-          Phase 3 MARCH study meets primary endpoint and demonstrates statistical significance across key endpoints in all PFIC types. Receives Best of Liver Meeting distinction.

-          RISE study in infants with ALGS shows safety and tolerability of LIVMARLI for ages ≥2 months.

-          Real-world evidence highlights LIVMARLI’s safety and tolerability in patients with ALGS.

-          Post-AASLD conference call to discuss MARCH data on November 9, 2022 at 8am ET/5am PT

Mirum Pharmaceuticals, Inc. (Nasdaq: MIRM), today presented new data from LIVMARLI® (maralixibat) oral solution studies, including two late-breaker presentations, at The Liver Meeting® of the American Association for the Study of Liver Diseases taking place November 4-7, 2022 in Washington, D.C.

“The MARCH-PFIC data provides comprehensive evidence that LIVMARLI is a potentially meaningful treatment option for patients with progressive familial intrahepatic cholestasis (PFIC). The statistically significant reduction in pruritus and serum bile acids, as well as improvements in bilirubin and growth, demonstrate a magnitude of treatment effect which exceeded expectations, suggesting higher doses not only improves response rates, but is also effective across PFIC types,” said Pam Vig, PhD, head of R&D at Mirum. “We look forward to discussing these data with regulatory agencies soon. In addition, interim safety data in Alagille syndrome (ALGS) underscores LIVMARLI’s safety and tolerability profile in infants as young as two months of age. We are thrilled to expand the growing body of clinical evidence for LIVMARLI in both PFIC and ALGS and to present our late breaking data at the AASLD conference.”

Oral session #5001: Efficacy and safety of maralixibat in patients with progressive familial intrahepatic cholestasis (MARCH-PFIC): a randomized placebo-controlled study

**Nominated for Best of Liver Meeting**

Late-breaker oral presentation by Professor Richard J. Thompson, King’s College, London

The Phase 3 MARCH study evaluated LIVMARLI 570 µg/kg BID in 93 patients across a broad range of PFIC types between ages one to 17 years old. The primary analysis (n=31) focused on patients with BSEP deficiency (PFIC2). The secondary analyses evaluated the All-PFIC cohort, which included all PFIC types (n=64). The full-study population of 93 patients was inclusive of the All-PFIC cohort, as well as a supplemental cohort of PFIC patients who had previously undergone surgery, had truncating mutations, no variants found, or other.

The primary and secondary endpoints were met with statistical significance. LIVMARLI demonstrated significant and rapid improvements in pruritus and serum bile acids, consistent across all PFIC types, with treatment effect greater than previously reported, with the higher dose tested in this study. In the All-PFIC cohort, over 60% of LIVMARLI-treated patients had a pruritus response and over half had a serum bile acid response achieving statistical significance versus placebo. The data also showed statistically significant improvements in bilirubin and growth.

Topline results

*Effect size compared the difference between LIVMARLI and placebo, averaged over the last 3 time periods using a repeated measures mixed effect model. Placebo adjusted. Numbers in tables may not sum due to rounding.

*Effect size compared the difference between LIVMARLI and placebo, averaged over the last 3 time periods using a repeated measures mixed effect model. Placebo adjusted.

The most common treatment emergent adverse event was diarrhea, which was predominantly mild and transient, with a median duration of 5.5 days. There were no severe cases. One patient had a treatment emergent adverse event of mild diarrhea that led to discontinuation.

View the presentation

Poster #5021: Safety and tolerability characterization of maralixibat in infants with ALGS from 2 months of age: Interim results from the RISE study

Late-breaker poster presentation By Professor Richard J. Thompson, King’s College, London

RISE is evaluating the safety of LIVMARLI in infant patients with ALGS and PFIC, younger than one year of age. The interim analysis only reported data from the ALGS cohort. Patients (n=8) received 380 µg/kg of LIVMARLI once per day. The youngest ALGS patient in the study was two months of age, with an average age of seven months. Safety during the study was assessed by treatment-emergent adverse events (TEAEs) and change from baseline to week 13. TEAEs were mostly grade 1 in severity and unrelated to LIVMARLI. Four patients experienced seven serious adverse events which were unrelated to LIVMARLI, all resolved, and none required a change in dose or discontinuation of LIVMARLI.

Based on the safety and tolerability data observed in RISE, LIVMARLI may be an effective treatment option for ALGS patients as young as two months of age.

View the presentation

Poster #4807: Real-world safety experience in patients with Alagille syndrome treated with maralixibat

Poster presented by Dr. Ryan Himes, Ochsner Hospital for Children

The objective of the study was to report real-world safety observations for patients enrolled in the LIVMARLI global expanded access program. All patients received LIVMARLI with a target dose of 380 µg/kg. The data cut included 37 patients. TEAEs were defined as those occurring on or after the first dose of LIVMARLI and within seven days from the last medication dose.

The majority of TEAEs were mild in severity and unrelated to LIVMARLI. Only one treatment discontinuation occurred which was potentially related to LIVMARLI due to transaminase elevation (grade 3) of unknown clinical significance. Overall, treatment-related gastrointestinal adverse events were observed in 8.1% of patients, were mild and did not lead to treatment discontinuations.

View the presentation

To view all presentations, visit the Publications and Presentations section of Mirum’s website.

Data Discussion and Q3 Business Update

Mirum will be hosting a conference call on Wednesday, November 9, 2022 at 8:00 a.m. ET/5:00 a.m. PT to discuss its third quarter 2022 financial results and will be joined by Professor Richard Thompson, King’s College, London, who will discuss the results from the Phase 3 MARCH study. To join the webcast, please visit the Events & Presentations section of Mirum’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) one year of age and older and is the only FDA-approved medication to treat cholestatic pruritus associated with Alagille syndrome. For more information, please visit LIVMARLI.com.

LIVMARLI is currently being evaluated in late-stage clinical studies in other rare cholestatic liver diseases including an open-label extension study in progressive familial intrahepatic cholestasis (PFIC), and in 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 bone fractures and gastrointestinal bleeding.

Prescribing information

About Mirum Pharmaceuticals

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 one year of age and older. In Europe, the European Committee for Medicinal Products for Human Use (CHMP) has issued a positive opinion for LIVMARLI for the treatment of cholestatic pruritus in patients with Alagille syndrome two months of age and older. A decision by the European Commission is expected by year-end 2022.

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 MARCH Phase 3 clinical trial for progressive familial intrahepatic cholestasis (PFIC) and 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 three potentially registrational studies including the VISTAS Phase 2b clinical trial for adults with primary sclerosing cholangitis, the OHANA Phase 2b clinical trial for pregnant women with intrahepatic cholestasis of pregnancy, and the VANTAGE Phase 2b clinical trial for adults with primary biliary cholangitis.

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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 discovery, development, and commercialization of our product candidates and technologies, the therapeutic potential of Company products, the continuation of our clinical trials, and any potential future collaborations. Such forward-looking statements are subject to risks and uncertainties that could cause actual results to differ materially from those expressed or implied in such statements. Applicable risks and uncertainties include those relating to our preclinical research and clinical programs and other risks and uncertainties that could cause actual results to differ materially from those expressed or implied in such statements. Applicable risks and uncertainties include those relating to our preclinical research and clinical programs and other risks identified under the heading “Risk Factors” included in our most recent Form 10-Q and Form 10-K filings and in other future filings with the SEC. The forward-looking statements contained in this press release reflect Mirum’s current views with respect to future events, and Mirum does not undertake and specifically disclaims any obligation to update any forward-looking statements, except as required by law.

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