• Year-End Cash Position: $241 million.
• Q4 2024 Collaboration Revenue: $0 compared to $900,000 in Q4 2023.
• Q4 2024 Research and Development Expenses: $11.7 million, down from $19 million in Q4 2023.
• Q4 2024 General Administrative Expenses: $7.7 million, down from $9.9 million in Q4 2023.
• Q4 2024 Net Loss: $16.6 million, compared to $24.8 million in Q4 2023.
• Full Year 2024 Collaboration Revenue: $80 million, up from $2.8 million in 2023.
• Full Year 2024 Research and Development Expenses: $63.4 million, down from $71.8 million in 2023.
• Full Year 2024 General Administrative Expenses: $36.4 million, down from $41.7 million in 2023.
• Full Year 2024 Restructuring Expenses: $2.1 million, compared to $0 in 2023.
• Full Year 2024 Net Loss: $9.7 million, compared to $97.3 million in 2023.
• Cash Equivalents and Marketable Securities at Year-End 2024: $241 million, up from $236.2 million at the end of 2023.
• Cash Guidance: Sufficient to fund operating requirements into at least 2027.

• Warning! GuruFocus has detected 2 Warning Signs with FULC.

Release Date: February 25, 2025

For the complete transcript of the earnings call, please refer to the full earnings call transcript.

Positive Points

• Fulcrum Therapeutics Inc (NASDAQ:FULC) has a strong cash position of $241 million, providing financial stability and the ability to fund operations into at least 2027.
• The company is making significant progress with its lead program, Poserrada, for the treatment of sickle cell disease, with ongoing Phase 1b trials showing promising patient enrollment.
• Fulcrum Therapeutics Inc (NASDAQ:FULC) received an $80 million upfront license payment from Sanofi, significantly boosting its collaboration revenue for 2024.
• Research and development expenses decreased by $8.4 million year-over-year, primarily due to cost-sharing reimbursements under the collaboration with Sanofi.
• The company is exploring additional opportunities in rare benign hematological conditions, with plans to submit an IND for Diamond Blackfan anemia in the fourth quarter of 2025.

Negative Points

• Fulcrum Therapeutics Inc (NASDAQ:FULC) reported no collaboration revenues in the fourth quarter of 2024, compared to $900,000 in the same period of 2023.
• The company experienced a net loss of $16.6 million for the fourth quarter of 2024, although this was an improvement from the $24.8 million loss in the same period of 2023.
• General administrative expenses decreased due to workforce reductions, indicating potential challenges in maintaining operational efficiency.
• The withdrawal of Oxbryta from the market has created challenges in patient recruitment for the Pioneer trial, although it also presents an opportunity for Poserrada.
• The company faces uncertainties regarding the FDA's acceptance of fetal hemoglobin as a surrogate endpoint for sickle cell disease treatment, which could impact future regulatory approvals.

Q & A Highlights

Q: Can you give us any color on when you would look to meet with the FDA regarding the 12 mg and 20 mg cohort readouts? Also, what do you think the bar is on fetal hemoglobin and VOC reduction now that there have been changes in the sickle cell space? A: We aim to complete the 12 mg and 20 mg cohorts before going back to the FDA to review the next steps. However, depending on the data, we might approach the agency earlier with the 12 mg cohort data. Regarding fetal hemoglobin, recent data suggests that even modest increases can significantly reduce VOCs. For example, a 1% increase in fetal hemoglobin can lead to a 4% to 8% reduction in VOCs. Once levels reach the mid-20% range, VOCs are nearly abolished. We plan to engage with the FDA on using fetal hemoglobin as a surrogate endpoint for future studies.

Q: Can you provide insight into the types of patients enrolling in the Pioneer trial, especially with the withdrawal of Oxbryta? A: The 10 patients enrolled so far come from both South Africa and the US and tend to be on the more severe side. We expect their baseline fetal hemoglobin to be lower than previous cohorts. We plan to release the full data set once available, and we remain on track to share data from the 12 mg cohort by mid-year.

Q: What is the process for advancing to the 20 mg cohort, and what will the DSMB evaluate? A: Once the 8th patient completes 30 days of dosing, the Data Monitoring Committee (DMC) will review the data. The DMC focuses primarily on safety and tolerability. They will also review fetal hemoglobin data and other hematological data, but the primary decision to progress to the 20 mg cohort will be based on safety and tolerability.

Q: What type of data should we expect mid-year and year-end, and will there be any early VOC event readouts? A: We will share baseline and end-of-study fetal hemoglobin levels, other biomarkers, and safety data. While we are tracking VOCs, the study's short duration makes it unlikely to see significant VOC reductions. We will provide descriptive data on VOCs, but the study is not focused on efficacy readouts for VOCs.

Q: Regarding the FSHD readout expected in March, what are the key takeaways, and is there interest in exploring FSHD with another program? A: The MDA presentation will focus on the primary endpoint, key secondary endpoints, and safety. We will publish a detailed manuscript later, including a broader array of secondary endpoints. While we do not plan to continue with Los Mapoma, other players in the FSHD field may be interested in the data for longer-term studies.

For the complete transcript of the earnings call, please refer to the full earnings call transcript.