Executive Summary

Q1 2025 was execution-focused: Neurogene reiterated timelines to deliver a registrational trial plan update for NGN‑401 in 1H 2025 and an updated Phase 1/2 data readout in 2H 2025, while emphasizing continued FDA collaboration and EXACT platform differentiation .
Operating spend rose as programs advanced: R&D increased to $17.8M (+31% y/y), G&A to $8.2M (+56% y/y), widening net loss to $22.6M vs. $16.9M a year ago; drivers were Rett clinical costs, CMC scale-up, and headcount .
Balance sheet remains strong: Cash, cash equivalents and short-term investments were $292.6M (runway into 2H 2027), supporting registrational readiness and manufacturing scale-up .
Near-term stock catalysts: (1) Registrational trial design update in 1H 2025 and (2) additional Phase 1/2 efficacy/safety data in 2H 2025 for NGN‑401 in Rett syndrome .

What Went Well and What Went Wrong

What Went Well

Clear regulatory and clinical timelines: “We have made significant progress in planning for our future registrational trial with NGN‑401… and expect to provide an update… during the first half of this year… [and] look forward to sharing updated interim clinical data… in the second half of 2025.” — CEO Rachel McMinn .
EXACT platform validation: Management highlighted a peer-reviewed Science Translational Medicine publication demonstrating EXACT’s ability to regulate transgene expression in nonclinical models, a core differentiator for NGN‑401’s therapeutic window in Rett .
Liquidity and runway: $292.6M of cash, cash equivalents and short-term investments with runway into 2H 2027 to fund registrational activities and CMC scale-up for NGN‑401 .

What Went Wrong

Wider losses as programs scale: Net loss increased to $22.6M (from $16.9M y/y) on higher Rett trial costs and employee-related expenses; R&D rose to $17.8M and G&A to $8.2M .
No revenue base: The company continues to operate pre-commercial with no product revenue; strategy requires sustained external capital and careful expense pacing .
Legacy safety overhang (prior quarter): After a high-dose (3E15 vg) SAE and death in Nov 2024, the program removed that dose; while the FDA allowed the 1E15 vg dose to proceed, investor focus remains on long-term safety at registrational scale .

Financial Results

Key P&L and liquidity metrics (USD Millions unless noted):

Metric	Q3 2024	Q4 2024	Q1 2025
R&D Expense	$16.285	$15.3	$17.760
G&A Expense	$5.895	$6.2	$8.159
Net Loss	$20.217	$19.5	$22.647
Net Loss per Share (Basic & Diluted)	$(1.19)	N/A	$(1.08)
Cash, Cash Equivalents & (Short‑Term) Investments (Period End)	$139.0	$312.4	$292.6

Year-over-year compares (3 months ended March 31):

Metric	Q1 2024	Q1 2025	Δ y/y
R&D Expense	$13.541	$17.760	+$4.219
G&A Expense	$5.238	$8.159	+$2.921
Net Loss	$16.921	$22.647	+$5.726
Net Loss per Share (Basic & Diluted)	$(1.00)	$(1.08)	$(0.08)

Estimates vs. actual (S&P Global consensus):

Coverage: No S&P Global consensus for Q1 2025 EPS or revenue was available at time of analysis (no values returned).
Actuals: EPS $(1.08) ; product revenue not reported (pre-commercial) .

Notes:

Neurogene operates as a single segment clinical-stage biotech; segment breakdown not applicable .
Drivers of expense growth: Rett trial costs, CMC scale-up, and headcount increases (R&D, G&A) .

Guidance Changes

Metric	Period	Previous Guidance	Current Guidance	Change
Cash Runway	Multi‑year	Into 2H 2027	Into 2H 2027	Maintained
Registrational Trial Plan Update (NGN‑401)	2025	Update in 1H 2025	On track for 1H 2025	Maintained
Additional Interim NGN‑401 Phase 1/2 Data	2025	2H 2025	2H 2025	Maintained

Earnings Call Themes & Trends

No Q1 2025 earnings call transcript was available; themes below reflect the past two quarters and Q1 2025 disclosures.

Topic	Previous Mentions (Q3 2024, Q4 2024)	Current Period (Q1 2025)	Trend
Registrational Pathway	FDA alignment on CMC scale-up; plan to provide trial design update in 1H 2025	On track for registrational trial plan update in 1H 2025	Steady progress
Safety/HLH Risk Management	SAE/death at 3E15 vg (Nov 2024); 3E15 vg removed; FDA allowed 1E15 vg to proceed	Focus on 1E15 vg; continued collaboration with FDA emphasized	Stabilizing at 1E15 vg
EXACT Technology Differentiation	Highlighted as addressing therapeutic window; interim data supportive	Peer‑reviewed publication in STM strengthens platform narrative	Positive validation
Manufacturing/CMC	In-house CGMP facility supports pivotal activities; CMC alignment with FDA	Runway supports CMC scale-up for registrational activities	Execution capacity intact
Liquidity/Runway	Private placement extended runway into 2H 2027	Cash/short-term investments $292.6M; runway into 2H 2027	Sustained funding base

Management Commentary

“We have made significant progress in planning for our future registrational trial with NGN‑401… and expect to provide an update… during the first half of this year… We also advanced the Phase 1/2 trial of NGN‑401, and we look forward to sharing updated interim clinical data… in the second half of 2025.” — Rachel McMinn, Ph.D., CEO .
Q1 spend drivers and liquidity: R&D up on Rett clinical trial costs and headcount; G&A up on headcount and corporate expenses; runway into 2H 2027 .

Q&A Highlights

No Q1 2025 earnings call transcript was available. Investor-relevant clarifications came via filings/press releases:
- High-dose 3E15 vg removed after SAE; FDA allowed continuation at 1E15 vg (prior quarter) .
- EXACT platform peer-reviewed validation and continued FDA dialogue highlighted .

Estimates Context

S&P Global consensus for Q1 2025 EPS and revenue was not available (no estimates returned). As such, no beat/miss assessment can be made for the quarter.
Given pre-commercial status and limited analyst coverage, estimate formation may remain sparse until the registrational program (Embolden) parameters are finalized and closer to data/approval timing .

Key Takeaways for Investors

Timeline intact: Registrational trial plan update in 1H 2025 and additional Phase 1/2 data in 2H 2025 are the next major catalysts for NGN‑401 .
Platform differentiation: EXACT’s peer‑reviewed data strengthens the thesis that controlled MeCP2 expression can widen the therapeutic window, a central need in Rett gene therapy .
Expense cadence: R&D and G&A rose with trial progress, CMC activities, and headcount; expect sustained elevated spend as programs advance .
Liquidity supports execution: $292.6M cash/short‑term investments and runway into 2H 2027 provide capacity to move into registrational activities and scale manufacturing .
Safety framing: The prior high‑dose SAE was addressed by removing 3E15 vg; ongoing focus is on 1E15 vg with continued FDA collaboration (risk remains a monitoring focal point) .
Stock setup: Near-term regulatory clarity (1H 2025) and clinical update (2H 2025) are likely stock movers; progress toward a registrational path and robust safety/efficacy profile will be key to sentiment .

Sources: Q1 2025 8‑K press release and filing ; Q1 2025 10‑Q financials and MD&A ; Q4 2024 8‑K press release ; Q3 2024 8‑K press release and financial tables .

Neurogene Inc. (NGNE)·Q1 2025 Earnings Summary