Fulcrum Therapeutics, Inc. Q1 FY2025 earnings call

• Welcomed Dae Gon Ha as Senior Vice President, Head of Strategy and Business Development.
• Progress with lead program pociredir: Enrolled 16 patients in 12 mg cohort (Cohort 3) of Phase 1b PIONEER trial for sickle cell disease, plan to share results in early Q3; Data Monitoring committee recommended continuing study with initiation of 20 mg cohort (Cohort 4) underway.
• Upcoming European Hematology Association meeting in June with two abstracts on pociredir (preclinical target engagement/reversibility of gene expression and clinical data from Phase 1 healthy volunteer study).
• Plan to submit IND for DBA in Q4 2025.
• Financials: R&D, G&A, net loss details as above; existing cash expected to fund operations into at least 2027.

No detailed product segment financial performance with revenue contribution provided in the transcript. Overall financials: Research and development expenses were $13.4 million for Q1 2025 compared to $19.8 million for Q1 2024. General and administrative expenses were $7 million for Q1 2025 compared to $10.1 million for Q1 2024. Net loss was $17.7 million for Q1 2025 compared to a net loss of $26.9 million for Q1 2024. Cash, cash equivalents, and marketable securities ended Q1 2025 at $226.6 million, a $14.4 million decrease from December 31, 2024.

• Existing cash, cash equivalents, and marketable securities expected to fund operating requirements into at least 2027.
• Plan to report data from Cohort 4 (20 mg cohort) of PIONEER trial by end of 2025.
• Expect to provide data from 12 mg cohort (Cohort 3) of PIONEER trial in early Q3.

Q: Could you talk some more about the quantum of data expected from the 12-milligram cohort of PIONEER midyear, range of follow-up duration for enrolled patients, and if there'll be data on markers of hemolysis in addition to fetal hemoglobin data?

A: Iain Fraser mentioned they'll provide hematological parameters (blood counts, bilirubin's, etc.) as indicators of hemolysis. For follow-up, all 16 patients have 3-month treatment duration and a subset with 4-week follow-up.

Q: Does the observed dosing provide specific data on the number of doses patients are receiving real time?

A: Alex Sapir explained they use AiCure tool where patients register taking the drug, show swallowing, etc., with 90% adherence; data captured but not necessarily real time but timely.

Q: Do you think you've gotten a representative sample of the broader demographic for the PIONEER trial, and if pociredir should work equally well or better in patients with higher baseline HbF?

A: Alex Sapir and Iain Fraser said it's a combination of right sites and patient interest; no reason to believe baseline levels determine response, with small increments in fetal hemoglobin being clinically meaningful.

Q: What's a win for you guys from the 12-week data?

A: Alex Sapir and Iain Fraser said any increase in fetal hemoglobin is beneficial, with small increments (4%-8% reduction in VOCs for 1% increase) being clinically meaningful.

Q: How much of the enrollment in the PIONEER trial could be attributed to loss of Oxbryta and getting more sites on board?

A: Alex Sapir said it's a combination of right sites, loss of Oxbryta leading patients to seek other options, and momentum around fetal hemoglobin induction. Iain Fraser added onboarding right sites takes time but is overcoming.

Q: Given shifts at the FDA, how are you thinking about impact to pociredir's development, and how are you differentiating novel HbF inducers in the discovery pipeline?

A: Iain Fraser said they'll interact with FDA at end of Phase 1 for 20 mg cohort, and are agnostically looking at compounds inducing HbF, monitoring other inducers in clinic.