- Data demonstrate significant benefit across broadest range of genetic PFIC types ever studied

- Significant improvements observed across multiple parameters including pruritus, serum bile acids, growth and bilirubin

Mirum Pharmaceuticals, Inc. (Nasdaq: MIRM) today announced that data from the Phase 3 MARCH-PFIC study evaluating LIVMARLI® (maralixibat) oral solution in patients with PFIC was published in The Lancet Gastroenterology and Hepatology.

The MARCH-PFIC study was the largest, randomized, double-blind, placebo-controlled study in patients with PFIC, confirming the efficacy and safety of LIVMARLI, an IBAT inhibitor, across a broad genetic range of PFIC types. The main efficacy analyses were performed in two groups which included the BSEP deficiency (BSEP or PFIC2) cohort and the All-PFIC cohort which included patients with BSEP (PFIC2), FIC1 (PFIC1), MDR3 (PFIC3), TJP2 (PFIC4), or MYO5B deficiencies.

The study met both the primary efficacy endpoint (mean change in pruritus severity score between baseline and the last 12 weeks of treatment [weeks 15-26]) and the key secondary endpoint (mean change in total serum bile acid concentration between baseline and the average of weeks 18, 22, and 26) with statistically significant and clinically meaningful improvements observed by Week 2 and sustained throughout the 26-week study in LIVMARLI-treated participants in both the BSEP and All-PFIC cohorts. Improvements in bilirubin concentrations, growth, and sleep disturbances with LIVMARLI versus placebo were also observed. There were no new safety signals for LIVMARLI throughout the treatment periods with the most common adverse event being diarrhea, which was mostly mild and transient.

The Phase 3 MARCH study presents the largest and most comprehensive dataset demonstrating the therapeutic benefit of an IBAT inhibitor across a broad range of PFIC types, including some which have not been previously studied. In addition to the clinical benefits observed, LIVMARLI significantly improved serum bile acids and bilirubin which are both known to be predictive of transplant-free survival. LIVMARLI represents a non-surgical, pharmacological option to improve outcomes for patients with PFIC.

“These data advance our understanding of LIVMARLI’s potential to provide meaningful improvements in pruritus and a number of parameters impacting patients with various PFIC types. The clinically meaningful reductions in serum bile acid and bilirubin levels also signify the potential for improvements in native liver survival in PFIC, a step forward in considering the long-term care and health of patients with PFIC,” said Dr. Alexander Miethke, Cincinnati Children’s Hospital and lead author on the publication. “LIVMARLI presents a new non-surgical treatment option in PFIC with strong efficacy data and safety demonstrated across a range of PFIC types, which is important for patients with PFIC types previously unstudied.”

“We are pleased to see these data published and recognized by The Lancet as they demonstrate meaningful improvements in many clinical signs and symptoms seen in PFIC patients,” said Pam Vig, PhD, chief scientific officer and head of research at Mirum. “Patients with PFIC suffer from cholestasis which can lead to debilitating cholestatic pruritus, as well as poor growth and progressive liver disease. These data demonstrate the significant impact LIVMARLI can have in this severe cholestatic setting.”

To read the full article, please visit the publication on The Lancet Gastroenterology and Hepatology’s website.

About LIVMARLI® (maralixibat) oral solution

LIVMARLI® (maralixibat) oral solution is an orally administered, once-daily, ileal bile acid transporter (IBAT) inhibitor approved by the U.S. Food and Drug Administration for the treatment of cholestatic pruritus in patients with Alagille syndrome (ALGS) three months of age and older and progressive familial intrahepatic cholestasis (PFIC) five years of age and older.

LIVMARLI is also the only approved IBAT inhibitor approved by the European Commission for the treatment of cholestatic pruritus in patients with ALGS two months and older, and by Health Canada for the treatment of cholestatic pruritus in ALGS. For more information for U.S. residents, please visit LIVMARLI.com.

Mirum has also submitted LIVMARLI for approval in Europe in PFIC for patients two months of age and older.

LIVMARLI has received Breakthrough Therapy designation for ALGS and PFIC type 2 and orphan designation for ALGS and PFIC. To learn more about ongoing clinical trials with LIVMARLI, please visit Mirum’s clinical trials section on the company’s website.

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.

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, CHOLBAM® (cholic acid) capsules, and CHENODAL® (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 five years of age and older. Mirum has submitted for approval in Europe for the treatment of PFIC in patients two months of age and older. 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 or liver disease. CHENODAL has received medical necessity recognition by the FDA to treat patients with cerebrotendinous xanthomatosis (CTX).

Mirum’s late-stage pipeline includes two investigational treatments for debilitating liver diseases. Volixibat, an IBAT inhibitor, is being evaluated in two potentially registrational studies including the Phase 2b VISTAS study for primary sclerosing cholangitis and Phase 2b VANTAGE study for primary biliary cholangitis. Lastly, CHENODAL, has been evaluated in a Phase 3 clinical study, RESTORE, to treat patients with CTX, with positive topline results reported in 2023.

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, the potential for LIVMARLI to provide meaningful resolution to pruritis in PFIC and the clinical significance of reduction of serum bile acids and total bilirubin on native liver survival. 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,” “goal,” “potential” 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 and the other risks described in Mirum’s filings with the Securities and Exchange Commission. 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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