Reported positive interim Phase 1 results for SPY003, a next-generation anti-IL-23 antibody, demonstrating the molecule was well-tolerated and exhibited an ~85-day half-life supporting quarterly or twice annual maintenance dosing Initiated Phase 2 SKYWAY basket study of SPY072 evaluating TL1A inhibition in rheumatoid arthritis ("RA"), psoriatic arthritis ("PsA"), and axial spondyloarthritis ("axSpA") Exhibit 99.1 Spyre Therapeutics Reports Third Quarter 2025 Financial Results and Provides Corporate Update O ...

Acquisition and Partnerships - The company acquired Pre-Merger Spyre on June 22, 2023, a pre-clinical stage biotechnology firm, to enhance its intellectual property portfolio[125]. - The company exercised options under the Paragon Agreement for multiple research programs, securing exclusive licenses for various antibody products targeting specific integrins and cytokines[157]. - The company is obligated to pay up to $22.0 million to Paragon upon achieving specific development milestones for each licensed product[158]. Clinical Trials and Product Development - The company has initiated the SKYLINE Phase 2 platform trial in May 2025, evaluating SPY001, SPY002, SPY003, and their combinations in patients with moderately to severely active ulcerative colitis (UC)[131]. - The SKYWAY Phase 2 basket trial for SPY072 in rheumatic diseases began in September 2025, with topline proof-of-concept data expected in 2026[133][135]. - SPY001, the most advanced product candidate, has shown a favorable safety profile and potential for quarterly or biannual maintenance dosing based on Phase 1 trial results[138]. - SPY002 and SPY072 have demonstrated complete suppression of free TL1A for up to 20-24 weeks at a single 100mg dose, advancing to the SKYLINE and SKYWAY trials respectively[142]. - SPY003, targeting IL-23, exhibited a favorable safety profile and a differentiated pharmacokinetic profile, supporting its advancement to the SKYLINE Phase 2 trial[146]. - The company plans to investigate combinations of its proprietary antibodies in clinical trials to evaluate potential greater efficacy compared to monotherapies in inflammatory bowel disease (IBD)[128]. - The company has completed enrollment for Phase 1 trials of SPY001, SPY002, SPY072, and SPY003, with interim results indicating favorable safety and pharmacokinetic profiles across all candidates[137][141][145]. Financial Performance - Research and development expenses increased by $14.7 million, or 13%, to $127.0 million for the nine months ended September 30, 2025, compared to $112.3 million for the same period in 2024[169]. - General and administrative expenses rose by $1.0 million, or 9%, to $11.6 million for the three months ended September 30, 2025, from $10.6 million in the same period of 2024[166]. - Total operating expenses for the three months ended September 30, 2025, were $56.9 million, an increase of $1.5 million, or 3%, from $55.4 million in 2024[162]. - Other income increased by $59.1 million for the three months ended September 30, 2025, primarily due to changes in the fair value of the contingent value right (CVR) liability[167]. - The net loss for the three months ended September 30, 2025, was $11.2 million, a significant improvement compared to a net loss of $69.0 million in the same period of 2024[162]. - External research and development expenses for the nine months ended September 30, 2025, totaled $98.2 million, compared to $98.0 million in 2024, reflecting a stable expenditure despite changes in project focus[171]. - The company reported a loss before income tax expense of $92.7 million for the nine months ended September 30, 2025, compared to a loss of $151.7 million in the same period of 2024[169]. - Compensation costs in internal research and development increased by 111% to $16.1 million for the nine months ended September 30, 2025, from $7.6 million in 2024[171]. - Internal research and development expenses increased to $28.8 million for the nine months ended September 30, 2025, up from $14.3 million in the same period of 2024, primarily due to an increase in headcount[172]. - General and administrative expenses rose by $0.4 million, or 1%, to $35.4 million for the nine months ended September 30, 2025, compared to $35.0 million in 2024, mainly driven by higher compensation costs[173]. - The company recognized a gain of $10.0 million related to the sale of the legacy Aeglea asset pegzilarginase during the nine months ended September 30, 2025, with no similar gain in 2024[174]. - Interest income increased to $17.7 million for the nine months ended September 30, 2025, from $15.5 million in 2024, attributed to higher investment balances[175]. - Other income, net, surged by $61.9 million for the nine months ended September 30, 2025, primarily due to changes in the fair value of the CVR liability[177]. - The company has an accumulated deficit of $1.1 billion as of September 30, 2025, having raised approximately $1.3 billion in gross proceeds since inception[179]. Cash Flow and Financial Position - Cash used in operating activities was $124.7 million for the nine months ended September 30, 2025, reflecting a net loss of $92.7 million[186]. - Cash provided by investing activities was $103.9 million for the nine months ended September 30, 2025, primarily from maturities and sales of marketable securities[188]. - Cash used in financing activities was $3.8 million for the nine months ended September 30, 2025, mainly due to a payment to CVR holders[190]. - As of September 30, 2025, the company held $486.2 million in cash, cash equivalents, and marketable securities, all denominated in U.S. dollars[196].

Exhibit 99.1 Waltham, Mass, August 5, 2025 - Spyre Therapeutics, Inc. ("Spyre" or the "Company") (NASDAQ:SYRE), a clinical-stage biotechnology company utilizing best-in-class antibody engineering, dose optimization, and rational therapeutic combinations to target improved efficacy and convenience in the treatment of inflammatory bowel disease ("IBD") and other immune-mediated diseases, today announced its second quarter 2025 financial results and provided program and corporate updates. "Spyre is entering a ...

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, DC 20549 ____________________________ FORM 10-Q ____________________________ (Mark One) (Address of principal executive offices including zip code) 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 ...

Announced first participant dosed in Phase 1 trial of SPY003, with interim PK and safety data readout on track for the second half of 2025 Exhibit 99.1 Spyre Therapeutics Reports First Quarter 2025 Financial Results and Provides Corporate Update On track for mid-year initiations of planned Phase 2 studies in ulcerative colitis ("UC") and rheumatoid arthritis ("RA"), providing for 7+ proof-of-concept readouts in 2026 & 2027 Reported extended follow-up Phase 1 data for SPY001, supporting that the molecule is ...

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 March 31, 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 i ...