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

Good morning, and welcome to the Mirum Pharmaceuticals Business Update Call. My name is Hillary, and I will be your operator today. [Operator Instructions] I would now like to hand the conference over to Andrew McKibben, SVP of Strategic Finance and Investor Relations. Andrew, please go ahead.

Thank you, Hillary, and good morning, everyone. I'd like to welcome you to Mirum's conference call to discuss top line results from the Phase III portion of the AZURE-1 study of brilovateig in chronic hepatitis delta along with 48-week data from the Phase IIb portion of the study. For our prepared remarks, I'm joined today by our Chief Executive Officer, Chris Peetz, our Executive Vice President of Clinical Development, Nancy Shulman; and Peter Radovich, our President and Chief Operating Officer. Also joining us for the Q&A portion of the call are Rob Myers, our Chief Medical Officer; and Eric Burhop, our Chief Financial Officer. Earlier today, Mirum issued a press release announcing these results. A copy of that release and our SEC filing, along with the presentation summarizing the data are available on the Investors section of our website. Before we start, I'd like to remind you that during the course of this conference call, we will be making certain forward-looking statements based on management's current expectations, including statements regarding Mirum's programs and market opportunities for its approved medicines and product candidates and financial guidance. These statements represent our judgment and knowledge of events as of today and inherently involve risks and uncertainties that may cause actual results to differ materially from the results discussed. We are under no duty to update these statements. Please refer to the risk factors in our latest Form 10-Q and subsequent SEC filings for more information about these risks and uncertainties. With that, I'd like to turn the call over to Chris. Chris?

Thanks, Andrew, and thank you for joining our call this morning. Today marks another defining moment for Mirum and more importantly, for patients with hepatitis delta. We are excited to announce that the Phase III portion of the AZURE-1 study demonstrated rapid, statistically significant and clinically meaningful improvement on the primary endpoint with Brelovitug. To put these results in context, hepatitis delta is the most reform of viral hepatitis with the potential for rapid progression to cirrhosis, liver disorder for treatment at 24 weeks led to urologic response and ALT normalization in the majority of patients. These results represent the first pivotal Phase III readout of the Azure program, and they positioned brulovitug as a well-tolerated single-agent human monoclonal antibody with potential to treat a wide range of hepatitis delta patients. We continue to expect top line results of the Phase III AZURE study in the fourth quarter, keeping us on track for a planned BLA submission in the first half of next year. Now this news comes just days after another important milestone for the company announced last Friday. The FDA approved a [indiscernible] tablets reduced the volume of total new heterotopic ossification in adult and pediatric patients aged 12 years and older with fibrodysplasia, osticans Progressive or FOP. [indiscernible] is now the fourth commercial medicine at Mirum. We brought AtebrIos into the rare genetic disease portfolio only in the second quarter this year. So this is fast progress and credit to the Insight team who did a fantastic job leading this through regulatory review. For today's updates, Nancy Shulman, EVP of Clinical Development, who designed and leads the Azure program will walk through the results. Peter will also provide comments on launch preparations from and the newly approved us, and I'm happy to welcome Dr. Rob Myers, who joined us last week as our Chief Medical Officer, for the Q&A portion of the call. Rob is a widely recognized hepatologist and physician scientists with more than 2 decades of experience developing novel medicines. He joined us from [indiscernible], where he was Chief Medical Officer and Head of Development. And before that, he spent a number of years at Gilead. He joins us at a busy time for our pipeline as we look to transition 3 programs from clinic to commercial in the near term. And finally, before diving in, I'd like to say thank you to the patients, investigators and study team around the world who made a 0.1 possible. Now over to Nancy.

Thank you, Chris. I'm very pleased to review the top line results from the Phase III portion of the 01 study, and I'll also walk through the top line 48-week results for the Phase IIb portion of the study. Like Chris, I'd like to extend my gratitude to all the participants, investigators and the dedicated Mirum study team who made this possible. As a reminder, hepatitis delta occurs only in the setting of hepatitis B virus co-infection because the hepatitis delta virus relies on hepatitis B surface antigen for viral assembly, entry and dissemination. Hepatitis Delta is the most severe form of viral hepatitis and relative to chronic hepatitis B alone, delta is associated with the more severe liver disease and more rapid progression to cirrhosis, liver cancer and liver failure. . For Lovatug is a fully human monoclonal antibody that binds hepatitis B surface antigen. It works by clearing hepatitis delta from the circulation and by preventing entry into liver cells. Before getting into the data, it's worth discussing the combined approvable endpoint recommended by the FDA, which includes both virologic response and ALT normalization. HDV RNA measures the degree of viral suppression, while ALT reflects ongoing liver inflammation, both are important. Although viral expression generally leads to reductions in inflammation, a virologic response alone does not necessarily mean that liver inflammation has resolved. Liver inflammation is the key driver to -- for progression to fibrosis, cirrhosis and liver cancer. In this setting, ALT is the most practical and widely accepted biomarker for assessing inflammatory activity within the liver. Now turning to the Phase III results. The Phase III portion of AZURE-1 enrolled 153 patients globally, randomized approximately 2 2:1 to receive Brelovitug 300-milligram once weekly self administered by subcutaneous injection at home. Brelovitug 900 milligrams once every 4 weeks administered in clinic by subcutaneous injection with an additional loading dose at week 2. or third arm was delayed treatment starting with a crossover at week 24 to the 300-milligram once weekly regimen. We enrolled a broad patient population with meaningful disease burden. There was no upper limit on ALT for study participation and at baseline, we had 18% who had ALT above 5x the upper limit of normal. 41% had cirrhosis and 20% had clinically significant portal hypertension. I'm very pleased to say that at week 24, Brelovitug met the primary endpoint. I'm going to focus on the results for the 300-milligram once weekly dose, but the numbers are highly significant for both arms. For the 300-milligram dose arm, 56% achieves the combined endpoint compared to 0 in the delayed treatment arm with a highly significant p-value. Virologic response was achieved in 86% compared to 0 in the delayed treatment arm. HDV RNA below the limit of quantification with our assay to 10 IUs per ml was achieved in 25% compared with 0 in the delayed treatment. And this includes 17% who were at Target mutein. ALT normalization was achieved in 63% of patients compared to 0 in the delayed treatment arm. Brelovitug was well tolerated with a safety profile consistent with the previously reported AZURE-1 Phase IIb results, there were no treatment-related serious or Grade 3 adverse events or discontinuations and low rates of flu licenses. Now turning over to the 48-week data from the Phase IIb portion of AZURE-1. As a reminder, the Phase IIb portion included the first 53 patients enrolled in the study. At EASL earlier this year, we presented the full week 24 results. Here, we provide an update out to week 48, which showed continued deepening of viral suppression and increasing rates of ALT normalization with ongoing treatment. A highlight is the proportion achieving HDV RNA below the lower limit of quantification, which again is 10 IUs is per mL. Remember, the average HDV RNA levels for these patients at baseline was around $0.5 million. So dropping these to less than 10 is a significant reduction. Finally, we also expect to present 2-year data from our original Phase II study showing continued improvements in ALT and HDV RNA in the cirrhotic patients at an upcoming medical conference. Overall, these results reinforce the compelling profile for Brelovitug as a well-tolerated, convenient single-agent potential therapy for patients with hepatitis delta including those with advanced disease. With that, I'll turn it over to Peter.

Thanks, Nancy. Hepatitis Delta is a natural extension of our rare disease commercialization strategy. bringing life-changing medicines to underserved and underdiagnosed patients is where Miramax cells and belobatab fits that profile. Let me start with the opportunity. We believe there are approximately 15,000 patients with hepatitis delta in the United States who are diagnosed, insured and under care today. Over the course of 2026 Mirum has supported several hepatitis delta disease awareness initiatives and engaged with hepatitis B providers from a broad array of clinical settings to better understand the delta diagnosis paradigm and disease burden. Through our disease state conversations, it's clear to us that delta testing in the United States has been extremely low and then most of the burden exists in nonacademic community settings. Thus, we believe the true U.S. prevalence is considerably larger with the significant majority of patients undiagnosed today. . And given our confidence in Brelovitug's robust single-agent profile shared today by Nancy, we are updating our peak sales guidance to at least $1 billion. We believe one of the strengths of the Mirum model is the efficiency of our commercial organization. Today, our rare liver team supports Live Marley in pediatric and adult liver care settings. Over time, we expect to leverage this capability, utilizing the same team to support 3 commercial medicines, Live Marley, Volixibat and Brelovitug. Now turning briefly to [indiscernible] is a once-daily oral ALK2 inhibitor designed to target the disease driving pathway at the center of FOP biology. As Chris mentioned, we received FDA approval late last week, and our rare genetic medicines team is ready to go. We're excited about the label and believe it can facilitate broad access for FOP patients age 12 and over. With product launch in October, we expect revenue to begin in the first quarter of 2027. This launch leverages the Mirum Rare Genetics team already in place supporting [indiscernible] as the physicians who care for FOP patients are concentrated in many of the same specialized centers. And most importantly, we are both grateful and enthusiastic about the opportunity to bring another high-impact medicine to a rare disease patient population in desperate need of treatment options. And with that, I'll turn it back to Chris. Chris.

Yes. Chris seems to be muted. So I will read the last section before we open it up for Q&A. Thanks, Peter. Today's updates are exciting for both patients and Mirum. I'm proud that we've built an industry-leading team in rare disease to deliver moments like this with a new approved therapy for FOP patients and strong Phase III results in hepatitis delta and our strategy is positioned for continued growth. Today, fewer than 5% of rare diseases have an approved treatment and even where treatments exist significant unmet need remains. The upcoming launch of AtebrIos is an immediate opportunity to put our business model to work to help patients with FOP. For hepatitis delta, these are the first pivotal Phase III results from the Azure program. The week 24 results reinforce our excitement about what Brelovitug can mean for patients with hepatitis delta as a highly active, well-tolerated potential medicine for a deadly disease. Looking ahead, we expect top line data from AZURE-4 a second Phase III study with a similar design to AZURE-1 in the fourth quarter, which keeps us on track for a BLA submission in the first half of next year. Once again, thank you to the patience and investigators who participated in AZURE-1 and a huge thank you to the Mirum team who are working relentlessly to bring these important medicines forward. And with that, operator, please open the line for questions.

[Operator Instructions] Your first question comes from the line from Yigal Nochomovitz from Citigroup.

Congratulations on the -- both the approval as well as the data this morning. So I was just curious if you could speak a little bit with regard to the read-through to Azure 4. Obviously, the endpoint there is a little bit more stringent. So could you just comment on how you see that playing out given the results in Azure with obviously, very strong 86% biologic response, although a lower T&D rate of 17% at week 24. And then just related to that, in terms of the filing, what's the latest commentary from the FDA with respect to meeting both Azure-1 and Azure-4? Is there a pathway where if it's just as one for whatever reason, you would still be in good position to file.

Thanks for the question a couple of quick comments, and I'll pass it over to Nancy to speak about the difference in study design into AZURE-4. But the one thing to say is overall, we're alignment with FDA on the AZURE-1 and 4 being part of the filing. And as your 4 is just around the corner. So we expect to be bringing those results in the fourth quarter and on track for that first half BLA submission. But Nancy to get into some of the details on AZURE-4.

Yes. Thanks, Chris. So actually, the endpoints are quite similar. AZURE-4 is a 24-week endpoint for the balobatag. It is the comparison we are comparing 24 weeks to 12 weeks. -- as we see here -- the control arm doesn't really improve from 12 to 24.

Your next question comes from the line of Ryan Deschner from Raymond James.

Congratulations on the strong readout. Are you seeing continued improvement in ALT and ALT normalization at time points later than the 48 weeks in the Phase IIb portion of AZURE-1 and I have a follow-up.

Yes. Just to put a couple of things in context, and I'll let Nancy speak again to the data. Here, we're providing the Phase III update, that's a 24-week end point. the long-term follow-up from the Phase IIb will be 48. And we have additional analyses out to 2 years plan from the Phase IIa. So painting a nice picture overall, but I'll let Nancy speak to some of the trends that we're seeing.

So the short answer to your question is yes. We do see continued reductions in ALT even when they're below -- below the upper a little bit normal. .

Got it. And then can you attribute the lack of mean reversion on the primary end point or ALT normalization, particularly 2 in this readout compared to the Phase IIb portion of AZURE-1.

Yes, that's a great question. So remember, there's a 20 -- approximately 20 patients in each of the Brelovitug arms in the IIB. And so these are -- remember, these are point estimates and they have confidence in enroll around them. And if you look at the confidence levels, they still overlap. So we think they're not really different. .

Your next question comes from the line of Josh Schimmer from Cantor Fitzgerald.

Congratulations on the results. I guess considering the community setting for HCV patients, how might that impact your overall commercial strategy, if at all? And maybe you can elaborate on some of the efforts you're planning to undertake to continue to identify new HDV patients.

Yes. Thanks for the question. Pretty active on this front. I'll let Peter kind of share what we've been up to.

Yes. Thanks for the question, Josh. Yes, indeed, many of the HBV patients and therefore, delta patients are not in Gastrology hepatology, many from our infectious disease or even primary care settings and kind of select areas often where in urban areas where and going procures. But we do actually have a team out in the field now, doing disease state awareness, scientific exchange. or so folks out there now interacting with those people, raising awareness of the disease and testing paradigms and hopefully, eventually new therapies. .

It seems that the analyst has dropped. So I will allow them to rejoin the queue in case there's a follow-up. We will move on to the next question, which is from James Condulis from Stifel.

Congrats on all the updates. Just a quick 1 as it relates to sort of efficacy and what you think matters most to docs in the real world. Just curious, is it the composite virologic response certain measures of urologic response. Just like curious what you hear from docs and then kind of on that point as it relates to the commercial opportunity and sort of the new estimate. Can you just kind of expand on what's driving that? .

Thanks for the question. I'll let answer Nancy and Rob to comment on the first portion and pass it over to Peter for the commercial.

Yes. So -- to answer your question, so I'm an [indiscernible] disease person Rob is a hepatologist so he can opine as well. Both ALT and HDV RNA responses are important. So -- we think that one of the things that I'll say is that there has been no actual data that shows the predictability of the degree of suppression and how that relates to clinical outcomes. So if you get to, say, 100 units IUs per ML or you get to [indiscernible] you get to T&D, there has been no data in hepatitis delta suggesting that 1 predicts better outcomes than the other. So we know that in hepatitis B, actually ALT normalization predicts endpoints such as liver cancer and progression to decompensation. more so than the degree of suppression, particularly T&D versus other. So I think both of our port, especially in the therapies that are going to require longer term.

Yes I agree 100% with Nancy, I think being Normalization in tandem are important -- we know that it's liver inflammation and liver cell injury, which drives fibrosis on the complications of hepatitis delta. So the biochemical responses we're seeing are very encouraging. I'll also say we're seeing reductions in liver stiffness, which seem to increase over time, which portend well for prognosis of these patients looking forward to presenting these data at an upcoming conference.

And then James, on the commercial aspect of the peak revenue update of your question. Yes, the primary driver of that is robust single-agent activity data that Nancy reviewed today. I feel really good about the profile and continued confidence is the primary driver of that. Also I would note that recent entrant in the U.S. out pricing at about PHP 285,000 per patient per year came in a bit above the price levels we had kind of assumed in the prior forecast we've communicated at the time of the Blue Jay transaction. .

Your next question comes from the line of Brian Skorney from Baird.

Congrats on 2 positive wins. Over the weekend. Just 2 quick ones for me. Just in terms of the 300-milligram dose itself, can you just relate what the minimal volume that dose fits into and thoughts on single auto-injector? And just on sort of competitive labeling ultimately, the liver tide has a box warning about severe hepatitis flares upon cessation of therapy. Maybe in the current dynamic, it's kind of a good thing to have on label as it emphasizes compliance. But -- just thinking of a competitive landscape, is the assumption that all of these would have on label learnings about hepatitis flares on stopping therapy? Is there any data to indicate that you would potentially get around that somehow?

Brian, thanks for the question. I think from the starting point, it's kind of probably too early to speak to be able on this and making some of those comparisons. But I'll pass it over to Nancy to talk a little bit about administration of the 300 and the overall profile.

Yes. Thanks, Chris. So the volume of the 300 milligrams is 2 mls, and it doesn't require reconstitution and then the answer is we are working towards an auto-injector or prefilled syringe and I can hand it over to Peter.

Sure. Yes. Yes, Brian. The presentation at launch is Nancy mentioned, liquid and [indiscernible], no compensation required, but we are working on auto-injector that helped to introduce in the life cycle. And just kind of putting this all together for the profile for Brelovitug that simple once-weekly administration with a single injection really a convenient option for patients especially when you put it in the context of not needing to have a cut off for baseline ALT or liver stiffness or some of the things that are top of mind for care of these patients.

Your follow-up question is from Kalpit Patel from Wolfe Research.

So in your Phase II and Phase III studies, you allowed patients with ALT greater than 5x upper limit of normal, whereas it looks like Vir is excluding them. So did those patients respond differently on any of the efficacy end points, either things like ALT normalization or T&D or any virologic measures? And if you exclude that subgroup, does the efficacy get better on any of those.

That's a great question. So the actual statistical comparisons between those who have hired the ALT at baseline versus those who don't the subgroups are not large enough to show statistical significance there's a trend, though, that if they're higher at baseline, it takes a little longer to get there.