Key Takeaways
- SYRE shares tumbled 14% in after-hours trading Tuesday following the company’s decision to discontinue SPY072 as a monotherapy for rheumatoid arthritis
- SPY072 demonstrated superiority over placebo in the SKYWAY Phase 2 study but fell short of Spyre’s internal efficacy benchmarks
- The study included 143 patients; safety profiles were favorable compared to placebo across all measures
- The company anticipates Phase 2 results for SPY072 in psoriatic arthritis and axial spondyloarthritis during Q4 2026
- Analysts maintain a Strong Buy rating on SYRE with a consensus price target of $124.73
Shares of Spyre Therapeutics (SYRE) plummeted up to 14% during after-hours trading Tuesday following the company’s announcement that SPY072 will not advance as a standalone rheumatoid arthritis therapy. Prior to the disclosure, the stock was hovering near $107.36.
Spyre Therapeutics, Inc., SYRE
The strategic shift came after Spyre reviewed topline data from the rheumatoid arthritis portion of its SKYWAY Phase 2 clinical trial. While SPY072 demonstrated statistically significant improvements over placebo across primary endpoints, the magnitude of benefit failed to satisfy the company’s proprietary threshold for advancing the drug as a monotherapy in this indication.
Examining the data more closely, the Low Dose cohort of SPY072 achieved a DAS28-CRP change from baseline of -1.9 compared to -1.3 in the placebo group at the 12-week mark. The High Dose arm recorded an ACR20 response rate of 63% against 43% for placebo. For ACR50, the Low Dose group hit 38% compared to just 19% in the control arm.
The study design incorporated three treatment arms totaling 143 enrolled patients. The High Dose arm consisted of 48 participants, the Low Dose arm included 48 patients, and 47 individuals received placebo.
From a safety perspective, the results were encouraging. Adverse events occurred in 27% of patients taking SPY072 compared to 36% in the placebo group, with the majority categorized as mild to moderate in severity.
The Road Ahead for SPY072
Spyre isn’t abandoning SPY072 completely. The biotech intends to continue investigating the compound through combination therapy strategies, notably by partnering it with an IL-17A/F inhibitor as part of its SPY772 development program targeting hidradenitis suppurativa. Results from this combination trial are projected for late 2027 or the first quarter of 2028.
Several important milestones remain on the horizon. The company expects to report Phase 2 results for SPY072 in both psoriatic arthritis and axial spondyloarthritis indications in the fourth quarter of 2026. These data releases will draw significant attention following Tuesday’s RA disappointment.
Management emphasized that the findings continue to validate the therapeutic promise of its TL1A antibody platform in autoimmune conditions, especially when utilized as part of combination regimens rather than single-agent approaches.
Analyst Community Remains Optimistic
Notwithstanding the after-hours decline, Wall Street’s outlook hasn’t changed. SYRE maintains a Strong Buy consensus rating from analysts, supported by 13 Buy recommendations and a single Hold rating.
The mean 12-month price objective stands at $124.73, implying approximately 16% potential appreciation from Tuesday’s pre-announcement price levels.
Looking at technical indicators, SYRE was positioned above its 20-day exponential moving average of $103.75 and its 50-day EMA of $96.37 prior to the announcement. The Williams %R indicator was also flashing a Buy signal, indicating the stock hadn’t entered overbought territory.
The critical inflection point for SYRE will arrive with the Q4 2026 clinical data releases in psoriatic arthritis and axial spondyloarthritis indications.
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