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Spyre Therapeutics, Inc. (SYRE)·Q2 2025 Earnings Summary

Executive Summary

  • EPS beat: Q2 2025 diluted EPS (common) was -$0.49 vs Wall Street consensus of -$0.71, a ~$0.22 beat; revenue remains $0, in line with expectations* .
  • Operating discipline: Net loss narrowed to $36.7M (QoQ -18.0%; YoY -5.5%) alongside modest OpEx control; other income stayed resilient at $5.2M .
  • Pipeline progression: Initiated SKYLINE-UC Phase 2 platform (UC) and set up SKYWAY-RD initiation in Q3 (RA, PsA, axSpA); TL1A Phase 1 data showed ~75-day half-life and full TL1A suppression through 20 weeks .
  • Balance sheet: $526.6M cash/marketable securities with runway into H2 2028, supporting nine proof-of-concept readouts across 2026–2027 .

What Went Well and What Went Wrong

What Went Well

  • Launch of SKYLINE-UC platform trial and progress toward SKYWAY-RD, accelerating multi-indication catalysis: “We are poised to generate nine proof-of-concept readouts… over the next two years” — Cameron Turtle, CEO .
  • Strong TL1A data package: SPY002 and SPY072 were well tolerated, showed ~75-day half-life, and suppressed free TL1A to LLOQ up to 20 weeks at single 100 mg doses, supporting quarterly or semiannual dosing .
  • Liquidity and funding clarity: $526.6M cash/marketable securities; expected runway into H2 2028 enabling efficient execution of platform and basket trials .

What Went Wrong

  • Cash burn ticked up QoQ: Net cash used in operating activities rose to $46.6M vs $41.0M in Q1 (reflecting clinical ramp) .
  • Contingent value right (CVR) liability increased materially: current CVR liability reached $59.9M (from $42.8M in Q1 and $25.1M in Q4), adding balance sheet complexity .
  • No product revenue; continued net losses: Persistent lack of revenue; net loss remains sizable at $36.7M despite improvement QoQ/YoY .

Financial Results

P&L and EPS (USD Millions, except EPS)

MetricQ4 2024Q1 2025Q2 2025
Net Loss ($)$(56.296) $(44.773) $(36.717)
Diluted EPS (Common) ($)$(0.81) $(0.60) $(0.49)
R&D Expense ($)$50.482 $41.623 $40.145
G&A Expense ($)$10.771 $11.944 $11.790
Other (Income) / Expense, Net ($)$4.958 $8.779 $5.218
Gain on Sale of IPR&D ($)$1.840 — $10.000

Liquidity and Cash Burn

MetricQ4 2024Q1 2025Q2 2025
Cash, Cash Equivalents & Marketable Securities ($)$603.1 $564.8 $526.6
Net Cash Used in Operating Activities ($)$37.2 $41.0 $46.6

Revenue and Margins

MetricQ4 2024Q1 2025Q2 2025
Revenue ($)$0 $0 $0
Gross Margin (%)N/A N/A N/A
Net Income Margin (%)N/A N/A N/A

KPIs and Clinical Metrics

KPIQ4 2024Q1 2025Q2 2025
SPY001 half-life / target engagement>90 days half-life; complete α4β7 occupancy to 12 weeks (300 mg) Extended follow-up supports Q6M dosing; complete saturation beyond 6 months (600 mg) SKYLINE-UC enrolling SPY001 Part A
Anti-TL1A PK/PDPreclinical: NHP half-life 24 days vs first-gen Interim SPY002 readout expected later Q2 ~75-day half-life; free TL1A suppressed through 20 weeks (100 mg)
Platform/Basket trialsPlan UC platform trial mid-2025 On track mid-year UC/RA starts SKYLINE-UC initiated; SKYWAY-RD expected Q3
PoC readouts outlook4 Phase 2 PoCs in 2026 7+ PoCs across 2026–2027 9 PoCs across 2026–2027

Note: No commercial segments; segment breakdown not applicable.

Guidance Changes

MetricPeriodPrevious GuidanceCurrent GuidanceChange
Cash runwayMulti-yearInto H2 2028 (Q4’24) Into H2 2028 reaffirmed (Q2’25) Maintained
SKYLINE-UC initiation2025Mid-2025 start (Q4’24) Initiated May 2025 (Q2’25) Achieved
SKYWAY-RD initiation2025Mid-2025 for RA (Q4’24) Q3 2025 basket (RA, PsA, axSpA) (Q2’25) Timing clarified
SPY003 Phase 1 interim20252H 2025 (Q4’24) Q4 2025 (Q2’25) Narrowed window
PoC readouts count2026–20274 (2026) 9 across 2026–2027 Raised

Earnings Call Themes & Trends

Note: A Q2 2025 earnings call transcript was not available in our document catalog; Spyre hosted a June 17 webcast focused on TL1A Phase 1 results .

TopicPrevious Mentions (Q4 2024, Q1 2025)Current Period (Q2 2025)Trend
TL1A program differentiationPreclinical potency; NHP half-life 2–3x first-gen; Phase 1 ongoing ~75-day half-life; full TL1A suppression to 20 weeks; advancing to Phase 2 UC and RD Strengthening evidence
Platform trial strategyPlan UC platform mid-2025; combinations envisioned SKYLINE-UC initiated; combinations slated for Part B Execution step-change
Rheumatology expansionRA Phase 2 mid-2025 (anti-TL1A) SKYWAY-RD Q3 initiation across RA, PsA, axSpA Scope broadened
Funding runwayInto H2 2028 Reiterated; supports 9 readouts Stable
Regulatory/geo/macro risksBIOSECURE, geopolitical tensions Similar cautionary context reiterated Unchanged
R&D execution cadenceMultiple FIH trials initiated; SPY003 FIH start SPY003 interim Q4 2025; Part A enrollment ongoing On track

Management Commentary

  • “Spyre is entering a new chapter as we begin to explore the potential of our pipeline to reshape the treatment paradigm in chronic immune-mediated diseases… we are poised to generate nine proof-of-concept readouts… and a strong balance sheet with expected runway into the second half of 2028” — Cameron Turtle, CEO .
  • “These interim results demonstrate clear benefits of our anti-TL1A approach versus first-generation molecules, underscoring the promise and potential of SPY002 and SPY072…” — Josh Friedman, SVP Clinical Development .
  • “The recently initiated SKYLINE-UC platform trial and the planned SKYWAY-RD basket trial leverage innovative and efficient designs…” — Sheldon Sloan, CMO .
  • “We are well-funded to deliver 9 proof-of-concept readouts over the next two years in markets totaling >$60B of annual revenue.” — Cameron Turtle, CEO .

Q&A Highlights

  • No Q2 2025 earnings call transcript was available; Spyre held a June 17 webcast to discuss TL1A Phase 1 results and clinical plans .
  • Guidance clarifications embedded in press releases: SKYLINE-UC initiation in May; SKYWAY-RD expected Q3; SPY003 interim now specified as Q4 2025 .

Estimates Context

MetricQ2 2025 ConsensusQ2 2025 ActualSurprise
Primary EPS Consensus Mean ($)-0.71*-0.49 +$0.22 (beat)*
Revenue Consensus Mean ($)0.00*0.00 In line*
Primary EPS - # of Estimates9*——
Revenue - # of Estimates10*——

Values retrieved from S&P Global.*

Implications: EPS beat largely driven by lower net loss and a $10.0M gain on sale of IPR&D milestones; OpEx contained and other income steady, offsetting clinical ramp .

Key Takeaways for Investors

  • EPS beat against consensus driven by mix of OpEx discipline, stable other income, and $10.0M milestone gain; watch durability as trials scale .
  • Clinical catalysts intensify: SKYLINE-UC underway; SKYWAY-RD initiation in Q3; SPY003 interim in Q4 — a cadence supportive of multi-quarter news flow .
  • TL1A program differentiation is substantive (~75-day half-life; 20-week TL1A suppression at low dose), supporting less frequent dosing and potential class leadership .
  • Liquidity remains robust ($526.6M) with runway into H2 2028, mitigating funding overhang amid platform/basket trial execution .
  • Balance sheet CVR liability increased; monitor pegzilarginase-related milestones and cash flow effects .
  • Near-term trading catalysts: basket initiation timing, any incremental Phase 1/Part A signals, and SPY003 interim — each can drive sentiment given scarcity of revenue .
  • Medium-term thesis: platform/basket structure may compress timelines to PoC and enable combination differentiation; risk remains clinical/regulatory execution and macro/geopolitical backdrop per safe-harbor disclosures .