SPY002-091 / Spyre Therap - LARVOL DELTA

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

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

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

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 First Participants Dosed in Phase 1 Trials of Novel Half-life Extended Anti-TL1A Antibodies (PRNewswire) - "The SPY002 Phase 1 Trials (NCT06672718 and NCT06622070) are double blind, placebo-controlled single-ascending dose studies in healthy volunteers. The studies are each 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 pharmacodynamic (PD) data from these trials are expected in the second quarter of 2025....Spyre expects to introduce SPY002 to its planned Phase 2 study in ulcerative colitis exploring quarterly monotherapies and combinations; the Company also intends to initiate a proof-of-concept Phase 2 study outside of IBD in 2025."

New P2 trial • P1 data • Trial status • Ulcerative Colitis

A Study of SPY002-072 in Healthy Volunteers (clinicaltrials.gov) - P1 | N=56 | Recruiting | Sponsor: Spyre Therapeutics, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open

A Study of SPY002-091 in Healthy Volunteers (clinicaltrials.gov) - P1 | N=56 | Recruiting | Sponsor: Spyre Therapeutics, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open

A Study of SPY002-091 in Healthy Volunteers (clinicaltrials.gov) - P1 | N=56 | Not yet recruiting | Sponsor: Spyre Therapeutics, Inc.

New P1 trial

CHARACTERIZATION OF TWO NOVEL EXTENDED HALF-LIFE MONOCLONAL ANTIBODY DRUG CANDIDATES TARGETING TL1A FOR THE TREATMENT OF IBD (UEGW 2024) - "Aims & SPY002-091 and SPY002-072 were evaluated in multiple in vitro and ex vivo assays and compared to other anti-TL1A mAbs in clinical development (MK-7240, RG6631, and TEV-48574). We have characterized two anti-TL1A antibodies that exhibit high selectivity and affinity for TL1A, demonstrate effective blockade of the TL1A interaction with DR3, and potently inhibit downstream cellular signaling. With an extended half-life observed in NHP, both SPY002-091 and SPY002-072 demonstrate therapeutic potential for effective and safe treatment of CD and UC with the advantage of infrequent SC dosing. Further preclinical and clinical studies are warranted to demonstrate this potential."

Crohn's disease • Fibrosis • Gastroenterology • Gastrointestinal Disorder • Inflammatory Bowel Disease • Oncology • Ulcerative Colitis • FASLG • TNFA

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

A Study of SPY002-072 in Healthy Volunteers (clinicaltrials.gov) - P1 | N=48 | Not yet recruiting | Sponsor: Spyre Therapeutics, Inc.

New P1 trial

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

Development and Characterization of SPY002, a Novel Extended Half-life Monoclonal Antibody Drug Candidate Targeting TL1A for the Treatment of IBD (ECCO-IBD 2024) - "Methods SPY002 was evaluated in multiple in vitro and ex vivo assays compared to other clinical anti-TL1A mAbs (PRA023/MK-7240, RVT-3101, and TEV-48574). With an extended half-life in NHP, SPY002 demonstrates therapeutic potential for effective and safe treatment of CD and UC with the advantage of infrequent SC dosing. Further preclinical and clinical studies are warranted to demonstrate this potential."

Crohn's disease • Inflammatory Bowel Disease • Ulcerative Colitis • FASLG • IFNG • TNFA

Spyre Therapeutics Announces Three Abstracts Accepted for Presentation at the 19th Annual Congress of the European Crohn's and Colitis Organisation (PRNewswire) - "Spyre Therapeutics, Inc...today announced three abstracts co-written with Spyre's research partner, Paragon Therapeutics, Inc., highlighting that the Company's co-lead product candidates, SPY001 and SPY002, have been accepted for presentation as posters at the upcoming 19th Annual Congress of the European Crohn's and Colitis Organisation (ECCO), held February 21-24, 2024, in Stockholm, Sweden....'We are eager to initiate Phase 1 clinical studies in each program this year.'"

Preclinical • Crohn's disease • Immunology • Inflammation • Inflammatory Bowel Disease • Ulcerative Colitis

Rebranded Spyre Therapeutics Secures $180M to Advance IBD Antibody Pipeline (BioSpace) - "Following a recent rebranding and executive team overhaul, Spyre Therapeutics announced Thursday it scored $180 million in private financing from existing and new investors....Spyre selling six million shares of common stock for $15 a share and 150,000 shares of its Series B preferred stock at $600 a pop. The biotech will use the proceeds, in addition to the $205 million in cash it had on hand as of September 30, 2023, to fund its programs. The cash runway is expected to last into the second half of 2026....Spyre’s lead candidates, SPY001 and SPY002 are best-in-class hopefuls already in IND-enabling studies."

Financing • Crohn's disease • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

Aeglea BioTherapeutics Announces Name Change to Spyre Therapeutics, Appoints CEO and Additional Directors, and Expands Leadership Team to Develop Next-Generation Therapeutic Combinations for the Treatment of IBD (PRNewswire) - "Aeglea BioTherapeutics, Inc...announced its name change to Spyre Therapeutics, Inc. Effective as of market open on November 28, 2023, Spyre will trade on Nasdaq under the ticker symbol 'SYRE'....SPY001 is currently progressing through IND-enabling studies and is expected to enter first-in-human ('FIH') studies in the first half of 2024. Healthy volunteer pharmacokinetics and pharmacodynamic data are expected by the end of 2024...Spyre expects to begin FIH studies of SPY002 in the second half of 2024 and healthy volunteer data is expected in the first half of 2025."

Clinical • 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

Aeglea BioTherapeutics Reports Second Quarter 2023 Financial Results (PRNewswire) - "SPY002 – a highly potent and selective anti-TL1A monoclonal antibody engineered with half-life extension technology. TL1A has emerged as one of the most promising targets in IBD and broader immunology indications. We expect to begin FIH studies of the SPY002 program in the second half of 2024 with healthy volunteer data expected in the first half of 2025."

Clinical data • New trial • Immunology • Inflammatory Bowel Disease

Aeglea BioTherapeutics Announces Acquisition of Spyre Therapeutics (PRNewswire) - "Aeglea BioTherapeutics...today announced it has completed the acquisition of Spyre Therapeutics, Inc. ('Spyre'), a privately held biotechnology company advancing a robust pipeline of antibody therapeutics with the potential to transform the treatment of inflammatory bowel disease (IBD)....Spyre is advancing a robust portfolio that harnesses both proven and novel mechanisms of action for addressing IBD. The company's two parallel lead programs—SPY001 and SPY002—target a4b7 and TL1A, respectively, and build upon the validation of these targets by existing commercial- and clinical-stage antibody therapeutics. Spyre's lead programs are projected to enter clinical studies in 2024, with clinical data for SPY001 expected by YE2024."

M&A • New trial • Crohn's disease • Immunology • Inflammation • Inflammatory Bowel Disease