Good afternoon. Thank you for attending the Mirum Pharmaceuticals Fourth Quarter and Year-End 2022 Financial Results and Business Update. My name is Matt, and I'll be your moderator for today's call. [Operator Instructions]. I'll now like to turn the conference over to our host, Andrew McKibben, Vice President of the Investor Relations and Finance.

Andrew, please go ahead..

Thanks, Matt, and good afternoon, everyone. I'd like to welcome you to Mirum Pharmaceuticals fourth quarter and full year 2022 conference call. I'm joined today by our President and CEO, Chris Peetz, our Chief Operating Officer, Peter Radovich, our Head of R&D, Pam Vig, and our CFO, Ian Clements.

Earlier today, Mirum issued a news release announcing the company's results for the fourth quarter and full year 2022. Copies of this news release and SEC filings can be found in the Investors Section of our website. Full details on updates from the quarter can be found in our news release and 10-K issued today.

Before we begin, I'd like to remind you that during the course of this conference call, we'll be making certain forward-looking statements about Mirum and our programs based on management's current expectations, including statements regarding Mirum's business plans, development programs, 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. In 2022, Mirum made remarkable progress, growing into our leadership position as a high-growth rare disease company focused on commercializing life-changing medicines.

And while we are all excited about our Q4 quarter-over-quarter sales growth of 48%, we are just getting started. Our clinical, regulatory and business achievements during the year with net product sales for LIVMARLI of $75 million, provide a strong base from which we will rapidly grow our business.

We have put in place a 5-part strategy to become a global leader in rare disease. First, build on the successful launch of LIVMARLI in Alagille syndrome in the U.S. LIVMARLI is the first and only treatment in Alagille syndrome to provide early improvements with long-term impact.

And we are still early in making LIVMARLI available to the addressable Alagille syndrome patient population. In the second half of last year, we expanded our field presence and investment in the U.S., and now anticipate 50% growth in U.S. LIVMARLI sales in 2023.

This is driven by the Mirum team and the tremendous potential of LIVMARLI for patients, which was highlighted this year by data showing that in Alagille syndrome patients showing [indiscernible] with LIVMARLI, 88% of them remain event-free at 6 years. Now second, grow LIVMARLI in markets outside the United States.

Following European approval in December, we have already launched in Germany, with France to follow shortly and further launches around the globe later this year and in 2024. Third part of our strategy, expand the label for LIVMARLI. At the end of last year, we presented LIVMARLI PFIC Phase III data.

This is the largest study conducted in this devastating disease, covering the widest range of PFIC types. In addition to impressive reductions in serum bile acid and pruritus, we saw placebo-controlled improvements in various markers of liver health, namely bilirubin and growth, the first I've seen is reported for IBAT clinical studies.

We have submitted our sNDA and are excited about bringing the strong data profile to prescribers and patients. On our third potential indication for LIVMARLI, we have also made good progress in the EMBARK study in Biliary Atresia and expect to announce data in the second half of this year.

Fourth, apply our expertise in IBAT inhibition to expand into adult cholestatic liver disease. Building on earlier IBAT inhibitor data in primary sclerosing cholangitis and primary biliary cholangitis, we are conducting potentially pivotal studies for volixibat in these two underserved indications.

And finally, the fifth part of our strategy, expand our development pipeline for business development activities. We are evaluating a number of interesting opportunities across rare and orphan diseases to leverage Mirum's industry-leading rare disease capabilities.

We entered 2023 with great momentum, and I am excited by what the Mirum team can achieve in the near future, providing patients with life-changing medicines that they've been waiting for. 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 $27.9 million in LIVMARLI net product sales in the fourth quarter of 2022, which represents a 48% growth over the third quarter.

Additionally, we reported $75.1 million in LIVMARLI net product sales for the full year 2022, which included $68 million in the United States and $7.1 million from international markets.

Needless to say, we are thrilled with LIVMARLI's performance in its first full year on the market, which represents one of the strongest rare pediatric launches in the industry. Now first, some comments on the U.S. business.

The growth we saw in Q4 was driven by more new patient starts and a consistent refill pages, which were both a direct result of our commercial team's strong execution. We estimate that about 20% of currently diagnosed and addressable patients with Alagille syndrome in the United States have received LIVMARLI since launch.

And as the results reported today demonstrate, our commercial team has been highly effective at driving the LIVMARLI launch further into the addressable market, and we remain confident in continued growth going forward, consistent with our guidance that 2023 LIVMARLI U.S. sales will grow by 50%. Now turning to international.

The $7.1 million in 2022 sales was predominantly in Q4 and came from partner markets in Eastern Europe and the Middle East where Mirum's distribution partners were able to engage in preapproval commercial access programs.

The Q4 international sales number included an inventory build as a result of full-year product orders for identified patients in these partner markets.

Looking forward to 2023, we expect to see continued demand growth and sales contribution from partner markets in Eastern Europe and the Middle East, as well as new partner markets coming online in Latin America and Asia, including Korea, where LIVMARLI was recently approved.

European commercialization has commenced following the December 2022 European Commission LIVMARLI approval. In early 2023, Germany became the first European country to launch and is off to a great start in the initial weeks out of the gate.

In France, our pre-approval access program for LIVMARLI was recently approved, enabling access to commercial LIVMARLI before full reimbursement. Beyond Germany and France, we expect other Western European countries to launch upon completion of pricing and reimbursement discussions later this year and into 2024.

Finally, our LIVMARLI marketing application is under review in Canada, which, if approved, would enable a launch later this year. In summary, LIVMARLI is the first and only treatment for Alagille syndrome that provides early improvements with long-term impact on event-free survival.

With approximately 600 Alagille patients treated globally to-date clinicians have gained familiarity with and confidence in LIVMARLI's robust clinical profile as well as its exceptional access and patient support. We believe this will propel a continued growth story for the Alagille syndrome launch going forward.

On that note, I'll turn the call over to Pam.

Pam?.

Thank you, Peter. 2022 was an outstanding year for our clinical team as we presented meaningful data, supporting both our commercial stage and pipeline programs.

At the end of last year, we presented groundbreaking Phase III data for LIVMARLI and PFIC, in which LIVMARLI drove a statistically significant reduction in pruritus and serum bile acids across the broadest genetic PFIC type study to-date, showing a magnitude of treatment effect, which is approximately double from previous studies and exceeded our expectations.

Notably, the majority of patients also achieved serum bile acid reductions below the threshold that is associated with transplant-free survival. And furthermore, LIVMARLI also drove early and significant placebo-controlled improvements in growth as well as in bilirubin, suggesting an improvement in the underlying liver health of these patients.

And as a reminder, bilirubin is an important indicator of disease progression in cholestatic disease and MARCH is the first study to demonstrate statistically significant differences in bilirubin versus placebo in PFIC. And it's remarkable that this was observed with only 6 months of treatment.

While these unprecedented clinical effects from the MARCH-PFIC study across broad genetic types situates LIVMARLI in a very strong position. And we are thrilled to deliver LIVMARLI to the broader PFIC population and regulatory approval.

Now as we look to biliary atresia, the bilirubin and serum bile acid reductions observed in PFIC are very encouraging. Both of these markers, particularly bilirubin, are strong prognostic indicators of disease progression and our primary endpoint will measure the 6-month change in billing from baseline.

We look forward to announcing this top-line data from the Phase IIb EMBARK study in the second half of this year. In the adult cholestatic indication, there is a similar significant unaddressed burden of cholestatic pruritus which is associated with the buildup of toxic bile acids severely affecting quality of life in these patients.

And in the setting of both CSC and PBC, about over 60% of patients have [indiscernible] pruritus of which about 80% or more are being treated with off-label and anti-secrete medications that are largely ineffective or offer only partial response.

And year-to-date the new options as highlighted by a PSC survey we presented last year were 75% of patients using 2 or more medications described only partial order release. Given the significant burden of these diseases, we're really excited to continue advancing volixibat in PSC and PBC with interim analysis expected later this year.

And lastly, I'm really proud of our team's academic and collaborative efforts as well as our continued scientific leadership, which was showcased throughout 2022 through our congress presentations and a number of publications characterizing the benefits of LIVMARLI in pruritus and beyond, mirroring what we're hearing from the real-world experience.

And 2023 is expected to be another outstanding year. And with that, I'll turn the call over to Ian to review our financial results.

Ian?.

Thanks, Pam. The press release and 10-K filed earlier today provide a full financial update. However, I'll call out a couple of the highlights here. First, from a revenue perspective.

Total revenue for the year ended December 31, 2022, was $77.1 million, including license revenue of $12 million or $2 million versus total revenue of $19.1 million for 2021. Of note, this is slightly higher than the $76 million preliminary estimates we announced back in January. Turning to operating expenses.

Total operating expenses, including cost of sales for the year ended December 31, 2022 were $208.3 million versus $192.6 million for the prior year. Mirum remains well funded with over 3 years of runway. And at the close of the year, we had $251.7 million on the balance sheet.

Additional details on all of our operating expenses and our cash balance are provided in our 10-K filing. Overall, our financial position is strong and supports our continued growth and value creation across both our global commercial business, and development pipeline. With that said, I'll turn the call back over to Chris.

Chris?.

Thanks, Ian. Mirum is poised for continued growth throughout the years ahead as we execute on commercial, regulatory and clinical value creation. We're in the midst of a strong launch in Alagille syndrome, growing the U.S.

business while launching in Europe and partner markets and unlocking expansion opportunities for LIVMARLI and volixibat ahead of us. We expect 2023 will be a catalyst-rich year.

In addition to the continuing strong commercial growth for LIVMARLI adoption in Alagille syndrome, we have the potential PFIC label expansion and data readouts for our pipeline programs as we get further into the year.

True to our name, Mirum, which comes from the Latin word for remarkable, our recent accomplishments and anticipated growth ahead in 2023 are full of unique potential as we work to bring important new medicines to patients around the world. And with that, operator, please open the call for questions..

Absolutely. [Operator Instructions] The first question is from the line of Jessica Fye with JPMorgan. Your line is now open..

I was hoping you could provide a little bit of a framework for how to think about Europe sales this year. I'm not sure if there's anything you can provide on that front? And then, second, I think in prepared remarks, you mentioned that 20% currently diagnosed and addressable patients have received LIVMARLI since launch.

Can you talk through how we get to $500 million peak sales for LIVMARLI in Alagille in the U.S. based on what we saw for 4Q sales. In particular, I'm sort of curious what market share is assumed in that forecast. And also how much upward drift in price per patient is anticipated due to growth? Thank you..

Thanks, Jessica, for the question. I give a couple of inter-comments, and I'll let Peter speak to some of the details in particular on how Europe launch will roll out and some of the market dynamics in the U.S. But I think just pointing to some pretty quick and easy math on Q4 U.S.

revenue is a little bit of rounding to this, but that's pretty close to a $100 million run rate at 20% penetrated. I think you can kind of get the picture of how that lines up with the $500 million or greater market opportunity that we talk about for the U.S.

With that kind of just a quick backdrop on the U.S., I'll hand over to Peter to maybe pick into the Europe question..

Sure. Happy to comment on that. And I think as you think about the international piece for LIVMARLI in 2023, it's probably like 3 components to think about. The key driver will be Germany. As I mentioned, we're in the market in Germany now, had a really strong start in the first handful of weeks.

That's really the one country will be it where we have kind of access to the full health care system with full reimbursement. The second kind of bucket for 2023 is really name patient sales program or pre-reimbursement approval programs.

I mentioned we have one in France that's opening up with commercial LIVMARLI, there's also a couple of others potentially in Western Europe as well as partner markets. Those kind of programs are what drove our Q4 2022 number and opportunities to participate in those programs, even in new geographies of Latin America.

Those are a little bit less predictable. We have clear visibility to high unmet medical need. We hear from clinicians about patients who are really, really interested in LIVMARLI. So at the clinical side is high visibility, but it's really kind of country-specific kind of pricing reimbursement mechanisms that have to be navigated there.

So that's the second bucket. And then I think the third bucket I'd kind of call out for 2023 is new country launches. So in Western Europe, we might have some new countries coming on at the end of the year or into 2024, depending on how pricing reimbursement timelines go.

I mentioned Canada which have approved by Health Canada, could support a launch with contribution from the private market to Canada at the end of the year. So there's a cup in that third bucket, there's a couple markets where you could start to see contribution in late '23, but really more likely in 2024..

The next question is from the line of Mani Foroohar with SVB Securities. Your line is now open..

A quick question more on the pipeline.

As we think about the sort of portfolio of readouts that you're coming throughout this year in Phase II, on what time horizon should we expect to get a little more clarity on what is and is not pivotal, just relative to when we're getting the data, I know there's a little bit of uncertainty around exactly what a pivotal endpoint might be, for example, in biliary atresia, et cetera.

How should we think about the gap between data and when we'll get a little bit of clarity on what an approval endpoint is or isn't?.

Thanks for the question, Mani. I can touch on a little bit of context to put on these readouts. And I'd point out that biliary atresia for LIVMARLI, you should think about it differently from the volixibat interims. And first commenting on the biliary atresia readout, we won't know at the primary analysis readout later this year.

That's going to involve some conversations with FDA interpretation of the data, building our case to understand what the next step is for that program, whether it's putting together a submission or planning for another study. The volixibat program, though, these studies are very different in their positioning as potentially pivotal studies.

We have already aligned with FDA on using pruritus as the registrational endpoints and the analysis plans for both of these studies. So think of these upcoming interims as really the dose selection to move into the pivotal portion.

So when each volixibat study gets to its interim analysis, they essentially convert into pivotal studies for that adaptive part 2. So we know once we cross that interim as long as the study is continuing. It is a pivotal study in all kind of forms and the input from FDA that you want for a pivotal study..

The next question is from the line of Josh Schimmer with Evercore..

Great.

First, for the commercial spend, how should we think about the step-up as you add new indications to the franchise, we had LIVMARLI or volixibat? And then for either product, but I guess, LIVMARLI, any updates or progress identifying a path forward for the ICP indication?.

Great. Thanks for the question, Josh. I'll pass it over to Peter to talk a little bit about commercial spend across the indications and products. But I can comment on the ICP question in the interim. Really interesting data that came out of the OHANA study, albeit very small patient numbers that we were looking at.

You can tell that volixibat is active for these patients. It addresses the pruritus, just a near and possible setting to conduct robust clinical studies in. So we are seeing interest in potential investigator-sponsored approaches. We'll continue to explore that. But kind of until those come together, don't have a formal update on the ICP program.

Peter, do you want to comment on commercial investment?.

Sure, happily. I think with LIVMARLI, the short answer is that it's largely stable. I think some of the puts and takes around that as we do geographic expansion with the first indication Alagille, we've already built a lot of that team and invested in a lot of the commercial activities.

There may be some kind of minor incremental things, but nothing big enough with the geographic expansion to change things. As we expand to PFIC, that we're going to take on the same geographies we're in now, and it's the same call universe.

Again, maybe some very modest things is not enough to kind of show up on an overall SG&A number in a meaningful way that we would do to support that launch. And biliary atresia also taken care of in the same physicians and children's hospitals that PFIC and Alagille. So really LIVMARLI pretty stable.

As we move to volixibat, that gets us into the adult setting, so obviously, we'll have to have a team that can reach adult GIs and hepatologists. But we'll look to leverage the team we have now and build from that as we get to those milestones..

The next question is from the line of Steve Seedhouse with Raymond James..

Hi. This is Ryan Deschner on for Steve Seedhouse. Curious, in biliary atresia, what the timelines you anticipate for completion of enrollment in EMBARK.

And then also, how will dosing in the EMBARK Phase to be handled? Will there be any sort of titration or starting dose?.

Ryan, thanks for the question. I'll pass it over to Pam to give a little color on the EMBARK study..

Yes. Thanks for the question. So we're just super excited about the EMBARK study even if this would be the first study to read out in the [indiscernible] IBAT inhibitor by the end of this year. So that speaks to the timing of when we expect the study to read out and complete enrollment.

With regard to your dosing question, the dose that we're using in this study is the same as our PFIC dosing, which is 600-microgram per kilogram twice a day. And what we saw in the PFIC study was really remarkable with regard to the [indiscernible] reduction. That were really unexpected.

And so that gives us a lot of encouragement, but we are hoping to see in this cellular [indiscernible] study. The dose is titrated, as it is with our other studies, but the step-up start to and early on in the study [indiscernible] thing throughout the remainder of the 6 months..

Got it. That's very helpful. And maybe if I could squeeze one more quick one in.

Do you expect the bigger seasonality effect as it did in 2022 to come in 3Q, while the other quarters, I guess, going into 2020 remain fairly comparable?.

We saw last year. It's kind of hard to tell us that is going to be a recurring phenomenon. The summer travel season was a little more of the same post-COVID last year. I think it's the simple way to put it. So a pretty good chance that we see some kind of effect like that where there are just fewer visits to start new patients.

But important to note that throughout our third quarter last year and what we expect this year is as refills and the persistence to continue to be a real highlight for families on drug that they stay on drug. It's a real highlight of the performance..

The next question is from the line of David Lebowitz with Citi. Your line is now open..

Considering that LIVMARLI is going to be in a competitive dynamic by the end of this year in two different markets, both LGS and PFIC.

How do you see that affecting your commercial approach? Is there any risk of any competition on pricing in the market?.

Thanks for the question, David. I'll make a couple of comments. I mean the one thing that's on pricing, that's not something that we would expect to see. And particularly given some of the nuances of the position that we see in the market.

And that LIVMARLI is really well positioned with such a great lead in terms of prescriber experience nearly 600 Alagille syndrome kids treated with LIVMARLI over the history of the program. That's a tremendous amount of experience and most of that being overwhelmingly positive.

So find ourselves in a position where I think we expect to see more of what we've seen in the launch to date, which is continued new patient starts and strong persistence compliance for patients that are on drug. And with the PFIC indication coming on really a step up in terms of what you'd expect to see for efficacy from the clinical profile.

That's going to be really powerful, excited for when our team can go out and talk about that data..

The next question is from the line of Brian Skorney with Baird. Your line is now open..

On the EMBARK study, I was hoping you could kind of talk through the relative importance as you see immune reduction in serum bile acid versus the proportion of patients with total bilirubin below 2mg/dL? And maybe even in context there, what the average baseline bilirubin we're seeing in EMBARK, as well as what the lower threshold is that you're allowing and also another size, why isn't a 6mg/dL cutoff also being included as prospectively defined endpoint given the Schneider paper?.

Yes. Thank you for the question. So basically, in biliary atresia, these kids, most patients continue to experience liver injury from accumulation of bile acids, right? And by reducing bile acid retention, you should improve BioFlo and bilirubin is an indicator of how well that bile is flowing. So you're looking at both of these as markers.

Early on after the size, when you can reduce bilirubin, that has been shown, as you're mentioning in the Schneider paper that if you are 2 or less, you have a really good chance of maintaining relative liver if you're between 2 and 6 it's kind of mid-range. And if you're greater than 6, you really are headed towards transplant.

And that's because the liver is, in fact, not functioning. So bilirubin the most predictive marker of transplant, is an indicator of bile flow in liver injury.

And I think that, as I mentioned, the data that we've seen from our PFIC study as a result of reducing bile acid retention in that setting and thereby reducing bilirubin is really encouraging for us on what we're hoping to see in the BA program under retail..

And just any comment on what the baseline in EMBARK would be from a bilirubin perspective?.

There is no threshold. All of these kids are coming in. They're all pretty sick. They've had a procedure. They've got information. They've got the accumulation of bile acids and they have validated bilirubin..

The next question is from the line of Ed Arce with H.C. Wainwright. Your line is now open..

A few for me. First, you mentioned earlier there were -- or have been since launch, about 20% of patients diagnosed and addressable have received LIVMARLI. I just wondered if you could discuss the difference between that and actual market share now, given there's some that, I would imagine some small numbers have cycled on or off.

Is that pretty close to market share, and if not, what are the differences there? And secondly, wondering about PFIC when you would expect to get the NDA acceptance letter and PDUFA date there? And then, lastly, just thinking about the cadence of the three readouts later this year, two in the second half and one in the middle of the year.

Just wondering if you could perhaps delineate a little more precisely what kind of gaps in between those we could expect or if maybe a couple are expected pretty close. Thanks so much..

Thanks, Ed, for the question. The first one kind of take through this year. On the first one, looking at market share, we continue to -- for the U.S. business, to really just highlight that these are real dispenses in that revenue number. So you can look at those numbers as very direct patient volume being to expense real demand.

So you can get a sense of that number just by looking at the U.S. net revenue number. In terms of some of the kind of milestone timing items, PDUFA data sign is typically about 2 months after submission.

So we expect that to be in the next month or so based on when we submitted the PFIC sNDA and then on the other kind of clinical end points or clinical readouts, don't really have any further color to get more precise than kind of midyear in the two in the second half..

The final question is from the line of Yasmeen Rahimi with Piper Sandler. Your line is now open..

Before I start my questions, just wanted to say thank you, Ian, and we will greatly miss you. Maybe the time of your last call, you're going to be hosting with that. So wish you the best of luck and thank you again for everything, definitely under how....

Yas, appreciate that..

I really wanted to say that. And then, in regard to my questions, obviously, a lot of investors are eagerly awaiting volixibat readouts.

And I think a fundamental question that comes up is what's going to be the translation? So obviously, we get the news that in PSC, you can move forward being a pivotal study? Like can you maybe help us understand sort of how much that de-risked PSC opportunity and also what that means for you to put more dollars and more into continuing to really be behind volixibat? That's sort of my question for you guys.

Thank you, again..

Thank you for the question. I'll have a couple of comments and then pass it over to Pam to talk a little bit about the interims, how it relates to the final data. I think the thing I'd say at the outset is, there is really strong proof of concept for IBAT in both of these indications already.

Some great clinical data from the Maralixibat program and PSC showing that you can reduce bile acids and pruritus in patients that have elevations coming in. So the patient population that's in this study. So I think we already have really strong critical derisking of knowing that an IBAT can be active in these settings on these end points.

Maybe Pam can speak a little bit to the specifics of the study design and the interims need..

Yes. Thanks, Yas, for the question. So just to add on to what Chris was saying. In our own PSC experience, we've seen that patients who have moderate to pruritis. And this is in an open-label study that with 70% itch reduction and almost 50% [thrombolysis] [ph] reduction in that population.

So again, showing that we know what this mechanism can do in the disease and frankly, also seen in Alagille and PFIC across whole set diseases. Now as you look to our statistical assumptions for the studies in the interim, for PSC, the interim includes 45 patients and that is triggered when all patients have reached week 12.

So that means some of the patients will be at 24, some will be beyond, but all patients will be week 12. And this is a really great way for us to look at observational differences and that will help us assess if we're on the right track for the final analysis.

The interim is not powered for significance by design, but it allows us to determine or in the zone for a positive final analysis.

And a couple of notes on our kind of confidence in the way that we've conducted the design or that we set up the design is that the [indiscernible] data in PBC showed statistical significance in their analysis when they looked at baseline over time. And they only had about 20 patients in each of those cohorts. And that was seen in their BID dosing.

And importantly, that was seen in the high dose in the BID dosing regimen. So we think given our dose, given our assumptions, given the number of patients we have, we're really confident about our assumptions and may even be overpowered..

Thanks so much..

Did that answer your question?.

Yes, that was extremely helpful. Thank you, Pam..

Thank you for your question. There are no additional questions waiting at this time. So I'll pass the conference back to Chris for any closing remarks..

Great. Thank you, operator. And I just want to say thanks again to everyone for joining today's call, and hope you have a great day. Goodbye..

That concludes the conference call. Thank you for your participation. You may now disconnect your lines..