Mirum Pharmaceuticals, Inc. · NASDAQ:MIRM

Mirum Pharmaceuticals — Technical Presentation (2017)

29 slides from Mirum Pharmaceuticals's technical presentation, 2017

Slide 1: Results of ITCH, A Multi-center Randomized Double-blind Placebo-controlled Trial of Maralixibat
Results of ITCH, A Mul1-‐center Randomized Double-‐blind Placebo-‐controlled Trial of Maralixibat, an Intes1nal Bile Salt Transport Inhibitor, for Pruritus in Alagille Syndrome Benjamin L. Shneider, Cathie Spino, Binita M. Kamath, John C. Magee, Peter F. Whi;ngton, Kenneth D. Setchell, Alexander
Slide 2: Sites
Sites Childhood Liver Disease Research Network ITCH Study Sites
Slide 3: Grant Support
Grant Support • Individual NIH NIDDK U01 grants to center principal inves;gators • Site-‐speciﬁc NIH CTSA grants • Coopera;ve Research and Development Agreement between the NIDDK and Lumena and Shire (which acquired Lumena)
Slide 4: Background
Background • Alagille Syndrome -‐ systemic gene;c disorder including bile duct paucity with severe cholestasis and pruritus – Emerick Hepatology 1999;29;822 • Pruritus refractory to medical therapy • Surgical interrup;on of enterohepa;c Biliary diversion circula;on can be eﬀec;ve – Wang Hepatology
Slide 5: Hypothesis
Hypothesis Interrup;on of the enterohepa;c circula;on of bile acids, in par;cular, mediates the eﬀect of surgery Therefore pharmacologic inhibi;on of ileal bile acid reclama;on using the ASBTi, Maralixibat, would mimic the eﬀect of surgery in Alagille Syndrome and ameliorate pruritus
Slide 6: Study Aims
Study Aims • Amongst pediatric par;cipants with Alagille Syndrome: – To evaluate the eﬀect of Maralixibat versus placebo on pruritus as measured by the Itch Reported Outcome (ItchRO) instrument – To evaluate the safety and tolerability of Maralixibat – To evaluate the eﬀect of Maralixibat versus pla
Slide 7: Major Entry Criteria
Major Entry Criteria Inclusion Exclusion • Alagille Syndrome • Signiﬁcant chronic diarrhea • 1 to 18 years of age • Surgical interrup;on EHC • Cholestasis • Liver transplant • ItchRO (Obs) > 2 • ALT > 15x ULN • Decompensated cirrhosis • Consent/assent • Bile acid or lipid resin • Sodium phenylbutyra
Slide 8: Study design
140yg/ko/day Maralixibat 140g/kg/day (n=8) 7oua/ka/day | Maralixibat 707g/kg/day (n=8) eeheed 35ya/ko/day { penn tayohg/day | OO i Placebo (n=12) Screening Dose Escalation Stable Dose Treatment Follow-up Up to 4 weeks 5 weeks 8 weeks 4 weeks* Study Study 08h 1 23 4 5 6 8 13 17 t = Clinic Visit @ =Ph
Slide 9: Study design
260ug/ko/day Maralixibat 280ug/kg/day (n=8) 140;q/ka/day / Maralixibat 140g/kg/day (n=8) 70 ctatéay Maralixibat 707g/kg/day (n=8) eeheed 35y9/kg/day penn ‘ayangftay| OO 1 Placebo (n=12) Screening Dose Escalation Stable Dose Treatment Follow-up Up to 4 weeks 5 weeks 8 weeks 4 weeks* f tetetfee ft t °
Slide 10: Assessment of Pruritus
Assessment of Pruritus ItchROTM Clinician Scratch Scale (CSS) Score Descrip1on 0 None 1 Rubbing or mild scratching when undistracted 2 Ac1ve scratching without evident skin abrasions 3 Abrasions evident 4 Cutaneous mu1la1on, hemorrhage and scarring evident Kamath B, Pa/ent 2017 (in press) Whi;ngton
Slide 11: ITCH End Points
ITCH End Points • Primary: Change from baseline to week 13 in ItchRO(Obs) • Secondary: Changes from baseline to week 13 in serum bile acids and liver biochemistries • Exploratory: Changes from baseline over ;me in – Primary and secondary outcomes – Clinical Scratch Score (CSS) • Safety
Slide 12: Statistical Analysis Plan
Sta1s1cal Analysis Plan • For primary and key secondary end points, – FIRST compared two highest tolerated doses of Maralixibat vs placebo – Compared pooled Maralixibat doses vs placebo – Compared each Maralixibat dose group vs placebo • Change from baseline to week 13 or end of treatment using ANCO
Slide 13: Enrolled (53)
Enrolled (53) Ineligible (15) Withdrawn (1) Dose in µg/kg/d Placebo (12) 70 (8) 140 (11) 280 (6) 1 lost to f/u 1 withdrawn
Slide 14: Participant Characteristics
Par1cipant Characteris1cs Demographics Laboratories Parameter Maralixibat Placebo Parameter Maralixibat Placebo (N = 25) (N = 12) (N = 25) (N=12) Age (yrs) 7.5 5.5 ItchRO (obs) 3.0 2.8 < 5 yrs 32% 50% CSS 3.0 2.9 Female 40% 50% Serum bile acid (µM) 222 205 Hispanic 20% 17% TB (mg/dL) 4.7 6.4 White 8
Slide 15: Participant Characteristics
Par1cipant Characteris1cs Demographics Laboratories Parameter Maralixibat Placebo Parameter Maralixibat Placebo (N = 25) (N = 12) (N = 25) (N=12) Age (yrs) 7.5 5.5 ItchRO (obs) 3.0 2.8 < 5 yrs 32% 50% CSS 3.0 2.9 Female 40% 50% Serum bile acid (µM) 222 205 Hispanic 20% 17% TB (mg/dL) 4.7 6.4 White 8
Slide 16: Participant Characteristics
Par1cipant Characteris1cs Demographics Laboratories Parameter Maralixibat Placebo Parameter Maralixibat Placebo (N = 25) (N = 12) (N = 25) (N=12) Age (yrs) 7.5 5.5 ItchRO (obs) 3.0 2.8 < 5 yrs 32% 50% CSS 3.0 2.9 Female 40% 50% Serum bile acid (µM) 222 205 Hispanic 20% 17% TB (mg/dL) 4.7 6.4 White 8
Slide 17: Primary End Point – ItchRO (Obs)
Primary End Point – ItchRO (Obs)
Slide 18: Primary End Point – ItchRO (Obs)
Primary End Point – ItchRO (Obs)
Slide 19: Primary End Point – ItchRO (Obs)
Primary End Point – ItchRO (Obs)
Slide 20: Primary End Point – ItchRO (Obs)
Primary End Point – ItchRO (Obs)
Slide 21: Secondary End Point – Serum Bile Acid
Secondary End Point – Serum Bile Acid
Slide 22: Secondary End Point – Serum Bile Acid
Secondary End Point – Serum Bile Acid
Slide 23: Secondary End Point – Total Bilirubin
Secondary End Point – Total Bilirubin
Slide 24: Secondary End Point – Total Bilirubin
Secondary End Point – Total Bilirubin
Slide 25: Secondary End Point - ALT
Secondary End Point - ALT 400 .066 422 3 142 605 2 > 404 2 bem <Q “Im o- oO - = -205 -40: T Ly T T T Ly Ds) “y) py AN ») Oy ee MO oS 0 e a Ng Vv & x” 9” ~ we as «& Treatment Group
Slide 26: Exploratory End Point - CSS
Exploratory End Point -‐ CSS
Slide 27: Exploratory End Point - CSS
Exploratory End Point -‐ CSS
Slide 28: Safety - TEAE
Safety -‐ TEAE • No deaths • Serious TEAE – 1 Maralixibat • Gastrointes;nal-‐Related Events – Maralixibat – 52% – Placebo – 58%
Slide 29: Conclusions
Conclusions • Although the pre-‐speciﬁed primary analyses of ItchRO were not all sta;s;cally signiﬁcant, the data suggest that Maralixibat was safe and may reduce pruritus in Alagille Syndrome. • Determina;on of op;mal dosing and further assessments of safety and eﬃcacy in children with cholestasis

Mirum Pharmaceuticals — Technical Presentation (2017) on 6ix

Mirum Pharmaceuticals — Technical Presentation (2017)

Slide 1: Results of ITCH, A Multi-center Randomized Double-blind Placebo-controlled Trial of Maralixibat

Slide 2: Sites

Slide 3: Grant Support

Slide 4: Background

Slide 5: Hypothesis

Slide 6: Study Aims

Slide 7: Major Entry Criteria

Slide 8: Study design

Slide 9: Study design

Slide 10: Assessment of Pruritus

Slide 11: ITCH End Points

Slide 12: Statistical Analysis Plan

Slide 13: Enrolled (53)

Slide 14: Participant Characteristics

Slide 15: Participant Characteristics

Slide 16: Participant Characteristics

Slide 17: Primary End Point – ItchRO (Obs)

Slide 18: Primary End Point – ItchRO (Obs)

Slide 19: Primary End Point – ItchRO (Obs)

Slide 20: Primary End Point – ItchRO (Obs)

Slide 21: Secondary End Point – Serum Bile Acid

Slide 22: Secondary End Point – Serum Bile Acid

Slide 23: Secondary End Point – Total Bilirubin

Slide 24: Secondary End Point – Total Bilirubin

Slide 25: Secondary End Point - ALT

Slide 26: Exploratory End Point - CSS

Slide 27: Exploratory End Point - CSS

Slide 28: Safety - TEAE

Slide 29: Conclusions