TLDR
- Guggenheim named Spyre Therapeutics its top biotech pick after positive Phase II data for SPY003 in ulcerative colitis
- SPY003 hit 20% clinical remission and 30% endoscopic remission in the SKYLINE-UC trial
- Baird reiterated Outperform with a $116 price target; Guggenheim holds a $130 target
- SYRE is up 442% year-to-date, trading around $90.79
- Key data from the larger SKYLINE Part B combination study is expected in 2027
Spyre Therapeutics (SYRE) is up over 2% on Wednesday, trading around $90.79, after Guggenheim named it the firm’s top biotech pick following Phase II trial results for its ulcerative colitis drug candidate SPY003.
Spyre Therapeutics, Inc., SYRE
The trial, known as SKYLINE-UC, evaluated SPY003 as a monotherapy across three arms with a combined 135 patients. SPY003 is a longer-acting anti-IL-23 monoclonal antibody.
Results showed 20% clinical remission, 30% endoscopic remission, and a negative 10.0 change in the Robarts Histopathology Index. Guggenheim said the data are consistent with other IL-23p19 comparator drugs already on the market.
Roughly 41% of patients enrolled were considered advanced therapy-experienced, meaning many had already tried and failed other treatments, including JAK inhibitors and IL-12/23 therapies. The safety profile came back clean, with no drug-related serious adverse events and no patients dropping out due to adverse events.
Guggenheim highlighted durability as the key advantage for SPY003, positioning it as a potential partner in combination therapy rather than just a standalone option.
What Analysts Are Saying
Baird also reiterated its Outperform rating on Wednesday, keeping its $116 price target in place. The firm said the SPY003 results were not a surprise given the well-established mechanism of action, but described them as incrementally positive.
Baird pointed out that the IL-23 inhibitory mechanism has already been validated by other approved drugs. The firm is focused on what comes next: the larger, placebo-controlled SKYLINE Part B study.
Guggenheim reiterated its Buy rating with a $130 target. Stifel also held its Buy rating with a $123 target. Mizuho lifted its price target to $120, citing the potential of SPY120 to achieve strong clinical remission rates.
Not everyone is bullish. Wolfe Research downgraded SYRE to Peerperform from Outperform, citing concerns around the evaluation of recent data and a lack of confidence in upcoming catalysts.
What Comes Next
The completion of Phase II Part A now opens the door for Part B, which is actively enrolling patients. That study will look at two dose levels of each monotherapy and three high-dose combination therapy arms, targeting the α4β7, TL1A, and IL-23 mechanisms together.
Topline induction data from Part B is expected in 2027. Baird said this is when the most important data for the company’s central thesis will arrive.
There is also a near-term catalyst to watch. Spyre’s SPY072 SKYWAY-RD readout in psoriatic arthritis and axial spondyloarthritis is expected in Q4 2026.
On the downside, Spyre recently reported that SPY072 in a rheumatoid arthritis sub-study did not meet its internal threshold for monotherapy development, despite showing statistically significant improvements over placebo. That result prompted the Wolfe Research downgrade.
Wall Street’s consensus remains a strong buy, with price targets ranging from $97 to $130. SYRE is up 442% year-to-date.
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