Regulatory & Clinical Strategy - Larimar Therapeutics expects to submit a BLA seeking accelerated approval for Nomlabofusp in Q2 2026[4, 5, 33, 34] - The BLA submission will include a safety database with at least 30 participants exposed for 6 months and a subset of at least 10 participants exposed for 1 year, with the majority on the 50 mg dose[4, 5, 34] - The FDA is open to using increases in skin FXN concentrations as a reasonably likely surrogate endpoint (RLSE) for accelerated approval, pending BLA review[5, 34] - A global Phase 3 study is intended as the confirmatory study, evaluating clinical outcomes including upright stability and mFARS, expected to be underway at the time of BLA submission[5] - The START Pilot Program continues to expedite the clinical and regulatory development of Nomlabofusp[29] Nomlabofusp & Friedreich's Ataxia (FA) - Nomlabofusp is a potential disease-modifying therapy designed to address the underlying FXN deficiency in FA[7, 34] - Friedreich's Ataxia affects approximately 20,000 patients globally, with about 5,000 in the U S[6] - Most FA patients produce only approximately 20-40% of normal frataxin (FXN) levels[6] - In the OLE study, Nomlabofusp 25 mg daily increased skin FXN levels to 72% of healthy volunteers at Day 90, compared to 16% at baseline[20, 19] - Larimar had $157.5 million in cash and investments as of March 31, 2025, with a projected cash runway into Q2 2026[35]

Del-brax Development and Regulatory Pathway - FDA has confirmed an accelerated approval pathway for delpacibart braxlosiran (del-brax) in the US [8] - The primary endpoint for accelerated approval is the reduction in the circulating biomarker cDUX [10, 59, 76] - A global confirmatory Phase 3 FORWARD trial has been initiated with 200 participants in a 1:1 randomized, double-blind, placebo-controlled design [10, 79] - The company anticipates topline data from the biomarker cohort of the FORTITUDE trial in Q2 2026 and a BLA submission in H2 2026 [10, 74] - The confirmatory Phase 3 FORWARD trial is designed to support full approval, with approximately 45 global sites [80, 83] FORTITUDE Trial Data - 12-month topline data from the FORTITUDE trial showed improved functional mobility in del-brax treated participants compared to placebo, as measured by 10MWRT and TUG [35, 39, 57] - Participants treated with del-brax also demonstrated improved muscle strength measured by QMT and improved upper limb function measured by RWS compared to placebo [42, 44, 57] - Del-brax showed a favorable long-term safety and tolerability profile in the FORTITUDE trial and its open-label extension (OLE) [10, 19, 57] - Over 60% of patients express that slowing or stopping the loss of muscle function would be the most meaningful outcome [30] cDUX Biomarker - cDUX is elevated 6- to 9-fold in people living with FSHD compared to healthy volunteers [59] - Del-brax treatment resulted in rapid and statistically significant reductions in cDUX and creatine kinase (CK) levels [59, 64]

Summary of the Conference Call for Disc Medicine (IRON) Company Overview - **Company**: Disc Medicine (Ticker: IRON) - **Event**: 2025 Jefferies Global Healthcare Conference - **Date**: June 05, 2025 Key Points Discussed Industry and Regulatory Environment - **FDA Interactions**: Positive and consistent interactions with the FDA regarding the NDA submission for Erythropoietic Protoporphyria (EPP) treatment, with alignment on using Protoporphyrin IX (PP9) as a surrogate endpoint for accelerated approval [4][11] - **NDA Timeline**: Projected NDA filing in the second half of 2025, with a pre-NDA meeting scheduled without issues [8][12] Market Opportunity for EPP Treatment - **Patient Population**: Estimated 20,000 patients in the U.S. with EPP, with 14,000 patients seeking treatment based on claims data [16][17] - **Engagement with Healthcare**: Approximately 6,000 patients show a higher degree of engagement with the medical system, indicating a target population for the launch [18] - **Commercial Strategy**: Plans to utilize advocacy groups and marketing strategies to activate the full patient opportunity [18][19] Launch Trajectory and Market Dynamics - **Launch Expectations**: Anticipated launch curve similar to other successful rare disease therapies, with high patient engagement and awareness [21] - **Disease Modifying Therapy**: The treatment is positioned as a disease-modifying therapy, addressing the underlying cause of EPP rather than just symptoms [23][24] Clinical Data and Efficacy - **PP9 Reduction**: Significant reduction in PP9 levels is expected to be a key indicator of treatment efficacy, with a robust response anticipated from KOLs [24][28] - **Phototoxic Reactions**: Previous trials showed a 75% reduction in phototoxic reactions at the highest dose, which would be impactful if replicated in larger trials [28][29] Competitive Landscape - **Other Treatments**: Awareness of competitors like Dursomelagon and other early-stage assets targeting EPP, but limited activity in the space [31][32] - **Anemia Program (974)**: Focus on anemia associated with chronic inflammation, particularly in myelofibrosis (MF) and chronic kidney disease (CKD) [35][36] Upcoming Data and Regulatory Path - **Data Readouts**: Anticipated data from EHA and ASH conferences, with a focus on long-term efficacy and safety [42][45] - **Regulatory Path for Anemia**: Clearer regulatory path established with the FDA for different patient groups in myelofibrosis, including non-transfusion dependent and lightly transfused patients [67][72] Patient Stratification and Efficacy - **Identifying Responders**: Potential to identify high responders based on baseline ferritin and EPO levels, which may guide treatment decisions [82][84] Additional Insights - **Market Dynamics**: The treatment landscape for anemia in myelofibrosis is evolving, with a focus on addressing unmet needs in patient care [39][60] - **Long-term Vision**: The company aims to position its therapies as first-line treatments for anemia in myelofibrosis, differentiating from competitors that target more niche populations [64][66] This summary encapsulates the critical discussions and insights from the conference call, highlighting the company's strategic direction, market opportunities, and clinical developments.