Mirum Pharmaceuticals Business Update Call - MIRUM PHARMACEUTICALS INC

Explicit Guidance:

• Peak Revenue Expectation: Reiterated guidance of $1 billion+ in peak annual sales for Livmarly, with the EXPAND study results providing confidence in reaching the "plus" portion of this estimate.
• Timeline for Submission: Planned Supplemental New Drug Application (sNDA) for the expanded indication (cholestatic pruritus in biliary atresia and other ultra-rare diseases) to be filed in the first half of next year.
• Pricing/Unit Economics: Anticipated net annualized revenue per patient of approximately $4,000–$5,000 (based on 50% higher dosing than the Alagille syndrome indication) and a 50% increase in dose per patient compared to the Alagille indication.
• Label Scope: Expectation that the new label will cover an age range similar to existing indications (infancy to young childhood with no upper limit), though specific label language is pending FDA review.

Business-Segment Outlook:

• Livmarly (Maralixibat):
  • Geography/Population: Expansion addresses an estimated 2,000 addressable patients in the U.S. and Europe (approx. 1,000 in the U.S.) suffering from cholestatic pruritus due to biliary atresia and other ultra-rare liver diseases.
  • Target Demographics: The study population was pediatric; commercial strategy focuses on pediatric prescribers and centers, though adult populations (e.g., adult PFIC, idiopathic cholestatic pruritus) exist outside the trial scope.
  • Launch Efficiency: No incremental commercial investment required for patient identification; patient pool is highly concentrated within existing Livmarly prescriber networks (liver centers).
• Other Pipeline Programs:
  • Etebrios (Etebros): Launch for FOP is on track to kick off this month; early feedback on approval is expected soon.
  • Berlovidide: Positive "Azure One" readout achieved; "Azure Four" study readout expected later this quarter.
  • BLA Plan: The BLA for Berlovidide is planned for submission in the first half of next year, based on the Azure One and Azure Four data.
  • Velixibat: VISTA study results in PFIC granted breakthrough designation; NDA submission planned for the second half of the year following regulatory interactions. Vantage study in PBC expected to report top-line data next quarter.
  • Market Opportunity: Notes that fewer than 5% of rare diseases currently have an approved treatment, positioning the company to capture significant unmet need in ultra-rare cholestatic liver diseases.

Market and Competitive Outlook:

• Competitive Landscape: Identified as having no approved medicines in the biliary atresia setting for cholestatic pruritus; limited competition observed even in the Alagille syndrome indication.
• Demand Trends: Patient identification driven by investigator interest, compassionate use, and off-label demand; high prescriber concentration suggests efficient market penetration.
• Clinical Differentiation: Data demonstrates a 70% reduction in serum bile acids and a 1.81-point reduction in pruritus (placebo-adjusted 0.98 points, p=0.0004); ~90% of biliary atresia patients and ~80% of the overall population achieved a sustained 1-point or greater improvement in itch.
• Safety Profile: Diarrhea (64%) and abdominal pain (20%) are expected adverse events; no patients discontinued due to diarrhea; safety consistent with prior clinical experience.

Macro / Industry Outlook:

• Regulatory Strategy: Management views the expanded indication as a candidate for Priority Review from the FDA due to the significant unmet medical need and severity of the disease.
• Regulatory Alignment: The EXPAND trial design was conducted "in alignment with and at the request of the FDA" to address challenges in enrolling ultra-rare disease patients, establishing a precedent for basket trials in this segment.

Strategic Initiatives:

• Pipeline Execution: Executing a multi-asset strategy for rare genetic liver diseases with four positive reads in the current year (EXPAND, Etebrios, Berlovidide Azure One, VISTA).
• Commercialization: Leveraging existing sales and medical affairs teams for the EXPAND expansion to minimize incremental costs; focusing on pediatric liver centers for patient acquisition.
• Label Expansion: Moving from a disease-specific label (Alagille/PFIC) to a mechanism-based approach targeting "cholestatic pruritus" across multiple ultra-rare etiologies.

Risks and Headwinds to Outlook:

• Regulatory Uncertainty: Final label language and indication scope are not yet finalized and depend on ongoing FDA review of the sNDA.
• Patient Identification Variability: While diagnosis of biliary atresia is robust, diagnosis rates for the "basket" of other ultra-rare non-biliary atresia diseases are variable; reliance on increased awareness to drive identification.
• Safety Signals: Continued monitoring of gastrointestinal tolerability (diarrhea, abdominal pain), though current data shows these are mild/moderate and non-discontinuing.
• Data Disclosure: Limited data availability for specific disease subgroups within the "other" bucket due to small sample sizes (1-2 patients per category), limiting granular efficacy presentation.

Management Tone on the Future:

• Confidence Level: Highly confident and optimistic ("great example," "very encouraged," "excited about what lies ahead").
• Strategic Validation: Views the EXPAND results as validation of the "patient need + scientific potential + efficient execution" business model.
• Growth Trajectory: Expresses strong confidence that the $1 billion+ peak sales guidance will be met or exceeded ("confidence in the plus part") due to the addressable population size and lack of competition.
• Forward Momentum: Describes the year as "remarkable" with a "lot of momentum" closing out the year, anticipating further approvals and readouts in the first half of next year.

Miscellaneous:

• Trial Design: EXPAND was a randomized, placebo-controlled study across 24 sites in the U.S. and globally, enrolling 46 pediatric patients over a 20-week treatment period.
• Open-Label Extension: OLE data is ongoing; further data cuts expected after an additional 20 weeks of treatment, showing consistent response rates.
• Prophylaxis: No prophylactic treatment (e.g., loperamide) was used for diarrhea in the trial; events were managed as they arose.