Mirum Pharmaceuticals Business Update Call - MIRUM PHARMACEUTICALS INC

Financial Performance:

• No specific quarterly revenue, earnings, or cash flow figures were disclosed; the call focused on clinical trial results.
• Current Livmarly peak sales guidance remains "$1 billion plus," with the EXPAND data reinforcing confidence in the upper end of this range.
• Estimated revenue for the new Biliary Atresia indication is projected to be comparable in total size to the Alagille Syndrome indication, though unit pricing is expected to be higher.
• Estimated annualized net revenue per patient for the Biliary Atresia expansion is approximately 50% higher than the Alagille/PFIC indication ($400–$500 net annually), driven by a ~50% higher dosing requirement due to patient weight.
• No incremental commercial expenses or dedicated investment are required for patient identification, as the target population overlaps significantly with existing Livmarly prescribers.

Guidance and Future Outlook:

• A supplemental New Drug Application (sNDA) for the Biliary Atresia indication is planned for submission in the first half of next year.
• Management anticipates the sNDA will be a candidate for FDA Priority Review due to the high unmet medical need.
• Long-term growth strategy relies on expanding the existing rare liver disease portfolio, including the upcoming approval of Etelcalcetide (FOP) and readouts for Velixibat (PBC and PFIC).
• The company projects continued growth in the rare genetic disease business, aiming to address fewer than 5% of rare diseases currently lacking approved treatments.

Business Segments and Product Lines:

• Livmarly (Maralixibat): Phase III EXPAND study met primary endpoint (statistically significant reduction in pruritus) and all secondary endpoints, including a 70% reduction in serum bile acids.
• Biliary Atresia: No approved treatments currently exist; the study included ~1,000 addressable patients in the U.S. and ~2,000 in the U.S. and Europe. Approximately 90% of Biliary Atresia patients achieved a ≥1-point reduction in pruritus.
• Pipeline Expansion:
  • Velixibat: VISTA study in Primary Biliary Cholangitis (PBC) on track for top-line data next quarter; VISTA results in PFIC previously granted Breakthrough Therapy designation; NDA submission planned for the second half of the year.
  • Otesantrazole (FOP): Launch of Etebrios is on track to begin this month.
  • Azure One/Four: Positive readout from Azure One provides confidence for the upcoming Azure Four study readout later this quarter, leading to a BLA submission in the first half of next year.
• Target Population: Label is expected to include patients from infancy to young childhood with no upper age limit; current study was exclusively pediatric, though commercial overlap includes adults with idiopathic cholestatic pruritus.

Market and Competitive Landscape:

• Competitive Advantage: No approved medicines exist for cholestatic pruritus in the Biliary Atresia setting, creating a first-in-class opportunity.
• Market Size: Estimated 2,000 patients in the U.S. and Europe with Biliary Atresia-related cholestatic pruritus, representing a comparable market opportunity to the existing Alagille Syndrome label.
• Diagnosis Trends: Biliary Atresia is well-diagnosed in infancy; however, the "non-Biliary Atresia" bucket consists of a long tail of ultra-rare diseases where diagnosis rates may increase as awareness of the new treatment grows.
• Customer Concentration: Target patients are highly concentrated within the existing network of liver specialists who currently prescribe Livmarly, minimizing the need for new sales infrastructure.

Risks and Challenges:

• Safety Profile: The drug caused diarrhea (64% of treated patients) and abdominal pain (20%), though all cases were mild to moderate, short-lived, and no patients discontinued treatment due to these events.
• Regulatory Uncertainty: Final label language and specific disease inclusions (e.g., naming specific ultra-rare conditions vs. broad classification) remain subject to FDA negotiations.
• Market Dilution: Concerns regarding the "diagnosis gap" in non-Biliary Atresia ultra-rare diseases could impact the speed of patient identification.
• Commercial Execution: While patient identification is efficient, the company must ensure prescriber adoption across a broad range of ultra-rare conditions not yet in the label.

Management Commentary and Tone:

• Tone: Highly optimistic and confident; management described the EXPAND results as "statistically significant and clinically meaningful" and a "great example" of their business model.
• Strategic Focus: Emphasized the value of a "basket trial" design (enrolling patients with different rare diseases sharing a common biology) to accelerate development in ultra-rare settings where traditional single-disease trials are not feasible.
• Confidence: Leadership expressed strong confidence in the IVAT (IBAT) inhibition mechanism, citing consistent results across five positive clinical studies.
• Leadership: Introduction of Chief Medical Officer Rob Myers highlighted his excitement and the strategic rationale behind the trial design.

Analyst Questions and Answers:

• Bile Acid Reduction: Management confirmed the ~70% reduction in serum bile acids is highly clinically meaningful, correlating directly with pruritus improvement across all subgroups.
• Pricing Strategy: No change in overall pricing strategy; per-patient revenue will be higher due to weight-based dosing increases required for Biliary Atresia patients.
• Label Age Range: Expected to mirror the existing Alagille/PFIC label (infancy to young childhood) with no upper age cap.
• Patient Response Rates: 90% of Biliary Atresia patients and 80% of the total population achieved a ≥1-point reduction in pruritus.
• Open-Label Extension (OLE): Ongoing with additional data cuts expected; patients rolling over maintain similar response profiles to the double-blind period.
• Adult Patients: The study was pediatric; however, a significant adult population with idiopathic cholestatic pruritus exists, though their specific disease prevalence (e.g., PFIC) is harder to pinpoint.
• Prophylaxis: No prophylaxis (e.g., loperamide) was used for diarrhea management; events were self-limiting.
• Addressable Population Clarification: The 1,000 U.S. Biliary Atresia figure refers specifically to patients with native livers, post-CASI (Corticosteroid and Vitamin K), and current pruritus, matching the profile of the Alagille label.

Other Key Points:

• The EXPAND study was conducted at 24 sites globally (US and international) over approximately one year.
• The "non-Biliary Atresia" group in the study represented roughly 50% of enrollments, indicating a substantial patient pool across various ultra-rare cholestatic diseases.
• Management noted that the study design was driven by investigator interest and compassionate use demands from the medical community.
• The company highlighted the efficiency of the "Mirim business model": pairing patient need with scientific potential and executing efficiently to deliver medicines to ultra-rare populations.