SYRE

A month has gone by since the last earnings report for Spyre Therapeutics (SYRE). Shares have lost about 16.6% in that time frame, underperforming the S&P 500. But investors have to be wondering, will the recent negative trend continue leading up to its next earnings release, or is Spyre Therapeutics due for a breakout? Before we dive into how investors and analysts have reacted as of late, let's take a quick look at its latest earnings report in order to get a better handle on the important catalysts. Q2 Loss Narrower than Expected, Pipeline Progresses Spyre incurred a loss of 36 cents per share in the second quarter of 2026, narrower than the Zacks Consensus Estimate of a loss of 71 cents. In the year-ago quarter, the company reported a loss of 49 cents per share.Spyre has no marketed products in its portfolio and hence did not generate any revenues in the quarter.Total operating expenses were $41.6 million in the second quarter, slightly below $41.9 million in the year-ago period. The latest figure reflected a $40 million gain related to the previously completed sale of an in-process research and development asset, pegzilarginase. The gain was triggered by Immedica Pharma’s sale of a priority review voucher.The gain reduced the impact of elevated clinical development spending on quarterly results. It followed a $30 million gain recognized in the first quarter of 2026 from milestones connected with the same legacy asset.Research and development expenses totaled $65.5 million in the second quarter, up 63.2% year over year. The increase was primarily due to higher manufacturing and clinical study expenses, along with increased headcount costs.General and administrative expenses increased 36.9% year over year to $16.1 million, driven by higher headcount costs.Spyre ended the quarter with cash, cash equivalents and marketable securities of $1.15 billion compared with $741.5 million as of March 31, 2026. In April 2026, the company raised $435.2 million in net proceeds through a public offering of common stock. Management expects the current cash position to fund operations into the second half of 2029. Since the earnings release, investors have witnessed a downward trend in estimates revision. The consensus estimate has shifted -10.44% due to these changes. Currently, Spyre Therapeutics has a poor Growth Score of F, however its Momentum Score is doing a lot better with an A. However, the stock has a grade of F on the value side, putting it in the lowest quintile for this investment strategy. Overall, the stock has an aggregate VGM Score of F. If you aren't focused on one strategy, this score is the one you should be interested in. Estimates have been broadly trending downward for the stock, and the magnitude of these revisions indicates a downward shift. Notably, Spyre Therapeutics has a Zacks Rank #3 (Hold). We expect an in-line return from the stock in the next few months. Spyre Therapeutics belongs to the Zacks Medical - Biomedical and Genetics industry. Another stock from the same industry, uniQure (QURE), has gained 4.5% over the past month. More than a month has passed since the company reported results for the quarter ended June 2026. uniQure reported revenues of $5.84 million in the last reported quarter, representing a year-over-year change of +11%. EPS of -$1.22 for the same period compares with -$0.69 a year ago. uniQure is expected to post a loss of $0.87 per share for the current quarter, representing a year-over-year change of +37%. Over the last 30 days, the Zacks Consensus Estimate remained unchanged. uniQure has a Zacks Rank #3 (Hold) based on the overall direction and magnitude of estimate revisions. Additionally, the stock has a VGM Score of F. Want the latest recommendations from Zacks Investment Research? Today, you can download 7 Best Stocks for the Next 30 Days. Click to get this free report Spyre Therapeutics, Inc. (SYRE) : Free Stock Analysis Report uniQure N.V. (QURE) : Free Stock Analysis Report This article originally published on Zacks Investment Research (zacks.com). Zacks Investment Research

Both doses of SPY072 demonstrated statistically significant benefits compared to placebo on one or more of the primary (change from baseline in DAS28-CRP), key secondary (ACR20), and exploratory endpoints (e.g., ACR50) SPY072 was well tolerated with rates of adverse events comparable to placebo Magnitude of effect did not meet the Company’s target to prioritize monotherapy development of SPY072 in rheumatoid arthritis (RA); results support the broad potential of Spyre’s TL1A antibodies in autoimmune disease and as combination components Topline data for SPY072 in psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA) on track for Q4 2026 and for SPY072 in combination with IL17-A/F in hidradenitis suppurativa (HS) in late 2027 or early 2028 WALTHAM, Mass., Aug. 25, 2026 (GLOBE NEWSWIRE) -- Spyre Therapeutics, Inc. (NASDAQ: SYRE), a clinical-stage biotechnology company committed to developing next-generation therapies that elevate the standard in immunology by delivering more complete disease control, greater durability, and a simpler treatment experience for patients, today announced topline results from the RA sub-study of its Phase 2 SKYWAY basket trial evaluating SPY072 in rheumatic diseases. Both doses of SPY072 demonstrated statistically significant benefits compared to placebo on one or more of the primary (change from baseline in DAS28-CRP), key secondary (ACR20), and exploratory endpoints (ACR50). SPY072 was well tolerated, with a safety profile consistent with the TL1A class. The results provide proof-of-mechanism for TL1A in RA and support its potential in other autoimmune diseases and as a combination component, but did not meet the Company’s internal bar to prioritize advancement of SPY072 in RA. “The SKYWAY trial was designed to explore the safety and efficacy of TL1A inhibition in a range of rheumatic diseases to identify opportunities for indication-leading products. The results today do not lead us to prioritize SPY072 as a monotherapy in RA. However, the favorable safety profile of TL1A inhibition alongside demonstrated efficacy across inflammatory bowel disease, HS, and now RA provide increased conviction that our long-acting TL1A antibodies have potential in a range of autoimmune diseases and as optimal combination components,” said Cameron Turtle, DPhil, Chief Executive Officer at Spyre. “We want to thank the patients, investigators, and site staff who participated in this study and look forward to results in PsA and axSpA next quarter. Additionally, we are excited to have initiated our SKYLIGHT trial of SPY072 in combination with IL-17A/F in HS, our fourth investigational combination of validated mechanisms in autoimmune indications with high unmet need.” SKYWAY-RA efficacy results SPY072 Low Dose demonstrated a statistically significant benefit compared to placebo on the primary endpoint (change from baseline in DAS28-CRP) at Week 12. Nominally significant improvements versus placebo were observed on the secondary endpoint (ACR20) with High Dose and on the exploratory endpoint (ACR50) with Low Dose. Results were generally comparable between advanced-therapy-naïve and advanced-therapy-experienced sub-groups. *p<0.05 for SPY072 versus placebo        **nominal p<0.05 for SPY072 versus placebo Both doses of SPY072 achieved target drug concentrations and provided complete and durable suppression of free TL1A through Week 12, suggesting complete target engagement. Safety results SPY072 was well tolerated with a safety profile consistent with the TL1A class. Rates of adverse events were comparable between active (27%) and placebo (36%) and generally mild or moderate. One Serious TEAE occurred on each arm, none deemed drug-related. One death occurred in a participant receiving placebo. The most common TEAEs were infections and infestations, occurring in 14% of SPY072-treated participants and 15% of placebo-treated participants. Next steps The Company remains at the forefront of evaluating potential first- and best-in-class monotherapies and combinations in I&I with numerous expected topline readouts over the next 12-18 months to prioritize programs for further development: About SKYWAY-RA The SKYWAY-RA sub-study is one of three sub-studies in the SKYWAY basket trial (NCT07148414) and is a randomized and placebo-controlled study evaluating two doses of SPY072 in patients with moderate to severely active RA with inadequate response to conventional or advanced therapies. The primary endpoint is the change from baseline to Week 12 in Disease Activity Score in 28 joints, C-reactive protein (DAS28-CRP) and the secondary endpoint is the proportion of patients achieving an ACR20 response at Week 12. About Spyre Therapeutics Spyre Therapeutics is a clinical-stage biotechnology company committed to developing next-generation therapies that elevate the standard in immunology by delivering more complete disease control, greater durability, and a simpler treatment experience for patients. Spyre's pipeline includes investigational extended half-life antibodies targeting α4β7, TL1A, IL-23, and IL-17A/F as well as rational combination programs. For more information, visit Spyre's website at www.spyre.com. Forward-Looking Statements Certain statements in this press release, other than purely historical information, may constitute "forward-looking statements" within the meaning of the federal securities laws, including for purposes of the safe harbor provisions under the United States Private Securities Litigation Reform Act of 1995. These statements include, but are not limited to, statements regarding: Spyre’s ability to achieve the expected benefits or opportunities with respect to its product candidates and combinations thereof, including its ability to develop next-generation therapies that elevate the standard in immunology by delivering more complete disease control, greater durability, and a simpler treatment experience for patients; the efficacy and safety of SPY072/ our TL1A antibodies and their broad potential in autoimmune diseases and as optimal combination components; the Company remaining at the forefront of evaluating potential first and best-in-class monotherapies and combinations in I&I; the expected timing of topline results from the PsA and axSpA SKYWAY sub-studies, SKYLIGHT trial in HS and SKYLINE part A and B in UC and the potential further development of these programs; the timing of and the Company’s ongoing development programs in inflammatory bowel disease and HS; and Spyre’s ongoing and future pre-clinical and clinical development activities. The words "opportunity," "potential," "milestones," "pipeline," "strategy," "anticipate," "believe," "could," "estimate," "expect," "may," "might," "plan," "possible," "predict," "should," "will," "would," "can, " "likely," "aim," and similar expressions (including the negatives of these terms) may identify forward-looking statements, but the absence of these words does not mean that a statement is not forward-looking. These forward-looking statements are based on current expectations and beliefs and involve a number of risks and uncertainties, many of which are beyond Spyre’s control, and other assumptions that may cause actual results or performance to be materially different from those expressed or implied by these forward-looking statements. These risks and uncertainties include, but are not limited to, uncertainties and risks arising from regulatory feedback, including potential disagreement by regulatory authorities with the Company’s interpretation of data and the Company’s clinical trials for its product candidates; the potential for interim data not being delivered within expected time frames or final data not being consistent with or different than the topline or interim data reported for our programs; the potential impact of Trump Administration policies and changes in law on our business; and those uncertainties and factors described in Spyre's most recent Annual Report on Form 10-K, as supplemented and updated by subsequent Quarterly Reports on Form 10-Q and any other filings that Spyre has made or may make with the Securities and Exchange Commission from time to time. You should not place undue reliance on forward-looking statements in this press release, which speak only as of the date they are made and are qualified in their entirety by reference to the cautionary statements herein. Spyre does not undertake or accept any duty to make any updates or revisions to any forward-looking statements. For Investors:      Eric McIntyre, Spyre TherapeuticsSVP of Finance and Investor [email protected] For Media:      Josie Butler, [email protected]

Announced positive topline induction data for SPY001 and SPY002 from Part A of the Phase 2 SKYLINE trial (“SKYLINE”), demonstrating best-in-class efficacy potential and a safety profile consistent with in-class comparators Announced enrollment completion for the Phase 2 SKYWAY basket trial (“SKYWAY”), with all three sub-studies over-enrolling on or ahead of schedule, which we believe reflects significant investigator enthusiasm for new treatment options in these indications Remain on track for 6 proof-of-concept Phase 2 readouts in 2026, with the rheumatoid arthritis (“RA”) sub-study in SKYWAY and the SPY003 Part A data from SKYLINE expected in September and the psoriatic arthritis (“PsA”) and axial spondyloarthritis (“axSpA”) sub-studies of SKYWAY expected in the fourth quarter $1.1 billion in cash, cash equivalents, and marketable securities as of June 30, 2026, with expected runway into the second half of 2029 WALTHAM, Mass., Aug. 04, 2026 (GLOBE NEWSWIRE) -- Spyre Therapeutics, Inc. (“Spyre” or the “Company”) (NASDAQ:SYRE), a clinical-stage biotechnology company committed to developing next-generation therapies that elevate the standard in immunology by delivering more complete disease control, greater durability, and a simpler treatment experience for patients, today announced its second quarter 2026 financial results and provided program and corporate updates. “Following encouraging Phase 2 results from both SPY001 and SPY002, as well as competitor results validating the promise of combination therapy, the case for our approach in IBD has strengthened considerably. We believe our three investigational combinations have the potential to deliver efficacy, safety, and convenience beyond what is achievable with today’s therapies,” said Cameron Turtle, DPhil, Chief Executive Officer of Spyre. “Beyond IBD, we are approaching a pivotal milestone with placebo-controlled Phase 2 proof-of-concept data for SPY072, an anti-TL1A monotherapy, in rheumatoid arthritis expected next month, representing a key opportunity to demonstrate the broader utility of this mechanism. If successful, we look forward to initiating pivotal development of SPY072 next year, while also exploring combination approaches outside IBD.” Development Pipeline Overview and Update The Company is developing next-generation therapies that elevate the standard in immunology, with an initial focus in inflammatory bowel disease (“IBD”) and rheumatic diseases, including RA, PsA, and axSpA. IBD is a chronic condition characterized by inflammation within the gastrointestinal tract, including two main disorders: ulcerative colitis (“UC”) and Crohn's disease (“CD”). In the United States, it is estimated that approximately 2.4 million individuals are diagnosed with IBD. RA, PsA, and axSpA are chronic inflammatory autoimmune conditions primarily characterized by pain, stiffness, and swelling of the joints, as well as impacts on the spine and skin. Together, these rheumatic conditions affect more than three million individuals in the United States. Existing therapies for these diseases today generally offer incomplete efficacy, meaningful safety warnings, and inconvenient dosing profiles. Each of the Company's monotherapy programs in IBD target validated mechanisms with the potential for safe and effective treatment of UC and CD with infrequent dosing as a monotherapy or in rational combinations. The Company is also studying its anti-TL1A program as a monotherapy in indications outside IBD, including RA, PsA, and axSpA. The Company has two ongoing Phase 2 clinical trials with proof-of-concept data readouts in 2026: SKYLINE Phase 2 Platform Trial in IBD - in May 2025, the Company initiated a Phase 2 induction and maintenance platform trial of SPY001, SPY002 and SPY003, as well as pairwise combinations thereof (six investigational agents in total), in patients with moderately to severely active UC. The trial consists of two parts: Part A: Open-label assessment of the safety and preliminary efficacy of a single dose level of each investigational monotherapy. Enrollment for Part A has completed, with SPY001 and SPY002 Part A topline induction data announced in Q2 2026, and topline data expected for SPY003 in September 2026. Part B: Randomized and placebo-controlled assessment of the safety and efficacy of monotherapies and combinations, designed to provide dose-ranging data on monotherapies, proof-of-concept, and contribution of components for combinations, with induction data expected in 2027. SKYLINE is currently enrolling participants into Part B of the trial. SKYWAY Phase 2 Basket Trial in Rheumatic Diseases (RA, PsA, and axSpA) - in September 2025, the Company initiated a Phase 2 randomized and placebo-controlled basket trial of SPY072 in patients with moderately to severely active RA, PsA, or axSpA. The trial consists of three sub-studies, all of which have completed enrollment on or ahead of schedule: RA sub-study: Double-blind, placebo-controlled safety and efficacy study of two dose levels of SPY072 at Week 12 with open-label follow-up through Week 36. Topline proof-of-concept data are expected in September 2026. PsA sub-study: Double-blind, placebo-controlled safety and efficacy study of a single dose level of SPY072 at Week 16 with open-label follow-up through Week 40. Topline proof-of-concept data are expected in the fourth quarter of 2026. axSpA sub-study: Double-blind, placebo-controlled safety and efficacy study of a single dose level of SPY072 at Week 16 with open-label follow-up through Week 40. Topline proof-of-concept data are expected in the fourth quarter of 2026. The investigational therapies being studied in the SKYLINE and SKYWAY clinical trials include: SPY001 – a highly potent and selective investigational monoclonal antibody targeting α4β7, engineered with half-life extension technology and formulated at high concentration with the goal of maximizing efficacy and enabling infrequent, subcutaneous maintenance dosing. SPY001 is being evaluated for the treatment of IBD in the SKYLINE study. SPY002 and SPY072 – two highly potent and selective, investigational anti-TL1A monoclonal antibodies, engineered with half-life extension technology and formulated at high concentration with the goal of maximizing efficacy and enabling infrequent, subcutaneous maintenance dosing. The Company believes TL1A has emerged as one of the most promising targets in IBD and broader immunology indications. SPY002 is being evaluated for the treatment of IBD in the SKYLINE study and SPY072 is being evaluated for the treatment of rheumatic diseases in the SKYWAY study. SPY003 – a highly potent and selective investigational monoclonal antibody targeting the p19 subunit of IL-23, engineered with half-life extension technology and formulated at high concentration with the goal of maximizing efficacy and enabling infrequent, subcutaneous maintenance dosing. SPY003 is being evaluated for the treatment of IBD in the SKYLINE study. Rational Combinations [SPY120, SPY130 and SPY230] – the Company is investigating combinations of our proprietary antibodies in clinical trials in order to evaluate whether combinations can potentially lead to best-in-class efficacy in IBD, with less frequent dosing. Preclinical data for SPY120 were presented at medical meetings, demonstrating that the combined inhibition of TL1A and α4β7 is superior to either monotherapy in mouse models of colitis and that the pharmacokinetic profiles of SPY001 and SPY002 were similar in non-human primates whether dosed as monotherapies or in combination. Preclinical data for SPY130 and SPY230 have also demonstrated enhanced efficacy and pharmacodynamics with SPY003 in combination with SPY001 and SPY002. The Company is enrolling each of its combinations in Part B of the SKYLINE trial. Second Quarter 2026 Financial Results Cash Position: As of June 30, 2026, Spyre had cash, cash equivalents, and marketable securities of $1,145.3 million. In April 2026, the Company raised $435.2 million in net proceeds from a public offering of common stock. Net cash used in operating activities was $69.9 million for the second quarter of 2026. Research and Development (R&D) expenses: R&D expenses totaled $65.5 million for the second quarter of 2026 and $40.1 million for the second quarter of 2025. The increase was primarily driven by higher manufacturing and clinical trial expenses, as well as higher headcount costs. General and Administrative (G&A) expenses: G&A expenses totaled $16.1 million for the second quarter of 2026 and $11.8 million for the second quarter of 2025. The increase was primarily driven by higher headcount costs. Gain on Sale of In-Process Research and Development Asset: During the second quarter of 2026, the Companyrecognized a gain of $40.0 million for an achieved milestone related to the 2023 sale of the global rights of thelegacy asset pegzilarginase to Immedica Pharma AB, specifically Immedica’s sale of a priority review voucher. Total Other Income: Other income totaled $5.4 million for the second quarter of 2026 compared to $5.2 million of other income in the second quarter of 2025. Net Loss: Net loss totaled $36.2 million and $36.7 million for the second quarters of 2026 and 2025, respectively. About Spyre TherapeuticsSpyre Therapeutics is a clinical-stage biotechnology company committed to developing next-generation therapies that elevate the standard in immunology by delivering more complete disease control, greater durability, and a simpler treatment experience for patients. Spyre's pipeline includes investigational extended half-life antibodies targeting α4β7, TL1A, and IL-23. For more information, please visit http://spyre.com. Safe Harbor / Forward Looking StatementsCertain statements in this press release, other than purely historical information, may constitute “forward-looking statements” within the meaning of the federal securities laws, including for purposes of the safe harbor provisions under the United States Private Securities Litigation Reform Act of 1995. These statements include, but are not limited to, statements regarding: the Company's future results of operations and financial position; its ability to achieve the expected benefits or opportunities with respect to its product candidates, including its ability to develop next-generation therapies that elevate the standard in immunology by delivering more complete disease control, greater durability, and a simpler treatment experience for patients; its business strategy, including its ability to successfully develop best-in-class therapeutics for IBD; the potential consistency of the SPY001, SPY002, SPY072 and SPY003 Phase 1 trial and Phase 2 trial final data readouts with previously disclosed data for the Company's programs; expectations regarding the drug delivery of the Company's product candidates, including in the form of a subcutaneous injection; the length of time that the Company believes its existing cash resources will fund its operations, including the expectation of cash runway extending into the second half of 2029; estimated market sizes and potential growth opportunities; its future clinical development activities, including the Company's plans for and timing of cohort initiation and data readouts for the ongoing SKYWAY Phase 2 basket trial and SKYLINE Phase 2 platform trial, the inclusion of each rational combination in Part B of the SKYLINE Phase 2 platform trial, the number of data readouts expected to be delivered in 2026 and 2027, the potential initiation of pivotal development of anti-TL1A monotherapy, including timing thereof, and exploration of combination approaches outside of IBD; the potential efficacy, tolerability, convenience, dosing profile, commercial viability and safety profile of its product candidates, including in combinations; the potential therapeutic benefits and economic value of its product candidates as monotherapies or in combinations; and Spyre’s business plans, milestones, and goals. The words "opportunity," "potential," “milestones,” “pipeline,” “strategy,” “anticipate,” “believe,” “could,” “estimate,” “expect,” “may,” “might,” “plan,” “possible,” “predict,” “should,” “will,” “would,” and similar expressions (including the negatives of these terms) may identify forward-looking statements, but the absence of these words does not mean that a statement is not forward-looking. These forward-looking statements are based on current expectations and beliefs and involve a number of risks and uncertainties, many of which are beyond Spyre’s control, and other assumptions that may cause actual results or performance to be materially different from those expressed or implied by these forward-looking statements. These risks and uncertainties include, but are not limited, uncertainties and risks arising from regulatory feedback, including potential disagreement by regulatory authorities with the Company’s interpretation of data and the Company’s clinical trials for its product candidates; the potential for interim data not being delivered within expected time frames or final data not being consistent with or different than the interim data reported for the Company’s programs; the potential impact of Trump Administration policies and changes in law on the Company’s business; and those uncertainties and factors described in Spyre's most recent Annual Report on Form 10-K, as supplemented and updated by subsequent Quarterly Reports on Form 10-Q and any other filings that Spyre has made or may make with the SEC from time to time. You should not place undue reliance on forward-looking statements in this press release, which speak only as of the date they are made and are qualified in their entirety by reference to the cautionary statements herein. Spyre does not undertake or accept any duty to make any updates or revisions to any forward-looking statements. Contact Information: Media ContactJosie Butler, [email protected] Investor ContactEric [email protected]

SPY002 met its primary endpoint with a statistically significant reduction of 10.7 points (p Secondary endpoints included clinical remission by modified Mayo Score of 33% and endoscopic improvement of 42% SPY002 was well tolerated with a safety profile consistent with the TL1A class SPY002 Phase 2 results delivered within one year of Phase 1 results, highlighting continued operational excellence; on track for multiple additional readouts this year WALTHAM, Mass., June 15, 2026 (GLOBE NEWSWIRE) -- Spyre Therapeutics, Inc. (NASDAQ: SYRE), a clinical-stage biotechnology company committed to developing next-generation therapies that elevate the standard in immunology by delivering more complete disease control, greater durability, and a simpler treatment experience for patients, today announced positive 12-week induction data from Part A of the Phase 2 SKYLINE trial of SPY002, a potential best-in-class anti-TL1A being investigated for the treatment of moderately-to-severely active ulcerative colitis (UC). “SPY002 demonstrated an indication-leading 10.7-point reduction in RHI and meaningful clinical remission and endoscopic outcomes in line with the anti-TL1A class and among the highest across therapeutic classes,” said Deanna Nguyen, M.D., SVP of Clinical Development and SKYLINE study lead. “Together with its target Q3-6M sub-cutaneous maintenance profile, these data build upon our impressive SPY001 results and reinforce our thesis that optimized monotherapy components are the foundation for potentially best-in-class combinations. We remain on track to report Part A data for SPY003 (anti-IL-23) in Q3, which, if successful, would complete proof-of-concept for our investigational monotherapy components. We are now enrolling Part B of the SKYLINE trial, which includes three combination arms with the potential to deliver best-in-disease efficacy, safety, and treatment experience.” SPY002 SKYLINE Part A Induction Topline Results SKYLINE is a two-part induction and maintenance platform trial of SPY001, SPY002, SPY003, as well as pairwise combinations thereof (six investigational agents total) in patients with moderately-to-severely active ulcerative colitis. Part A is an open-label assessment of the safety and efficacy of a single dose level of each investigational monotherapy, and Part B is a randomized and placebo-controlled assessment of the safety and efficacy of investigational monotherapies (two dose levels) and combinations. SPY002 is an extended half-life investigational antibody targeting TL1A, an upstream cytokine implicated in chronic inflammation and fibrosis in IBD. Initial 12-week findings from SKYLINE Part A demonstrated that SPY002 met all key objectives. The study population consisted of 35% advanced therapy-exposed participants with a mean disease duration of 7.0 years, a mean baseline RHI score of 16.9 ± 8.5 (SD), a mean modified Mayo Score of 6.9 ± 1.0 (SD), and 56% of whom had a baseline endoscopy score of 3. Efficacy: SPY002 achieved the primary endpoint, demonstrating a statistically significant 10.7-point reduction in RHI score (p<0.0001), robust rates of clinical remission and endoscopic improvement, and a meaningful change in mMS, results that are among the highest reported in UC. Safety: SPY002 was well tolerated with a safety profile consistent with the TL1A class. There were twenty subjects with treatment-emergent adverse events (TEAEs) during the induction treatment period. Two serious adverse events (SAEs) were reported, both deemed not drug-related. One case was for hospitalization for exacerbation of UC, the other case was for worsening of heart failure in a subject with a history of heart failure. The most common adverse events (AEs) (occurring in ≥ 2 patients) were arthralgia (n=2), hypertension (n=3), nausea (n=2), UC (n=2), and viral respiratory tract infection (n=2). 1Hospitalization for exacerbation of UC in one subject, deemed not drug-related.2Hospitalization for worsening heart failure in one subject with history of heart failure and atrial fibrillation, who was subsequently diagnosed with worsening of aortic stenosis; deemed not drug-related.3One case each of nausea, hypertension, and arthralgia.4Exacerbation of UC, deemed not drug-related. About Spyre Therapeutics Spyre Therapeutics is a clinical-stage biotechnology company committed to developing next-generation therapies that elevate the standard in immunology by delivering more complete disease control, greater durability, and a simpler treatment experience for patients. Spyre's pipeline includes investigational extended half-life antibodies targeting α4β7, TL1A, and IL-23. For more information, visit Spyre's website at www.spyre.com. Forward-Looking Statements Certain statements in this press release, other than purely historical information, may constitute "forward-looking statements" within the meaning of the federal securities laws, including for purposes of the safe harbor provisions under the United States Private Securities Litigation Reform Act of 1995. These statements include, but are not limited to, statements regarding: Spyre’s ability to achieve the expected benefits or opportunities with respect to its product candidates, including their potential commercialization and its ability to develop next-generation therapies that elevate the standard in immunology by delivering more complete disease control, greater durability, and a simpler treatment experience for patients; the potential for the three combination arms to deliver best-in-disease efficacy, safety, and treatment experiences; Spyre’s ongoing and future clinical development activities, including Spyre’s plans for data readouts for the ongoing SKYLINE trial. The words "opportunity," "potential," "milestones," "pipeline," "strategy," "anticipate," "believe," "could," "estimate," "expect," "may," "might," "plan," "possible," "predict," "should," "will," "would," and similar expressions (including the negatives of these terms) may identify forward-looking statements, but the absence of these words does not mean that a statement is not forward-looking. These forward-looking statements are based on current expectations and beliefs and involve a number of risks and uncertainties, many of which are beyond Spyre’s control, and other assumptions that may cause actual results or performance to be materially different from those expressed or implied by these forward-looking statements. These risks and uncertainties include, but are not limited to, uncertainties and risks arising from regulatory feedback, including potential disagreement by regulatory authorities with the Company’s interpretation of data and the Company’s clinical trials for its product candidates; the potential for interim data not being delivered within expected time frames or final data not being consistent with or different than the topline or interim data reported for our programs; the potential impact of Trump Administration policies and changes in law on our business; and those uncertainties and factors described in Spyre's most recent Annual Report on Form 10-K, as supplemented and updated by subsequent Quarterly Reports on Form 10-Q and any other filings that Spyre has made or may make with the SEC from time to time. You should not place undue reliance on forward-looking statements in this press release, which speak only as of the date they are made and are qualified in their entirety by reference to the cautionary statements herein. Spyre does not undertake or accept any duty to make any updates or revisions to any forward-looking statements. For Investors:      Eric McIntyre, Spyre TherapeuticsSVP of Finance and Investor [email protected] For Media:      Josie Butler, [email protected]

Announced positive topline induction data from Part A of the Phase 2 SKYLINE trial of SPY001, demonstrating best-in-class efficacy potential and a safety profile consistent with the α4β7 class Announced over-enrollment and acceleration of topline readout to the third quarter of 2026 of the rheumatoid arthritis (“RA”) sub-study of the Phase 2 SKYWAY basket trial Remain on track for 6 proof-of-concept readouts in 2026 across the SKYLINE and SKYWAY Phase 2 trials Further strengthened the balance sheet with $463 million gross proceeds from an underwritten public offering of common stock $1.2 billion in pro forma cash, cash equivalents, and marketable securities as of March 31, 2026, with expected runway into the second half of 2029 WALTHAM, Mass., May 05, 2026 (GLOBE NEWSWIRE) -- Spyre Therapeutics, Inc. (“Spyre” or the “Company”) (NASDAQ:SYRE), a clinical-stage biotechnology company pioneering long-acting antibodies and antibody combinations to redefine the standard of care for inflammatory bowel disease (“IBD”) and rheumatic diseases (“RD”), today announced its first quarter 2026 financial results and provided program and corporate updates. “With our first Phase 2 readout of the year supporting a potential best-in-class profile for SPY001 in IBD, we have begun to deliver on the promise of what we believe is one of the most ambitious and differentiated pipelines in our industry. This result opened the possibility that our monotherapies could become valuable products in IBD and further strengthened our conviction that our combination therapies have the potential to deliver paradigm-changing efficacy for the more than two million Americans suffering from IBD,” said Cameron Turtle, DPhil, Chief Executive Officer of Spyre. “We have now begun enrolling our IBD combination therapies across the world and look forward to unveiling additional monotherapy results over the next few months and combination data next year. Outside IBD, we are advancing a potentially first- and best-in-class anti-TL1A antibody across multiple rheumatic diseases, where we continue to execute ahead of schedule and see significant opportunity for this mechanism paired with a convenient dosing profile. Collectively, we believe our assets, strategy, and execution position Spyre to deliver meaningful outcomes for patients and substantial long-term value for shareholders.” Development Pipeline Overview and Update The Company is pioneering long-acting antibodies and antibody combinations to redefine the standard of care in IBD and rheumatic diseases. IBD is a chronic condition characterized by inflammation within the gastrointestinal tract, including two main disorders: ulcerative colitis (“UC”) and Crohn's disease (“CD”). In the United States, it is estimated that approximately 2.4 million individuals are diagnosed with IBD. RA, PsA, and axSpA are chronic inflammatory autoimmune conditions primarily characterized by pain, stiffness, and swelling of the joints, as well as impacts on the spine and skin. Together, these rheumatic conditions affect more than three million individuals in the U.S. Existing therapies for these diseases today generally offer incomplete efficacy, meaningful safety warnings, and inconvenient dosing profiles. Each of the Company's monotherapy programs in IBD target validated mechanisms with the potential for safe and effective treatment of UC and CD with infrequent dosing as a monotherapy or in rational combinations. The Company is also studying its anti-TL1A program as a monotherapy in indications outside IBD, including RA, PsA, and axSpA. The Company has two ongoing Phase 2 clinical trials with proof-of-concept data readouts in 2026: SKYLINE Phase 2 Platform Trial in IBD - in May 2025, the Company initiated a Phase 2 induction and maintenance platform trial of SPY001, SPY002, SPY003, as well as pairwise combinations thereof (six investigational agents in total) in patients with moderately to severely active UC. The trial consists of two parts: Part A: Open-label assessment of the safety and preliminary efficacy of a single dose level of each investigational monotherapy. Enrollment for Part A has completed, with SPY001 Part A topline induction data announced in April 2026, and topline data expected for SPY002 and SPY003 in mid-2026 and the third quarter of 2026, respectively. Part B: Randomized and placebo-controlled assessment of the safety and efficacy of monotherapies and combinations, designed to provide dose-ranging data on monotherapies, proof-of-concept, and contribution of components for combinations, with induction data expected in 2027. SKYLINE is currently enrolling participants into Part B of the trial. SKYWAY Phase 2 Basket Trial in Rheumatic Diseases (RA, PsA, axSpA) - in September 2025, the Company initiated a Phase 2 randomized and placebo-controlled basket trial of SPY072 in patients with moderately to severely active RA, PsA, or axSpA. The trial consists of three sub-studies: RA sub-study: Double-blind, placebo-controlled safety and efficacy study of two dose levels of SPY072 at Week 12 with open-label follow-up through Week 36. This sub-study has completed enrollment ahead of schedule and topline proof-of-concept data are expected in the third quarter of 2026. PsA sub-study: Double-blind, placebo-controlled safety and efficacy study of a single dose level of SPY072 at Week 16 with open-label follow-up through Week 40. Enrollment continues in this sub-study and topline proof-of-concept data are expected in the fourth quarter of 2026. axSpA sub-study: Double-blind, placebo-controlled safety and efficacy study of a single dose level of SPY072 at Week 16 with open-label follow-up through Week 40. Enrollment continues in this sub-study and topline proof-of-concept data are expected in the fourth quarter of 2026. The investigational therapies being studied in the SKYLINE and SKYWAY clinical trials include: SPY001 – a highly potent and selective investigational monoclonal antibody targeting α4β7, engineered with half-life extension technology and formulated at high concentration with the goal of maximizing efficacy and enabling infrequent, subcutaneous maintenance dosing. In April 2026, topline induction results were presented for SPY001 from Part A of the SKYLINE trial in ulcerative colitis subjects. 43 subjects were dosed with SPY001 and 41 subjects completed the induction period. SPY001 was well tolerated with a safety profile consistent with the α4β7 class. SPY001 achieved the primary endpoint, demonstrating a statistically significant reduction in the Robart’s Histopathology Index (RHI) score of 9.2 points (p<0.0001). The rates of key secondary endpoints of clinical remission and endoscopic improvement were clinically meaningful at 40% and 51%, respectively. SPY002 and SPY072 – two highly potent and selective, investigational anti-TL1A monoclonal antibodies, engineered with half-life extension technology and formulated at high concentration with the goal of maximizing efficacy and enabling infrequent, subcutaneous maintenance dosing. The Company believes TL1A has emerged as one of the most promising targets in IBD and broader immunology indications. SPY002 is being evaluated for the treatment of IBD in the SKYLINE study and SPY072 is being evaluated for the treatment of rheumatic diseases in the SKYWAY study. In June 2025, interim healthy volunteer data from two Phase 1 trials (one for SPY002 and one for SPY072) were presented, demonstrating favorable safety profiles, meaningfully differentiated PK profiles supporting potential Q3M or Q6M maintenance dosing, and complete suppression of free TL1A through up to 20 weeks at single 100mg doses. Longer-term data from these Phase 1 trials were presented at medical meetings in late 2025, providing further support for these potential best-in-class profiles. Based on these interim results, SPY002 was advanced to the SKYLINE Phase 2 platform trial, and SPY072 was advanced to the SKYWAY Phase 2 basket trial. SPY003 – a highly potent and selective investigational monoclonal antibody targeting the p19 subunit of IL-23, engineered with half-life extension technology and formulated at high concentration with the goal of maximizing efficacy and enabling infrequent, subcutaneous maintenance dosing. In November 2025, interim healthy volunteer data from a Phase 1 trial were disclosed, demonstrating that SPY003 exhibited a favorable safety profile and a meaningfully differentiated PK profile supporting potential Q3M or Q6M maintenance dosing. Additional data from this Phase 1 trial were presented at the 21st Congress of the European Crohn’s and Colitis Organisation ("ECCO") in February 2026, providing further support for this potential best-in-class profile. Based on these interim results, SPY003 was advanced to the SKYLINE Phase 2 platform trial. Rational Combinations – the Company plans to investigate combinations of our proprietary antibodies in nonclinical studies and clinical trials in order to evaluate whether combinations can potentially lead to best-in-class efficacy in IBD, with less frequent dosing. In February and May 2025, preclinical data for SPY120 were presented at medical meetings, demonstrating that the combined inhibition of TL1A and α4β7 is superior to either monotherapy in mouse models of colitis and that the PK profiles of SPY001 and SPY002 were similar in non-human primates whether dosed as monotherapy or in combination, while also demonstrating no drug effects on PK. Preclinical data for SPY130 and SPY230 have demonstrated enhanced efficacy and pharmacodynamics with SPY003 in combination with SPY001 and with SPY002. The Company is enrolling each of its combinations in Part B of the SKYLINE trial. First Quarter 2026 Financial Results Cash Position: As of March 31, 2026, Spyre had cash, cash equivalents, and marketable securities of $741.5 million. Pro forma cash of $1,176.8 million as of March 31, 2026, also reflects $435.3 million in net proceeds from the recently closed April 2026 underwritten public offering of common stock. Net cash used in operating activities was $57.4 million for the first quarter of 2026. Research and Development (R&D) expenses: R&D expenses totaled $60.4 million for the first quarter of 2026 and $41.6 million for the first quarter of 2025. The increase was primarily driven by higher manufacturing and clinical trial expenses, as well as higher headcount, partially offset by lower early-stage R&D activities. General and Administrative (G&A) expenses: G&A expenses totaled $15.2 million for the first quarter of 2026 and $11.9 million for the first quarter of 2025. The increase was primarily driven by higher headcount. Gain on Sale of In-Process Research and Development Asset: During the first quarter of 2026, the Company recognized a gain of $30.0 million for achieved milestones related to the 2023 sale of the global rights of the legacy Aeglea asset pegzilarginase to Immedica, specifically the FDA approval of pegzilarginase. Total Other (Expense) Income: Other expense totaled $23.4 million for the first quarter of 2026 compared to $8.8 million of other income in the first quarter of 2025, primarily driven by changes in the fair value of the contingent value right (CVR) liability. Net Loss: Net loss totaled $69.0 million and $44.8 million for the first quarters of 2026 and 2025, respectively. About Spyre Therapeutics Spyre Therapeutics is a clinical-stage biotechnology company pioneering long-acting antibodies and antibody combinations to redefine the standard of care for inflammatory bowel disease (“IBD”) and rheumatic diseases. Spyre's pipeline includes investigational extended half-life antibodies targeting α4β7, TL1A, and IL-23. For more information, please visit http://spyre.com. Safe Harbor / Forward Looking Statements Certain statements in this press release, other than purely historical information, may constitute “forward-looking statements” within the meaning of the federal securities laws, including for purposes of the safe harbor provisions under the United States Private Securities Litigation Reform Act of 1995. These statements include, but are not limited to, statements regarding: the Company's future results of operations and financial position; its ability to achieve the expected benefits or opportunities with respect to its product candidates, including their potential commercialization, the possibility that its monotherapies could become valuable assets in IBD and the potential paradigm-shifting efficacy of its combination therapies; its business strategy, including its ability to successfully develop best-in-class therapeutics for IBD, RA, PsA, axSpA and other immune-mediated diseases that meaningfully improve both efficacy and convenience compared to today's standard of care and the Company's ability to develop first-in-class therapeutics for RD; the potential consistency of the SPY001, SPY002, SPY072 and SPY003 Phase 1 trial and Phase 2 trial final data readouts with previously disclosed data for the Company's programs; expectations regarding the drug delivery of the Company's product candidates, including in the form of a subcutaneous injection; the length of time that the Company believes its existing cash resources will fund its operations, including the expectation of cash runway extending into the second half of 2029; estimated market sizes and potential growth opportunities; its nonclinical and future clinical development activities, including the Company's plans for and timing of cohort initiation and data readouts for the ongoing SKYWAY Phase 2 basket trial and SKYLINE Phase 2 platform trial, enrollment of clinical trials and, the inclusion of each rational combination in Part B of the SKYLINE Phase 2 platform trial and the number of data readouts expected to be delivered in 2026 and 2027; the potential efficacy, tolerability, convenience, commercial viability and safety profile of its product candidates, including in combinations; the planned dosing regimen for SPY001, SPY002, SPY072 and SPY003, and combinations thereof, including the potential for a Q3M or Q6M dosing profile and the potential for such dosing profile to be the leading product profile in IBD and RD; the potential therapeutic benefits and economic value of its product candidates as monotherapies or in combinations and their extended half-life; and Spyre’s business plans, milestones, and goals. The words "opportunity," "potential," “milestones,” “pipeline,” “strategy,” “anticipate,” “believe,” “could,” “estimate,” “expect,” “may,” “might,” “plan,” “possible,” “predict,” “should,” “will,” “would,” and similar expressions (including the negatives of these terms) may identify forward-looking statements, but the absence of these words does not mean that a statement is not forward-looking. These forward-looking statements are based on current expectations and beliefs and involve a number of risks and uncertainties, many of which are beyond Spyre’s control, and other assumptions that may cause actual results or performance to be materially different from those expressed or implied by these forward-looking statements. These risks and uncertainties include, but are not limited, uncertainties and risks arising from regulatory feedback, including potential disagreement by regulatory authorities with the Company’s interpretation of data and the Company’s clinical trials for its product candidates; the potential for interim data not being delivered within expected time frames or final data not being consistent with or different than the interim data reported for the Company’s programs; the potential impact of Trump Administration policies and changes in law on the Company’s business; and those uncertainties and factors described in Spyre's most recent Annual Report on Form 10-K, as supplemented and updated by subsequent Quarterly Reports on Form 10-Q and any other filings that Spyre has made or may make with the SEC from time to time. You should not place undue reliance on forward-looking statements in this press release, which speak only as of the date they are made and are qualified in their entirety by reference to the cautionary statements herein. Spyre does not undertake or accept any duty to make any updates or revisions to any forward-looking statements. Contact Information: Media Contact Josie Butler, 1AB [email protected] Investor Contact Eric McIntyre [email protected] (1) Includes $3.1 million and $2.5 million in related party expenses for the three months ended March 31, 2026 and 2025, respectively. (2) Includes related party expenses of $0.3 million for the three months ended March 31, 2026 and 2025, respectively.

On track for 6 proof-of-concept readouts in 2026 across the SKYLINE and SKYWAY Phase 2 trials Part A readouts from SKYLINE platform trial in ulcerative colitis ("UC") expected to begin in the second quarter, with enrollment continuing ahead of schedule Enrollment on track in Phase 2 SKYWAY basket trial evaluating TL1A inhibition in rheumatoid arthritis ("RA"), psoriatic arthritis ("PsA"), and axial spondyloarthritis ("axSpA"), with fourth quarter readouts expected in each sub-study Strengthened the balance sheet with an underwritten public offering of common stock in October 2025 and announced the appointment of Kate Tansey Chevlen as Chief Commercial Officer (CCO) $757 million of cash, cash equivalents, and marketable securities as of December 31, 2025, with expected runway into the second half of 2028 WALTHAM, Mass., Feb. 19, 2026 (GLOBE NEWSWIRE) -- Spyre Therapeutics, Inc. ("Spyre" or the "Company") (NASDAQ:SYRE), a clinical-stage biotechnology company pioneering long-acting antibodies and antibody combinations to redefine the standard of care for inflammatory bowel disease (“IBD”) and rheumatic diseases, today announced its fourth quarter and full year 2025 financial results and provided program and corporate updates. “This year is a pivotal period for Spyre as we begin to unveil results from our two groundbreaking Phase 2 trials with the potential to identify multiple products that leapfrog today's standard of care and provide substantially improved therapies for patients suffering from severe autoimmune diseases. In IBD, we plan to reveal initial safety and efficacy data for our optimized antibodies against the most compelling targets in the space. If successful, these results would support our view that our antibodies are the ideal components for combination therapies with the potential to transform the treatment paradigm in this disease,” said Cameron Turtle, DPhil, Chief Executive Officer of Spyre. “Beyond IBD, we are moving full speed ahead with a potentially first- and best-in-class anti-TL1A antibody in a basket study of three rheumatic diseases. Numerous sources of evidence support potential efficacy of TL1A inhibition in these indications, and our quarterly or twice-annual subcutaneous dosing profile could be the leading product profile in these large markets. Taken together, we believe our assets, strategy, and execution can deliver meaningful value for patients, physicians, and shareholders alike.” Development Pipeline Overview and Update The Company is pioneering long-acting antibodies and antibody combinations to redefine the standard of care in IBD and rheumatic diseases. IBD is a chronic condition characterized by inflammation within the gastrointestinal tract, including two main disorders: ulcerative colitis ("UC") and Crohn's disease ("CD"). In the United States, it is estimated that approximately 2.4 million individuals are diagnosed with IBD. RA, PsA, and axSpA are chronic inflammatory autoimmune conditions primarily characterized by pain, stiffness, and swelling of the joints, as well as impacts on the spine and skin. Together, these rheumatic conditions affect more than three million individuals in the U.S. Existing therapies for these diseases today generally offer incomplete efficacy, meaningful safety warnings, and inconvenient dosing profiles. Each of the Company's monotherapy programs in IBD target validated mechanisms with the potential for safe and effective treatment of UC and CD with infrequent dosing as a monotherapy or in rational combinations. The Company is also studying its anti-TL1A program as a monotherapy in indications outside IBD, including RA, PsA, and axSpA. The Company has two ongoing Phase 2 clinical trials with proof-of-concept data readouts beginning in 2026: SKYLINE Phase 2 Platform Trial in IBD - in May 2025, the Company initiated a Phase 2 induction and maintenance platform trial of SPY001, SPY002, SPY003, as well as pairwise combinations thereof (six investigational agents in total) in patients with moderately to severely active UC. The trial consists of two parts: Part A: Open-label assessment of the safety and preliminary efficacy of a single dose level of each investigational monotherapy, with induction data expected beginning in the second quarter of 2026. Part B: Randomized and placebo-controlled assessment of the safety and efficacy of investigational monotherapies (two dose levels) and combinations, with induction data expected in 2027. SKYLINE is currently enrolling subjects into Part A of the trial, with Part B expected to begin enrolling after all arms in Part A complete enrollment. SKYWAY Phase 2 Basket Trial in Rheumatic Diseases (RA, PsA, axSpA) - in September 2025, the Company initiated a Phase 2 randomized and placebo-controlled basket trial of SPY072 in patients with moderately to severely active RA, PsA, or axSpA. The trial consists of three sub-studies, each expected to provide proof-of-concept data in the fourth quarter of 2026: RA sub-study: Double-blind, placebo-controlled safety and efficacy study of two dose levels of SPY072 at Week 12. PsA sub-study: Double-blind, placebo-controlled safety and efficacy study of a single dose level of SPY072 at Week 16. axSpA sub-study: Double-blind, placebo-controlled safety and efficacy study of a single dose level of SPY072 at Week 16. The investigational therapies being studied in the SKYLINE and SKYWAY clinical trials include: SPY001 – a highly potent and selective investigational monoclonal antibody targeting α4β7, engineered with half-life extension technology and formulated at high concentration with the goal of maximizing efficacy and enabling infrequent, subcutaneous maintenance dosing. In May 2025, extended follow up data were presented at Digestive Disease Week ("DDW") 2025 from the Phase 1 healthy volunteer trial, demonstrating a favorable safety profile across all dose groups, a meaningfully differentiated pharmacokinetic ("PK") profile supporting potential Q3M or Q6M maintenance dosing, and rapid and complete saturation of α4β7 receptors beyond six months with a single dose of 600mg. Based on these interim results, SPY001 was advanced into the SKYLINE Phase 2 platform trial. SPY002 and SPY072 – two highly potent and selective, investigational anti-TL1A monoclonal antibodies, engineered with half-life extension technology and formulated at high concentration with the goal of maximizing efficacy and enabling infrequent, subcutaneous maintenance dosing. The Company believes TL1A has emerged as one of the most promising targets in IBD and broader immunology indications. SPY002 is being evaluated for the treatment of IBD in the SKYLINE study and SPY072 is being evaluated for the treatment of rheumatic diseases in the SKYWAY study. In June 2025, interim healthy volunteer data from two Phase 1 trials (one for SPY002 and one for SPY072) were presented, demonstrating favorable safety profiles, meaningfully differentiated PK profiles supporting potential Q3M or Q6M maintenance dosing, and complete suppression of free TL1A through up to 20 weeks at single 100mg doses. Longer-term data from these Phase 1 trials were presented at medical meetings in late 2025, providing further support for these potential best-in-class profiles. Based on these interim results, SPY002 was advanced to the SKYLINE Phase 2 platform trial, and SPY072 was advanced to the SKYWAY Phase 2 basket trial. SPY003 – a highly potent and selective investigational monoclonal antibody targeting the p19 subunit of IL-23, engineered with half-life extension technology and formulated at high concentration with the goal of maximizing efficacy and enabling infrequent, subcutaneous maintenance dosing. In November 2025, interim healthy volunteer data from a Phase 1 trial were disclosed, demonstrating that SPY003 exhibited a favorable safety profile and a meaningfully differentiated PK profile supporting potential Q3M or Q6M maintenance dosing. Additional data from this Phase 1 trial were presented at the 21st Congress of the European Crohn’s and Colitis Organisation ("ECCO") in February 2026, providing further support for this potential best-in-class profile. Based on these interim results, SPY003 was advanced to the SKYLINE Phase 2 platform trial. Rational Combinations – the Company plans to investigate combinations of our proprietary antibodies in nonclinical studies and clinical trials in order to evaluate whether combinations can potentially lead to best-in-class efficacy in IBD, with less frequent dosing. In February and May 2025, preclinical data for SPY120 were presented at medical meetings, demonstrating that the combined inhibition of TL1A and α4β7 is superior to either monotherapy in mouse models of colitis and that the PK profiles of SPY001 and SPY002 were similar in non-human primates whether dosed as monotherapy or in combination, while also demonstrating no drug effects on PK. Preclinical data for SPY130 and SPY230 have demonstrated enhanced efficacy and pharmacodynamics with SPY003 in combination with SPY001 and with SPY002. The Company expects to include each of its rational combinations in Part B of the SKYLINE trial. Fourth Quarter 2025 Financial Results Cash Position: As of December 31, 2025, Spyre had cash, cash equivalents, and marketable securities of $756.5 million. In October 2025, the Company raised $316.2 million in gross proceeds, before deducting $19.8 million in underwriting discounts and other offering expenses, from a public offering of common stock. Net cash used in operating activities was $44.6 million for the fourth quarter of 2025. Research and Development (R&D) expenses: R&D expenses totaled $44.6 million for the fourth quarter of 2025 and $50.5 million for the fourth quarter of 2024. The decrease was primarily driven by lower early-stage R&D activities, partially offset by higher clinical trial expenses. General and Administrative (G&A) expenses: G&A expenses totaled $12.5 million for the fourth quarter of 2025 and $10.8 million for the fourth quarter of 2024. The increase was primarily driven by higher headcount. Total Other Expense (Income): For the fourth quarter of 2025, other expense totaled $5.4 million primarily driven by changes in the fair value of the contingent value right (CVR) liability, partially offset by interest earned on the Company's cash and marketable securities. For the fourth quarter of 2024, other income totaled $5.0 million primarily driven by interest earned on the Company's cash and marketable securities. Net Loss: Net loss totaled $62.5 million and $56.3 million for the fourth quarters of 2025 and 2024, respectively. About Spyre Therapeutics Spyre Therapeutics is a clinical-stage biotechnology company pioneering long-acting antibodies and antibody combinations to redefine the standard of care for inflammatory bowel disease (“IBD”) and rheumatic diseases ("RD"). Spyre's pipeline includes investigational extended half-life antibodies targeting α4β7, TL1A, and IL-23. For more information, please visit http://spyre.com. Safe Harbor / Forward Looking Statements Certain statements in this press release, other than purely historical information, may constitute "forward-looking statements" within the meaning of the federal securities laws, including for purposes of the safe harbor provisions under the United States Private Securities Litigation Reform Act of 1995. These statements include, but are not limited to, statements regarding: the Company's future results of operations and financial position; its business strategy, including the Company's ability to deliver meaningful value for patients, physicians and shareholders through its assets, strategy and execution, including its ability to successfully develop best-in-class therapeutics for IBD or RD that meaningfully improve both efficacy and convenience compared to today's standard of care and the Company's ability to develop first-in-class therapeutics for RD; the potential consistency of the SPY001, SPY002, SPY072 and SPY003 Phase 1 trial final data readouts with previously disclosed data for our programs; the sufficiency of the Company's funding to support the development of its assets, including expectations of cash runway extending into the second half of 2028; the length of time that the Company believes its existing cash resources will fund its operations; estimated market sizes and potential growth opportunities; its nonclinical and future clinical development activities, including the expected timing and results of the ongoing SKYWAY Phase 2 basket trial and SKYLINE phase 2 platform trial, including timing of cohort initiation and data readouts for the ongoing SKYWAY Phase 2 basket trial and SKYLINE Phase 2 platform trial, enrollment of clinical trials, the inclusion of each rational combination in Part B of the SKYLINE Phase 2 platform trial and the number of data readouts expected to be delivered in 2026 and 2027, and related regulatory feedback; the potential efficacy, tolerability, convenience, commercial viability and safety profile of its product candidates, including in combinations; the potential viability of the Company's antibodies as ideal components for combination therapies; the planned dosing regimen for SPY001, SPY002, SPY072 and SPY003, including the potential for a Q3M or Q6M dosing profile and the potential for such dosing profile to be the leading product profile in IBD and RD; the potential therapeutic benefits and economic value of its product candidates as monotherapies or in combinations and their extended half-life; and Spyre’s business plans, milestones, and goals. The words "opportunity," "potential," "milestones," "pipeline," "strategy," "anticipate," "believe," "could," "estimate," "expect," "may," "might," "plan," "possible," "predict," "should," "will," "would," and similar expressions (including the negatives of these terms) may identify forward-looking statements, but the absence of these words does not mean that a statement is not forward-looking. These forward-looking statements are based on current expectations and beliefs and involve a number of risks and uncertainties, many of which are beyond Spyre’s control, and other assumptions that may cause actual results or performance to be materially different from those expressed or implied by these forward-looking statements. These risks and uncertainties include, but are not limited, uncertainties and risks arising from regulatory feedback, including potential disagreement by regulatory authorities with the Company’s interpretation of data and the Company’s clinical trials for its product candidates; the potential for interim data not being delivered within expected time frames or final data not being consistent with or different than the interim data reported for our programs; the potential impact of Trump Administration policies and changes in law on our business; and those uncertainties and factors described in Spyre's most recent Annual Report on Form 10-K, as supplemented and updated by subsequent Quarterly Reports on Form 10-Q and any other filings that Spyre has made or may make with the SEC from time to time. You should not place undue reliance on forward-looking statements in this press release, which speak only as of the date they are made and are qualified in their entirety by reference to the cautionary statements herein. Spyre does not undertake or accept any duty to make any updates or revisions to any forward-looking statements. Contact Information: Media Contact Josie Butler, 1AB [email protected] Investor Contact Eric McIntyre [email protected] (1) Includes $1.0 million and $5.8 million in related party expenses for the three months ended December 31, 2025 and 2024, respectively. Includes $10.5 million and $40.1 million in related party expenses for the years ended December 31, 2025 and 2024, respectively. (2) Includes $0.2 million and $0.3 million in related party expenses for the three months ended December 31, 2025 and 2024, respectively. Includes $1.0 million and $1.1 million in related party expenses for the years ended December 31, 2025 and 2024, respectively.