SPY001 / Spyre Therap - LARVOL DELTA

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

Development and Characterization of a Novel Extended Half-life Monoclonal Antibody Drug Candidate Targeting Integrin ɑ4β7 for the Treatment of IBD (ECCO-IBD 2024) - "Methods The novel humanized monoclonal IgG1 antibody SPY001 binds to the same ɑ4β7 epitope as vedolizumab and includes a YTE modification within the Fc region to increase half-life via increased affinity for the neonatal Fc receptor (FcRn), thereby favoring recycling into the circulation over degradation. It offers the 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 • VCAM1

A Novel Monoclonal Antibody Drug Candidate SPY001 Targeting Integrin ɑ4β7 for the Treatment of IBD Demonstrates Prolonged Half-Life in Non-Human Primates (ECCO-IBD 2024) - "Methods The humanized monoclonal IgG1 antibody SPY001 binds to the same ɑ4β7 epitope as vedolizumab and includes a YTE modification within the Fc region to increase its serum half-life via increased affinity for the neonatal Fc receptor (FcRn), thereby favoring recycling into the circulation over degradation. It offers the 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

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 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