Executive Summary

Q4 2024 delivered tighter OpEx and a narrower net loss as Fulcrum pivoted resources to hematology; R&D fell to $11.7M (from $19.0M y/y) and G&A to $7.7M (from $9.9M y/y), driving a smaller net loss of $16.6M (vs. $24.8M y/y) .
Cash, cash equivalents and marketable securities ended 2024 at $241.0M with runway into at least 2027; 2025 cash burn guided to $55–$65M (midpoint $60M) .
Lead program pociredir (oral HbF inducer for SCD) advanced: 10 patients enrolled in the 12 mg cohort; mid‑2025 data for 12 mg and YE‑2025 for 20 mg remain on track—a key stock catalyst path over the next 6–12 months .
No Q4 collaboration revenue (vs. $0.9M y/y); FY24 recognized $80.0M from Sanofi’s upfront license payment earlier in the year, underscoring reliance on financing/collaboration rather than recurring revenue near‑term .

What Went Well and What Went Wrong

What Went Well
- Enrollment momentum and timeline confidence: “We remain on track to share…data from the 12 mg dose cohort in mid‑2025 and…20 mg…by the end of the year.” – Alex Sapir, CEO .
- Operating discipline post‑portfolio realignment: Q4 R&D $11.7M (vs. $19.0M y/y) and G&A $7.7M (vs. $9.9M y/y) as workforce reduction and Sanofi cost sharing reduced spend .
- Liquidity and burn visibility: Ended 2024 with $241.0M; runway into at least 2027; 2025 cash burn plan $55–$65M (midpoint ~$60M) .
What Went Wrong
- No quarterly revenue: Collaboration revenue was $0 in Q4 (vs. $0.9M y/y), highlighting lack of recurring revenue catalysts pre‑pociredir readouts .
- Restructuring costs: FY24 included $2.1M restructuring expense tied to workforce reduction (none in FY23), reflecting the cost of strategic pivoting .
- Losmapimod discontinued: Phase 3 REACH failure and program suspension reduce diversification; management will present full data (March 19, 2025) but has no plans to invest further in FSHD .

Financial Results

Quarterly P&L snapshot (USD Millions, except per-share amounts)

Metric	Q2 2024	Q3 2024	Q4 2024
Collaboration Revenue ($M)	$80.0	$0.0	$0.0
R&D Expense ($M)	$17.261	$14.639	$11.713
G&A Expense ($M)	$10.247	$8.424	$7.716
Restructuring Expense ($M)	$0.000	$2.063	$0.000
Total Operating Expenses ($M)	$27.508	$25.126	$19.429
Other Income, net ($M)	$2.917	$3.430	$2.861
Net Income (Loss) ($M)	$55.409	$(21.696)	$(16.568)
Diluted EPS ($)	$0.87	$(0.35)	$(0.31)

Q4 year-over-year (USD Millions, except per-share amounts)

Metric	Q4 2023	Q4 2024	y/y
Collaboration Revenue ($M)	$0.871	$0.0	Down
R&D Expense ($M)	$18.999	$11.713	Down
G&A Expense ($M)	$9.864	$7.716	Down
Other Income, net ($M)	$3.236	$2.861	Down
Net Loss ($M)	$(24.756)	$(16.568)	Narrowed
Diluted EPS ($)	$(0.40)	$(0.31)	Narrowed

Balance sheet and liquidity (end of period)

Metric	Q2 2024	Q3 2024	Q4 2024
Cash, Cash Equivalents & Marketable Securities ($M)	$273.778	$257.234	$241.021
Working Capital ($M)	$267.587	$252.980	$238.879
Total Assets ($M)	$294.256	$279.008	$260.718
Stockholders’ Equity ($M)	$273.790	$257.291	$243.034

Notes:

Margins not meaningful due to absence of product revenue. Q2 revenue reflects Sanofi upfront recognition; Q3 and Q4 have no collaboration revenue .
OpEx improvements driven by REACH discontinuation and Sanofi cost sharing; G&A lower post workforce reduction .

Guidance Changes

Metric	Period	Previous Guidance	Current Guidance	Change
Cash Runway	Multi‑year	Into at least 2027 (Q3 update)	Into at least 2027 (Q4)	Maintained
2025 Cash Burn	FY 2025	~$55–$65M (Q3)	~$55–$65M; midpoint ~$60M (reiterated on call)	Maintained
YE24 Cash	FY 2024	End 2024 ≈ $240M (Q3)	Actual YE24 $241.0M	Outcome slightly ahead

Earnings Call Themes & Trends

Topic	Previous Mentions (Q-2 and Q-1)	Current Period (Q4 2024)	Trend
Pociredir clinical progress (enrollment, readouts)	Q2: progressing Phase 1b; cohorts set at 12 mg and 20 mg . Q3: reiterated progress; planned 2025 data .	10 patients enrolled in 12 mg; data mid‑2025 (12 mg) and YE‑2025 (20 mg) reaffirmed .	Positive execution; timelines intact.
Regulatory strategy (HbF as surrogate)	Q3: considering FDA engagement on HbF surrogate endpoint post‑Phase 1b .	Company pursuing discussions with FDA on HbF as surrogate; recognizes no precedents but cites robust genetic/epidemiologic/gene therapy data .	Increasing regulatory focus; potential pathway clarification in 2025.
Operating discipline and burn	Q3: guided YE24 cash ≈$240M; 2025 burn $55–$65M .	YE24 ended $241.0M; 2025 burn guidance reiterated ($55–$65M) .	Spending control sustained.
FSHD/losmapimod	Q2: REACH topline expected; Sanofi ex‑US deal . Q3: REACH failed; program suspended; workforce reduction ~40% .	Presenting full REACH dataset Mar 19, 2025; no plans to continue losmapimod internally .	Program exit formalized; focus shifted to hematology.
Patient access dynamics (Oxbryta withdrawal)	Q3: Enrollment framework tightened; acknowledging Oxbryta withdrawal .	Oxbryta withdrawal eases eligibility; protocol now allows concomitant crizanlizumab/L‑glutamine; high adherence via AiCure .	Enrollment tailwind; enhanced adherence monitoring.

Management Commentary

Strategy and momentum: “We remain on track to share important clinical data this year, including data from the 12 mg dose cohort in mid‑2025 and…20 mg…by the end of the year.” – Alex Sapir, CEO .
Liquidity: “We ended 2024 with cash…of $241 million…[and] expect…cash…will be sufficient to fund…into at least 2027.” – Alan Musso, CFO .
HbF–VOC linkage: “Each 1% increase in HbF was…associated with a 4%–8% reduction in…VOCs…once HbF reaches the mid‑20% range, patients experience a near abolition of VOCs.” – Iain Fraser, SVP Early Development .
Regulatory plan: “We…plan to engage with the agency on the use of fetal hemoglobin as a surrogate endpoint…for our next study…” – Alex Sapir .
Enrollment and compliance: “10 patients…enrolled to date come from both South Africa and the U.S.…adherence…north of 90%” (AiCure tool) – Alex Sapir .
DSMB and 20 mg cohort: Review triggers after the 8th patient completes 30 days; progression decision is primarily safety/tolerability‑based – Alex Sapir and Iain Fraser .

Q&A Highlights

FDA engagement and endpoints: Company intends to consult FDA on HbF as a surrogate endpoint; acknowledges no prior approvals solely on HbF but cites converging lines of evidence (genetic/epidemiologic/gene therapy) .
Enrollment population and Oxbryta: Post‑withdrawal, eligibility effectively eased; sites in U.S. and South Africa; patient adherence “north of 90%” via AiCure .
DSMB and dose escalation: DMC meeting scheduled once criteria met; primary focus safety/tolerability to open 20 mg cohort .
Mid‑year readout scope: Expect HbF levels, hematologic biomarkers (e.g., reticulocytes, RDW), safety; VOC data will be descriptive given 3‑month dosing .
Spending/Runway: Restructuring completed; 2025 cash burn ~$55–$65M; runway into at least 2027 .

Estimates Context

Wall Street consensus (S&P Global) for Q4 2024 revenue and EPS was not retrievable today due to data access limits; as a result, vs‑estimate comparisons are unavailable and will be updated when SPGI access is restored. Management does not provide product revenue guidance; near‑term P&L is driven by OpEx and collaboration accounting .

Key Takeaways for Investors

Two clear catalysts: pociredir 12 mg cohort data in mid‑2025 and 20 mg cohort by YE‑2025; positive HbF and safety signals could be meaningful stock drivers in a post‑Oxbryta oral‑therapy vacuum .
Execution improving: Sequential declines in R&D and G&A reflect focus and cost control; net loss narrowed y/y; FY25 burn firmly bracketed, extending runway into 2027 .
Regulatory de‑risking path: Planned discussions with FDA on HbF as a surrogate endpoint could clarify registrational strategy; watch for feedback later in 2025 .
Enrollment tailwinds: Oxbryta withdrawal and allowance of concomitant crizanlizumab/L‑glutamine may aid recruitment; adherence tools (AiCure) support data quality .
Risk balance: No recurring revenue and dependency on trial outcomes elevate binary risk; DMC safety read to open the 20 mg cohort is a gating event .
Portfolio focus: Losmapimod exit concentrates resources on hematology; inherited aplastic anemia IND planned for 4Q25 offers medium‑term pipeline breadth .
Trading setup: With defined mid‑2025/YE‑2025 data windows and disciplined burn, the name screens as a catalyst‑driven biotech into readouts; valuation sensitivity will hinge on HbF magnitude/safety profile and regulatory receptivity to surrogate endpoints .

Appendices

Selected operational KPIs

KPI	Q2 2024	Q3 2024	Q4 2024
Pociredir PIONEER status	Phase 1b ongoing; 12 mg then 20 mg cohorts defined	Progressing; 2025 data plan reiterated	10 patients enrolled in 12 mg; 12 mg mid‑2025, 20 mg YE‑2025 readouts
DMC/20 mg progression	N/A	N/A	DMC review after 8th patient completes 30 days; focus on safety/tolerability
Cash runway	Into 2027 (as of 6/30/24)	Into at least 2027 (as of 9/30/24)	Into at least 2027 (as of 12/31/24)
2025 cash burn guide	N/A	$55–$65M	$55–$65M (midpoint ~$60M)

All figures are GAAP unless noted. Source documents: Q4 2024 8‑K/press release and earnings call transcript; prior quarters’ 8‑Ks and Q3 call cited throughout .

Fulcrum Therapeutics, Inc. (FULC)·Q4 2024 Earnings Summary