Announced positive topline induction data for SPY003 from Part A of the Phase 2 SKYLINE trial ("SKYLINE"), completing proof-of-concept for all three monotherapies in inflammatory bowel disease ("IBD"). SKYLINE Part B is enrolling ahead of schedule, enabling the Company to increase enrollment and provide topline induction results for three potential best-in-indication combinations, which are expected in Q3 2027
Reported positive topline results for SPY072 in rheumatoid arthritis ("RA") sub-study of the Phase 2 SKYWAY basket trial ("SKYWAY"), though with a magnitude of benefit insufficient to prioritize advancement. SPY072 was well-tolerated but did not meet its primary endpoint in the psoriatic arthritis ("PsA") or axial spondyloarthritis ("axSpA") SKYWAY sub-studies. SPY072 will not be advanced in rheumatic disease
Initiated a new Phase 2 trial ("SKYLIGHT") designed to provide clinical proof-of-concept for dual TL1A and IL-17A/F inhibition in hidradenitis suppurativa ("HS"). Raised over $400 million in gross proceeds from an underwritten public offering in October to fund a pivotal program in HS with SPY072, our potential best-in-class TL1A monotherapy
$1.5 billion in pro forma cash, cash equivalents, and marketable securities as of September 30, 2026, with expected runway into the second half of 2029
WALTHAM, Mass., Nov. 03, 2026 (GLOBE NEWSWIRE) -- Spyre Therapeutics, Inc. ("Spyre" or the "Company") (NASDAQ:SYRE), a clinical-stage biotechnology company committed to developing next-generation therapies that elevate the standard in immunology by delivering more complete disease control, greater durability, and a simpler treatment experience for patients, today announced its third quarter 2026 financial results and provided program and corporate updates.
"We are increasingly well-positioned to deliver on our ambition of elevating the standard of care across immunology. In IBD, our three compelling Phase 2 monotherapy readouts and a growing body of supportive clinical evidence strengthen our conviction that our combination products have the potential to transform the treatment paradigm. The combination portion of our SKYLINE trial is enrolling faster than expected enabling an increased enrollment target, and we plan to deliver topline data in Q3 2027 with the potential for efficacy, safety, and convenience that meaningfully surpasses today's standard of care," said Cameron Turtle, DPhil, Chief Executive Officer of Spyre. "Beyond IBD, we were thrilled to see excellent external proof-of-concept data for TL1A in hidradenitis suppurativa, supporting the expansion of our pipeline to include a pivotal monotherapy program as well as a combination study with the current standard of care, IL17-A/F. Collectively, we believe the breadth of our pipeline, strength of our clinical data, and continued execution position Spyre to potentially deliver meaningful advances for patients across multiple large markets and substantial long-term value for shareholders."
Development Pipeline Overview and Update
The Company is 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. The Company's pipeline includes extended half-life antibodies targeting <ALPHA>4<BETA>7, TL1A, IL-23 and IL-17A/F (each as defined below), as well as rational combination programs, in large therapeutic areas of focus, each with high unmet need.
-- In Gastroenterology, the Company is advancing three potential first- and
best-in-class combination programs in inflammatory bowel disease ("IBD").
IBD is a chronic condition characterized by inflammation within the
gastrointestinal tract, including two main disorders: ulcerative colitis
("UC") and Crohn's disease ("CD"). In the United States, it is estimated
that approximately 2.4 million individuals are diagnosed with IBD and the
global market is forecasted to exceed $40 billion by 2030.
-- In Dermatology, the Company is advancing a potential first- and
best-in-class anti-TL1A + IL-17A/F combination program in hidradenitis
suppurativa ("HS"). Additionally, the Company plans to advance a
potential best-in-class anti-TL1A monotherapy agent into pivotal studies
for HS in 2027. HS is a chronic inflammatory skin condition characterized
by recurrent, painful nodules and abscesses, primarily in areas such as
the underarms and groin. The disease can progress to draining tunnels and
permanent scarring, substantially impacting patients' quality of life. It
is estimated that the disease affects approximately 3.0 million patients
in the United States, with the global market forecasted to exceed $10
billion by 2035.
The Company has three ongoing Phase 2 clinical trials with meaningful proof-of-concept data readouts in 2026 and 2027:
SKYLINE Phase 2 Platform Trial in IBD - in May 2025, the Company initiated a Phase 2 induction and maintenance platform trial of SPY001 (long-acting anti-<ALPHA>4<BETA>7), SPY002 (long-acting anti-TL1A) and SPY003 (long-acting anti-IL-23), as well as pairwise combinations thereof (six investigational agents in total), in patients with moderately to severely active UC. The trial consists of two parts:
-- Part A: Open-label assessment of the safety and preliminary efficacy of a
single dose level of each investigational monotherapy. Enrollment for
Part A has completed, with initial SPY001, SPY002 and SPY003 Part A
topline induction data announced in April 2026, June 2026, and September
2026, respectively.
-- SPY001, SPY002, and SPY003 were well-tolerated with a safety
profile consistent with in-class comparators. SPY001, SPY002, and
SPY003 all achieved their respective primary endpoints,
demonstrating a statistically significant reduction in the
Robart's Histopathology Index ("RHI") score of 9.2 points, 10.7
points, and 10.0 points, respectively. Rates of key secondary
endpoints of clinical remission and endoscopic improvement were
clinically meaningful at 40% and 51%, respectively, for SPY001,
33% and 42%, respectively, for SPY002, and 20% and 30%,
respectively, for SPY003. The change in the modified Mayo Score
from baseline at Week 12 for both SPY001 and SPY002 was -3.7, and
for SPY003 was -3.5, reflecting consistency across secondary
endpoints.
-- Part B: Randomized and placebo-controlled assessment of the safety and
efficacy of monotherapies and combinations, designed to provide
dose-ranging data on monotherapies, proof-of-concept, and contribution of
components for combinations, with induction data expected in the third
quarter of 2027. Study is enrolling ahead of schedule enabling an
increased enrollment target.
SKYLIGHT Phase 2 Trial in HS - in September 2026, the Company initiated its SKYLIGHT Phase 2 trial of SPY072 in subjects with moderately to severely active HS who are initiating bimekizumab. The trial serves as a surrogate proof-of-concept study for the Company's internal SPY772 combination program combining SPY072 (long-acting anti-TL1A) and SPY007 (long-acting anti-IL-17A/F). Topline Week 16 results are planned in late 2027 or early 2028.
SKYWAY Phase 2 Basket Trial in Rheumatic Diseases - in September 2025, the Company initiated a Phase 2 randomized and placebo-controlled basket trial of SPY072 in patients with moderately to severely active RA, PsA, or axSpA. The trial consists of three sub-studies:
-- RA sub-study: Double-blind, placebo-controlled safety and efficacy study
of two dose levels of SPY072 at Week 12 with open-label follow-up through
Week 36. Topline proof-of-concept data were released in August 2026. Both
doses of SPY072 demonstrated statistically significant benefits compared
to placebo on one or more of the primary (change from baseline in
DAS28-CRP), key secondary (ACR20), and exploratory endpoints (ACR50).
SPY072 was well tolerated, with a safety profile consistent with the TL1A
class. While SPY072 demonstrated clinical activity in RA, the results did
not meet the Company's internal bar to prioritize advancement of SPY072
in RA.
-- PsA and axSpA sub-studies: Double-blind, placebo-controlled safety and
efficacy studies of a single dose level of SPY072 at Week 16 with
open-label follow-up through Week 40. The Company announced that SPY072
was well-tolerated, but neither sub-study met its primary endpoint of
ACR20 response in PsA or change from baseline in ASDAS in axSpA.
The Company does not plan to advance SPY072 in rheumatic diseases.
The investigational therapies being studied in the Company's clinical trials include:
SPY001 -- a highly potent and selective investigational monoclonal antibody targeting the <ALPHA>4<BETA>7 integrin ("<ALPHA>4<BETA>7"), engineered with half-life extension technology and formulated at high concentration with the goal of maximizing efficacy and enabling infrequent, subcutaneous maintenance dosing. SPY001 is being evaluated for the treatment of IBD in the SKYLINE study.
SPY002 and SPY072 -- two highly potent and selective, investigational anti-tumor necrosis factor-like ligand 1A ("TL1A") monoclonal antibodies, engineered with half-life extension technology and formulated at high concentration with the goal of maximizing efficacy and enabling infrequent, subcutaneous maintenance dosing. The Company believes TL1A has emerged as one of the most promising targets in IBD and broader immunology indications. SPY002 is being evaluated for the treatment of IBD in the SKYLINE study and SPY072 is being developed for the treatment of HS, both as a monotherapy and as part of a combination.
SPY003 -- a highly potent and selective investigational monoclonal antibody targeting the p19 subunit of interleukin 23 ("IL-23"), engineered with half-life extension technology and formulated at high concentration with the goal of maximizing efficacy and enabling infrequent, subcutaneous maintenance dosing. SPY003 is being evaluated for the treatment of IBD in the SKYLINE study.
SPY007 -- a preclinical-stage program designed to bind to interleukin 17A ("IL-17A") and interleukin 17F ("IL-17F"), while incorporating half-life extending modifications. SPY007 is being developed for the treatment of HS in combination with SPY072.
Rational Combinations (SPY120, SPY130, SPY230, and SPY772) -- the Company is investigating combinations of its proprietary antibodies in clinical trials in order to evaluate whether combinations can potentially lead to best-in-class efficacy in several inflammatory diseases, with less frequent dosing.
-- The Company is currently enrolling its SPY120, SPY130, and SPY230
combinations in Part B of the SKYLINE trial, with an expected induction
read-out in 2027.
-- The Company's SPY772 combination program aims to target multiple
inflammatory pathways involved in HS, pairing its novel anti-TL1A
(SPY072) with SPY007, its anti-IL-17A/F. The goal is to use this
long-acting, co-formulated combination in future advanced clinical
development, pending the results from the Company's SKYLIGHT
proof-of-concept trial.
Third Quarter 2026 Financial Results
Cash Position: As of September 30, 2026, Spyre had cash, cash equivalents, and marketable securities of $1,071.9 million. Pro forma cash of $1,467.9 million as of September 30, 2026, with expected runway into the second half of 2029, also reflects $378.0 million in net proceeds from the recently closed October 2026 underwritten public offering of common stock and $18.0 million in October 2026 at-the-market (ATM) sales. Net cash used in operating activities was $77.5 million for the third quarter of 2026.
Research and Development (R&D) expenses: R&D expenses totaled $89.2 million for the third quarter of 2026 and $45.2 million for the third quarter of 2025. The increase was primarily driven by higher manufacturing costs and clinical trial expenses.
General and Administrative (G&A) expenses: G&A expenses totaled $16.6 million for the third quarter of 2026 and $11.6 million for the third quarter of 2025. The increase was primarily driven by increased headcount and professional services fees.
Total Other Income (Expense): Other income totaled $9.6 million for the third quarter of 2026 compared to $45.7 million of total other income in the third quarter of 2025. The change was primarily due to changes in the fair value of the contingent value right ("CVR") liability in the prior period.
Net Loss: Net loss totaled $96.1 million and $11.2 million for the third quarters of 2026 and 2025, respectively.
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 <ALPHA>4<BETA>7, TL1A, IL-23, and IL-17A/F as well as rational combination programs.
For more information, please visit http://spyre.com.
Safe Harbor / Forward Looking Statements
Certain statements in this press release, other than purely historical information, may constitute "forward-looking statements" within the meaning of the federal securities laws, including for purposes of the safe harbor provisions under the United States Private Securities Litigation Reform Act of 1995. These statements include, but are not limited to, statements regarding: the Company's future results of operations and financial position; its ability to achieve the expected benefits or opportunities with respect to its product candidates, including its ability to develop next-generation therapies that elevate the standard in immunology by delivering more complete disease control, greater durability, and a simpler treatment experience for patients; the potential continued speed of enrollment in SKYLINE, the ability to reach the increased enrollment target and the Company's plans to deliver topline data in Q3 2027 with the potential for efficacy, safety, and convenience that meaningfully surpasses today's standard of care; its business strategy, including its ability to successfully develop best-in-class therapeutics for IBD and HS and deliver meaningful advances for patients across multiple large markets and substantial long-term value for shareholders; the potential for the Company's combination products to transform the treatment paradigm; the potential for the Company's product candidates in development, including rational combination programs, to be first-in-class and/or best-in-class therapies in IBD and HS; the potential for future clinical readouts from the Company's programs to further establish the utility of TL1A inhibition across autoimmune diseases; expectations regarding the drug delivery of the Company's product candidates, including in the form of a subcutaneous injection; the length of time that the Company believes its existing cash resources will fund its operations, including the expectation of cash runway extending into the second half of 2029; estimated market sizes and potential growth opportunities; its current and future clinical development activities, including the Company's plans for and timing of cohort initiation and data readouts for the ongoing SKYLINE Phase 2 platform trial and SKYLIGHT Phase 2 trial, the advancement of a potential best-in-class anti-TL1A monotherapy agent into pivotal studies for HS in 2027, and the potential of using SPY772 in future advanced clinical development; the potential efficacy, tolerability, convenience, dosing profile, commercial viability and safety profile of its product candidates, including rational combinations; the potential therapeutic benefits and economic value of its product candidates as monotherapies or in combinations, including the potential for efficacy, safety and convenience to meaningfully surpass today's standard of care; and Spyre's business plans, milestones, and goals. The words "opportunity," "potential," "milestones," "pipeline, " "strategy," "anticipate," "believe," "could," "estimate," "expect," "may," "might," "plan," "possible," "predict," "should," "will," "would, " and similar expressions (including the negatives of these terms) may identify forward-looking statements, but the absence of these words does not mean that a statement is not forward-looking. These forward-looking statements are based on current expectations and beliefs and involve a number of risks and uncertainties, many of which are beyond Spyre's control, and other assumptions that may cause actual results or performance to be materially different from those expressed or implied by these forward-looking statements. These risks and uncertainties include, but are not limited, uncertainties and risks arising from regulatory feedback, including potential disagreement by regulatory authorities with the Company's interpretation of data and the Company's clinical trials for its product candidates; the potential for interim data not being delivered within expected time frames or final data not being consistent with or different than the interim data reported for the Company's programs; the potential impact of Trump Administration policies and changes in law on the Company's business; and those uncertainties and factors described in Spyre's most recent Annual Report on Form 10-K, as supplemented and updated by subsequent Quarterly Reports on Form 10-Q and any other filings that Spyre has made or may make with the SEC from time to time. You should not place undue reliance on forward-looking statements in this press release, which speak only as of the date they are made and are qualified in their entirety by reference to the cautionary statements herein. Spyre does not undertake or accept any duty to make any updates or revisions to any forward-looking statements.
Contact Information:
For Investors:
Eric McIntyre, Spyre Therapeutics
SVP of Finance and Investor Relations
Eric.mcintyre@spyre.com
For Media:
Josie Butler, 1AB
josie@1abmedia.com
Spyre Therapeutics, Inc.
Condensed Consolidated Balance Sheets
(Unaudited, in thousands, except share and per share
amounts)
September 30, December 31,
2026 2025
ASSETS
CURRENT ASSETS
Cash and cash equivalents $ 82,727 $ 85,721
Marketable securities 989,180 670,812
Prepaid expenses and other current
assets 27,821 21,248
Total current assets 1,099,728 777,781
---------- ----------
TOTAL ASSETS $ 1,099,728 $ 777,781
========== ==========
LIABILITIES AND STOCKHOLDERS' EQUITY
CURRENT LIABILITIES
Accounts payable $ 9,466 $ 8,904
CVR liability -- 22,820
Accrued and other current
liabilities 30,595 26,947
Related party accounts payable 82 14
Total current liabilities 40,143 58,685
Non-current CVR liability 6,760 3,860
Other non-current liabilities 1,290 --
TOTAL LIABILITIES 48,193 62,545
---------- ----------
Commitments and Contingencies
CONVERTIBLE PREFERRED STOCK AND
STOCKHOLDERS' EQUITY
Series A non-voting convertible
preferred stock, $0.0001 par value;
1,086,341 shares authorized as of
September 30, 2026 and December 31,
2025; 346,045 shares issued and
outstanding as of September 30,
2026 and December 31, 2025. 146,425 146,425
Series B non-voting convertible
preferred stock, $0.0001 par value;
271,625 shares authorized as of
September 30, 2026 and December 31,
2025; nil and 16,667 shares issued
and outstanding as of September 30,
2026 and December 31, 2025,
respectively. -- 9,395
Preferred stock, $0.0001 par value;
8,642,034 shares authorized as of
September 30, 2026 and December 31,
2025; no shares issued and
outstanding as of September 30, 2026
and December 31, 2025. -- --
Common stock, $0.0001 par value;
400,000,000 shares authorized as of
September 30, 2026 and December 31,
2025; 89,953,997 shares and
78,189,811 shares issued and
outstanding as of September 30,
2026 and December 31, 2025,
respectively. 16 15
Additional paid-in capital 2,239,437 1,686,167
Accumulated other comprehensive
(loss) income (5,382) 869
Accumulated deficit (1,328,961) (1,127,635)
TOTAL STOCKHOLDERS' EQUITY 1,051,535 715,236
---------- ----------
TOTAL LIABILITIES, CONVERTIBLE
PREFERRED STOCK AND STOCKHOLDERS'
EQUITY $ 1,099,728 $ 777,781
========== ==========
Spyre Therapeutics, Inc.
Condensed Consolidated Statements of Operations
(Unaudited, in thousands, except share and per share
amounts)
Three Months Ended Nine Months Ended
September 30, September 30,
2026 2025 2026 2025
---------- ----------
Operating expenses:
Research and
development(1) $ 89,169 $ 45,247 215,083 127,015
General and
administrative(2) 16,550 11,641 47,916 35,375
Gain on sale of
in-process
research and
development
asset -- -- (70,000) (10,000)
Total operating
expenses 105,719 56,888 192,999 152,390
---------- ---------- ---------- ----------
Loss from operations (105,719) (56,888) (192,999) (152,390)
Other income
(expense):
Interest income 10,625 5,379 27,673 17,746
Other (expense)
income, net (1,027) 40,326 (36,000) 41,956
Total other
income
(expense) 9,598 45,705 (8,327) 59,702
---------- ---------- ---------- ----------
Loss before income
tax benefit (96,121) (11,183) (201,326) (92,688)
Income tax benefit -- -- -- 15
Net loss $ (96,121) $ (11,183) $ (201,326) $ (92,673)
---------- ---------- ---------- ----------
Net loss per share,
basic and diluted,
Series A Preferred
Stock $ (37.60) $ (5.97) $ (81.74) $ (49.53)
Weighted-average
Series A non-voting
convertible
preferred stock
outstanding, basic
and diluted 346,045 346,045 346,045 346,045
Net loss per share,
basic and diluted,
Series B Preferred
Stock $ -- $ (5.97) $ (81.74) $ (49.53)
Weighted-average
Series B non-voting
convertible
preferred stock
outstanding, basic
and diluted -- 16,667 10,623 16,667
Net loss per share,
basic and diluted,
common $ (0.94) $ (0.15) $ (2.04) $ (1.24)
Weighted-average
common stock
outstanding, basic
and diluted 88,410,821 60,414,223 84,255,008 60,338,541
(1) Includes related party expenses of $0.1 million and $7.0 million for the three months ended September 30, 2026 and 2025, respectively. Includes related party expenses of $3.2 million and $9.6 million for the nine months ended September 30, 2026 and 2025, respectively.
(2) Includes related party expenses of $0.3 million for the three months ended September 30, 2026 and 2025, and $0.8 million for the nine months ended September 30, 2026 and 2025.
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