Executive Summary

Q4 2024 delivered a sharp increase in collaboration revenue to $22.6M, driving a materially narrower net loss of $10.5M (-$0.18 EPS) versus Q3, with cash, cash equivalents, and marketable securities at $246.7M at year-end .
The quarter was defined by clinical/regulatory momentum: FDA Breakthrough Therapy Designation for zorevunersen, positive long-term OLE data, and global alignment on a single registrational Phase 3 (EMPEROR) study; EMPEROR initiation remains on track for Q2 2025 .
Post-quarter, Stoke signed a global commercialization collaboration (ex-US/Canada/Mexico) with Biogen, securing $165M upfront, shared development costs (30/70), up to $385M milestones, and royalties (low double digits to high teens), extending runway to mid-2028; CEO transition announced concurrently (Interim CEO Ian F. Smith) .
Consensus estimates from S&P Global for Q4 2024 were unavailable due to access limits; beat/miss vs Street cannot be determined at this time (see Estimates Context) [GetEstimates error—S&P Global].*
Near-term stock reaction catalysts: Phase 3 study initiation (Q2 2025), regulatory interactions under BTD, and Biogen partnership milestones; leadership transition may add headline risk but continuity is emphasized by the Board .

What Went Well and What Went Wrong

What Went Well

Regulatory momentum: FDA granted Breakthrough Therapy Designation for zorevunersen, supported by evidence of substantial improvement over available therapies in clinical studies .
Durable efficacy and cognitive/behavior benefits: OLE data showed sustained seizure reductions (e.g., 87% median reduction at month eight in the 70mg→45mg cohort) and continuous improvements in Vineland-3 measures through two years; generally well-tolerated .
Strengthened strategic and financial position: Biogen collaboration adds global commercialization expertise and capital ($165M upfront; shared costs; milestones/royalties), while EMPEROR remains on track for Q2 2025, extending runway to mid-2028 .
- “With a strong financial position, we are well-capitalized to advance through Phase 3 and prepare for launch readiness,” — Edward M. Kaye, M.D., CEO .

What Went Wrong

No product revenue; revenue is primarily collaboration/license-related, with opex growth reflecting advancing programs (R&D $23.4M; G&A $12.8M in Q4) .
Leadership transition introduces execution risk: CEO Edward M. Kaye stepping down (advisory role), with interim leadership appointment; near-term stability emphasized but transition is non-trivial .
Street estimate comparison unavailable; lack of an earnings call transcript for Q4 limits insight into real-time guidance Q&A and any intra-quarter dynamics (see Estimates Context and Q&A Highlights) [ListDocuments earnings-call-transcript search returned none] [GetEstimates error—S&P Global].*

Financial Results

P&L Snapshot (USD Millions, EPS in USD)

Metric	Q2 2024	Q3 2024	Q4 2024
Revenue ($MM)	$4.831	$4.894	$22.614
Research & Development ($MM)	$21.136	$22.205	$23.424
General & Administrative ($MM)	$13.037	$12.692	$12.844
Loss from Operations ($MM)	$(29.342)	$(30.003)	$(13.654)
Net Loss ($MM)	$(25.695)	$(26.430)	$(10.483)
Diluted EPS ($)	$(0.46)	$(0.47)	$(0.18)

Margins (Calculated from reported figures)

Metric	Q2 2024	Q3 2024	Q4 2024
Net Income Margin %	(−531.8%)	(−540.1%)	(−46.4%)
EBIT Margin %	(−607.3%)	(−613.4%)	(−60.4%)

Note: Margins are calculated using Net Loss/Revenue and Loss from Operations/Revenue; source numbers cited in each cell .

Liquidity and Runway

Metric	Q2 2024	Q3 2024	Q4 2024
Cash, Cash Equivalents & Marketable Securities ($MM)	$282.0	$269.2	$246.7

KPIs (Clinical Program Highlights)

KPI	Q4 2024
OLE cohort seizure reduction (median at month eight for 70mg→45mg regimen)	87%
OLE cognitive/behavior outcomes	Continuous improvements in multiple Vineland-3 measures through 2 years
Safety overview	Generally well tolerated; TEAEs consistent; CSF protein elevations without clinical manifestations

Guidance Changes

Metric	Period	Previous Guidance	Current Guidance	Change
EMPEROR Phase 3 initiation	Q2 2025	“Provide Phase 3 update by year-end” (Q3)	“On track to initiate in Q2 2025” (Q4)	Clarified/firmed timeline
Cash runway	Through mid-2028	Not specified prior	“Anticipated to fund operations to mid-2028 (incl. $165M upfront and eligible Biogen proceeds)”	Introduced/extended runway
Biogen collaboration (ex-US/CA/MX)	Effective Feb–Mar 2025	N/A	$165M upfront; 30/70 dev. cost share; up to $385M milestones; royalties low double digits–high teens	New partnership

Earnings Call Themes & Trends

(Note: No Q4 2024 earnings call transcript available in filings; themes reflect press releases and prior quarters.)

Topic	Previous Mentions (Q2 & Q3)	Current Period (Q4)	Trend
Regulatory/legal progression	Partial Clinical Hold removed; ongoing global regulatory discussions for single Phase 3	FDA Breakthrough Therapy Designation; global alignment; EMPEROR timing confirmed	Accelerating/regulatory de-risking
R&D execution & dosing regimen	Proposed 70mg loading → 45mg maintenance; AES/EEC data planning	OLE data confirm durability and cognition/behavior improvements under 70mg→45mg regimen	Positive continuity/validation
Commercialization strategy	Focus on clinical/regulatory steps; no partner disclosed	Biogen global collaboration (ROW), Stoke retains US/CA/MX; launch readiness emphasized	Commercial path clarified
Financial runway	$282.0M (Q2); $269.2M (Q3) cash & securities	$246.7M at year-end; extended runway to mid-2028 with Biogen funds	Strengthened runway post-collaboration
Leadership & governance	No change highlighted	CEO transition to Interim CEO Ian F. Smith; Board-led search	Transition with continuity emphasis

Management Commentary

“Recent milestones – including Breakthrough Therapy Designation, positive data supporting our Phase 3 dosing regimen and global regulatory alignment – have catalyzed the Dravet community and put us on track to initiate EMPEROR in the second quarter.” — Edward M. Kaye, M.D., CEO .
“We are pleased to have Ian step in as Interim CEO… will support continued advancement of our strategic and growth initiatives.” — Arthur Tzianabos, Ph.D., Interim Executive Chairman .
“I am deeply committed to Stoke’s mission and to advancing zorevunersen as a disease-modifying medicine for the treatment of Dravet syndrome.” — Ian F. Smith, Interim CEO .
“The substantial and durable reductions in seizures… and continuous gains in multiple measures of behavior and cognition… have never been seen before in studies of Dravet syndrome.” — Joseph Sullivan, M.D., UCSF (AES commentary) .
“These data… support a highly differentiated mechanism of action for zorevunersen.” — Barry Ticho, M.D., Ph.D., CMO .

Q&A Highlights

No Q4 2024 earnings call transcript was available in the document set; Q&A specifics cannot be provided at this time [ListDocuments earnings-call-transcript search returned none].
Press communications clarified Phase 3 regimen (70mg loading doses followed by 45mg maintenance) and timing (Q2 2025 initiation) .
Collaboration terms with Biogen (territory split, financial structure) and cash runway extension were disclosed via press releases rather than Q&A commentary .

Estimates Context

Wall Street consensus (S&P Global) for Q4 2024 revenue and EPS could not be retrieved due to access limits; therefore, beat/miss vs Street cannot be determined at this time [GetEstimates error—S&P Global].*
Given the substantial step-up in Q4 collaboration revenue ($22.6M vs $4.9M in Q3), Street models may need to reflect timing of revenue recognition tied to collaboration agreements; investors should re-examine run-rate assumptions and opex trajectory ahead of Phase 3 initiation .

Key Takeaways for Investors

Zorevunersen’s regulatory and clinical momentum (BTD + robust OLE data) materially de-risks the Phase 3 path; Phase 3 initiation (Q2 2025) is a key upcoming catalyst .
The Biogen collaboration provides capital, global commercial capability ex-US/CA/MX, and extends runway to mid-2028, reducing financing overhang through pivotal readout (anticipated 2H 2027) .
Q4’s revenue inflection came from collaboration/license recognition, not product sales; model sensitivity should focus on collaboration accounting and R&D cadence as EMPEROR ramps .
Leadership transition is a watch item; Board emphasizes continuity and search for permanent CEO while interim leadership includes experienced operator Ian F. Smith (ex-Vertex) .
Clinical safety profile remains supportive; cognitive/behavior measures are emerging as differentiating endpoints beyond seizure control — an important Phase 3 positioning element .
Near-term trading: headline volatility around leadership and regulatory milestones is possible; medium-term thesis hinges on successful Phase 3 execution, regulatory interactions under BTD, and commercial readiness with Biogen .
Revisit Street expectations once S&P consensus access is restored; the Q4 step-up and 2025 collaboration cash flows may shift earnings trajectory and funding outlook (mid-2028 runway) .

*Values and consensus comparisons were intended to be retrieved from S&P Global but were unavailable due to access limits at the time of analysis.

Stoke Therapeutics, Inc. (STOK)·Q4 2024 Earnings Summary