What question did this study set out to answer?

To evaluate the efficacy and safety of three long-acting monoclonal antibodies as single agents and in combinations for ulcerative colitis treatment.

January 23, 2026

P0978SKYLINE-UC: The First Platform Study in Ulcerative Colitis Assessing Efficacy and Safety of Three Long-Acting Antibodies Administered as Single Agents and in Combinations

Key Points

To evaluate the efficacy and safety of three long-acting monoclonal antibodies as single agents and in combinations for ulcerative colitis treatment.
Ongoing platform study with a master protocol for operational efficiency.
Includes an open-label Part A and randomized placebo-controlled Part B.
Part A assesses single-agent efficacy and safety; Part B explores single agents and combination therapies.
Predicted to reduce sample size by 45% compared to separate studies.
Preliminary efficacy and safety data expected in 2026 for Part A and 2027 for Part B.

Abstract

Abstract Background SPY001, SPY002, and SPY003 are investigational monoclonal antibodies to α4β7, TL1A, and IL-23, respectively, which are validated targets in IBD. All three antibodies incorporate YTE modifications in the Fc region for half-life extension, potentially enabling quarterly or semiannual dosing either as monotherapy or combination treatments. Preclinical data suggest at least additive effectiveness for the pairwise combinations in preventing colitis development. The aim of this study is to assess the efficacy Part B data are anticipated to be available in 2027. Conclusion SKYLINE-UC is an innovative platform study that will evaluate 6 interventions, including 3 single agents and 3 pairwise combinations. The study is designed to provide proof of concept for each investigational monotherapy and combination compared to placebo, dose-ranging data on each monotherapy, and a preliminary assessment of the additive and/or synergistic benefit of combinations. Conflict of interest: Danese, Silvio: Personal Fees: AbbVie, Alimentiv, Allergan, Amgen, Applied Molecular Transport, AstraZeneca, Athos Therapeutics, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Celltrion, Dr Falk Pharma, Eli Lilly, Enthera, Ferring Pharmaceuticals Inc., Gilead, Hospira, Inotrem, Janssen, Johnson & Johnson, Morphic, MSD, Mundipharma, Mylan, Pfizer, Roche, Sandoz, Sublimity Therapeutics, Takeda, Teladoc Health, TiGenix, UCB Inc., Vial, Vifor Lecture fees from Abbvie, Amgen, Ferring Pharmaceuticals Inc., Gilead, Janssen, Mylan, Pfizer, Takeda Jairath, Vipul: Consulting Fees: Abbvie, Alimentiv, Amgen, Anaptys Bio, Asahi Kasei, Asieris, Astra Zeneca, Attovia, Blackbird Labs, BMS, Boehringer Ingleheim, Biomebank, Caldera, Calluna, Catalytic Health, Celltrion, Ensho, Enthera, Exeliome Biosciences, Ferring, Fresenius Kabi, Gilead, Granite Bio, GSK, Janssen, Lilly, Merck, Mountainfield, MRM Health, Nxera, Organon, OSE Immunotherapeutics, Pendopharm, Pioneering Medicine, Pfizer, Prometheus, Roche/Genentech, Sanofi, SCOPE, Shattuck Labs, Sorriso, Spyre, Synedgen, Takeda, Teva, Tillotts, Union Therapeutics, Ventus, Ventyx, Vividion, Xencor, Zealand Pharma. Lu, Jd: Employee and shareholder of Spyre Therapeutics Zinder, Matthew: Employee and shareholder of Spyre Therapeutics Vugmeyster, Yulia: Employee and shareholder of Spyre Therapeutics Friedman, Joshua: Employee and shareholder of Spyre Therapeutics Huyghe, Mira: Employee and shareholder of Spyre Therapeutics Sloan, Sheldon: Employee and shareholder of Spyre Therapeutics Ms. Nguyen, Deanna: Employee and shareholder of Spyre Therapeutics

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Cite This Study

Danese et al. (Thu,) studied this question.

synapsesocial.com/papers/69731005c8125b09b0d1fb7f https://doi.org/https://doi.org/10.1093/ecco-jcc/jjaf231.1159

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