Jefferies has reiterated in a new research note that Spyre Therapeutics (NASDAQ: SYRE) remains its favorite small- and mid-cap biotech name looking toward 2027, with the brokerage highlighting the company's long-acting combination therapies in inflammatory bowel disease (IBD).
Spyre is currently advancing three combination regimens targeting ulcerative colitis and Crohn's disease, all of which are expected to report Phase II clinical trial data in 2027. Jefferies believes existing clinical and real-world study results provide positive support for Spyre's development strategy.
Three combination therapies advancing in parallel, with key clinical data expected in 2027
Spyre's core strategy is to combine drugs with different mechanisms of action into long-acting combination formulations, aiming to improve efficacy while reducing dosing frequency for patients. The three combination therapies the company is developing are: SPY130, which combines an IL-23 inhibitor with an alpha-4-beta-7 integrin inhibitor; SPY230, which combines an IL-23 inhibitor with a TL1A inhibitor; and SPY120, which combines an alpha-4-beta-7 integrin inhibitor with a TL1A inhibitor.
Jefferies noted that data Spyre released earlier this year on its long-acting alpha-4-beta-7 therapy already showed positive efficacy signals, and that the relevant treatment targets have a favorable safety foundation, giving the company certain advantages in developing combination therapies. All three products are expected to report Phase II clinical data in 2027, and those results will serve as an important basis for assessing their efficacy, safety, and future development prospects.
Real-world study shows some combination regimens achieved clinical remission rates above 90%
Jefferies placed particular emphasis on the COMBEII real-world study presented at the 2026 United European Gastroenterology Week (UEGW). The study followed 249 patients with inflammatory bowel disease in Spain and compared the clinical performance of different combination treatment strategies.
The data showed that combination treatment with a JAK inhibitor and an IL-23 inhibitor achieved a clinical remission rate of 100%, while combination treatment with an integrin inhibitor and an IL-23 inhibitor achieved a clinical remission rate of 91%, making them the two best-performing combination approaches in the study. On safety, 12% of patients in the study experienced adverse events, 2% experienced serious adverse events, and 5.2% discontinued treatment due to toxicity, with no treatment-related deaths reported.
Jefferies believes these results indicate that combining therapeutic mechanisms across different inflammatory pathways may further improve clinical outcomes for patients with inflammatory bowel disease. In particular, the combination of an integrin inhibitor and an IL-23 inhibitor is mechanistically similar to SPY130, which Spyre is developing. However, the COMBEII study evaluated other combination therapies, and its results cannot be directly equated with the clinical efficacy of Spyre's candidate drugs, which still need to be validated in the company's own clinical trials.
Rheumatoid arthritis program makes positive progress as multiple investment banks maintain bullish stance
Beyond its inflammatory bowel disease pipeline, Spyre recently announced topline results from the Phase II SKYWAY-RA clinical program. The study showed that the company's SPY072/TL1A treatment regimen demonstrated evidence of efficacy in patients with rheumatoid arthritis, providing new clinical support for its TL1A-related development program.
After the data were released, UBS and JPMorgan both initiated coverage of Spyre with positive ratings, while Baird, Guggenheim, and Stifel also reiterated their prior buy or outperform ratings. As of the close on October 15, Spyre shares rose 1.87% to $80.10.
Looking ahead to the next year, Jefferies' main focus remains the Phase II clinical results for the three inflammatory bowel disease combination therapies. These data will determine whether the company can translate positive signals from existing target research and other combination therapies into real clinical competitiveness for its own candidate drugs.
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