SPY001 / Spyre Therap - LARVOL DELTA

SPY001-101: A Study of SPY001-001 in Healthy Volunteers (clinicaltrials.gov) - P1 | N=96 | Completed | Sponsor: Spyre Therapeutics, Inc. | Active, not recruiting ➔ Completed

First-in-human • Trial completion

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

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

COMBINED INHIBITION OF INTEGRIN Β7 AND TL1A, INTEGRIN Β7 AND IL-23, OR TL1A AND IL-23 ARE SUPERIOR TO THEIR CONSTITUENT MONOTHERAPIES IN MOUSE TNBS-INDUCED COLITIS (UEGW 2025) - "Towards this end, Spyre Therapeutics is developing half-life extended antibody drug candidates that can be administered in combination, inhibiting the clinically validated IBD targets α4β7 integrin (SPY001), TL1A (SPY002), and IL-23 (SPY003). Combination therapy with anti-β7 + anti-TL1A, anti-β7 + anti-IL-23 or anti-TL1A + anti-IL-23 resulted in efficacy superior to their constituent monotherapies in the murine TNBS model of colitis. These data support and provide biologic rationale for the advancement of antibody combinations into human clinical trials for inflammatory bowel disease."

Preclinical • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • IL23A

SKYLINE-UC Phase 2 Platform Trial (GlobeNewswire) - "In May 2025, the Company initiated a Phase 2 induction and maintenance platform trial of SPY001, SPY002, SPY003, as well as pairwise combinations thereof (six active investigational agents in total) in patients with moderately to severely active UC. The trial consists of two parts: Part A: Open-label assessment of the safety and preliminary efficacy of a single dose level of each investigational monotherapy, with induction data expected in 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-UC is currently enrolling subjects into the SPY001 arm of Part A."

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. | N=35 ➔ 645 | Trial completion date: Jun 2027 ➔ Mar 2028

Enrollment change • Trial completion date • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • Ulcerative Colitis

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) - "Building on these encouraging Phase 1 results, Spyre is advancing SPY002 into the SKYLINE-UC platform trial – initiated in May 2025 – for ulcerative colitis. SKYLINE-UC is expected to include SPY001 (anti-α4β7), SPY002 (anti-TL1A), SPY003 (anti-IL-23), and combinations thereof under an efficient single master protocol...Part A: Induction data are expected in 2026; Part B: Induction data are expected in 2027."

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=35 | Recruiting | Sponsor: Spyre Therapeutics, Inc.

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

COMBINED INHIBITION OF TL1A AND INTEGRIN β7 IS SUPERIOR TO EITHER MONOTHERAPY IN MOUSE MODELS OF COLITIS AND COADMINISTRATION OF SPY001 AND SPY002 DEMONSTRATES NO DRUG-DRUG EFFECTS ON EXPOSURE IN NON-HUMAN PRIMATES (DDW 2025) - "Coadministration of SPY001 and SPY002 in NHPs demonstrated no drug-drug effects on PK. These preclinical results support the advancement of the combination of SPY001 and SPY002 into clinical trials."

Monotherapy • Preclinical • Gastroenterology • Gastrointestinal Disorder • Immunology

INTERIM PK DATA FOR SPY001, A NOVEL HALF-LIFE EXTENDED MONOCLONAL ANTIBODY TARGETING α4β7, SUGGEST A POTENTIAL FOR Q3M OR Q6M MAINTENANCE DOSING FOR INFLAMMATORY BOWEL DISEASE (DDW 2025) - "Vedolizumab, a mAb to the immune cell trafficking regulator α4β7, is approved for the treatment of moderately to severely active IBD with either Q8W IV or Q2W SC maintenance dosing. SPY001 was well tolerated with all adverse events being mild and typical of a Phase 1 study. These interim results support advancement of SPY001 into clinical trials in IBD as both a monotherapy and in combination therapy."

Clinical • PK/PD data • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • CD8

Spyre Therapeutics Announces Poster Presentations at Digestive Disease Week (DDW) 2025 Including Up to Eight months of Follow-up from an Ongoing Phase 1 Trial of SPY001 (PRNewswire) - P1 | N=NA | "Updated results from our ongoing Phase 1 trial of SPY001, our novel half-life extended α4β7 antibody for the treatment of IBD, continues to show that SPY001 is well tolerated, has a half-life of more than three-fold compared to vedolizumab based on population PK modeling, and sustains target engagement at expected Phase 2 trough concentrations. This longer follow-up data strengthens the potential for SPY001 to demonstrate improved induction responses with greater exposures as well as durable responses with quarterly or biannual maintenance dosing...Spyre presented expanded preclinical data on combined inhibition of α4β7 integrin and TL1A cytokine in murine colitis models. Data presented demonstrate that combined inhibition of α4β7 integrin and TL1A cytokine is superior to either monotherapy in mouse models of colitis....plans to initiate a Phase 2 platform trial in ulcerative colitis in mid-2025."

New P2 trial • P1 data • Preclinical • Inflammatory Bowel Disease • Ulcerative Colitis

Spyre Therapeutics Reports Fourth Quarter and Full Year 2024 Financial Results and Provides Corporate Update (PRNewswire) - "Reported positive interim pharmacokinetic ('PK') and safety data in Phase 1 trial of SPY001 in November 2024 and strengthened the balance sheet with a $230 million public offering...$603 million of cash, cash equivalents, and marketable securities as of December 31, 2024, with expected runway into the second half of 2028...'Additionally, the expansion of SPY002 into a Phase 2 rheumatoid arthritis trial this year represents a key step in addressing a pressing unmet need in a disease that affects millions across the globe'....SPY003 remains on track to initiate a FIH trial in the first quarter of 2025, with healthy volunteer interim data expected in the second half of 2025....Research and Development (R&D) expenses: R&D expenses totaled $50.5 million for the fourth quarter of 2024 and $33.7 million for the fourth quarter of 2023. The increase was primarily driven by nonclinical and clinical development, as well as manufacturing expenses, for the Company's pipeline candidates."

Clinical data • Commercial • New trial • Immunology • Inflammatory Bowel Disease

SPY001-101: A Study of SPY001-001 in Healthy Volunteers (clinicaltrials.gov) - P1 | N=96 | Active, not recruiting | Sponsor: Spyre Therapeutics, Inc. | Recruiting ➔ Active, not recruiting | Trial completion date: Aug 2025 ➔ May 2026 | Trial primary completion date: Aug 2025 ➔ May 2026

Enrollment closed • Trial completion date • Trial primary completion date

Combined inhibition of TL1A and integrin β7 is superior to either monotherapy in mouse models of colitis and coadministration of SPY001 and SPY002 demonstrates no drug-drug effects on exposure in non-human primates (ECCO-IBD 2025) - "Coadministration of SPY001 and SPY002 in NHPs demonstrated no drug-drug effects on PK. These preclinical results support the advancement of the combination of SPY001 and SPY002 into clinical trials."

Monotherapy • Preclinical • Immunology • Inflammatory Bowel Disease

Spyre Therapeutics Highlights 2025 Priorities and Robust Pipeline of Upcoming Clinical Readouts (PRNewswire) - "Phase 2 platform trial in ulcerative colitis (UC) remains on track for initiation in mid-2025 with SPY001 (α4β7), followed by SPY002 (TL1A), SPY003 (IL-23), and combinations thereof, with initial results expected in 2026....Announces indication expansion into rheumatoid arthritis (RA) with SPY002; Phase 2 RA trial initiation anticipated in mid-2025 with topline results in 2026....We reported outstanding interim Phase 1 results for SPY001 suggesting the potential for quarterly or twice-annual dosing with a molecule that has the potential to match or exceed the efficacy of the current best-selling product in IBD and look forward to reporting interim Phase 1 results for SPY002 and SPY003 in 2025."

New P2 trial • P1 data • P2 data • Rheumatoid Arthritis • Ulcerative Colitis

Spyre Therapeutics Announces Positive Interim Results from Phase 1 Healthy Volunteer Trial for SPY001, Its Novel Half-Life Extended anti-α4β7 Antibody for the Treatment of Inflammatory Bowel Disease, with a Half-Life of >90 Days Supporting the Potential for Both Q3M & Q6M Maintenance Dosing (PRNewswire) - P1 | N=116 | NCT06448247 | Sponsor: Spyre Therapeutics, Inc. | "Spyre Therapeutics, Inc....announced positive interim Phase 1 data from its first-in-human trial of SPY001, an investigational novel, extended half-life monoclonal antibody targeting α4β7. SPY001 was well tolerated with pharmacokinetic ('PK') data demonstrating a half-life of >90 days and pharmacodynamic ('PD') data demonstrating complete target engagement at all time points available....Single doses of SPY001 up to 1,000 mg and multiple doses of 600 mg were well tolerated with a favorable safety profile consistent with existing third-party data of the anti-α4β7 class...This Phase 2 ulcerative colitis trial is expected to initiate in mid-2025 with SPY001 and placebo arms, with SPY002, SPY003, and combination arms to be added following clinical data, nonclinical data, and regulatory feedback."

New P2 trial • P1 data • Crohn's disease • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

Spyre Therapeutics to Host Conference Call and Webcast to Report Interim Results from Phase 1 Healthy Volunteer Trial for SPY001, its Novel Half-Life Extended Anti-α4β7 Antibody for the Treatment for Inflammatory Bowel Disease on November 12, 2024 (PRNewswire) - "Following the announcement, the Company will host a conference call and webcast at 8:00am ET to discuss the results."

P1 data • Inflammatory Bowel Disease

SPY001-101: A Study of SPY001-001 in Healthy Volunteers (clinicaltrials.gov) - P1 | N=116 | Recruiting | Sponsor: Spyre Therapeutics, Inc. | N=72 ➔ 116

Enrollment change

A NOVEL MONOCLONAL ANTIBODY DRUG CANDIDATE SPY001 TARGETING INTEGRIN Ɑ4Β7 FOR THE TREATMENT OF IBD: IN VITRO PROPERTIES AND NON-HUMAN PRIMATE PHARMACOKINETICS AND SAFETY (UEGW 2024) - "SPY001 is a novel humanized monoclonal IgG1 with an extended half-life relative to that of vedolizumab in Tg276 mice and cynomolgus monkeys. Repeat-dose toxicity studies at doses up to 160 mg/kg showed no SPY001-related adverse events and a safety profile supportive of progression into clinical development. SPY001 offers the potential for effective and safe treatment of CD and UC with the advantage of infrequent SC dosing."

PK/PD data • Preclinical • Crohn's disease • Gastroenterology • Gastrointestinal Disorder • Inflammatory Bowel Disease • Ulcerative Colitis • VCAM1

Spyre Therapeutics Announces Expected Acceleration of SPY003 (IL-23p19) Clinical Timelines and Presentations at UEGW supporting Spyre's Portfolio of Potentially Best-in-Class Antibodies and Combinations (PRNewswire) - "Spyre Therapeutics, Inc...announced updated pipeline progress and timelines, as well as scientific presentations at the United European Gastroenterology Week ('UEGW') Congress. First-in-human dosing of SPY003 (anti-IL-23) in healthy volunteers is now expected to start during the first quarter of 2025....The company expects to share interim data from the accelerated first-in-human trial in the second half of 2025. Spyre presented preclinical data on SPY003 for the first time at UEGW, expanding its portfolio of half-life extended antibodies to three validated targets in IBD....Additional preclinical data for SPY001 (anti-α4β7) and SPY002 (anti-TL1A) presented at UEGW....For SPY002, characterization of the two development candidates planned for first-in-human studies in Q4 2024 is further described."

Clinical data • New trial • Preclinical • Immunology • Inflammatory Bowel Disease

Spyre Therapeutics Announces First Participants Dosed in Phase 1 Trial of SPY001, its Novel Half-life Extended anti-α4β7 Antibody, for the Treatment of Inflammatory Bowel Disease (PRNewswire) - "Spyre Therapeutics, Inc...announced that it has initiated dosing of healthy volunteers in its first clinical trial of SPY001, an investigational novel half-life extended anti-α4β7 monoclonal antibody....We expect interim safety and PK data from this trial by year-end 2024. Pending data from the Phase 1 trial, the company anticipates progressing into Phase 2 development with SPY001 in 2025."

New P2 trial • P1 data • Trial status • Immunology • Inflammatory Bowel Disease

SPY001-101: A Study of SPY001-001 in Healthy Volunteers (clinicaltrials.gov) - P1 | N=72 | Recruiting | Sponsor: Spyre Therapeutics, Inc.

New P1 trial