SPY230 / Spyre Therap - LARVOL DELTA

Next steps (GlobeNewswire) - "Clinical proof-of-concept across all three IBD programs strengthens the biological rationale for Spyre’s combination strategy and sets the stage for Part B of the SKYLINE trial, which is actively enrolling. Part B includes two dose levels of each monotherapy as well as three high-dose combination arms (SPY120, SPY130, and SPY230), which the Company believes have the potential to deliver best-in-disease efficacy, safety, and treatment experience. Topline induction data from Part B are expected in 2027."

P2 data • Ulcerative Colitis

SKYLINE-UC: The First Platform Study in Ulcerative Colitis Assessing Efficacy and Safety of Three Long-Acting Antibodies Administered as Single Agents and in Combinations (ACG 2026) - "The Phase 2 study SKYLINE-UC aims to assess the efficacy and safety of SPY001, SPY002, and SPY003 as single agents and in pairwise combinations (SPY120, SPY130, SPY230) in ulcerative colitis through a patient-centric study design that shares placebo and monotherapy data to minimize placebo exposure and overall enrollment. Evaluating three combinations in a platform study is estimated to reduce sample size by 45% compared to investigating the same hypotheses in separate studies. Part A data are anticipated to be available in 2026; Part B data are anticipated to be available in 2027. SKYLINE-UC is an innovative platform study that will evaluate 6 interventions, including 3 single agents and 3 pairwise combinations."

Clinical • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • Ulcerative Colitis • IL23A

SKYLINE-UC: The First Platform Study in Ulcerative Colitis Assessing Efficacy and Safety of Three Long-Acting Antibodies Administered as Single Agents and in Combinations (AOCC-IMKASID 2026) - "The Phase 2 study SKYLINE-UC aims to assess the efficacy and safety of SPY001, SPY002, and SPY003 as single agents and in pairwise combinations (SPY120, SPY130, SPY230) in ulcerative colitis through a patient-centric study design that shares placebo and monotherapy data to minimize placebo exposure and overall enrollment. 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 mono-therapy, and preliminary assessment of potential additive and/or synergistic benefits of combinations. Keywords: Ulcerative Colitis, Platform Trial, Combination Therapy, Half-life Extension, Proof Of Concept"

Clinical • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • Ulcerative Colitis • IL23A

Additionally, Spyre announced today that recruitment for Part A of SKYLINE is now closed and enrollment is open for Part B… (GlobeNewswire) - "...which includes three monotherapy cohorts (SPY001, SPY002, and SPY003) and three combination cohorts (SPY120, SPY130, and SPY230) into which participants may be randomized versus a shared placebo. Proof-of-concept induction data for the remaining cohorts of Part A are now expected mid-2026 (SPY002) and Q3 2026 (SPY003). Part B induction data (all cohorts) remain on track for 2027."

P2 data • Trial status • Ulcerative Colitis

Anti-TL1A and anti-IL-23 combination therapy is superior to its constituent monotherapies in mouse anti-CD40 colitis (ECCO-IBD 2026) - "Conclusion The combination of anti-TL1A and anti-IL-23 was more efficacious in mouse anti-CD40 colitis than anti-TL1A and anti-IL-23 monotherapies. These preclinical results support advancement of SPY230 in the ongoing SKYLINE-UC Phase 2 platform study in UC."

Combination therapy • Preclinical • Immunology • Inflammatory Bowel Disease • IL23A

SKYLINE-UC: The First Platform Study in Ulcerative Colitis Assessing Efficacy and Safety of Three Long-Acting Antibodies Administered as Single Agents and in Combinations (ECCO-IBD 2026) - "The aim of this study is to assess the efficacy & safety of SPY001, SPY002, and SPY003 as single agents & in pairwise combinations (SPY120 [SPY001 & SPY002], SPY130 [SPY001 & SPY003], SPY230 [SPY002 & SPY003]) in UC through a patient-centric study design that enables sharing of data from placebo and monotherapy treatment arms, thereby minimizing the number of participants assigned to placebo and enrolled overall. 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."

Clinical • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis • IL23A

Disproportionality analysis of semaglutide-associated bile-duct cancer: A vigibase study. (PubMed, Indian J Gastroenterol) - "While this study identifies a potential safety signal between semaglutide use and bile duct cancer, causality cannot be established. These findings underscore the importance of ongoing pharmacovigilance and the need for long-term observational studies and randomized controlled trials."

Journal • Biliary Cancer • Cardiovascular • Cholangiocarcinoma • Diabetes • Metabolic Disorders • Oncology • Pancreatic Cancer • Solid Tumor • Thyroid Gland Carcinoma • Thyroid Gland Medullary Carcinoma

Additionally, we are pleased to share new preclinical data demonstrating that each of our combination programs (α4β7 + TL1A, α4β7 + IL-23, and TL1A + IL-23) exhibit superior efficacy relative to constituent monotherapies in rodent TNBS-induced colitis models... (GlobeNewswire) - "The poster will be available for viewing during the UEGW Congress..."

Preclinical • Inflammatory Bowel Disease • Ulcerative Colitis