Spyre Therapeutics Announces Strong Phase 2 SKYLINE Part A Results for SPY001 in Ulcerative Colitis

WALTHAM, Mass., April 13, 2026 – Spyre Therapeutics, Inc. (NASDAQ: SYRE), a clinical-stage biotechnology company focused on innovative therapies for inflammatory bowel disease (IBD) and rheumatic diseases, has announced highly positive topline data from Part A of its Phase 2 SKYLINE trial. The trial assesses the efficacy and safety of SPY001, a next-generation anti-α4β7 antibody being developed for moderate-to-severe ulcerative colitis (UC).

Key Highlights for Investors

• SPY001 meets primary endpoint: The drug demonstrated a statistically significant reduction of 9.2 points (p<0.0001) from baseline at Week 12 in the Robart’s Histopathology Index (RHI) score, which was the primary endpoint for the trial.
• Strong Secondary Outcomes:
  • Clinical remission rate by modified Mayo score reached 40% at week 12.
  • Endoscopic improvement rate was 51%.
  • Change in Modified Mayo Score was -3.7 points.
• Favorable Safety Profile: SPY001 was well tolerated. Only 6 out of 43 patients (14%) experienced treatment-emergent adverse events (TEAEs), with one serious adverse event (SAE)—chest pain in a patient with pre-existing cardiac conditions—which was not drug related. There were no drug-related severe adverse events, no AEs leading to study discontinuation, and no deaths reported.
• Strategic Trial Progress: Recruitment for Part A is now complete, and Part B is underway. Part B will include three monotherapy cohorts (SPY001, SPY002 [anti-TL1A], SPY003 [anti-IL23]) and three combination cohorts (SPY120, SPY130, SPY230), all randomized against a shared placebo group.
• Upcoming Catalysts:
  • Proof-of-concept induction data for SPY002 and SPY003 in Part A expected mid-2026 and Q3 2026, respectively.
  • All Part B induction data readouts on track for 2027.
• Company Commentary: Management emphasized the potential best-in-class profile for SPY001, citing improved epitope targeting, potency, extended half-life, and enhanced induction dosing compared to vedolizumab. Additionally, the company views SPY001 as a strong backbone for future combination therapies with its other pipeline antibodies, SPY002 and SPY003.

Shareholder-Relevant and Price-Sensitive Information

• Clinical Success and Competitive Position: The robust efficacy and safety data position SPY001 as a potential best-in-class therapy for ulcerative colitis. These results could significantly impact the company’s valuation and competitive standing in the IBD field, especially as SPY001 was intentionally designed to improve on established therapies like vedolizumab.
• Pipeline Expansion and Upcoming Data Readouts: The transition to Part B and the inclusion of combination cohorts with anti-TL1A and anti-IL23 antibodies represent significant pipeline expansion with multiple value-creating catalysts anticipated over the next 12-18 months.
• Trial Execution and Enrollment: The company reported rapid enrollment and positive investigator enthusiasm, which may indicate strong support from the clinical community, likely reducing operational risk and accelerating timelines.
• Low Placebo Allocation in Part B: This design feature may further improve the probability of clinical success and is likely to be favorably viewed by both investigators and investors.
• Market Differentiation and Potential: SPY001’s extended half-life and dosing convenience, along with its potential as a combination therapy backbone, could set a new standard in IBD treatment, expanding the addressable market and improving commercial prospects.

Additional Details for Investors

The SKYLINE trial is a multi-part, platform study evaluating SPY001, SPY002, SPY003, and their pairwise combinations (six investigational agents in total) in patients with moderately to severely active UC. Part A was an open-label assessment of single-dose monotherapies, while Part B is a randomized, placebo-controlled study with two dose levels and combinations.

SPY001 targets the α4β7 integrin, a key mediator of immune cell migration to the gut, with the potential for improved efficacy, durability, and convenience compared to existing antibody therapies. The management team believes the molecule’s profile supports its use both as a monotherapy and as a platform for rational combination therapies targeting other inflammatory pathways.

The company will host a webcast event with more details and will provide ongoing updates as additional data from both monotherapy and combination cohorts become available.

Forward-Looking Statements

Certain statements in this article may constitute forward-looking statements, including remarks regarding the clinical development, timing of data readouts, and potential commercial prospects of Spyre’s pipeline. These statements are based on current expectations and are subject to risks and uncertainties, including regulatory interactions, trial outcomes, and broader market conditions. Investors are advised to review the company’s filings with the SEC for a fuller discussion of risks.

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