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 clinical data and regulatory designations.

• Pipeline includes discovery programs for benign hematological diseases and novel HbF inducers.

• $352.3 million in cash as of 12/31/2025, with a runway into 2029 to support key 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, anemia, and reduced life expectancy.

• Despite recent therapeutic advances, unmet need remains due to limited efficacy, safety concerns, and access barriers for gene therapies.

Pociredir clinical data and efficacy

• 20 mg cohort showed a mean absolute HbF increase from 7.1% to 19.3% at 12 weeks, with 58% of patients reaching ≥20% HbF.

• All patients achieved at least a 6.5% absolute increase in HbF, with pan-cellular induction and improved red blood cell health.

• Consistent reductions in hemolysis markers (LDH, bilirubin) and improvements in anemia (>1 g/dL Hb increase) observed.

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