Fulcrum Therapeutics (FULC) Goldman Sachs 45th Annual Global Healthcare Conference summary

Company overview and value drivers

• Focuses on rare diseases with high unmet need, using oral therapies to modify gene expression, primarily in FSHD and sickle cell disease.

• Anticipates pivotal phase III data for losmapimod in FSHD in Q4 this year, a major milestone.

• FSHD affects 30,000 in the U.S. and 750,000 globally, with no current treatment options.

Clinical development and trial design

• Losmapimod targets DUX4 gene expression, aiming to preserve muscle function in FSHD.

• Phase II study missed the primary endpoint but showed functional improvements and reduced muscle fat infiltration.

• Reachable Workspace, a novel, objective functional endpoint, is the primary endpoint in phase III.

• Phase III is a 48-week, 1:1 randomized, placebo-controlled trial with 260 patients, powered at 96%.

• Key secondary endpoints include MRI fat infiltration, patient-reported outcomes, and shoulder abductor dynamometry.

Regulatory and commercial strategy

• Regulators recognize Reachable Workspace as a novel endpoint; FDA is engaged and supportive of its use.

• Commercial focus is on U.S. market, with 20-30% of patients currently genetically diagnosed; genetic testing expected to rise with drug approval.

• No current standard of care; patients are managed symptomatically, with many ultimately wheelchair-bound.

• Most patients except those severely progressed are considered candidates for losmapimod.

• U.S. launch infrastructure modeled after recent neuromuscular drug launches, with 40-50 sales reps.