WALTHAM, Mass., Sept. 08, 2025 (GLOBE NEWSWIRE) -- Spyre Therapeutics, Inc. (NASDAQ: SYRE) (the “Company” or “Spyre”), a clinical-stage biotechnology company advancing best-in-class antibody engineering, dose optimization, and rational therapeutic combinations for the treatment of Inflammatory Bowel Disease (“IBD”) and other immune-mediated diseases, today announced that management will participate in a fireside chat and investor meetings at the Stifel 2025 Virtual Immunology and Inflammation Forum. Firesid ...

Exhibit 99.1 Spyre Therapeutics Reports Second Quarter 2025 Financial Results and Provides Corporate Update Reported positive interim Phase 1 results for two next-generation TL1A antibodies, demonstrating both were well-tolerated, exhibited pharmacokinetic ("PK") profiles supporting quarterly or biannual dosing, and full TL1A engagement through up to 20 weeks of follow-up Initiated Phase 2 SKYLINE-UC platform study, evaluating three optimized monotherapies and three potentially paradigm-changing combination ...

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, DC 20549 ____________________________ FORM 10-Q ____________________________ (Mark One) x QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the quarterly period ended June 30, 2025 OR o TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the transition period from to Commission File Number: 001-37722 SPYRE THERAPEUTICS, INC. (Exact Name of Registrant as Specified in ...

Core Insights - Spyre Therapeutics reported positive interim Phase 1 results for two next-generation TL1A antibodies, indicating they were well-tolerated and supported quarterly or biannual dosing with full TL1A engagement for up to 20 weeks [1][2] - The company initiated the Phase 2 SKYLINE-UC platform study to evaluate three optimized monotherapies and three potentially paradigm-changing combinations for ulcerative colitis [1][3] - Spyre is on track to begin the Phase 2 SKYWAY-RD basket study for TL1A inhibition in rheumatoid arthritis, psoriatic arthritis, and axial spondyloarthritis in Q3 2025 [1][10] - The company has a strong cash position of $526.6 million as of June 30, 2025, with an expected runway into the second half of 2028 [1][11] Development Pipeline Overview - Spyre's approach combines advanced antibody engineering, dose optimization, and rational therapeutic combinations to enhance efficacy and convenience in treating inflammatory bowel disease (IBD) and other immune-mediated diseases [3][15] - IBD affects approximately 2.4 million individuals in the U.S., while rheumatoid arthritis (RA), psoriatic arthritis (PsA), and axial spondyloarthritis (axSpA) affect over 1.5 million and nearly 3 million individuals, respectively [3][4] Financial Performance - Research and Development (R&D) expenses for Q2 2025 totaled $40.1 million, up from $32.6 million in Q2 2024, primarily due to increased clinical trial expenses [12] - General and Administrative (G&A) expenses were $11.8 million for Q2 2025, slightly higher than $11.5 million in Q2 2024 [12] - The net loss for Q2 2025 was $36.7 million, compared to a net loss of $38.8 million in Q2 2024, including non-cash stock-based compensation expenses [14][24]

Company Overview - Spyre Therapeutics anticipates 9 proof-of-concept readouts in 2026-27 for IBD and beyond[6, 113] - The company had $565 million in cash as of March 31, 2025, with an expected runway into the second half of 2028[8] - Spyre's next-generation antibodies are engineered to match or exceed the potency of first-generation molecules[13] Clinical Trials and Programs - SKYLINE-UC Phase 2 platform study is evaluating SPY001, SPY002, SPY003 and pairwise combinations in ulcerative colitis[35, 68] - SKYWAY-RD Phase 2 basket trial is evaluating SPY072 in rheumatoid arthritis, psoriatic arthritis, and axial spondyloarthritis, with initiation anticipated in Q3 2025[37, 38] - The company is transitioning to a mid-stage development company with two innovative Phase 2 clinical trials[35] Pipeline and Target Profiles - SPY001, SPY002, and SPY003 are being developed with a target profile of 2-4 chronic doses per year[26] - Spyre is developing potential paradigm-changing combination therapies in IBD, such as SPY120 (α4β7+TL1A), SPY130 (α4β7+IL-23), and SPY230 (TL1A+IL-23)[28, 29] - SPY072 is a potential first-in-class anti-TL1A for rheumatologic conditions, targeting Q3M-Q6M dosing[12, 34] Market and Unmet Needs - Approximately 24 million individuals in the U S are diagnosed with IBD (~1 3M UC and ~1 0M CD)[44] - Over 3 million individuals in the U S are diagnosed with RA (>1 5M), PsA (~1M), and axSpA (~1M)[80]

Pipeline and Strategy - Spyre Therapeutics is developing next-generation monotherapies and paradigm-changing combinations for IBD and beyond, with potential subcutaneous Q3M-Q6M dosing [6] - The company's portfolio aims for superior efficacy and convenience compared to existing IBD biologics, potentially breaking the efficacy ceiling with combinations [7, 8] - Spyre's MOAs were rationally chosen based on attractive risk-benefit profiles, targeting an ~$8B 2030 IBD sales market for α4β7 and a ~$7B market for TL1A [11] SPY Programs and Clinical Development - SPY001 has a half-life of >90 days, exceeding expectations, and showed target engagement in Phase 1, with potential for twice-yearly maintenance dosing [18, 25] - SPY002 has a half-life of ~24 days in NHP PK studies, while Tulisokibart has a half-life of ~12 days [18] - SPY003 has a half-life of ~30 days in NHP PK studies, while Risankizumab has a half-life of ~9 days [18] - A Phase 2 platform trial is planned to enable multiple placebo-controlled readouts of monotherapies and combinations in ulcerative colitis, with ~600 patients [33, 34] TL1A and Rheumatoid Arthritis - TL1A is implicated in a wide range of human diseases, including Rheumatoid Arthritis (RA), where it is elevated in patients and exacerbates arthritis in murine models [41, 44, 46] - Spyre's anti-TL1A antibody (SPY002) meets or exceeds the efficacy of etanercept (anti-TNF) in rat models of RA [49]

Summary of Spyre Therapeutics Inc (SYRE) Update / Briefing June 17, 2025 Company Overview - **Company**: Spyre Therapeutics Inc (SYRE) - **Focus**: Development of next-generation anti-TL1A antibodies for inflammatory bowel disease (IBD) and rheumatologic diseases Key Points and Arguments Phase I Clinical Trial Results - Positive interim results for two anti-TL1A molecules (SPY-two and SPY-seventy two) were announced, indicating favorable safety profiles and complete target engagement at low doses [2][5][21] - Both molecules demonstrated a half-life of approximately 75 days for SPY-two, supporting quarterly or biannual dosing [16][21] - The trials showed low rates of adverse events, with no serious adverse events reported [14][21] Phase II Development Plans - Plans to advance SPY-two into the Skyline UC study and SPY-seventy two into the Skyway RD study [22][31] - The Skyline UC study will explore safety and efficacy of three long-acting monotherapies and three combination therapies in ulcerative colitis [5][10] - The Skyway RD study will evaluate SPY-seventy two in three rheumatologic diseases, leveraging a basket design for efficiency [31][32] Market Potential and Value Creation - The development plan targets markets with over $60 billion in annual revenue, with multiple paths to substantial value creation [11] - The company aims to address unmet needs in IBD and rheumatologic diseases, potentially transforming treatment paradigms with innovative therapies [6][28] Study Design and Efficiency - The innovative platform and basket designs of the studies are expected to provide 35% to 40% cost savings compared to separate studies [10][33] - The Skyline UC study is designed to require 40% fewer patients, enhancing operational efficiency [26][27] Immunogenicity and Safety - Ongoing analysis of anti-drug antibodies (ADA) shows no apparent impact on pharmacokinetics (PK) or pharmacodynamics (PD) [60][92] - The company believes its combination therapies will have superior safety profiles compared to existing treatments, particularly those with known safety issues [61][82] Future Catalysts - Anticipated readouts include open-label results from the Skyline UC study in 2026 and placebo-controlled results for SPY-seventy two in 2026 [39][80] - The company is well-funded to execute its studies, with a cash runway extending into the second half of 2028 [39] Additional Important Content - The company emphasizes the potential for its anti-TL1A antibodies to provide improved options for patients and physicians, with a focus on both efficacy and convenience [6][28] - The design of the studies is patient-centric, aiming to reduce operational complexity and enhance patient recruitment [27][28] - The company is exploring the role of TL1A in rheumatologic diseases, supported by preclinical evidence of its efficacy [31][36] This summary captures the essential information from the conference call, highlighting the company's strategic direction, clinical trial results, and future plans.

Clinical Trial Updates - SPY002 and SPY072 met Phase 1 objectives, and the company plans to advance both into Phase 2[18] - The company is launching SKYLINE-UC, a Phase 2 platform study in ulcerative colitis evaluating three monotherapies and three combinations[11, 58] - The company is unveiling SKYWAY-RD, a Phase 2 basket study evaluating anti-TL1A in three rheumatologic conditions[11, 75] - The company anticipates 9 proof-of-concept readouts in 2026-27 for the treatment of IBD and beyond[25, 103] SPY002 and SPY072 Phase 1 Results - In a Single Ascending Dose (SAD) study, 11 out of 40 (28%) subjects in the SPY002 group experienced at least one Treatment Emergent Adverse Event (TEAE)[36] - In a Single Ascending Dose (SAD) study, 14 out of 40 (35%) subjects in the SPY072 group experienced at least one Treatment Emergent Adverse Event (TEAE)[38] - SPY002 demonstrated an approximate 75-day half-life[40, 42] - SPY002 and SPY072 suppressed free TL1A through 20-weeks of follow-up at the lowest dose tested[43] Trial Design and Cost Efficiency - The Phase 2 platform trial in UC is expected to achieve 40% cost savings compared to individual Phase 2 studies[24] - The Phase 2 basket trial in rheumatological diseases is expected to achieve 35% cost savings compared to individual Phase 2 studies[24] Financial Runway - The company has $565 million cash with runway into the second half of 2028[103]

Core Insights - Spyre Therapeutics announced positive interim Phase 1 results for SPY002 and SPY072, two novel monoclonal antibodies targeting TL1A, indicating their potential as next-generation therapies for immune-mediated diseases [1][2][3] Clinical Trials and Results - SPY002 and SPY072 met all Phase 1 objectives, demonstrating safety and tolerability with single doses up to 1500 mg, and a prolonged half-life of approximately 75 days, which is over three times greater than first-generation anti-TL1A antibodies [2][9] - The SKYLINE-UC platform trial for ulcerative colitis was initiated in May 2025, evaluating optimized monotherapies and combinations [1][3] - The SKYWAY-RD basket trial for SPY072 in rheumatoid arthritis, psoriatic arthritis, and axial spondyloarthritis is expected to begin in Q3 2025 [1][4] Future Development Plans - The company plans to advance SPY002 into the SKYLINE-UC trial and initiate the SKYWAY-RD trial for SPY072, with expectations for multiple proof-of-concept data readouts in 2026 and 2027 [3][5][7] - The SKYLINE-UC trial will include SPY001, SPY002, SPY003, and their combinations under a single master protocol [3][8] Market Potential - The company is well-funded with a cash runway extending into the second half of 2028, aiming to deliver nine proof-of-concept readouts in markets exceeding $60 billion in annual revenue [7][14]

Company Overview - Spyre Therapeutics, Inc. is a clinical-stage biotechnology company focused on developing next-generation products for inflammatory bowel disease (IBD) and other immune-mediated diseases through advanced antibody engineering and therapeutic combinations [3]. Upcoming Events - The company will report interim results from the Phase 1 SPY002 healthy volunteer trials on June 17, 2025, and will host a conference call and webcast at 8:00 am ET to discuss these results [1]. Product Pipeline - Spyre's pipeline includes investigational extended half-life antibodies targeting α4β7, TL1A, and IL-23, which are aimed at treating IBD and other immune-mediated diseases [3].