DISC MEDICINE CORPORATE CALL - DISC MEDICINE INC

Financial Performance:

• No specific quarterly revenue, earnings, or cash flow metrics were disclosed as the company remains pre-commercial; financial focus is on R&D execution and capital allocation for the upcoming NDA resubmission.
• The company maintains a favorable safety profile with no study discontinuations in the bitapertin treatment arm, supporting long-term product viability.
• Operational efficiency highlighted by the rapid completion of the Apollo Phase III trial (183 participants enrolled in 10 months, exceeding the 150 target).

Guidance and Future Outlook:

• Plans to resubmit the New Drug Application (NDA) to the FDA by the end of 2026.
• Anticipates an FDA decision (approval) by mid-2027 under a standard Phase III approval pathway.
• Targets EMA submission in 2027 for European regulatory approval.
• Future pipeline timeline: Phase III initiation expected for CELCO-Divart and DISC-3405 in 2027, with additional data presentations for these assets by end of 2026.
• Long-term safety data from the Helios extension study indicates persistent PP9 reduction and continued improvement in light tolerance over multiple years.

Business Segments and Product Lines:

• Bitapertin (EPP/XLP): Successfully met all co-primary and secondary endpoints in the Apollo Phase III trial; targets the root cause (PP9) rather than symptoms.
• Pipeline Assets:
  • CELCO-Divart (antibody suppressing hepcidin): Evaluated in anemia of myelofibrosis; positive Phase II readouts earlier in 2024.
  • DISC-3405 (antibody inducing hepcidin): Evaluated in polycythemia vera and sickle cell disease; positive Phase II readouts earlier in 2024.
• Commercial Readiness: Launching a new PP9 testing program in November 2026 to reduce diagnostic barriers and identify patients.
• Patient Access: Expanding Expanded Access Program (EAP) and continuing Helios open-label extension (approx. 150 patients currently) to support patients pre-approval.

Market and Competitive Landscape:

• Target Population: Estimated 14,000 diagnosed U.S. patients aged 12+; 6,000 "engaged" patients with active claims represent the immediate launch opportunity.
• Demographics: 60% commercial insurance, 25% Medicare, 15% Medicaid coverage.
• Competitive Differentiation: First therapy to demonstrate robust PP9 reduction alongside significant increases in light tolerance and 71% reduction in phototoxic reactions (vs. placebo); contrasts with competitors like dersimalligan which do not address the underlying metabolic pathology.
• Market Expansion: High awareness among academic centers; community physicians eager to learn and treat once awareness is raised. Significant unmet need exists among undiagnosed patients and younger pediatric populations (<12).

Risks and Challenges:

• Safety Profile: Dizziness reported as the most common adverse event (50% in treatment vs. 11% in placebo); generally mild, moderate, transient, and not dose-limiting. No data yet on restarting drug after temporary pause for this AE.
• Regulatory Path: Transitioning from a priority review voucher strategy to a standard approval pathway for the NDA resubmission.
• Diagnostic Delays: Significant barrier where many patients (especially children <12) remain undiagnosed due to lengthy diagnostic journeys; mitigated by new PP9 testing program.
• Commercial Ramp: Need to rapidly re-engage commercial team and expand community specialist network post-approval.

Management Commentary and Tone:

• Tone: Highly confident, optimistic, and relieved; described results as "unprecedented," "robust," and a "permanent change" in drug development focus.
• Team Performance: CEO praised the operational and statistical execution of the first multinational Phase III trial and the team's ability to deliver despite high anxiety.
• Patient Impact: Emphasized the life-changing potential of the drug to eliminate light intolerance and phototoxic pain, moving from a lifestyle of avoidance to normalcy.

Analyst Questions and Answers:

• Regulatory Approval: Confirmed that the clean Apollo data set is sufficient for NDA resubmission; no additional non-clinical or CMC data expected beyond what was previously aligned.
• Pediatric Voucher: With inclusion of adolescents and rare pediatric disease designation, the company is eligible to apply for a Pediatric Rare Disease Priority Review Voucher upon approval.
• Real-World Adoption: Dizziness is expected to have minimal impact on real-world use as it is transient; strong physician and patient enthusiasm noted in field visits.
• Market Penetration: "Engaged" patients are expected to adopt quickly; broader market growth relies on education and the new testing program to funnel undiagnosed patients into the system.
• Ex-US Strategy: Active pursuit of EMA submission in 2027; European market viewed as meaningful with demographic frequency similar to the U.S., though with higher territorial complexity.
• Data Consistency: Phase II and Phase III data show consistent reduction in phototoxic reactions (~71-75%), reinforcing the product's mechanism of action.

Other Key Points:

• Trial Design: Apollo was a randomized, double-blind, placebo-controlled trial (60mg bitapertin vs. placebo) for 6 months; 183 participants (34 adolescents aged 12-17).
• Statistical Significance: 45.8% reduction in whole-blood PP9 (p<0.0001); 12.2-hour improvement in monthly time in light (p=0.001); 71% reduction in phototoxic reactions (p<0.0001).
• Quality of Life: Highly significant improvements in patient global impression of change and severity scores (p<0.0001).
• Future Plans: Intent to present detailed Apollo data at a future medical conference; focus on labeling that includes secondary endpoints (phototoxic reaction reduction, time to prodrome) to enhance prescriber utility.