DISC MEDICINE CORPORATE CALL - DISC MEDICINE INC

Explicit Guidance:

• NDA Resubmission: Plan to resubmit New Drug Application (NDA) for bitapertin to the FDA by the end of the current year.
• FDA Decision Timeline: Anticipate an FDA decision regarding the NDA by mid-2027.
• EMA Submission: Expect to submit for European Medicines Agency (EMA) approval in 2027.
• Phase III Start Dates: Expect to begin Phase III studies for DISC-3405 (polycythemia vera and sickle cell disease) and CELLO-Divart (anemia of myelofibrosis) in 2027.
• Data Presentation: Anticipate presenting additional data for DISC-3405 and CELLO-Divart by the end of 2026.

Business-Segment Outlook:

• Bitapertin (EPP/XLP): Aiming to establish a new standard of care targeting the underlying pathophysiology (PP9 production) for erythropoietic protoporphyria (EPP) and X-linked protoporphyria (XLP).
• Market Opportunity: Anchors on ~14,000 diagnosed patients (age 12+) in the U.S., with ~6,000 "engaged" patients (multiple/recent claims) as the proximal launch target.
• Pediatric Expansion: Plans to pursue approval in the adolescent population (ages 12-17) as a subset of the initial label; a separate, smaller Phase III study is planned for children under 12 after a Pediatric Investigation Plan (PIP) alignment with European regulators.
• Pipeline Progress: CELLO-Divart (hepcidin suppression for myelofibrosis) and DISC-3405 (hepcidin induction for polycythemia vera/sickle cell) are on track following positive Phase II readouts earlier in the year.
• Commercialization: Rebuilding sales and medical affairs teams; confident in rapid ramp-up capabilities given prior experience and current market readiness activities.

Market and Competitive Outlook:

• Adoption Trajectory: Expects relatively quick adoption among the "engaged" patient population concentrated in top 120 U.S. centers of excellence.
• Broader Market Penetration: Anticipates a slower, but steady, funneling of the larger undiagnosed/under-diagnosed patient base (the remaining ~8,000 diagnosed patients) as disease awareness increases and diagnostic barriers are removed via a new PP9 testing program.
• Competitive Landscape: Positioning bitapertin as the only oral treatment targeting the root cause of the disease, offering a differentiated profile over existing management strategies (sun avoidance, protective clothing).
• Geographic Expansion: Views the European market as meaningful, with similar demographic frequency to the U.S., though acknowledging greater territorial complexity.
• Diagnostic Barriers: Launching a PP9 testing program in November to accelerate diagnosis and reduce barriers to treatment initiation.

Macro / Industry Outlook:

• Regulatory Environment: Pursuing standard Phase III traditional approval pathway (rather than accelerated approval) for bitapertin; eligible for a Rare Pediatric Disease Priority Review Voucher (PRV) upon successful approval due to inclusion of adolescents.
• Payer Mix: Historical research indicates 60% commercial insurance, 25% Medicare, and 15% Medicaid coverage among EPP patients.

Strategic Initiatives:

• NDA Filing: Execution of a resubmission to the FDA utilizing the robust Apollo Phase III dataset, which addresses previous gaps.
• Patient Access Programs: Expansion of the Expanded Access Program (EAP) and the Helios open-label extension study to treat patients during the regulatory review; currently ~150 patients in Helios with high demand in EAP.
• Commercial Readiness: Intensifying disease awareness campaigns, identifying regional opinion leaders, and engaging community specialists to broaden the physician network beyond top academic centers.
• R&D Expansion: Continuing to develop bitapertin for other severe blood disorders following the success of the EPP trial.

Risks and Headwinds to Outlook:

• Regulatory Timeline: Approval and commercial launch are contingent on meeting the anticipated mid-2027 FDA decision date; delays in the review process could impact timing.
• Safety Signals: While dizziness is the most common adverse event (50% in treatment group), it is mild to moderate, transient, and has not led to study discontinuations; future real-world usage remains to be fully characterized.
• Diagnostic Delays: A significant portion of the addressable market remains undiagnosed or unengaged; success relies on overcoming diagnostic latency and expanding provider awareness in community settings.
• Labeling Scope: Initial focus is on adults and adolescents; the timeline for initiating and completing the Phase III study for children under 12 remains a variable dependent on regulatory alignment.

Management Tone on the Future:

• Confidence Level: High confidence; management describes the Apollo data as "unprecedented," "robust," and a "significant scientific advancement."
• Strategic Momentum: Describes Apollo as the company's "first Phase III win," signaling a shift toward a larger portfolio of "rapidly advancing" new medicines.
• Operational Efficiency: Highlights the speed of trial execution (10 months for 183 patients) and the "fast timeline" of the study as a testament to team capability.
• Commitment: Emphasizes an "urgent" move toward regulatory engagement and a strong commitment to patient support via EAP and extension studies.

Miscellaneous:

• Investigational Status: Bidipurton (bitapertin), Silcodibart, and DISC-3405 remain investigational and unapproved globally.
• Clinical Data Scale: Bitapertin has been studied in over 4,000 clinical trial participants with up to 2.5 years of exposure in EPP patients.
• Key Trial Metrics: Apollo demonstrated a 45.8% reduction in whole-blood PP9 and a 12.2-hour improvement in monthly time in light without pain (statistically significant p < 0.001).