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Spyre Therapeutics, Inc. (SYRE)·Q3 2025 Earnings Summary

Executive Summary

  • Q3 2025 printed a significant EPS beat versus Wall Street: actual EPS was $-0.15 vs consensus of $-0.74*, driven largely by a $40.3M swing to other income on CVR fair value changes *.
  • Pro forma liquidity strengthened to $782.7M after an October follow-on, extending expected cash runway into 2H 2028; quarter-end cash, cash equivalents and marketable securities were $486.2M .
  • Pipeline execution advanced: SPY003 Phase 1 interim data showed an ~85-day half-life supporting quarterly or twice-annual dosing; SKYWAY (TL1A in RA/PsA/axSpA) initiated and SKYLINE (UC platform) enrolling SPY001 and SPY002 .
  • 2026 set up with six Phase 2 proof-of-concept readouts across SKYLINE and SKYWAY; management emphasized indication-leading profiles and infrequent dosing as key strategic differentiation .

What Went Well and What Went Wrong

What Went Well

  • SPY003 Phase 1 interim data established a differentiated ~85-day half-life with clean tolerability, unlocking IL‑23 combinations (SPY130, SPY230) for SKYLINE Part B: “our fourth successful first-in-human trial in the past year” .
  • Clinical execution on timelines: SKYWAY basket trial initiated in September; SKYLINE Part A actively enrolling SPY001 and SPY002, with SPY003 enrollment imminent .
  • Balance sheet durability: pro forma cash of $782.7M post offering and explicit runway guide into 2H 2028 .
  • CEO tone confident on platform breadth: “fully unlocking…innovative Phase 2 trials…potential indication-leading profiles…poised to deliver meaningful value” .

What Went Wrong

  • No revenue; continuing operating losses highlight funding dependence typical of clinical-stage biotech (net loss $11.2M in Q3; cumulative deficit $1.1B) .
  • R&D and G&A remain elevated as trials scale: R&D $45.2M (+1% YoY) and G&A $11.6M (+9% YoY) in Q3 .
  • EPS beat was aided by non-operating CVR liability revaluation ($40.3M other income), limiting read-through to core operations .

Financial Results

EPS vs Estimates and Actuals

MetricQ1 2025Q2 2025Q3 2025
Primary EPS Consensus Mean (USD)-0.84*-0.71*-0.74*
Actual EPS (USD)$-0.60 $-0.49 $-0.15

Values marked * are consensus estimates retrieved from S&P Global.

Key implication: EPS beats in all three quarters; the Q3 beat was substantial given CVR-driven other income uplift .

Operating Profile and Liquidity

MetricQ1 2025Q2 2025Q3 2025
Research & Development Expense ($MM)$41.6 $40.1 $45.2
General & Administrative Expense ($MM)$11.9 $11.8 $11.6
Other Income (Expense), net ($MM)$2.3 $(0.7) $40.3
Net Loss ($MM)$44.8 $36.7 $11.2
Net Cash Used in Operating Activities ($MM)$41.0 $46.6 $37.1
Cash, Cash Equivalents & Marketable Securities ($MM, period-end)$564.8 $526.6 $486.2
Pro Forma Cash ($MM, period-end)——$782.7

Notes:

  • Pro forma cash reflects October 2025 offering proceeds; sequential cash decline through Q3 pre-offering reflects operating cash burn .
  • Q3 other income uplift primarily from CVR liability fair value decrease .

Year-over-Year Q3 Comparison

MetricQ3 2024Q3 2025
R&D Expense ($MM)$44.7 $45.2
G&A Expense ($MM)$10.6 $11.6
Other Income (Expense), net ($MM)$(13.6) $45.7
Net Loss ($MM)$69.0 $11.2
Cash, Cash Equivalents & Marketable Securities ($MM)—$486.2

KPIs (Program and Financing Execution)

KPIQ1 2025Q2 2025Q3 2025
SKYLINE Platform Trial statusPlanned mid-2025 initiation Initiated; SPY001 enrolling SPY001 & SPY002 enrolling; SPY003 starting soon
SKYWAY Basket Trial statusPlanned Q3 initiation Expected Q3 initiation Initiated Sept 2025
SPY003 Phase 1 statusFIH initiated Mar 2025 Interim PK data expected 2H 2025 Interim data positive; ~85-day half-life
Equity Financing——$296.5M net proceeds (Oct 2025)
Cash Runway Guidance2H 2028 2H 2028 2H 2028

Guidance Changes

MetricPeriodPrevious GuidanceCurrent GuidanceChange
Cash RunwayThrough 2028“Runway into 2H 2028” (Q1/Q2) “Runway into 2H 2028” (Q3) Maintained
SKYWAY (TL1A in RA/PsA/axSpA)Q3 2025 initiation“Expected to initiate in Q3 2025” Initiated Sept 2025 Achieved
SKYLINE Part A Enrollment2025SPY001 enrolling SPY001 & SPY002 enrolling; SPY003 to start soon Expanded
SPY003 Phase 1 Readout2H 2025“Interim data expected 2H 2025” Interim data positive; advancing to SKYLINE Delivered/Advancing
2026 Proof-of-Concept Readouts2026Prior framing “7+ PoC in 2026–27” (Q1) / “9 PoC in 2026–27” (Q2) “On track for 6 PoC readouts in 2026” Clarified scope for 2026

No revenue/EPS/OpEx margin guidance was provided; dividends not applicable .

Earnings Call Themes & Trends

Note: A Q3 2025 earnings call transcript was not available in the document set searched.

TopicPrevious Mentions (Q-2 and Q-1)Current Period (Q3 2025)Trend
Extended half-life dosingSPY001/002/072 PK supported Q3M/Q6M dosing; SPY003 interim expected SPY003 ~85-day half-life; quarterly/twice-annual dosing reiterated Strengthening
Platform trials (SKYLINE/ SKYWAY)SKYLINE initiated; SKYWAY expected Q3 SKYWAY initiated; SKYLINE enrolling multiple arms Execution progressing
Combination strategy (SPY120/130/230)Preclinical synergy data; Part B inclusion planned Additional preclinical efficacy; Part B inclusion reiterated Building evidence
Balance sheet & runway$565–$527M cash; runway into 2H 2028 $486M cash; $783M pro forma; runway maintained Strengthened via equity
CVR liability dynamicsN/ACVR fair value decrease drove other income Non-operating tailwind
Regulatory/macro riskStandard forward-looking statements and risk factors Expanded risk disclosures (BIOSECURE Act, geopolitics) Elevated focus

Management Commentary

  • CEO: “With optimized monotherapies and uniquely differentiated combination therapies in IBD, and a potential first- and best-in-class anti-TL1A therapy in rheumatic diseases… we are poised to deliver meaningful value for patients and shareholders alike” .
  • Clinical Development SVP on SPY003: “our fourth successful first-in-human trial in the past year… advancing SPY003 into SKYLINE represents a pivotal step in realizing our vision for a comprehensive IBD portfolio…” .

Q&A Highlights

A Q3 2025 earnings call transcript was not available; no Q&A themes could be extracted from primary documents searched.

Estimates Context

  • Q3 2025 EPS beat: actual $-0.15 vs consensus $-0.74*, aided by CVR fair value decrease and interest income *.
  • Q2 2025 EPS beat: actual $-0.49 vs consensus $-0.71* *.
  • Q1 2025 EPS beat: actual $-0.60 vs consensus $-0.84* *.
  • Revenue consensus was $0 for all periods given clinical-stage status (no revenue)*.

Values marked * are consensus estimates retrieved from S&P Global.

Key Takeaways for Investors

  • Repeated EPS beats, including a large Q3 beat, are driven by non-operating items; core operating spend will continue as Phase 2 programs scale .
  • Liquidity and runway are robust post-offering ($782.7M pro forma; guide to 2H 2028), reducing near-term financing overhang .
  • Clinical catalysts intensify in 2026: six proof-of-concept readouts across UC and rheumatic indications; success in any sub-study could re-rate the program value .
  • SPY003’s ~85-day half-life enhances the dosing convenience narrative and strengthens combination optionality for SKYLINE Part B .
  • Execution trend is positive: SKYWAY initiated on schedule; SKYLINE enrolling multiple arms; SPY003 advancing—portfolio breadth mitigates single-asset risk .
  • Watch CVR liability impacts on reported P&L—material quarter-to-quarter swings can obscure underlying operating trajectory .
  • Near-term trading: equity supply from October raise is behind the name; focus shifts to enrollment updates and any interim data signals. Medium term: platform design offers multiple shots on goal with differentiated, infrequent dosing positioning .

Citations:

  • Q3 press release and 8-K exhibits
  • Q3 10-Q (financials, MD&A, liquidity, risk)
  • Q2 2025 8-K
  • Q1 2025 8-K

Consensus estimates disclaimer: Values marked * are retrieved from S&P Global.