Fulcrum Therapeutics (FULC) Stifel 2024 Healthcare Conference summary

Strategic focus and pipeline updates

• Refined mission centers on developing oral therapies for rare benign hematology diseases, with a primary focus on sickle cell disease and earlier-stage assets for inherited anemias like Diamond-Blackfan and Fanconi anemia.

• Pociredir is the lead candidate, currently in a Phase Ib trial targeting sickle cell disease, with recent market changes such as the withdrawal of Oxbrita increasing unmet need.

• The company is enrolling additional patients in 12 mg and 20 mg cohorts to replicate promising initial results showing dose-dependent increases in fetal hemoglobin.

• The trial design now targets more severely affected patients with limited therapeutic options, reflecting updated inclusion/exclusion criteria post-clinical hold.

• Expansion to 20 active sites is planned by year-end, with strong investigator support and sufficient eligible patient pools due to recent therapy withdrawals.

Clinical trial progress and data strategy

• Enrollment is ongoing, with 14 active sites and a goal of 20; patient recruitment was delayed by the need to activate new, more appropriate sites.

• Data from the 12 mg cohort is expected to be available in early 2025, with 20 mg cohort results to follow later in 2025 or early 2026.

• Separate data readouts for each cohort are planned to provide timely updates and potentially inform regulatory discussions.

• The Drug Safety Monitoring Committee will review safety data after the eighth patient in the 12 mg cohort completes 30 days of dosing before advancing to the 20 mg cohort.

• Discussions are ongoing about protocol amendments to allow extension studies for patients post-Phase Ib.

Regulatory and risk-benefit considerations

• The FDA has not mandated specific meeting points; engagement will depend on the strength of the 12 mg data and internal review.

• Safety concerns stem from preclinical data and analogies to other drugs, but no clear dose-response for malignancy risk has been observed; efficacy and tolerability will guide dose selection.

• The withdrawal of voxelotor has increased the unmet need, which is recognized by the FDA and may influence regulatory flexibility.

• Two regulatory engagement paths are planned: one focused on risk-benefit with the hematology division, and another on using fetal hemoglobin as a surrogate endpoint for accelerated approval.

• Future trials may incorporate both early surrogate endpoints and longer-term clinical outcomes to support accelerated approval and subsequent label updates.