Fulcrum Therapeutics, Inc. Q2 FY2024 earnings call

• Alex reported that Fulcrum is on track to report top-line data for the Phase 3 REACH trial of losmapimod by the end of October, previously expected in the fourth quarter. They're building the team for potential NDA filing and U.S. commercial launch of losmapimod, and working with Sanofi for global filings. - Losmapimod is an oral small molecule inhibiting DUX4 expression for FSHD, with ~30,000 U.S. patients. The Phase 3 REACH trial enrolled 260 patients, with 98% choosing to enroll in Part B. - Pociredir is an oral HBF inducer for sickle cell disease. Phase 1b PIONEER trial is taking longer due to academic site activation lead times, expected to have data in 2025. - Alan discussed cash position: cash, cash equivalents, and marketable securities were $273.8M as of June 30, 2024, up from $236.2M in Dec 2023, driven by Sanofi's $80M upfront. Research and development expenses decreased slightly, general and administrative expenses decreased. Net income was $55.4M in Q2 2024 vs. net loss of $23.8M in Q2 2023. Cash runway expected to fund operations into 2027.

No detailed product segment financial performance with revenue contribution % provided in the transcript.

• On losmapimod: On track to report Phase 3 REACH trial top-line data by end of October. - Cash runway: Existing cash expected to fund operating requirements into 2027. - For foreseeable future, excluding potential milestones, expected to be in loss position in 2024.

No explicit detailed risk bullet points, but mention of longer-than-expected enrollment for pociredir Phase 1b trial due to academic site activation lead times and narrow inclusion-exclusion criteria.

Q: About validating reachable workspace for the agency, specific metrics, magnitude of changes, and multiple analyses; also cash runway guidance into '27.

A: Iain explained no preestablished criteria for reachable workspace, working to evaluate clinical meaningfulness. Alan mentioned cash runway funds clinical milestones, commercial activity, and ongoing pociredir trial and preclinical work.

Q: On reachable workspace endpoint with two data sets, derisking it?

A: Iain said others using the endpoint is encouraging, agency has been hearing about it, no alternative primary endpoint suggested.

Q: On pociredir Cohort 3 enrollment delay, reasons, progress update, and initiatives to accelerate; A: Alex said delay due to academic site activation lead times, many sites not matching inclusion/exclusion criteria, working to speed up with quick contract returns, expect data in 2025.

Q: On losmapimod's minimally clinically relevant difference on RWS, single number or range; A: Iain explained it's about within-patient change, focus on proportions of patients exceeding meaningful score difference, range may emerge at top-line data.

Q: On losmapimod powering, FSHD type 1/2 inclusion, sensitivity analysis; A: Iain said powering was based on FSHD type 1, over-enrollment pushed total, baseline characteristics include type 2 but powering initially based on type 1.

Q: On payer engagement for losmapimod, tailwinds, challenges; A: Alex said payer research showed no existing treatments, expect pricing similar to other rare diseases, working on genetic testing access.

Q: On FDA requests for losmapimod mechanism of action data; A: Iain said FDA focus on endpoints, not asked for more mechanism data, robust preclinical and in vitro data exist.

Q: On REACH 3 guidance revision; A: Alex said it's just fine-tuning, confident in reporting top-line by end of October