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DATE

Wednesday, Aug. 5, 2026 at 4:30 p.m. ET

CALL PARTICIPANTS

  • SVP of Strategic Finance and Investor Relations - Andrew McKibben
  • Chief Executive Officer - Christopher Peetz
  • President and Chief Operating Officer - Peter Radovich
  • Chief Financial Officer - Eric H. Bjerkholt
  • Chief Development Officer - Lara Longpre

TAKEAWAYS

  • Net Product Sales -- $176.2 million for the second quarter, rising from $127.8 million in the second quarter of 2025.
  • LIVMARLI Net Product Sales -- $128.7 million, representing 46% growth over the prior year's second quarter.
  • Bile Acid Medicines Net Product Sales -- $47.5 million, an increase of 20% compared to the second quarter of 2025.
  • Full Year 2026 Net Product Sales Guidance -- $680 million to $700 million, updated based on strong commercial demand across the portfolio.
  • LIVMARLI U.S. Sales -- $92 million, driven by durable growth in Alagille syndrome and new patient starts in progressive familial intrahepatic cholestasis.
  • LIVMARLI International Sales -- $37 million, reflecting expansion across direct and partner markets.
  • Unrestricted Cash, Cash Equivalents, and Investments -- $561.3 million as of June 30, 2026, compared to $391.4 million at the end of 2025.
  • Total Operating Expenses -- $218.8 million for the second quarter, which included $16.4 million in non-recurring acquired in-process research and development expenses.
  • Research and Development Expense -- $76.3 million, with $28.8 million dedicated to the development of brelovitug.
  • Selling, General, and Administrative Expense -- $65.6 million, excluding stock-based compensation.
  • Stock-Based Compensation and Non-Cash Expenses -- $37.3 million, comprising stock-based compensation, intangible amortization, and other non-cash items.
  • Convertible Senior Notes Issuance -- $690 million aggregate principal at 0% coupon due in 2032, issued to improve the company's capital structure.
  • 2029 Convertible Notes Settlement -- $237.2 million in aggregate principal settled, representing 75% of the outstanding notes.
  • Cash Contribution Margin -- high-50s %, representing a 5 percentage point improvement over the prior year.
  • Addressable Adult PFIC Population -- 2,000 patients in the United States, with a similar number estimated in the European market.
  • Zilurgisertib License Expense -- $16.4 million, recorded as an upfront payment during the second quarter.
  • Volixibat Safety Database -- over 600 subjects across the clinical program to date, including more than 180 primary sclerosing cholangitis patients.
  • VANTAGE Study Enrollment -- over 330 patients randomized, completing the enrollment phase for the study in primary biliary cholangitis.
  • Diagnosed FOP Patients in the U.S. -- 300 patients, primarily managed in specialized treatment centers.
  • LIVMARLI Peak Revenue Potential -- over $1 billion, supported by expansion into adult PFIC and additional cholestatic conditions.
  • Cost of Sales -- $23.2 million, excluding intangible amortization and stock-based compensation expense.
  • Net Loss -- $67.2 million, or $1.06 per share, compared to a net loss of $5.9 million in the second quarter of 2025.

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RISKS

  • Peetz stated, "This engagement will delay the planned timing of our NDA submission, which we are now targeting for the first half of next year," after the FDA recommended conducting a Phase 3 study for volixibat in primary sclerosing cholangitis.

SUMMARY

Mirum Pharmaceuticals, Inc. (MIRM +0.75%) reported total product sales of $176.2 million for the second quarter of 2026, supported by demand for LIVMARLI and its bile acid portfolio. Management raised the full-year net product sales guidance to a range of $680 million to $700 million. The company is advancing several pipeline candidates, including zilurgisertib for fibrodysplasia ossificans progressiva and brelovitug for chronic hepatitis delta virus, with multiple regulatory and clinical milestones expected by the end of the year. Strategic focus includes expanding the adult PFIC patient population and engaging with the FDA to resolve clinical study requirements for volixibat in primary sclerosing cholangitis.

  • The FDA granted Breakthrough Therapy and Orphan Drug Designations for volixibat in cholestatic pruritus due to primary sclerosing cholangitis based on results from the VISTAS study.
  • CEO Peetz stated, "We are positioned to move quickly once we have further clarity from the agency," regarding ongoing discussions to supplement the volixibat regulatory submission.
  • Management expects top-line results from the Phase 3 AZURE-1 and AZURE-4 studies for brelovitug in chronic hepatitis delta virus during the third and fourth quarters of 2026.
  • The PROGRESS study of zilurgisertib showed an efficacy profile that management believes will support a potential U.S. launch in the fourth quarter following a Sept. 26, 2026, PDUFA date.
  • President Radovich noted that the adult PFIC market represents a "meaningful opportunity to continue expanding diagnosis through education" as genetic testing becomes more routine in adult practice.
  • Top-line data from the EXPAND study of LIVMARLI in additional rare cholestatic conditions is anticipated in the fourth quarter.
  • Management confirmed that the VANTAGE study in primary biliary cholangitis is on track for a top-line readout in the first quarter of 2027.

INDUSTRY GLOSSARY

  • ALK2: Activin receptor-like kinase 2, a protein receptor often mutated in patients with fibrodysplasia ossificans progressiva.
  • ALGS: Alagille syndrome, a genetic disorder that can cause severe liver disease and other systemic complications.
  • BLA: Biologics License Application, a request to the FDA to market a biological product in the United States.
  • Brelovitug: An investigational monoclonal antibody designed to treat chronic hepatitis delta virus infection.
  • BSEP: Bile salt export pump, a protein responsible for transporting bile acids out of liver cells.
  • FOP: Fibrodysplasia ossificans progressiva, a rare genetic disorder where soft tissues permanently transform into bone.
  • HDV: Hepatitis delta virus, a viral infection that occurs only in people who are also infected with hepatitis B.
  • IBAT: Ileal bile acid transporter, a protein involved in reabsorbing bile acids in the small intestine.
  • PBC: Primary biliary cholangitis, a chronic disease where the bile ducts in the liver are slowly destroyed.
  • PDUFA: Prescription Drug User Fee Act, which establishes target dates for the FDA to complete drug reviews.
  • PFIC: Progressive familial intrahepatic cholestasis, a group of rare genetic disorders that cause progressive liver damage.
  • Pruritus: Severe itching, a common and debilitating symptom of various cholestatic liver diseases.
  • PSC: Primary sclerosing cholangitis, a chronic liver disease characterized by inflammation and scarring of the bile ducts.
  • SNDA: Supplemental New Drug Application, an application to add a new indication or make changes to an already approved drug.
  • Volixibat: An investigational oral agent designed to selectively inhibit the ileal bile acid transporter.
  • Zilurgisertib: An investigational oral small molecule inhibitor being developed for the treatment of FOP.

Full Conference Call Transcript

Operator: Good afternoon, and welcome to Mirum Pharmaceuticals Second Quarter 26 Earnings Conference Call. My name is Alexandra, 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.

Andrew McKibben: Thank you, Alexandra, and good afternoon, everyone. I would like to welcome you to Mirum Pharmaceuticals second quarter 26 conference call. I am joined today by our Chief Executive Officer, Christopher Peetz our President and Chief Operating Officer, Peter Radovich and Eric H. Bjerkholt, our Chief Financial Officer. Lara Longpre, our Chief Development Officer, will be joining us for the Q&A portion of the call. Joanne Quan, our Chief Medical Officer, could not be with us today due to a family matter. Earlier today, Mirum issued a press release announcing the company's results for the second quarter of 26. Copies of the press release and our SEC filings are available on the Investors section of our website.

Before we start, I would 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 filings for more information about these risks and uncertainties.

With that said, I would like to turn the call over to Christopher. Christopher?

Christopher Peetz: Thanks, Andrew, and good afternoon, everyone. At Mirum, we are growing a rare disease leader focused on delivering high impact medicines for often overlooked diseases. This quarter demonstrates continued progress with strong commercial execution on our approved medicines as we head into the potential launch of our fourth commercial medicine later this year. We have a busy pipeline with multiple pivotal readouts in the quarters ahead, all delivered with the strength in capital structure and overall financial performance, giving us greater capacity to invest throughout the business. In the second quarter, our commercial business generated $176 million in net product sales, reflecting strong demand across the portfolio and excellent execution by our team.

Based on this performance, we are increasing our full year 2026 net product sales guidance to $680 million to $700 million Fueled by the strong commercial performance, we are driving towards the next phase of Mirum's growth with multiple milestones over the coming months. Our next commercial milestone will be the potential launch of Zilurgisertib for FOP with the PDUFA date next month. This is fast progress for a program added to our rare genetic business, only in the second quarter. Peter will cover more of the launch profile in his remarks. Moving to the pipeline for our rare liver business, important to spend some time today on volixibat and PSC. Which just had some key U. S. Regulatory interactions.

First, as a reminder of the background of the study of volixibat in cholestatic pruritus in PSC, we designed this adaptive study with input from the FDA as a pivotal trial for this difficult clinical setting. Including alignment on study duration, endpoints, and analysis plan. As we have announced previously and presented at EASL this year, VISTAS met its primary endpoint showing highly significant improvements in pruritus in the primary cohort. With consistent significant results also observed in a second cohort of patients with milder baseline pruritus. We are excited to share that the FDA has now granted breakthrough therapy designation for volixibat in cholestatic pruritus due to PSC based on these strong results.

We see this as recognition of the potential for volixibat to address a serious unmet need in PSC As planned, we recently held a pre NDA discussion with the agency about the submission of an NDA based on the VISTA study. In the meeting, the FDA recommended conducting a phase 3 study. We believe the VISTA study provides a robust and clear dataset to characterize the use of volixibat in patients with pruritus due to PSC, and is a clinically and statistically highly persuasive study.

VISTAS is the largest randomized clinical study conducted in patients with pruritus due to PSC with an extensive overall data package that includes more than 180 PSC patients, randomized 1-year safety exposure data for over 100 PSC patients and growing, results from an independent committee evaluating liver safety, all totaling over 600 subjects across the clinical program to date. So while we are not currently aligned on the NDA submission package, we will be engaging in discussions with the FDA on how to further supplement our planned submission based on the VISTA study. This engagement will delay the planned timing of our NDA submission, which we are now targeting for the first half of next year.

We are positioned to move quickly once we have further clarity from the agency. We will provide updates as we work towards our goal of bringing a much needed therapy to this unaddressed clinical setting. In parallel, the VANTAGE study in PBC is progressing well, and has completed enrollment reaching over 330 patients randomized. In PBC, our earlier breakthrough therapy designation has enabled more dialogue with the agency during the conduct of the study. We have recent feedback from FDA for Vantage to serve as a pivotal study of volixibat in pruritus due to PBC if the study is successful at its Q1 top line readout next year.

Our next clinical readout for the rare liver business is expected to be volovitug's AZURE-1 top line results later this quarter. This is the readout of the Phase III portion following strong results in phase IIb portion earlier this year, and we also continue to expect the AZURE-4 data in the Q4, which keeps us on track for a potential BLA submission for this breakthrough therapy designated program in the first half of next year. And rounding out the rare liver pipeline highlights, the Phase III EXPAND study of Livmarli and additional rare cholestatic conditions remain on track for top-line data in the Q4.

So putting this all together, we are advancing these clinical programs from a position of financial strength. Our commercial business continues to generate meaningful cash, providing the capacity to invest in potential launches, clinical development, opportunistic business development, where we see a compelling strategic fit and the potential to create value. I am proud of the team's progress and the promise of our current medicines and pipeline I am excited about what lies ahead for Mirum. And with that, I will turn the call over to Peter to discuss our commercial performance and launch readiness in more detail. Peter?

Peter Radovich: Thanks, Christopher. The second quarter was another strong quarter for Mirum's commercial business. With total net product sales of $176 million for Livmarli and the bile acid medicines both continue to perform well And based on the demand we see, we are increasing our full year 2026 net product sales guidance to $680 million to $700 million. Second quarter net product sales for Livmarli were $129 million, with the U. S. Contributing 92 million Alagille growth remains durable, supported by continued new patient starts, sustained persistence on therapy, and weight based dose increases. PFIC continues to be an important driver of growth, fueled by new diagnosis. We are particularly encouraged by the growing contribution from adult PFIC patients.

We are seeing an increase in prescriptions from adult liver providers as awareness of later onset PFIC grows. And genetic testing becomes more routine. Based on claims data as well as insights from 2 years in market, we now estimate an addressable adult PFIC population of at least 2,000 patients in The United States with likely a similar number in Europe. And because genetic testing remains less established in adult practice, then the 2,000 addressable patients do not yet have a PFIC diagnosis. And we see a meaningful opportunity to continue expanding diagnosis through education. Internationally, Livmarli continues to grow across our direct and partner markets. Contributing $37 million for the quarter.

We are seeing contributions from established markets, and expanding reimbursement in additional geographies. On the rare genetic disease side of the business, our bile acid medicines continue to provide steady contribution generating $48 million in net product sales for the quarter. Like our rare liver business, our rare genetics-- our rare genetics business is also poised for growth with the recent addition of Zilurgisertib for FOP. Data from the pivotal Phase II progress study of Zilurgisertib presented at ENDO showed a compelling clinical profile in FOP patients ages 12 and older.

Based on the strong efficacy observed and the convenience of oral dosing, we believe Zilurgisertib has the potential to offer an attractive profile to patients with this severely debilitating disease. If approved by the FDA, the initial launch opportunity is expected to focus on patients ages 12 and older, with potential future expansion into younger patients supported by additional cohorts in the PROGRESS study. And following a recent late cycle meeting with the FDA, we believe the NDA is proceeding as expected towards the September PDUFA date and we are preparing for potential U. S. Launch in the Q4. The U. S.

Launch will heavily leverage the rare genetics team we have in place now that currently markets our bile acid medicine. As the physicians who manage FOP are largely concentrated in the same specialized centers where CTEXLI and CHOLBAM are prescribed. Building on the efficiency of our rare genetics business. Also, a marketing application for Zilurgisertib has been submitted in Europe. And we will provide updates as this filing progresses. Overall, we are pleased with the continued execution across the commercial organization. We are seeing strong demand throughout the existing portfolio, while making the investments necessary to support the next wave of potential launches. We believe that we are well positioned for the remainder of the year and beyond.

With that, I will turn it over to Eric to discuss the financial results. Eric?

Eric H. Bjerkholt: Thanks, Peter, and good afternoon, everyone. Today, I will walk through the financials of another excellent quarter from Mirum. Net product sales for the second quarter were $176 million compared to net product sales of $128 million in the second quarter of last year. Cash equivalents and investments as of June 30 were $561 million compared with $391 million at the beginning of the year. In the second quarter and first half of 26, the cash contribution margin from our commercial business was in the high-50s percent approximately a 5 percentage point improvement over the year before.

Total operating expense for the quarter ended June 30 was $290 million, $19 million of which includes 16 million of in-process R&D expense associated with the upfront payment for licensing Zilurgisertib. R&D expense of $76 million including $29 million related to the development of volovitug, SG&A expense of $66 million, and cost of sales of $23 million, all excluding stock based compensation expense and intangible amortization. Stock based compensation, intangible amortization, and other noncash expenses totaled $37 million for the quarter. Operating cash flow was positive in the second quarter despite the expected increase in R&D expense.

During the quarter, we significantly improved our capital structure through the issuance of $690 million aggregate principal amount of 0% coupon convertible notes due in June 2032. Net proceeds from the offering were $672 million. In conjunction with this financing, we settled 75% of the outstanding 2029 notes added $197 million of cash to the balance sheet and significantly reduced our interest expense. These transactions further strengthen our balance sheet and extend our financial flexibility to execute our strategy. Our commercial business continues to scale and our pipeline includes multiple near term value drivers. With that, I will turn the call back to Christopher for closing remarks.

Christopher Peetz: Thanks, Eric. Taking stock of where we are we are continuing to drive our strategy to bring important medicines to underserved rare disease patients. Commercial business is thriving, now tracking towards 680 to $700 million in net product sales for the year. Livmarli is well on its way to realizing its over $1 billion peak revenue potential. And our rare genetics team is thrilled about the potential launch of Zilurgisertib for FOP patients in the coming months. On the pipeline, we are focused on a collaborative discussion with FDA on the VISTA study in PSC. Clinical results are clear, and breakthrough therapy designation gives us further opportunity to engage with FDA.

All said, we have a plan to advance volixibat for PSC patients. The balance of the pipeline is firing on all cylinders. Recapping our upcoming clinical milestones, we expect clinical readouts from the Phase III AZURE-1 and AZURE-4 studies of volovitug over the balance of the year which will enable our planned BLA submission in the first half of next year. Next quarter, we also expect to announce top line results from the EXPAND study of Livmarli and additional rare cholestatic diseases setting up the potential for an sNDA next year as well. And into 2027, we expect top line results from the VANTAGE study of volixibat in PBC in Q1.

And finally, we are on track with MRN-338, with proof of concept data in fragile X syndrome next year. Importantly, we are building an organization capable of reaching many more people living with overlooked rare diseases while delivering strong financial performance. I want to thank the Mirum team for their continued focus and execution, and to the patients, families, and physicians who continue to partner with us in this work. With that, operator, please open the call for questions.

Operator: We will now begin the question and answer session. Please limit yourself to 1 question and 1 follow-up. If you would like to ask a question, please press *1 to raise your hand. To withdraw your question, press *1 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 standby while we compile the Q and A roster. Your first question comes from the line of Ryan Deshner with Raymond James. Your line is now open. Please go ahead.

Ryan Deschner: Hi. Good afternoon. Congrats on the strong results. Curious what your overall take is on the potential read through from the BOLD study evaluating odevixibat in patients with biliary atresia? And I have a follow-up question.

Christopher Peetz: Thanks, Ryan, for the question. The BOLD study and the study of note in our pipeline that includes biliary atresia patients, the EXPAND study I mean, to put it simply, are asking very different questions. I would equate the BOLT study more to what we ran previously with EMBARK, looking at patients in the very acute setting trying to reduce bilirubin or extend transplant free survival. The question we are asking in EXPAND ties much more to where we have seen IBAT perform quite well in other settings. We are looking at older patients than what was in BOLD and in EMBARK and evaluating pruritus changes it is something that we have seen an impact from IBAT therapy.

Over and over again now in different clinical settings. So we feel there is not really a read through or connection between BOLD, and what we are looking at in the upcoming EXPAND readout.

Ryan Deschner: Appreciate it. And then, just on the PSC regulatory discussions, what key topics do you anticipate sort of addressing with these future discussions? Thank you.

Christopher Peetz: Yeah, thanks for the follow-up on that. I mean, just to kind of reiterate some of the background here. We did extensively discuss the VISTA study design with FDA Back in the pre IND setting, the FDA acknowledged that pivotal intent. Described the design as reasonable, gave direct feedback on duration, analysis plan, all these things that designed the study that we read out so successfully earlier this year. And frankly, the situation now that we have seen is in the meeting, there was a new team from FDA. And so we think there is a lot of work to kind of get them up to speed on the backdrop here.

So the history designing and conducting VISTA and what the study means in a PSC setting. So we think it is going to be an iterative approach to kind of get them up to speed, only with the current data package, but with the history of the program. Very helpful. Thanks, Christopher. Thanks for the questions.

Operator: Your next question comes from the line of Gavin Clark-Gartner with Evercore ISI. Your line is now open. Please go ahead.

Gavin Clark-Gartner: Hey, guys. Thanks for taking the questions. First, what was this new FDA team's rationale to conduct an additional phase 3? Like, was it more of a safety database question, or was it more around the efficacy side?

Christopher Peetz: Follow-up, Gavin. You know, the comments about a phase 3 recommendation from them. Really were not specific. So we do not have great clarity on what specifically they are looking for. There were comments across the board on more general on efficacy which we think VISTAs very clearly addresses, and they actually commented on that in the meeting. On the safety side, in the discussion, the couple of things that were brought up were IDD safety and the backdrop with IVAT GI effects. And liver safety, You know, those were designed into VISTAs as key things to evaluate.

So we think it is all there in the VISTA study, and it is more this is more about familiarity with study design and some of the questions that were asked. Another thing I would point out is that the breakthrough designation actually was issued after the meeting. So I think that is gives us a great opportunity to go back in and build up familiarity with this dataset and work toward an NDA.

Gavin Clark-Gartner: Okay. That makes sense. And just a quick follow-up. Is this a team that you have engaged with before on any of your other programs? Do you have any experience working with them? And I kind of on a similar point, what other regulatory precedents would support approval based on the similar type of phase 2 b setting? Thank you.

Christopher Peetz: Thanks for the follow-up. In terms of the team, a lot of times the correspondences written, so you do not have perfect clarity on who is behind some of the written correspondence. So it is hard to answer that question to be honest. In terms of precedent, I mean, really have looked across all the IBAD settings where you are seeing an Alagille where the first approval was based on 4-week randomized withdrawal data. All the way to the more recent LIVMARLI approval in PBC pruritus with a 6-month placebo controlled study that frankly looks a lot like VISTAS. it is a little bit larger because PBC is a more prevalent indication.

So there is pretty clear precedent for IBAT in cholestatic pruritus. Settings. That line up with VISTAs. It goes back to the whole way that we designed the study in the prior conversations with the agency. I am sorry. I may have misheard something. Did you say that this was only happening via written correspondence, or was this pre NDA in person with the FDA or virtually? The pre the pre NDA was in person. So when you were asking about prior and other interactions, some of those have been written. So we do not know who is behind some of the other written correspondence. This meeting was in person. Okay. Got it. Thanks so much. Yeah.

Thanks for the question.

Operator: Your next question comes from the line of Mike Ulz with Morgan Stanley. Your line is now open. Please go ahead.

Rohit Bhasin: Hi. This is Rohit Bhasin on for Mike. Thanks for taking our questions. Just based on your conversation with the FDA, do you see any read through to the PBC Vantage study Is it possible they will request a phase 3 trial for that 1? And also, in terms of commercial prep for FOP, can you talk about where you currently stand in what is outstanding? Thanks.

Christopher Peetz: Thanks, Rohit. I will speak to PBC and then pass it over to Peter to talk about FOP. On the VANTAGE study, as you may recall, we were granted breakthrough designation after the interim analysis in 2024. So that actually gave us a great opportunity to have conversations similar to what we expect to go through here with VISTAs. So in the correspondence after the breakthrough designation on Vantage, actually received a pretty clear feedback from FDA on what we should do to consider Vantage a pivotal study. And we were able to address those.

So primarily, the comments related to the overall size, that is part of why we have ended up with over 3 hundred and 30 patients in Vantage. And also the analysis plan and some of the specifics on how the pruritus endpoint is analyzed.

Peter Radovich: And, Rohit, yeah, with regards the commercial prep for Zilurgisertib potential approval and launch in Q4. that is going really well. As I mentioned, we did were able to drop that in the bats of our rare genetics team and had a couple territories there. A lot of, you know, typical prelaunch activity and profiling accounts. And understanding where the treaters are. These patients are well identified. there is about 300 or so diagnosed and managed in The US and highly specialized centers Had a had a good presence at the end of meeting earlier this summer as well. So excited about the progress of the end of the review and Working towards launch readiness in Q4. Thank you.

Thanks for the question.

Operator: Your next question comes from the line of Brian Skorney with Baird. Your line is now open. Please go ahead.

Brian Skorney: Hey. Good afternoon, team. I am gonna be annoying and also ask about FDA's issues with VISTAs, just given that it seems like a pretty straightforward data set. Can you just refresh our memories? Is the review team here is this within the Division of Hepatology? Is Kati Donahue, the Office Director? Was she involved in the meeting? Is Frank Anania still the Division Director and was he in the meeting?

And you know, I mean, I hear they were not very clear about why they wanted phase 3, but, I mean, did they sort of mention, like, a need for replication it just seems like the key value here is so robust that there is not really another question that could be answered with a phase 3 other than maybe longer term follow-up? So, yeah, any sort of guidance there is helpful.

Christopher Peetz: Thanks for the question, Brian. On some of the specifics of people kind of in the room, I would say is, you know, the office leadership, we think maybe has changed, and leadership was not in the room in our review meeting. And kind of getting into some of the I mean, specifically on efficacy, you know, the I think it is like you are pointing out, I think it is very easily addressed by the VISTA data. And getting breakthrough afterwards, I think, is a nod in that direction. So I have given some of the discussion in the room, I think that is something that we can readily address through iterative conversation with FDA.

I do not know if that helps answer your question. Yeah.

Brian Skorney: So maybe if I could just ask 1 thing on the PDUFA with Zilurgisertib. I think you would have had probably the late cycle review meeting in the last month or so. Just any commentary on how that went? Your level of confidence going into labeling discussions?

Peter Radovich: Yeah. Thanks for the question, Brian. That yeah. We did have the late cycle meeting, Meeting went very well. So we are you know, we feel the application is progressing, you know, quite well towards the PDUFA date. So Full systems go to prepare for potential launch in Q4. Great. Thank you. Thanks for the questions.

Operator: Your next question comes from the line of Kalpit Patel with Wolfe Research. Your line is now open. Please go ahead.

Yesha Patel: Yeah. Hey. Good afternoon. Thanks for taking the question. 1 more on the regulatory interaction here. In your communication with the agency, has there been any dialogue so far on running a post approval confirmatory study instead? Of running a phase 3. Or should investors assume that, you know, a Phase III is what is in the works right now?

Christopher Peetz: Thanks for the question. I think the direct answer is that conversation with FDA did not get to that level of specifics for post approval requirements. I can comment a little bit on the pathway here that using pruritus is the basis for full approval. So we do not expect to have a post approval study in the sense of kind of confirmatory accelerated approval type format. What we would expect and has been added for other IBAT approvals is some level of post approval registry or kind of long term monitoring. So and so we do think that would be appropriate for this setting as well. Okay. Thank you. Thanks for the questions.

Operator: Your next question comes from the line of James Condulis with Stifel. Your line is now open. Please go ahead.

James Condulis: Hey. Thanks for taking my question. and congrats on a great Live Marley quarter. Just maybe to be annoying again, 1 more on PSC. I guess, like, to clarify, is a phase 3 on the table, or, you know, are you confident that this can be resolved you know, through, like you said, iterations on sort of the data Just wondering sort of, like, what your base case is and, you know, sort of what informs your confidence of guiding to a first half 27 resubmission? Thanks.

Christopher Peetz: Yeah. Thanks for the question, James. And as we looked at this proposal for a phase 3, and given the VISTA results, I think the key question is what would you learn from another study in this setting? And VISTA is the largest ever conducted in PSC pruritus with clear, definitive results. it is a big enough safety database for a setting like PSC. So do not see what would be gained by going down that road. And find that just the weight of evidence here is really convincing. So I feel good about where we stand now with breakthrough designation. To work through this. Thanks. Thanks for your question.

Operator: Your next question comes from the line of Lisa Walter with RBC. Your line is now open. Please go ahead.

Lisa Walter: Good afternoon. Thanks for taking our questions. Kind of 1 more on the NDA filing delay here for velexibat. Could this mean that we see more BD in the near term as potentially PSC revenues may now be pushed out? And I just wanna ask as well, could you add any clarity on whether the FDA is still accepting pruritus as an approvable endpoint? Thanks so much.

Christopher Peetz: Thanks for the questions, Lisa. You know, first thing on I will answer your second part first, which is absolute clarity that pruritus is an approvable endpoint. that is what this discussion is all focused on. So there is there is no question there. On the BD front, you know, we always approached BD on being always active and always opportunistic. So do not see this really relating to overall level of activity we have or our criteria and what we are looking to bring in. Thanks for the question.

Operator: Your next question comes from the line of Joe Schwartz with Leerink Partners. Your line is now open. Please go ahead.

Analyst: Hi. Thanks. Hypothetically, if the FDA does not budge, does VantagePVC have any ability to strengthen the volixibat regulatory package for PSC. For instance, if, a filing in PBC is an NDA, and a filing in PSC as an sNDA, could that order of operations be successful without having to do another Phase III?

Christopher Peetz: Joe, thanks for the question. What I would say is potentially, and we are getting into some hypothetical down the road. The base plan is to get the PSC NDA submitted first. But as we think about the VANTAGE data, another large randomized study playing into a very related pruritus condition, I do see some weight to that. And how we approach that in terms of parallel or sequenced NDAs is something that we will get to if we end up in that scenario. Okay. Thanks. And then question on volovitug.

Did any baseline characteristics for patients enrolled in the interim analysis cohort of Azure 1 appear to correlate with better response in the phase 2 b portion of the trial. And how do the baseline characteristics for patients enrolled in the full Azure 1 population and Azure 4 compare? I mean, the quick answer to that is no. Nothing obvious that really comes out. We see response for volovitug across really all patients. So, it is a very broad based response. And that cuts across baseline viral RNA levels, ALT levels, geography, kind of every way we have looked at it, consistently see patients responding to volovitug. Thank you. Thanks for the question.

Operator: Your next question comes from the line of Jessica Fye with JP Morgan. Your line is now open. Please go ahead.

Jessica Fye: Hey, guys. Good afternoon. Thanks for taking my question. So more on volixibat. When you, I think in your prepared remarks referred to some options to supplement the VISTAs trial, Curious what you could supplement it with. And second, just based on where we stand right now, what gives you the confidence to outline first half of 27 as the new PSC filing timeline. Thank you.

Christopher Peetz: Yeah. Thanks for the questions, Jessica. Yeah. In terms of supplementing it, the real simple 1 is actually something I mentioned in the prepared remarks as well, is kind of the data cutoff timing. Where we are able to pretty easily allow more safety data to accrue, like to get to 100 patients at the 12 month mark in the open label follow-up. So that was 1 of the kinda quick offerings in there. I think some of the other things could be towards things that were mentioned in earlier questions and what could be offered up for post marketing registry work and things like that.

In terms of the timing, we feel first half is very achievable, and it is really based on having enough room to have an iteration or 2 with FDA. So it is less about time we need to prepare the submission, frankly, because we are-- things are ready to go quite quickly after we kinda have the input we need. it is more about that iteration with FDA. Really, that is that is kind of an estimate based on experience.

You know, we have we have done the thing the applications like this before back to the original Alagille application where it took a couple of meetings along the way to kind of build up to that NDA filing for Livmarli in Alagille, And so it is it is a type of situation that we have worked through before.

Operator: Your next question comes from the line of Joseph Thome with TD Cowen. Your line is now open. Please go ahead.

Joseph Thome: Hi there. Good afternoon, and thank you for taking my questions. Maybe just in setting expectations in terms of when we should hear next steps on sort of the filing progress? I guess, what are you anticipating in terms of relaying kind of your FDA interactions to the street? And then I think in your prepared remarks, you indicated that this necessarily will not flip over to PBC, and that you have some feedback that Vantage will be a registrational study. I guess, to your knowledge, is that this new group that conveyed that information 1 point of clarification just on the updated guidance.

Is there anything for FOP in your updated product guidance, or would that be above and beyond? What you have outlined today? Thank you.

Christopher Peetz: Thanks for the questions. I will take the first couple and pass it over for the FOP question. You know, in terms of providing an update, our view is that this is likely an iterative process, and so we would plan to give an update when we have kind of a material update. So you do not wanna be sharing the blow by blow on what might be e email correspondence even with FDA. And shifting on to the PBC question, those interactions were written correspondence, so do not know exactly if it is the same exact people behind it, but what gives a lot of comfort there is recency. Right? So this has happened over the past year.

That we have had those PDC written correspondence.

Eric H. Bjerkholt: And on guidance, the 680 to 700 million does not include FOP. So anything we see in Q4 would be above and beyond, although we really expect the revenue to start more in 2020 Thank you.

Operator: Your next question comes from the line of Jonathan Wolleben with Citizens. Your line is now open. Please go ahead.

Jonathan Wolleben: Hey, Christopher. I am wondering if you could just you know, talk us through what this iterative dialogue looks like in terms of you know, using breakthrough therapy designation or formal meeting status and, you know, scheduling of these, just for a little bit more expectations on that flow of information between you and the agency.

Christopher Peetz: Yeah. Thanks for the follow-up, John. 1 of the benefits of breakthrough designation is it does allow for more frequent advice from FDA, more frequent interactions And so quite simply, that just means we will be able to reach out more in informally and also have more advice meetings. How those sequence out really depends on how the dialogue with FDA progresses. So we cannot really give too much more specific at this point. But we will keep you guys updated as we make progress through it.

Operator: Your next question comes from the line of Ramakanth Swayampakula. With h c Wainwright Your line is now open. Please go ahead.

Swayampakula Ramakanth: Thank you. This is Swayampakula Ramakanth from H.C. Wainwright. Couple of really quick questions. You know, based on the interactions that you have had so far, for the PSC, PSC indication you know, are you planning to make any changes at all in your approach for the for the PBC indication, you know, once the VANTAGE data comes out, And, also, if you do go ahead and submit in the first half 27, you know, notwithstanding the recommendation. You know, did you run into a risk of refuse to file kind of a situation? And let's say everything goes fine and you still continue to apply, would you expect an AdCom at the end of this?

Christopher Peetz: Thanks, RK, for the question. In terms of the PBC approach and given the recent interactions, I think we have direct input for that indication for vantage. So feel like that is on a good course. So it would not make changes at this point what we are doing in PBC. We have kind of already made recent adjustments to accommodate what FDA asked for having Vantage being confirmed as a pivotal study.

And then on some of these questions about submission risks, I think is how I would describe the question, that is the reason for this iterative interaction with FDA is try to work through things that might be an RTF risk and try and get those off the table. And frankly, you know, an AdCom might be something that could be helpful given the huge impact that volixibat has shown in a really terrible setting for patients. You know, the relief, dryness relief, improvement in sleep and fatigue that patients experience with volixibat treatment. Is really life changing. So I think that could be 1 way that this gets highlighted. Thank you. Thanks for answering my questions.

Thanks for the question.

Operator: There are no further questions at this time.

Christopher Peetz: We will now turn the call back to Christopher Peetz for closing remarks. Great. Well, thank you all for joining us today, and hope you have a great afternoon.

Operator: This concludes today's call. Thank you for attending. You may now disconnect.