Mirum Pharmaceuticals, Inc. · NASDAQ:MIRM
Mirum Pharmaceuticals — Technical Presentation (August 2020)
16 slides from Mirum Pharmaceuticals's technical presentation, Aug 19, 2020
Slide 1: Serum bile acid control in long-term maralixibat-treated patients and native liver survival
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 INDIGO Study Richard Thompson,1 Deirdre Kelly,2 Alexander Miethke,3 Sanjay Rajwal,4 Nisre
Slide 2: Author Disclosures
Author Disclosures I disclose the following financial relationships with commercial interest Consultancy: Mirum, Albireo Pharma, GenerationBio, Qing Bile Therapeutics, Horizon Pharma, Alnylam, Sana Biotechnology, EVOX Therapeutics Share options: Qing Bile Therapeutics, GenerationBio Confidential 2
Slide 3: Background and Treatment Landscape for BSEP Deficiency
Background and Treatment Landscape for BSEP Deficiency • Also called Progressive familial intrahepatic cholestasis Type 2 (PFIC2) - Rare genetic defect of ABCB11 gene - Cholestasis and end stage liver disease, severe pruritus, lipid-soluble vitamin deficiency, growth deficit • No approved pharmacolo
Slide 4: Native Liver Survival +/- Surgical Biliary Diversion (NAPPED)
Native Liver Survival +/- Surgical Biliary Diversion (NAPPED) Van Wessel et al., 2020 4
Slide 5: Serum Bile Acid reduction: Predictive of Long-Term Native Liver Survival
Serum Bile Acid reduction: Predictive of Long-Term Native Liver Survival Serum bile acid control after surgical biliary diversion is associated with native liver survival to 15 years (NAPPED) van Wessel et al., 2020 5
Slide 6: Maralixibat: ASBT Inhibitor which Interrupts Enterohepatic Circulation
Maralixibat: ASBT Inhibitor which Interrupts Enterohepatic Circulation Redirects bile Clinical effects seen in acid flow by inhibiting cholestasis reuptake by ASBT ASBTi clinical studies show: ü Reductions in pruritus Interrupts recirculation of bile acids to the liver ü Reduction in sBA ü Impact on
Slide 7: INDIGO: Open-label Phase 2 Study of Maralixibat in PFIC
INDIGO: Open-label Phase 2 Study of Maralixibat in PFIC INDIGO Phase 2 • N = 33 children with PFIC Dose increased Maralixibat • 19 non-truncating (BSEP) Long-term Maralixibat 280 µg/kg extension 280 µg/kg • 6 truncating (BSEP) Once daily Twice daily • 8 PFIC1 Study endpoints: Serum bile acids, pruri
Slide 8: Patient Characteristics and Demographics
INDIGO: Patient Characteristics and Demographics Overall Non-truncating BSEP Deficiency Overall baseline demographics non-truncating BSEP n = 19 Median age (range), year 3 (1–13) Boys, n (%) 6 (32) White, n (%) 18 (95) Serum bile acid (range) µmol/L 373.4 (34.3, 601.4) ALT (range) U/L 116 (13, 379)
Slide 9: Patient Disposition
INDIGO: Patient Disposition Subjects Ongoing with >5 years of Maralixibat Treatment Seven sBA responders (75% reduction or <102µmol/L, per NAPPED); 1 non-responder remains on study 9
Slide 10: sBA Response on Maralixibat is Observed Early for Responders
INDIGO: sBA Response on Maralixibat is Observed Early for Responders 7th Responder (did not respond until twice daily dosing) Early sBA response observed at 280µg/kg/day for 6 subjects; between 2-4 weeks on maralixibat 10
Slide 11: Maralixibat sBA Response is Maintained Long-Term
INDIGO: Maralixibat sBA Response is Maintained Long-Term Twice daily dosing initiated • No clinical events have been observed • 2 patients have come off the transplant waiting list • 7th sBA responder observed after twice daily dosing at week 97 11
Slide 12: Improved Growth, Pruritus and Liver Enzymes
INDIGO: Improved Growth, Pruritus and Liver Enzymes sBA responders remain on maralixibat >5 years with improvements across multiple parameters Week 240 (n=7) Mean Mean P valuea Value Change sBA (SE) µmol/L 57.8 (92.1) -241.8 (68.1) 0.016 ALT (SE) U/L 23.7 -34.1 (15.7) 0.08 AST (SE) U/L 28.9 -33.3 (1
Slide 13: Serum Bile Acid Control Associated with Native Liver Survival
INDIGO: Serum Bile Acid Control in Long-Term Maralixibat- Treated Patients is Associated with Native Liver Survival 100% maralixibat sBA responders remain transplant free after >5 years of treatment 13
Slide 14: Treatment-Emergent Adverse Events (TEAEs) in all Patients (N = 19)
INDIGO: Treatment-Emergent Adverse Events (TEAEs) in all Patients (N = 19) TEAEs Participants, Most frequently Participants, n (%) reported TEAEs n (%) Nasopharyngitis 12 (63.2) Any TEAE 19 (100.0) Potentially maralixibat-related 15 (78.9) Vomiting 12 (63.2) Leading to discontinuationa 3 (15.8) Coug
Slide 15: Summary and Conclusions
Summary and Conclusions • Patients with serum bile acid control with long-term (>5 years) maralixibat treatment experience native liver survival, along with: - normalization and/or reductions of ALT, AST and bilirubin, if elevated at baseline - Improved growth - Controlled pruritus • In line with NA
Slide 16: Author Affiliations
Author Affiliations Richard Thompson,1 Deirdre Kelly,2 Sanjay Rajwal,3 Alexander Miethke,4 Nisreen Soufi,5 Irena Jankowska,6 Cara Mack,7 Alain Lachaux,8 Thomas Jaecklin,9 Pamela Vig,10 Andrew J Wardle,10 Robert H. Squires,11 Kathleen M. Loomes12 • 1Institute of Liver Studies, King's College London,
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