Executive Summary

Q3 2025 EPS of -$0.74 modestly beat Wall Street consensus of -$0.758 (15 estimates) on lower-than-feared loss per share; net loss was $126.9M and total operating expenses were $137.4M . EPS consensus values marked with an asterisk are from S&P Global (SPGI)*.
Liquidity remains strong with $872.9M in cash, cash equivalents and marketable securities at quarter-end, supporting commercial readiness and pipeline execution .
Regulatory timeline updated: FDA classified Denali’s clinical pharmacology update for tividenofusp alfa (MPS II) as a Major Amendment, extending PDUFA from Jan 5, 2026 to Apr 5, 2026; launch preparations continue .
Pipeline execution advanced: DNL126 (MPS IIIA) Phase 1/2 enrollment completed; CTA/IND submissions filed for DNL628 (OTV:MAPT; Alzheimer’s) and DNL952 (ETV:GAA; Pompe), reinforcing the TV platform expansion .
Leadership transition announced alongside Board strengthening, an incremental positive for commercialization readiness and governance continuity .

What Went Well and What Went Wrong

What Went Well

Completed Phase 1/2 enrollment for DNL126 (MPS IIIA), supporting an accelerated approval path; prior data showed CSF heparan sulfate reductions including normalization, and a supportive safety profile .
Advanced TV-enabled pipeline breadth: submitted regulatory applications to initiate studies for DNL628 (OTV:MAPT; Alzheimer’s) and DNL952 (ETV:GAA; Pompe), enlarging the platform’s reach across CNS and muscle disease .
Management tone confident on commercialization: “Momentum is building across Denali as we prepare for the anticipated launch of tividenofusp alfa with an experienced and focused commercial team in place” — Ryan Watts, Ph.D., CEO .

What Went Wrong

FDA extended tividenofusp alfa’s PDUFA date by three months to Apr 5, 2026 due to a Major Amendment; while not related to efficacy/safety/biomarkers, it pushes the expected approval timing and may temper near-term sentiment .
Operating expenses increased year over year: R&D rose to $102.0M (vs. $98.2M prior year) and G&A to $35.5M (vs. $24.9M prior year), reflecting manufacturing ramp and launch preparation costs .
Continued lack of product revenue and widened loss vs. prior year: net loss of $126.9M (vs. $107.2M prior year) amid higher OpEx; press release statements did not report revenue line items for Q3 .

Financial Results

Income Statement and Operating Metrics

Metric	Q1 2025	Q2 2025	Q3 2025
Net Loss ($USD Millions)	$132.97	$124.12	$126.90
Net Loss per Share (EPS, $USD)	-$0.78	-$0.72	-$0.74
Research & Development Expense ($USD Millions)	$116.23	$102.70	$101.95
General & Administrative Expense ($USD Millions)	$29.35	$32.27	$35.48
Total Operating Expenses ($USD Millions)	$145.58	$134.96	$137.43
Interest & Other Income, net ($USD Millions)	$12.61	$10.84	$10.53

Liquidity

Metric	Q1 2025	Q2 2025	Q3 2025
Cash, Cash Equivalents & Marketable Securities ($USD Millions)	~$1,050.0	~$977.4	~$872.9

EPS vs. Estimates (Q3 2025)

Metric	Q3 2025
EPS Actual ($USD)	-$0.74
Primary EPS Consensus Mean ($USD)	-$0.758*
Surprise ($USD)	+$0.018*
Primary EPS – # of Estimates	15*

Revenue vs. Estimates (Q3 2025)

Metric	Q3 2025
Revenue Actual ($USD)	N/A (not disclosed in press release statements)
Revenue Consensus Mean ($USD Millions)	$1.00*
Revenue – # of Estimates	15*

Values marked with an asterisk were retrieved from S&P Global (SPGI)*.

Guidance Changes

Metric	Period	Previous Guidance	Current Guidance	Change
Tividenofusp alfa PDUFA target date	U.S. BLA review	Jan 5, 2026	Apr 5, 2026	Extended 3 months (FDA Major Amendment)
DNL126 (ETV:SGSH) development path	MPS IIIA	Accelerated approval path aligned; enrollment nearing completion	Phase 1/2 enrollment completed; confirmatory Phase 3 planning ongoing	Advanced (operational milestone)
Financial guidance (Revenue, margins, OpEx, OI&E, tax rate, segment guidance, dividends)	FY/Q3 2025	Not provided	Not provided	Maintained (no financial guidance provided)

Earnings Call Themes & Trends

Note: An earnings call transcript for Q3 2025 was not available after searching company and aggregator sources (no transcript in our document catalog) and web sources; thus themes are derived from Q1–Q3 earnings releases and related press updates .

Topic	Previous Mentions (Q2 & Q1)	Current Period (Q3 2025)	Trend
Regulatory/legal (tividenofusp alfa)	BLA accepted for priority review with Jan 5, 2026 PDUFA target	Major Amendment extended PDUFA to Apr 5, 2026; engagement with FDA continues	Timeline extended; regulatory engagement ongoing
R&D execution (DNL126)	FDA alignment on CSF HS surrogate; enrollment near completion	Phase 1/2 enrollment completed; Phase 3 planning continues	Advancing per plan
TV platform expansion (OTV/ETV)	Plan to submit one to two regulatory applications in 2025	CTA/IND submitted for DNL628 (OTV:MAPT) and DNL952 (ETV:GAA)	Execution achieved
Manufacturing & supply chain	In-house clinical biomanufacturing facility launched (Salt Lake City)	Manufacturing operations contributed to higher R&D and personnel expenses	Scaling capability with cost ramp
Partnerships (Takeda, Biogen)	DNL593 Phase 1/2 ongoing; BIIB122 LUMA fully enrolled, readout 2026	Collaboration momentum maintained; 2026 LUMA readout reiterated	Steady progress

Management Commentary

“Momentum is building across Denali as we prepare for the anticipated launch of tividenofusp alfa with an experienced and focused commercial team in place.” — Ryan Watts, Ph.D., CEO .
“We appreciate the FDA’s continued collaboration throughout the review process… We continue to prepare for the potential approval and commercial launch of tividenofusp alfa.” — Ryan Watts, Ph.D., CEO .
“We are thrilled to welcome Tim to our Board… as we continue to grow and advance towards the potential approval and launch of our first product.” — Ryan Watts, Ph.D., CEO .
“I am honored to join Denali as the team prepares for commercialization of its first medicine and advances its TransportVehicle (TV) platform…” — Tim Van Hauwermeiren .
“I am deeply grateful for the trust placed in me to lead our Development organization at this important time for Denali.” — Peter Chin, M.D. .

Q&A Highlights

Q3 2025 earnings call transcript was not available after comprehensive search; therefore, Q&A themes and clarifications cannot be provided. Denali plans Investor Day on Dec 4, 2025 in NYC to provide strategic and launch-readiness updates, which may serve as a proxy venue for investor Q&A .

Estimates Context

EPS beat: Actual -$0.74 vs. consensus -$0.758 (15 estimates), a ~$0.02 beat; this modest surprise likely reflects disciplined OpEx relative to expectations and interest income contribution amid no product revenue (*SPGI). Actual EPS cited from the press release .
Revenue: Company did not disclose Q3 revenue line items in the condensed statements, consistent with a pre-commercial profile; consensus revenue ($1.00M; 15 estimates) appears minimal and not a core driver (*SPGI).
Implications: Near-term estimate revisions likely modest on EPS given the small beat; more material changes may focus on timing for tividenofusp alfa launch given the PDUFA extension to Apr 5, 2026 . Values marked with an asterisk were retrieved from S&P Global (SPGI)*.

Key Takeaways for Investors

Ticker catalyst re-timed: PDUFA extension to Apr 5, 2026 modestly delays the pivotal regulatory event; however, FDA noted no issues related to efficacy/safety/biomarkers, which anchors the thesis near term .
Commercial readiness on track: Management highlights launch preparations and leadership transitions supportive of go-to-market execution for tividenofusp alfa .
Pipeline durability: DNL126 advanced with Phase 1/2 enrollment completion and accelerated approval path aligned with FDA, adding a second potential rare disease revenue stream medium term .
Platform expansion: CTA/IND filings for DNL628 and DNL952 broaden optionality across Alzheimer’s and Pompe disease, reinforcing the TV platform’s multi-modality applicability .
Cash runway: ~$872.9M in cash and marketable securities underpins operations and launch readiness without near-term financing pressure .
Near-term events: Dec 4 Investor Day could provide detailed launch plans, pricing/access strategy, and pipeline timelines—key for trading setups around regulatory milestones .
2026 readouts: BIIB122 (LUMA Phase 2b) and ongoing studies provide medium-term data catalysts, informing broader PD strategy and multi-asset valuation .

Additional sources used:

Q3 2025 8-K item 2.02 and Exhibit 99.1 press release (financials, programs, liquidity, quotes) .
Q2 2025 8-K press release (financials, programs) .
Q1 2025 8-K press release (financials, programs, manufacturing) .
Oct 13, 2025 press release (FDA review extension and rationale) .
Nov 6, 2025 leadership press release (Board addition, CMO transition, quotes) .

Search notes for transcript:

No Q3 2025 earnings call transcript found in document catalog and web search; press coverage mirrored the earnings release content .

Denali Therapeutics Inc. (DNLI)·Q3 2025 Earnings Summary