Fulcrum Therapeutics (FULC) Corporate presentation summary

Strategic focus and pipeline

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

• Pociredir is positioned as a potential best-in-class oral HbF inducer for sickle cell disease (SCD), with robust and rapid increases in HbF and early evidence of clinical benefit.

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

• $333.3 million in cash as of March 31, 2026, with a runway into 2029, fully funding anticipated registrational milestones.

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.

• Patients experience severe symptoms, including painful VOCs, chronic anemia, and reduced life expectancy.

• Despite recent therapeutic advances, significant unmet needs persist due to limited efficacy, safety concerns, and access barriers for current treatments.

Pociredir clinical data and efficacy

• In the 20 mg cohort, pociredir achieved a mean absolute HbF increase of 12.2% (from 7.1% to 19.3%) at week 12.

• 58% of patients reached ≥20% HbF at week 12, with all patients achieving at least a 6.5% absolute increase.

• Markers of hemolysis and anemia improved, including >1 g/dL increase in hemoglobin and reductions in LDH, bilirubin, reticulocytes, and RDW.

• 58% of patients in the 20 mg cohort reported zero VOCs during the 12-week treatment period, compared to expected baseline rates.