Mirum Pharmaceuticals, Inc. (MIRM) Earnings Call Transcript & Summary

Good afternoon. My name is Jeff Fye. I'm a senior biotech analyst at JPMorgan, and we're continuing the 40th JPMorgan Healthcare Conference today with Mirum. I'm joined by the company's CEO, Chris Peetz, who's going to give a presentation on the company, and then we'll go into some Q&A. [Operator Instructions] So without any further delay, let me turn it over to Chris Peetz.

Thanks, Jess. Thanks for hosting us this year as well. And I appreciate everybody's interest in Mirum Pharmaceuticals. It's an exciting time for us, and I'll go through some of our updates as well as a little background on our programs. But first, just to kick off, I'll be making forward-looking statements. So we would refer you to our SEC filings for more complete disclosure on risk factors and other information on the company. Calling out some page numbers as we go through the corporate deck here and starting on Page 3. Mirum is a leading developer of rare liver disease medicines and so exciting to be in market now with Live Marley, the first and only approved agent for treatment of cholestatic pruritus in Alagille syndrome. This is a $500 million or greater opportunity in the U.S. alone. And beyond our current approval in the U.S., we're tracking towards regulatory approval in Europe and additional geographies. Behind LIVMARLI and Alagille syndrome, we have a pipeline of 5 late-stage indications across our 2 products and a team that has done this before, a team with experience across many liver and orphan launches and excited about what we're going to unlock from the value in our pipeline and what we'll continue to build in Mirum in the years and quarters to come. Page 4, a quick update on LIVMARLI, which was approved at the end of September as we have now one quarter in market. I'll give some color on how the launch has gone as we get further into the presentation. But first, just to note that the feedback from the physicians and families has been overwhelmingly positive and such a great moment to now have a new therapy available for families dealing with Alagille syndrome. Page 5 is a pipeline snapshot of our programs, as mentioned, approved in the U.S. and in review in Europe for treatment of cholestatic liver disease in patients with Alagille syndrome in the -- in Europe with an expected decision in the second half of this year, preparing to launch in Europe ourselves. And on the pediatric side, have a Phase III study in PFIC that we're very excited to announce today has completed recruitment. We'll have the 6-month primary endpoint from that study expected to be shared now in the second half of this year as the final patients are completing their screening visits currently. Our third indication on the pediatric sciences biliary atresia, a Phase IIb study enrolling there. We expect top line data from that study next year. Then on the adult side, 3 larger, more prevalent indications in primary sclerosing cholangitis, intrahepatic cholestasis of pregnancy and primary biliary cholangitis with upcoming interim analyses that will inform both the registrational doses and the registrational portion of these studies, worth noting that on all of these programs, the 3 volixibat studies, these are adaptive studies with registrational intent in the confirmatory portion. On Page 6, a little bit about the mechanism of our programs, both LIVMARLI and volixibat. They are both oral, minimally absorbed IBAT inhibitors. So they block the reabsorption of bile acids within the GI tract, a quite direct mechanism in settings of cholestasis where bile acid overload leads to multiple downstream complications from liver damage and a hallmark symptom of very extreme pruritus across many of these indications and settings. So LIVMARLI and volixibat both potently disrupt that reabsorption and cause a depletion of some of the excess bile acids in the body. In settings of cholestasis, we've seen dramatic reductions in serum bile acids. We've seen improvements in pruritus and now in long-term follow-up, we've seen improvements in transplant-free survival, hand event through survival, showing the potential for impacting this pathway in settings of cholestasis. Now to dive a bit into our programs. I'll spend a moment on Alagille syndrome. Page 8 gives a snapshot of the disease background. Alagille syndrome is a genetic disorder that is typically caused by spontaneous mutations. So not always a familial genetic disorder, which means that it's a consistent prevalence across the globe. In the U.S., we estimate there are 2,000 to 2,500 children diagnosed with Alagille syndrome in care being tracked by a specialist and that the vast majority of these kids suffered from pruritus. And the pruritus in this setting cannot be overstated. It is devastating and is one of the leading indications for liver transplant in children with Alagille syndrome. And the prognosis is not great for these kids with 6 in 10 progressing to transplant or death by adulthood. Now LIVMARLI in the setting has now been extensively studied and with data sets up to 6 years has allowed us to look at long-term outcomes. And Page 9 gives us a snapshot of what ultimately we're hoping to achieve in this setting by addressing the cholestasis and pruritus is to improve long-term outcomes for these children. This is an analysis that was presented late last year at the American Association of the Study of Liver Diseases as a late-breaking best of liver meeting presentation showing that the LIVMARLI-treated patients compared to a matched cohort of similar baseline criteria and quite pronounced improvement in event-free survival with 6 years of follow-up. So 0.3 hazard ratio and a quite significant p-value. Page 10 also gives a snapshot of our pivotal data from the ICONIC study that we're excited to share was recently published in The Lancet. Great to see this kind of recognition for a rare disease in a journal like Lancet and the key findings from the ICONIC study here on the page showing that in this randomized withdrawal design, when all patients are on drug for the first 18 weeks, there's a dramatic and pronounced reduction in pruritus scores and in a placebo-controlled randomized withdrawal period, you see patients on placebo go back to their baseline values and able to recapture that treatment effect on pruritus when they return to therapy. Important to note as well that the response that we've seen has been durable out now, in some cases, 5 and 6 years. From the safety standpoint, we have a snapshot on Page 11. The most common adverse events are typically treatment initiation, mild transient GI effects directly related to the mechanism of clear bile acids for the GI tract. And with the data set of 5 years of follow-up, we can look at essentially 100 person-year exposure rates and see how favorable the safety profile is compared to some of the natural history sets where many of the things that we see in the study are actually quite similar to the background of Alagille syndrome as a disease. Now on Page 12, we'll touch on our commercial strategy, which is quite focused. So care for Alagille syndrome is centralized and what we estimate to be about 125 accounts that have some pediatric hepatology or pediatric gastroenterology practice, which allows us to be quite targeted in our field efforts as we have been out with the Mirum team, creating awareness of a new treatment option, awareness of the disease severity and burden and with actually quite promising results in our first few months in market and excited to share some of that data here today. It all centers around the patient journey with LIVMARLI centers around Mirum Access Plus, which is our fully integrated patient hub. And it's important to note that this is integrated into an exclusive specialty pharmacy provider, which allows us to have complete tracking and support for patients from the prescription all the way to the dispense so that the physicians also get the support they need as they go through the insurance authorization steps and then long-term support for patients while they're on LIVMARLI. Page 13 gives the highlights from our first 3 months end market, and it's been just a remarkable start for LIVMARLI in Alagille syndrome. Again, we are tracking towards a total opportunity of over $500 million in the U.S. and what we're seeing early in market confirms this opportunity. With our first 3 months in market, we estimate the Q4 preliminary net sales of $3.0 million. A couple of points on how to interpret this number and how it might project forward as we do expect quarter-over-quarter growth into and throughout the year. This $3 million in our exclusive distribution channel represents actual patient dispensers. So there is no inventory at the U.S. pharmacy in our distribution model, what you see here is actual patient dispenses, revenues recognized when the family receives drug. So in terms of metrics for the launch and guide you towards net revenue, that is the actual commercial expenses that we have through our channel. One other data point to keep in mind in looking at this is that in the first few months as we were establishing reimbursable pathways for patients, about 40% of total disbursements were free drug. So the total demand number relative to this 3 million net sales is actually quite a bit larger. And now heading into the first quarter, over 90% of patients we estimate in the U.S. have a reimbursable pathway. So we do expect those free drug disbursements to improve as we move into the quarters ahead. On Page 14, expanding this beyond the U.S. as well, where we are commercializing in the U.S. and Europe ourselves. European approval expected in the second half of this year and getting the team in place for early launches across the territory and support from a number of leading licensing and distribution partners in their respective countries. I couldn't be more excited about the interest from the companies that have come around the table to help us expand the reach of LIVMARLI around the globe. Many of these partner companies are pursuing either early commercial access programs or expedited approval filings. So expect to hear more as we go through the year on approvals and early reimbursement from some of these partner markets. Now touching a bit on the pipeline. Page 16 gives a snapshot of PFIC as a disease state, also a setting of quite severe cholestasis in the pediatric setting where pruritus is again the -- one of the key objectives for treatment as it is a leading cause for liver transplant in this setting. And only about 20% of patients with PFIC will ultimately make it to adulthood with their native liver. It's a disease of bile acid transporters. And with an approach with LIVMARLI, we expect to, again, deplete that excess bile pool and some of the downstream impacts of it. Page 17 gives a snapshot of our Phase II data of LIVMARLI in patients with PFIC type 2 where we saw quite dramatic improvements in serum bile acids, and pruritus and even in high z-score over time. Most importantly, as we followed up these patients long term on Page 18, we see that those with serum bile acid response do see improved long-term transplant-free survival. So showing the promise that LIVMARLI potentially impacts the long-term outcomes for patients with PFIC as well. On Page 19 gives a snapshot of our confirmatory study in PFIC, the MARCH-PFIC Phase III study. We have completed recruitment. The last few patients right now are -- have their final screening visits scheduled, and we expect a data readout from the 6-month primary endpoint on pruritus to be in the second half of this year. Important items to note in the study design is that in addition to looking at more PFIC subtypes than we saw in the Phase II program, we're also looking at a higher dose of LIVMARLI. And our early work suggests that higher doses will have an increased bile acid clearing effect. So we're optimistic about what we might see in terms of improved response from the Phase II program. So data, again, expected from the MARCH-PFIC study later this year. On Page 21, a bit of background on biliary atresia, the third pediatric indication where we are active in enrolling patients with LIVMARLI. Biliary atresia is a much more aggressive disease that presents upon birth. And in biliary atresia there's an emergency procedure called the Kasai procedure that reestablishes connectivity of the bile ducts to the GI tract and the treatment opportunity for LIVMARLI is immediately after that surgical procedure. The surgical procedure can result in disease control and even prolonged transplant-free survival, but not in most patients actually. So the rates of transplant by the age of 2 are as high as 50% or greater, showing that if we can potentially disrupt the bile accumulation and prevent that salts of bile acids on the liver, we might extend transplant-free survival. And we're measuring that on Page 22 in the EMBARK study, a 6-month study, placebo-controlled looking at bilirubin at 6 months. Bilirubin is one of the most predictive markers of transplant-free survival in the post-Kasai treatment setting, heading towards data readout from this study expected next year. So several exciting developments across the pediatric program, and I'll shift now to our adult programs. Page 24 has a bit of background on the settings where we're evaluating volixibat in settings of adult cholestasis. Three indications that are quite a bit more prevalent than what we're looking at in the pediatric indications, cholestasis of pregnancy, PSC and PBC across all of these settings, the commonalities are elevated bile acids are a real problem that lead to poor outcomes and the same hallmark pruritus burden of the disease that you see in the pediatric setting and very limited treatment options across these settings with ICP and PSC having no approved therapies at all. Page 25, a snapshot on volixibat, which is a highly potent, highly active iBAT inhibitor, the data we've seen today shows that it's quite active on disrupting the bile acid pathway and leading to increased excretion of bile acid targeting what we see as the root issue in the cholestasis across all of these settings. On Page 26, a bit of the biology of ICP, where the spontaneous cholestasis leads to increased biles and exposure for the fetus, pruritus for the mother. And we're looking at approaching both of these problems in our study, I jumped ahead to Page 28, which has the OHANA Phase IIb study design, which looks at the serum bile acid levels and also the pruritus in the mother and the outcomes for the pregnancy. The study has 2 parts -- 2 cohorts to think about, one is the placebo-controlled randomized data of 2 doses of volixibat versus placebo and another open-label cohort and we expect to see first data from the open-label cohort later this year. Finally, for the volixibat program on Page 29, looking at PSC and PBC, these are immunoinflammatory rare liver diseases. But again, the elevated bile acids lead to progressive liver damage, for quality of life, pruritus, fatigue and ultimately leads to liver transplant in many cases. And by approaching iBAT as a mechanism, we hope to deplete the excess bile exposure for these patients. We've discussed our program in the 2 studies on Page 30 and 31 with FDA, have buy-in on these designs, using pruritus as an outcome for approval in the confirmatory portion of these studies. And for PSC, it's worth noting this is a real landmark step forward for the development of new treatment options for PSC where consensus around approval endpoints has been difficult to date and using pruritus as the near-term outcome allows a pathway for potential approval for volixibat based on the eventual data out of VISTAS study. We do expect an interim analysis from VISTAS towards the end of this year and from the VANTAGE PBC study, looking at interim analysis tracking towards next year 2023. So taking a step back and putting this all together on Page 33. We're so excited today to share what has been a fast and quite productive first few months in market with Alagille syndrome as we start to unlock the potential of this indication and realize the real value to patients and caregivers that LIVMARLI provides for Alagille syndrome. But it's just the start of where we're going with our programs, with the additional pediatric indications and then ultimately, the adult indications, showing tremendous upside potential for Mirum and our pipeline. Page 34 snaps on the financial side that we have the resources to develop and commercialize our programs. We recently closed the sale of our PRV for $110 million and ended the year with an estimated cash of $261.5 million. And that funds all the milestones ahead of us on Page 35 with early access programs outside the U.S. starting now and the expectation for continued quarter-over-quarter growth from LIVMARLI in the U.S. heading towards MARCH-PFIC data in the second half of this year, potential approval in Europe for Alagille syndrome for LIVMARLI and then also other partner markets that will follow that and the advancement of our pipeline with volixibat having interim data from the PSC and ICP studies later this year. So tying that all together on Page 36, I couldn't be more proud of the team that we've brought together and the impact that LIVMARLI is already having out in market and all of the great developments that we have in the year to come and invite you to stick around here for the Q&A session and talk more about any of the follow-up items. And also I'll note that I have some of my team members from the Mirum team, that will join for Q&A session.

Great. Thanks, Chris, for that presentation. [Operator Instructions] In the meantime, one of the questions we've gotten since you reported preliminary revenue for 4Q is what that implies for the number of patients who were treated with LIVMARLI in the fourth quarter. Any way to kind of throw some color on that?

Absolutely. And it's the reason why we are basically just providing a net revenue number because it is very transparent for the actual patient demand. So with our average price per patient of an estimated -- based on the average patient rate, it's about $392,000 gross per patient annualized. You can look at a monthly figure of about $30,000 is equivalent to roughly a patient month of treatment. So you can use that versus the net revenue number to give a metric of how many patient months of commercial drug have been dispensed.

And what about free drug? Were there also patients getting free drug in the quarter who might click over to being paid patients now that you've got reimbursement, I think the slide said north of 90%?

That's right. We do. And for -- across the full 3 months of Q4, about 60% of our dispenses were commercial paid drug. So that's the $3.0 million and another 40% were free drug. We do expect that 40% to track more towards an industry standard of 10% or so of free direct dispenses long term. So that -- another metric to think about how that evolves into the next couple of quarters?

Got it. Other questions here. Can you say more about the LIVMARLI launch and sales force? And are you comfortable with estimates?

Actually, I'll ask Peter Radovich, our Chief Operating Officer, to comment a bit on the dynamic of the field team.

Sure. The field team dynamic has been very positive. I think across our stakeholder groups, whether it be physicians and healthcare professionals and the 125 key accounts, caregivers, other healthcare professionals, the launch has really exceeded our expectations. We've been able to reach all 125 accounts very quickly and have had prescribing from a broad base of those 125. So it's really not -- it's not like it's kind of the top few that are driving that. So I've seen a broad base of adoption and now we're kind of getting to the point where 3 months ago, it was really only the physicians who participated in the clinical program. We kind of have the first-hand experience. And now that just that base of firsthand experience and positive feedback from physicians as well as families is much broader. So it's really rewarding thing to observe.

What about the part -- and I like this question. Now what about the part about being comfortable with analyst estimates?

Well, I'd say that the analyst estimates heading into this announcement, actually, we're quite comfortable with them.

With the -- I guess there's a question for this in almost every session. But with the current COVID surge, how is that affecting your launch at all? Is that something you're kind of seeing interfere with the uptake or so much?

Peter, do you want to jump in?

Sure, happy to. Just, we had to be nimble. It changes week to week. And as you can imagine, a lot of geographic variability, different practices occurring in different parts of the country. We've been able to achieve our goals. We've used a broad array of kind of tactics and activities, much more use of virtual programming, virtual engagements to different means. So I think that, overall, we've been able to get to where we want to get to, of course, would much prefer to be back in the 2019 world where we could do both virtual and live and hopefully, we'll be there as we head into 2022. I know everyone hopes for that.

With the MARCH study in PFIC coming out, I guess, in the back half of the year, what are the efficacy measures that you're going to be focusing on that could further support the products activity? And how do you plan to release the data?

So I can touch on the release of data plans, and then I'll pass it over to Pam, our Head of R&D, to talk a little bit more about what we can expect to see from that study. And the update plans that we expect to provide would be a material top line update on the primary end point. but we'll want to preserve a lot of the detailed data for scientific presentation, but we will share top line findings when we conduct the analysis.

Yes. Thanks for the question, Jess. So with regard to the MARCH-PFIC study, we're looking at broad across all PFIC subtypes. Pruritus is a primary endpoint at 6 months. We're also looking at serum bile acid, which we know is a strong prognostic marker of transplant-free survival, and we've shown that data already from our 5-year transplant-free survival data from INDIGO Phase II. So as we look forward, we're confident that LIVMARLI will be effective in this patient population. We saw in our INDIGO Phase II study that higher doses were actually really important. We had additional responses at the higher doses. So going even higher in the MARCH-PFIC Phase III study, we're hopeful that we'll see on aggregate higher rates of response.

A couple more questions coming in here. So thanks, everybody, for asking questions. Can you talk about start forms versus actually filled scripts, whether they are paid or free?

Yes. I'll ask Peter to give a little update on the dynamic on how this works within the Mirum Access Plus system and what we're seeing in terms of that time to fill dynamic?

Sure. Yes. So the way the process works, it indeed does start with a prescription or an enrollment form. And we've been actually -- it's a big area for us to monitor our hub, our Mirum Access Plus hub in terms of a quality metric. And we've been really pleased. We've actually seen paid dispenses occur as fast as days, quite frankly or around a week. On average, it's a couple of weeks but have been able to kind of go from prescription to fill pretty quickly and get that medicine to patients. We -- yes, I think so. Leave it there.

Yes. I think I'd also comment that from the reimbursements standpoint, there's been some nice early wins. The receptivity from payers for this product because of the dramatic impact that it has and the high unmet need in the setting has actually exceeded our expectations in the first few months.

We just entered this one is how long it's taking to go from start form to build script? Is that a couple of weeks?

Yes. I think that's about -- you can think of a couple of weeks as the average. That's right. And -- but in some cases, it can occur faster is that a comment on that.

Maybe turning to volixibat. Can you help us understand the market potential for volixibat in ICP, PSC and PBC?

Absolutely, yes. The -- overall, these are 3 really interesting high unmet need settings and each on its own could easily be 500 million or more. I'd say that the caveat we have is that ICP is potentially dramatically underdiagnosed and so it could be quite a bit larger than how we look at it from just the background of the published literature in terms of the incidence of this and spend a moment to talk about PSC in particular, where there are approximately 30,000 estimated prevalent cases in the U.S. The majority of them experienced pruritus and much of it quite severe and debilitating. It's often referred to as the suicide itch within the circles of PSC and so to have a new treatment available would be quite game changing for patients with PSC. So the impact of this setting is quite substantial for what we think is possible with volixibat treatment. So from an overall market opportunity, again, in the U.S. alone, you can see 500 million or greater is the way that we look at volixibat in PSC.

And can you walk through what you expect to see with the interim analysis of Phase IIB OHANA study in ICP that could provide enough support for registrational path and talk about how you plan to release that data?

Yes. Actually, there's -- I'll add a question and then pass it over to Pam to actually do the answering. So it's also worth talking about the PSC interim because these are 2 different formats and worth making sure that the expectations, there's an understanding of what we'll be able to share from the 2 analyses. So I'll hand it over to Pam.

Yes. So for -- maybe I'll start with the PSC first, and then I'll go back to OHANA. So for PSC, this is an interim analysis, which will inform both 4 dose selection as well as determine any reestimation of sample size that's required in part 2 for the potentially registrational phase. And the analysis is closed, and this is really important because we want to conserve patients from Part 1 so that they can be counted in Part 2. We know that PSC is smaller than PBC and ICP. So this is an improvement with the FDA on how we can maximize the number of patients that we have for the potential registrational portion. So with that said, as we look at the interim analysis coming this year, no news will be good news and study just will keep going and we'll inform on that when that happens. For the OHANA study, any change in serum bile acid is really meaningful. As Chris mentioned on one of the slides earlier, even 1 micromole change can be quite meaningful for fetal outcomes. So we'll be looking at trends on fetal outcomes, we're looking at pruritus, which is an important secondary endpoint and all of that information in addition to dose selection and safety will inform for the Part 2 potentially registrational portion of that study as well.

So I guess maybe 2 follow-ups to that. What's the right framework to think about the communication around each of those interims? And I think on one of the last slides, it looked like the ICP update was kind of before the PSC update, both kind of second half next to them, but on the slide, it was first for ICP. So is that the order in which to expect them?

Not necessarily. I mean they're both second half and how they play out, just depends on how patients enroll, frankly. So that's more of a formatting on the slide. In terms of what we will share for PSC, you can expect that if the no news is good news outcome, you can expect an announcement to the effect of that interim analysis has occurred and the study continues as planned. That means that we -- there was an observed effect within one of the doses and the first portion to carry into the registrational portion. With ICP, it's a new setting. And so we wanted to have more of an open analysis of the data, have a first look at open-label data as well. So we'll be able to share more as we're looking at it. With PSC, the registrational considerations are a lot more well understood and characterized and so we can go straight into the confirmatory portion. That's one of the key differences between those 2.

Okay. On the primary endpoint of serum bile acid in OHANA, what's the magnitude of delta you want to see between the treatment arm and the placebo arm to consider it meaningful? And do you expect a dose response?

These -- a couple of comments there, and I'll ask Pam to clean up afterwards as well. The first one on dose response, both doses of volixibat were chosen because they are on the high end of the spectrum. So the low dose that we're using in these studies, we do expect to have substantial activity and we wanted to make sure we didn't leave anything on the table. So it is quite possible that these are both maximally effective doses, and you might not have a distinction between the 2 because they're both pretty far into the dose response curve on fecal bile acids and the 7 alpha C4 measures of activity that we look at. And then in terms of serum bile acid change, as Pam noted, any change is linked to better outcomes. And so just a statistical difference between drug and placebo would mean that it's a meaningful improvement. It kind of all depends on the mix of where we land for baseline values, but any reduction in serum bile acids translates to an expected reduction in risk to the pregnancy.

Got it. And is there any secondary endpoint that you're measuring in OHANA that the FDA has highlighted as maybe most supportive for the potential registrational strategy?

FDA has been quite clear that they're focused on pruritus as an outcome for approval across all of the volixibat studies. The -- a different answer -- an answer to a different question, is that EMA has also highlighted an interest in the pregnancy outcomes. So that composite endpoint that we look at for preterm labor, stillbirth and neonatal intensive care stays. So at that endpoint, we would expect that could play more of a role in the European conversation though FDA has focused on exclusively pruritus as the outcome for approval.

Okay. And what do you see as the potential duration of treatment with volixibat in ICP?

We expect it to be in the average range of 3 or 4 months for patients. Once we get products out in market and available that's around the time when a confirmatory diagnosis usually happens. And for subsequent pregnancies, the ICP typically recurs and so forth, second or third pregnancies, you'd expect a longer duration of treatment.

Got it. And what about the Phase IIb VANTAGE study in PBC? How is enrollment progressing there?

So just kicked off. Maybe I can ask Pam to just touch on a couple of the highlights on the VANTAGE design, but we're tracking towards likely having an interim next year.

Sorry, I can't get off [indiscernible]. So yes, so the study design on VANTAGE is that we're -- there's about 260 PBC patients that will be enrolled patients have moderate to severe pruritus. We're looking at 2 different doses in the interim analysis, as Chris mentioned, that's 20 BID and ABID, both are pretty effective. So at the interim, we'll have a look and determine reestimation of [indiscernible] and take a dose forward for [indiscernible]. As far as where we are, sites are coming on board. We're very active in bringing new sets on and screening started and we're on track for 2023.

Great. And then coming back around to VISTAS in PSC when can we expect full data from that study?

The -- it could follow as quickly as a year or so afterwards, but there is the potential for size adjustment at the interim analysis. So we don't quite have a precision on that until we actually get through the interim. But it's in that range. One thing to note is that the study will continue to enroll as the analysis is being conducted. So we will continue to recruit patients and work towards the full enrollment set while that analysis is being conducted.

Maybe we can pull in for a couple of questions. How should we think about OpEx in 2022 relative to 2021?

Yes. If you look at the last quarter, the quarters -- in the later quarters in '21, we're running at about a kind of $40 million to $50 million per quarter operating expense. I anticipate that that's kind of a good baseline to operate from as we think about the coming quarters.

And what's your cash runway and which clinical milestones does it take you through?

So as Chris had outlined earlier in the actual formal presentation remarks, ended the year we estimated at just $261.5 million and obviously, revenues coming in as well this year, which is exciting. Our runway is predicted to be 3-plus years. So all of the milestones that we've been talking about today around the volixibat studies, obviously, through the MARCH study as well from a clinical perspective, all incorporated into our runway calculations.

Got it. Okay. I probably have time for one more coming in here on the portal. Can you talk about how you envision the cadence of scripts in '22 basically asking like, was there a bolus of patients or I guess not?

No. I mean the expectation we had going in so far is playing out as expected, that we expect a gradual continued build over the quarters as we work further into market. And it's a pattern of a physician writes a first prescription or 2. And based on that treatment experience, then it starts to go deeper into their patients that they look after with Alagille syndrome. As Peter noted, great signs early on that the prescribing base is broad that are going through those first trial prescriptions and do expect it to continue to build quarter-over-quarter.

Great. So we're out of time. So we'll leave it there. But thanks so much for the presentation and thoughtful Q&A, and thanks, everyone, for listening in.

Thanks so much for hosting us.

Thank you, Jess.

Thank you, Jess.