Spyre Therapeutics, Inc.
For the period ended Mar 31, 2026. Filed May 5, 2026.
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A company's report for each of its first three quarters. The financial statements are not audited. It shows how the business has moved since the last annual report, and what management says changed.
Mar 31, 2026 · Filed May 5, 2026
SYRE$103.86+7.5%Stored close · as of Nov 6, 2026
What changed in Management’s Discussion and Analysis?
Read the current filingPrevious report: 10-Q
Period ended 2025-09-30; filed 2025-11-04.
0001636282-25-000102
Item 2. Management’s Discussion and Analysis of Financial Condition and Results of OperationsCurrent report: 10-Q
Period ended 2026-03-31; filed 2026-05-05.
0001636282-26-000050
Item 2. Management’s Discussion and Analysis of Financial Condition and Results of OperationsThe baseline is this issuer’s latest earlier reporting period of the same form that was filed before the current report. A previous 10-Q is a different quarter, not a year-over-year comparison. Amendments are excluded.
Compared 96 previous paragraphs and 101 current paragraphs.
41 unchanged; 37 reworded; 21 added; 14 removed; 4 previous and 2 current paragraphs rearranged.
Tables are not compared: 5 previous and 3 current tables excluded. Dates, whitespace, punctuation and numbering changes are ignored; changes to financial figures remain significant.
A changed paragraph is not evidence that risk increased or decreased. An unchanged paragraph does not establish that risk stayed the same.
Added paragraphs (21)
Current report
We are a biotechnology company pioneering long-acting antibodies and antibody combinations to redefine the standard of care for inflammatory bowel disease (“IBD”) and rheumatic diseases. Our pipeline includes extended half-life antibodies targeting α4β7, TL1A, and IL-23 in development as monotherapies and pair-wise combinations..
Current report
Our Strategy
Current report
Our goal is to develop next-generation therapeutics to redefine the standard of care for the treatment of IBD and other immune-mediated diseases, relying on three strategic pillars:
Current report
•Advancing a portfolio of next-generation monotherapies - novel antibody candidates engineered for optimized potency, selectivity, and pharmacokinetics (“PK”) against validated IBD targets
Current report
•Evaluating paradigm-changing IBD combinations - fixed-dose-combinations of our engineered investigational antibodies designed to enable superior efficacy, safety, and convenience
Current report
•Expansion of our anti-TL1A program into additional indications - pipeline-in-a-product potential in diseases with first-in-class and best-in-class opportunity, starting with rheumatoid arthritis (“RA”), psoriatic arthritis (“PsA”), and axial spondyloarthritis (“axSpA”)
Current report
Figure 1. Spyre portfolio
Current report
Figure 2. SKYLINE trial design
Current report
mMS=modified mayo score; RHI=Robarts Histopathology Index; HEMI=Histo-Endoscopic Mucosal Improvement; P=primary endpoint; S=secondary endpoint. Initiation of each cohort subject to regulatory clearance.
Current report
Figure 3. SKYWAY trial design
Current report
RF=rheumatoid factor; ACPA= Anti-citrullinated protein antibodies; cs/b/tsDMARD=conventional synthetic, biologic, or targeted synthetic disease modifying antirheumatic drugs; BASDAI=Bath Ankylosing Spondylitis Disease Activity Index; P=primary endpoint; S=secondary endpoint; E=exploratory endpoint. IR=inadequate response
Current report
Initial topline induction results from Part A of the SKYLINE trial in ulcerative colitis subjects were presented in April 2026. 43 subjects were dosed with SPY001 and 41 subjects completed the induction period. Baseline characteristics were consistent with expectations (Figure 4). SPY001 was well tolerated with a safety profile consistent with the α4β7 class. There were six subjects with treatment-emergent adverse events (TEAEs) during the induction treatment period, with one serious adverse event (SAE), deemed not drug-related. The most common AE (occurring in ≥ 2 subjects) was back pain (n=2) (Figure 5). SPY001 achieved the primary endpoint, demonstrating a statistically significant reduction in the RHI score of 9.2 points (p<0.0001). Rates of key secondary endpoints of clinical remission and endoscopic improvement were clinically meaningful at 40% and 51%, respectively (Figure 6).
Current report
Figure 4. SPY001 disposition and baseline demographics from SKYLINE Part A Induction Topline
Current report
1 Two subjects withdrew consent.
Current report
Figure 5. SPY001 safety summary from SKYLINE Part A Induction Topline
Current report
*Chest pain in a 68-year-old male with history of coronary artery disease and angina pectoris, type 2 diabetes mellitus, hypertension, and hypercholesterolemia who presented with chest pain. ECG and cardiac enzymes did not show signs of a myocardial infarction.
Current report
Figure 6. SPY001 efficacy summary from SKYLINE Part A Induction Topline
Current report
Primary endpoint of ΔRHI was analyzed using per protocol analysis set and t-test was applied to test against the null hypothesis of ΔRHI =0 (N=41); Secondary endpoints including Clinical Remission and Endoscopic Improvement rates were analyzed using full analysis set (N=43).
Current report
Based on these preclinical data, in addition to our positive interim Phase 1 results for SPY002 and SPY003, SPY230 was advanced into Part B of the SKYLINE Phase 2 platform trial.
Current report
Cash Provided by Financing Activities
Current report
Cash provided by financing activities for the three months ended March 31, 2025 was $0.1 million.
Removed paragraphs (14)
Previous report
Item 2. Management's Discussion and Analysis of Financial Condition and Results of Operations
Previous report
Acquisition of Pre-Merger Spyre
Previous report
On June 22, 2023, we acquired Pre-Merger Spyre pursuant to that certain Agreement and Plan of Merger (the “Acquisition Agreement”), dated June 22, 2023, by and among us, Aspen Merger Sub I, Inc., a Delaware corporation and a wholly owned subsidiary of the Company, Sequoia Merger Sub II, LLC, a Delaware limited liability company and one of our wholly owned subsidiaries, and Pre-Merger Spyre. Pre-Merger Spyre was a pre-clinical stage biotechnology company that was incorporated on April 28, 2023 under the direction of Peter Harwin, a Managing Member of Fairmount, for the purpose of holding rights to certain intellectual property being developed by Paragon. Fairmount is a founder of Paragon.
Previous report
Through the Asset Acquisition, we received the option to license certain intellectual property rights related to certain research programs (collectively, the "Option"). On July 12, 2023, we exercised the Option with respect to one of these research programs to be granted an exclusive license to all of Paragon's rights, title and interest in and to intellectual property rights, including inventions, patents, sequence information and results, under SPY001, our α4β7 integrin program, to develop and commercialize antibodies and products worldwide in all therapeutics disorders. We expect any patents pursued non-provisionally and that mature into issued patents to expire no earlier than 2044, subject to any disclaimers or extensions. On December 14, 2023, we exercised the Option under the Paragon Agreement to be granted an exclusive license to all of Paragon’s rights, title and interest in and to intellectual property rights, including inventions, patents, sequence information and results, under SPY002 (formerly SPY002-091) and SPY072 (formerly SPY002-072), our TL1A programs, to develop and commercialize antibodies and products worldwide in all therapeutics disorders. We expect any patents pursued non-provisionally and that mature into issued patents to expire no earlier than 2044, subject to any disclaimers or extensions. On June 5, 2024, we exercised the Option under the Paragon Agreement to be granted an exclusive license to all of Paragon’s rights, title and interest in and to intellectual property rights, including inventions, patents, sequence information and results, under SPY003, our IL-23 program, to develop and commercialize antibodies and products worldwide solely in inflammatory bowel disease ("IBD") indications. We expect any patents pursued non-provisionally and that mature into issued patents to expire no earlier than 2045, subject to any disclaimers or extensions. The license agreements pertaining to SPY001 (the "SPY001 License Agreement") and SPY002 and SPY072 (the "SPY002 and SPY072 License Agreement") between the Company and Paragon were executed in the second quarter of 2024, and the license agreement pertaining to SPY003 (the "SPY003 License Agreement" and, together with the SPY001 License Agreement and the SPY002 and SPY072 License Agreement, the "License Agreements") between the Company and Paragon was executed in October 2024 and subsequently amended and restated on February 24, 2025. See the section titled “Paragon Agreement” in this Quarterly Report for more discussion about the Paragon Agreement and the License Agreements.
Previous report
Following the Asset Acquisition, we have significantly reshaped the business into a clinical stage biotechnology company focused on developing next generation therapeutics for patients living with IBD, including ulcerative colitis ("UC") and Crohn's disease ("CD"), and rheumatic diseases ("RD"), including rheumatoid arthritis ("RA"), psoriatic arthritis ("PsA"), and axial spondyloarthritis ("axSpA"). Our portfolio of novel and proprietary monoclonal antibody product candidates has the potential to address unmet needs in IBD and RD care by improving efficacy, safety, and/or dosing convenience relative to products currently available or product candidates in development. We have engineered our product candidates with the aim to bind potently and selectively to their target epitopes and to exhibit extended pharmacokinetic ("PK") half-lives through modifications in the Fc domain, which modifications are designed to increase affinity to human FcRn and increase antibody recycling. We anticipate that half-life extension will enable less frequent administration as compared to marketed or development-stage mAbs that do not incorporate half-life extension modifications. In addition to the development of our product candidates as potential monotherapies, we plan to investigate combinations of our proprietary antibodies in nonclinical studies and clinical trials in order to evaluate whether combinations (co-administration or co-formulation of multiple monoclonal antibodies) can lead to greater efficacy, as compared to monotherapies in IBD. We intend to deliver our product candidates through convenient, infrequently self-administered, subcutaneous maintenance injections, although the specific delivery mechanism or technology has not been selected given our early stage.
Previous report
Topline proof-of-concept data for all three indications are expected in 2026.
Previous report
These preclinical data, in addition to our positive interim Phase 1 results for SPY002 and SPY003, support SPY230 being advanced in Part B of the SKYLINE Phase 2 platform trial.
Previous report
Comparison of the Nine Months Ended September 30, 2025 and 2024
Previous report
Research and Development Expenses. Research and development expenses increased by $14.7 million, or 13%, to $127.0 million for the nine months ended September 30, 2025, from $112.3 million for the nine months ended September 30, 2024. The increase was primarily driven by higher clinical development activities, increased compensation costs and higher intellectual property license and sub-licensing fees, partially offset by lower early-stage research and development.
Previous report
General and Administrative Expenses. General and administrative expenses increased by $0.4 million, or 1%, to $35.4 million for the nine months ended September 30, 2025, from $35.0 million for the nine months ended September 30, 2024. The increase was primarily attributable to an increase in compensation costs due to an increase in general and administrative headcount.
Previous report
Interest Income. Interest income was $17.7 million and $15.5 million for the nine months ended September 30, 2025 and 2024, respectively. The increase was primarily due to higher investment balances.
Previous report
Other income, net. Other income, net for the nine months ended September 30, 2025 increased by $61.9 million versus the nine months ended September 30, 2024 primarily driven by changes in the fair value of the CVR liability, which was primarily driven by changes in the likelihood of achievement of certain milestones and receipt of certain cash consideration within the CVR term, changes in estimated reimbursement rates compared to reimbursement target rates, changes in estimated cash flow dates, and an increase in risk-adjusted discount rates, partially offset by time value of money adjustments..
Previous report
In March 2024, we completed a private placement of 121,625 shares of Series B Preferred Stock at $1,480.00 per share resulting in net proceeds of approximately $168.9 million after deducting approximately $11.2 million of placement agent and other offering costs.
Previous report
Cash (Used in) Provided by Financing Activities
Reworded paragraphs (37)
Previous wording
We are advancing a pipeline of monoclonal antibodies (“mAbs”) for the treatment of IBD and RD. The following table summarizes our pipeline and development strategy, including our initiated SKYLINE Phase 2 platform study evaluating SPY001, SPY002, SPY003, and pairwise combinations thereof in patients with moderately to severely active UC and our initiated SKYWAY basket study evaluating SPY072 in three rheumatic diseases: RA, PsA, and axSpA.
Current wording
We are advancing a pipeline of monoclonal antibodies (“mAbs”) for the treatment of IBD and other immune-mediated diseases. The following table (Figure 1) summarizes our pipeline and development strategy, including our SKYLINE Phase 2 platform trial evaluating SPY001, SPY002, SPY003, and pairwise combinations thereof in subjects with moderately to severely active UC and our SKYWAY basket trial evaluating SPY072 in three rheumatic diseases: RA, PsA, and axSpA:
Previous wording
In May 2025, we initiated our SKYLINE Phase 2 platform trial evaluating SPY001, SPY002, SPY003, as well as pairwise combinations thereof (six active investigational agents in total), in patients with moderately to severely active UC. The trial consists of two parts:
Current wording
In May 2025, we initiated our SKYLINE Phase 2 platform trial evaluating SPY001, SPY002, SPY003, as well as pairwise combinations thereof (six investigational agents in total), in subjects with moderately to severely active UC (Figure 2). The trial consists of two parts:
Previous wording
•Part A: Open-label assessment of the safety and preliminary efficacy of a single dose level of each investigational monotherapy, with induction data expected in 2026.
Current wording
•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 initial SPY001 Part A topline induction data announced in April 2026, and initial topline data expected for SPY002 and SPY003 in mid-2026 and the third quarter of 2026, respectively.
Previous wording
SKYLINE is currently enrolling subjects into the SPY001 and SPY002 arms of Part A, with SPY003 expected to begin enrolling in the coming months. Part B is expected to begin enrolling after Part A completes enrollment.
Current wording
SKYLINE is currently enrolling subjects into Part B of the trial.
Previous wording
In September 2025, we initiated our SKYWAY 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:
Current wording
In September 2025, we initiated our SKYWAY Phase 2 randomized and placebo-controlled basket trial of SPY072 in subjects with moderately to severely active RA, PsA, or axSpA (Figure 3). The trial consists of three sub-studies:
Previous wording
•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.
Current wording
•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.
Previous wording
•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.
Current wording
•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.
Previous wording
•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.
Current wording
•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.
Previous wording
Our most advanced product candidate, SPY001, is a highly potent, highly selective, and humanized monoclonal immunoglobulin G1 antibody designed to bind selectively to the α4β7 integrin being developed for the treatment of IBD (UC and CD). The α4β7 integrin is a protein found on the surface of immune cells. This integrin regulates the migration of immune cells to the gut where they contribute to the inflammatory process in IBD. By selectively binding to the α4β7 integrin, SPY001 is designed to prevent the interaction of these immune cells with MAdCAM-1, a molecule expressed on endothelial cells lining the blood vessels in the gut. This interaction is responsible for guiding lymphocytes from the bloodstream into the gut tissue, where they cause inflammation. By blocking the interaction between α4β7 integrin and MAdCAM-1, SPY001 aims to reduce the recruitment of immune cells to the gut, leading to a decrease in inflammation. Since it specifically targets the gut immune system, SPY001 is designed to minimize systemic immunosuppressive effects unrelated to IBD pathology.
Current wording
SPY001 is a highly potent, highly selective, and humanized monoclonal immunoglobulin G1 investigational antibody designed to bind selectively to the α4β7 integrin being developed for the treatment of IBD (UC and CD). The α4β7 integrin is a protein found on the surface of immune cells. This integrin regulates the migration of immune cells to the gut where they contribute to the inflammatory process in IBD. By selectively binding to the α4β7 integrin, SPY001 is designed to prevent the interaction of these immune cells with MAdCAM-1, a molecule expressed on endothelial cells lining the blood vessels in the gut. By blocking the interaction between α4β7 integrin and MAdCAM-1, SPY001 aims to reduce the recruitment of immune cells to the gut, leading to a decrease in inflammation. Since it specifically targets the gut immune system, SPY001 is designed to minimize systemic immunosuppressive effects unrelated to IBD pathology.
Previous wording
SPY001 demonstrates similar potency and selectivity as synthesized vedolizumab in preclinicalin vitro models including surface plasmon residence and cellular adhesion assays. We initiated a first-in-human ("FIH") Phase 1 trial for SPY001 in June 2024. The SPY001 Phase 1 trial is a double blind, placebo-controlled trial in healthy volunteers and consists of a single-ascending dose ("SAD") component and a multi-ascending dose ("MAD") component. The trial design includes enrolling 56 healthy adult participants into five SAD cohorts and two MAD cohorts in the main portion of the study. The primary endpoint is safety, with PK and anti-drug antibodies ("ADA") serving as secondary endpoints. Additional cohorts have been added to the study to evaluate PK in healthy volunteers of various ethnicities to facilitate subsequent global clinical trials. Phase 1 trial enrollment is now complete.
Current wording
(“MAD”) component. The trial enrolled 56 healthy adult participants into five SAD cohorts and two MAD cohorts in the main portion of the trial. The primary endpoint was safety, with PK and anti-drug antibodies (“ADA”) serving as secondary endpoints. Additional cohorts were added to the trial to evaluate PK in healthy volunteers of various ethnicities to facilitate subsequent global clinical trials. The Phase 1 study is now complete.
Previous wording
Interim results were initially presented in November 2024, with additional data presented in May 2025 with up to eight months of follow up. To date, SPY001 has demonstrated a favorable safety profile across all dose groups, a meaningfully differentiated PK profile supporting potential quarterly or twice annual maintenance dosing, and rapid and complete saturation of α4β7 receptors beyond six months with a single dose of 600mg. Based on these results, SPY001 was advanced into the SKYLINE Phase 2 platform clinical trial, which initiated in May 2025.
Current wording
Interim results were initially presented in November 2024, with additional data presented in May 2025 with up to eight months of follow up. To date, SPY001 has demonstrated a favorable safety profile across all dose groups, a meaningfully differentiated PK profile supporting potential quarterly or twice annual maintenance dosing, and rapid, complete saturation of α4β7 receptors beyond six months with a single dose of 600mg. Based on these results, SPY001 was advanced into the SKYLINE Phase 2 platform clinical trial.
Previous wording
For our anti-TL1A program, we nominated two highly potent, highly selective, and fully human mAb candidates designed to bind to tumor necrosis factor-like ligand 1A (“TL1A”). SPY002 (formerly SPY002-091) is being developed for the treatment of IBD (UC and CD) and SPY072 (formerly SPY002-072) is being developed for the treatment of RD. TL1A is a protein that plays a role in regulating the immune system and is elevated in the gut tissue of individuals with IBD and serum or synovial tissue of individuals with RA, PsA, and axSpA. TL1A interacts with its receptor, death receptor 3 (“DR3”), which is expressed in various immune cells, including T cells and fibroblast-like synoviocytes. This interaction triggers signaling pathways that contribute to inflammation and joint injury in RD, leading to symptomology, such as pain and swelling. SPY002 and SPY072 have been designed to block the interaction between TL1A and DR3, and thereby inhibit the downstream signaling events to dampen the inflammatory response. By neutralizing TL1A, we believe that SPY002 and SPY072 have the potential to modulate the immune response in IBD and RD patients, potentially reducing disease activity.
Current wording
TL1A is a protein that plays a role in regulating the immune system and is elevated in gut tissue of individuals with IBD and serum or synovial tissue of individuals with RA, PsA, and axSpA. TL1A interacts with its receptor, death receptor 3 (“DR3”), which is expressed in various immune cells, including T cells and fibroblast-like synoviocytes. This interaction triggers signaling pathways that contribute to inflammation and joint injury in RD, leading to symptomology, such as pain and swelling. SPY002 and SPY072 have been designed to block the interaction between TL1A and DR3, and thereby inhibit the downstream signaling events to dampen the inflammatory response. By neutralizing TL1A, we believe that SPY002 and SPY072 have the potential to modulate the immune response in IBD and rheumatic disease patients, potentially reducing disease activity.
Previous wording
SPY002 and SPY072 bind TL1A with subnanomolar potency in preclinical cellular assays. We initiated FIH Phase 1 trials for SPY002 and SPY072 in the fourth quarter of 2024. The Phase 1 trials were each double blind, placebo-controlled evaluations in healthy volunteers, consisting of five SAD cohorts. Each trial enrolled 40 healthy adult participants across the five SAD cohorts in the main portion of the study. The primary endpoint is safety, with PK and ADAs serving as secondary endpoints, and PD markers as exploratory endpoints. Phase 1 trial enrollment is now complete.
Current wording
SPY002 and SPY072 bind and inhibit TL1A with subnanomolar potency in preclinical cellular assays. We initiated FIH Phase 1 trials for SPY002 and SPY072 in the fourth quarter of 2024. The Phase 1 trials were each double blind, placebo-controlled evaluations in healthy volunteers, consisting of five SAD cohorts. Each trial enrolled 40 healthy adult participants across the five SAD cohorts in the main portion of the trial. The primary endpoint is safety, with PK and ADAs serving as secondary endpoints, and PD markers as exploratory endpoints. Phase 1 trial enrollment is complete.
Previous wording
Phase 1 data were presented in June 2025 and October 2025, with up to 24-weeks of follow up. To date, SPY002 and SPY072 have demonstrated favorable safety profiles, meaningfully differentiated PK profiles supporting potential quarterly or twice annual maintenance dosing, and complete suppression of free TL1A through up to 20-24 weeks at single 100mg doses. Based on these interim results, SPY002 has advanced to the SKYLINE Phase 2 platform trial and SPY072 has advanced to the SKYWAY Phase 2 basket trial.
Current wording
Phase 1 data were presented in June 2025 and October 2025, with up to 24-weeks of follow up. To date, SPY002 and SPY072 have demonstrated favorable safety profiles, meaningfully differentiated PK profiles supporting potential quarterly or twice annual maintenance dosing, and complete suppression of free TL1A through up to 20-24 weeks at single 100mg doses. Based on these results, SPY002 was advanced to the SKYLINE Phase 2 platform trial in UC subjects and SPY072 was advanced to the SKYWAY Phase 2 basket trial in RA, PsA, and axSpA subjects.
Previous wording
Interim Phase 1 data were disclosed in November 2025 demonstrating that SPY003 exhibited a favorable safety profile and a meaningfully differentiated PK profile supporting quarterly or twice annual maintenance dosing. SPY003 will now advance to the SKYLINE Phase 2 platform trial.
Current wording
Interim Phase 1 data were disclosed in November 2025, and additional data were presented in February 2026 with up to 20 weeks of follow-up, demonstrating that SPY003 exhibited a favorable safety profile and a meaningfully differentiated PK profile supporting quarterly or twice annual maintenance dosing. Based on these results, SPY003 was advanced to the SKYLINE Phase 2 platform trial.
Previous wording
SPY120 combines SPY001 (anti-α4β7) and SPY002 (anti-TL1A) antibodies, pairing two mechanisms studied in third-party clinical trials targeting non-overlapping sites of action.
Current wording
SPY120 combines SPY001 (anti-α4β7) and SPY002 (anti-TL1A) antibodies, pairing two complementary mechanisms studied in third-party clinical trials targeting non-overlapping sites of action.
Previous wording
These preclinical data, in addition to our positive interim Phase 1 results for SPY001 and SPY002, support SPY120 being advanced in Part B of the SKYLINE Phase 2 platform trial.
Current wording
Based on these preclinical data, in addition to our positive interim Phase 1 results for SPY001 and SPY002, SPY120 was advanced into Part B of the SKYLINE Phase 2 platform trial.
Previous wording
These preclinical data, in addition to our positive interim Phase 1 results for SPY001 and SPY003, support SPY130 being advanced in Part B of the SKYLINE Phase 2 platform trial.
Current wording
Based on these preclinical data, in addition to our positive interim Phase 1 results for SPY001 and SPY003, SPY130 was advanced into Part B of the SKYLINE Phase 2 platform trial.
Previous wording
In May 2023, Pre-Merger Spyre entered into the Paragon Agreement with Paragon and Parapyre. Pursuant to the Paragon Agreement, the Option provided for the right to acquire the intellectual property rights related to certain research programs from Paragon in accordance with a license agreement to be entered into following each exercise of the Option.
Current wording
Pursuant to the Paragon Agreement, we received the option to license the intellectual property rights related to four research programs (collectively, the “Option”) from Paragon in accordance with a license agreement to be entered into following each exercise of the Option.
Previous wording
On July 12, 2023, December 14, 2023 and June 5, 2024, we exercised our Option available under the Paragon Agreement with respect to the SPY001, SPY002, SPY072 and SPY003 research programs, respectively. In May 2024, we signed license agreements with Paragon for rights to royalty-bearing, world-wide, exclusive licenses to develop, manufacture, commercialize or otherwise exploit certain antibodies and products targeting ɑ4β7 integrin (SPY001 program) and TL1A (SPY002 and SPY072 programs) and, in October 2024, we signed a license agreement for rights to a royalty-bearing, world-wide, exclusive license to develop, manufacture, commercialize or otherwise exploit certain antibodies and products targeting IL-23 (SPY003 program) in the field of IBD. The SPY003 License Agreement was subsequently amended and restated in February 2025 to, among other things, clarify each party's rights and obligations with respect to license exclusivity and patent prosecution.
Current wording
On July 12, 2023, December 14, 2023 and June 5, 2024, we exercised our Option available under the Paragon Agreement with respect to the SPY001, SPY002 and SPY003 research programs, respectively. In May 2024, we signed license agreements with Paragon for rights to royalty-bearing, world-wide, exclusive licenses to develop, manufacture, commercialize or otherwise exploit certain antibodies and products targeting ɑ4β7 integrin (SPY001 program) (the “SPY001 License Agreement”) and TL1A (SPY002 and SPY072 programs) (the “SPY002 and SPY072 License Agreement”) and, in October 2024, we signed a license agreement for rights to a royalty-bearing, world-wide, exclusive license to develop, manufacture, commercialize or otherwise exploit certain antibodies and products targeting IL-23 (SPY003 program) (the “SPY003 License Agreement” and, together with the SPY001 License Agreement and the SPY002 and SPY072 License Agreement, the “License Agreements”) in the field of IBD. The SPY003 License Agreement was subsequently amended and restated in February 2025. The Option with respect to one additional program remains unexercised under the Paragon Agreement.
Previous wording
Under the terms of each License Agreement, we are obligated to pay Paragon up to $22.0 million upon the achievement of specific development, regulatory and clinical milestones for the first product under each agreement, respectively, that achieves such specified milestones, including a milestone payment of $3 million upon the first dosing of a human patient in a Phase 2 trial. With respect to the SPY002 and SPY072 License Agreement only, on a product by product basis, we are obligated to pay sublicensing fees of up to approximately $20 million upon the achievement of mostly commercial milestones.
Current wording
Under the terms of each License Agreement, we are obligated to pay Paragon up to $22.0 million upon the achievement of specific development, regulatory and clinical milestones for the first product under each agreement, respectively, that achieves such specified milestones, including a milestone payment of $5 million upon the first dosing of a human patient in a Phase 3 trial. With respect to the SPY002 and SPY072 License Agreement only, on a product by product basis, we are obligated to pay sublicensing fees of up to approximately $20 million upon the achievement of mostly commercial milestones. Subject to the execution of the Option with respect to the remaining research program, we expect to be obligated to make similar payments upon and following the execution of a license agreement with respect to such research program.
Previous wording
Research and Development Expenses. Research and development expenses increased by $0.5 million, or 1%, to $45.2 million for the three months ended September 30, 2025, from $44.7 million for the three months ended September 30, 2024. The increase was primarily driven by higher clinical trial expenses, intellectual property license and sub-licensing fees, manufacturing expenses, and increased compensation costs partially offset by lower early-stage research and development costs.
Current wording
Research and Development Expenses. Research and development expenses increased by $18.8 million, or 45%, to $60.4 million for the three months ended March 31, 2026, from $41.6 million for the three months ended March 31, 2025. The increase was primarily driven by higher clinical trial expenses , manufacturing expenses, and increased compensation costs partially offset by lower early-stage research and development costs.
Previous wording
External research and development expenses include costs associated with third parties contracted to conduct research and development activities on our behalf, including through Paragon, contract research organizations, contract manufacturing organizations, and third-party laboratories. For the three months ended September 30, 2025 and 2024, external research and development costs accounted for $34.3 million and $38.9 million, respectively. Preclinical expenses decreased primarily due to a reduction in early-stage research and development activities given our pipeline's advancement coupled with lower intellectual property license and sub-licensing fees. IBD expenses increased primarily due to an increase in clinical development activities related to ongoing or planned clinical trials and intellectual property licensing and sub-licensing fees partially offset by lower manufacturing costs. Rheumatic diseases costs increased due to increases in manufacturing costs, clinical development costs, and intellectual property licensing and sub-licensing fees. External stock-based compensation decreased due to our obligations ending under the Parapyre Option Obligation.
Current wording
External research and development expenses include costs associated with third parties contracted to conduct research and development activities on our behalf, including through Paragon, contract research organizations, contract manufacturing organizations, and third-party laboratories. For the three months ended March 31, 2026 and 2025, external research and development costs accounted for $46.3 million and $33.5 million, respectively. Preclinical expenses decreased primarily due to a reduction in early-stage research and development activities given our pipeline's advancement. IBD expenses increased primarily due to an increase in manufacturing costs and clinical development activities related to ongoing or planned clinical trials. Rheumatic diseases costs increased due to increases in manufacturing costs and clinical development costs.
Previous wording
Internal research and development expenses include compensation and related costs associated with our research and development employees. For the three months ended September 30, 2025 and 2024, internal research and development costs accounted for $10.9 million and $5.8 million, respectively. The increase was primarily driven by an increase in compensation costs due to an increase in research and development headcount.
Current wording
Internal research and development expenses include compensation and related costs associated with our research and development employees. For the three months ended March 31, 2026 and 2025, internal research and development costs accounted for $14.2 million and $8.1 million, respectively. The increase was primarily driven by an increase in compensation costs due to an increase in research and development headcount.
Previous wording
General and Administrative Expenses. General and administrative expenses increased by $1.0 million, or 9%, to $11.6 million for the three months ended September 30, 2025, from $10.6 million for the three months ended September 30, 2024. The increase was primarily attributable to an increase in compensation costs due to an increase in general and administrative headcount.
Current wording
General and Administrative Expenses. General and administrative expenses increased by $3.3 million, or 28%, to $15.2 million for the three months ended March 31, 2026, from $11.9 million for the three months ended March 31, 2025. The increase was primarily attributable to an increase in compensation costs due to an increase in general and administrative headcount.
Previous wording
Gain on Sale of In-Process Research and Development Asset. During the nine months ended September 30, 2025, the Company recognized a gain of $10.0 million for an achieved milestone related to the 2023 sale of the global rights of the legacy Aeglea asset pegzilarginase to Immedica, driven by a favorable reimbursement decision for pegzilarginase in Europe. There was no similar gain or loss during the nine months ended September 30, 2024.
Current wording
Gain on Sale of In-Process Research and Development Asset. During the three months ended March 31, 2026, the Company recognized a gain of $30.0 million for an achieved milestone related to the 2023 sale of the global rights of the legacy Aeglea asset pegzilarginase to Immedica, driven by regulatory approval of pegzilarginase in the United States. There was no similar gain or loss during the three months ended March 31, 2025.
Previous wording
Other income (expense), net. Other income, net for the three months ended September 30, 2025 increased by $59.1 million versus the three months ended September 30, 2024 primarily driven by changes in the fair value of the CVR liability, which was primarily driven by changes in the likelihood of achievement of certain milestones and receipt of certain cash consideration within the CVR term, changes in estimated reimbursement rates compared to reimbursement target rates, and changes in estimated cash flow dates.
Current wording
Other (expense) income, net. Other (expense) income, net for the three months ended March 31, 2026 increased by $32.6 million versus the three months ended March 31, 2025 primarily driven by changes in the fair value of the CVR liability, which was primarily driven by changes in the likelihood of achievement of certain milestones, changes in the risk-adjusted discount rates and time value of money adjustments.
Previous wording
Since our inception and through September 30, 2025, we have funded our operations by raising an aggregate of approximately $1.3 billion of gross proceeds from the sale and issuance of convertible preferred stock and common stock, pre-funded warrants, the collection of grant proceeds, and the licensing of our product rights for commercialization of pegzilarginase in Europe and certain countries in the Middle East. As of September 30, 2025, we had an accumulated deficit of $1.1 billion. In October 2025, we raised an additional approximately $296.5 million in net proceeds from a public underwritten offering of our common stock.
Current wording
Since our inception and through March 31, 2026, we have funded our operations by raising an aggregate of approximately $1.7 billion of gross proceeds from the sale and issuance of convertible preferred stock and common stock, pre-funded warrants, the collection of grant proceeds, and the licensing of our product rights for commercialization of pegzilarginase in Europe and certain countries in the Middle East. As of March 31, 2026, we had an accumulated deficit of $1.2 billion. In April 2026, we raised an additional approximately $435.3 million in net proceeds from a public underwritten offering of our common stock.
Previous wording
In September 2024 and December 2024, we sold an aggregate of 777,432 shares of common stock under an ATM offering program resulting in net proceeds of approximately $20.5 million after deducting sales agent commissions and other offering costs.
Current wording
On September 6, 2024, the Company entered into a sales agreement (the “Sales Agreement”) with TD Securities (USA) LLC as its agent, pursuant to which the Company may issue and sell up to $200.0 million of shares of common stock under an at-the-market (“ATM”) offering program. During the year ended December 31, 2025, we sold an aggregate of 445,668 shares of common stock under the ATM offering program at an average price per share of $33.772 resulting in net proceeds of $14.8 million, after deducting sales agent commissions and other offering costs of $0.3 million. During the three months ended March 31, 2026, the Company sold an aggregate of 296,396 shares of common stock under the ATM offering program at an average price per share of $33.566 resulting in net proceeds of $9.7 million after deducting sales agent commissions and other offering costs of $0.2 million. As of March 31, 2026, $154.1 million remained available for sale under the Sales Agreement.
Previous wording
In October 2025, we sold 17,094,594 shares of our common stock in an underwritten public offering, inclusive of 2,229,729 shares pursuant to the full exercise of the underwriters' over-allotment option, under our shelf registration statement on Form S-3 at a price per share of $18.50, resulting in net proceeds of $296.5 million after deducting approximately $19.8 million of underwriting discounts and other offering costs.
Current wording
In October 2025, we sold 17,094,594 shares of our common stock in an underwritten public offering, inclusive of 2,229,729 shares pursuant to the full exercise of the underwriters' over-allotment option, under our shelf registration statement on Form S-3 at a price per share of $18.50, resulting in net proceeds of $296.4 million after deducting approximately $19.9 million of underwriting discounts and other offering costs.
Previous wording
In November 2024, we sold 8,366,250 shares of our common stock in an underwritten public offering, inclusive of 1,091,250 shares pursuant to the full exercise of the underwriters' over-allotment option, under our shelf registration statement on Form S-3 at a price per share of $27.50, resulting in net proceeds of $215.9 million after deducting approximately $14.2 million of underwriting discounts and other offering costs.
Current wording
In April 2026, we sold an aggregate of 7,475,000 shares of our common stock, inclusive of 975,000 shares pursuant to the full exercise of the underwriters' over-allotment option, at a public offering price per share of $62.00, resulting in net proceeds of approximately $435.3 million after deducting approximately $28.1 million of underwriting discounts and other offering costs.
Previous wording
Cash used in operating activities for the nine months ended September 30, 2025 was $124.7 million and primarily reflected a net loss of $92.7 million adjusted for a $10.0 million non-operating gain on sale of in-process research and development and a $42.2 million decrease in the fair value of the CVR liability, partially offset by non-cash expenses of $27.8 million for share-based compensation expense and a $3.7 million change in net operating assets and liabilities driven primarily by timing of payments to vendors.
Current wording
Cash used in operating activities for the three months ended March 31, 2026 was $57.4 million and primarily reflected a net loss of $69.0 million adjusted for a $30.0 million non-operating gain on sale of in-process research and development and a $30.3 million increase in the fair value of the CVR liability, partially offset by non-cash expenses of $12.8 million for share-based compensation expense, $2.1 million in net accretion of discount on marketable securities.
Previous wording
Cash used in operating activities for the nine months ended September 30, 2024 was $120.2 million and reflected a net loss of $151.7 million. Our net loss was offset in part by non-cash expenses of $35.6 million for share-based compensation expense and a $19.6 million increase in the fair value of the CVR liability, offset by a $15.3 million net change in operating assets and liabilities and $9.0 million in net accretion of discount on marketable securities. The net change in operating assets and liabilities was primarily driven by timing of payments to vendors.
Current wording
Cash used in operating activities for the three months ended March 31, 2025 was $41.0 million and reflected a net loss of $44.8 million coupled with $2.6 million in net accretion of discount on marketable securities and a $2.4 million non-cash gain from the decrease of the CVR liability fair value, partially offset by stock-based compensation of $8.9 million.
Previous wording
Cash provided by investing activities for the nine months ended September 30, 2025 was $103.9 million and primarily consisted of $277.4 million in maturities and sales of marketable securities, $7.0 million in proceeds from the sale of in-process research & development asset partially offset by $180.5 million in purchases of marketable securities.
Current wording
Cash provided by investing activities for the three months ended March 31, 2026 was $56.6 million and primarily consisted of $107.7 million in maturities and sales of marketable securities and $30.0 million in proceeds from the sale of in-process research & development asset, partially offset by $81.2 million in purchases of marketable securities.
Previous wording
Cash used in investing activities for the nine months ended September 30, 2024, was $182.7 million and primarily consisted of $366.2 million in purchases of marketable securities, partially offset by $183.4 million in maturities and sales of marketable securities.
Current wording
Cash used in investing activities for the three months ended March 31, 2025 was $0.1 million.
Previous wording
Cash provided by financing activities for the nine months ended September 30, 2024, was $185.3 million, which primarily consisted of the net proceeds from the issuance of the Series B Preferred Stock in the March 2024 PIPE of $168.9 million, $11.8 million in net proceeds from the issuance of common stock in connection with the ATM, and $6.2 million from proceeds from stock option exercises and sales of Common Stock under our 2016 Employee Stock Purchase Plan and the exercise of pre-funded warrants.
Current wording
Cash provided by financing activities for the three months ended March 31, 2026 was $12.3 million, which primarily consisted of $9.8 million net proceeds from the issuance of common stock in connection with the ATM offering program and $2.7 million proceeds from stock option exercises and sales of common stock under our Employee Stock Purchase Plan, partially offset by $0.2 million payment of deferred offering costs.
Previous wording
Through the Asset Acquisition, we received the Option to license certain intellectual property rights related to certain research programs. The exercise of the Option allows for us to enter into an exclusive license agreement with Paragon for the respective research program. Thus far we have exercised the Option and entered into license agreements with respect to SPY001, SPY002, SPY072 and SPY003. Under the terms of each License Agreement, we are obligated to pay Paragon up to $22.0 million based on specific development, regulatory and clinical milestones for the first product under each agreement. As of September 30, 2025, we have incurred a total of $18.0 million of milestone fees out of a total maximum of $66.0 million in potential milestone fees across all License Agreements. As of September 30, 2025, $3.0 million in milestone fees remain outstanding and payable. With respect to the SPY002 and SPY072 License Agreement only, on a product by product basis, we are obligated to pay sublicensing fees of up to approximately $20 million upon the achievement of mostly commercial milestones. As of September 30, 2025, we have incurred $1.7 million of sublicensing fees of which $1.0 million is outstanding and payable.
Current wording
Through the Asset Acquisition, we received the Option to license certain intellectual property rights related to certain research programs. The exercise of the Option allows for us to enter into an exclusive license agreement with Paragon for the respective research program. Thus far we have exercised the Option and entered into license agreements with respect to SPY001, SPY002, SPY072 and SPY003. Under the terms of each License Agreement, we are obligated to pay Paragon up to $22.0 million based on specific development, regulatory and clinical milestones for the first product under each agreement. As of March 31, 2026, we have incurred a total of $21 million of milestone fees out of a total maximum of $66.0 million in potential milestone fees across all License Agreements. As of March 31, 2026 no achieved milestone fees are outstanding and payable. With respect to the SPY002 and SPY072 License Agreement only, on a product by product basis, we are obligated to pay sublicensing fees of up to approximately $20 million upon the achievement of mostly commercial milestones. As of March 31, 2026, we have incurred $2.6 million of sublicensing fees of which none is outstanding and payable.
Rearranged current paragraphs (2)
Current report — wording carried from elsewhere
SPY001 demonstrates similar potency and selectivity as synthesized vedolizumab in preclinicalin vitro models including surface plasmon residence and cellular adhesion assays. We initiated a first-in-human (“FIH”) Phase 1 trial for SPY001 in June 2024. The SPY001 Phase 1 trial was a double blind, placebo-controlled trial in healthy volunteers consisting of a single-ascending dose (“SAD”) component and a multi-ascending dose
Current report — wording carried from elsewhere
For our anti-TL1A program, we nominated two highly potent, highly selective, and fully human mAb candidates designed to bind to tumor necrosis factor-like ligand 1A (“TL1A”). SPY002 (formerly SPY002-091) is being developed for the treatment of IBD (UC and CD) and SPY072 (formerly SPY002-072) is being developed for the treatment of RD.
Rearranged previous paragraphs (4)
Previous report — wording carried elsewhere
The following table summarizes our results of operations for the nine months ended September 30, 2025 and 2024, together with the changes in those items in dollars and as a percentage:
Previous report — wording carried elsewhere
External research and development expenses include costs associated with third parties contracted to conduct research and development activities on our behalf, including through Paragon, contract research organizations, contract manufacturing organizations, and third-party laboratories. For the nine months ended September 30, 2025 and 2024, external research and development costs accounted for $98.2 million and $98.0 million, respectively. Preclinical expenses decreased primarily due to a reduction in early-stage research and development activities given our pipeline's advancement coupled with lower intellectual property license and sub-licensing fees. IBD expenses increased primarily due to increases in clinical development costs related to ongoing or planned clinical trials and intellectual property licensing and sub-licensing fees partially offset by decreased manufacturing costs. Rheumatic diseases costs increased due to increases in manufacturing, clinical development costs, and intellectual property licensing and sub-licensing fees. External stock-based compensation decreased due to our obligations ending under the Parapyre Option Obligation.
Previous report — wording carried elsewhere
Internal research and development expenses include compensation and related costs associated with our research and development employees. For the nine months ended September 30, 2025 and 2024, internal research and development costs accounted for $28.8 million and $14.3 million, respectively. The increase was primarily driven by an increase in research and development headcount.
Previous report — wording carried elsewhere
Cash used in financing activities for the nine months ended September 30, 2025 was $3.8 million, which primarily consisted of a $5.3 million payment to CVR holders partially offset by $1.6 million proceeds from stock option exercises and sales of common stock under our Employee Stock Purchase Plan.