Fulcrum Therapeutics, Inc. (FULC)·Q1 2024 Earnings Summary

Executive Summary

• Entered a collaboration and ex-U.S. license with Sanofi for losmapimod: $80.0M upfront, up to $975.0M in milestones, tiered ex-U.S. royalties (low-teens to mid-twenties), and 50/50 global development cost sharing; Fulcrum will supply clinical and commercial product initially, enabling nondilutive funding for a planned U.S. launch in 2026 .
• Q1 2024 financials: collaboration revenue $0, net loss $26.870M, EPS $(0.43); higher R&D tied to REACH advancement; G&A down on lower compensation costs .
• Cash runway extended: cash/marketable securities $213.314M at 3/31/24 and pro forma ~$293.3M including Sanofi upfront; runway now guided “into 2027” vs “into 2026” previously—a key de-risking catalyst ahead of REACH Phase 3 topline in Q4 2024 .
• Operational progress: REACH trial enrolled 260 patients; as of late April, 146 completed 48 weeks and 144 opted into open-label; PIONEER (pociredir) reinitiated with Cohorts 3 (12 mg) and 4 (20 mg), ~10 patients each .

What Went Well and What Went Wrong

What Went Well

• Strategic ex-U.S. partnership with Sanofi accelerates global reach, mitigates first-launch execution risk, and funds U.S. launch with nondilutive capital: “We will receive $80 million upfront... eligible to receive up to $975 million... share equally in global development cost” .
• REACH execution strong: enrollment complete (260), high transition to open-label (144 of 146 completing 48 weeks), supporting patient engagement and unmet need .
• Runway extended into 2027; management highlighted the nondilutive upfront and cost sharing with Sanofi as drivers of financial durability .

What Went Wrong

• No collaboration revenue in Q1 (down from $0.295M YoY) and widened net loss to $26.870M; R&D rose with REACH advancement .
• Regulatory endpoint work remains ongoing: company is still correlating reachable workspace (RSA/RWS) changes with patient-meaningful outcomes in coordination with FDA COA group, adding timing and execution risk until fully validated .
• PIONEER timelines for data disclosure remain undefined until “critical mass” of patients enroll and complete dosing, limiting near-term catalysts from the SCD program .

Financial Results

Selected Balance Sheet

KPIs and Operational Milestones

Note: Segment breakdown and product margins are not applicable; the company has no approved products and reported no collaboration revenue in Q1 2024 .

Guidance Changes

Earnings Call Themes & Trends

Management Commentary

• “We are super excited to announce our collaboration and license agreement with Sanofi… Sanofi will obtain exclusive commercialization rights for losmapimod outside of the U.S., and that will allow Fulcrum to focus our efforts on planning for a strong U.S. commercial launch in 2026.” — Alex Sapir .
• “We will receive $80 million upfront… eligible to receive up to an additional $975 million… along with tiered royalties starting in the low teens of annual net sales… The companies will also share equally in the global development cost.” — Alex Sapir .
• “As of the end of April… 146 of the 260 patients had completed the 48-week treatment period, and 144… elected to continue into the open-label extension.” — Alex Sapir .
• “On a pro forma basis… considering the $80 million milestone… cash, cash equivalents and marketable securities were $293.3 million… sufficient to fund… into 2027.” — Alan Musso .

Q&A Highlights

• Manufacturing and supply under the Sanofi deal: Fulcrum will continue global clinical and commercial supply initially; Sanofi has flexibility to take over in future .
• REACH endpoint and competitive positioning: Losmapimod reduces DUX4 and downstream gene expression in vitro; ongoing work to demonstrate clinical meaningfulness of RSA/RWS and secondary endpoints (MRI MFI, dynamometry, QoL) .
• Deal process and diligence: Competitive process with multiple parties; Sanofi had broad access to confidential program info; no blinded REACH data seen by any party .
• Ex-U.S. regulatory comfort: EMA engagement acknowledged endpoints and design, with limited opportunities to change mid-trial—overall viewed as reasonable .
• Pociredir timing: Company will disclose Cohort 3 data timing after a “critical mass” is enrolled and all 10 complete 3 months; similar plan for Cohort 4 .

Estimates Context

• S&P Global consensus for Q1 2024 EPS and revenue was unavailable at time of request due to data access limits. As a result, we cannot quantify beats/misses versus Wall Street for this quarter at this time (values from S&P Global were not retrievable).
• Actuals reported: collaboration revenue $0 and EPS $(0.43)—analysts may revise forward estimates to reflect extended runway, Sanofi deal economics, and REACH execution status ahead of Q4 2024 topline .

Key Takeaways for Investors

• The Sanofi ex-U.S. license is strategically and financially accretive, adding nondilutive capital, sharing costs, and de-risking global commercialization while Fulcrum focuses on a U.S. launch in 2026 .
• REACH remains on track for Q4 2024 topline with robust patient retention into open-label—an indicator of perceived benefit/unmet need; meaningfulness work with FDA COA is a key gating item for approvability narrative .
• Runway extended into 2027 (pro forma ~$293.3M cash), reducing financing overhang through major catalysts and supporting buildout of commercial capabilities .
• Near-term stock catalysts: additional details on RSA meaningfulness, any regulatory feedback updates, and PIONEER enrollment progress/timing disclosures; Sanofi deal terms/royalty structure create an ex-U.S. monetization path .
• Risk monitor: zero revenue, increasing R&D as REACH advances, endpoint validation timelines, and execution on SCD trial reinitiation; however, partner support and extended runway mitigate several operational risks .
• Actionable: Position for REACH topline by assessing probability of success based on Phase 2b signals (RSA, MFI) and FDA COA alignment; consider value from ex-U.S. royalties/milestones and U.S. launch economics contingent on positive data .
• Medium-term thesis: If REACH is positive and COA supports approvability, losmapimod could be first to market in FSHD with multi-year lead; pociredir offers optionality in SCD with oral HbF induction differentiation .

Management and Press Release Sources: 8‑K and press materials for Q1 2024 ; Earnings call transcript Q1 2024 ; Prior quarters Q3 2023 and Q4 2023 8‑Ks . Additional relevant press release (FSHD conference abstracts) published after Q1: June 12, 2024 .