Slide 1: MARCH-PFIC Phase 3 Topline Results
MARCH-PFIC Phase 3 Topline Results October 24, 2022
Slide 2: Forward-Looking Statements
Forward-Looking Statements This presentation contains "forward-looking" statements that are based on our management’s beliefs and assumptions and on information currently available to management. Forward-looking statements include all statements other than statements of historical fact contained in
Slide 3: PFIC: Progressive Diseases of Bile-Related Transporters
PFIC: Progressive Diseases of Bile-Related Transporters Progressive Familial Intrahepatic Cholestasis (PFIC) • Genetic disease of bile transporters, PFIC sub-types impact different transporters. PFIC2 is the most common. resulting in cholestasis • Severe pruritus, common indication for FIC1 surgery
Slide 4: MARCH-PFIC: Phase 3 Study Design
MARCH-PFIC: Phase 3 Study Design Enrolled All Genetic PFIC Types; n=93 Primary Endpoint PFIC2: n=31 • Improvement in pruritus in PFIC2 n=31 PFIC21 LIVMARLI 570 µg/kg BID* Secondary Endpoints All-PFIC: n=64 R • Additional pruritus and sBA 1:1 assessments in PFIC2 and All-PFIC n=31 PFIC21 n=33 PFIC1,
Slide 5: Key Demographics and Baseline Characteristics
Key Demographics and Baseline Characteristics PFIC2 All-PFIC Full-Study LIVMARLI Placebo Overall LIVMARLI Placebo Overall LIVMARLI Placebo Overall Variable (n=14) (n=17) (n=31) (n=33) (n=31) (n=64) (n=47) (n=46) (n=93) 6.3 4.2 5.1 4.9 4.4 4.6 4.8 4.7 4.7 Age (years); mean (SD) (5.24) (3.56) (4.45) (
Slide 6: Statistically Significant Improvement in Pruritus
Statistically Significant Improvement in Pruritus PFIC2 All-PFIC (n=31) (n=64) LIVMARLI Placebo LIVMARLI Placebo (n=14) (n=17) (n=33) (n=31) 0.0 0.0 Change from baseline in pruritus morning Change from baseline in pruritus morning -0.2 -0.2 -0.4 -0.4 -0.6 -0.6 Improvement -0.6 -0.6 score (ItchRO[Obs
Slide 7: Statistically Significant Improvement in Serum Bile Acids
Statistically Significant Improvement in Serum Bile Acids PFIC2 All-PFIC (n=31) (n=64) LIVMARLI Placebo LIVMARLI Placebo (n=33) (n=31) (n=14) (n=17) 100 100 Change from baseline in serum BA, µmol/L Change from baseline in serum BA, µmol/L 50 50 11 3 0 0 Improvement -50 -50 -100 -100 -150 -176 -157 -
Slide 8: Summary of Treatment Emergent Adverse Events
Summary of Treatment Emergent Adverse Events LIVMARLI Placebo Treatment Emergent Adverse Event (TEAE) (n=47) (n=46) Any TEAE, n (%) 47 (100%) 43 (93.5%) Severe TEAE, n (%) 3 (6.4%) 3 (6.5%) Serious TEAE, n (%) 5 (10.6%) 3 (6.5%) TEAE leading to discontinuation, n (%) 1 (2.1%) 0 TEAE leading to death
Slide 9: Broad Effects Observed in All-PFIC
Broad Effects Observed in All-PFIC • Proportion of pruritus score assessments < 1 point was 62% for LIVMARLI versus 28% for placebo (p<0.0001) • Responses in sBA and pruritus were rapid • NAPPED sBA response criteria met in 51.5% of patients* • Pruritus and sBA effects have been sustained into the o