Fulcrum Therapeutics (FULC) 44th Annual J.P. Morgan Healthcare Conference summary

Strategic focus and pipeline

• Focus on developing oral small molecules to modify gene expression for rare diseases, with initial 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 life expectancy reduction of over 20 years.

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

Pociredir clinical data and efficacy

• 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% at 6 weeks, with over half of patients exceeding 20% HbF after 12 weeks.

• All patients achieved at least a 6.5% HbF increase, translating to a projected 30%-60% reduction in VOCs.

• Markers of hemolysis (LDH, bilirubin, reticulocytes) and anemia improved, with total hemoglobin rising by 0.8g/dL in 6 weeks.

• Observed VOCs were lower than expected during the study period, with 8 of 12 patients experiencing none.