Spyre Therapeutics Drops Rheumatoid Arthritis Monotherapy Plan After Mixed Phase 2 Data — BigGo Finance

Spyre Therapeutics (SYRE) said it will not advance its investigational antibody SPY072 as a standalone treatment for rheumatoid arthritis after Phase 2 trial data fell short of the company’s internal efficacy benchmark, sending shares down as much as 14% in extended trading on Tuesday.

The Waltham, Massachusetts-based biotech reported top-line results from the rheumatoid arthritis arm of its SKYWAY basket study, which evaluated two doses of the long-acting anti-TL1A antibody in patients with moderately to severely active disease who had inadequate responses to conventional or advanced therapies.

Both dose levels achieved statistically significant improvements over placebo on the primary endpoint, which measured change from baseline in Disease Activity Score in 28 joints with C-reactive protein, or DAS28-CRP, at week 12. The low dose produced a 1.9-point reduction compared with 1.3 points for placebo, while the high dose delivered a 1.5-point reduction.

Secondary endpoints also showed encouraging signals. ACR20 and ACR50 response rates were numerically higher for the high and low doses, respectively. Researchers observed comparable outcomes between patients new to advanced therapies and those with prior exposure, according to the company.

The drug demonstrated robust target engagement, with both doses achieving targeted drug concentrations and maintaining complete suppression of free TL1A through week 12. The safety profile was generally consistent with the TL1A class, with adverse events reported in 27% of the treatment arm versus 36% in the placebo group.

Despite proof-of-mechanism for TL1A inhibition in rheumatoid arthritis, the magnitude of benefit did not meet the threshold Spyre had set internally to prioritize advancement of SPY072 as a monotherapy in the indication. The company confirmed it is shifting development focus toward broader autoimmune indications and combination approaches.

“The SKYWAY-RA study achieved proof-of-mechanism for TL1A inhibition in RA with encouraging activity across both doses,” the company said in its announcement, while acknowledging the results were insufficient to justify continued development as a solo therapy.

The decision marks a strategic pivot rather than an outright abandonment of the asset. Spyre is now exploring where SPY072 may fit within combination frameworks, including its SPY772 program, which pairs the antibody with an IL-17A/F inhibitor for hidradenitis suppurativa. That combination will be evaluated in the Phase 2 SKYLIGHT proof-of-concept study, with top-line data expected in late 2027 or early 2028.

The SKYWAY basket study continues to evaluate SPY072 across two additional rheumatic indications. Enrollment in psoriatic arthritis and axial spondyloarthritis sub-studies was completed in June, and Spyre expects to report top-line proof-of-concept data from both in the fourth quarter of 2026.

Investors reacted swiftly to the news. Shares fell nearly 4% in after-hours trading on Tuesday, according to one report, while TipRanks data showed the decline reached as much as 14% at one point. The stock closed the regular session at $107.36, above both its 20-day exponential moving average of $103.75 and its 50-day exponential moving average of $96.37.

Year to date, Spyre shares have surged 227.8%, compared with 10.8% growth for the broader biotech industry, reflecting strong investor enthusiasm for the company’s TL1A franchise ahead of the readout.

Wall Street analysts remain broadly constructive on the stock. The consensus rating stands at Strong Buy, with 13 Buy recommendations and one Hold. The average 12-month price target of $124.73 implies roughly 16% upside from current levels.

Technical indicators also point to continued momentum. TipRanks’ Technical Analysis tool currently shows a Strong Buy signal on a one-day time frame, backed by 15 Bullish, five Neutral, and two Bearish signals. The Williams %R indicator suggests the stock is not overbought and has room to run.

The company’s broader pipeline strategy now hinges on the upcoming psoriatic arthritis and axial spondyloarthritis readouts in the fourth quarter, which will provide a clearer picture of SPY072’s potential in indications where TL1A biology may play a more central role.

Spyre’s decision to halt monotherapy development in rheumatoid arthritis underscores the increasingly competitive landscape for autoimmune treatments, where companies are setting higher internal benchmarks for differentiation before committing resources to late-stage development.