Volixibat Data from Mirum's VANTAGE PBC Study Showcased at EASL

- 28-week data from the Phase 2b VANTAGE PBC study highlights statistically significant improvements in pruritus and numeric improvements in fatigue, the two most burdensome symptoms of PBC

- Seventy percent of patients treated with volixibat experienced a ≥50% reduction in serum bile acids

- Volixibat treated patients experienced reductions in IL-31

Mirum Pharmaceuticals, Inc. (NASDAQ:MIRM) today presented new data from its Phase 2b VANTAGE study at the European Association for the Study of the Liver (EASL) meeting in Amsterdam, the Netherlands. The VANTAGE study is evaluating volixibat in patients with cholestatic pruritus caused by primary biliary cholangitis (PBC).

"The extended VANTAGE analysis provides encouraging insights into the potential impact that volixibat may have in treating the most severe and bothersome symptoms for patients living with PBC, including pruritus and fatigue," said Joanne Quan, MD, chief medical officer at Mirum. "We are also encouraged by the reductions seen in IL-31 in conjunction with sBA reductions, showing the potential for volixibat treatment to help alter the inflammatory condition present in PBC."

Data from the interim analysis of VANTAGE were highlighted with new analyses through week 28. Patients were randomized to receive volixibat 20mg BID, 80mg BID, or placebo BID. The primary endpoint of the study was mean change in weekly averaged daily itch score, as measured by the adult ItchRO scale, from baseline to Week 17-Week 28. Volixibat treatment led to rapid (as early as week 1) and sustained reductions in ItchRO with the volixibat combined dose group achieving a statistically significant 3.78-point reduction from Baseline (p<0.0001) and a placebo-adjusted response of 2.51 (p=0.0004). Each volixibat dose achieved statistically significant and similar responses (20mg BID: -2.4 [P=0.0039]; 80mg BID: -2.6 [P=0.0010]). The analysis also provided data across secondary endpoints showing reductions in serum bile acids (sBA) and quality of life (QoL) measures. Overall, 70% of patients who received volixibat achieved ≥50% reduction in sBA. Further, the data showed improvement from baseline in health-related quality of life, including fatigue and sleep, for patients treated with volixibat. Reductions from baseline were observed in inflammatory biomarker IL-31 in patients treated with volixibat.

No new safety signals were observed, and adverse events were similar between the 20 mg and 80 mg treatment groups. The most common adverse event was diarrhea (77%) with all cases mild to moderate; one case resulted in discontinuation. Given the similar results with both efficacy and safety between the 20mg BID and 80mg doses BID, the 20mg BID dose was selected for the confirmatory portion of the VANTAGE study.

To view the presentation, please visit the Publications & Presentations on Mirum's website.

About the VANTAGE Study

VANTAGE is a randomized, double-blind, placebo-controlled study evaluating the efficacy and safety of volixibat in patients with pruritus caused by primary biliary cholangitis (PBC). Patients were randomized to receive volixibat 20mg BID (n=10), 80mg BID (n=10), or placebo BID (n=11). The primary endpoint of the study was mean change in weekly averaged daily itch score, as measured by the adult ItchRO scale (an 11 point scale where 0 = no itch and 10 = worst itch imaginable), from baseline to Week 17-Week 28. VANTAGE is designed as a two-part study: the first part is intended to confirm dose (completed) and the second intended to be the confirmatory portion (currently enrolling patients). In the first part of the study, patients were randomized to receive either volixibat 20mg BID, 80mg BID, or placebo BID; the second part of the study randomized patients to receive either volixibat 20mg BID (the selected dose based on part one) or placebo BID.

About Primary Biliary Cholangitis

Primary Biliary Cholangitis (PBC) is a chronic, progressive, immune-mediated condition leading to the destruction of small intrahepatic bile ducts. The disease impacts an estimated 230,000 patients in the United States and the European Union, with women predominantly affected (a sex ratio of 9:1). Key clinical features and symptoms include cholestatic pruritus, fatigue, sicca syndrome, abdominal pain, cirrhosis, and hepatocellular carcinoma. Cholestatic pruritus (itch) and fatigue are two of the most debilitating symptoms and greatly affect overall health-related quality of life (HRQoL). Cholestatic pruritus can affect up to 80% of individuals and is thought to result in part from accumulation of toxic bile acids.

About Volixibat

Volixibat is an oral, minimally absorbed agent designed to selectively inhibit the ileal bile acid transporter (IBAT). Volixibat may offer a novel approach in the treatment of adult cholestatic diseases by blocking the recycling of bile acids, through inhibition of IBAT, thereby reducing bile acids systemically and in the liver. Volixibat is currently being evaluated in Phase 2b studies for primary sclerosing cholangitis (PSC) (VISTAS study), and primary biliary cholangitis (PBC) (VANTAGE study). In June, Mirum announced positive interim results from the Phase 2b VANTAGE study showing statistically significant improvement in pruritus as well as reductions in serum bile acids and improvements in fatigue for patients treated with volixibat. No new safety signals were observed, and the most common adverse event was diarrhea with all cases mild to moderate. Volixibat has been granted breakthrough therapy designation for the treatment of PBC.

About LIVMARLI® (maralixibat) oral solution and LIVMARLI® (maralixibat) tablets

LIVMARLI^® (maralixibat) is an orally administered, ileal bile acid transporter (IBAT) inhibitor approved by the U.S. Food and Drug Administration for two pediatric cholestatic liver diseases, in both liquid and tablet formulations. It is approved for the treatment of cholestatic pruritus in patients with Alagille syndrome (ALGS) in the U.S. three months of age and older and in Europe for patients two months of age and older. It is also approved in the U.S. for the treatment of cholestatic pruritus in patients with progressive familial intrahepatic cholestasis (PFIC) 12 months of age and older and in Europe for the treatment of PFIC in patients three months of age and older. For more information for U.S. residents, please visit LIVMARLI.com.

LIVMARLI is currently being evaluated in the Phase 3 EXPAND study in additional settings of cholestatic pruritus. To learn more about ongoing clinical trials with LIVMARLI, please visit Mirum's clinical trials section on the company's website.

U.S. IMPORTANT SAFETY INFORMATION

Limitation of Use: LIVMARLI is not for use in PFIC type 2 patients who have a severe defect in the bile salt export pump (BSEP) protein.

LIVMARLI can cause side effects, including:

Liver injury. Changes in certain liver tests are common in patients with Alagille syndrome and PFIC but can worsen during treatment. These changes may be a sign of liver injury. In PFIC, this can be serious or may lead to liver transplant or death. Your healthcare provider should do blood tests and physical exams before starting and during treatment to check your liver function. Tell your healthcare provider right away if you get any signs or symptoms of liver problems, including nausea or vomiting, skin or the white part of the eye turns yellow, dark or brown urine, pain on the right side of the stomach (abdomen), bloating in your stomach area, loss of appetite or bleeding or bruising more easily than normal.

Stomach and intestinal (gastrointestinal) problems. LIVMARLI can cause stomach and intestinal problems, including diarrhea and stomach pain. Your healthcare provider may advise you to monitor for new or worsening stomach problems including stomach pain, diarrhea, blood in your stool or vomiting. Tell your healthcare provider right away if you have any of these symptoms more often or more severely than normal for you.

A condition called Fat Soluble Vitamin (FSV) Deficiency caused by low levels of certain vitamins (vitamin A, D, E, and K) stored in body fat is common in patients with Alagille syndrome and PFIC but may worsen during treatment. Your healthcare provider should do blood tests before starting and during treatment and may monitor for bone fractures and bleeding which have been reported as common side effects.

LIVMARLI is available in oral solution or tablet formulations and is taken by mouth 30 minutes before a meal. For Alagille syndrome, LIVMARLI is taken one time each day in the morning. For PFIC, LIVMARLI is taken two times each day. If you take the oral solution, use the oral dosing dispenser to measure your dose.

US Prescribing Information

EU SmPC

Canadian Product Monograph

About Mirum Pharmaceuticals, Inc.

Mirum Pharmaceuticals, Inc. is a biopharmaceutical company dedicated to transforming the treatment of rare diseases affecting children and adults. Mirum has three approved medications: LIVMARLI® (maralixibat) oral solution/LIVMARLI® (maralixibat) tablets, CHOLBAM® (cholic acid) capsules, and CTEXLI™ (chenodiol) tablets.

LIVMARLI, an IBAT inhibitor, is approved for the treatment of two rare liver diseases affecting children and adults. It is approved for the treatment of cholestatic pruritus in patients with Alagille syndrome in the U.S. (three months and older), in Europe (two months and older), and in other regions globally. It is also approved in the U.S. in cholestatic pruritus in PFIC patients 12 months of age and older; in Europe, it is approved for patients with PFIC three months of age and older. Mirum has initiated the Phase 3 EXPAND study, a label expansion opportunity for LIVMARLI in additional settings of cholestatic pruritus. CHOLBAM is FDA-approved for the treatment of bile acid synthesis disorders due to single enzyme deficiencies and adjunctive treatment of peroxisomal disorders in patients who show signs or symptoms of liver disease.

CTEXLI is FDA-approved for the treatment of cerebrotendinous xanthomatosis (CTX) in adults. Mirum's late-stage pipeline includes two investigational treatments for several rare diseases.

Volixibat, an IBAT inhibitor, is being evaluated in two potentially registrational studies including the Phase 2 VISTAS study for primary sclerosing cholangitis (PSC) and Phase 2b VANTAGE study for primary biliary cholangitis. Volixibat has been granted Breakthrough Therapy Designation for the treatment of cholestatic pruritus in patients with PBC. Mirum is also planning for a Phase 2 study evaluating MRM-3379, a PDE4D inhibitor for the treatment of Fragile X syndrome, a rare genetic neurocognitive disorder.

To learn more about Mirum, visit mirumpharma.com and follow Mirum on Facebook, LinkedIn, Instagram and Twitter (X).

Forward-Looking Statements

Statements contained in this press release regarding matters that are not historical facts are "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995. Such forward-looking statements include statements regarding, among other things, data from Mirum's volixibat studies, including the VANTAGE study of volixibat in patients with pruritus due to PBC and such implications for patients in real world settings. Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. Words such as "will," "could," "can," "would," "potential," "hope," "opportunity," and similar expressions are intended to identify forward-looking statements. These forward-looking statements are based upon Mirum's current expectations and involve assumptions that may never materialize or may prove to be incorrect. Actual results could differ materially from those anticipated in such forward-looking statements as a result of various risks and uncertainties, which include, without limitation, risks and uncertainties associated with Mirum's business in general, the impact of macroeconomic and geopolitical developments, and the other risks described in Mirum's Annual Report on Form 10-K for the year ended December 31, 2024, filed with the U.S. Securities and Exchange Commission on February 26, 2025, and subsequent filings with the U.S. Securities and Exchange Commission, which are available at www.sec.gov. All forward-looking statements contained in this press release speak only as of the date on which they were made and are based on management's assumptions and estimates as of such date. Mirum undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made, except as required by law.

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