Executive Summary

Neurogene advanced NGN-401 meaningfully: first patient dosed in the Embolden registrational trial; 12 of 13 sites initiated; enrollment expected to complete in 3–6 months .
Positive interim pediatric Phase 1/2 data showed durability and multidomain gains with an aggregate 35 developmental milestones/skills across eight participants; safety remained generally well tolerated at 1E15 vg with no evidence of HLH .
Cash runway extended to fund planned operations through Q1 2028, up from “early 2028” in Q2 and “2H 2027” in Q1, improving financing visibility .
Street consensus EPS and revenue estimates for Q3 2025 were unavailable via S&P Global; focus remains on clinical/regulatory catalysts rather than near-term financial beats/misses .
Near-term stock catalysts: Embolden enrollment completion in 3–6 months, continued trial site conversion, and 2026 Phase 1/2 data update; ESGCT data highlighting ICV delivery superiority vs IT-L supports best-in-class narrative .

What Went Well and What Went Wrong

What Went Well

“We significantly advanced our NGN-401 gene therapy clinical program for Rett syndrome...first participant in the Embolden registrational trial...rapidly enroll the trial in the next three to six months” — Rachel McMinn, Ph.D. .
Positive interim pediatric data: all eight participants showed functional gains; aggregate 35 developmental milestones/skills gained; durability out to 24 months in longest follow-ups .
ESGCT preclinical route-of-administration data: ICV achieved superior brain biodistribution vs IT-L; evidence supports multidomain clinical gains and provides no liver-sparing benefit to IT-L relative to ICV .

What Went Wrong

Safety SAEs (related Grade 2) in Pt:5 due to abnormal nerve conduction; resolved to normal range; also confounding leg fracture unrelated to NGN-401 affected Month 12 gross motor assessment .
Mild liver enzyme elevations observed in most participants, consistent with known AAV risks; continued monitoring applied .
Shift in additional Phase 1/2 data timing to 2026, pushing a data catalyst out from the 2H 2025 signal indicated earlier in the year .

Financial Results

Operating Metrics vs Prior Quarters

Metric ($USD Millions)	Q1 2025	Q2 2025	Q3 2025
Cash, Cash Equivalents & Short-Term Investments	$292.6	$274.5	$265.4
R&D Expense	$17.8	$19.4	$17.2
G&A Expense	$8.2	$6.7	$6.6
Net Loss	$22.6	$22.0	$21.0

YoY Comparison (Q3 2025 vs Q3 2024)

Metric ($USD Millions)	Q3 2024	Q3 2025	YoY Change
R&D Expense	$16.3	$17.2	+$0.9 (+5.5%)
G&A Expense	$5.9	$6.6	+$0.7 (+11.9%)
Net Loss	$20.2	$21.0	+$0.8 (+4.0%)

Estimates vs Actuals (Q3 2025)

Metric	Consensus	Actual
Revenue ($USD)	Unavailable*	Unavailable*
EPS ($USD)	Unavailable*	Unavailable*

Values marked with * retrieved from S&P Global; consensus unavailable.

Segment Breakdown

No commercial revenue or segment reporting disclosed in the company’s Q3 press release .

KPIs (Clinical and Operational Progress)

KPI	Q1 2025	Q2 2025	Q3 2025
Phase 1/2 pediatric participants with reported efficacy	Planning; no update disclosed	Efficacy data for first 4 participants: aggregate 23 skills across core domains	8 participants; aggregate 35 developmental milestones/skills; durability and continued skill acquisition
Safety profile at 1E15 vg	Ongoing; HLH algorithm incorporated	No evidence of HLH; transient ferritin elevations without clinical symptoms	Generally well tolerated; no HLH; mild liver enzymes; SAEs related nerve conduction resolved
Embolden trial sites initiated	Planning	Initiation activities underway	12 of 13 sites initiated
Embolden first participant dosed	Not yet	Not yet	First participant dosed in Q4’25
Cash runway guidance	Into 2H 2027	Into early 2028	Through Q1 2028

Guidance Changes

Metric	Period	Previous Guidance	Current Guidance	Change
Cash runway	Multi-year	Into 2H 2027	Through Q1 2028	Raised (extended)
Cash runway	Multi-year	Into early 2028	Through Q1 2028	Raised (clarified)
Embolden enrollment completion	Near-term	Initiation activities underway (no timeline)	Complete enrollment in 3–6 months	New timeline (raised specificity)
Additional Phase 1/2 data	Timing	Updated clinical efficacy/safety data in 2H 2025	Additional clinical data in 2026	Deferred to 2026
Route-of-administration positioning	Preclinical	ICV preferred in preclinical models	ESGCT data: ICV superior biodistribution vs IT-L; no liver-sparing for IT-L	Strengthened evidence base

Earnings Call Themes & Trends

Note: No Q3 2025 earnings call transcript was found in the company’s filings catalog for the period; management did discuss clinical results at the Stifel 2025 Healthcare Conference webcast .

Topic	Previous Mentions (Q1 & Q2)	Current Period	Trend
Regulatory interactions (START, RMAT, trial design)	Ongoing FDA dialogue; written agreement on Embolden design; conversion of Phase 1/2 to registrational trial	Embolden initiated; first participant dosed; 12/13 sites initiated	Progressing toward execution
HLH monitoring/treatment algorithm	HLH algorithm implemented; no evidence of HLH at 1E15 vg	No HLH observed; transient lab changes without clinical HLH	Risk managed; consistent safety
Delivery route (ICV vs IT-L)	ICV preferred in models; planning	ESGCT: ICV superior biodistribution vs IT-L; comparable peripheral organ transduction	Reinforced ICV thesis
Manufacturing readiness	42,000 sq ft Houston facility; in-house AAV capabilities	Same capabilities highlighted; CGMP supports pivotal development	Stable capacity
Cash runway	Into 2H 2027 (Q1); into early 2028 (Q2)	Through Q1 2028	Extended visibility

Management Commentary

“The positive interim clinical data...which showed multidomain, durable gains with continued developmental/milestone skill acquisition, underscore NGN-401's therapeutic promise. With cash runway through the first quarter of 2028, we are in a strong financial position...” — Rachel McMinn, Ph.D., CEO .
“Updated interim data...all pediatric participants...gained developmental milestones/skills or experienced functional gains...These skill gains far exceed the bar for our Embolden registrational trial...” — Rachel McMinn, Ph.D. .
KOL perspective: interim results show durable gains up to 24 months, translating into reduced caregiver burden and greater ability to express needs/wants — Bernhard Suter, M.D. (Texas Children’s, Baylor) .

Q&A Highlights

No formal earnings call transcript available for Q3 2025; management indicated discussion at Stifel 2025 Healthcare Conference (webcast), focusing on Embolden trial progress, interim efficacy durability, and ICV delivery rationale .

Estimates Context

S&P Global Wall Street consensus for Q3 2025 EPS and revenue was unavailable; NGNE remains a pre-commercial clinical-stage company with investor focus on clinical and regulatory milestones rather than near-term P&L beats/misses .

Metric	Q3 2025 Consensus	Notes
Primary EPS Consensus Mean	Unavailable*	Coverage limited; pre-revenue focus
Revenue Consensus Mean	Unavailable*	No commercial revenue disclosed
Primary EPS – # of Estimates	Unavailable*	—
Revenue – # of Estimates	Unavailable*	—

Values marked with * retrieved from S&P Global.

Key Takeaways for Investors

Embolden enrollment timeline (3–6 months) sets up a near-term catalyst path; first patient dosed and 12/13 sites initiated indicate execution momentum .
Interim pediatric data with 35 milestones/skills and durability strengthens efficacy signal; aligns with caregiver/practical outcomes that payors and KOLs deem meaningful .
ESGCT findings reinforce ICV superiority vs IT-L for CNS biodistribution, supporting the mechanistic case for NGN-401’s multidomain gains and best-in-class positioning .
Safety profile at 1E15 vg remains manageable (mild/moderate TEAEs; no HLH); isolated nerve conduction SAEs resolved; continued monitoring prudent for liver enzyme elevations .
Cash runway through Q1 2028 reduces financing overhang and underwrites pivotal activities, manufacturing, and clinical execution into major 2026 data catalysts .
Data timing shift to 2026 moderates near-term update cadence; trading stance should weigh accelerated Embolden enrollment vs deferred broader data to 2026 .
Manufacturing scale and in-house control (Houston facility) offers CMC flexibility and timeline ownership for pivotal readiness and potential commercial conversion of clinical sites .

Appendix: Additional Clinical Data Highlights

Aggregate safety data: TEAEs related to NGN-401 (N=9 participants, 59 events); SAEs related to NGN-401 (N=1 participant, 2 events); no HLH; seizures well controlled; no ICV procedure-related AEs; no signs of MeCP2 overexpression .
Participant-level improvements demonstrate gains across fine motor, gross motor, and communication domains with durability and skill accumulation over time (e.g., Pt:1 11 skills; Pt:2 10 skills; Pt:3 6 skills; Pt:8 3 skills at early timepoint) .

Sources: NGNE Form 8-K and Exhibits (Nov 13, 2025), NGNE press release (Nov 12, 2025), NGNE Form 8-Ks (Aug 11, 2025; May 9, 2025).

Neurogene Inc. (NGNE)·Q3 2025 Earnings Summary