- Late-breaking poster presentation features LIVMARLI® data showing long-term maintenance of response in patients with PFIC

- Four poster presentations highlight LIVMARLI PFIC data as well as a poster with proof-of-concept trial data from volixibat study in intrahepatic cholestasis of pregnancy

Mirum Pharmaceuticals, Inc. (NASDAQ: MIRM) today announced new data from its LIVMARLI and volixibat programs presented at The Liver Meeting®, the American Association for the Study of Liver Diseases (AASLD) annual meeting in Boston, Massachusetts.

Data were presented from the Phase 3 MARCH study and MARCH-ON extension evaluating the efficacy and safety of LIVMARLI in patients with progressive familial intrahepatic cholestasis (PFIC) as well as the Phase 2 OHANA study evaluating the efficacy and safety of volixibat in patients with intrahepatic cholestasis of pregnancy (ICP).

MARCH was the largest and most genetically diverse trial of PFIC to date, enrolling patients with deficiencies of BSEP, FIC1, MDR3, TJP2, AND MYO5B, as well as those clinically diagnosed with PFIC but without a known genetic variant.

“PFIC is a chronic, debilitating cholestatic liver disease characterized by elevated bile acids and pruritus so severe that patients can be listed for liver transplant even in the absence of disease progression. We are excited to share the long-term benefits observed across multiple measures including reductions in pruritus, serum bile acids, improved liver health and growth for patients with PFIC treated with maralixibat in multiple genetic types which have not previously been reported,” said Pam Vig, PhD, head of research and development at Mirum. “We are also pleased to share the findings from the OHANA study of volixibat in patients with ICP, showing a clear impact of volixibat on serum bile acids and pruritus in this cholestatic setting.”

A summary of these data presented is featured below. Full presentations can be found within the Publications and Presentations section of Mirum’s website.

Late-breaker Poster Presentation

Poster 5048-C: Long-term maintenance of response and improved liver health with maralixibat in patients with progressive familial intrahepatic cholestasis (PFIC): 2-year data from the MARCH-ON study

The MARCH-ON extension study evaluated the long-term efficacy and safety of maralixibat in patients with PFIC who received maralixibat in the original MARCH study for 26 weeks and continued for up to two years and those who were on placebo who went on to receive maralixibat for up to one year. Significant and sustained improvements in pruritus severity, serum bile acid (sBA) levels, total bilirubin, and growth were observed with up to two years of maralixibat treatment across the broadest range of genetic PFIC types studied to date. The placebo-maralixibat group demonstrated rapid (as early as three weeks) and significant improvements in pruritus severity and sBA levels similar to those observed in the original MARCH maralixibat group. No new safety signals were observed. The most common treatment emergent adverse events were GI, occurred early in treatment, and were mild and transient in nature. These data suggest overall improved liver health with maralixibat treatment in patients with PFIC that can be maintained long-term.

Other Poster Presentations

Poster 4602-C: Improvements in pruritus with maralixibat are associated with improved quality of life for patients with progressive familial intrahepatic cholestasis: Data from the MARCH-PFIC trial

Pruritus is known to be one of the most burdensome symptoms of PFIC, occurring in the majority of patients and leading to sleep disturbance, self-mutilation, and decreased school performance, further contributing to impaired quality of life. An exploratory endpoint in the MARCH study was to evaluate if a clinically significant reduction in pruritus following treatment with maralixibat was associated with an improvement in quality of life. These data demonstrated that clinically significant reductions in pruritus were associated with meaningful improvements in quality of life, as evaluated across several domains. The maralixibat group demonstrated significant differences between pruritus responders and non-responders for PedsQL, PedsQL-SF, PedsQL-PF, and a trend toward significance with FI-T. Clinically meaningful improvements (MCID >4-5 points) across all HRQoL scales were experienced by maralixibat responders. The placebo group showed no significant differences between pruritus responders and non-responders in any of the assessments. These data suggest that benefits of maralixibat may extend beyond pruritus and yield meaningful improvements in quality of life as well.

Poster 4604-C: Maralixibat leads to significant improvement in cholestatic pruritus for children with progressive familial intrahepatic cholestasis due to TJP2 or MYO5B deficiency: Data from the MARCH-PFIC trial

The MARCH study assessed the broadest set of genetic types associated with PFIC. The most common causes of PFIC are deficiencies in BSEP (PFIC2), FIC 1, MDR3, TJP2, and MYO5B. Patients with TJP2 deficiency have a predisposition to developing hepatocellular carcinoma. The goal of this analysis was to understand maralixibat’s potential to provide improvement across key markers of the disease in patients with these two rare genetic variants (TJP2, n=7, MYO5B, n=4). The results demonstrated that all patients with either a TJP2 or MYO5B deficiency receiving maralixibat achieved substantial improvements in pruritus and reductions in sBA while patients who received placebo experienced little benefit. Bilirubin levels were normalized in one participant with MYO5B deficiency who received maralixibat. MARCH is the first trial demonstrating benefit of IBAT inhibition for TJP2 and MYO5B deficiencies and these data support the use of maralixibat in patients with these genetic types.

Poster 4605-C: Maralixibat leads to significant improvements in cholestatic pruritus for children with progressive familial intrahepatic cholestasis without a genetic diagnosis: Data from the MARCH-PFIC trial

The MARCH study evaluated patients (n=8) with a PFIC clinical diagnosis without an identified genetic variant. The objective of this analysis was to understand the efficacy and safety of maralixibat treatment for patients clinically diagnosed with PFIC but without a known genetic variant. Data demonstrated that maralixibat was associated with improvements in pruritus, sBA levels, total bilirubin, and direct bilirubin, as compared to placebo. No new safety signals were observed. These data demonstrate the utility of treating patients with PFIC but without a known genetic variant with maralixibat.

Poster 4547-C: Efficacy, safety and tolerability of volixibat in patients with intrahepatic cholestasis of pregnancy: A case series of 4 patients

Intrahepatic cholestasis of pregnancy (ICP) is a cholestatic liver disease impacting pregnant woman. ICP is characterized by elevated sBA and cholestatic pruritus, often impairing sleep and quality of life. Elevated sBAs pose significant risk to the unborn fetus. A Phase 2 open-label study, OHANA, was conducted with volixibat, a minimally absorbed IBAT inhibitor, to evaluate the efficacy and safety in four patients with ICP. Volixibat demonstrated improvements in pruritus and sBA levels, signaling proof of concept for volixibat in cholestatic disease. No clinically meaningful changes in liver enzyme levels or hematology parameters were observed after volixibat treatment. The most common TEAEs were GI in nature, transient and moderate in severity.

About LIVMARLI® (maralixibat) oral solution

LIVMARLI® (maralixibat) oral solution is an orally administered, once-daily, ileal bile acid transporter (IBAT) inhibitor and the only approved medication 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.

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 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 is 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

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 cholestatic pruritus in patients with Alagille syndrome in the U.S. (three months and older), in Europe (two months and older), and in Canada. 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. Cholbam is FDA-approved for the treatment of bile acid synthesis disorders due to single enzyme defects 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 three investigational treatments for debilitating liver diseases. The LIVMARLI development program includes the Phase 2b EMBARK study for biliary atresia. Mirum’s second investigational IBAT inhibitor is volixibat, which 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.

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

Forward-Looking Statements

This press release includes forward-looking statements pertaining to the Company’s planned participation at a scientific conference, including data presentation title and synopsis, which may include discussion of the Company’s clinical and research data, including the therapeutic potential and/or commercial viability of our products and product candidates in various liver disease indications. 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. The accuracy of such statements is subject to a number of risks, uncertainties and assumptions including, but are not limited to, the following factors: the uncertainties inherent in research and development; the uncertainties inherent in business and financial planning, including, without limitation, risks related to Mirum’s business and prospects, adverse developments in our focused markets, or adverse developments in the U.S. or global regulatory environment or economies generally; the continued impact of COVID-19 on our business, operations and financial results; and competitive developments. Other factors that might cause such a difference include those discussed in the Company’s filings with the SEC. 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.

Abbreviations:

PedsQL-SF – Social functioning

PedsQL-PF – Physical functioning

FI-T – Family Impact Total Scale

HRQoL – Health Related Quality of Life

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