Mirum Pharmaceuticals, Inc. · NASDAQ:MIRM

Mirum Pharmaceuticals — Technical Presentation (July 2019)

15 slides from Mirum Pharmaceuticals's technical presentation, July 2019

  1. Slide 1: Phase 2 placebo-controlled withdrawal study of maralixibat in children with Alagille syndrome

    Phase 2 placebo-controlled withdrawal study of the ASBT inhibitor maralixibat in children with Alagille syndrome 48-week efficacy analysis ICONIC Study Emmanuel Gonzales, Ekkehard Sturm, Michael Stormon, Etienne M Sokal, Winita Hardikar, Florence Lacaille, Dorota Gliwicz-Miedzińska, Loreto Hierro, T

  2. Slide 2: Author affiliations

    Author affiliations Emmanuel Gonzales,1 Ekkehard Sturm,2 Michael Stormon,3 Etienne Sokal,4 Winita Hardikar,5 Florence Lacaille,6 Dorota Gliwicz-Miedzińska,7 Loreto Hierro,8 Thomas Jaecklin,9 Joan Gu,10 Nirav K. Desai,10 Alejandro Dorenbaum,11 Ciara Kennedy,12 Alastair Baker,13 Emmanuel Jacquemin1 1.

  3. Slide 3: Alagille syndrome is a rare cause of pediatric cholestasis

    Alagille syndrome is a rare cause of pediatric cholestasis Alagille syndrome (ALGS) is a genetic multisystemic developmental disease - Also known as syndromic intrahepatic bile duct paucity or arteriohepatic dysplasia - Autosomal dominant, with mutations in JAG1 (> 90% of cases) or NOTCH2 - Characte

  4. Slide 4: Maralixibat is an oral, minimally absorbed, selective inhibitor of ASBT

    Maralixibat is an oral, minimally absorbed, selective inhibitor of ASBT (apical sodium-dependent bile acid transporter) Clinical effects of Maralixibat redirects bile Cholesterol bile acids acid flow by inhibiting ASBT inhibition reuptake of bile acid CYP7A1 • ASBT inhibitors, including maralixibat,

  5. Slide 5: ICONIC: Phase 2 placebo-controlled double-blind drug-withdrawal study of maralixibat in children with ALGS

    ICONIC: Phase 2 placebo-controlled double-blind drug- withdrawal study of maralixibat in children with ALGS • Higher dose of maralixibat than previous ALGS trials1,2 ICONIC: • Randomized placebo-controlled withdrawal design Results from a Week 0–18 Week 18–22 Week 22–48 pre-specified >2 years (18 we

  6. Slide 6: ICONIC - Methodology

    ICONIC - Methodology Key inclusion criteria • Children 1–18 years with ALGS (clinical and/or genetic criteria) • Chronic cholestasis (clinical/biochemical criteria) • Significant pruritus (>2 on Itch Reported Outcome [Observer] - ItchRO[Obs]; 0–4) • No biliary diversion, liver transplant or decompen

  7. Slide 7: Disposition, demographics and disease characteristics

    Disposition, demographics and disease characteristics Disposition and demographics Baseline characteristics, mean (SD) Enrolled, n 31 ItchRO(Obs) score, 0–4 2.9 (0.5) Mean age, years (range) 5.4 (1–15) CSS score, 0–4 3.3 (0.9) Male, % 61.3 sBA, µmol/L 283 (211) Genotype, n (%): JAG1 31 (100) C4, ng/

  8. Slide 8: Significant improvements in sBA levels versus placebo and baseline

    Significant improvements in sBA levels versus placebo and baseline sBA in all patients sBA during randomized withdrawal MRX-MRX-MRX in subjects with ≥50% sBA reduction (n = 13) MRX-PBO-MRX between week 18 and 22 (µmol/L) Baseline sBA 283 (211) µmol/L MRX vs PBO week 18 to (n = 16) baseline in sBA le

  9. Slide 9: Improvements in ItchRO(Obs) scores maintained during randomized withdrawal with maralixibat

    Improvements in ItchRO(Obs) scores maintained during randomized withdrawal with maralixibat MRX-MRX-MRX (n = 13) Baseline ItchRO(Obs) MRX-PBO-MRX 2.9 (0.5) MRX vs Pbo week 18 to (n = 16) baseline in ItchRO(Obs) score in ItchRO(Obs) score between week 22, p < 0.0001 Mean (SEM) change from LS Mean (SE

  10. Slide 10: Improvements from baseline in Clinician Scratch Scale scores throughout the study

    Improvements from baseline in Clinician Scratch Scale scores throughout the study Clinician Scratch Scale scores **** † **** Mean (SD) 3.3 (0.90) 1.5 (1.33) 1.5 (1.37) Mean (SD) 2.1 (1.12) 2.9 (1.12) Proportion of patients (%) Proportion of patients in overall population (%) **** p < 0.0001, change

  11. Slide 11: Improvements from baseline in cholesterol levels and clinician xanthoma scores

    Improvements from baseline in cholesterol levels and clinician xanthoma scores MRX-MRX-MRX Serum cholesterol and C4 (n = 13) Xanthoma MRX-PBO-MRX (n = 16) Mean (SD) Baseline Week 18 Week 48 Baseline CXS Mean (SD) change from baseline 0.9 (1.3) in clinician xanthoma scale Serum cholesterol, 512.1 417

  12. Slide 12: Improvements over time in caregiver HRQoL scores

    Improvements over time in caregiver HRQoL scores Health-related Quality of Life scale • Caregiver-rated PedsQL score (0–100) Open-label period (week 0–18 and week 22–48) • Significant mean (SD) improvement at week 18: 11 (17) points, p = 0.001 • Significant mean (SD) improvement at week 48: 10 (19)

  13. Slide 13: Maralixibat was generally well tolerated

    Maralixibat was generally well tolerated Maralixibat Withdrawal, week 18–22 Maralixibat AE, regardless of relatedness week 0–18 Maralixibat Placebo week 22–48 n (%) (n = 31) (n = 13) (n = 16) (n = 29) Any AE 30 (96.8%) 7 (53.8%) 12 (75.0%) 25 (86.2%) Mild or moderate 24 (77.4%) 7 (53.8%) 11 (68.8%)

  14. Slide 14: Summary and conclusions

    Summary and conclusions • ICONIC investigated the highest dose of maralixibat in patients with ALGS to date • Maralixibat significantly reduced pruritus and sBA levels over time and vs placebo in children with ALGS • Maralixibat also improved xanthomas and quality of life • Treatment effects were ma

  15. Slide 15: Acknowledgments

    Acknowledgments • Hôpital Bicêtre, Paris, France • University Hospital for Children and Adolescents, Tübingen, Germany • Children’s Hospital at Westmead, Westmead, Sydney, Australia • Cliniques Universitaires St Luc, Brussels, Belgium • Royal Children’s Hospital Melbourne, Parkville, Australia • Hôp

Mirum Pharmaceuticals — Technical Presentation (July 2019) on 6ix