A Remarkable

Turning Point

Impacting the lives of those living 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

MARALIXIBAT Preclinical Phase 1 Phase 2b/Phase 3 Registration
Alagille Syndrome
(ALGS)*		 PDUFA Sept. 29, 2021 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

*Proposed indication: Cholestatic pruritus in patients with ALGS 1 year of age and older.

**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.

MARALIXIBAT
Alagille Syndrome (ALGS)*
Phase
PDUFA Sept. 29, 2021 REGISTRATION
MAA submitted in Europe
MARALIXIBAT
Progressive Familial Intrahepatic
Cholestasis (PFIC)
Phase
MARCH Phase 3 study enrolling Phase 2b/Phase 3
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

*Proposed indication: Cholestatic pruritus in patients with ALGS 1 year of age and older.

**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.

Maralixibat

About maralixibat

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).

Maralixibat has been granted Breakthrough Therapy designation for the treatment of pruritus in patients 1 year of age and older with ALGS and for the treatment of PFIC2.2 Orphan Drug Designation was also granted to maralixibat for the treatment of patients with PFIC, ALGS, and biliary atresia in the United States, and finally, was granted Rare Pediatric Disease Designation by the US Food and Drug Administration in ALGS.3,4

Until maralixibat is approved and available for prescribing,
the medication is available to patients with ALGS through
Mirum’s expanded access program

Mode of action

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. This leads to lower levels of bile acids systemically, thereby potentially reducing bile acid–mediated liver damage and the related effects and complications.1

Maralixibat’s safety profile has been well validated as an investigational treatment for ALGS and PFIC based on data from clinical trials spanning nearly a decade.5,6

What we’ve seen in clinical studies in ALGS

In the Phase 2 ICONIC study, children with ALGS taking maralixibat saw profound and durable reductions in:

  • Itch (pruritus)1

  • Disfiguring cholesterol deposits under the skin (xanthomas)1

  • Bile acids1
What we’ve seen in clinical studies in PFIC

In the Phase 2 INDIGO study, patients with PFIC2 who achieved serum bile acid (sBA) response during a 5-year analysis were shown to have significant improvement in transplant-free survival.6 Those patients who achieved sBA response also had significant improvements in pruritus, liver parameters, quality of life, and growth.

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

Clinical trials in biliary atresia

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

LEARN MORE ABOUT OUR CLINICAL TRIALS
Maralixibat safety profile

Maralixibat is generally well-tolerated, and the most frequent adverse events observed in clinical study were mild to moderate diarrhea and abdominal pain. A recent integrated safety analysis from more than 5 years of data in 86 patients showed that the majority of gastrointestinal (GI) events occurred within the first 4 weeks of treatment and lasted less than 1 week in duration. No patients observed in the study discontinued treatment due to GI events.5,6

Volixibat

About volixibat

Volixibat is a minimally absorbed, orally administered investigational therapy designed to selectively inhibit apical sodium-dependent bile acid transporter (ASBT), 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.7

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.7

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 ASBT inhibition), resulting in dose-related increase in 7αC4.7

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

We have seen tremendous clinical results with maralixibat in our studies evaluating the treatment for patients with primary familial intrahepatic cholangitis (PFIC); however, there may be patients that may not respond to apical sodium-dependent acid transporter (ASBT) inhibition. 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.8

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 maralixibat

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

Evaluating the efficacy and safety of 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 maralixibat for the treatment of cholestatic pruritus in eligible patients 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 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 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 Acess Program (EAP) for Alagille syndrome (ALGS) has sites open globally, offering access to 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. Kamath BM, Raman RK, Garner W, Tucker E, Vig P, Gonzales E. Gastrointestinal tolerability of maralixibat in patients with Alagille
    syndrome: an integrated analysis of short- and long-term treatment. Presented at: 6th World Congress of Pediatric
    Gastroenterology, Hepatology and Nutrition; June 2021.
  6. 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.
  7. 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.
  8. 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