Spyre Therapeutics Reports Positive Phase 2 SPY003 Data In Ulcerative Colitis
(RTTNews) - Spyre Therapeutics, Inc. (SYRE) announced positive 12-week induction results from Part A of the Phase 2 SKYLINE trial evaluating SPY003, an investigational extended half-life anti-IL-23 antibody, in patients with moderately-to-severely active ulcerative colitis (UC).
SPY003 met the study's primary endpoint, demonstrating a statistically significant 10.0-point reduction from baseline in Robart's Histopathology Index (RHI) score at Week 12 (p0.0001).
The study also showed a 20% clinical remission rate and a 30% endoscopic improvement rate at Week 12, while the modified Mayo Score declined by 3.5 points.
The SKYLINE Part A population included 44 participants, with 41% previously exposed to advanced therapies. Participants had a mean disease duration of 7.1 years and a mean baseline RHI score of 17.2.
Spyre said the 10.0-point RHI reduction with SPY003 was comparable to the 9.2-point reduction reported for SPY001 and the 10.7-point reduction for SPY002, supporting clinical proof-of-concept across all three components of its IBD combination strategy.
SPY003 was generally well tolerated, with a safety profile consistent with the IL-23 class.
A total of 19 participants (43%) experienced treatment-emergent adverse events.
Three serious adverse events were reported, all of which were considered unrelated to treatment.
The most common adverse events affecting at least two participants were arthralgia, nasopharyngitis and urinary tract infection.
One drug-related adverse event, Grade 1 pruritus, was reported and resolved without intervention or treatment interruption.
No adverse events led to treatment discontinuation, and no drug-related serious adverse events or deaths were reported.
With the SPY003 results, Spyre has now established clinical proof-of-concept for SPY001, SPY002 and SPY003, which target a4ß7, TL1A and IL-23, respectively.
SKYLINE Part B is actively enrolling and will evaluate the individual therapies at two dose levels as well as three high-dose pairwise combinations: SPY120, SPY130 and SPY230.
The company expects topline induction data from SKYLINE Part B in 2027.
Spyre believes the combinations could potentially provide improved efficacy, safety and dosing compared with existing treatments for inflammatory bowel disease.
Spyre is also advancing SPY072 in the SKYWAY Phase 2 trial for psoriatic arthritis and axial spondyloarthritis, with topline data expected in the fourth quarter of 2026.
The company is further evaluating SPY072 in combination with an IL-17A/F therapy in the SKYLIGHT program for hidradenitis suppurativa, with topline results expected in late 2027 or early 2028.
Spyre's pipeline includes investigational extended half-life antibodies targeting a4ß7, TL1A, IL-23 and IL-17A/F, along with rational combination programs aimed at developing next-generation therapies for immunology and inflammatory diseases.
SYRE closed Friday's trade at $88.98, up 1.98%. In the premarket trading, the stock is trading down 1.07% at $88.03.
