Mirum Pharmaceuticals, Inc. Common Stock Study result

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 brelovitug 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 Bjerkholt, 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 a 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 thanks 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 severe form of viral hepatitis, with the potential for rapid progression to cirrhosis, liver cancer, and liver-related death. In AZURE-1, brelovitug treatment at 24 weeks led to virologic response and ALT normalization in the majority of patients. These results represent the first pivotal Phase III readout of the AZURE program, and they position brelovitug as a well-tolerated, single-agent, fully 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-4 study in the fourth quarter, keeping us on track for a planned BLA submission in the first half of next year. This news comes just days after another important milestone for the company announced last Friday. The FDA approved Atebrioz tablets to reduce the volume of total new heterotopic ossification in adult and pediatric patients aged 12 years and older with fibrodysplasia ossificans progressiva, or FOP. Atebrioz is now the fourth commercial medicine at Mirum. We brought Atebrioz 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 for brelovitug and the newly approved Atebrioz. I am 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 scientist with more than two decades of experience developing novel medicines. He joins us from OrsoBio, 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 three programs from clinic to commercial in the near term. Finally, before diving in, I would like to say thank you to the patients, investigators, and study team around the world who made AZURE-1 possible. Now, over to Nancy. Nancy?

Thank you, Chris. I am very pleased to review the top-line results from the Phase III portion of the AZURE-1 study, and I will also walk through the top-line 48-week results for the Phase II-B portion of the study. Like Chris, I would 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's 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. Brelovitug 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 is 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 suppression 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 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-to-2-to-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 5 times the upper limit of normal. 41% had cirrhosis, and 20% had clinically significant portal hypertension. I am very pleased to say that at week 24, brelovitug met the primary endpoint. I am 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% achieved the combined endpoint compared to zero in the delayed treatment arm with a highly significant P value.

Virologic response was achieved in 86% compared to zero in the delayed treatment arm. HDV RNA below the limit of quantification with our assay, this is 10 IU/mL, was achieved in 25% compared with zero in the delayed treatment. This includes 17% who were at target not detected. ALT normalization was achieved in 63% of patients compared to zero 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-like symptoms. 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 IU/mL. Remember, the average HDV RNA levels for these patients at baseline was around a half a 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 will 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 Mirum excels, and brelovitug fits that profile. Let me start with the opportunity. We believe there are approximately 15,000 patients with hepatitis delta in the U.S. 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 is clear to us that delta testing in the U.S. has been extremely low and that most of the burden exists in non-academic community settings. Thus, we believe the true U.S. prevalence is considerably larger, with the significant majority of patients undiagnosed today.