SPY072 / Spyre Therap - LARVOL DELTA

Spyre Therapeutics Announces Topline Results from the Rheumatoid Arthritis Sub-study of the SKYWAY Phase 2 Trial of SPY072 (GlobeNewswire) - "Both doses of SPY072 demonstrated statistically significant benefits compared to placebo on one or more of the primary (change from baseline in DAS28-CRP), key secondary (ACR20), and exploratory endpoints (ACR50). SPY072 was well tolerated, with a safety profile consistent with the TL1A class. The results provide proof-of-mechanism for TL1A in RA and support its potential in other autoimmune diseases and as a combination component, but did not meet the Company’s internal bar to prioritize advancement of SPY072 in RA."

P2 data • Rheumatoid Arthritis

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

Topline data for SPY072 in psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA) on track for Q4 2026 and for SPY072 in combination with IL17-A/F in hidradenitis suppurativa (HS) in late 2027 or early 2028 (GlobeNewswire)

P2 data • Hidradenitis Suppurativa • Psoriatic Arthritis • Spondylarthritis

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

SKYWAY Phase 2 Basket Trial in Rheumatic Diseases (RA, PsA, and axSpA) (GlobeNewswire) - "RA sub-study: Double-blind, placebo-controlled safety and efficacy study of two dose levels of SPY072 at Week 12 with open-label follow-up through Week 36. Topline proof-of-concept data are expected in September 2026; PsA sub-study: Double-blind, placebo-controlled safety and efficacy study of a single dose level of SPY072 at Week 16 with open-label follow-up through Week 40. Topline proof-of-concept data are expected in the fourth quarter of 2026; axSpA sub-study: Double-blind, placebo-controlled safety and efficacy study of a single dose level of SPY072 at Week 16 with open-label follow-up through Week 40. Topline proof-of-concept data are expected in the fourth quarter of 2026."

P2 data • Ankylosing Spondylitis • Immunology • Psoriatic Arthritis • Rheumatoid Arthritis

Spyre Therapeutics Announces Launch of SPY772 Program and Initiation of Phase 2 SKYLIGHT Trial in Hidradenitis Suppurativa (The Manila Times) - "To test the hypothesis of the SPY772 program, the company also announced the initiation of SKYLIGHT, a randomized Phase 2 proof-of-concept trial evaluating dual inhibition of TL1A and IL-17A/F in Hidradenitis Suppurativa (HS)....SKYLIGHT is a randomized, placebo-controlled Phase 2 proof-of-concept study expected to enroll approximately 150 adults with moderate-to-severe HS. Participants will receive background bimekizumab therapy and either SPY072 or placebo. The primary endpoint is the proportion of patients achieving a HiSCR75 response at Week 16. Topline results are expected in late 2027 or early 2028."

New molecule • New P2 trial • P2 data • Hidradenitis Suppurativa

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

TL1A inhibition is efficacious in mouse models of collagen-induced arthritis (CIA) and imiquimod-induced (IMQ) psoriasis (EULAR 2026) - P2 | "Objectives Compare the biological activity of anti-TL1A in mouse models of rheumatoid arthritis (CIA) and psoriasis (IMQ) to positive controls adalimumab (anti-TNF antibody; CIA and IMQ) and an anti-IL-23 antibody (IMQ). Taken together, the data suggest that anti-TL1A therapy has the potential to improve joint (RA, PsA) and skin (PsA) symptoms associated with rheumatic diseases. These data support the ongoing clinical trial of SPY072 in patients with rheumatic disease (SKYWAY-RD, NCT07148414)."

Preclinical • Ankylosing Spondylitis • Dermatology • Immunology • Inflammatory Arthritis • Psoriasis • Psoriatic Arthritis • Rheumatoid Arthritis • Rheumatology • Seronegative Spondyloarthropathies • Spondylarthritis • IL23A

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

Spyre Therapeutics Announces Completion of Enrollment in SKYWAY Basket Trial Evaluating SPY072 (anti-TL1A) in RA, PsA, and axSpA (GlobeNewswire) - "Company reiterates expected Q3 2026 readout for rheumatoid arthritis (RA) and Q4 2026 readouts for PsA and axSpA...'With SKYWAY and SKYLINE Part A now fully enrolled, we are on track for the remaining five of our six planned Phase 2 readouts in 2026.'....Preclinical data supporting the efficacy of anti-TL1A in rheumatic diseases will be presented on June 4 at the 2026 European Congress of Rheumatology (EULAR) in London."

Enrollment closed • P2 data • Preclinical • Ankylosing Spondylitis • Immunology • Psoriatic Arthritis • Rheumatoid Arthritis

Discovery, development, and characterization of SPY002 and SPY072, two novel extended half-life monoclonal antibodies targeting TL1A: in vitro properties, in vivo pharmacology, pharmacokinetics, and preclinical safety. (PubMed, MAbs) - "In a rat collagen-induced arthritis model, anti-TL1A antibody treatment effectively reduced arthritis severity, with similar efficacy to the TNF antagonist etanercept. In humanized mouse Imiquimod-induced psoriasis and 2,4,6‑trinitrobenzene sulfonic acid colitis models, anti-TL1A demonstrated similar efficacy to anti-IL-23 and anti-TNF antibodies. These findings characterize two novel extended half-life TL1A antibodies and support the ongoing Phase 2 clinical development of SPY002 and SPY072 for immune-mediated diseases such as inflammatory bowel disease and rheumatic diseases."

Journal • PK/PD data • Preclinical • Crohn's disease • Dermatology • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • Oncology • Psoriasis • Rheumatology • Ulcerative Colitis • IL23A

SKYWAY Phase 2 Basket Trial in Rheumatic Diseases (RA, PsA, axSpA) (GlobeNewswire) - "This sub-study has completed enrollment ahead of schedule and topline proof-of-concept data are expected in the third quarter of 2026...PsA sub-study...Enrollment continues in this sub-study and topline proof-of-concept data are expected in the fourth quarter of 2026...axSpA sub-study...Enrollment continues in this sub-study and topline proof-of-concept data are expected in the fourth quarter of 2026."

P2 data • Ankylosing Spondylitis • Psoriatic Arthritis • Rheumatoid Arthritis

Spyre Announces Acceleration of Expected Topline Readout of SKYWAY Rheumatoid Arthritis Sub-study to Q3 2026 (GlobeNewswire) - "Recruitment for the rheumatoid arthritis (RA) sub-study of the SKYWAY basket trial is complete; Week 12 topline data now expected in Q3 2026. Recruitment for the psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA) sub-studies of SKYWAY remain on track; Week 16 topline readouts expected in Q4 2026. SKYLINE platform trial in ulcerative colitis (UC) continues to enroll ahead of schedule; Part A readouts to begin in Q2 2026."

Enrollment status • P2 data • Psoriatic Arthritis • Rheumatoid Arthritis • Spondylarthritis • Ulcerative Colitis

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

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

Spyre Therapeutics Announces Positive Interim Phase 1 Results for SPY003, Its Novel, Half-Life Extended anti-IL-23 Antibody (GlobeNewswire) - "SPY003 was well tolerated at all dose levels, with a favorable safety profile consistent with the anti-IL-23 class. There were two Grade 2 or above treatment-emergent adverse events (TEAEs), both deemed not treatment-related, and no serious adverse events were observed in the study....SPY003 expected to advance to the ongoing Part A of the SKYLINE Ph2 platform trial. SKYLINE and SKYWAY trials are expected to provide 6 proof-of-concept readouts in 2026."

P1 data • P2 data • Trial status • Inflammatory Bowel Disease • Psoriatic Arthritis • Rheumatoid Arthritis • Spondylarthritis

Spyre Therapeutics Announces Poster Presentations at American College of Rheumatology (ACR) Convergence 2025 (The Manila Times) - "'The data continue to show SPY072 is well tolerated, has a differentiated PK profile supporting quarterly or twice-yearly dosing, and suppresses free TL1A through 20 weeks at the lowest dose....Additionally, we are pleased to share new preclinical data demonstrating that anti-TL1A antibody treatment meets or exceeds the efficacy of etanercept in a rodent model of collagen-induced arthritis...'"

P1 data • Preclinical • Rheumatoid Arthritis

SKYWAY-RD: A Study of SPY072 in Rheumatic Disease (clinicaltrials.gov) - P2 | N=285 | Recruiting | Sponsor: Spyre Therapeutics, Inc. | Trial primary completion date: Mar 2028 ➔ Oct 2026

Trial primary completion date • Ankylosing Spondylitis • Hematological Disorders • Immunology • Inflammatory Arthritis • Psoriatic Arthritis • Rheumatoid Arthritis • Rheumatology • Seronegative Spondyloarthropathies • Spondylarthritis

Spyre Therapeutics Doses First Patient in Pioneering Phase 2 SKYWAY Basket Trial of SPY072, the First Anti-TL1A Antibody Studied in Rheumatic Diseases (GlobeNewswire) - "SKYWAY study is evaluating SPY072 in patients with moderate-to-severely active rheumatoid arthritis (RA), psoriatic arthritis (PsA), and axial spondyloarthritis (axSpA). Proof-of-concept data for all three indications are expected in 2026."

P2 data • Trial status • Psoriatic Arthritis • Rheumatoid Arthritis • Spondylarthritis

SKYWAY-RD: A Study of SPY072 in Rheumatic Disease (clinicaltrials.gov) - P2 | N=285 | Recruiting | Sponsor: Spyre Therapeutics, Inc.

New P2 trial • Ankylosing Spondylitis • Hematological Disorders • Immunology • Inflammatory Arthritis • Psoriatic Arthritis • Rheumatoid Arthritis • Rheumatology • Seronegative Spondyloarthropathies • Spondylarthritis

SKYWAY-RD: Basket Phase 2 trial of anti-TL1A in Three Rheumatologic Conditions (PRNewswire) - "SKYWAY-RD is a planned Phase 2 randomized and placebo-controlled basket trial of SPY072 in patients with moderately to severely active RA, PsA, or axSpA with inadequate response to conventional or advanced therapies. RA sub-study: Double-blind, placebo-controlled safety and efficacy study of two dose levels of SPY072 through Week 12 with open-label follow-up through Week 36; PsA sub-study: Double-blind, placebo-controlled safety and efficacy study of a single dose level of SPY072 through Week 16 with open-label follow-up through Week 40; axSpA sub-study: Double-blind, placebo-controlled safety and efficacy study of a single dose level of SPY072 through Week 16 with open-label follow-up through Week 40...Topline proof-of-concept data are expected in 2026."

New P2 trial • P2 data • Immunology • Inflammation • Psoriatic Arthritis • Rheumatoid Arthritis

Spyre Therapeutics Announces Positive Interim Phase 1 Results for Two Next-Generation TL1A Antibody Programs, and Provides Clinical Development Updates Expected to Deliver 9 Phase 2 Readouts (PRNewswire) - P1 | N=56 | NCT06622070 | NCT06672718 | Sponsor: Spyre Therapeutics, Inc | "Interim results from the Phase 1 trials for SPY002 and SPY072, with data reported as of May 30, 2025, met all Phase 1 objectives, supporting their potential to become next-generation anti-TL1A monotherapies in immune-mediated diseases or as elements of combination therapies. Single doses of up to 1500 mg for SPY002 and SPY072 were well tolerated with no serious adverse events reported, exhibited a prolonged half-life supportive of quarterly or less frequent dosing, and suppressed free TL1A through 20 weeks of follow up available for the lowest dose tested...SPY002 half-life is estimated at ~75 days across IV and SC SAD cohorts, more than 3-fold greater than first-generation anti-TL1As; SPY072 showed comparable PK to SPY002 at clinically relevant doses through available follow up; waiting for comparable follow-up to accurately estimate half-life."

P1 data • Immunology • Inflammation • Ulcerative Colitis

Spyre Therapeutics Reports First Quarter 2025 Financial Results and Provides Corporate Update (PRNewswire) - "In January 2025, the Company announced its intent to study one of its anti-TL1A antibodies in RA, with Phase 2 trial initiation expected in mid-2025 and topline results in 2026. With class-leading potency and half-life established in preclinical studies, SPY002 has the potential to become the first-in-class and best-in-class anti-TL1A treatment for RA...Company announced initiation of first-in-human ('FIH') trials of both SPY002 candidates, with healthy volunteer interim data expected in the second quarter of 2025...In March 2025, the Company initiated a FIH trial of SPY003, with healthy volunteer interim data expected in the second half of 2025....The Company expects to initiate a Phase 2 clinical trial in 2025 that is intended to include each of its rational combinations, as well as all three of its lead monotherapy programs."

Clinical data • New P2 trial • Immunology • Inflammatory Bowel Disease • Rheumatoid Arthritis