Spyre Therapeutics (NASDAQ: SYRE) posts positive Phase 2 SPY002 ulcerative colitis data
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 SPY002 in moderately-to-severely active ulcerative colitis. SPY002 met its primary endpoint with a statistically significant 10.7-point reduction in Robarts Histopathology Index score at Week 12 (p<0.0001).
Key secondary measures included clinical remission by modified Mayo Score in 33% of patients and endoscopic improvement in 42%. SPY002 was described as well tolerated: 41.7% of the 48 treated patients experienced treatment-emergent adverse events, with two serious events deemed not drug-related, three drug-related adverse events, no adverse events of special interest, and no deaths.
Positive
- None.
Negative
- None.
Insights
Phase 2 SPY002 data show strong efficacy signals with a clean safety profile.
Spyre Therapeutics released 12-week Phase 2 SKYLINE Part A data for SPY002 in ulcerative colitis. The drug met its primary endpoint with a 10.7-point Robarts Histopathology Index reduction (p<0.0001), alongside 33% clinical remission and 42% endoscopic improvement, which the company characterizes as among the highest reported in UC.
Safety appears manageable: among 48 patients, 41.7% had treatment-emergent adverse events, with only 3 drug-related adverse events, 2 serious events deemed not drug-related, no adverse events of special interest, and no deaths. This balance of efficacy and tolerability is important for an anti-TL1A antibody targeting chronic inflammatory bowel disease.
The company states it is now enrolling Part B of SKYLINE, which will test SPY002 and other agents, including combinations, in randomized, placebo-controlled settings. Future Part B readouts and planned SPY003 Part A data in Q3 will be key to confirming durability, dose response, and the potential of combination regimens.
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
Primary endpoint RHI change: 10.7-point reduction
Clinical remission rate: 33%
Endoscopic improvement rate: 42%
+5 more
8 metrics
Primary endpoint RHI change
10.7-point reduction
Week 12 Robarts Histopathology Index change for SPY002, p<0.0001
Clinical remission rate
33%
Week 12 clinical remission by modified Mayo Score for SPY002
Endoscopic improvement rate
42%
Week 12 endoscopic improvement in SPY002-treated ulcerative colitis patients
SPY002 safety population
48 patients (n=48)
SKYLINE Part A induction cohort size
Patients with any AE
20 patients (41.7%)
SPY002-treated subjects with treatment-emergent adverse events
Serious adverse events
2 patients (4.2%)
Both serious adverse events deemed not drug-related
Drug-related adverse events
3 patients (6.3%)
One case each of nausea, hypertension, and arthralgia
Deaths reported
0
No deaths during the SPY002 induction treatment period
Key Terms
Robarts Histopathology Index, modified Mayo Score, treatment-emergent adverse events, serious adverse events, +2 more
6 terms
Robarts Histopathology Index medical
"SPY002 met its primary endpoint with a statistically significant reduction of 10.7 points ... in Robart’s Histopathology Index (RHI) score"
modified Mayo Score medical
"Secondary endpoints included clinical remission by modified Mayo Score of 33% and endoscopic improvement of 42%"
A modified Mayo score is a simplified clinical measure used to gauge severity and improvement in ulcerative colitis by combining patient symptoms and a clinician’s assessment, typically leaving out the full endoscopic exam. For investors, it matters because changes in this score are often used as a trial endpoint to show a treatment’s benefit; clearer, faster improvements can speed regulatory decisions, affect drug valuation, and influence market confidence. An everyday analogy: it’s like a shorter vehicle inspection that focuses on visible problems rather than a full engine tear-down.
treatment-emergent adverse events medical
"There were twenty subjects with treatment-emergent adverse events (TEAEs) during the induction treatment period."
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 events medical
"Two serious adverse events (SAEs) were reported, both deemed not drug-related."
Serious adverse events are significant problems or negative outcomes that occur during a medical treatment or clinical trial, such as severe side effects, hospitalizations, or life-threatening conditions. They matter to investors because such events can impact a company's reputation, lead to regulatory scrutiny, or delay the development of new products, ultimately affecting the company’s financial performance.
Phase 2 SKYLINE trial medical
"positive initial 12-week induction topline data from Part A of the Phase 2 SKYLINE trial of SPY002"
anti-TL1A medical
"SPY002, a potential best-in-class anti-TL1A being investigated for the treatment of moderately-to-severely active ulcerative colitis"
anti-TL1A is a laboratory-made antibody that binds to TL1A, a protein that helps drive and amplify inflammation in certain immune-related diseases. For investors, it matters because anti-TL1A drugs are a targeted therapeutic approach; their success in clinical trials and approval can reduce disease activity for patients and create a potential new revenue stream, while also carrying the usual clinical, regulatory and market-adoption risks.
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): June 15, 2026
_______________________________________________________
(Exact name of Registrant as Specified in Its Charter)
_______________________________________________________
| (State or Other Jurisdiction of Incorporation) | (Commission File Number) | (IRS Employer Identification No.) | ||||||
| (Address of Principal Executive Offices) | (Zip Code) | |||||||
Registrant’s Telephone Number, Including Area Code: | ||
| Not Applicable | ||
(Former Name or Former Address, if Changed Since Last Report)
_______________________________________________________
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:
| Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425) | |||||
| Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12) | |||||
| Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b)) | |||||
| Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c)) | |||||
Securities registered pursuant to Section 12(b) of the Act:
| Title of each class | Trading Symbol(s) | Name of each exchange on which registered | ||||||||||||
(Nasdaq Global Select Market) | ||||||||||||||
Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§ 230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§ 240.12b-2 of this chapter).
Emerging growth company o
If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. o
Item 7.01 Regulation FD Disclosure.
SPY002 SKYLINE Part A Induction Topline Results
On June 15, 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 SPY002 for the treatment of moderately-to-severely active ulcerative colitis (“UC”).
A copy of the press release is attached hereto as Exhibit 99.1. The information in this Item 7.01 of this Current Report on Form 8-K, including Exhibit 99.1 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 June 15, 2026, the Company announced positive initial 12-week induction topline data from Part A of the Phase 2 SKYLINE trial of SPY002 for the treatment of moderately-to-severely active UC.
SPY002 SKYLINE Part A Induction Topline Results
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 Robarts Histopathology Index (“RHI”) score of 16.9 ± 8.5 (SD), a mean modified Mayo Score (“mMS”) 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.
Endpoint (Week 12) | SPY002 | ||||
Change in RHI from baseline Primary endpoint | -10.7 (p<0.0001) | ||||
Clinical remission rate | 33% | ||||
Endoscopic improvement rate | 42% | ||||
Change in modified Mayo Score | -3.7 | ||||
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).
SPY002 (n=48) | |||||
Subjects with any AE (n, %) | 20 (41.7%) | ||||
Severe (Grade ≥ 3) AE | 2 (4.2%)1,2 | ||||
Drug-related AE | 3 (6.3%)3 | ||||
AE leading to drug discontinuation | 2 (4.2%)2,4 | ||||
SAE | 2 (4.2%)1,2 | ||||
Drug-related SAE | 0 | ||||
AEs of special interest | 0 | ||||
Death | 0 | ||||
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.
Item 9.01 Financial Statements and Exhibits.
(d)Exhibits
Exhibit Number | Description | |||||||
| 99.1 | Press release issued by Spyre Therapeutics, Inc. regarding Data, dated June 15, 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: | June 15, 2026 | By: | /s/ Cameron Turtle | ||||||||
| Cameron Turtle Chief Executive Officer | |||||||||||
Exhibit 99.1
Spyre Announces Potential Best-in-Class SPY002 (anti-TL1A) Part A Induction Results from SKYLINE Trial in Moderate-to-Severe Ulcerative Colitis Patients
SPY002 met its primary endpoint with a statistically significant reduction of 10.7 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 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.”
1
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.
Endpoint (Week 12) | SPY002 | ||||
Change in RHI from baseline Primary endpoint | -10.7 (p<0.0001) | ||||
Clinical remission rate | 33% | ||||
Endoscopic improvement rate | 42% | ||||
Change in modified Mayo Score | -3.7 | ||||
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
2
(n=2), hypertension (n=3), nausea (n=2), UC (n=2), and viral respiratory tract infection (n=2).
SPY002 (n=48) | |||||
Subjects with any AE (n, %) | 20 (41.7%) | ||||
Severe (Grade ≥ 3) AE | 2 (4.2%)1,2 | ||||
Drug-related AE | 3 (6.3%)3 | ||||
AE leading to drug discontinuation | 2 (4.2%)2,4 | ||||
SAE | 2 (4.2%)1,2 | ||||
Drug-related SAE | 0 | ||||
AEs of special interest | 0 | ||||
Death | 0 | ||||
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,
3
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 Therapeutics
SVP of Finance and Investor Relations
Eric.mcintyre@spyre.com
For Media:
Josie Butler, 1AB
josie@1abmedia.com
4
FAQ
What did Spyre Therapeutics (SYRE) announce about the SPY002 SKYLINE Part A trial?
Spyre Therapeutics announced positive 12-week induction data from Part A of the Phase 2 SKYLINE trial of SPY002 in moderately-to-severely active ulcerative colitis, reporting that SPY002 met all key objectives, including its primary histologic endpoint and important clinical and endoscopic secondary measures.
How effective was SPY002 in the Phase 2 SKYLINE ulcerative colitis study?
SPY002 achieved the primary endpoint with a 10.7-point reduction in Robarts Histopathology Index score at Week 12 (p<0.0001). Secondary outcomes included clinical remission by modified Mayo Score in 33% of patients and endoscopic improvement in 42%, which the company describes as among the highest reported in ulcerative colitis.
What safety profile did SPY002 show in Spyre Therapeutics’ SKYLINE Part A trial?
SPY002 was described as well tolerated with a safety profile consistent with the TL1A class. Among 48 treated patients, 41.7% experienced treatment-emergent adverse events, 4.2% had serious adverse events deemed not drug-related, 6.3% had drug-related adverse events, and there were no deaths or adverse events of special interest.
How many patients experienced adverse events with SPY002 in the Phase 2 trial?
In the SPY002 SKYLINE Part A cohort of 48 patients, 20 patients, or 41.7%, had treatment-emergent adverse events. Two patients (4.2%) experienced serious adverse events deemed not drug-related, and three patients (6.3%) had drug-related adverse events, with no deaths reported during the induction period.
What was the patient population in Spyre Therapeutics’ SPY002 SKYLINE Part A study?
The study enrolled moderately-to-severely active ulcerative colitis patients, with 35% previously exposed to advanced therapies. Participants had a mean disease duration of 7.0 years, mean baseline Robarts Histopathology Index score of 16.9, mean modified Mayo Score of 6.9, and 56% had a baseline endoscopy score of 3.
What are Spyre Therapeutics’ next steps after the SPY002 SKYLINE Part A results?
Spyre Therapeutics reported it is now enrolling Part B of the SKYLINE trial, which includes randomized, placebo-controlled arms for investigational monotherapies and combinations. The company also plans to report Part A data for its anti-IL-23 antibody SPY003 in the third quarter, completing monotherapy proof-of-concept goals.