Fulcrum Therapeutics (FULC) Corporate presentation summary

Strategic focus and pipeline

• Developing oral small molecules to modify gene expression in rare diseases, focusing on benign hematology.

• Pociredir is positioned as a potential best-in-class oral HbF inducer for sickle cell disease (SCD), with robust, rapid, and clinically meaningful pan-cellular increases in HbF.

• Discovery programs are advancing for benign hematological diseases to ensure long-term pipeline sustainability.

• $352.3 million in cash as of 12/31/2025, with a projected runway into 2029.

Sickle cell disease landscape and unmet need

• SCD affects approximately 7.7 million people worldwide, with high prevalence in Sub-Saharan Africa, the US, and Europe.

• SCD is characterized by painful vaso-occlusive crises (VOCs), chronic anemia, and high mortality, with a life expectancy reduction of over 20 years.

• Despite recent therapeutic advances, there remains a lack of broadly effective, durable oral therapies and significant access barriers for gene therapies.

Pociredir clinical data and efficacy

• Pociredir demonstrated a 9.9% mean absolute increase in HbF at week 6 in the 20 mg cohort, with 58% of patients reaching ≥20% HbF at their latest visit.

• All patients in the 20 mg cohort achieved at least a 6.5% absolute HbF increase from baseline.

• The 20 mg cohort showed consistent progression toward pan-cellular HbF induction and improvements in anemia and hemolysis.

• Reductions in markers of hemolysis (LDH, indirect bilirubin) and improvements in red blood cell morphology and erythropoiesis were observed.

• 67% of patients in the 20 mg cohort reported no VOCs during the 12-week treatment period, compared to expected baseline rates.