Fulcrum Therapeutics, Inc. Q1 FY2024 earnings call

• Collaboration with Sanofi: Sanofi gains exclusive commercial rights for losmapimod outside the U.S., with Fulcrum focusing on a U.S. launch in 2026. Fulcrum receives $80 million upfront, up to $975 million in milestones, and tiered royalties. Both parties share global development costs for losmapimod.
• Losmapimod updates: Phase II ReDUX4 trial published in Lancet Neurology showed functional, structural, and patient-reported outcomes improvement. Phase III REACH trial enrolled 260 patients, with 146 completing 48 weeks of treatment and 144 continuing to an open-label phase. On track for Q4 2024 top-line data.
• Pociredir updates: FDA lifted clinical hold on Phase Ib PIONEER study. Activating new sites for Cohort 3 (12mg once daily, ~10 patients) and Cohort 4 (20mg once daily, ~10 patients). Encouraging data on HbF increase observed.
• Appointed Chief Medical Officer Dr. Patrick Horn (unable to attend due to family emergency).

As of March 31, 2024, cash, cash equivalents, and marketable securities were $213.3 million, down from $236.2 million on December 31, 2023. On a pro forma basis including the $80 million upfront from Sanofi, this amount rises to $293.3 million. Collaboration revenue in Q1 2024 was $0, compared to $0.3 million in Q1 2023. Research and development expenses were $19.8 million in Q1 2024, an increase of $3.1 million from Q1 2023, primarily due to advancements in the REACH clinical trial. General and administrative expenses decreased by $1.4 million in Q1 2024, mainly from lower employee compensation costs. Net loss for Q1 2024 was $26.9 million, up from $24.8 million in Q1 2023.

• Cash, cash equivalents, and marketable securities, including Sanofi's upfront payment, are expected to fund operations into 2027.
• On track to report top-line data for the Phase III REACH trial in the fourth quarter of 2024.

Q: Walk through manufacturing for Sanofi partnership and final work on Phase III losmapimod.

A: Paul Bruno stated Sanofi has flexibility to take over manufacturing in future, and Iain Fraser mentioned Phase III REACH trial is on track with no delays expected.

Q: Competitive landscape for FSHD, losmapimod's impact on downstream genes.

A: Iain Fraser explained losmapimod reduces DUX4 expression in vitro, along with downstream genes, and discussed challenges in clinic due to tissue variability but clear pathway in myotube cultures.

Q: Priorities for US launch, Sanofi's benefits.

A: Alexander Sapir noted key priorities include hiring a strong Chief Commercial Officer and focusing on market access; Sanofi brings strong neuromuscular franchise, regulatory, and clinical expertise.

Q: Clinical meaningfulness of RWS in losmapimod, site activation in pociredir.

A: Iain Fraser detailed steps for clinical meaningfulness (patient survey, cross-sectional study, REACH study exit interviews) expected around Q4 2024; Alexander Sapir said pociredir will share data when 10 patients complete 3-month dosing in each cohort.

Q: Sanofi deal timeline, ex-US regulator comfort on REACH endpoint.

A: Paul Bruno said deal conversations ongoing over a year; Iain Fraser mentioned engagement with European regulators, understanding of REACH study endpoints.

Q: Partner receptiveness to RWS endpoint.

A: Paul Bruno said Fulcrum educated partners on RWS, and Sanofi's neuromuscular expertise made it an ideal partner for novel endpoints