SYRE Stock Sinks After Mixed SKYWAY Study Data in Rheumatoid Arthritis

Spyre Therapeutics SYRE announced top-line data from the rheumatoid arthritis (RA) sub-study of its phase II SKYWAY basket study evaluating SPY072, an investigational long-acting anti-TL1A antibody.

The randomized, placebo-controlled SKYWAY-RA study evaluated two doses (high and low) of SPY072 in patients with moderately to severely active RA who had an inadequate response to conventional or advanced therapies. The primary endpoint was the change from baseline in Disease Activity Score in 28 joints, C-reactive protein (DAS28-CRP) at week 12, while ACR20 response at week 12 was a key secondary endpoint.

Key Highlights of SYRE’s Phase II SKYWAY-RA Study

The SKYWAY-RA study data highlighted SPY072’s encouraging activity in RA across both doses. At week 12, the low dose achieved a statistically significant improvement in DAS28-CRP from baseline, with a reduction of 1.9 points compared with 1.3 points for placebo. The high dose produced a 1.5-point reduction. ACR20 and ACR50 responses were numerically higher, at the high and low doses of SPY072, respectively.

Both doses achieved the targeted drug concentrations and maintained complete suppression of free TL1A through week 12, confirming robust target engagement. The treatment was generally well-tolerated, and the safety profile was consistent with the TL1A class.

Spyre Shifts Focus Away From RA Monotherapy

Despite demonstrating proof-of-mechanism for TL1A inhibition in RA, the magnitude of benefit did not meet Spyre’s internal threshold to advance SPY072 as an RA monotherapy, which investors interpreted as a setback for the program. Consequently, the company is shifting its development focus toward broader autoimmune indications and combination therapies.

The update likely disappointed investors, with Spyre shares falling nearly 4% in after-hours trading on Tuesday.

Year to date, Spyre’s shares have skyrocketed 227.8% compared with the industry’s 10.8% growth.

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More on Spyre’s SPY072

The SKYWAY basket study is evaluating SPY072 across three rheumatic diseases: RA, psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA). In June, Spyre completed enrollment in PsA and axSpA sub-studies. The company expects to report top-line proof-of-concept data from both studies in the fourth quarter of 2026.

Earlier this month, Spyre expanded its development strategy into hidradenitis suppurativa (HS), evaluating a long-acting combination of SPY072 and SPY007 (anti-IL-17A/F). The combination will be evaluated in the phase II SKYLIGHT proof-of-concept study, with top-line data expected in late 2027 or early 2028.

SYRE’s Zacks Rank & Stocks to Consider

Spyre currently carries a Zacks Rank #3 (Hold).

Some better-ranked stocks in the biotech sector are Amneal Pharmaceuticals AMRX, currently sporting a Zacks Rank #1 (Strong Buy), while AC Immune ACIU and Precigen PGEN carry a Zacks Rank #2 (Buy) each. You can see the complete list of today’s Zacks #1 Rank stocks here.

Over the past 30 days, earnings per share estimates for Amneal Pharmaceuticals have increased from $1.00 to $1.02 for 2026. Over the same period, estimates for earnings per share increased from $1.12 to $1.21 for 2027. AMRX shares have risen 42.2% year to date.

Amneal Pharmaceuticals beat earnings in each of the trailing four quarters, delivering an average surprise of 32.82%.

Over the past 30 days, estimates for AC Immune’s 2026 loss per share have narrowed from 84 cents to 60 cents. Over the same period, earnings estimates for 2027 remained unchanged at 17 cents. ACIU shares have declined 7% year to date.

AC Immune’s earnings beat estimates in each of the trailing four quarters, with the average surprise being 33.25%.

Over the past 30 days, estimates for Precigen’s 2026 loss per share have improved from a loss of two cents to earnings per share of 25 cents. Over the same period, earnings estimates for 2027 have risen from 25 cents to 86 cents. PGEN shares have gained 74.2% year to date.

Precigen’s earnings beat estimates in three of the trailing four quarters and missed in the remaining one, with the average surprise being 108.96%.

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