SPY002 / Spyre Therap - LARVOL DELTA

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

Spyre Announces Potential Best-in-Class SPY003 (anti-IL-23) Part A Induction Results from SKYLINE Trial, Completing Proof-of-Concept for All Three Components of its IBD Combinations (GlobeNewswire) - "Initial 12-week findings from SKYLINE Part A demonstrated that SPY003 met all key objectives. The study population consisted of 41% advanced therapy-exposed participants with a mean disease duration of 7.1 years, a mean baseline RHI score of 17.2 ± 8.3 (SD), a mean modified Mayo Score of 6.9 ± 1.2 (SD), and 59% of whom had a baseline endoscopy score of 3. SPY003 achieved the primary endpoint, demonstrating a statistically significant 10.0-point reduction in RHI score (p<0.0001), robust rates of clinical remission and endoscopic improvement, and a meaningful change in mMS. The 10.0-point reduction in RHI observed in participants receiving SPY003 is in line with the 9.2- and 10.7-point reductions observed in participants receiving SPY001 and SPY002, respectively, and all are among the largest improvements observed in UC trials to date."

P2 data • Ulcerative Colitis

EFFICACY AND SAFETY OF HALF-LIFE EXTENDED ANTIBODIES SPY001, SPY002, AND SPY003 FOR INDUCTION TREATMENT OF MODERATELY TO SEVERELY ACTIVE ULCERATIVE COLITIS (UEGW 2026) - No abstract available

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

SPY002-072-101: A Study of SPY002-072 in Healthy Volunteers (clinicaltrials.gov) - P1 | N=40 | Completed | Sponsor: Spyre Therapeutics, Inc. | Recruiting ➔ Completed | Trial primary completion date: Apr 2026 ➔ Jul 2026

First-in-human • Trial completion • Trial primary completion date

Targeting the TL1A pathway in inflammatory bowel disease: mechanistic insights and emerging therapeutic pipeline. (PubMed, Inflamm Bowel Dis) - "Three anti-TL1A monoclonal antibodies (tulisokibart, afimkibart, and duvakitug) have advanced to phase 3 trials across multiple global programs, with phase 2 clinical remission rates of 26%-48% in ulcerative colitis (placebo-adjusted differences 15-26 percentage points) and endoscopic response rates of 26%-48% in Crohn's disease, alongside favorable safety profiles...The pipeline has expanded to at least 19 development programs, including extended half-life antibodies (XmAb942, SPY002, and BCD-261), bispecifics combining TL1A with IL-23 or α4β7 (RO7837195, XmAb412, LQ080, and ALX001), a first-in-class oral anti-TL1A nanobody, and a first-in-class DR3 receptor antagonist (SL-325). We discuss therapeutic positioning and timing, the opportunity in acute severe UC, and the unusual standing of IBD as the lead indication for this mechanism class."

Journal • Review • Crohn's disease • Fibrosis • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • Oncology • Ulcerative Colitis • CD40LG • IL23A • TNFA • TNFRSF25 • TNFSF15

SPY002-091-101: A Study of SPY002-091 in Healthy Volunteers (clinicaltrials.gov) - P1 | N=50 | Completed | Sponsor: Spyre Therapeutics, Inc. | Active, not recruiting ➔ Completed

First-in-human • Trial completion

A Study of SPY072 in Adults With Moderate to Severe Hidradenitis Suppurativa (The SKYLIGHT Trial) (clinicaltrials.gov) - P2 | N=150 | Not yet recruiting | Sponsor: Spyre Therapeutics, Inc.

New P2 trial • Dermatology • Hidradenitis Suppurativa • Immunology

SKYLINE Phase 2 Platform Trial in IBD (GlobeNewswire) - "Part A: Open-label assessment of the safety and preliminary efficacy of a single dose level of each investigational monotherapy. Enrollment for Part A has completed...topline data expected for SPY003 in September 2026....Part B: Randomized and placebo-controlled assessment of the safety and efficacy of monotherapies and combinations, designed to provide dose-ranging data on monotherapies, proof-of-concept, and contribution of components for combinations, with induction data expected in 2027."

P2 data • Ulcerative Colitis

SKYLINE-UC: A Study of Long-acting Antibodies Alone and in Combinations for Moderate to Severe Ulcerative Colitis (clinicaltrials.gov) - P2 | N=645 | Recruiting | Sponsor: Spyre Therapeutics, Inc. | Trial primary completion date: Jun 2026 ➔ Jun 2027

Trial primary completion date • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • 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

SKYLINE-LTE: Long-term Safety and Efficacy of Multiple Long-acting Antibodies Alone and in Combinations for IBD (clinicaltrials.gov) - P2 | N=645 | Enrolling by invitation | Sponsor: Spyre Therapeutics, Inc.

New P2 trial • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • Ulcerative Colitis

SPY123-202: Long-term Safety and Efficacy of Multiple Long-acting Antibodies Alone and in Combination for Inflammatory Bowel Disease (clinicaltrialsregister.eu) - P1/2 | N=102 | Not yet recruiting | Sponsor: Spyre Therapeutics Inc.

New P1/2 trial • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • Ulcerative Colitis

Spyre Announces Potential Best-in-Class SPY002 (anti-TL1A) Part A Induction Results from SKYLINE Trial in Moderate-to-Severe Ulcerative Colitis Patients (GlobeNewswire) - "Initial 12-week findings from SKYLINE Part A demonstrated that SPY002 met all key objectives. The study population consisted of 35% advanced therapy-exposed participants with a mean disease duration of 7.0 years, a mean baseline RHI score of 16.9 ± 8.5 (SD), a mean modified Mayo Score of 6.9 ± 1.0 (SD), and 56% of whom had a baseline endoscopy score of 3...Efficacy: SPY002 achieved the primary endpoint, demonstrating a statistically significant 10.7-point reduction in RHI score (p<0.0001), robust rates of clinical remission and endoscopic improvement, and a meaningful change in mMS, results that are among the highest reported in UC...SPY002 was well tolerated with a safety profile consistent with the TL1A class."

P2 data • Ulcerative Colitis

SPY002-091-101: A Study of SPY002-091 in Healthy Volunteers (clinicaltrials.gov) - P1 | N=50 | Active, not recruiting | Sponsor: Spyre Therapeutics, Inc. | Recruiting ➔ Active, not recruiting | Trial primary completion date: Feb 2026 ➔ Aug 2026

Enrollment closed • First-in-human • Trial primary completion date

Extended Interim Phase 1 Results for SPY072, a Novel Half-Life Extended Monoclonal Antibody Targeting TL1A, Suggest A Potential for Q3M or Q6M Maintenance Dosing for Rheumatic Disease (EULAR 2026) - "Objectives SPY002-072 (SPY072) is an investigational fully human IgG1 monoclonal antibody that specifically binds to TL1A and blocks the interaction of TL1A with its receptor, known as death receptor 3 (DR3). SPY072 was well tolerated, with all adverse events being non-serious and typical of a Phase 1 study in healthy volunteers. These results support the ongoing Phase 2 basket trial of SPY072 in RA, PsA, and axSpA (EUCT 2025-521791-63-00)."

Clinical • First-in-human • P1 data • Ankylosing Spondylitis • Immunology • Inflammation • Inflammatory Arthritis • Psoriasis • Psoriatic Arthritis • Rheumatoid Arthritis • Rheumatology • Seronegative Spondyloarthropathies • Spondylarthritis • TNFRSF25

SKYWAY-RD: A Study of SPY072 in Rheumatic Disease (clinicaltrials.gov) - P2 | N=285 | Active, not recruiting | Sponsor: Spyre Therapeutics, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Ankylosing Spondylitis • Hematological Disorders • Immunology • Inflammatory Arthritis • Psoriatic Arthritis • Rheumatoid Arthritis • Rheumatology • Seronegative Spondyloarthropathies • Spondylarthritis • CRP • IL17A

Development Pipeline Overview and Update (The Manila Times) - "SKYLINE Phase 2 Platform Trial in IBD...topline data expected for SPY002 and SPY003 in mid-2026 and the third quarter of 2026, respectively....Part B: Randomized and placebo-controlled assessment of the safety and efficacy of monotherapies and combinations, designed to provide dose-ranging data on monotherapies, proof-of-concept, and contribution of components for combinations, with induction data expected in 2027....SKYLINE is currently enrolling participants into Part B of the trial."

P2 data • Trial status • Ulcerative Colitis

SKYLINE-UC: A Study of Long-acting Antibodies Alone and in Combinations for Moderate to Severe Ulcerative Colitis (clinicaltrials.gov) - P2 | N=645 | Recruiting | Sponsor: Spyre Therapeutics, Inc.

Trial initiation date • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • Ulcerative Colitis

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

SPY123-201: A Study of Long-acting Antibodies Alone and in Combinations for Moderate to Severe Ulcerative Colitis (clinicaltrialsregister.eu) - P1/2 | N=238 | Recruiting | Sponsor: Spyre Therapeutics Inc.

New P1/2 trial • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis • IL23A

SPY002-072-201: SPY002-072 in Adults with Moderately to Severely Active Rheumatologic Disease (clinicaltrialsregister.eu) - P1/2 | N=236 | Recruiting | Sponsor: Spyre Therapeutics Inc.

New P1/2 trial • Hematological Disorders • Rheumatology • CRP • IL17A

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

Rational Combinations – the Company plans to investigate combinations of our proprietary antibodies in nonclinical studies and clinical trials in order to evaluate whether combinations can potentially lead to best-in-class efficacy in IBD, with less frequent dosing. (GlobeNewswire) - "The Company expects to include each of its rational combinations in Part B of the SKYLINE trial."

New trial • Preclinical • Trial status • Inflammatory Bowel Disease • Ulcerative Colitis

The Company has two ongoing Phase 2 clinical trials with proof-of-concept data readouts beginning in 2026 (GlobeNewswire) - "Enrollment on track in Phase 2 SKYWAY basket trial evaluating TL1A inhibition in rheumatoid arthritis ('RA'), psoriatic arthritis ('PsA'), and axial spondyloarthritis ('axSpA'), with fourth quarter readouts expected in each sub-study...SKYLINE Phase 2 Platform Trial in IBD...Part A: Open-label assessment of the safety and preliminary efficacy of a single dose level of each investigational monotherapy, with induction data expected beginning in the second quarter of 2026; Part B: Randomized and placebo-controlled assessment of the safety and efficacy of investigational monotherapies (two dose levels) and combinations, with induction data expected in 2027...SKYLINE is currently enrolling subjects into Part A of the trial, with Part B expected to begin enrolling after all arms in Part A complete enrollment."

P2 data • Trial status • Ankylosing Spondylitis • Psoriatic Arthritis • Rheumatoid Arthritis • Ulcerative Colitis

Spyre Therapeutics Poised for Transformational 2026 With Six Expected Proof-of-Concept Readouts Beginning in Q2 (GlobeNewswire) - "SKYLINE (NCT07012395) is a Phase 2 platform trial of SPY001 (anti-α4β7), SPY002 (anti-TL1A), SPY003 (anti-IL-23), and pairwise combinations thereof (six investigational long-acting agents in total) in patients with moderately to severely active ulcerative colitis...Enrollment in Part A has exceeded expectations with SPY001 enrollment completed ahead of schedule. Readouts for Part A are now expected to begin in Q2....SKYWAY (NCT07148414) is a Phase 2 basket trial of SPY072 (anti-TL1A) in patients with moderate to severely active RA, PsA, or axSpA. Enrollment is on track, and all indications are expected to readout in 4Q 2026."

Enrollment status • P2 data • Ankylosing Spondylitis • Psoriatic Arthritis • Rheumatoid Arthritis • Ulcerative Colitis