Spyre Therapeutics’ stock is up nearly 30% after its ulcerative colitis (UC) candidate has demonstrated competitive remission-prompting potential during a Phase II study, leading analysts to tout the drug as a potential best-in-class therapy in this indication.
In the open-label, Part A of the Phase II SKYLINE study (NCT07012395), patients with moderate-to-severe active UC were given an induction course of either Spyre’s α4β7-targeting antibody SPY001, the company’s TL1A blocker SPY002 or its IL-23 inhibitor, SPY003. This topline readout covers data from the SPY001 treatment cohort.
Go deeper with GlobalData
Discover B2B Marketing That Performs
Combine business intelligence and editorial excellence to reach engaged professionals across 36 leading media platforms.
During this portion of the study, SPY001 met the trial’s primary endpoint – triggering a statistically significant 9.2-point drop from baseline in patient Robart’s histopathology index (RHI) scores at week 12.
The gut-selective anti-α4β7 therapy, which was administered intravenously in this portion of the trial, also prompted clinical remission and endoscopic improvement in 40% and 51% of those receiving the drug over a 12-week period.
Alongside its promising efficacy, SPY001 was also well tolerated in this study, with six of 43 (14%) of patients experiencing an adverse event (AE) of any grade. Spyre says that none of these AEs were linked to treatment with the drug.
After the data was released, Spyre’s stock, listed on the Nasdaq exchange, rose 29.7% to $66.50 at market open on 13 April from a $51.29 close on 10 April.
SPY001 differs from other anti-α4β7 therapies on the market due to its extended half-life, Spyre says, which means the drug is being developed to treat UC on a Q3M and Q6M maintenance dosing schedule.
Following the positive preliminary outcomes of the SKYLINE trial, Spyre will enrol patients for Part B of the study, which will look at the potential of each drug as a monotherapy and in combinations – with induction data from this portion of the trial expected in 2027. Spyre will also share induction data from the remaining Part A cohorts for SPY002 and SPY003 in the second and third quarter of 2026, respectively.
SPY001’s “best-in-class” potential
In a 13 April investor call, Spyre’s CEO, Camron Turtle, touted SPY001’s potential as a best-in-class α4β7 blocker – a drug class that is currently dominated by Takeda’s blockbuster therapy, Entyvio (vedolizumab), which GlobalData expects will reach its sales peak of $6.9bn in 2030.
According to senior GlobalData analyst, Ophelia Chan, the SKYLINE results are highly encouraging, as they suggest that SPY001 may have the potential to exceed the historic therapeutic ceiling of the anti-α4β7 class. Chan added that the drug’s “gut selective biology, strong early efficacy and substantially improved dosing convenience” could position SPY001 to compete more broadly with other therapies in the advanced UC therapeutic space.
“If this efficacy, safety and convenience are sustained in later studies, SPY001 could emerge as a potential best-in-class anti-α4β7 agent and a highly attractive option for maintenance-heavy chronic IBD care, particularly as a more convenient successor to current gut-selective maintenance therapy in UC,” Chan added.
In a 7 April pre-readout research note, Guggenheim analysts noted that SPY001 has the “best value proposition for this induction study” in their eyes, as well as the greatest potential as a standalone monotherapy treatment.
Spyre seeks combination glory in IBD
While Turtle backs SPY001’s potential as a monotherapy in UC, he said that IL-23 or TIL-1A combinations will likely “provide additive efficacy”, adding that combination products priced like a single drug could pose as a more attractive option to patients and physicians alike.
According to Chan, SPY001’s broader IBD opportunity will likely depend on whether the drug demonstrates potential in Crohn’s disease, and if Spyre can successfully use the therapy as a backbone for combination regimens with SPY002 and SPY003.
“In this case, SPY001’s commercial upside may come not only from displacing older, gut-selective monotherapy, but also from anchoring a differentiated combination strategy across the wider IBD market,” Chan commented.
In a recent research note, analysts at LifeSci Capital explained that key opinion leaders in the space expect long-acting biologics, dosed between Q3M and Q6M, as well as co-formulated combinations, will “define the next era of care,” while double-digit remission improvements over monotherapies will be needed to alter long-standing treatment approaches.
Guggenheim analysts echoed this sentiment, caveating that Wall Street will be looking for a 10-15% efficacy improvement seen when using combinations over monotherapy.
