On track for 6 proof-of-concept readouts in 2026 across the SKYLINE and SKYWAY Phase 2 trials
Part A readouts from SKYLINE platform trial in ulcerative colitis ("UC") expected to begin in the second quarter, with enrollment continuing ahead of schedule
Enrollment on track in Phase 2 SKYWAY basket trial evaluating TL1A inhibition in rheumatoid arthritis ("RA"), psoriatic arthritis ("PsA"), and axial spondyloarthritis ("axSpA"), with fourth quarter readouts expected in each sub-study
Strengthened the balance sheet with an underwritten public offering of common stock in
“This year is a pivotal period for Spyre as we begin to unveil results from our two groundbreaking Phase 2 trials with the potential to identify multiple products that leapfrog today's standard of care and provide substantially improved therapies for patients suffering from severe autoimmune diseases. In IBD, we plan to reveal initial safety and efficacy data for our optimized antibodies against the most compelling targets in the space. If successful, these results would support our view that our antibodies are the ideal components for combination therapies with the potential to transform the treatment paradigm in this disease,” said
Development Pipeline Overview and Update
The Company is pioneering long-acting antibodies and antibody combinations to redefine the standard of care in IBD and rheumatic diseases. IBD is a chronic condition characterized by inflammation within the gastrointestinal tract, including two main disorders: ulcerative colitis ("UC") and Crohn's disease ("CD"). In
Each of the Company's monotherapy programs in IBD target validated mechanisms with the potential for safe and effective treatment of UC and CD with infrequent dosing as a monotherapy or in rational combinations. The Company is also studying its anti-TL1A program as a monotherapy in indications outside IBD, including RA, PsA, and axSpA.
The Company has two ongoing Phase 2 clinical trials with proof-of-concept data readouts beginning in 2026:
SKYLINE Phase 2 Platform Trial in IBD - in
- Part A: Open-label assessment of the safety and preliminary efficacy of a single dose level of each investigational monotherapy, with induction data expected beginning in the second quarter of 2026.
- Part B: Randomized and placebo-controlled assessment of the safety and efficacy of investigational monotherapies (two dose levels) and combinations, with induction data expected in 2027.
SKYLINE is currently enrolling subjects into Part A of the trial, with Part B expected to begin enrolling after all arms in Part A complete enrollment.
SKYWAY Phase 2 Basket Trial in Rheumatic Diseases (RA, PsA, axSpA) - in
- RA sub-study: Double-blind, placebo-controlled safety and efficacy study of two dose levels of SPY072 at Week 12.
- PsA sub-study: Double-blind, placebo-controlled safety and efficacy study of a single dose level of SPY072 at Week 16.
- axSpA sub-study: Double-blind, placebo-controlled safety and efficacy study of a single dose level of SPY072 at Week 16.
The investigational therapies being studied in the SKYLINE and SKYWAY clinical trials include:
SPY001 – a highly potent and selective investigational monoclonal antibody targeting a4ß7, engineered with half-life extension technology and formulated at high concentration with the goal of maximizing efficacy and enabling infrequent, subcutaneous maintenance dosing.
- In
May 2025 , extended follow up data were presented at Digestive Disease Week ("DDW") 2025 from the Phase 1 healthy volunteer trial, demonstrating a favorable safety profile across all dose groups, a meaningfully differentiated pharmacokinetic ("PK") profile supporting potential Q3M or Q6M maintenance dosing, and rapid and complete saturation of a4ß7 receptors beyond six months with a single dose of 600mg. - Based on these interim results, SPY001 was advanced into the SKYLINE Phase 2 platform trial.
SPY002 and SPY072 – two highly potent and selective, investigational anti-TL1A monoclonal antibodies, engineered with half-life extension technology and formulated at high concentration with the goal of maximizing efficacy and enabling infrequent, subcutaneous maintenance dosing. The Company believes TL1A has emerged as one of the most promising targets in IBD and broader immunology indications. SPY002 is being evaluated for the treatment of IBD in the SKYLINE study and SPY072 is being evaluated for the treatment of rheumatic diseases in the SKYWAY study.
- In
June 2025 , interim healthy volunteer data from two Phase 1 trials (one for SPY002 and one for SPY072) were presented, demonstrating favorable safety profiles, meaningfully differentiated PK profiles supporting potential Q3M or Q6M maintenance dosing, and complete suppression of free TL1A through up to 20 weeks at single 100mg doses. Longer-term data from these Phase 1 trials were presented at medical meetings in late 2025, providing further support for these potential best-in-class profiles. - Based on these interim results, SPY002 was advanced to the SKYLINE Phase 2 platform trial, and SPY072 was advanced to the SKYWAY Phase 2 basket trial.
SPY003 – a highly potent and selective investigational monoclonal antibody targeting the p19 subunit of IL-23, engineered with half-life extension technology and formulated at high concentration with the goal of maximizing efficacy and enabling infrequent, subcutaneous maintenance dosing.
- In
November 2025 , interim healthy volunteer data from a Phase 1 trial were disclosed, demonstrating that SPY003 exhibited a favorable safety profile and a meaningfully differentiated PK profile supporting potential Q3M or Q6M maintenance dosing. Additional data from this Phase 1 trial were presented at the 21stCongress of the European Crohn’s andColitis Organisation ("ECCO") inFebruary 2026 , providing further support for this potential best-in-class profile. - Based on these interim results, SPY003 was advanced to the SKYLINE Phase 2 platform trial.
Rational Combinations – the Company plans to investigate combinations of our proprietary antibodies in nonclinical studies and clinical trials in order to evaluate whether combinations can potentially lead to best-in-class efficacy in IBD, with less frequent dosing.
- In February and
May 2025 , preclinical data for SPY120 were presented at medical meetings, demonstrating that the combined inhibition of TL1A and a4ß7 is superior to either monotherapy in mouse models of colitis and that the PK profiles of SPY001 and SPY002 were similar in non-human primates whether dosed as monotherapy or in combination, while also demonstrating no drug effects on PK. - Preclinical data for SPY130 and SPY230 have demonstrated enhanced efficacy and pharmacodynamics with SPY003 in combination with SPY001 and with SPY002.
- The Company expects to include each of its rational combinations in Part B of the SKYLINE trial.
Fourth Quarter 2025 Financial Results
Cash Position: As of
Research and Development (R&D) expenses: R&D expenses totaled
General and Administrative (G&A) expenses: G&A expenses totaled
Total Other Expense (Income): For the fourth quarter of 2025, other expense totaled
Net Loss: Net loss totaled
About
For more information, please visit http://spyre.com.
Safe Harbor / Forward Looking Statements
Certain statements in this press release, other than purely historical information, may constitute "forward-looking statements" within the meaning of the federal securities laws, including for purposes of the safe harbor provisions under the United States Private Securities Litigation Reform Act of 1995. These statements include, but are not limited to, statements regarding: the Company's future results of operations and financial position; its business strategy, including the Company's ability to deliver meaningful value for patients, physicians and shareholders through its assets, strategy and execution, including its ability to successfully develop best-in-class therapeutics for IBD or RD that meaningfully improve both efficacy and convenience compared to today's standard of care and the Company's ability to develop first-in-class therapeutics for RD; the potential consistency of the SPY001, SPY002, SPY072 and SPY003 Phase 1 trial final data readouts with previously disclosed data for our programs; the sufficiency of the Company's funding to support the development of its assets, including expectations of cash runway extending into the second half of 2028; the length of time that the Company believes its existing cash resources will fund its operations; estimated market sizes and potential growth opportunities; its nonclinical and future clinical development activities, including the expected timing and results of the ongoing SKYWAY Phase 2 basket trial and SKYLINE phase 2 platform trial, including timing of cohort initiation and data readouts for the ongoing SKYWAY Phase 2 basket trial and SKYLINE Phase 2 platform trial, enrollment of clinical trials, the inclusion of each rational combination in Part B of the SKYLINE Phase 2 platform trial and the number of data readouts expected to be delivered in 2026 and 2027, and related regulatory feedback; the potential efficacy, tolerability, convenience, commercial viability and safety profile of its product candidates, including in combinations; the potential viability of the Company's antibodies as ideal components for combination therapies; the planned dosing regimen for SPY001, SPY002, SPY072 and SPY003, including the potential for a Q3M or Q6M dosing profile and the potential for such dosing profile to be the leading product profile in IBD and RD; the potential therapeutic benefits and economic value of its product candidates as monotherapies or in combinations and their extended half-life; and Spyre’s business plans, milestones, and goals. The words "opportunity," "potential," "milestones," "pipeline," "strategy," "anticipate," "believe," "could," "estimate," "expect," "may," "might," "plan," "possible," "predict," "should," "will," "would," and similar expressions (including the negatives of these terms) may identify forward-looking statements, but the absence of these words does not mean that a statement is not forward-looking. These forward-looking statements are based on current expectations and beliefs and involve a number of risks and uncertainties, many of which are beyond Spyre’s control, and other assumptions that may cause actual results or performance to be materially different from those expressed or implied by these forward-looking statements. These risks and uncertainties include, but are not limited, uncertainties and risks arising from regulatory feedback, including potential disagreement by regulatory authorities with the Company’s interpretation of data and the Company’s clinical trials for its product candidates; the potential for interim data not being delivered within expected time frames or final data not being consistent with or different than the interim data reported for our programs; the potential impact of
Contact Information:
Media Contact
josie@1abmedia.com
Investor Contact
eric.mcintyre@spyre.com
Consolidated Balance Sheets (Unaudited, in thousands, except share and per share amounts) | |||||||
| 2025 | 2024 | ||||||
| ASSETS | |||||||
| CURRENT ASSETS | |||||||
| Cash and cash equivalents | $ | 85,721 | $ | 89,423 | |||
| Marketable securities | 670,812 | 513,665 | |||||
| Prepaid expenses and other current assets | 21,248 | 5,386 | |||||
| Total current assets | 777,781 | 608,474 | |||||
| Other non-current assets | — | 10 | |||||
| TOTAL ASSETS | $ | 777,781 | $ | 608,484 | |||
| LIABILITIES AND STOCKHOLDERS’ EQUITY | |||||||
| CURRENT LIABILITIES | |||||||
| Accounts payable | $ | 8,904 | $ | 666 | |||
| CVR liability | 22,820 | 25,080 | |||||
| Accrued and other current liabilities | 26,947 | 27,711 | |||||
| Related party accounts payable | 14 | 603 | |||||
| Total current liabilities | 58,685 | 54,060 | |||||
| Non-current CVR liability | 3,860 | 36,620 | |||||
| TOTAL LIABILITIES | 62,545 | 90,680 | |||||
| Commitments and Contingencies | |||||||
| CONVERTIBLE PREFERRED STOCK AND STOCKHOLDERS’ EQUITY | |||||||
| Series A non-voting convertible preferred stock, | 146,425 | 146,425 | |||||
| Series B non-voting convertible preferred stock, | 9,395 | 9,395 | |||||
| Preferred stock, | — | — | |||||
| Common stock, | 15 | 13 | |||||
| Additional paid-in capital | 1,686,167 | 1,334,223 | |||||
| Accumulated other comprehensive income | 869 | 180 | |||||
| Accumulated deficit | (1,127,635 | ) | (972,432 | ) | |||
| TOTAL CONVERTIBLE PREFERRED STOCK AND STOCKHOLDERS’ EQUITY | 715,236 | 517,804 | |||||
| TOTAL LIABILITIES, CONVERTIBLE PREFERRED STOCK AND STOCKHOLDERS’ EQUITY | $ | 777,781 | $ | 608,484 | |||
Consolidated Statements of Operations (Unaudited, in thousands, except share and per share amounts) | |||||||||||||||
| Three Months Ended | Twelve Months Ended | ||||||||||||||
| 2025 | 2024 | 2025 | 2024 | ||||||||||||
| Operating expenses: | |||||||||||||||
| Research and development(1) | 44,638 | 50,482 | 171,653 | 162,790 | |||||||||||
| General and administrative(2) | 12,534 | 10,771 | 47,909 | 45,776 | |||||||||||
| Gain on sale of in-process research and development asset | — | — | (10,000 | ) | — | ||||||||||
| Total operating expenses | 57,172 | 61,253 | 209,562 | 208,566 | |||||||||||
| Loss from operations | (57,172 | ) | (61,253 | ) | (209,562 | ) | (208,566 | ) | |||||||
| Other (expense) income: | |||||||||||||||
| Interest income | 7,139 | 5,776 | 24,885 | 21,312 | |||||||||||
| Other (expense) income, net | (12,497 | ) | (818 | ) | 29,459 | (20,713 | ) | ||||||||
| Total other (expense) income | (5,358 | ) | 4,958 | 54,344 | 599 | ||||||||||
| Loss before income tax expense | (62,530 | ) | (56,295 | ) | (155,218 | ) | (207,967 | ) | |||||||
| Income tax (expense) benefit | — | (1 | ) | 15 | (51 | ) | |||||||||
| Net loss | $ | (62,530 | ) | $ | (56,296 | ) | $ | (155,203 | ) | $ | (208,018 | ) | |||
| Net loss per share, basic and diluted, Series A Preferred Stock | $ | (27.92 | ) | $ | (32.28 | ) | $ | (79.02 | ) | $ | (127.21 | ) | |||
| Weighted-average Series A non-voting convertible preferred stock outstanding, basic and diluted | 346,045 | 346,045 | 346,045 | 374,387 | |||||||||||
| Net loss per share, basic and diluted, Series B Preferred Stock | $ | (27.92 | ) | $ | (32.28 | ) | $ | (79.02 | ) | $ | (127.21 | ) | |||
| Weighted-average Series B non-voting convertible preferred stock outstanding, basic and diluted | 16,667 | 16,667 | 16,667 | 85,208 | |||||||||||
| Net loss per share, basic and diluted, common | $ | (0.70 | ) | $ | (0.81 | ) | $ | (1.98 | ) | $ | (3.18 | ) | |||
| Weighted-average common stock outstanding, basic and diluted | 75,088,910 | 55,259,227 | 64,056,442 | 47,027,638 | |||||||||||
(1) Includes
(2) Includes
