TLDR
- SYRE dropped 14% in after-hours trading Tuesday after scrapping SPY072 as a standalone RA treatment
- Both doses of SPY072 beat placebo in the SKYWAY Phase 2 trial but failed to meet Spyre’s own internal performance threshold
- The trial enrolled 143 participants; adverse events were comparable to or lower than placebo
- Spyre expects Phase 2 data for SPY072 in psoriatic arthritis and axial spondyloarthritis in Q4 2026
- Wall Street keeps a Strong Buy consensus on SYRE with an average price target of $124.73
Spyre Therapeutics (SYRE) fell as much as 14% in after-hours trading on Tuesday after the company said it will not move SPY072 forward as a solo treatment for rheumatoid arthritis. The stock was trading around $107.36 before the news broke.
Spyre Therapeutics, Inc., SYRE
The decision followed topline results from the RA sub-study of its SKYWAY Phase 2 trial. Both doses of SPY072 beat placebo on key endpoints, but the effect was not large enough to clear Spyre’s own internal bar for monotherapy development in RA.
In the numbers, SPY072 Low Dose posted a change from baseline in DAS28-CRP of -1.9 versus -1.3 for placebo at Week 12. The High Dose hit a 63% ACR20 response rate compared to 43% for placebo. Low Dose reached 38% on ACR50 versus 19% for placebo.
The trial ran across three arms with 143 participants total. 48 received the High Dose, 48 received the Low Dose, and 47 were on placebo.
On the safety side, things looked clean. Adverse events hit 27% of SPY072 participants versus 36% on placebo, with most events rated mild or moderate.
What Comes Next for SPY072
Spyre is not walking away from SPY072 entirely. The company plans to keep exploring it in combination approaches, including pairing it with an IL-17A/F inhibitor in its SPY772 program for hidradenitis suppurativa. Data from that combination study is expected in late 2027 or early 2028.
The company also has upcoming catalysts. Phase 2 data for SPY072 in psoriatic arthritis and axial spondyloarthritis are expected in Q4 2026. Those readouts will be closely watched after Tuesday’s RA miss.
Spyre said the results still support the broader potential of its TL1A antibodies in autoimmune disease, particularly as combination components rather than as standalone therapies.
Wall Street Still Backing the Stock
Despite the after-hours drop, analyst sentiment has not shifted. SYRE carries a Strong Buy consensus from Wall Street, backed by 13 Buy ratings and one Hold.
The average 12-month price target sits at $124.73, pointing to around 16% upside from pre-announcement levels.
From a technical standpoint, SYRE was trading above both its 20-day exponential moving average of $103.75 and its 50-day EMA of $96.37 heading into the announcement. Williams %R was also showing a Buy signal, suggesting the stock had not been overbought.
The next major test for SYRE will be the Q4 2026 data readouts in psoriatic arthritis and axial spondyloarthritis.
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