Fulcrum Therapeutics, Inc. Q4 FY2024 earnings call

• Pociredir Phase 1b PIONEER trial: Enrolled 10th patient in 12 mg cohort, 20 mg cohort open; data from 12 mg cohort in mid-2025, 20 mg by year-end.
• Sickel cell disease: High unmet need for oral therapies, pociredir as first-in-class oral HbF inducer.
• Other hematological conditions: IND-enabling studies for inherited aplastic anemias, plan to submit IND for Diamond-Blackfan anemia by end-2024.
• Financials: Cash position of $241 million, guidance to fund operations into 2027.

For the fourth quarter of 2024, collaboration revenue was $0 compared to $900,000 in Q4 2023. R&D expenses were $11.7 million vs. $19 million in Q4 2023. G&A expenses were $7.7 million vs. $9.9 million in Q4 2023. Net loss was $16.6 million vs. $24.8 million in Q4 2023. For the full year 2024, collaboration revenue was $80 million vs. $2.8 million in 2023. R&D expenses were $63.4 million vs. $71.8 million in 2023. G&A expenses were $36.4 million vs. $41.7 million in 2023. Net loss was $9.7 million vs. $97.3 million in 2023. Cash position ended 2024 at $241 million, sufficient to fund operations into at least 2027.

• Cash guidance: Existing cash expected to fund operations into at least 2027.
• Pociredir data: Mid-2025 for 12 mg cohort, year-end for 20 mg cohort.
• FDA engagement: Discussing use of HbF as surrogate endpoint for next pociredir study.

• Dependence on clinical trial outcomes for pociredir.
• Regulatory uncertainties with FDA approval processes.
• Competition in the sickle cell and hematological diseases space.

Q: Can you give color on when you would look to meet with the FDA as it relates to the 12 milligram and 20 milligram cohort readouts? And what do you think the bar is on fetal hemoglobin and VOC reduction?

A: Iain Fraser and Alex Sapir discussed FDA engagement, use of HbF as surrogate, and that small HbF increases reduce VOCs, mid-25% HbF near abolishes VOCs.

Q: Can you give us any insight into the types of patients who have been enrolling in PIONEER today and the DSMB hurdle for the 20 milligram cohort?

A: Enrolling sicker patients, adherence rates high, DMC reviews safety and tolerability, scheduled to review data after 8th patient completes 30 days.

Q: Can you give more granularity on the type of data that we're going to be getting first mid-year and then year-end, especially around VOC events?

A: Share HbF levels, biomarkers, baseline VOCs, but short study may not show VOC reduction.

Q: Can you give insight into the FSHD readout and follow-on programs?

A: FSHD data to be presented in March, no plans to continue losmapimod, others may explore longer term study.

Q: Can you talk about operating expenses in 2025 and restructuring?

A: Restructuring completed, cash burn expected $55-65 million in 2025.

Q: Can you talk about enrollment complications and DSMB safety assessment?

A: OXBRYTA withdrawal eased enrollment, DSMB reviews safety labs, no specific safety signals from prior studies.

Q: How receptive is the FDA to data on HbF induction and VOC reduction, and BD pipeline?

A: Engaging FDA on HbF as surrogate, evaluating BD opportunities in benign hematological diseases, preclinical oncology evaluation