Executive Summary

Q4 2024 headline: minimal collaboration revenue (~$0.001M) and GAAP EPS of -$0.90, missing third-party consensus EPS of -$0.80; revenue was far below a ~$2.28M consensus, reflecting limited collaboration activity in the quarter .
Strategic pivot extended cash runway to “into 2028” (from “at least into H1 2027”), driven by pipeline prioritization on 4D-150 (wet AMD, DME) and 4D-710 (CF) while pausing or terminating non-core programs .
Clinical execution remained a bright spot: 4D-150 showed robust and durable activity with favorable tolerability across wet AMD (PRISM) and DME (SPECTRA); FDA aligned on a single registrational trial path for DME in combination with wet AMD Phase 3 datasets .
2025 catalysts: 4FRONT-1 Phase 3 initiation (enrollment began March 2025) and 4FRONT-2 expected in Q3 2025; topline data from both trials expected in H2 2027—key stock drivers alongside ongoing DME Phase 3 planning .

What Went Well and What Went Wrong

What Went Well
- 4D-150 continued to demonstrate strong durability and reduced injection burden in wet AMD (e.g., 83–94% reduction, injection-free rates up to 80% in recently diagnosed subgroup) with favorable tolerability across up to three years of follow-up .
- DME progress: 32-week SPECTRA Part 1 data showed +8.4 letter BCVA gain, -194 µm CST reduction, and 86% reduction in injection burden at 3E10 vg/eye dose with no intraocular inflammation; FDA alignment on a single Phase 3 trial basis for BLA when combined with wet AMD Phase 3 .
- Runway extension into 2028 from focused resource allocation on core programs (4D-150, 4D-710) reduces near-term financing risk as pivotal programs ramp .
What Went Wrong
- Q4 financials missed third-party EPS consensus (-$0.90 vs -$0.80) and revenue was effectively de minimis vs ~$2.28M expectation—underscoring inherent volatility of collaboration revenue and lack of commercial product revenues .
- Operating intensity rose during 2024 with R&D of $141.3M and G&A of $46.6M for the year (vs $97.1M and $36.5M in 2023), reflecting late-stage development investment, which weighs on losses absent material revenue .
- Several non-core/early programs were paused/terminated (e.g., 4D-110, 4D-125; pausing 4D-175, 4D-725, 4D-310 pending financing/partners), narrowing optionality and signaling capital discipline but also reducing broader pipeline near-term upside .

Financial Results

Quarterly results vs prior quarters and consensus

Metric	Q2 2024	Q3 2024	Q4 2024
Revenue ($USD Thousands)	$5	$3	$1
GAAP EPS ($)	-$0.63	-$0.79	-$0.90
EPS Consensus ($)	N/A	N/A	-$0.80
Revenue Consensus ($USD Millions)	N/A	N/A	$2.28

Annual context (FY2024 vs FY2023)

Metric	FY 2023	FY 2024
Collaboration & License Revenue ($USD Thousands)	$20,723	$37
R&D Expense ($USD Thousands)	$97,096	$141,299
G&A Expense ($USD Thousands)	$36,494	$46,579
Total Operating Expenses ($USD Thousands)	$133,590	$187,878
Net Loss ($USD Thousands)	$(100,837)	$(160,868)
Cash, Cash Equivalents & Marketable Securities ($USD Thousands)	$299,186	$505,460

KPIs and clinical execution (selected)

Wet AMD (PRISM) at 3E10 vg/eye: broad population 83% injection burden reduction; recently diagnosed subgroup 94% injection burden reduction; injection-free up to 80%; favorable tolerability across up to 3 years .
DME (SPECTRA Part 1, 3E10 vg/eye): +8.4 letters BCVA; -194 µm CST; 86% injection burden reduction; no IOI observed .

Guidance Changes

Metric	Period	Previous Guidance	Current Guidance	Change
Cash Runway	Corporate	“At least into H1 2027” (Q2/Q3 2024)	“Into 2028” (Feb 28, 2025)	Raised runway
4D-150 (wet AMD) Phase 3 – 4FRONT-1 Start	Program Timing	“Q1 2025” (Q3 2024)	March 2025 (executing; enrolled first patients by May)	Affirmed/initiated
4D-150 (wet AMD) Phase 3 – 4FRONT-2 Start	Program Timing	Not previously dated beyond “global program”	Q3 2025	Set timing
4D-150 (DME) Pivotal Path	Regulatory	Part 2 of SPECTRA contemplated	FDA aligned: single Phase 3 (SPECTRA Part 2 no longer needed) acceptable for BLA when combined with wet AMD Phase 3	Streamlined path
4D-150 Wet AMD Topline (Phase 3)	Milestone	Not previously specified	H2 2027 for both 4FRONT-1 and 4FRONT-2	Set milestone

Note: No quantitative 2025 OpEx, OI&E, margin, or tax guidance disclosed; company provides runway and program milestones .

Earnings Call Themes & Trends

(Transcript not publicly available at time of review; themes reflect company disclosures across quarters.)

Topic	Previous Mentions (Q2 & Q3 2024)	Current Period (Q4 2024)	Trend
4D-150 wet AMD efficacy/tolerability	Interim PRISM data: 89% injection reduction at 24w; safety favorable; 4FRONT Phase 3 design previewed	52-week/interim data reinforced 83–94% reduction with durable control and favorable IOI profile	Strengthening efficacy/tolerability narrative
DME (SPECTRA) clinical progress	SPECTRA Part 1 interim data expected late 2024/early 2025	32-week topline: +8.4 letters BCVA, -194 µm CST, 86% injection reduction; no IOI	Positive activity; clean safety
Regulatory path (DME)	Planning/updates pending	FDA alignment: single Phase 3 acceptable for BLA with wet AMD Ph3 data	De-risked pathway
Phase 3 initiation (wet AMD)	4FRONT-1 “Q1 2025”	4FRONT-1 expected March 2025; 4FRONT-2 in Q3 2025	Executing to plan
Pipeline focus/cash discipline	Robust org build; broad pipeline	Strategic focus on 4D-150 & 4D-710; pausing/terminations extend runway into 2028	Sharpened focus; extended runway
Safety (IOI)	Low-grade IOI rates; favorable comparison to anti-VEGF agents	Up to 3 years follow-up at 3E10 vg/eye with highest IOI noted as 1+ vitreous cells in 2.8% of patients	Consistently favorable

Management Commentary

“2024 was a landmark year for 4DMT, driven by groundbreaking clinical advancements toward Phase 3 trials... 4D-150's potential to become the first backbone therapy for retinal vascular diseases...” — David Kirn, M.D., Co-founder & CEO .
“Presented positive 52-week results... 83% reduction in injection burden [broad]... 94% [recently diagnosed]... 4D-150 continues to be well tolerated during up to three years of follow-up...” .
“FDA aligned with proposed single Phase 3 clinical trial being acceptable for the basis of a BLA submission for 4D-150 in DME... SPECTRA Part 2 no longer needed...” .
“Strategically focused pipeline... As a result, cash runway extended into 2028...” .

Q&A Highlights

The company scheduled its earnings call for Feb 28, 2025 at 4:00 PM ET; a public transcript was not available at the time of review, so Q&A details could not be assessed .

Estimates Context

S&P Global consensus was unavailable via our feed at the time of analysis. Third-party data indicate Q4 2024 EPS consensus of -$0.80 vs actual -$0.90 (miss by $0.10); revenue consensus ~$2.28M vs actual ~$0.001M (effectively nil collaboration revenue) .
Given the strategic shift (pipeline focus) and minimal collaboration revenue, near-term models likely center on OpEx trajectory, cash runway, and clinical catalysts rather than top-line contributions; revisions may reflect reduced collaboration revenue assumptions and timing of pivotal trial costs .

Financial Tables: Estimate vs Actual (Q4 2024)

Metric	Consensus	Actual	Surprise
GAAP EPS ($)	-$0.80	-$0.90	-$0.10
Revenue ($USD Millions)	$2.28	$0.001	-$2.279 (≈-99.96%)

Key Takeaways for Investors

The story is firmly clinical: durable efficacy and clean safety for 4D-150 in wet AMD and DME, plus streamlined DME registration path, are the core valuation drivers .
Runway into 2028 reduces near-term financing overhang as pivotal development ramps; focus on 4D-150/4D-710 should improve capital efficiency .
Near-term financials will remain noisy given minimal collaboration revenue; monitor R&D cadence vs milestones and any partnering to offset OpEx .
Phase 3 milestones (4FRONT-1/2 progress, site activation, enrollment velocity) and DME Phase 3 design finalization are the next catalysts likely to move the stock .
Watch for additional durability updates (PRISM 2-year/18-month datasets) in 2025 to reinforce the long-acting “backbone therapy” narrative .
Competitive lens: if non-inferiority on BCVA with major injection-burden reduction holds in Phase 3, 4D-150 could reshape anti-VEGF treatment paradigms; pricing flexibility cited via low COGS may support adoption .
Risk skew: clinical, regulatory, and execution risks remain; pausing non-core programs concentrates risk in 4D-150/4D-710 but clarifies the investment case .

References:

FY/Q4 2024 8-K and press release: ; -,
Q3 2024 press release (financials/ops): -
Q2 2024 press release (financials/ops): -
Dec 16, 2024 R100/4D-150 preclinical publication PR: -
Jan 10, 2025 DME SPECTRA interim PR: -
Third-party earnings/consensus snapshots:
Q1 2025 update on Phase 3 enrollment:

4D Molecular Therapeutics, Inc. (FDMT)·Q4 2024 Earnings Summary