growing for LIVMARLI, or are there other areas that are contributing to that growth? For the second question, for the PSC-IBD subgroup data that you will be presenting, can you comment if those data have been submitted previously to the FDA, or are these new analyses that need to be sent? Thank you.
Thanks for the question. I mean, I can just touch on the PSC one briefly and then hand the guidance question over to Peter. I mean, these are new analyses, so kind of more in detail review of data that FDA had not seen previously.
Yeah, Kalpit, on the guidance question, we do see strength across the portfolio, continued growth in Alagille syndrome, bile acid products doing very well. But yeah, adult PFIC is the biggest driver, and we have line of sight now after several quarters of this cadence of $10 million-$15 million quarter-on-quarter step up for that to persist through this year and through next year as well.
Okay, thank you.
Thanks for the question.
Your next question is from Ryan Deschner with Raymond James. Your line is now open. Please go ahead.
Thanks for the question, and congrats on the quarter. I am curious on your expectations for the relative launch trajectory for ATEBRIOZ, and if you would expect, at least early on, any signs of a bolus coming in for that to slow down later on in the early launch. Just curious on your thoughts there. Thanks.
Ryan, thanks for the question. I will let Peter speak to that and probably even speak to the broader portfolio as we roll into next year.
Yeah. ATEBRIOZ's early adoption and inbound interest has been really strong, and we are excited about that. I think if I were to compare ATEBRIOZ's launch trajectory and adoption curve to LIVMARLI, it probably will be faster. I think take LIVMARLI, we are in Alagille syndrome. It has been about five years since the original FDA approval, and about 50% of addressable patients with Alagille syndrome have gone on LIVMARLI, and we are still seeing growth quarter-over-quarter. I think if you were to think about that as a comparator, we would expect ATEBRIOZ to be faster adoption dynamics at this point.
The one thing I would add on is, as you look at Q4 and even into next year, the cadence of growth we have seen for total revenue in this kind of $10 million-$15 million a quarter, we fully expect that to continue throughout next year.
Thank you very much.
Thanks for the question.
Your next question is from James Condulis with Stifel. Your line is now open. Please go ahead.
Hey, thanks for taking my question, and maybe just one on PSC, and appreciate there's only so much you can say. But I think you've mentioned in the past that in the discussion with the FDA, there was nothing really new, you felt was new that wasn't already in the original VISTAS study. Just curious if that's still the case from your perspective. Then just in general, do you expect there to be a sort of formal alignment here, kind of ahead of filing, or is it just sort of TBD in terms of how the discussion evolves? Thanks a lot.
Yeah, James, thanks for the follow-up there. Overall, because this situation we're seeking multiple different interaction points, multiple meetings, we're not providing kind of meeting-by-meeting updates. Really what I can say is we're pointing towards that first half NDA. To kind of remind on the goal here is, given that the dataset is so robust and there's a lot to review, the goal of the interactions we're having is to get more familiarity with the dataset before submission, not necessarily in all cases complete alignment.
Makes sense. Thank you.
Thanks for the question.
Your next question is from Jessica Fye with JPMorgan. Your line is now open. Please go ahead.
Hey, guys. Good afternoon. Thanks for taking my question. I was looking at the press release, and it looks like there is a lot of regulatory submissions going in in the first half of 2027, and I was curious if you could just speak to kind of the organizational bandwidth to bring in additional assets via business development during what seems like a really busy time. Basically, should we expect a little breather on the BD side in the near term while you get all these things into the FDA?
Yeah, Jess, thanks for the question. Yeah, it is a very busy first half of the year for submissions. You are absolutely spot on with that. We have done a lot. We saw this coming, so we have done a lot to organize for it, and we are in really good shape from a team standpoint on having these efforts staffed, and expect that we will be able to manage through it without issue. In terms of what it means for BD, we continue to be opportunistic. So if the right opportunity comes, we want to be able to pursue it. However, more of an earlier clinical stage opportunity would be a little easier to add in at this point. But that doesn't mean we are not continuing to have an opportunistic lens on all opportunities.
Does that include commercial stage?
Yeah, absolutely. I mean, I'd pass over to Peter to kind of talk about our lens on, again, more broadly on BD scope and targets that we like.
Yeah, I mean, as Chris mentioned, I think our philosophy is you always have to be active. And we look clinical stage through commercial stage. We think about rare disease as a capability in the therapeutic area in and of itself, so it has the know-how to be successful with rare disease medicines, whether it's development, regulatory, patient finding, patient access. Feel really good about the capabilities we've built there and kind of look broadly for underappreciated rare disease assets where we think we could potentially add value.
Great. Thank you.
Thanks for the question.
Your next question is from Yigal Nochomovitz from Citi. Your line is now open. Please go ahead.
Hi, guys. Thank you for taking the questions, and congrats on the strong quarter. I just wanted to switch topics onto HDV and the AZURE-4 readout. Obviously, that is a second phase III trial, which is good, but can you just speak to what additional nuances or additional learnings you might glean from AZURE-4 to further drive the strength of the BLA. Then with regard to the HDV market, could you just talk to what you are watching for in terms of HDV diagnosis rates potentially expanding as you get closer to a launch? Thank you.
Yeah, thanks for the question, Yigal. I will ask Rob to maybe recap some of AZURE-4 design and rationale, and then let Peter speak to the market question.
Yeah, thanks, Chris. AZURE-4 is an important part of the registrational package for brelovitug in the U.S. Just as a reminder, it's designed very similarly to AZURE-1, with the exception of patients in the late treatment arm crossing over at 12 weeks instead of 24 weeks. In terms of our expectations, of course, we expect to see complementarity or consistency in the virologic responses and ALT normalization, as well as safety to that which we observed in AZURE-1.
Then in terms of the question on HDV diagnosis rates and how we see this undeveloped market developing over time, we actually have a small team that's pretty active now doing disease state education and awareness with the providers across the country who manage hepatitis B patients and in areas where they likely have undiagnosed delta patients as well. I think one of the things we've learned as we've been out in the field is there's really been very little testing to date. There's papers that show single-digit percentages of, low single-digit percentages of hep B patients have ever received a delta test.
I think one of the big pushbacks from providers historically has been lack of therapies for this condition. I think we're seeing that change now and look to see increased interest in testing over time and excited about the early trends we're seeing.
Thanks.
Thanks for the question.
Your next question is from Mike Ulz with Morgan Stanley. Your line is now open. Please go ahead.
Good afternoon. Thanks for taking the question, and congratulations on the strong quarter as well. Maybe just a follow-up on volixibat and the upcoming VANTAGE data next quarter. Can you just remind us what the bar is on pruritus and then what you think is sort of a meaningful benefit there? Thanks.
Thanks, Mike, for the question. I can make a couple observations and ask Rob to maybe speak to expectations. I think the one thing that I point towards is for this study, we have the interim readout, so we know what's possible for volixibat. Really substantial improvements versus placebo, over a 2-point placebo-adjusted difference. That is really compelling and competitive if we're anywhere in the ballpark of what we saw in the interim. Rob, do you have anything to add on to that?
Yeah, no, just that the interim data were quite compelling. As mentioned, we see over a 2-point placebo-adjusted improvement in the volixibat arms. We've done a bit of work to validate the Adult ItchRO to show that this magnitude of reduction is actually clinically important. We feel very confident going into the readout next quarter.
Great. Thank you.
Thanks for the question.
Your next question is from Lisa Walter with RBC Capital Markets. Your line is now open. Please go ahead.
Oh, great. Thanks for taking our question, and congrats on the quarter. Maybe just given the recent challenges with the FDA and PSC, just curious if the same group of regulators will also be reviewing your filings for biliary atresia as part of the EXPAND study, as well as a potential filing for PBC. If so, what gives you confidence that the FDA will understand those rare diseases a little bit better and your trial designs better versus what we have seen for PSC? Any color here would be helpful. Thanks so much.
Thanks, Lisa, for the question. From a simple standpoint, these are all with the liver division. However, knowing who is assigned to the review, something we do not have visibility to at this point in time. What I would say is for VANTAGE and for EXPAND, really clear dialogue along the way on study design, all of the choices we made in those studies, and some of it quite recent interactions. So, do feel confident in our position heading into those submissions. The one thing I would add on is what the contrast of that to PSC is that interactions with PSC were really mostly in 2019 and 2020, so a bit more distant just from a time standpoint.
Your next question is from Joe Schwartz with Leerink Partners. Your line is now open. Please go ahead.
Thanks very much. Can you talk about what we should watch for at AASLD for brelovitug in terms of the full AZURE-1 presentation, what our focus should be, and will any updates from the phase II trials be presented too? Then we noticed that the brelovitug BLA is now described as subject to supportive AZURE-4 results. Is that new caution or just standard language? Can you talk about what counts as supportive? Given that AZURE-4's control group waits only 12 weeks, would you file on AZURE-1 plus the phase II-B data if AZURE-4 were more mixed?
Thanks for the question, Joe. On that last point, there is nothing new here. AZURE-1 and 4 have always been the proposed phase III package for brelovitug. The simple way to think of it is the study was designed with the FDA before orphan designation was granted, so they were looking for two pivotals. Really nothing different from patient population overall dynamics here that would suggest a big difference between the two. It is just about having two pivotals. Now we do have orphan designation, so hindsight, hard to say how that would have been treated, but that is the case and has always been the plan for submission. I will ask Rob to maybe give the highlights and directions for AASLD.
Yeah, we have some exciting data on brelovitug at AASLD. As you mentioned, we will present the AZURE-1 results in full, 24-week data, phase III data, and as well, the 48-week phase IIb component. Lastly, we have an abstract on patients with cirrhosis from the original phase II study who have been treated out to two years. Really, that entire data package, it is robust. I mean, it tells us that we do see excellent rates of virologic suppression and ALT normalization as early as week 24, but that with prolonged treatment, greater virologic suppression, greater rates of ALT normalization, including in patients with advanced disease, cirrhosis, and quite significantly elevated ALT. So, I think the brelovitug package is quite strong. Looking forward to our AZURE-4 data by the end of this year.
Thanks for the color.
Thanks for the questions.
Your next question is from Jon Wolleben with Citizens JMP. Your line is now open. Please go ahead.
Hey, thanks for taking the question. Was hoping to get some more color on how you guys are thinking about your peak sales guidance in HDV and then PBC/PSC, just given the relative prevalence and moving dynamics in those markets. What's underlying that billion dollars, or is that just a simple guidepost to think of as a starting point? Just wondering how granular you guys have gotten internally there.
Yeah, thanks for the question, Jon. The one thing I'd say is overall, meant to be an approach in how we give these on giving kind of greater than a certain target. Important lens to put on it as you're thinking about it, but Peter can speak a little bit to some of the color on how we came to these numbers.
Yeah. Yeah, thanks, Jon. I think in delta, the guidance of greater than $1 billion, there's a lot of ways to get there, quite frankly. I mean, even if you just look at the U.S. market and today, about 15,000 patients diagnosed with insurance under management, you'd only really need to get a few thousand of those on therapy chronically to get towards that greater than $1 billion guidance. Obviously, we know this is an underdiagnosed disease, and as we commented, very low rates of testing have happened historically in the U.S. Not to mention, there's a substantial international opportunity for brelovitug as well. I think, say the theme there is a lot of ways to get to greater than $1 billion. As you move over to volixibat, PSC, PBC, similar, addressable patient populations in the U.S.
For PSC, about 20,000 patients with PSC and pruritus.
You know, no competition there. PBC, a larger addressable market with about 50,000 addressable patients in the U.S., but, you know, a bit more competition. I think you could kind of do the math a number of different ways to get to the kind of numbers you would need to get to get to the greater [inaudible].
Real helpful. Thanks, Chris.
Thanks for the question.
Your next question is from Charles Wallace with H.C. Wainwright. Your line is now open. Please go ahead.
Hi. Thanks for taking my question. This is Charles on for R.K. For my first question, I was wondering how should we think about the R&D spend going forward, fourth quarter and then also 2027 with the placebo-controlled portion of AZURE-1 and 4 studies completing? I will come back with my second question.
Yeah. Thanks for the question. Speak to some of those trends.
Yeah. We like to measure it both in absolute terms and also as a percent of revenue. As I alluded to in my comments of the past couple quarters, we have been around 50% of revenue. We think that is going to continue at about that pace for two more quarters, and then subsequently decrease quite rapidly, I think, to 10% of revenue. That should be true long term as well.
Great. For my second question, beyond the AZURE-4 results, what additional items remain before you can file the BLA in the first half? Thank you. For brelovitug.
Yeah. Thanks for the question on that. For brelovitug, it really just comes down to pulling together the submission. All of the work streams from both the clinical studies and the CMC submission, all tracking towards being ready first half. All that's a lot of document prep and write-up that's left to do.
All right. Thanks for taking my questions.
Thanks for the questions.
Your next question is from Joseph Thome with TD Cowen. Your line is now open. Please go ahead.
Hi there. Good afternoon. Thank you for taking my questions. Maybe another one on HDV. We may have several agents approved for HDV, I guess, currently or over the next couple years here. What do you see as sort of the main differentiating features of brelovitug based on the data you have in hand that will drive adoption of brelovitug over some of these others? Then second, when we think about the potential cadence of BA coming online for LIVMARLI, obviously the FDA did ask you to do this based on requests. Is there a pocket of patients ready to come on therapy rapidly, or will it be gradual? How should we think about the cadence of that launch? Thank you.
Great. Thanks for the questions, Joe. I'll quickly make a couple of observations on HDV and let Peter add to it and speak to BA as well. The one thing I'd say is, when we put together the transaction with Bluejay around brelovitug, what we found really exciting about this program is that you had a fully human antibody, those single treatment that could drive continued improvement over time to some really impressive response rates, both on normalizing liver inflammation and on controlling and lowering viral levels. A lot of that data is what we're looking forward to sharing this weekend at AASLD to show updates on what that can get to at two years. That kind of gives the answer to how we think about our positioning with HDV. I'll pass over to Peter to touch up and add the BA comments.
I think it's very well stated on HDV and on the BA question, these patients are at the same centers, the pediatric liver docs that prescribe LIVMARLI today for pediatric PFIC and Alagille patients. So, the patients are there, as you noted in your question. The study was really started as a response to inbound interest from clinicians to use the product in this way. So, it's a pretty captive audience who are very familiar with the product, who have these patients in their clinics and under management now.
Great. Thank you.
Thanks for your questions.
There are no further questions at this time. I will now turn the call back to Chris Peetz, CEO, for closing remarks.
Great. Thanks, everyone, for joining today's call. Looking forward to a strong end of the year and a busy 2027. Good afternoon, everyone.
This concludes today's call. Thank you so much for attending. You may now disconnect.