Fulcrum Therapeutics (FULC) investor relations material

Strategic focus and pipeline

• Focused on developing oral small molecules to modify gene expression for rare diseases, with a primary emphasis on sickle cell disease.

• Lead asset, pociredir, is a fetal hemoglobin inducer with Fast Track and Orphan designation, and patents extending to 2040.

• Early-stage pipeline includes discovery efforts in other benign hematological conditions and oncology.

• Strong cash position of $352 million, providing runway into at least 2029.

Sickle cell disease landscape and unmet need

• Sickle cell disease affects 7.7 million globally, with significant prevalence in the US and Europe, primarily impacting Black and brown populations.

• Patients experience chronic pain, acute vaso-occlusive crises (VOCs), and a substantial reduction in life expectancy.

• Recent withdrawals of Adakveo and Oxbrita, and limited uptake of gene therapies, highlight persistent unmet needs.

• Oral, once-daily fetal hemoglobin inducers are positioned as a promising alternative due to ease of use and efficacy.

Clinical data and efficacy of pociredir

• Phase Ib study tested 2mg, 6mg, 12mg, and 20mg doses in sickle cell patients, focusing on safety, HbF induction, hemolysis markers, anemia, and VOCs.

• 20mg cohort showed robust HbF increase from 7% to 16.9% in 6 weeks; over half of patients exceeded 20% HbF after 12 weeks.

• All patients achieved at least a 6.5% HbF increase, correlating with meaningful reductions in VOCs.

• Markers of hemolysis (LDH, bilirubin, reticulocytes, red cell distribution width) decreased, and total hemoglobin increased by 0.8g/dL in 6 weeks.

• Observed 5 VOCs in 12 patients over 12 weeks, versus 16 expected, with 8 patients experiencing no VOCs.