Mirum Pharmaceuticals, Inc. · NASDAQ:MIRM
Mirum Pharmaceuticals — Technical Presentation (September 2021)
18 slides from Mirum Pharmaceuticals's technical presentation, Sep 21, 2021
Slide 1: Phase 2 open-label study of maralixibat in children with PFIC: 48-week interim analysis
Phase 2 open-label efficacy and safety study of the apical sodium-dependent bile acid transporter inhibitor maralixibat in children with progressive familial intrahepatic cholestasis: 48-week interim efficacy analysis Richard J Thompson King's College London, London, UK Study funded by Shire Develop
Slide 2: Co-authors
Co-authors ▪ Deirdre A Kelly,1 Patricia McClean,2 Alexander G Miethke,3 Nisreen Soufi,4 Christine Rivet,5 Irena Jankowska,6 Cara L Mack,7 Palaniswamy Karthikeyan,8 Joan Gu,9 Thomas Jaecklin,10 Robert H Squires,11 Kathleen M Loomes12 1. Birmingham Children's Hospital, Birmingham, UK 2. Leeds General
Slide 3: Disclosures
Disclosures ▪ Note to authors: AASLD will add a disclosures slide based on the information you provided for the abstract submission
Slide 4: Maralixibat: potential treatment for children with PFIC
Maralixibat: potential treatment for children with progressive familial intrahepatic cholestasis (PFIC) ▪ PFIC is a group of debilitating childhood genetic disorders characterized by defects in bile acid transport ▪ Patients with PFIC lack approved pharmacotherapies to relieve pruritus and to preven
Slide 5: INDIGO: phase 2 open-label safety and efficacy study of maralixibat in children with PFIC
INDIGO: phase 2 open-label safety and efficacy study of maralixibat in children with PFIC Screening Dose Stable Stable Long-term exposure ≤ 6 weeks escalation dosing dosing 59 weeks 4 weeks 4 weeks 5 weeks Maralixibat 280 µg/kg/day or maximum tolerated dose 280 µg/kg/day 140 µg/kg/day 70 µg/kg/day 3
Slide 6: Inclusion/exclusion criteria and outcomes
Inclusion/exclusion criteria and outcomes Key inclusion criteria Key outcomes ▪ Aged 1–18 years ▪ Levels of cholestasis biomarkers ▪ Clinically diagnosed PFIC – sBA (primary efficacy measure) – ALT, AST, bilirubin and C4 in serum ▪ Two mutant ABCB11 or ATB8B1 alleles ▪ Pruritus assessments – ItchRO(
Slide 7: Disposition, demographics and disease characteristics
Disposition, demographics and disease characteristics Enrolled participant Disposition to week 48 characteristics (n = 33) Diagnosis, n Reached week 48, n 29 PFIC1 (ATP8B1 mutation) 8 Efficacy data available, n 26 PFIC2 (ABCB11 mutation) 25 PFIC1 6 Age, years, median (range) 3.0 (1–13) PFIC2 20 Boys
Slide 8: Efficacy measures at baseline and changes at week 48
Efficacy measures at baseline and changes at week 48 sBA, ALT, Total bilirubin, C4, ItchRO(Obs) PedsQL µmol/L UI/L mg/dL ng/mL score total score Baseline, mean (range) 352 108 2.9 4.2 2.3 61.5 (34, 602) (13, 438) (0.1, 15.1) (0.1, 47.3) (0.1, 3.8) (18.1, 85.9) Change from baseline to week 48, mean (
Slide 9: Responders at week 48: 6/26 patients, all with PFIC2
Responders at week 48: 6/26 patients, all with PFIC2 Responders (n = 6) Response indicators (n = 6) Diagnosis, n sBA levels, n PFIC1 (ATP8B1 mutation) 0 Normalized (≤ 8.5 µmol/L) 4 PFIC2 (ABCB11 mutation) 6 Reduced by ≥ 70% or ≥ 80% from baseline 2 Reached week 48, n 6 ItchRO score, n Zero (no pruri
Slide 10: Responder A (girl aged 3 years)
Responder A (girl aged 3 years) ALT and AST levels Bilirubin levels C4 levels Baseline elevations normalized Baseline elevations normalized > 2.5-fold increase within 2–3 months within 2–3 months by week 2 † ≥ 70%; ‡ ≥ 80% reduction from baseline § ≥ 0.5; ¶ ≥ 1.0; # ≥ 1.33 point reduction from basel
Slide 11: Responder B (boy aged 10 years)
Responder B (boy aged 10 years) ALT and AST levels Bilirubin levels C4 levels Baseline elevations normalized Always within normal range > 6-fold increase within 2–3 months by week 4 † ≥ 70%; ‡ ≥ 80% reduction from baseline § ≥ 0.5; ¶ ≥ 1.0; # ≥ 1.33 point reduction from baseline
Slide 12: Responder C (girl aged 6 years; sister of responder B)
Responder C (girl aged 6 years; sister of responder B) ALT and AST levels Bilirubin levels C4 levels Always within normal range Always within normal range 4-fold increase by week 2 † ≥ 70%; ‡ ≥ 80% reduction from baseline § ≥ 0.5; ¶ ≥ 1.0; # ≥ 1.33 point reduction from baseline
Slide 13: Responder D (girl aged 4 years)
Responder D (girl aged 4 years) ALT and AST levels Bilirubin levels C4 levels Always within normal range Always within normal range 6-fold increase by week 2 † ≥ 70%; ‡ ≥ 80% reduction from baseline § ≥ 0.5; ¶ ≥ 1.0; # ≥ 1.33 point reduction from baseline
Slide 14: Responder E (boy aged 3 years)
Responder E (boy aged 3 years) ALT and AST levels Bilirubin levels C4 levels Always within normal range Always within normal range Nearly 9-fold increase by week 2 † ≥ 70%; ‡ ≥ 80% reduction from baseline § ≥ 0.5; ¶ ≥ 1.0; # ≥ 1.33 point reduction from baseline
Slide 15: Responder F (girl aged 1 year)
Responder F (girl aged 1 year) ALT and AST levels Bilirubin levels C4 levels AST: always within normal range Always within normal range > 5-fold increase ALT: mild non-resolving elevation by week 13 † ≥ 70%; ‡ ≥ 80% reduction from baseline § ≥ 0.5; ¶ ≥ 1.0; # ≥ 1.33 point reduction from baseline
Slide 16: Treatment-emergent adverse events (TEAEs) in the safety population (N = 33)
Treatment-emergent adverse events (TEAEs) in the safety population (N = 33) TEAEs Participants, Most frequently reported Participants, n (%) TEAEs n (%) Any TEAE 33 (100) Pyrexia 15 (45) Potentially maralixibat-related 22 (67) Diarrhoea 14 (42) Leading to discontinuation 1 (3) Cough 13 (39) Leading
Slide 17: Summary and conclusions
Summary and conclusions ▪ ASBT blockade with maralixibat appears to benefit a subset of children with PFIC2 – Normalization or substantial reduction in sBA levels – Complete or substantial relief of pruritus – Improvement in HRQoL – Normalization of bilirubin and liver enzyme levels, if elevated ▪ G
Slide 18: Acknowledgements
Acknowledgements ▪ We thank the participants, caregivers, investigators and co-ordinators involved in the study
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