Executive Summary

Q4 2024: Neurogene reported net loss of $19.5M, R&D of $15.3M, G&A of $6.2M, and ended FY with $312.4M in cash, cash equivalents and marketable securities; management reiterated cash runway into 2H 2027 .
Clinical update remains constructive: low-dose NGN-401 (1E15 vg) showed durable, concordant efficacy across Rett domains; EMA granted PRIME designation, enhancing regulatory support in Europe .
Safety surprise: a treatment-related SAE (hyperinflammatory syndrome) occurred in a high-dose (3E15 vg) participant; FDA allowed trial continuation at 1E15 vg, while high-dose cohorts were paused—net effect is program focus on low-dose with maintained regulatory momentum .
Guidance maintained: registrational trial plans update in 1H 2025 and additional interim Phase 1/2 data in 2H 2025; added EMA PRIME and confirmed protocol change to low-dose-only .
Street estimates: S&P Global consensus data were not available for NGNE Q4 2024; no earnings-call transcript was found. We benchmark results vs prior quarters and prior-year given lack of consensus [GetEstimates: Q4 2024 empty].

What Went Well and What Went Wrong

What Went Well

Low-dose NGN-401 efficacy strengthened: all four pediatric low-dose participants achieved “much improved” CGI-I and 28–52% reductions in RSBQ, with clinically meaningful gains in hand function, gross motor, and communication beyond natural history expectations .
Regulatory tailwinds: EMA PRIME designation for NGN-401 improves access to early dialogue and potential accelerated pathways; FDA START participation and RMAT designation previously secured, with alignment on potency assay and CMC scale-up .
Funding visibility: $312.4M year-end cash and reiterated runway into 2H 2027 following the November 2024 $200M private placement, supporting registrational trial readiness and manufacturing scale-up .

Management quotes:

“We remain on track to provide an update on the registrational trial plans in the first half of 2025… [and] plan to share additional interim clinical data… including from our 11 years and older cohort.” — Rachel McMinn, Ph.D., CEO .
“The favorable safety and efficacy data for NGN-401 at the 1E15 vg dose demonstrate its potential to have a meaningful impact on the disease course of Rett syndrome.” — Rachel McMinn, Ph.D. .

What Went Wrong

Safety at high dose: a serious hyperinflammatory syndrome in a recent high-dose (3E15 vg) participant led to pausing and discontinuation of further high-dose enrollment, concentrating development at low-dose only .
Rising OpEx: R&D increased vs prior year given trial costs and preclinical pipeline spend; G&A rose due to headcount and corporate costs tied to public company requirements .
NGN-101 program halted: decision not to move forward with CLN5 Batten disease program following RMAT denial; management evaluating options, which may limit near-term multi-asset optionality .

Financial Results

Metric ($USD Millions)	Q4 2023	Q3 2024	Q4 2024
Net Loss	$2.4 net income	$(20.2)	$(19.5)
R&D Expenses	$12.2	$16.3	$15.3
G&A Expenses	$2.5	$5.9	$6.2

Notes:

Revenue/EPS: Q4 press release did not disclose revenue or EPS; in Q3 2024, licensing revenue was $0 (quarter) and $0.925M (nine months), and EPS was $(1.19) per share for Q3 2024 . S&P Global consensus estimates for Q4 2024 were unavailable [GetEstimates: Q4 2024 empty].
Runway/Cash: Year-end cash, cash equivalents and marketable securities were $312.4M; management reiterated runway into 2H 2027 .

Guidance Changes

Metric	Period	Previous Guidance	Current Guidance	Change
Registrational trial plans update (NGN-401)	1H 2025	Update in 1H 2025	Update in 1H 2025	Maintained
Additional interim Phase 1/2 data	2H 2025	Additional data in 2H 2025	Additional data in 2H 2025 (includes >11 yrs cohort)	Maintained/Expanded
Dosing plan	Ongoing	1E15 vg ongoing; 3E15 vg paused post SAE	Proceed at 1E15 vg only; no further 3E15 vg enrollment	Lowered (high dose discontinued)
EMA PRIME status	2025	N/A	PRIME designation received	Raised (new positive)
Cash runway	Through 2H 2027	2H 2027	2H 2027	Maintained

Earnings Call Themes & Trends

Note: No earnings-call transcript found for Q4 2024.

Topic	Previous Mentions (Q-2 and Q-1)	Current Period (Q4 2024)	Trend
Efficacy in Rett (low-dose)	Interim data: CGI-I “much improved” in all low-dose participants; RSBQ −28% to −52%; functional gains beyond natural history	Durable improvements reaffirmed; expanded age cohort; planned additional data 2H 2025	Strengthening at 1E15 vg
Safety profile	Low-dose: favorable safety; high-dose: Grade 2–3 transaminase elevations resolved with steroids	High-dose SAE (hyperinflammatory syndrome); program now focused on low-dose with FDA concurrence	Risk management; dose optimization
Regulatory interactions	START and RMAT, potency assay & CMC scale-up alignment; registrational planning	EMA PRIME added; timing for registrational trial update maintained	Improving optionality
Manufacturing	In-house cGMP capabilities highlighted	Continued emphasis on scale-up readiness for registrational activities	Consistent execution
Funding	$200M PIPE extends runway to 2H 2027	Year-end cash $312.4M; runway reiterated	Stable capital position

Management Commentary

“We believe 2024 was a year of significant progress… NGN-401 was generally well-tolerated at the 1E15 vg dose… we remain on track to provide an update on the registrational trial plans in the first half of 2025.” — Rachel McMinn, Ph.D., CEO .
On safety and dosing: “The FDA… allowed Neurogene to proceed with the Phase 1/2 trial using the 1E15 vg dose (low-dose cohort)… [We] do not plan to enroll any further participants at the 3E15 vg dose level.” .

Q&A Highlights

No Q4 2024 earnings call transcript available. Notable clarifications:

Regulatory: FDA allowed continued dosing at 1E15 vg after review of safety data; high-dose enrollment discontinued; aligns program focus on the clinically active and tolerable low-dose .
Clinical: Prior interim data describe cross-scale efficacy concordance and autonomic improvements (sleep efficiency improved to ~90–>95% in participants with baseline deficits) .

Estimates Context

Wall Street consensus (S&P Global) for Q4 2024 EPS and revenue was unavailable; comparison vs estimates cannot be provided. Management did not disclose Q4 EPS or revenue in the press release. We benchmarked performance vs prior quarter and prior year instead [GetEstimates: Q4 2024 empty] .

KPIs (Clinical Efficacy – Low-Dose Pediatric Cohort)

KPI	LD:1	LD:2	LD:3	LD:4
CGI-I improvement (points)	2	2	2	2
RSBQ change from baseline (%)	−28%	−52%	−29%	−28%
Functional gains vs natural history	Yes (multi-domain)	Yes (multi-domain)	Yes	Early hand function gains

Financial and Operating Drivers (Why)

R&D up vs prior year due to NGN-401 Phase 1/2 clinical trial costs, increased headcount, and preclinical pipeline investment; Q4 R&D $15.3M vs $12.2M PY .
G&A increased with scaling public-company infrastructure, professional fees, and office-related costs; Q4 G&A $6.2M vs $2.5M PY .
Net loss narrowed Q/Q (Q4 $19.5M vs Q3 $20.2M) as R&D moderated quarter-over-quarter while G&A slightly increased; FY net loss rose due to full-year operating scale-up and absence of 2023 one-time bargain purchase gain .
Clinical program focus: shift to low-dose post SAE concentrates resources where benefit-risk is favorable, supports registrational planning efficiency .

Key Takeaways for Investors

Low-dose (1E15 vg) NGN-401 remains the core path: reproducible efficacy across Rett domains and supportive safety profile underpin registrational trial planning in 1H 2025—near-term catalyst path is intact .
Safety reset at high dose reduces risk but also removes a dose-scaling option; program strategy now prioritizes low-dose durability and breadth of response, which has been clinically demonstrated to date .
PRIME + START + RMAT give multi-region regulatory leverage; potency assay and CMC alignment de-risk registrational readiness and potential review timelines .
Cash runway to 2H 2027 supports execution through pivotal planning and ongoing data updates; reduces financing overhang in the near term .
Batten program discontinuation narrows pipeline, but resource focus likely accelerates NGN-401; medium-term pipeline expansion remains planned (one program into clinic in 2025) .
Watch for 1H 2025 registrational trial design specifics (population scope, endpoints, comparator strategy), and 2H 2025 interim updates, including adolescent/adult cohort signals—key stock catalysts .
No Street consensus available; trade the narrative on regulatory milestones and clinical durability at low-dose; downside risk remains tied to safety events, enrollment cadence, and regulatory feedback [GetEstimates: Q4 2024 empty] .

Source Documents Read (Step 1 Confirmation)

Q4 2024 8-K and press release (full): financial results and corporate updates .
Related corporate presentation (March 2025 Exhibit): background, pipeline, clinical detail .
Prior quarter Q3 2024 8-K and press release with detailed financial tables .
Interim efficacy data 8-K (Nov 11, 2024) and webcast slides (study update) –.
Safety update 8-K (Nov 18, 2024) –.
Q3 2024 10-Q for financial detail and drivers –.

S&P Global estimates disclaimer: S&P Global consensus data for Q4 2024 were not available; thus, no estimates are shown, and no beat/miss analysis versus Street is provided [GetEstimates: Q4 2024 empty].

Neurogene Inc. (NGNE)·Q4 2024 Earnings Summary