SPY003 / Spyre Therap - LARVOL DELTA

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

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

Spyre Therapeutics Announces First Participant Dosed in Phase 1 Trial of SPY003, its Novel Half-life Extended IL-23 Antibody (PRNewswire) - "Spyre Therapeutics...announced that it has initiated dosing in a healthy volunteer, Phase 1 clinical trial of its investigational half-life extended anti-IL-23 monoclonal antibody, SPY003. This milestone marks our fourth on-time clinical trial initiation in nine months....The SPY003 Phase 1 Trial (NCT06873724) is a double-blind, placebo-controlled single-ascending dose study in healthy volunteers. The study is expected to enroll approximately 56 healthy adult participants. The primary endpoint is safety, with pharmacokinetics (PK) serving as a secondary endpoint. Interim safety, PK, and ADA data from this trial are expected in the second half of 2025."

P1 data • Trial status • Inflammatory Bowel Disease

SPY003-207 in Health Volunteers (clinicaltrials.gov) - P1 | N=64 | Recruiting | Sponsor: Spyre Therapeutics, Inc.

New P1 trial

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

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

DEVELOPMENT AND CHARACTERIZATION OF SPY003, A NOVEL EXTENDED HALF-LIFE MONOCLONAL ANTIBODY DRUG CANDIDATE TARGETING IL-23 FOR THE TREATMENT OF IBD (UEGW 2024) - "Aims & SPY003 was evaluated in multiple in vitro and ex vivo assays compared to risankizumab (RIS) and guselkumab (GUS). SPY003 exhibits high selectivity and affinity for IL-23 and potently inhibits downstream cellular signaling. With an extended half-life in NHP, SPY003 demonstrates therapeutic potential for effective and safe treatment of CD and UC with the potential advantage of twice a year SC dosing. Further preclinical and clinical studies are warranted to demonstrate this potential."

Crohn's disease • Gastroenterology • Gastrointestinal Disorder • Inflammatory Bowel Disease • Ulcerative Colitis • CD8 • IL17A • IL23A • STAT3

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 Reports Second Quarter 2024 Financial Results and Provides Corporate Update (PRNewswire) - "The Company expects to begin FIH trials of both SPY002 candidates in the second half of 2024 with healthy volunteer interim data expected in the first half of 2025. If successful, the Company expects one SPY002 candidate would then advance into further clinical development....The Company nominated its potential best-in-class development candidate in June 2024 and expects to initiate IND-enabling studies in the second half of 2024. The Company expects to initiate FIH trials in the first half of 2025....R&D expenses totaled $32.6 million for the second quarter of 2024 and $17.4 million for the second quarter of 2023. The increase was driven by preclinical and clinical development and manufacturing expenses for the Company's IBD pipeline, partially offset by a decrease in expenses associated with the Company's legacy rare disease pipeline as well as a non-recurring credit from Paragon Therapeutics related to SPY003 development costs."

Clinical data • Commercial • New trial • Crohn's disease • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

Spyre Therapeutics Reports First Quarter 2024 Financial Results and Provides Corporate Update (PRNewswire) - "The Company has nominated two lead SPY002 development candidates and exercised its option to exclusively license related intellectual property rights under its agreement with Paragon Therapeutics....The Company expects to begin FIH studies of one or both SPY002 candidates in the second half of 2024 with healthy volunteer interim data expected in the first half of 2025. If successful, one SPY002 candidate would then advance into additional clinical development....SPY003 – a highly potent and selective investigational monoclonal antibody targeting the p19 subunit of IL-23, engineered with half-life extension technology....The Company expects to nominate a development candidate in mid-2024 and move into IND-enabling studies in the second half of 2024. The Company expects to initiate FIH studies in the first half of 2025."

Clinical data • New molecule • New trial • Crohn's disease • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

Aeglea BioTherapeutics Reports Third Quarter 2023 Financial Results and Provides Corporate Update (PRNewswire) - "SPY001 is currently progressing through IND-enabling studies and is expected to enter first-in-human ('FIH') studies in the first half of 2024. Interim data from a healthy volunteer study are expected by the end of 2024....The Company expects to begin FIH studies of the SPY002 program in the second half of 2024 with healthy volunteer interim data expected in the first half of 2025....SPY003...An IND/CTN is expected in 2025....Research and Development (R&D) expenses: R&D expenses totaled $24.7 million for the third quarter of 2023 and $12.0 million for the third quarter of 2022. This increase was primarily related to increases in preclinical development and manufacturing expenses for the Company's IBD pipeline, partially offset by a decrease in expenses associated with the legacy Aeglea rare disease pipeline."

Clinical data • Commercial • IND • New trial • Crohn's disease • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis