SPY120 / 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 (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

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

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

Spyre Therapeutics Announces Poster Presentation at the 20th Congress of the European Crohn’s and Colitis Organisation (PRNewswire) - "Spyre Therapeutics, Inc...today announced a poster presentation at the 20th Congress of the European Crohn's and Colitis Organisation (ECCO), held February 19-22, 2025, in Berlin, Germany, showing that combined inhibition of α4β7 integrin and TL1A cytokine is superior to either monotherapy in mouse models of colitis and coadministration demonstrates no drug-drug effects on exposure in non-human primates (NHPs)...'We are thrilled to share these recent preclinical findings supporting the combination potential for our SPY120 program...demonstrating that combined inhibition of the α4β7 integrin and TL1A cytokine provide additive or greater than additive efficacy relative to inhibition of either target alone,'...'We look forward to testing all three potential best-in-indication combinations in our Phase 2 trial in ulcerative colitis patients which is expected to begin mid-year.'"

New P2 trial • Preclinical • Inflammatory Bowel Disease • Ulcerative Colitis