Spyre Therapeutics — Third Quarter 2026 Earnings Summary

Financial Performance:

• Reported a net loss of $96.1 million for the third quarter of 2026, compared to a net loss of $11.2 million for the same period in 2025.
• Research and development expenses totaled $89.2 million for the third quarter of 2026, an increase from $45.2 million in the third quarter of 2025, driven by higher manufacturing costs and clinical trial expenses.
• General and administrative expenses were $16.6 million for the third quarter of 2026, up from $11.6 million in the third quarter of 2025, primarily due to increased headcount and professional services fees.
• Total other income was $9.6 million for the third quarter of 2026, a decrease from $45.7 million in the third quarter of 2025, primarily due to changes in the fair value of the contingent value right (CVR) liability in the prior period.
• Net cash used in operating activities was $77.5 million for the third quarter of 2026.
• As of September 30, 2026, cash, cash equivalents, and marketable securities totaled $1,071.9 million.
• Pro forma cash, cash equivalents, and marketable securities as of September 30, 2026, were $1,467.9 million, reflecting $378.0 million in net proceeds from an October 2026 underwritten public offering and $18.0 million in October 2026 at-the-market sales.
• Total assets were $1,099.7 million as of September 30, 2026, compared to $777.8 million as of December 31, 2025.
• Total liabilities were $48.2 million as of September 30, 2026, compared to $62.5 million as of December 31, 2025.
• Stockholders' equity was $1,051.5 million as of September 30, 2026, compared to $715.2 million as of December 31, 2025.

Guidance and Future Outlook:

• The Company expects its cash runway to extend into the second half of 2029.
• Topline induction results for three potential best-in-indication combinations in the SKYLINE Part B trial are expected in the third quarter of 2027.
• The Company plans to advance a potential best-in-class anti-TL1A monotherapy agent into pivotal studies for hidradenitis suppurativa (HS) in 2027.
• Topline Week 16 results for the SKYLIGHT Phase 2 trial in HS are planned for late 2027 or early 2028.
• The Company anticipates delivering topline data in Q3 2027 with the potential for efficacy, safety, and convenience that meaningfully surpasses today's standard of care.

Business Segments and Product Lines:

• IBD (SKYLINE Trial): Completed Part A of the Phase 2 trial, achieving positive topline induction data for all three monotherapies (SPY001, SPY002, SPY003).
  • SPY001, SPY002, and SPY003 all achieved primary endpoints, demonstrating statistically significant reductions in Robart's Histopathology Index scores of 9.2, 10.7, and 10.0 points, respectively.
  • Clinical remission rates were 40% (SPY001), 33% (SPY002), and 20% (SPY003); endoscopic improvement rates were 51%, 42%, and 30%, respectively.
  • Modified Mayo Score changes from baseline at Week 12 were -3.7 for SPY001 and SPY002, and -3.5 for SPY003.
  • SKYLINE Part B is enrolling ahead of schedule, enabling an increased enrollment target.
• Rheumatic Diseases (SKYWAY Trial): Reported positive topline results for SPY072 in the rheumatoid arthritis (RA) sub-study, though the magnitude of benefit was insufficient to prioritize advancement. SPY072 did not meet primary endpoints in the psoriatic arthritis (PsA) or axial spondyloarthritis (axSpA) sub-studies. The Company will not advance SPY072 in rheumatic diseases.
• Hidradenitis Suppurativa (SKYLIGHT Trial): Initiated a new Phase 2 trial (SKYLIGHT) to provide clinical proof-of-concept for dual TL1A and IL-17A/F inhibition in HS.
• Pipeline Updates:
  • SPY001 (anti-α4β7), SPY002 (anti-TL1A), and SPY003 (anti-IL-23) are being evaluated for IBD.
  • SPY072 (anti-TL1A) is being developed for HS as a monotherapy and in combination with SPY007 (anti-IL-17A/F).
  • SPY007 is a preclinical-stage program targeting IL-17A and IL-17F.

Market and Competitive Landscape:

• The US IBD market is estimated to affect approximately 2.4 million individuals, with the global market forecasted to exceed $40 billion by 2030.
• The US HS market is estimated to affect approximately 3.0 million patients, with the global market forecasted to exceed $10 billion by 2035.
• The Company aims to develop first- and best-in-class combination programs in IBD and HS.

Risks and Challenges:

• Forward-looking statements involve risks including regulatory feedback, potential disagreement by regulatory authorities with data interpretation, and the possibility of interim or final data differing from expectations.
• Risks include the potential impact of Trump Administration policies and changes in law on the Company's business.
• There is a risk that clinical trials may not be delivered within expected time frames or that results may not support advancement of product candidates.
• The Company does not plan to advance SPY072 in rheumatic diseases due to insufficient benefit magnitude in RA and failure to meet primary endpoints in PsA and axSpA.

Management Commentary and Tone:

• CEO Cameron Turtle stated the Company is "increasingly well-positioned to deliver on our ambition of elevating the standard of care across immunology."
• Management expressed strong conviction that combination products have the potential to transform the treatment paradigm in IBD, citing compelling Phase 2 monotherapy readouts.
• The CEO noted that the breadth of the pipeline, strength of clinical data, and continued execution position Spyre to deliver meaningful advances for patients and substantial long-term value for shareholders.
• Management highlighted the "excellent external proof-of-concept data for TL1A in hidradenitis suppurativa" supporting the expansion of the pipeline.

Other Key Points:

• The Company raised over $400 million in gross proceeds from an underwritten public offering in October 2026 to fund a pivotal program in HS with SPY072.
• The CVR liability was $0 as of September 30, 2026, compared to $22.8 million in current liabilities and $3.9 million in non-current liabilities as of December 31, 2025.
• Series B non-voting convertible preferred stock outstanding decreased from 16,667 shares as of December 31, 2025, to nil as of September 30, 2026.
• Common stock issued and outstanding increased from 78,189,811 shares as of December 31, 2025, to 89,953,997 shares as of September 30, 2026.
• The Company announced a gain on the sale of in-process research and development assets of $70.0 million for the nine months ended September 30, 2026, compared to $10.0 million in the same period of 2025.