Mirum Pharmaceuticals, Inc. · NASDAQ:MIRM
Mirum Pharmaceuticals — Technical Presentation (June 2023)
18 slides from Mirum Pharmaceuticals's technical presentation, Jun 23, 2023
Slide 1: Maralixibat Leads to Significant Reductions in Bilirubin for Patients With PFIC: Data From MARCH-PFIC
Maralixibat Leads to Significant Reductions in Bilirubin for Patients With Progressive Familial Intrahepatic Cholestasis: Data From MARCH-PFIC Lorenzo D’Antiga1, Alexander Miethke2, Douglas Mogul3, Tiago Nunes3, Will Garner3, Pamela Vig3, Richard J. Thompson4 1Department of Paediatric Hepatology, Ga
Slide 2: Progressive Familial Intrahepatic Cholestasis (PFIC)
Progressive Familial Intrahepatic Cholestasis (PFIC) • Genetic disorders resulting in disrupted bile composition and chronic cholestasis1 • PFIC causes debilitating pruritus, impaired growth, reduced quality of life and progressive liver disease, with most patients undergoing liver transplantation2-
Slide 3: Aim
Aim To further characterise the impact of maralixibat on bilirubin in patients with PFIC as part of the MARCH trial PFIC, progressive familial intrahepatic cholestasis. 3
Slide 4: Maralixibat: IBAT Inhibitor That Interrupts Enterohepatic Circulation
Maralixibat: IBAT Inhibitor That Interrupts Enterohepatic Circulation Redirects bile Clinical effects of acid flow by inhibiting reuptake by IBAT maralixibat in cholestasis: Improvements in pruritus1-3 Interrupts recirculation Reduction in peripheral sBA1-3 of bile acids to the liver Five-year
Slide 5: MARCH: Phase 3 Study Design
MARCH: Phase 3 Study Design Key Entry Criteria Maralixibat • Diagnosis of PFIC 570 µg/kg BID* • Age ≥ 12 months and R MARCH-ON < 18 years at Baseline Phase 3 open-label 1:1 • Persistent, extension study Placebo moderate-to-severe pruritus • sBA ≥ 3 × ULN Baseline 6 months *Maralixibat 570 µg/kg is e
Slide 6: MARCH: Study Populations
MARCH: Study Populations BSEP cohort: nt-BSEP (n = 31) All-PFIC cohort (n = 64) Full-study FIC1 (n = 13), MDR3 (n = 9), TJP2 (n = 7) population and MYO5B (n = 4); (N = 93) total n = 33 Heterozygosis* (n = 2), t-BSEP (n = 9), Exploratory cohort variants not found (n = 8), fluctuating sBA (n = 2) (n =
Slide 7: MARCH: Study Populations
MARCH: Study Populations BSEP cohort: nt-BSEP (n = 31) All-PFIC cohort (n = 64) Full-study FIC1 (n = 13), MDR3 (n = 9), TJP2 (n = 7) population and MYO5B (n = 4); (N = 93) total n = 33 Heterozygosis* (n = 2), t-BSEP (n = 9), Exploratory cohort variants not found (n = 8), fluctuating sBA (n = 2) (n =
Slide 8: MARCH: Efficacy Endpoints
MARCH: Efficacy Endpoints Secondary Endpoints (BSEP and All-PFIC cohorts): Mean change in morning ItchRO(Obs) severity score between Baseline and average of the last 12 weeks in the All-PFIC cohort Mean change in total sBA level between Baseline and average of Primary Endpoint (BSEP cohort): the
Slide 9: MARCH: Efficacy Endpoints
MARCH: Efficacy Endpoints Secondary Endpoints (BSEP and All-PFIC cohorts): Mean change in morning ItchRO(Obs) severity score between Baseline and average of the last 12 weeks in the All-PFIC cohort Mean change in total sBA level between Baseline and average of Primary Endpoint (BSEP cohort): the
Slide 10: Key Demographics and Baseline Characteristics
MARCH: Key Demographics and Baseline Characteristics Maralixibat Placebo Variable (n = 33) (n = 31) Age, years 4.9 4.4 Male, % 52 42 Pruritus, ItchRO(Obs) 2.85 2.73 Total sBA, µmol/L 254 272 UDCA usage, % 82 97 Rifampicin usage, % 55 48 Alanine aminotransferase, U/L 88 127 Total bilirubin, µmol/L 70
Slide 11: Change From Baseline in Total and Direct Bilirubin
MARCH: Change From Baseline in Total and Direct Bilirubin Serum Total Bilirubin MMRM Analysis Serum Direct Bilirubin MMRM Analysis Maralixibat Placebo Maralixibat Placebo (n = 33) (n = 31) (n = 33) (n = 31) 40.0 40.0 Change from Baseline, µmol/L Change from Baseline, µmol/L 20.0 20.0 Improvement Imp
Slide 12: Change From Baseline in Patients With Abnormal Total and Direct Bilirubin at Baseline
MARCH: Change From Baseline in Patients With Abnormal Total and Direct Bilirubin at Baseline Abnormal Total Bilirubin at Baseline* Abnormal Direct Bilirubin at Baseline* Abnormal is > 20.5 µmol/L Abnormal is > 5.1 µmol/L Maralixibat Placebo Maralixibat Placebo 40.0 (n = 26) (n = 20) 40.0 (n = 30) (n
Slide 13: Total Bilirubin Normalisation
MARCH: Total Bilirubin Normalisation Improvement in Total Bilirubin Among Worsening in Total Bilirubin Among Individuals With Abnormal Levels at Baseline Individuals With Normal Levels at Baseline Abnormal is > 20.5 µmol/L Normal is ≤ 20.5 µmol/L 100 p = 0.0024† 100 p = 0.13† Patients with normalise
Slide 14: Direct Bilirubin Normalisation
MARCH: Direct Bilirubin Normalisation Improvement in Direct Bilirubin Among Individuals With Abnormal Levels at Baseline Abnormal is > 5.1 µmol/L p = 0.015† 100 Δ: 0.29 (95% CI: 0.051, 0.51) Patients with normalised values at study end,* % 75 No participants in either the maralixibat or placebo grou
Slide 15: Relationship Between Total Bilirubin Normalisation and Changes in Serum Bile Acids
MARCH: Relationship Between Total Bilirubin Normalisation and Changes in Serum Bile Acids Percent Change in Serum Bile Acids With and Without Normalised Total Bilirubin p < 0.001* p = 0.004* 100 94.9 Median serum bile acid 75 reduction, % 50 p = 0.022* 25 19.0 3.3 0 With normalised WithoutCategory n
Slide 16: Conclusions
Conclusions • MARCH is the largest Phase 3 trial conducted in children with PFIC that included PFIC types that had not previously been studied • Maralixibat is the only IBAT inhibitor to demonstrate significant decreases in total and direct bilirubin compared with placebo in children across PFIC typ
Slide 17: Acknowledgements
Acknowledgements • The authors would like to thank the clinical trial participants and their families, and investigators for their participation in the MARCH clinical study 17
Slide 18: Author Disclosures
Author Disclosures • A. Miethke is a consultant and has a sponsored research agreement with Mirum Pharmaceuticals, Inc. • D. Mogul, T. Nunes, W. Garner and P. Vig are employees of and shareholders in Mirum Pharmaceuticals, Inc. • R.J. Thompson is a consultant for Mirum Pharmaceuticals, Inc., Albireo
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