Mirum Pharmaceuticals, Inc. · NASDAQ:MIRM
Mirum Pharmaceuticals — Q3 2024 Earnings Presentation
54 slides from Mirum Pharmaceuticals's earnings presentation, Nov 12, 2024
Slide 1: Mirum Pharmaceuticals: Transforming Lives in Rare Disease
Mirum Pharmaceuticals: Transforming Lives in Rare Disease N o v e m b e r 2 0 2 4
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: Established leader in life-changing rare disease medicines
Established leader in life -changing rare disease medicines Standard of Approved Pipeline 3 Care Medicines 4 Indications 5 Indications
Slide 4: Strong Execution Positions Mirum as a High-Growth, Global Biotech
Strong Execution Positions Mirum as a High-Growth, Global Biotech 2018 2021 2023 2024+ 2 $330-335M 2024 Net Product Sales Guidance Increased Founded November 2018 Approved Sept, 20211 3 Commercial Medicines LIVMARLI Approved for PFIC3 (Alagille Syndrome) Global Commercial Footprint Positive Interims
Slide 5: Commercial Portfolio with Pipeline of Growth Opportunities
Commercial Portfolio with Pipeline of Growth Opportunities 3 APPROVED RARE DISEASE PRODUCTS, 5 ADDITIONAL INDICATIONS IN DEVELOPMENT IN HIGH-NEED ORPHAN INDICATIONS Indication Patients (US+EU) Preclinical Phase 1 Phase 2b/Phase 3 Approved Alagille Syndrome1 4,000 – 5,500 FDA and EMA Approved Progres
Slide 6: 2024 Strategic Goals to Build Value
2024 Strategic Goals to Build Value I N D U S T R Y L E A D I N G T E A M D E L I V E R I N G R E M A R K A B L E T R E AT M E N T S TO PAT I E N T S W O R L D W I D E Drive Continued Growth Across All Leverage IBAT Inhibition Expertise Three Commercial Medicines in Adult Cholestatic Liver Disease P
Slide 7: Commercial Overview
Commercial Overview
Slide 8: Efficient Global Rare Disease Commercial Execution
Efficient Global Rare Disease Commercial Execution Track Record of Commercial Success • Three commercial medicines Net Product Sales1 • Enhanced scale and focus in $330-335M3 pediatric rare disease • Model maximizes engagement & patient support $179M2 $75M • Streamlined international model in place
Slide 9: LIVMARLI Oral Solution in ALGS and PFIC
LIVMARLI® (maralixibat) Oral Solution in ALGS and PFIC Long-term data sets showing significant effects on pruritus and event-free survival (ALGS)
Slide 10: IBAT Inhibition In Cholestatic Liver Disease
IBAT Inhibition In Cholestatic Liver Disease Targeting IBAT Removes Circulating Bile Acids Addressing Toxic Bile Acid Accumulation Cholestatic Liver Disease Targeting IBAT Lowers Bile Acids IBAT Inhibition Clinical Benefits1-5 Defined by impaired bile flow & Mechanism directly addressing bile Transp
Slide 11: LIVMARLI: Positioned for Long Term Growth in ALGS and PFIC
LIVMARLI: Positioned for Long Term Growth in ALGS and PFIC STRONG FOUNDATION FOR CONTINUED GROWTH • Alagille Syndrome: Consistent quarterly growth – Increasing Penetration in Prevalent Patients – ~200/year: Annual newborn incidence in direct markets – Strong adherence & persistence; payor reimbursem
Slide 12: ALGS: A Debilitating Disease with Severe Cholestasis
ALGS: A Debilitating Disease with Severe Cholestasis Alagille Syndrome Genetic disease leading to severe cholestasis, unbearable pruritus and multi- system effects Lowers Serum Bile Acids 83% of patients experienced ≥20% reduction in sBA levels 88% Significantly of participants experienced ≥1 point
Slide 13: PFIC: Progressive Diseases of Bile-Related Transporters
PFIC: Progressive Diseases of Bile-Related Transporters PFIC (Progressive Familial Intrahepatic Cholestasis) Multiple genetic subtypes Significant Improvements in Pruritus, Serum Bile Acids, and Bilirubin Severe pruritus Stunted growth Improvements Consistent Across Multiple Subtypes Impaired QoL (P
Slide 14: Well-Characterized Safety Profile of LIVMARLI
Well-Characterized Safety Profile of LIVMARLI Safety Data Most common adverse GI adverse reactions 6% of patients of LIVMARLI includes 5 events were diarrhea were generally mild or experienced dose reductions Years of follow-up from 3 and abdominal pain moderate severity or interruptions due to rand
Slide 15: Bile Acid Portfolio
Bile Acid Portfolio CHOLBAM & chenodiol
Slide 16: Bile Acid Replacement Therapies for Rare Genetic Diseases
Bile Acid Replacement Therapies for Rare Genetic Diseases Bile acid replacement therapies provide bile acids the liver cannot produce Impaired bile acid synthesis Bile acid replacement therapies Driven by single-enzyme defects and peroxisomal (PEX) disorders 7-DHC Smith-Lemli-Optiz Syndrome (SLOS) ✓
Slide 17: Profitable Business with Strong Commercial Synergies
Profitable Business with Strong Commercial Synergies Bile Acid Portfolio Addresses Multiple High Need Settings1 Consistent Year-over-Year Growth2 Net Product Sales ($M) Genetic disorder with toxic cholestanol CTX & bile alcohol build-up ~1-2k 109 * FDA medical necessity status US Prevalence 103 96 R
Slide 18: Pipeline
Pipeline Significant expansion opportunities within pipeline indications
Slide 19: LIVMARLI
LIVMARLI
Slide 20: LIVMARLI Label Expansion Opportunity in Cholestatic Pruritus
LIVMARLI Label Expansion Opportunity in Cholestatic Pruritus Broad unmet need in multiple rare cholestatic conditions Pruritus In Rare Characteristic Estimated Addressable Cholestatic Settings Cholestatic Burden US Patients e.g. Biliary Atresia, Secondary Elevated sBA Sclerosing Cholangitis, others
Slide 21: EXPAND Phase 3 Study
EXPAND Phase 3 Study Primary Endpoint Day 1 20wk +20wks Change in pruritus from Patients with LIVMARLI 285ug/kg BID1 Baseline to 20wk Cholestatic Pruritus LIVMARLI n~45 PBO Open Label Extension Primary Endpoint Secondary Endpoints Safety & tolerability Key Inclusion Criteria Markers of disease and Q
Slide 22: Volixibat
Volixibat IBAT Inhibitor for Cholestasis in Adults
Slide 23: PSC & PBC: Immuno-inflammatory Rare Liver Disease
PSC & PBC: Immuno-inflammatory Rare Liver Disease Elevated Bile Acid Levels Drive Severe Symptom Burden (Pruritus, Fatigue) and Progressive Liver Disease Bile Acid Overload Obstruction of bile flow via impairment of intrahepatic and extrahepatic bile ducts Bile Acid Accumulation PSC: fibrotic strict
Slide 24: Primary Sclerosing Cholangitis
Primary Sclerosing Cholangitis
Slide 25: PSC: Pruritus is Common and Often Moderate to Severe
PSC: Pruritus is Common and Often Moderate to Severe No Approved Therapies; Pruritus Is A Significant Burden Primary Sclerosing Cholangitis (PSC) Patient Reported Pruritus is Often Moderate to Severe 54,000 patients across US & EU Median worst itch score from last itching episode2 8 ~65% with active
Slide 26: IBAT Inhibition Reduces Pruritus and Serum Bile Acids in PSC
IBAT Inhibition Reduces Pruritus and Serum Bile Acids in PSC 70 Mean (SE) ItchRo Weekly Sum Score (Max = 70) 60 Pruritus 50 40 CAMEO Study -70% 30 20 Δ -28.3 (-42.2, -14.3) P = 0.0078 IBAT inhibitor Proof of Concept in PSC 10 Data from patients with ItchRO >3 at Baseline, n=8 0 Baseline Week 14/ET S
Slide 27: Phase 2b Study of Volixibat in PSC Patients with Cholestatic Pruritus
Phase 2b Study of Volixibat in PSC Patients with Cholestatic Pruritus Positive Interim Analysis Exceeded prespecified efficacy and safety thresholds for continuation PSC patients with moderate-to-severe pruritus 28wk 2+ years VLX 20mg BID1 VLX Open Label 20 mg BID dose selected PBO Extension Confirm
Slide 28: Primary Biliary Cholangitis
Primary Biliary Cholangitis
Slide 29: PBC: Most Prevalent Cholestatic Liver Disease
PBC: Most Prevalent Cholestatic Liver Disease Significant Global Opportunity Across 1st & 2nd Line Settings Primary Biliary Cholangitis (PBC) 230,000 patients across US & EU Similar rate of pruritus in 1st & 2nd line 1st line Often moderate-to-severe, impacting QoL therapy patients (ALP <1.67xULN) N
Slide 30: Phase 2b Study of Volixibat in PBC Patients with Cholestatic Pruritus
Phase 2b Study of Volixibat in PBC Patients with Cholestatic Pruritus Positive Interim Analysis Rapid and statistically significant improvement in pruritus PBC patients with moderate-to-severe pruritus 28wk 2+ years Reductions in sBA and VLX 20mg BID1 VLX Open Label improvements in fatigue PBO Exten
Slide 31: VANTAGE Interim Analysis: Baseline Characteristics Well Balanced
VANTAGE Interim Analysis: Baseline Characteristics Well Balanced Volixibat BID 20mg Volixibat BID 80 mg Placebo Characteristic (n=10) (n=10) (n=10) 53.9 52.3 62.1 Age (years), mean (SD) (15.83) (5.91) (10.26) 8 9 9 Female, n (%) (80) (90) (90) 6.8 6.3 6.5 Adult ItchRO Score, mean (SD) (1.58) (1.75)
Slide 32: VANTAGE Interim Analysis: Reduction in Pruritus from Baseline
VANTAGE Interim Analysis: Reduction in Pruritus from Baseline RAPID AND STATISTICALLY SIGNIFICANT REDUCTIONS IN PRURITUS Placebo volixibat 20 mg volixibat 80 mg volixibat 20+80 mg (n=10) (n=10) (n=10) (n=20) 0 LS Mean change (SE) in the Adult ItchRO** -1 score from Baseline -2 -3 -1.50 (0.585)* p=0.
Slide 33: VANTAGE Interim Analysis: Other Observations
VANTAGE Interim Analysis: Other Observations • Significant reduction in pruritus as early as Week 1 • Significant improvements in fatigue at Week 16 • 75% of patients on volixibat achieved >50% reduction in sBA • No new safety signals: – No clinically meaningful changes in liver laboratory tests for
Slide 34: MRM-3379
MRM-3379 PDE4D Inhibitor for FXS
Slide 35: Fragile X Syndrome (FXS): Rare X-Linked Genetic Disorder
Fragile X Syndrome(FXS): Rare X-Linked Genetic Disorder Mutation in the X-linked FMR1 gene decreases cAMP • Leading inherited form of intellectual disability and autism spectrum disorder FMRP cAMP cAMP cAMP cAMP • Symptoms more pronounced in males • Diagnosed by genetic testing ~50,000 Males in the
Slide 36: MRM-3379: Selective PDE4D inhibitor for FXS
MRM-3379: Selective PDE4D inhibitor for FXS PDE4D MRM-3379 Regulates cellular signaling by breaking down cAMP Highly expressed in brain regions critical for learning, memory, • Oral, selective PDE4D inhibitor emotional regulation • 5:1 brain/plasma ratio, potentially increasing therapeutic window •
Slide 37: Mirum
Mirum Dedicated to transforming the treatment of rare diseases
Slide 38: Mirum is a Leading High-Growth, Global Rare Disease Biotech
Mirum is a Leading High-Growth, Global Rare Disease Biotech 2024 Value Drivers Growing commercial business Continued strong revenue growth $179M 2023 net product sales1 LIVMARLI: Continued US/Intl demand growth 2024 net product sales guidance increased to $330-335M Bile Acid portfolio: Growth in lin
Slide 39: Thank You
Thank You ©2024 Mirum Pharmaceuticals, Inc. All rights reserved. All service marks, trademarks and tradenames appearing in this presentation are the property of their respective owners. Solely for convenience, the trademarks and tradenames referred to in this presentation appear without the ® and sy
Slide 40: Supplemental Materials
Supplemental Materials
Slide 41: LIVMARLI Important Safety Information
LIVMARLI (maralixibat) oral solution Important Safety Information IMPORTANT SAFETY INFORMATION LIVMARLI can cause serious side effects, including: Liver injury: Changes in certain liver tests are common in patients but may worsen during treatment with LIVMARLI. These changes may be a sign of liver i
Slide 42: CHOLBAM Important Safety Information
CHOLBAM Important Safety Information LIMITATIONS OF USE The safety and effectiveness of CHOLBAM on extrahepatic manifestations of bile acid synthesis disorders due to single enzyme defects or peroxisomal disorders, including Zellweger spectrum disorders, have not been established. IMPORTANT SAFETY I
Slide 43: ICONIC: ALGS Pivotal Study Shows Significant Long-term Benefit
Supplemental Material ICONIC: ALGS Pivotal Study Shows Significant Long-term Benefit Clinically meaningful and sustained improvements in pruritus, sBA, growth, and QoL from baseline.1 Reduced Pruritus 0 -0.5 84% ItchRO(Obs) -1 of participants experienced -1.5 clinically meaningful improvements -2 (≥
Slide 44: Significant Improvement in Transplant-Free Survival in Patients with ALGS
Supplemental Material Significant Improvement in Transplant-Free Survival in Patients with ALGS Treated with LIVMARLI Post-hoc Analysis of Long-Term Impact: >1-point reduction in ItchRO[Obs] was a predictor of transplant-free survival* Transplant-Free Survival Over 6 Years of Treatment with LIVMARLI
Slide 45: MARCH PFIC: Positive Phase Data Across Broad Spectrum of PFIC Types
Supplemental Material MARCH PFIC: Positive Phase 3 Data Across Broad Spectrum of PFIC Types Significant Pruritus Improvements in All-PFIC Patients, PDUFA date March 13, 2024 LIVMARLI Placebo (n=33) (n=31) 0.0 Change from baseline in pruritus morning score Proportion of pruritus score -0.5 -0.6 asses
Slide 46: MARCH PFIC: Significant Improvements in Markers of Liver Disease
Supplemental Material MARCH PFIC: Significant Improvements in Markers of Liver Disease Significant Improvements in All-PFIC Patients (PFIC1, PFIC2, PFIC3, PFIC4, PFIC6) Serum Bile Acid Bilirubin1 50 4 LIVMARLI (n=33) Placebo (n=31) LIVMARLI Placebo Change from baseline in serum BA, µmol/L 3 3 Change
Slide 47: PFIC: sBA Response Associated with Transplant-Free Survival
Supplemental Material PFIC: sBA Response Associated with Transplant-Free Survival INDIGO Phase 2: 100% 5-yr transplant free survival in sBA responders* 100 sBA Responders 90 80 70 60 TFS (%) 50 40 30 20 10 Log-Rank p=0.0006 0 52 104 156 208 260 312 Time from enrolment (weeks) Loomes K et al. Hepatol
Slide 48: RESTORE Phase 3: Potentially NDA enabling for CTX
Supplemental Material RESTORE Phase 3: Potentially NDA enabling for CTX, Orphan Exclusivity THE FIRST AND ONLY PHASE 3 PLACEBO-CONTROLLED STUDY IN CTX RESTORE Phase 3 Primary Endpoint Double-blind placebo controlled cross-over withdrawal study • Change from baseline in urine total 23S-pentol 8wks 4w
Slide 49: RESTORE Phase 3 study: All Primary and Secondary Endpoints Met
Supplemental Material RESTORE Phase 3 study: All Primary and Secondary Endpoints Met Clinically meaningful improvements in primary and secondary endpoints; NDA filing planned 1H 2024 Difference at end of DB period (placebo relative to chenodiol) (95% CI) Primary p<0.0001 Adverse Events Urine 23S-Pen
Slide 50: Intellectual Property Overview
Intellectual Property Overview
Slide 51: LIVMARLI IP Coverage in the United States to 2040+
LIVMARLI IP Coverage in the United States to 2040+ Indication Method of Treatment: Dosing (2031, 2040) Orange Book Listed – Patent No. 11,229,647 / 11,497,745 / 11,918,578 / 11,260,053 Method of Treatment (2032, 2037) Orange Book Listed – Patent No. 11,376,251 ALGS Orphan Designation (2030) [Pending
Slide 52: IP Coverage for Pipeline Indications in the United States
IP Coverage for Pipeline Indications in the United States Indication Composition of Matter (2027) Patent No. 7,956,085 Eligible for Orphan Designation, 7 years from approval PBC Volixibat PSC [Pending] Method of Treatment: Dosing (2032, 2040) [Pending] Additional Dosing (2042) CTX Orphan Designation
Slide 53: LIVMARLI IP Coverage in the Europe to 2040+
LIVMARLI IP Coverage in the Europe to 2040+ Indication Method of Treatment: [Approved for Grant]Dosing Method(2031, of 2040) Treatment: Dosing (2040) Orange Book Listed – Patent No. 11,229,647 / 11,497,745 / 11,918,578 / 11,260,053 Method of Orphan Treatment (2032) Designation (2034) 1 Orange Book L
Slide 54: IP Coverage for Pipeline Indications in Europe
IP Coverage for Pipeline Indications in Europe Indication Composition of Matter Method of Treatment: (2027) Dosing (2031, 2040) Patent No. 2,084,172 Orange Book Listed – Patent No. 11,229,647 / 11,497,745 / 11,918,578 / 11,260,053 Method for Eligible of Treatment (2032) Orphan Designation, 10 years
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