• First and only data evaluating IBAT inhibition in treating primary sclerosing cholangitis (PSC)
• Data provided proof-of-concept for Phase 2b VISTAS study evaluating volixibat, an IBAT inhibitor, in patients with PSC

Mirum Pharmaceuticals, Inc. (Nasdaq: MIRM) today announced that Hepatology Communications published data from the CAMEO study evaluating the safety, tolerability, and efficacy of LIVMARLI® (maralixibat) oral solution in patients with primary sclerosing cholangitis (PSC).

The CAMEO study was the first proof-of-concept study evaluating an ileal bile acid transporter (IBAT) inhibitor in patients with pruritus associated with PSC, a cholestatic liver disease. The open-label study (n=27) evaluated the safety and tolerability of LIVMARLI for 14 weeks in adults with PSC measuring pruritus, serum bile acid levels, and liver function.

In this open-label Phase 2 pilot study, pruritus scores and serum bile acid concentration decreased over the 14 weeks of treatment with LIVMARLI. Participants whose sBA was elevated above normal at baseline achieved a 40% reduction (n=18). Similarly, participants with an average pruritus score of ≥3 out of 10 at baseline achieved a 70% improvement in pruritus (n=8). (The most common treatment emergent adverse events (TEAEs) were gastrointestinal related (diarrhea, nausea, and abdominal pain). The TEAEs were generally tolerable and consistent with the expected mechanism of action of IBAT inhibitors.

The full publication including additional data from the analysis can be accessed in Hepatology Communications.

“PSC is a rare, chronic, progressive cholestatic liver disease. Patients with PSC frequently suffer from severe pruritus that negatively impacts their quality of life,” said Christopher Bowlus, MD, chief of gastroenterology and hepatology at University of California, Davis, and lead author on the publication. “Treatment options for pruritus in patients with PSC are limited and unproven. The early data observed in the CAMEO study provides evidence that IBAT inhibitors may provide benefit to patients with PSC suffering from pruritus.”

“These are the first published data on the potential for IBAT inhibition for the treatment of patients with PSC,” said Pam Vig, PhD, head of research and development at Mirum. “The CAMEO study with LIVMARLI lays the foundation for the Phase 2b VISTAS study with volixibat, a minimally absorbed IBAT inhibitor, which is currently recruiting patients. We are grateful to the clinicians and patients who participated in the CAMEO study and thank them for their contribution.”

About Primary Sclerosing Cholangitis

Primary sclerosing cholangitis (PSC) is a rare, serious, idiopathic chronic cholestatic liver disease characterized by cholestasis, progressive inflammation, and destruction of bile ducts, which may lead to fibrosis, cirrhosis, portal hypertension, cancer, and ultimately liver failure. It is estimated that approximately 29,000 people in the United States and approximately 50,000 people in Europe suffer from PSC with no approved therapies. The underlying etiology of PSC is not completely understood, but it is thought to arise from a combination of genetic and environmental factors. The median age at diagnosis is approximately 35 years, and approximately 70% of PSC patients have inflammatory bowel disease, principally ulcerative colitis. Signs and symptoms of PSC may include, but are not limited to, pruritus, extreme fatigue, jaundice, and abdominal discomfort. The eventual buildup of bile acids from continued bile duct injury and obstruction damages liver cells and is thought to contribute to the progression of liver failure. Complications involving the biliary tree are common and include cholangitis, as well as ductal strictures and gallstones, the latter of which frequently require endoscopic or surgical interventions. PSC also increases the risk of development of malignancies, with cholangiocarcinoma being the most common. PSC is the fifth leading indication for liver transplantation; however, the post-transplant recurrence rate of PSC is up to 25%.

About Volixibat

Volixibat is an oral, minimally absorbed investigational 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. Phase 1 and Phase 2 studies of volixibat demonstrated on-target fecal bile acid excretion, a pharmacodynamic marker of IBAT inhibition, in addition to decreases in LDL cholesterol and increases in 7αC4 which are markers of bile acid synthesis. Volixibat has been evaluated in more than 400 individuals across multiple clinical trials. The most common adverse events reported were mild to moderate gastrointestinal events observed in the volixibat groups.

Volixibat is currently being evaluated in Phase 2b studies for primary sclerosing cholangitis (VISTAS clinical trial) and primary biliary cholangitis (VANTAGE clinical trial).

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) 3 months of age and older. LIVMARLI is also approved by the European Commission for the treatment of cholestatic pruritus in patients with ALGS two months and older. It is the only approved medication to treat cholestatic pruritus associated with Alagille syndrome. For more information for U.S. residents, please visit LIVMARLI.com.

Mirum has also submitted LIVMARLI for approval in the U.S. (in cholestatic pruritus in PFIC patients three months of age and older) and in Europe (in PFIC for patients two months of age and older).

LIVMARLI is currently being evaluated in late-stage clinical studies in other rare cholestatic liver diseases including biliary atresia. LIVMARLI has received Breakthrough Therapy designation for ALGS and PFIC type 2 and orphan designation for ALGS, PFIC and biliary atresia. To learn more about ongoing clinical trials with LIVMARLI, please visit Mirum’s clinical trials section on the company’s website.

IMPORTANT SAFETY INFORMATION

LIVMARLI can cause side effects, including:

Changes in liver tests. Changes in certain liver tests are common in patients with Alagille syndrome and can worsen during treatment with LIVMARLI. These changes may be a sign of liver injury and can be serious. Your healthcare provider should do blood tests 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) or loss of appetite.

Stomach and intestinal (gastrointestinal) problems. LIVMARLI can cause stomach and intestinal problems, including diarrhea, stomach pain, and vomiting during treatment. 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. FSV deficiency is common in patients with Alagille syndrome but may worsen during treatment. Your healthcare provider should do blood tests before starting and during treatment.

Other common side effects reported during treatment were gastrointestinal bleeding and bone fractures.

US Prescribing Information

EU SmPC

About Mirum Pharmaceuticals, Inc.

Mirum Pharmaceuticals, Inc. is a biopharmaceutical company dedicated to transforming the treatment of rare liver diseases. Mirum’s approved medication is LIVMARLI^® (maralixibat) oral solution which is approved in the U.S. for the treatment of cholestatic pruritus in patients with Alagille syndrome three months of age and older, and in Europe for the same indication in patients two months of age and older.

Mirum has also submitted LIVMARLI for approval in the U.S. (in cholestatic pruritus in PFIC patients three months of age and older) and in Europe (in PFIC for patients two months of age and older).

Mirum’s late-stage pipeline includes two investigational treatments for debilitating liver diseases affecting children and adults. LIVMARLI, an oral ileal bile acid transporter (IBAT) inhibitor, is currently being evaluated in clinical trials for pediatric liver diseases and includes the EMBARK Phase 2b clinical trial for patients with biliary atresia. In addition, Mirum has an expanded access program open across multiple countries for eligible patients with ALGS and PFIC.

Mirum’s second investigational treatment, volixibat, an oral IBAT inhibitor, is being evaluated in two potentially registrational studies including the VISTAS Phase 2b clinical trial for adults with primary sclerosing cholangitis and the VANTAGE Phase 2b clinical trial for adults with primary biliary cholangitis.

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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 the potential efficacy or clinical benefit of Livmarli or other IBAT Inhibitors on primary sclerosing cholangitis, the potential for volixibat clinical trials to meet or exceed any clinical endpoints, and any expected financial result or clinical benefit from Mirum’s development of IBAT inhibitors. 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, the impact of the COVID-19 pandemic, 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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