Mirum Pharmaceuticals Inc. Q1 2023 Earnings Call

With and confident in the <unk> robust clinical profile as well as exceptional access and patient support.

And we believe this provides a strong competitive position propelling a continued growth story in <unk> syndrome with exciting pediatric cholestasis indication expansion opportunities just on the horizon.

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

Thanks Peter.

First quarter, we achieved important milestones in our pipeline that support the growth of our programs and our ability to impact more patients.

As a reminder, the central problem in all of these diseases study and our pipeline is accumulation of bylaw.

And across six public delek setting either inhibition has been shown to directly reduce toxic bile acid accumulation the associated debilitating symptomatic burden and analogy I'll live Marley showed improved long term outcomes versus standard of care.

The benefits of profound I bet inhibition was shown by the impressive data from our March pediatric Phase III study announced at the end of last year, and we're happy to share that our supplemental NDA submission was accepted <unk> date of December 13th of this year at.

And in April we also submitted for approval of live Marley in <unk> to the EMA for patients two months of age and older.

Now the data from the March PK study proved our hypothesis, where greater I bet inhibition using higher dosing regimen would look marley drove a highly statistically significant reductions in both <unk> and serum bile acids across the broadest range of genetic pubic types studied to date.

In addition, early in statistically significant improvements in growth as well as in bilirubin were seen in patients treated with the Marley, where 40% of patients with abnormal bilirubin levels at baseline normalized their bilirubin versus zero in the placebo group now.

Now these data suggest an overall clinical improvement beyond Corrado for these patients and we have had strong positive feedback from the physician community and if approved look forward to the opportunity to expand with <unk> to a broad patient population.

We're also happy to announce that we remain on track for topline 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 <unk> inhibitor in this study and we're really excited to share more when the study is completed.

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

And the dosing regimen in the VA study is the same as the March peak 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 cosmetic indication.

We expect interim analysis from our studies that go with that in both PFC and PBC in the second half of this year.

We have previously shown that marked reduction in pruritus and serum bile acids can be achieved with <unk> inhibition in PSC underscoring the potential for <unk> 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 lowers bile acids.

Building off of our learnings from our pediatric program.

We are dosing at a higher level and the IV dosing regimen, which adds to our confidence in this upcoming interim analyses.

And finally, I am 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 where.

We're committed to leveraging our deep experience across all of its cholesteric disease settings, as we continue our scientific leadership.

And with that I'll turn the call back over to Chris Chris.

Thanks Pam.

<unk> is poised for continued growth throughout the years ahead.

We anticipate the 2023 will be another transformative year with strong commercial growth potential pubic label expansion topline data of the first randomized data set either inhibitor in biliary atresia and interim analyses from our potentially pivotal fourth for that service.

We remain excited about the growth prospects and potential of <unk> as we work to provide new medicines to patients with rare disease.

And with that operator, please open the call for questions.

Thank you.

Ladies and gentlemen, if you'd like to ask a question. Please press star followed by one on platform key patent now perfect.

Ask your question, please ensure you're pulling some real good locally.

We have our first question comes from Jessica Fye from Jpmorgan Jessica Your line is now open.

Hi, This is Nick on for Jeff. Thanks for taking our questions. Two quick ones for me one could you just talk about a little bit about the factors that resulted in that timing shift for the fees to be Vista trial from mid 2023, and second half 'twenty three is that more of a narrowing or a shift.

Yeah, Hi, I'm happy to answer that question. Thanks for the question.

So the reason for the delay in the PSC study is really a slight delay in 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 theyre not compliance. They also get kicked out because we want to make sure that they can remain in the study and then also some for each for that.

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'd been some PBC trials in the past that have run into issues with high placebo responses on it can you kind of just discuss how.

The vantage trials designed to help kind of mitigate those risks.

Yeah. 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 the study design, we baked some of that into the assumptions for our analysis and we also adjusted our study.

Bind to accommodate for a placebo failures and 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 then taking that into account.

Great. Thanks, so much.

Thanks for the questions.

Thank you.

Our next question comes from Manny <unk> from SVP Securities money. 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.

We will define.

But also at what point would patients be.

You did it how long would they be treated as expectation here that you would pursue a lifelong study would you expect from your clinical feedback.

<unk> indicates a successful commercialization.

After one year two years some period of time look to withdraw patients' whether we go on drug for life.

Thanks, Marty for the question.

I wanted to just kind of first comment biliary atresia is the most common indication for transplant liver transplant and pediatrics so really.

In terms of scale of unmet need and impact. It can have this is a really important indication.

I'll ask Peter to maybe speak to a little bit of how to think about how this evolves over time and duration of treatment is there are there are some nuances on how we think the syndication can build over time.

Yes, I think as you think about that piece of them any earlier.

Biliary atresia is.

More common than allergy landscape it by by a fair bit when you think about it from a consumer perspective, probably threefold more.

Comment on newborn incidence of nausea, but because of the dynamics that Christmas describing there's much less of a prevalent pool, there because it's generally pretty rapidly progressive and heads towards liver transplant.

So we would envision in the early years after approval.

The eligible patient population would be kind of on the order of kids who were born.

Within the last 12 to maybe 36 months, but as you if the drug if the drug does what we hope it doesn't get patients on therapy, and again, hopefully keep them from liver transplant that would build over time and I think it could be could be bigger than the other two indications.

That's very helpful.

And when we talk about what the drug hopes when can do obviously is a little less certainty around the regulatory dynamic here.

It doesn't particularly at <unk>.

Give us a sense of how you think about.

Target effects, our target product profile.

And is there more certainty in your view on the need to show for clinical uptick or is that also a little bit up in the air as a 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 dataset is unblinded.

The regulators are data driven.

They do have patient interest in mind.

We show a really convincing dataset 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.

That will be the basis for really.

Good cases and strong conversation on it why.

The embark study.

Good potential potentially supports.

Approval in biliary atresia, we do need to generate that data and it's all kind of baked into the study design.

I think the one thing.

0.2. In addition to the bilirubin data that Pam talked about from the <unk> study I'm just looking at mean change in bilirubin.

There are also categories that are really well established on.

Risk profile for transplant.

Level of bilirubin at three months, so we have a close eye on that being able to down catheter.

Categorized patients onto a bilirubin score.

Above six two to six and below two.

For bilirubin, each step is a meaningful difference in risk of outcomes. So we'll look at those and.

Kind of respond or a shift table format.

Alright, that's very helpful. Thanks, guys.

Thanks for the question.

Thank you.

With our next question comes from Steve <unk> from Raymond James Steve. Your line is now open.

Two questions for me this is Ryan Deschner on first these veto.

The first one.

More than a year into the launch.

Have you seen an appreciable step up in sales due to the increases in average patient weight and how often are treating physician, suggesting.

Dose for growth in other regions.

Thanks for the question.

What we see there is I think about once a year.

Patients are weighed and considered for dose increases we do see dose increases.

And the real world setting.

Consistent with the prescribing information.

Preliminarily.

Really the majority of those.

The growth, we're seeing is just de novo demand and new patient starts.

Excellent and then.

Also.

And what areas do you anticipate potentially being able to differentiate from our.

Competitor go to Victor that in biliary atresia.

Yes.

In terms of thanks for the question there in terms of biliary atresia.

Time to having a randomized data set.

It was a big part of our thinking and our strategy here embark study are on track to have data second half of this year.

We will give us.

A really sizable lead in terms of.

Having data on live barley.

Really robust data set on with Marley in this setting.

We also have a feature of this study is not in the build base study.

We're at six months patients roll on to open up their open label therapy.

So the effect of starting treatment later is really important to look at it from.

The prevalent patients that are out there.

So that's a really key part that we're looking at here.

Then lastly, similar to what we've seen in the other settings.

Our higher dose with Marley.

We expect to have a bigger clinical impact.

I feel like we have.

Really advanced our understanding of how to dose either inhibitors and.

Really, particularly that's going to show up in our topline data.

Okay.

Thank you very much.

Thanks for the questions.

Thank you.

We have our next question comes from demand China Chatterji from city given Jonathan Your line is now open.

Hi, thank.

Thanks for taking our call I'm on for David Leibowitz from Citi.

We were wondering if you could comment on the ex U S inventory build and what should we expect in terms of the fee and started to the 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 theres really very little if any.

Effectively zero inventory true demand sales there as we as we get started.

And those countries, we do have.

Some other the balance of the sales and international are named patient programs.

And distributor markets of markets that were not directly selling them, but our partners are.

Central Eastern Europe Middle East.

And generally what happens in those dynamics as theirs.

No country specific mechanism in 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 even some cases, we've seen 12 months of supply ordered for one patient so.

That's that's kind of where.

Youre 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 dynamics, we see and in terms of.

Visibility in the guidance, we have for 50% growth is based on the U S sales and international setting we're really excited about the feedback we're getting and we're.

We're excited that Germany has gone really well and I think that's sort of a patient physician perspective looks a lot like the U S. But.

It's just too early to provide firm guidance on international given that we've just kind of get started there.

That's very helpful. Thank you.

Thanks for the question.

Thank you.

Sure.

Our next question comes from Ed Arce from H C Wainwright.

Your line is now open.

Hi, everyone. This is Thomas Yip, asking a couple of questions.

First congratulations on a very impressive quarter.

So just trying to tease out this off of the 600 patients.

Oh.

<unk> syndrome breast and treated with Marty globally.

Can you tell us roughly what percentage stay on chronic treatment.

If you can provide some more.

Major factors for patients to stay on with Marty or.

Right.

Pay off a mortgage.

As long as well would be appreciated.

Alright, thanks for the question.

The 600 number really we see as a really strong statement on familiarity with and interest in prescribing with Marley that number comes from all sources over the history of the program for patients with <unk> syndrome, who have been.

Prescribed or been part of a 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.

By country or by source.

But what I can say is that.

Across all of the different ways that patients have found their way to lift Marley clinical study.

Ended 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.

Staying with.

With the program.

Because of the profound impact that it can have.

Thanks, Thanks for clarification.

Sticking with Houston from.

With the U S label expansion.

Down two or three months of age and above.

Can you just tell us.

Your expectations are for top line and then also from a strategic standpoint as well.

Yeah on the label expansion for <unk> down to three months of age really important stuff, because that's where most.

Ah patients are diagnosed so allows with marley as a treatment option early on.

Overall topline impacts now 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 and we'll look at how we've pulled that into our guidance as well.

Got it.

Switching gear to <unk>.

Be safe.

With the application submitted to the EMA in Europe .

Once you would expect the next milestone.

So you shouldn't be opinion, perhaps.

Yeah.

Yes, so the producer date, we shared in December excited about that M D.

The potential timing for an opinion would be from <unk>. It would be late Q3 or in Q4.

Got it.

One final question. This one is financial.

With the convertible offering closed in April .

Tell us what's your estimated cash one way out too.

So similar to as described in the prepared remarks.

Really are fully funded with our current business 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.

The.

The long term here continue to grow the products.

Got it understood. Thank you so much. Thank you guys for taking my questions looking forward to.

Richard Richard Davis.

Yeah, Thanks for the questions.

Thank you.

Our next question comes from Brian <unk> from Baird. Brian Your line is now open.

Hi, This is Luke on for Brian .

Just a couple on embarks do you have an update on the scope of detail you might expect to include.

With the topline readout beyond just bilirubin in particular or maybe any outcome data.

Are you able to generally characterize the geographic dispersion of the enrolled patients in terms of.

Us versus other territories.

So thanks for the question and overall on a top line and your other than the primary.

Can't really speak to specifically what also be in there other than getting material updates.

<unk> disclosed.

Study is not powered for outcomes at that time points.

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 <unk> 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 plan, yes, we don't see a need for incremental opex for P. J. It's straightforward in fact, the pubic patients or take probably taken care of.

By a subset of the prescribers.

Prescribed with Marley today for <unk> syndrome.

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

Thanks for the questions.

Thank you.

As a reminder, ladies and gentlemen, if you would like to ask any further question. Please press star followed by one path on can you Pat now.

We have no further questions from the line.

Great. Thank you operator and thank.

Thank you to everyone for joining today's call I Hope you have a great day goodbye.

Thank you.

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

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Yes.

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Okay.

Yes.