Stifel reiterated its Buy rating and $123 price target for Spyre Therapeutics Inc. (NASDAQ: SYRE) following mixed results from a rheumatoid arthritis sub-study of the SKYWAY Phase 2 trial for the company’s SPY072 drug.
The rheumatoid arthritis proof-of-concept sub-study met statistical significance on some endpoints and doses but fell short of demonstrating a competitive effect size to support monotherapy development. Safety outcomes aligned with expectations, though the trial faced challenges in meeting internal thresholds for prioritizing SPY072 as a standalone treatment. Spyre’s stock, trading at $107.36, remains near its 52-week high of $110.17 and has surged 529% over the past year, with a market capitalization of $9.47 billion.
The company also reported positive Phase 2 results for SPY002, an experimental ulcerative colitis drug, in the SKYLINE trial. SPY002 achieved its primary endpoint with a statistically significant reduction in Robart’s Histopathology Index score. Analysts noted that ulcerative colitis combination therapy data represents the majority of Spyre’s current valuation, despite the setback in rheumatoid arthritis.
Stifel emphasized the expansion thesis for TL1A outside inflammatory bowel disease, citing mechanistic and genetic rationale as key drivers for the therapeutic theme. The firm’s $123 price target implies roughly 15% upside from current levels. Mizuho raised its price target to $120, citing promising data for SPY001 and SPY002, while Wolfe Research downgraded Spyre to Peerperform due to valuation concerns.
Looking ahead, Spyre expects additional proof-of-concept datasets in axial spondyloarthritis and psoriatic arthritis by the fourth quarter of 2026. Phase 2 data for ulcerative colitis combination therapy is anticipated next year, with data from a planned hidradenitis suppurativa study expected in late 2027 or early 2028. The study will evaluate SPY001 in combination with IL-17A/F, following positive topline results from Merck and Recursion Pharmaceuticals’ Tulisokibart.
Separately, Fairmount Healthcare Fund II L.P. sold over 4.6 million shares, reducing its holdings to zero, according to regulatory filings.
