Executive Summary

Q4 results reflect disciplined cost control and program execution: net loss improved to $12.7M ($0.20 EPS) vs $19.3M ($0.31) in Q3 and $16.8M ($0.30) in Q4’23, driven by lower R&D and G&A .
Cash runway extended into 1Q 2027 following a restructuring and shift to an outsourced analytical testing model, reducing annual operating costs by ~$9–$11M; runway previously guided to end of Q2 2026 .
Clinical biomarkers continue to validate PBFT02’s mechanism: CSF PGRN rose from <3 ng/mL at baseline to 13–27 ng/mL at 6 months and 22–34 ng/mL at 12 months; plasma NfL declined ~13% at 12 months vs +29% natural history, supporting potential disease-modifying effect .
Milestone timing adjusted: 12‑month Dose 1 readout shifted from 1H 2025 to 2H 2025; pivotal/regulatory feedback moved from 2H 2025 to 1H 2026 to accommodate Dose 2 exploration—near-term stock catalysts center on biomarker updates and regulatory clarity .

What Went Well and What Went Wrong

What Went Well

Robust, durable CNS target engagement: PBFT02 increased CSF PGRN in all treated FTD‑GRN patients with durability to 18 months in the longest follow-up, supporting a potential best-in-class profile (“robust, durable progranulin expression”) .
Biomarker trends encouraging: plasma NfL declined ~13% at 12 months (n=2) vs +29% expected from natural history, an early sign consistent with slowing neurodegeneration .
Capital efficiency gains and manufacturing readiness: runway extended to 1Q 2027 via outsourcing/testing model; high-productivity suspension manufacturing process established to support late-stage development (“well-positioned for late-stage development”) .

Quote: “We are pleased to report strong performance in 2024… well-positioned for late-stage development” — Will Chou, M.D., CEO .

What Went Wrong

Milestone delays: 12‑month Dose 1 data shifted to 2H 2025 (from 1H 2025) and pivotal/regulatory feedback to 1H 2026 (from 2H 2025), extending the registrational timeline .
Safety SAEs in early dosing required protocol changes: initial patient experienced venous sinus thrombosis and hepatotoxicity; later patient had asymptomatic VST—managed via revised immunosuppression (steroids), but underscores safety vigilance in CNS AAV programs .
Balance sheet dilution and lower assets versus prior year (end-2024 assets $102.4M vs $150.5M), reflecting cash burn despite cost actions .

Financial Results

P&L and Cash Metrics (Quarterly)

Metric	Q2 2024	Q3 2024	Q4 2024
R&D Expense ($USD Millions)	$10.4	$8.7	$9.6
G&A Expense ($USD Millions)	$6.5	$7.3	$4.7
Net Loss ($USD Millions)	$16.0	$19.3	$12.7
EPS (Basic & Diluted, $)	$(0.26)	$(0.31)	$(0.20)
Cash, Cash Equivalents & Marketable Securities ($USD Millions, end of period)	$91.8	$84.8	$76.8

YoY context (Q4): R&D $9.6M vs $12.1M; G&A $4.7M vs $6.3M; net loss $12.7M ($0.20) vs $16.8M ($0.30) in Q4’23 .

KPIs (Clinical Biomarkers)

KPI	Q2 2024	Q3 2024	Q4 2024
CSF PGRN at 6 months (ng/mL)	21.7–27.3 (n=2)	Sustained elevation; up to 10x from baseline; plateau by ~6 months	13–27 (n=4)
CSF PGRN at 12 months (ng/mL)	N/A reported	Maintained elevation; example patient reached 34.2	22–34 (n=2)
Plasma NfL 12‑month change vs baseline	N/A reported	N/A reported	~−13% (n=2) vs +29% natural history
Plasma PGRN levels	Remained below healthy reference up to 6 months	Remained below healthy reference up to 12 months	Remained below healthy reference

Note: “N/A reported” reflects absence of a disclosed figure in the cited quarter; ranges and examples are per disclosures.

Guidance Changes

Metric	Period	Previous Guidance	Current Guidance	Change
Cash runway	Corporate	Fund operations to end of Q2 2026	Fund operations into 1Q 2027	Raised runway
12‑month Dose 1 data (FTD‑GRN)	Readout timing	1H 2025	2H 2025	Delayed
Interim Dose 2 data (FTD‑GRN)	Readout timing	Not previously specified	2H 2025	New timing
Regulatory feedback on pivotal/registrational trial (FTD‑GRN)	Regulatory	2H 2025	1H 2026	Delayed
Initiate dosing (FTD‑C9orf72)	Clinical start	1H 2025	1H 2025 reiterated	Maintained

Drivers: Dose 2 introduction (50% of Dose 1) to support registrational dialogue, and operating model changes (outsourced analytics) underpin timeline and runway adjustments .

Earnings Call Themes & Trends

No Q4 2024 earnings call transcript was available in the document set; themes below reflect disclosed press releases and presentations.

Topic	Previous Mentions (Q2 & Q3)	Current Period (Q4)	Trend
R&D execution and dosing	IDMC clearance; enrollment of Cohort 2 (FTD‑GRN) and plan to start FTD‑C9orf72 in 1H 2025	First FTD‑GRN patient enrolled for Dose 2; plan to initiate FTD‑C9orf72 dosing 1H 2025	Continued execution; broadened to Dose 2
Manufacturing readiness	In‑house process development progress	Suspension-based, GMP‑ready process completed; potency assay alignment with FDA	Advanced to late‑stage readiness
Financial discipline	Runway guided to end of Q2 2026	Runway extended to 1Q 2027 via restructuring/outsourcing	Improved liquidity horizon
Biomarkers (CSF PGRN, plasma NfL)	Early Cohort 1 elevations at 6–12 months; plasma PGRN remained below normal	Robust, durable CSF PGRN; −13% plasma NfL vs +29% natural history	Strengthening biomarker dataset
Regulatory path	ALS pathway feedback targeted 2H 2024; pivotal feedback 2H 2025	Pivotal/registrational feedback targeted 1H 2026	Timeline extended

Management Commentary

“We are pleased to report strong performance in 2024… and are well‑positioned for late‑stage development.” — Will Chou, M.D., President & CEO .
“Dose 1 PBFT02 consistently increased CSF PGRN… translated to early signals of improvement in a disease progression biomarker when compared to published natural history data.” — Will Chou, M.D. .
“We will transition to an outsourced analytical testing model and have restructured our organization… we expect existing cash resources will be sufficient to fund operations into the first quarter of 2027.” — Will Chou, M.D. .

Q&A Highlights

No Q4 2024 earnings call transcript was available; therefore, Q&A highlights and any guidance clarifications from a live call are not accessible in the current source set [ListDocuments returned none for earnings-call-transcript].

Estimates Context

Wall Street consensus estimates via S&P Global were unavailable at the time of retrieval (tool limit exceeded). As a result, we cannot provide an EPS or revenue beat/miss assessment for Q4 2024 based on SPGI consensus. We attempted to fetch “Primary EPS Consensus Mean” and “Revenue Consensus Mean” for Q2–Q4 2024 but did not receive values due to a daily request limit exceeded. Estimates comparison is therefore not possible at this time using S&P Global data.

Key Takeaways for Investors

Program validation continues via CNS biomarker strength: durable CSF PGRN elevations and plasma NfL reductions vs natural history bolster mechanistic confidence heading into Dose 2 exploration and C9orf72 expansion .
Extended cash runway into 1Q 2027 reduces near‑term financing risk and supports late‑stage enabling activities—positive for execution continuity amid biomarker and regulatory milestones .
Timeline shifts (data readout to 2H 2025; pivotal feedback to 1H 2026) temper near‑term registrational visibility; monitor for interim Dose 2 biomarker signals to confirm dose strategy .
Safety profile manageable under revised immunosuppression; continued vigilance warranted in AAV CNS programs (VST management, hepatotoxicity surveillance) .
Manufacturing and analytical readiness (suspension process, potency assay alignment) de‑risk scale‑up and CMC for advanced development phases .
Trading implications: near‑term catalysts include 2H 2025 biomarker updates and any regulatory feedback; in absence of revenue/earnings beats, stock moves likely tied to clinical/regulatory narrative and liquidity trajectory .
Medium‑term thesis: a one‑time therapy with best‑in‑class PGRN profile could address high unmet need in FTD‑GRN/C9orf72; maintaining biomarker and safety momentum while securing a registrational pathway is key to value inflection .

Appendix: Prior Quarter Highlights (for trend)

Q3 2024: Net loss $19.3M ($0.31 EPS); cash & securities $84.8M; Cohort 2 (FTD‑GRN) enrollment and dosing; maintained CSF PGRN elevations up to 12 months; runway to end of Q2 2026 .
Q2 2024: Net loss $16.0M ($0.26 EPS); cash & securities $91.8M; FDA alignment to expand upliFT‑D to FTD‑C9orf72; early CSF PGRN increases at 6 months; pediatric program out‑licensing .

Citations:
Q4 2024 press release and 8‑K exhibit:
Q3 2024 press release and financial tables:
Q2 2024 press release and financial tables:
January 10, 2025 update/restructuring 8‑K:

Passage BIO, Inc. (PASG)·Q4 2024 Earnings Summary