Ulcerative colitis trial shows strong SPY001 data for Spyre (NASDAQ: SYRE)
Filing Impact
Filing Sentiment
Form Type
8-K
Rhea-AI Filing Summary
Spyre Therapeutics reported positive 12-week induction results from Part A of its Phase 2 SKYLINE trial of SPY001 in moderate-to-severely active ulcerative colitis. SPY001 met the primary endpoint with a statistically significant 9.2-point reduction in Robarts Histopathology Index (p<0.0001).
Key secondary endpoints were also encouraging, with clinical remission by modified Mayo Score in 40% of patients and endoscopic improvement in 51%. Among 43 treated patients, 14% experienced treatment-emergent adverse events and one serious event, which investigators deemed not drug-related, supporting a safety profile consistent with the α4β7 class. Part A recruitment is closed and Part B, including monotherapy and combination cohorts, is now enrolling with additional readouts expected in 2026 and 2027.
Positive
- SPY001 met its primary endpoint in SKYLINE Part A with a 9.2-point Robarts Histopathology Index reduction (p<0.0001), alongside 40% clinical remission and 51% endoscopic improvement, indicating a potentially strong efficacy profile in ulcerative colitis.
Negative
- None.
Insights
Strong Phase 2 efficacy and clean safety profile make this a notable value inflection for Spyre.
The SKYLINE Part A data show SPY001 achieving a 9.2-point Robarts Histopathology Index reduction at Week 12 (p<0.0001), with 40% clinical remission and 51% endoscopic improvement. For a mid-stage ulcerative colitis program, this combination of histologic and clinical outcomes is meaningfully strong.
Safety appears favorable: only 6 of 43 patients had treatment-emergent adverse events, one serious and deemed not drug-related, aligning with expectations for the α4β7 class. This mitigates a key development risk and supports continued dose and combination exploration.
The transition to Part B, with multiple monotherapy and combination cohorts already enrolling and additional data planned for mid-2026, Q3 2026, and 2027, sets up a series of future clinical catalysts. Overall, this filing represents a materially positive clinical milestone rather than a routine update.
8-K Event Classification
3 items: 7.01, 8.01, 9.01
3 items
Item 7.01
Regulation FD Disclosure
Disclosure
Material non-public information disclosed under Regulation Fair Disclosure, often investor presentations or guidance.
Item 8.01
Other Events
Other
Voluntary disclosure of events the company deems important to shareholders but not covered by other items.
Item 9.01
Financial Statements and Exhibits
Exhibits
Financial statements, pro forma financial information, and exhibit attachments filed with this report.
Key Figures
SPY001 Robarts Histopathology Index change: 9.2-point reduction
Clinical remission rate: 40% of patients
Endoscopic improvement rate: 51% of patients
+3 more
6 metrics
SPY001 Robarts Histopathology Index change
9.2-point reduction
Primary endpoint, Week 12 in SKYLINE Part A
Clinical remission rate
40% of patients
Secondary endpoint, modified Mayo Score at Week 12
Endoscopic improvement rate
51% of patients
Secondary endpoint at Week 12
Patients treated with SPY001
43 patients (n=43)
SKYLINE Part A induction cohort size
Treatment-emergent adverse events
6 patients (14%)
SPY001 safety summary in induction period
Serious adverse events
1 patient (2%)
Serious AE deemed not drug-related
Key Terms
Robarts Histopathology Index, clinical remission, endoscopic improvement, treatment-emergent adverse events, +2 more
6 terms
Robarts Histopathology Index medical
"SPY001 met its primary endpoint with a statistically significant reduction of 9.2 points (p<0.0001) from baseline at Week 12 in Robart’s Histopathology Index"
clinical remission medical
"Secondary endpoints included clinical remission by modified Mayo Score of 40% and endoscopic improvement of 51%"
A state in which a patient’s disease symptoms have largely disappeared or dropped to a level so low they no longer interfere with daily life, as judged by doctors or trial measurements. For investors, reaching clinical remission in a drug trial or treatment program is like flipping a switch that shows the therapy can work — it boosts the odds of regulatory approval, broader use, and future sales, while still not guaranteeing a permanent cure.
endoscopic improvement medical
"Secondary endpoints included clinical remission by modified Mayo Score of 40% and endoscopic improvement of 51%"
Endoscopic improvement is a visible reduction in inflammation, ulcers, or other tissue damage seen through an endoscope—a thin camera doctors use to look inside the body, often the digestive tract. For investors, it matters because these camera-confirmed changes serve as direct, objective evidence that a medical treatment is healing tissue, much like before-and-after photos; strong endoscopic results can drive regulatory approvals, wider use by doctors, and commercial uptake.
treatment-emergent adverse events medical
"There were six subjects with treatment-emergent adverse events during the induction treatment period, with one serious adverse event"
Events or symptoms that either appear for the first time or get worse after a patient starts a treatment; think of new or intensified side effects that show up once medicine or a medical device is used. Investors watch these closely because they affect whether a therapy can gain regulatory approval, be prescribed widely, or face legal and commercial setbacks—similar to how early customer complaints can sink a new product’s prospects.
serious adverse event medical
"There were six subjects with treatment-emergent adverse events during the induction treatment period, with one serious adverse event ("SAE"), deemed not drug-related"
A serious adverse event is an unexpected medical problem tied to a treatment or trial that leads to death, is life‑threatening, requires (or prolongs) hospitalization, causes lasting disability, or results in a birth defect. Investors care because such events can prompt regulatory investigations, clinical holds, added safety studies, or product withdrawals—like a major car recall that halts sales, adds costs and damages trust, potentially affecting a company’s value and timelines.
α4β7 medical
"SPY001, a potential best-in-class anti-α4β7 being investigated for the treatment of moderate-to-severely active ulcerative colitis"
UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
WASHINGTON, D.C. 20549
_______________________________________________________
FORM 8-K
_______________________________________________________
CURRENT REPORT
Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934
Date of Report (Date of earliest event reported): April 13, 2026
_______________________________________________________
(Exact name of Registrant as Specified in Its Charter)
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Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions:
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Item 7.01 Regulation FD Disclosure.
SPY001 SKYLINE Part A Induction Topline Results
On April 13, 2026, Spyre Therapeutics, Inc. (“Spyre” or the “Company”) issued a press release announcing positive initial 12-week induction topline data from Part A of the Phase 2 SKYLINE trial of SPY001 for the treatment of moderate-to-severely active ulcerative colitis (“UC”). The Company will host a conference call and webcast today, Monday, April 13, 2026 at 8:00 a.m., Eastern Time, to discuss the topline data from Part A of the Phase 2 SKYLINE trial of SPY001.
A copy of the press release and data presentation that will be referenced on the call are attached hereto as Exhibit 99.1 and Exhibit 99.2, respectively. The information in this Item 7.01 of this Current Report on Form 8-K, including Exhibit 99.1 and Exhibit 99.2 attached hereto, is intended to be furnished and shall not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended (the “Exchange Act”) or otherwise subject to the liabilities of that section, nor shall it be deemed incorporated by reference in any filing under the Securities Act of 1933, as amended, or under the Exchange Act, except as expressly set forth by specific reference in such filing.
Item 8.01 Other Events.
On April 13, 2026, the Company announced positive initial 12-week induction topline data from Part A of the Phase 2 SKYLINE trial of SPY001 for the treatment of moderate-to-severely active UC. Additionally, the Company announced that recruitment for Part A of the SKYLINE Trial is now closed and enrollment is open for Part B, which includes three monotherapy cohorts (SPY001, SPY002, and SPY003) and three combination cohorts (SPY120, SPY130, and SPY230) into which participants may be randomized versus a shared placebo. Proof-of-concept induction data for the remaining cohorts of Part A are now expected mid-2026 (SPY002) and Q3 2026 (SPY003). Part B induction data (all cohorts) remain on track for 2027.
SPY001 SKYLINE Part A Induction Topline Results
Initial 12-week findings from SKYLINE Part A demonstrated that SPY001 met or exceeded all key objectives.
Efficacy: SPY001 achieved the primary endpoint, demonstrating a statistically significant reduction in the Robarts Histopathology Index (“RHI”) score of 9.2 points (p<0.0001). Rates of key secondary endpoints of clinical remission and endoscopic improvement were clinically meaningful.
Endpoint | Week 12 Result | ||||
Change in RHI from baseline Primary endpoint | -9.2 (p<0.0001) | ||||
Clinical remission rate | 40% | ||||
Endoscopic improvement rate | 51% | ||||
Change in Modified Mayo Score | -3.7 | ||||
Safety: SPY001 was well tolerated with a safety profile consistent with the α4β7 class. There were six subjects with treatment-emergent adverse events during the induction treatment period, with one serious adverse
event (“SAE”), deemed not drug-related. The most common adverse event (“AE”) (occurring in ≥ 2 patients) was back pain (n=2).
SPY001 (n=43) | |||||
Subjects with any AE (n, %) | 6 (14%) | ||||
Severe (Grade ≥ 3) AE | 1 (2%)* | ||||
Drug-related AE | 0 | ||||
AE leading to study discontinuation | 0 | ||||
SAE | 1 (2%)* | ||||
Drug-related SAE | 0 | ||||
AEs of special interest | 0 | ||||
Death | 0 | ||||
*Chest pain in a 68-year-old male with history of coronary artery disease and angina on nitroglycerin prn, type 2 diabetes mellitus, hypertension, and hypercholesterolemia who presented with chest pain and was ruled out for a myocardial infarction
Forward-Looking Statements
Certain statements in this Current Report on Form 8-K, 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 ongoing and future clinical development activities, including Spyre’s plans for and timing of cohort initiation and data readouts for the ongoing SKYLINE trial and ongoing SKYWAY trial and enrollment of clinical trials; the inclusion of each rational combination in Part B of the SKYLINE Phase 2 platform trial; and Spyre’s business plans, milestones, strategy 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 involve a number of risks, uncertainties (some of which are beyond the Company’s control) or 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 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 filed with the U.S. Securities and Exchange Commission (“SEC”), as well as discussions of potential risks, uncertainties, and other important factors included in the Company’s other filings it makes with the SEC from time to time. Should one or more of these risks or uncertainties materialize, or should any of the Company’s assumptions prove incorrect, actual results may vary in material respects from those projected in these forward-looking statements. Nothing in this Current Report on Form 8-K should be regarded as a representation by any person that the forward-looking statements set forth therein will be achieved or that any of the contemplated results of such forward-looking statements will be achieved. You should not place undue reliance on forward-looking statements in this Current Report on Form 8-K, which speak only as of the date they are made and are qualified in their entirety by reference to the cautionary statements herein. The Company does not undertake or accept any duty to make any updates or revisions to any forward-looking statements. This Current Report on Form 8-K does not purport to summarize all of the conditions, risks and other attributes of an investment in the Company.
Item 9.01 Financial Statements and Exhibits.
(d) Exhibits
Exhibit Number | Description | |||||||
| 99.1 | Press release issued by Spyre Therapeutics, Inc. regarding Data, dated April 13, 2026. | |||||||
| 99.2 | Spyre Therapeutics, Inc. Data Presentation, dated April 13, 2026. | |||||||
| 104 | Cover Page Interactive Data File (embedded within the Inline XBRL document) | |||||||
SIGNATURES
Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.
| SPYRE THERAPEUTICS, INC. | |||||||||||
| Date: | April 13, 2026 | By: | /s/ Cameron Turtle | ||||||||
Cameron Turtle Chief Executive Officer | |||||||||||
Exhibit 99.1
Spyre Announces Potential Best-in-Class SPY001 Part A Induction Results from SKYLINE Trial in Moderate-to-Severe Ulcerative Colitis Patients
SPY001 met its primary endpoint with a statistically significant reduction of 9.2 points (p<0.0001) from baseline at Week 12 in Robart’s Histopathology Index (RHI) score
Secondary endpoints included clinical remission by modified Mayo Score of 40% and endoscopic improvement of 51%
SPY001 was well tolerated with a safety profile consistent with the α4β7 class
Recruitment for SKYLINE Part A closed, now enrolling Part B monotherapy and combination cohorts
Management will host a conference call today at 8:00 a.m. ET
WALTHAM, Mass., April 13, 2026 (GLOBE NEWSWIRE) – Spyre Therapeutics, Inc. (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 positive 12-week induction data from Part A of the Phase 2 SKYLINE trial of SPY001, a potential best-in-class anti-α4β7 being investigated for the treatment of moderate-to-severely active ulcerative colitis (UC).
“SPY001 was designed to improve upon vedolizumab’s proven activity in IBD by matching its epitope and potency while increasing target coverage through an extended half-life and greater induction dosing. Our data today support the hypothesis that this approach could lead to a best-in-class anti-α4β7 product across safety, efficacy, and convenience,” said Deanna Nguyen, M.D., SVP of Clinical Development and SKYLINE study lead. “Beyond SPY001’s potential as a monotherapy, we continue to believe that its gut-selective mechanism makes it an ideal backbone for combination therapy alongside our cytokine-targeting investigational antibodies SPY002 (anti-TL1A) or SPY003 (anti-IL23). We have begun enrolling these combinations globally and look forward to unveiling proof-of-concept data next year.”
Additionally, Spyre announced today that recruitment for Part A of SKYLINE is now closed and enrollment is open for Part B, which includes three monotherapy cohorts (SPY001, SPY002, and SPY003) and three combination cohorts (SPY120, SPY130, and SPY230) into which participants may be randomized versus a shared placebo. Proof-of-concept induction data for the remaining cohorts of Part A are now expected mid-2026 (SPY002) and Q3 2026 (SPY003). Part B induction data (all cohorts) remain on track for 2027.
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“On behalf of the Spyre team, I’d like to thank the patients and investigators whose partnership has made this progress possible as we advance the study with the goal of delivering paradigm-changing combinations for IBD patients,” said Sheldon Sloan, M.D. MBE, Chief Medical Officer of Spyre Therapeutics. “Thanks to our team’s outstanding execution, we enrolled Part A with exceptional speed and now transition to Part B. We expect heightened investigator enthusiasm given these promising results for SPY001, a low placebo allocation for the remainder of the trial, and a unique opportunity to evaluate perhaps the three most promising combinations in development.”
SPY001 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.
SPY001 is an extended half-life investigational antibody targeting α4β7, an integrin central to immune cell trafficking to the gut. Initial 12-week findings from SKYLINE Part A demonstrated that SPY001 met or exceeded all key objectives.
Efficacy: 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 and support SPY001’s potential best-in-class profile.
Endpoint | Week 12 Result | ||||
Change in RHI from baseline Primary endpoint | -9.2 (p<0.0001) | ||||
Clinical remission rate | 40% | ||||
Endoscopic improvement rate | 51% | ||||
Change in Modified Mayo Score | -3.7 | ||||
Safety: 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 patients) was back pain (n=2).
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SPY001 (n=43) | |||||
Subjects with any AE (n, %) | 6 (14%) | ||||
Severe (Grade ≥ 3) AE | 1 (2%)* | ||||
Drug-related AE | 0 | ||||
AE leading to study discontinuation | 0 | ||||
SAE | 1 (2%)* | ||||
Drug-related SAE | 0 | ||||
AEs of special interest | 0 | ||||
Death | 0 | ||||
*Chest pain in a 68-year-old male with history of coronary artery disease and angina on nitroglycerin prn, type 2 diabetes mellitus, hypertension, and hypercholesterolemia who presented with chest pain and ruled out for a myocardial infarction
Webcast Details
Spyre Therapeutics’ webcast of the SPY001 Phase 2 SKYLINE Part A data will begin today at 8:00 a.m. ET. The webcast can be accessed via this link or the Investors section of the Company’s website at https://ir.spyre.com/news-events/events. A replay of the webcast will be available following the call.
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, 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; Spyre’s ongoing and future clinical development activities, including Spyre’s plans for and timing of cohort initiation and data readouts for the ongoing SKYLINE trial and ongoing SKYWAY trial and enrollment of clinical trials; the inclusion of each rational combination in Part B of the SKYLINE Phase 2 platform trial; expectations regarding investigator enthusiasm and placebo allocation; the potential for SPY001 to be an ideal backbone for combination therapy; the potential therapeutic benefits of Spyre’s product candidates as monotherapies or in combinations, including potency, convenience, durability, and dosing profile, and their extended half-life;
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potential growth opportunities; and Spyre’s business plans, milestones, strategy 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 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 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 Therapeutics
SVP of Finance and Investor Relations
Eric.mcintyre@spyre.com
For Media:
Josie Butler, 1AB
josie@1abmedia.com
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FAQ
What did Spyre Therapeutics (SYRE) report in its SPY001 SKYLINE Part A trial?
Spyre Therapeutics reported positive 12-week induction data from Part A of its Phase 2 SKYLINE trial of SPY001 in moderate-to-severely active ulcerative colitis, including a statistically significant improvement in histology and meaningful clinical remission and endoscopic response rates.
How effective was SPY001 in the Phase 2 SKYLINE Part A ulcerative colitis study for SYRE?
SPY001 achieved a 9.2-point reduction in Robarts Histopathology Index at Week 12 (p<0.0001), with 40% clinical remission by modified Mayo Score and 51% endoscopic improvement, suggesting a robust combination of histologic and clinical benefits in ulcerative colitis patients.
What safety profile did SPY001 show in Spyre Therapeutics’ (SYRE) SKYLINE Part A trial?
SPY001 was well tolerated, with 6 of 43 patients (14%) experiencing treatment-emergent adverse events, one serious event (2%) deemed not drug-related, and no drug-related serious events, discontinuations, or deaths, consistent with the expected α4β7 class safety profile.
What are the next steps for Spyre Therapeutics’ (SYRE) SKYLINE trial after SPY001 Part A data?
Recruitment for SKYLINE Part A is closed, and enrollment is open for Part B, which includes three monotherapy and three combination cohorts. Additional proof-of-concept induction data are anticipated in mid-2026 and Q3 2026, with Part B induction data planned for 2027.
Which investigational antibodies are included in Spyre Therapeutics’ (SYRE) SKYLINE platform trial?
The SKYLINE platform includes SPY001 (anti-α4β7), SPY002 (anti-TL1A), and SPY003 (anti-IL-23), as well as pairwise combinations SPY120, SPY130, and SPY230, evaluated as monotherapies and combinations against a shared placebo in ulcerative colitis.
How many patients were treated with SPY001 in Spyre Therapeutics’ SKYLINE Part A and what were AE rates?
In SKYLINE Part A, 43 patients received SPY001. Treatment-emergent adverse events occurred in 6 patients (14%), with one serious adverse event (2%) considered not drug-related, and there were no drug-related AEs leading to discontinuation, no AEs of special interest, and no deaths.