Operator Ladies and gentlemen, welcome to the Mirum Pharmaceuticals Reports First Quarter 2023 Financial Results and Profile Business Update. My name is Glenn, and I will be the operator for today's call. [Operator Instructions]. I'll now hand over to your host, Andrew McKibben to begin. Andrew, please go ahead..

Thanks, Glenn, and good afternoon, everyone. I'd like to welcome you to Mirum Pharmaceuticals' first quarter 2023 conference call. I'm joined today by our President and CEO, Chris Peetz; our Chief Operating Officer, Peter Radovich, and our Head of Research and Development, Pam Vig.

Earlier today, Mirum issued a news release announcing the company's results for the first quarter of 2023. Copies of this news release and SEC filings can be found in the Investors section of our website. Full details and updates from the quarter can be found in our news release and 10-Q issued today.

Before we begin, I'd like to remind you that during the course of this conference call, we will be making certain forward-looking statements about Mirum and our programs based on management's current expectations, including statements regarding Mirum's current and future business plans, development programs, and regulatory expectations, strategies, prospects, market opportunities and financial forecasts and guidance.

Mirum is under no duty to update these statements, and they are subject to numerous risks and uncertainties, and actual results could differ materially from the results anticipated by these statements. Investors should read the risk factors set forth in Mirum's 10-K for the year ended December 31, 2022, and any subsequent reports filed with the SEC.

With that said, I'd like to turn the call over to Chris.

Chris?.

Thank you, Andrew, and good afternoon to everyone joining us on the call today. It's been another exceptional quarter for Mirum, as we continue to advance our leadership position as a high growth rare disease company focused on life-changing medicines.

Our clinical, regulatory and business achievements in the first quarter with total revenue of $31.6 million are driven by our team's passion and expertise in addressing urgent unmet needs for patients with rare disease.

With our five part strategy to become a global leader in rare disease in place, we're pleased with the progress we've already made in 2023. First, we've continued to build on the successful launch of LIVMARLI in Alagille syndrome in the U.S., tracking well on our guidance of 50% year-over-year net product sales growth driven by new patient starts.

Second, our international business is also building well with the recent launch in Germany and early access programs in France and other international partner markets. We look forward to additional launches around the globe later this year and into 2024. Third, we've accomplished an important step in our strategy to expand the label for LIVMARLI.

In the first quarter, we announced label expansion to include patients three months and older. In addition, we submitted a supplemental NDA and European equivalent with our positive LIVMARLI PFIC Phase 3 data.

Our team is preparing for the December 13 PDUFA date and is excited about bringing LIVMARLI as a new treatment option advancing care for PFIC patients. We also anticipate providing top-line data from the EMBARK study in Biliary Atresia in the second half of this year, a third potential indication for LIVMARLI.

And fourth, in advancing into adult indications, we are conducting potentially pivotal studies for Volixibat in Primary Sclerosing Cholangitis and Primary Biliary Cholangitis and look forward to providing interim updates from these studies in the second half of this year.

And the fifth part of our strategy, we continue to evaluate opportunities across rare diseases for leverage Mirum's industry-leading capabilities. We also recently took a significant step towards enabling our strategy with convertible note financing of approximately $316 million aggregate principal amount.

This financing enabled the repurchase of the nearly 10% royalty committed to our prior royalty investor and added additional growth capital to the balance sheet. We were excited to see the high level of interest in supporting our strategy in this well oversubscribed transaction.

We continue to project that our balance sheet provides three plus years of runway beyond cash flow breakeven. We have started 2023 off with great momentum, and I'm excited about what the Mirum team is poised to achieve this year and beyond as we provide patients with life-changing medicines.

And with that, I'll pass the call over to Peter to discuss our commercial business in more detail before Pam gives an R&D update.

Peter?.

Thanks, Chris. We are pleased with the $29.1 million in LIVMARLI net product sales in the first quarter of 2023, which included $24.7 million from the U.S. and $4.4 million from international markets. The U.S. growth was driven by the addition of new patients as well as a strong retail cadence.

And we're pleased to report that substantially all of the key pediatric liver accounts in the U.S. have prescribed LIVMARLI. Based on their positive clinical experience and ease of access with Mirum Access Plus, health care professionals report that they intend to increase the use of LIVMARLI across their Alagille syndrome patients.

Taken together, the U.S. business performance is tracking well against our guidance for 50% growth in 2023 net product sales. Now turning to international markets. In Q1, we launched LIVMARLI in Germany, and it's off to a great start.

We've already converted early access program patients to commercial drug, and we have seen impressive de novo demand, in line with what we saw in the U.S. launch.

Pricing and reimbursement discussions are ongoing in major European markets, which we expect to unfold throughout 2023, with full launches in European countries beyond Germany starting in 2024.

Also, we expect named patient sales in European and distributor markets to continue throughout 2023, although we anticipate quarter-to-quarter variability in order patterns.

In summary, LIVMARLI is in a strong position after year and a half in market as the first and only treatment for Alagille syndrome that is providing rapid symptomatic relief and long-term improvement in outcomes. LIVMARLI is becoming standard of care in treating cholestatic pruritus with over 600 Alagille syndrome patients treated globally to date.

Clinicians have gained familiarity with and confidence in LIVMARLI's robust clinical profile as well as its exceptional access in patient support.

And we believe this provides a strong competitive position, propelling a continued growth story in Alagille syndrome with exciting pediatric cholestasis indication expansion opportunities just on the horizon. And on that note, I'll turn the call over to Pam.

Pam?.

Thanks, Peter. In the first quarter, we achieved important milestones in our pipeline that support the growth of our programs and ability to impact more patients. As a reminder, that such a problem in all of these diseases studied in our pipeline is accumulation of bile acids.

In a classic cholestatic setting, IBAT inhibition has been shown to directly reduce toxic bile acid accumulation, the associated debilitating symptomatic burden and an Alagille LIVMARLI showed improved long-term outcomes versus standard of care.

The benefits of profound IBAT inhibition was shown by the impressive data from our March PFIC Phase 3 study announced at the end of last year. And we're happy to share that our supplemental NDA submission was accepted in the PDUFA date of December 13 of this year.

And in April, we also submitted for approval of LIVMARLI in PFIC to the EMA for patients two months of age and older.

Now the data from the March PFIC study proved our hypothesis with greater IBAT inhibition using higher dosing ratio for LIVMARLI drove a highly statistically significant reduction in both pruritus and serum bile acids across the broadest range of genetic PFIC types studied to date.

In addition, early and statistically significant improvements in growth as well as in bilirubin, we've seen in patients treated with LIVMARLI, where 40% of patients with abnormal bilirubin levels that they find normalized for bilirubin versus zero in the placebo group.

Now these data suggest an overall clinical improvement beyond pruritus for these patients, and we have heard strong positive feedback from the physician community and if approved, look forward to the opportunity to expand LIVMARLI to a broad pivot population.

We're also happy to announce that we remain on track for top-line data readout for our Biliary Atresia program for the second half of this year. This study will provide the first placebo-controlled data for an IBAT inhibitor in this study, and we're really excited to share them all when the study is completed.

As a reminder, the primary endpoint is the Biliary Atresia study assessment bilirubin at 26 weeks as bilirubin is the most predictive marker of disease progression and transplant in this setting.

And the dosing regimen in the BA study is the same as the March PFIC study and the bilirubin improvements we observed in March are extremely encouraging as we look forward to our Biliary Atresia readout. Now turning to our pipeline programs in adult cholestatic indications.

We expect interim analysis from our studies of Volixibat in both PSC and PBC in the second half of this year. We've previously shown that marked reductions in pruritus and serum bile acids can be achieved with IBAT inhibition in PSC, underscoring the potential for Volixibat in this setting.

And currently, there are no approved therapies for PSC and roughly 60% of patients are being actively managed for pruritus with largely ineffective off-label therapies, none of which lower bile acids.

Building off of our learnings from our pediatric program, we are dosing at a higher level and BID dosing regimen, which adds to our confidence in these upcoming interim analysis. And finally, I'm proud of our team's academic and collaborative efforts as we continue to advance the benefit for patients from clinical studies to the real world.

We're committed to leveraging our deep experience across all of these cholestatic disease settings as we continue our scientific leadership. And with that, I'll turn the call back over to Chris.

Chris?.

Thanks, Pam. Mirum is poised for continued growth throughout the years ahead.

We anticipate that 2023 will be another transformative year with strong commercial growth, potential PFIC label expansion, top-line data of the first randomized dataset of an IBAT inhibitor in Biliary Atresia and interim analysis from our potentially pivotal Volixibat studies.

We remain excited about the growth prospects and potential of Mirum as we work to provide new medicines to patients with rare disease. And with that, operator, please open the call for questions..

Thank you. [Operator Instructions]. We have our first question comes from Jessica Fye from JPMorgan. Jessica your line is now open..

Hey, this is Nick on for Jess. Thanks for taking our questions. Two quick ones for me.

One, could you just talk a little bit about the factors that resulted in that timing shift for the Phase 2b VISTAS trial from mid-2023 to the second half '23? Is that more of a narrowing or a shift?.

Yes, hi. I'm happy to answer that question. Thanks for the question. So the reason for the delay in the PSC study, it's really a slight delay and mostly based on screen sales and there's a number of reasons why patients are screening out.

One is the mix of lab values some pruritus for compliance during screening where they have to put in their pruritus scoring. And if they're not compliant, they also get kicked out, because we want to make sure that they can remain in the study. And then also some for itch score that is not meeting the minimum threshold to enter the study.

What we're doing with some of this is we've got plans on advancing tools and education on how we standardize training and interpretation of those itch scores and just continuing to drive forward, and we're starting to see more movement and good activity..

Great. And as a quick follow-up. I know there have been some PBC trials in the past that have run into issues with high placebo responses on itch.

Can you kind of just discuss how the VANTAGE trial is designed to help kind of mitigate those risks?.

Yes. Thanks for the question. So in our PBC clarity study, as you know, we -- there was a -- we ourselves had a placebo response rate. So we took those learnings applied them into this study design.

We baked some of that into the assumptions for our analysis, and we also adjusted our study designed to accommodate for placebo failures in account for that. I don't think I can give specifics about the way that we're doing that in the trial, but we have thought very deeply about that and taken that into account..

Great. Thanks so much..

Thanks for the questions..

Thank you. Our next question comes from Mani Foroohar from SVB Securities. Mani your line is now open..

A quick question on Biliary Atresia.

How should we think about the scale of the opportunity, both in terms of the number of patients, which I think is fairly well defined, but also at what point would patients be treated and how long would they be treated? Is the expectation here that you'd pursue a lifelong study? Or would you expect it from your clinical feedback that position in the case of a successful study commercialization would after one year, two years, some period of time, look to withdraw patients rather than leave them on drug for life?.

Thanks, Mani, for the question. I'll -- I mean, I want to just kind of first comment, Biliary Atresia is the most common indication for transplant in liver transplant and pediatrics. So really in terms of scale of unmet need and impact you can have, this is a really important indication.

I shall ask Peter to maybe speak to a little bit of how to think about how this evolves over time, the duration of treatment, because there are some nuances on how we think this indication can build over time..

Yes. And I think as you think about that piece there Mani, the Biliary Atresia is more common than Alagille and PFIC by a fair bit when you think about it from an incident perspective, probably on threefold more common on newborn incidents in Alagille.

But because of the dynamics that Chris is describing, there's much less of a prevalent pool there, because it's generally pretty rapidly progressive and heads towards liver transplant.

So we'd envision in the kind of early years after approval, the eligible patient population being kind of on the order of kids who are born within the last 12 to maybe 36 months.

But as you -- if the drug does what we hope it does and get patients on therapy and, again, hopefully keep them from liver transplant that would build over time and I think could be better than the other two indications..

That's very helpful. And when we talk about what the drug hopes one can do. Obviously, it's a little less certainty around the regulatory dynamic here, because it doesn't internally ask [indiscernible].

Can you give us a sense of how you think about target effects by, target product profile? And is there more certainty in your view on what need to show for clinical uptake? Or is that also a little bit up in the air as our regulatory questions?.

Thanks for the question there. I mean there's a couple of aspects to consider and thinking about the regulatory conversations that we'll have after this data set is unblinded, regulators are data-driven. And they do have patient interest in mind.

And so I think if we show a really convincing data set paired with advancing some of the understanding of the disease and the importance of bilirubin, which is some work we're also doing in parallel. That will be the basis for a really good case and strong conversation on why the EMBARK study could potentially support approval in Biliary Atresia.

We do need to generate that data, and that's all kind of baked into the study design. I think the one thing that I'd point to in addition to the bilirubin data that Pam talked about from the PFIC study, just looking at mean change in bilirubin.

There's also categories that are really well established on risk profile for transplant in terms of level of bilirubin at three months. So we have a close eye on that being able to down categorize patients on the bilirubin score. It's above 6%, 2% to 6% and below 2% for bilirubin. Each step is a meaningful difference in risk of outcome.

So we'll look at those in a kind of responder or shift table format..

All right. That's very helpful. Thanks guys..

Thanks for the question..

Thank you. We have our next question comes from Steve Seedhouse from Raymond James. Steve your line is now open..

Hi, two questions from me. This is Ryan Deschner on for Steve Seedhouse.

The first -- now that we're more than a year into LIVMARLI launch, have you seen an appreciable step-up in sales due to the increases in average patient weight? And how often are treating physicians adjusting dose for growth in other reasons?.

Thanks for the question. What we see there is I think about once a year, patients are weighed and they're considered for dose increases. We do see dose increases in the real world setting is consistent with the prescribing information for LIVMARLI. Really, the majority of the growth we're seeing is just de novo demand and new patient starts..

Excellent.

And then also, in what areas do you anticipate potentially being able to differentiate from competitor odevixibat in Biliary Atresia?.

In terms of -- thanks for the question, Ryan. In terms of Biliary Atresia, I think the time to having a randomized data set was a big part of our thinking and our strategy here.

The EMBARK study on track to have data second half of this year will give us a really sizable lead in terms of having data on LIVMARLI, a really robust data set on LIVMARLI in this setting. We also have a feature of the study that is not in the bill base study, where at six months, patients roll on to open-label therapy.

So the effect of starting treatment later is really important to look at from the prevalent patients that are out there. So that's a really key part that we're looking at here. And then lastly, similar to what we've seen in the other settings, our higher dose of LIVMARLI, I think, is we expect to have a bigger clinical impact.

So I feel like we've really advanced our understanding of how to dose IBAT inhibitors and really think that that's going to show up in our top-line data..

Thank you very much..

Thanks for the questions..

Thank you. We have our next question coming from Debanjana Chatterjee [ph] from Citi. Debanjana your line is now open..

Hi, thanks for taking our call. I'm on for David Lebowitz from Citi. So we were wondering if you could comment on the ex U.S. inventory build? And what should we expect in terms of the sale strategy ex U.S.

going forward?.

Yes. The -- in terms of the $4.4 million in sales we saw in Q1, a lot of that was from Germany and Western Europe, where there's really very little effectively zero inventory, true demand sales there as we get started in those countries.

We do have some other -- the balance of the sales in international our named patient programs in distributor markets or markets that we're not directly selling in, but our partners are Central Eastern Europe, Middle East.

And generally, what happens in those dynamics is there's a country-specific mechanism and individual patient identified the physician and the -- our distributor partner works through a local reimbursement access mechanism. Oftentimes, those patients get three, six and even in some cases, we've seen 12 months of supply ordered for one patient.

So that's kind of where -- so obviously, you're not going to see a consistent refill cadence every 30 days like you see in the U.S. with those kind of orders. So that's kind of the dynamic we see. And in terms of visibility and the guidance we have for 50% growth is based on the U.S.

sales in international setting, we're really excited about the feedback we're getting, and we're excited that Germany has gone really well. And I think from the sort of the patient position perspective, looks a lot like the U.S. But it's just too early to provide firm guidance on international given that we just kind of get started there..

That's very helpful. Thank you..

Thanks for the question..

Thank you. We have our next question comes from Ed Arce from H.C. Wainwright. Ed your line is now open..

This is Thomas here asking a couple of questions for Ed. First, congratulations on the very impressive quarter. So just trying to tease out the -- of the 600 patients with Alagille syndrome that's being treated with LIVMARLI globally.

Can you tell us roughly what percentage stay on chronic segment? And if you can provide some major factors for patients to stay on LIVMARLI or by first stay off LIVMARLI as well -- that would be appreciated?.

Hi, thanks for the question. We -- the 600 number really we see as a really strong statement on familiarity with and interest in prescribing LIVMARLI. That number comes from all sources over the history of the program for patients with Alagille syndrome who have been prescribed or been part of the clinical study protocol.

So it's really kind of all sources that feed into that. Not really a number that makes sense to parse out to the -- by country or by source.

But what we can say is that across all of the different ways that patients had found their way to LIVMARLI clinical study, expanded access program, commercial products, compassionate use products in different formats. You do see the same profile of really high compliance, high persistence.

Some of these patients six plus years staying with the program, because of the profound impact that it can have..

Thanks for the proper finishing [ph]. Perhaps sticking with Alagille syndrome. With the U.S. label expansion down to three months of age and above.

Can you just tell us what were your expectations are both for top-line and also from a strategic standpoint as well?.

Yes, on the label expansion for Alagille down to three months of age, really important step because that's where most patients are diagnosed. So it allows LIVMARLI as a treatment option early on. Overall, top-line impacts.

Keep in mind that these are younger, smaller patients, really important for the long-term view, but staying consistent with our guidance of 50% year-over-year growth in the U.S. And international, as we get further in, we'll look at how we fold that into guidance as well..

Got it. And then perhaps switching gears to PFIC with the application submitted to the EMA in Europe.

When should we expect your next milestone, including CHMP opinion perhaps?.

Yes. So the PDUFA date we shared in December, excited about that, and the potential timing for an opinion would be -- from CHMP would be late Q3 or in Q4..

Got it. Perhaps one final question. This one is financial.

With the convertible offering growth in April, can you tell us what's your estimated cash runway out to?.

Yes. So similar to described in the prepared remarks, really are fully funded with the current business to cash flow breakeven and positive. So three plus years really meant to just be an indicator of the strength that we have there and see runway to operate the business for the long-term here and continue to grow the products..

Got it. Understood. Thank you so much. Thank you again for taking our questions. Looking forward to the Biliary Atresia data..

Yes. Thanks for the question..

Thank you. We have our next question comes from Brian Skorney from Baird. Brian your line is now open..

Hi, this is Luke on for Brian. Just a couple on EMBARK. Do you have an update on the scope of detail you might expect to include with the top-line readout beyond just bilirubin in particular or maybe any outcomes data? And then are you able to generally characterize the geographic dispersion of the enrolled patients in terms of U.S.

versus other territories? Thanks..

So thanks for the question. And overall, on top-line, other than the primary, you can't really speak to specifically what else would be in there other than getting material updates disclosed. The study is not powered for outcomes at that time point. So unclear if we would have anything to share on that point.

And then geographic presence of sites really around the globe, and we're seeing activity across all geographies, nothing really to point to there..

Great. Thanks. And then just one on the PFIC launch.

Do you think this will be a lean add-on? Or do you see any need to invest further into the commercial team?.

I'll ask Peter to maybe describe some of the launch plans..

Yes. We don't see a need for incremental OpEx for PFIC. It's straightforward. In fact, the PFIC patients are probably taking care by a subset of the prescribers who've prescribed LIVMARLI today for Alagille syndrome..

Great. I'll back in queue. Thank you..

Thanks for the questions..

Thank you. [Operator Instructions]. We have no further questions on the line..

Great. Thank you, operator. And thank you to everyone for joining today's call. Hope you have a great day. Bye-bye..

Thank you. Ladies and gentlemen, this concludes today's call. Thank you for joining. You may now disconnect your lines..