A Remarkable

Turning Point

Impacting the lives of those with rare liver disease is more than a mission—it’s our calling. At Mirum, our work is in service of closing treatment gaps to open a world of possibilities for patients and their families.

Patients and families play a crucial role in our clinical trial designs and approaches. We work with them to help identify what matters most as our investigational treatments are evaluated. This includes the development of surveys, pruritus (itch) severity scales, and e-diaries that help create a better understanding of the burdens of rare liver diseases.

Development pipeline

LIVMARLITM (maralixibat) Preclinical Phase 1 Phase 2b/Phase 3 Registration
Alagille Syndrome
(ALGS)		 Now approved in the U.S. MAA submitted in Europe
Progressive
Familial Intrahepatic
Cholestasis (PFIC)		 MARCH Phase 3 study enrolling
Biliary Atresia (BA) EMBARK study enrolling
VOLIXIBAT
Primary Sclerosing
Cholangitis (PSC)		 VISTAS study enrolling
Intrahepatic
Cholestasis of
Pregnancy (ICP)		 OHANA study enrolling
Primary Biliary
Cholangitis (PBC)		 Phase 2b initiation H2 2021
GENE THERAPY PROGRAMS: VTX-803 AND VTX-802*
PFIC3
PFIC2

PDUFA: Prescription Drug User Fee Act
MAA: Marketing Authorization Application

*VTX-803 and VTX-802 are proprietary gene therapy programs under development by Vivet Therapeutics. Mirum has the option to
in-license up to the investigational new drug (IND) filing.

LIVMARLITM (maralixibat)
Alagille Syndrome (ALGS)
Phase
Now approved in the U.S. REGISTRATION
MAA submitted in Europe
LIVMARLITM (maralixibat)
Progressive Familial Intrahepatic
Cholestasis (PFIC)
Phase
MARCH Phase 3 study enrolling Phase 2b/Phase 3
LIVMARLITM (maralixibat)
Biliary Atresia (BA)
Phase
EMBARK study enrolling Phase 2b/Phase 3 REGISTRATION
VOLIXIBAT
Primary Sclerosing
Cholangitis (PSC)
Phase
VISTAS study enrolling Phase 2b/Phase 3 REGISTRATION
VOLIXIBAT
Intrahepatic Cholestasis
of Pregnancy (ICP)
Phase
OHANA study enrolling Phase 2b/Phase 3 REGISTRATION
VOLIXIBAT
Primary Biliary
Cholangitis (PBC)
Phase
Phase 2b initiation H2 2021 Phase 2b/Phase 3 REGISTRATION
GENE THERAPY PROGRAMS: VTX-803 AND VTX-802*
PFIC3
Phase
PRECLINICAL REGISTRATION
GENE THERAPY PROGRAMS: VTX-803 AND VTX-802*
PFIC2
Phase
PRECLINICAL REGISTRATION

PDUFA: Prescription Drug User Fee Act
MAA: Marketing Authorization Application

*VTX-803 and VTX-802 are proprietary gene therapy programs under development by Vivet Therapeutics. Mirum has the option to
in-license up to the investigational new drug (IND) filing.

LIVMARLI (maralixibat)

About LIVMARLI (maralixibat)

LIVMARLI (maralixibat) is a novel, minimally absorbed, orally administered liquid.1 It’s an investigational medicine being evaluated as a treatment for rare liver diseases, including Alagille syndrome (ALGS), progressive familial intrahepatic cholestasis (PFIC) and biliary atresia (BA).

LIVMARLI (maralixibat) has been approved by the FDA for the treatment of cholestatic pruritus in patients with Alagille syndrome (ALGS) 1 year of age and older.

LIVMARLI (maralixibat) has also been granted Breakthrough Therapy designation for the treatment of PFIC2.2 Lastly, Orphan Drug Designation was granted to LIVMARLI (maralixibat) for the treatment of patients with PFIC and biliary atresia in the United States.3,4

Connect with a physician to learn more about
LIVMARLI (maralixibat) and discuss access:
FOR U.S. PATIENTS: MIRUM ACCESS PLUS PROGRAM
FOR PATIENTS OUTSIDE OF THE U.S.: MIRUM EXPANDED ACCESS PROGRAM

Mode of action

LIVMARLI (maralixibat) works by blocking an important bile acid transport protein on the surface of the small intestine. This results in more bile acids being excreted in the feces, which then leads to lower levels of bile acids systemically.1

What we’ve seen in clinical studies in ALGS

In the Phase 2 ICONIC study, children with ALGS taking LIVMARLI (maralixibat) saw significant reductions in itch (pruritus).1

What we’ve seen in clinical studies in PFIC

INDIGO was a Phase 2 open label study with more than 5 years of data. Patients with PFIC2 who achieved serum bile acid (sBA) response were shown to have promising results across an array of parameters.5

A Phase 3 MARCH-PFIC clinical trial was initiated to expand our understanding of LIVMARLI (maralixibat) efficacy in patients with PFIC 1, 2, 3, and 4 across 2 cohorts.

Clinical trials in biliary atresia

This Phase 2b EMBARK study evaluating LIVMARLI (maralixibat) in pediatric patients with biliary atresia was initiated in early 2021.

LEARN MORE ABOUT OUR CLINICAL TRIALS
LIVMARLI (maralixibat) safety profile

LIVMARLI can cause serious side effects, including:

Changes in liver tests: Changes in certain liver tests are common in patients with Alagille syndrome but may worsen during treatment with LIVMARLI. These changes may be a sign of liver injury and can be serious. Your health care provider should do blood tests before starting and during treatment to check your liver function. Stomach and intestinal (gastrointestinal) problems: LIVMARLI can cause stomach and intestinal problems, including diarrhea, stomach pain, and vomiting during treatment. Fat Soluble Vitamin Deficiency: This vitamin deficiency is common in patients with Alagille syndrome but may worsen during treatment.

Volixibat

About volixibat

Volixibat is a minimally absorbed, orally administered investigational therapy designed to selectively inhibit ileal bile acid transporter (IBAT), a protein that is primarily responsible for recycling bile acids from the intestine to the liver. We believe that volixibat may offer a novel approach in the treatment of rare liver diseases impacting both adults and children by blocking the recycling of bile acids, thereby reducing bile acids systemically. Volixibat is currently being studied in intrahepatic cholestasis of pregnancy, primary sclerosing cholangitis, and primary biliary cholangitis.6

Mode of action

Volixibat works by blocking an important bile acid transport protein on the surface of the small intestine. This results in more bile acids being excreted in the feces. This leads to lower levels of bile acids systemically, thereby potentially reducing bile acid–mediated liver damage and its related effects and complications. Additionally, volixibat is designed to be minimally absorbed into the bloodstream.6

What we’ve seen in clinical trials

Data from Phase 1 and Phase 2 clinical trials of volixibat in more than 400 people demonstrated Increases in fecal bile acid excretion (a marker of IBAT inhibition), resulting in dose-related increase in 7αC4.6

Volixibat clinical trials

We are now evaluating volixibat’s potential in several cholestatic diseases including the Phase 2b VISTAS study for patients with primary sclerosing cholangitis (PSC) and the Phase 2b OHANA study for patients with intrahepatic cholestasis of pregnancy (ICP) with near term plans for a Phase 2b study for adult patients with primary biliary cholangitis (PBC).

LEARN MORE ABOUT OUR CLINICAL TRIALS

Gene therapies

Although many patients may respond to ileal bile acid transporter (IBAT) inhibition in progressive familial intrahepatic cholestasis (PFIC); there may be patients that may not respond to IBAT inhibition at all. As a result, we have entered into a partnership with Vivet Therapeutics for their 2 gene therapy programs.

VTX-803 and VTX-802 work to address the root cause of PFIC through correction of the defective multidrug resistance protein 3 (MDR3) transporter for PFIC3 and the bile salt export pump functions for PFIC2. While currently in early evaluation, it is our hope that this cutting-edge technology could one day offer a cure for patients living with PFIC3 and PFIC2.

VTX-803 has received Orphan Drug Designation by the US Food and Drug Administration.

Vivet Therapeutics’ experienced gene therapy team will lead the early evaluation of VTX-803 and VTX-802 until investigational new drug (IND) submission, and Mirum has the option to lead the clinical development and commercialization globally.7

VTX-803

VTX-803 is an adeno-associated virus (AAV) gene therapy program currently being evaluated in preclinical studies for PFIC, subtype 3.

VTX-802

VTX-802 is an AAV gene therapy program currently being evaluated in preclinical studies for PFIC, subtype 2.

Our clinical
trials

At Mirum, working together with the rare liver disease community is paramount.
Patients and their families play an integral role in helping us evaluate investigational
therapies through clinical trials and obtain the evidence we need for regulatory
approval in the U.S. and beyond.

For more information about Mirum’s clinical trials, please contact:

Clinical trials for LIVMARLI (maralixibat)

Progressive Familial Intrahepatic Cholestasis (PFIC)
Phase 3 MARCH Study — Enrolling

Evaluating the efficacy and safety of LIVMARLI (maralixibat) in patients with PFIC.

View full study details on www.clinicaltrials.gov
Alagille Syndrome (ALGS)
Expanded Access Program for Patients With ALGS

Mirum’s Expanded Access Program offers access to LIVMARLI (maralixibat) for the treatment of cholestatic pruritus in eligible patients outside of the U.S. with ALGS who do not have access to ongoing clinical trials.

View study details on WWW.CLINICALTRIALS.GOV
PFIC and ALGS
PFIC and ALGS Progressive Familial Intrahepatic Cholestasis (PFIC) and Alagille syndrome (ALGS) Phase 2 RISE Study — Enrolling

Evaluating the safety and tolerability of LIVMARLI (maralixibat) in infants with PFIC or ALGS.

View full study details on WWW.CLINICALTRIALS.GOV
Biliary Atresia (BA)
Phase 2b EMBARK Study — Enrolling

Evaluating the efficacy and safety of LIVMARLI (maralixibat) in infants with BA after Kasai procedure.

View full study details on www.clinicaltrials.gov

Clinical trials for volixibat

Primary Sclerosing Cholangitis (PSC)
Phase 2b VISTAS Study — Enrolling

Evaluating efficacy and safety of volixibat in patients with itching caused by PSC.

View full study details on WWW.CLINICALTRIALS.GOV
Intrahepatic Cholestasis of Pregnancy (ICP)
Phase 2b OHANA Study — Enrolling

Evaluating the efficacy, safety, and tolerability of volixibat in patients with ICP and elevated bile acid concentrations.

View full study details on WWW.CLINICALTRIALS.GOV

Expanded access program

Clinical development is a critical part of evaluating experimental therapies as potential impactful medicines for people with rare liver diseases. We are committed to rigorous testing of experimental treatments in order to secure regulatory approval and enable the medicine to be available to as many patients as quickly as possible.

Mirum’s Expanded Access Program (EAP) for Alagille syndrome (ALGS) has sites open globally, offering access to LIVMARLI (maralixibat) for the treatment of cholestatic pruritus in eligible patients with ALGS who do not have access to ongoing clinical trials. To learn more about the program and for a list of open sites, please visit WWW.ALGSEAP.COM.

At this time, we are not able to offer expanded access to our investigational treatments in diseases other than ALGS or in regions other than those listed on the EAP website.

References

  1. Gonzales E, Sturm E, Stormon E, et al. Durability of treatment effect with long-term maralixibat in children with Alagille syndrome. Oral presentation at: American Association for the Study of Liver Diseases Annual Meeting (The Liver Meeting); November 8-12, 2019; Boston, MA.
  2. Mirum Pharmaceuticals Announces Breakthrough Therapy Designation for Maralixibat for the Treatment of Pruritus Associated with Alagille Syndrome. Mirum Pharmaceuticals, Inc. Accessed June 2, 2021. https://ir.mirumpharma.com/news-releases/news-release-details/mirum-pharmaceuticals-announces-breakthrough-therapy-designation
  3. Mirum Pharmaceuticals Completes Successful Pre-NDA Meeting with FDA for Maralixibat. Mirum Pharmaceuticals, Inc. Accessed June 2, 2021.
  4. Mirum Pharmaceuticals Announces Completion of Rolling NDA Submission for Maralixibat in Alagille Syndrome. Mirum Pharmaceuticals, Inc. Accessed June 2, 2021. https://ir.mirumpharma.com/news-releases/news-release-details/mirum-pharmaceuticals-announces-completion-rolling-nda
  5. Thompson R. Serum bile acid control in long-term maralixibat-treated patients is associated with native liver survival in children with progressive familial intrahepatic cholestasis due to bile salt export pump deficiency. Presented at: EASL 2020; August 2020. Accessed April 29, 2021.
  6. Key CC, McKibben A, Chien E, et al. A Phase 1 dose-ranging study assessing fecal bile acid excretion by volixibat, an apical sodium‑dependent bile acid transporter inhibitor, and coadministration with loperamide.
  7. Mirum Pharmaceuticals and Vivet Therapeutics Enter into Exclusive Worldwide Option and License Agreement for Vivet’s Gene Therapy Programs Targeting Progressive Familial Intrahepatic Cholestasis. Mirum Pharmaceuticals, Inc. Accessed June 2, 2021. https://ir.mirumpharma.com/news-releases/news-release-details/mirum-pharmaceuticals-and-vivet-therapeutics-enter-exclusive

LIVMARLI (maralixibat) oral
solution is now approved by the FDA
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