Fulcrum Therapeutics (NasdaqGM:FULC) FY Conference Transcript

Fulcrum Therapeutics Conference Call Summary Company Overview - Company: Fulcrum Therapeutics (NasdaqGM: FULC) - Focus: Development of small molecule technology to modify gene expression for rare diseases with high unmet needs [1][2] Key Product: Posiradir - Indication: Treatment of sickle cell disease - Designation: Fast track and orphan designation granted - Market Size: Approximately 7.7 million patients globally, with 100,000 in the U.S. and 55,000 in Europe and the UK [4] - Mechanism: PRC2 inhibitor that increases fetal hemoglobin levels, reducing vaso-occlusive crises (VOCs) [8][11] Clinical Data and Efficacy - Clinical Trial: Phase 1B open-label study with 16 patients - Baseline Fetal Hemoglobin: 7.6% at the start of the study - Results: - Fetal hemoglobin increased to 16.2%, an absolute increase of 8.6 percentage points [13] - 50% of patients achieved fetal hemoglobin levels greater than 20% [14] - 50% reduction in expected VOCs, with 50% of patients reporting no VOCs during the study [19] - Hemolysis Markers: Significant decreases in LDH, bilirubin (37% decrease), reticulocyte counts (30% decrease), and red cell distribution width (30% decrease) [17] Future Development - Next Steps: Dosing in a 20 mg cohort, targeting approximately 10 patients, with data expected by year-end [21][22] - Regulatory Plans: End of phase 1B meeting to discuss initiation of the next study, potentially a registrational study [23] Financial Position - Cash Balance: $214 million as of the end of Q2, providing a runway into 2028 [2] Industry Context - Competitive Landscape: Previous therapies like Adakveo and Oxbryta faced challenges, with Adakveo pulled from Europe and Oxbryta withdrawn from the market due to efficacy issues [5][6] - Market Need: High burden of VOCs remains, with limited effective therapies available, highlighting the potential impact of Posiradir [6][21] Conclusion - Transformative Potential: Posiradir aims to provide a once-daily oral treatment that could significantly improve the quality of life for sickle cell patients compared to existing therapies [11][21]