Spyre Therapeutics(SYRE) - 2025 Q2 - Quarterly Results

Executive Summary & Corporate Update Spyre Therapeutics reported positive Phase 1 results, initiated Phase 2 trials, and maintains a strong financial position, with the CEO outlining a vision for reshaping immune-mediated disease treatments Highlights of Q2 2025 Spyre Therapeutics reported positive interim Phase 1 results for two next-generation TL1A antibodies, initiated the Phase 2 SKYLINE-UC study, and is on track for Q3 initiation of the SKYWAY-RD basket study. The company also reported a strong cash position with an expected runway into the second half of 2028 - Positive interim Phase 1 results for two next-generation TL1A antibodies, demonstrating good tolerability, PK profiles supporting quarterly or biannual dosing, and full TL1A engagement through up to 20 weeks[1] - Initiated Phase 2 SKYLINE-UC platform study for ulcerative colitis (UC) and on track for Q3 initiation of Phase 2 SKYWAY-RD basket study for rheumatoid arthritis (RA), psoriatic arthritis (PsA), and axial spondyloarthritis (axSpA)[1] - On track to report interim Phase 1 data for SPY003 in Q4 2025, with 9 proof-of-concept readouts planned in 2026 & 2027 across IBD and rheumatic diseases[1] Cash, Cash Equivalents, and Marketable Securities | As of June 30, 2025 | Amount (in millions) | | :------------------ | :----- | | Cash, cash equivalents, and marketable securities | $526.6 | | Expected runway | into H2 2028 | CEO's Strategic Vision CEO Cameron Turtle emphasized Spyre's entry into a new chapter, aiming to reshape treatment paradigms for chronic immune-mediated diseases through its pipeline. The launch of SKYLINE-UC and upcoming SKYWAY-RD trials are key to identifying indication-leading products, with nine proof-of-concept readouts expected in the next two years, supported by robust science and a strong balance sheet - Spyre is entering a new chapter to explore its pipeline's potential to reshape treatment paradigms in chronic immune-mediated diseases[2] - The SKYLINE-UC and SKYWAY-RD trials are expected to generate nine proof-of-concept readouts in IBD and rheumatic conditions over the next two years[2] - The company is positioned to drive value for patients and investors, backed by robust science, a committed team, and a strong balance sheet with expected runway into the second half of 2028[2] Development Pipeline Overview This section details Spyre's approach to developing next-generation therapies for IBD and immune-mediated diseases, including monotherapy and combination programs, with updates on Phase 2 clinical trials Company Approach and Disease Focus Spyre Therapeutics employs best-in-class antibody engineering, dose optimization, and rational therapeutic combinations to maximize efficacy, safety, and convenience in treating Inflammatory Bowel Disease (IBD) and other immune-mediated diseases. The company targets chronic conditions like Ulcerative Colitis (UC), Crohn's Disease (CD), Rheumatoid Arthritis (RA), Psoriatic Arthritis (PsA), and axial Spondyloarthritis (axSpA), which affect millions in the U.S. and face issues of underdiagnosis and inadequate efficacy - Spyre's approach combines antibody engineering, dose optimization, and rational therapeutic combinations to maximize efficacy, safety, and convenience in IBD and other immune-mediated diseases[3] - IBD affects approximately 2.4 million individuals in the U.S., while RA and PsA each affect over 1.5 million, and axSpA affects nearly 3 million, with underdiagnosis and inadequate efficacy being significant challenges[3][4] - Monotherapy programs target validated mechanisms for safe and effective treatment of UC and CD with infrequent dosing, and the anti-TL1A program is also being studied in RA, PsA, and axSpA[4] Monotherapy Programs Spyre's pipeline includes three investigational monoclonal antibodies: SPY001 (targeting α4β7), SPY002/SPY072 (targeting TL1A), and SPY003 (targeting IL-23 p19 subunit). All are engineered with half-life extension technology and high concentration formulations to enable infrequent, subcutaneous maintenance dosing and maximize efficacy. SPY002 is for IBD, and SPY072 is for rheumatic diseases - Spyre's monotherapy programs include SPY001 (α4β7), SPY002/SPY072 (TL1A), and SPY003 (IL-23 p19), all designed for infrequent, subcutaneous maintenance dosing[5][6][7] - TL1A is considered one of the most promising targets in IBD and broader immunology, with SPY002 developed for IBD and SPY072 for rheumatic diseases[6] SPY001 (α4β7) SPY001 is a highly potent and selective investigational monoclonal antibody targeting α4β7, engineered for extended half-life and high concentration to enable infrequent, subcutaneous maintenance dosing. Interim Phase 1 healthy volunteer data showed a favorable safety profile, a differentiated PK profile supporting potential Q3M or Q6M maintenance dosing, and rapid, complete saturation of α4β7 receptors. Based on these results, SPY001 advanced into the SKYLINE-UC Phase 2 trial in May 2025 - SPY001 is an α4β7 antibody engineered for extended half-life and high concentration, aiming for infrequent subcutaneous maintenance dosing[5] - Interim Phase 1 data for SPY001 demonstrated a favorable safety profile, PK profile supporting potential Q3M or Q6M maintenance dosing, and complete α4β7 receptor saturation[9] - SPY001 advanced into the SKYLINE-UC Phase 2 platform trial, which initiated in May 2025[9] SPY002 & SPY072 (TL1A) SPY002 and SPY072 are highly potent and selective anti-TL1A monoclonal antibodies, designed with half-life extension and high concentration for infrequent, subcutaneous maintenance dosing. Interim Phase 1 healthy volunteer data showed favorable safety, differentiated PK profiles supporting potential Q3M or Q6M maintenance dosing, and complete suppression of free TL1A for up to 20 weeks. SPY002 is expected to advance to the SKYLINE-UC Phase 2 trial, and SPY072 to the SKYWAY-RD Phase 2 basket trial, both in Q3 2025 - SPY002 (for IBD) and SPY072 (for rheumatic diseases) are anti-TL1A antibodies engineered for extended half-life and high concentration, targeting infrequent subcutaneous maintenance dosing[6] - Interim Phase 1 data for SPY002 and SPY072 showed favorable safety, PK profiles supporting potential Q3M or Q6M maintenance dosing, and complete suppression of free TL1A[9] - SPY002 is expected to advance to SKYLINE-UC Phase 2, and SPY072 to SKYWAY-RD Phase 2, both in Q3 2025[9] SPY003 (IL-23) SPY003 is a highly potent and selective investigational monoclonal antibody targeting the p19 subunit of IL-23, engineered for extended half-life and high concentration to enable infrequent, subcutaneous maintenance dosing. A first-in-human (FIH) trial was initiated in March 2025, with interim healthy volunteer data expected in Q4 2025. Preclinical data demonstrated comparable potency to risankizumab, a greater than three-fold longer pharmacokinetic half-life, and high selectivity for IL-23 - SPY003 targets the p19 subunit of IL-23, engineered for extended half-life and high concentration for infrequent subcutaneous maintenance dosing[7] - FIH trial for SPY003 initiated in March 2025, with interim healthy volunteer data expected in Q4 2025[9] - Preclinical data for SPY003 showed comparable potency to risankizumab, a >3x longer PK half-life, and high selectivity for IL-23[9] Rational Combination Programs Spyre plans to investigate combinations of its proprietary antibodies in nonclinical and clinical studies to achieve best-in-class efficacy in IBD with less frequent dosing. Preclinical data for SPY120 (TL1A + α4β7) demonstrated superiority over monotherapy in mouse models of colitis and no drug effects on PK in NHPs. Additionally, preclinical data for SPY130 and SPY230 (SPY003 in combination with SPY001 and SPY002, respectively) showed enhanced efficacy and pharmacodynamics. These combinations are expected to be included in Part B of the SKYLINE-UC trial - Spyre plans to investigate proprietary antibody combinations to achieve best-in-class efficacy in IBD with less frequent dosing[8] - Preclinical data for SPY120 (TL1A + α4β7) showed superiority over monotherapy in colitis models and no PK drug effects[8][10] - Preclinical data for SPY130 and SPY230 (SPY003 + SPY001/SPY002) demonstrated enhanced efficacy and pharmacodynamics[16] - Rational combinations are expected to be included in Part B of the SKYLINE-UC trial[16] Clinical Trial Updates Spyre is advancing its pipeline through two key Phase 2 platform trials: SKYLINE-UC for ulcerative colitis and SKYWAY-RD for rheumatic diseases. These trials are designed to efficiently generate proof-of-concept data for monotherapies and combinations - Spyre is conducting two key Phase 2 platform trials: SKYLINE-UC for UC and SKYWAY-RD for rheumatic diseases, aiming for efficient proof-of-concept data generation[2] SKYLINE-UC Phase 2 Platform Trial The SKYLINE-UC Phase 2 induction and maintenance platform trial for moderately to severely active UC patients was initiated in May 2025. It evaluates SPY001, SPY002, SPY003, and pairwise combinations (six active investigational agents). Part A is an open-label assessment of monotherapy safety and preliminary efficacy, with induction data expected in 2026. Part B is a randomized, placebo-controlled assessment of monotherapies (two dose levels) and combinations, with induction data expected in 2027. Enrollment is currently underway for the SPY001 arm of Part A - SKYLINE-UC Phase 2 trial for UC initiated in May 2025, evaluating SPY001, SPY002, SPY003, and pairwise combinations[11] - Part A (open-label monotherapy) induction data expected in 2026; Part B (randomized monotherapy/combination) induction data expected in 2027[16] - The trial is currently enrolling subjects into the SPY001 arm of Part A[11] SKYWAY-RD Phase 2 Basket Trial The SKYWAY-RD Phase 2 randomized and placebo-controlled basket trial for moderately to severely active RA, PsA, or axSpA patients is expected to initiate in Q3 2025. This trial will evaluate SPY072 across three sub-studies, each designed to provide proof-of-concept data in 2026. The RA sub-study will assess two dose levels of SPY072 at Week 12, while the PsA and axSpA sub-studies will each assess a single dose level of SPY072 at Week 16 - SKYWAY-RD Phase 2 basket trial for RA, PsA, or axSpA is expected to initiate in Q3 2025, evaluating SPY072[12] - The trial consists of three sub-studies (RA, PsA, axSpA), each expected to provide proof-of-concept data in 2026[12] - Sub-studies include RA (two dose levels, Week 12 data), PsA (single dose, Week 16 data), and axSpA (single dose, Week 16 data)[17] Second Quarter 2025 Financial Results This section provides an overview of Spyre's financial performance for Q2 2025, highlighting cash position, operating expenses, other income, and net loss Cash Position As of June 30, 2025, Spyre held $526.6 million in cash, cash equivalents, and marketable securities, providing an expected operational runway into the second half of 2028. Net cash used in operating activities for Q2 2025 was $46.6 million Cash Position | Metric | Q2 2025 (in millions) | | :---------------------------------- | :---------- | | Cash, cash equivalents, and marketable securities | $526.6 | | Net cash used in operating activities | $46.6 | | Expected runway | into H2 2028 | Cash and Marketable Securities (in thousands) | Asset | June 30, 2025 (in thousands) | December 31, 2024 (in thousands) | | :------------------------ | :------------ | :---------------- | | Cash and cash equivalents | $81,659 | $89,423 | | Marketable securities | $444,921 | $513,665 | | Total | $526,580 | $603,088 | Operating Expenses Research and Development (R&D) expenses increased to $40.1 million in Q2 2025 from $32.6 million in Q2 2024, primarily due to higher clinical trial expenses and compensation costs, partially offset by lower early-stage R&D. General and Administrative (G&A) expenses remained relatively stable at $11.8 million in Q2 2025 compared to $11.5 million in Q2 2024 Operating Expenses (in thousands) | Expense Category | Q2 2025 (in thousands) | Q2 2024 (in thousands) | YoY Change | | :----------------------- | :------ | :------ | :--------- | | Research and development | $40,145 | $32,636 | +22.9% | | General and administrative | $11,790 | $11,511 | +2.4% | - Increase in R&D expenses was primarily driven by higher clinical trial expenses and increased compensation costs, partially offset by lower early-stage R&D activities[13] Other Financial Items Spyre recognized a $10.0 million gain in Q2 2025 from the sale of an in-process research and development asset, specifically related to a milestone achieved for pegzilarginase. Other income for Q2 2025 was $5.2 million, slightly down from $5.3 million in Q2 2024 Other Financial Items (in thousands) | Item | Q2 2025 (in thousands) | Q2 2024 (in thousands) | | :------------------------------------------ | :------ | :------ | | Gain on sale of in-process R&D asset | $(10,000) | $0 | | Other income (Interest income + Other (expense) income, net) | $5,218 | $5,310 | - The $10.0 million gain was due to achieved milestones related to the 2023 sale of pegzilarginase global rights to Immedica, driven by a favorable reimbursement decision in Europe[14] Net Loss Spyre reported a net loss of $36.7 million for Q2 2025, a slight improvement from the $38.8 million net loss in Q2 2024. This includes non-cash stock-based compensation expenses of $9.4 million and $8.7 million for Q2 2025 and Q2 2024, respectively Net Loss (in thousands) | Metric | Q2 2025 (in thousands) | Q2 2024 (in thousands) | YoY Change | | :-------------------------------- | :------ | :------ | :--------- | | Net loss | $(36,717) | $(38,837) | -5.5% | | Non-cash stock-based compensation | $9,400 | $8,700 | +8.0% | Net Loss Per Share (Common Stock) | Metric | Q2 2025 ($) | Q2 2024 ($) | YoY Change | | :-------------------------------- | :------ | :------ | :--------- | | Net loss per share, basic and diluted, common | $(0.49) | $(0.59) | -16.9% | About Spyre Therapeutics This section provides a concise overview of Spyre Therapeutics as a clinical-stage biotechnology company focused on developing next-generation products for IBD and other immune-mediated diseases Company Overview Spyre Therapeutics is a clinical-stage biotechnology company focused on developing next-generation products for inflammatory bowel disease (IBD) and other immune-mediated diseases. The company achieves this by combining best-in-class antibody engineering, dose optimization, and rational therapeutic combinations, with a pipeline of investigational extended half-life antibodies targeting α4β7, TL1A, and IL-23 - Spyre Therapeutics is a clinical-stage biotechnology company developing next-generation products for IBD and other immune-mediated diseases[18] - The company's approach involves best-in-class antibody engineering, dose optimization, and rational therapeutic combinations[18] - Spyre's pipeline includes investigational extended half-life antibodies targeting α4β7, TL1A, and IL-23[18] Safe Harbor / Forward Looking Statements This section contains standard disclaimers regarding forward-looking statements, emphasizing inherent risks and uncertainties in future projections Disclaimer and Risk Factors This section contains standard forward-looking statements regarding Spyre's future financial results, business strategy, clinical development activities, potential efficacy and safety of product candidates, and cash runway. It cautions readers that these statements are subject to risks, uncertainties, and assumptions, including regulatory feedback, clinical data consistency, macroeconomic conditions, and geopolitical instability, and that actual results may differ materially. The company disclaims any obligation to update these statements - The press release contains forward-looking statements regarding future financial position, business strategy, clinical development, and product candidate potential[20] - These statements are subject to risks and uncertainties, including regulatory feedback, potential inconsistencies in clinical data, macroeconomic conditions, and geopolitical instability[21][22] - Readers should not rely on forward-looking statements as predictions of future events, and the company undertakes no obligation to update them except as required by law[23] Contact Information This section provides essential contact details for media and investor inquiries Media and Investor Contacts This section provides contact details for media and investor inquiries - Contact information for media (Josie Butler, 1AB) and investors (Eric McIntyre) is provided[24] Consolidated Financial Statements This section presents Spyre's detailed financial statements, including balance sheets and statements of operations, for the specified periods Consolidated Balance Sheets The consolidated balance sheets show the company's financial position as of June 30, 2025, and December 31, 2024. Total assets decreased from $608.484 million at year-end 2024 to $538.832 million at Q2 2025, primarily due to a decrease in marketable securities. Total liabilities increased, mainly driven by a significant rise in CVR liability. Total stockholders' equity decreased from $517.804 million to $455.773 million Consolidated Balance Sheets (Selected Items, in thousands) | Item | June 30, 2025 (in thousands) | December 31, 2024 (in thousands) | Change (in thousands) | | :-------------------------------- | :------------ | :---------------- | :----- | | ASSETS | | | | | Cash and cash equivalents | $81,659 | $89,423 | $(7,764) | | Marketable securities | $444,921 | $513,665 | $(68,744) | | Total current assets | $538,832 | $608,474 | $(69,642) | | TOTAL ASSETS | $538,832 | $608,484 | $(69,652) | | LIABILITIES | | | | | CVR liability (current) | $59,900 | $25,080 | $34,820 | | Non-current CVR liability | $0 | $36,620 | $(36,620) | | Total current liabilities | $83,059 | $54,060 | $28,999 | | TOTAL LIABILITIES | $83,059 | $90,680 | $(7,621) | | STOCKHOLDERS' EQUITY | | | | | Accumulated deficit | $(1,053,922) | $(972,432) | $(81,490) | | TOTAL STOCKHOLDERS' EQUITY | $455,773 | $517,804 | $(62,031) | - Total assets decreased by approximately $69.7 million, primarily due to a reduction in marketable securities[26] - Current CVR liability significantly increased from $25.080 million to $59.900 million, while non-current CVR liability became zero[26] - Accumulated deficit increased by $81.490 million, reflecting the net loss for the period[26] Consolidated Statements of Operations The consolidated statements of operations detail the company's financial performance for the three and six months ended June 30, 2025, and 2024. For Q2 2025, the net loss was $36.7 million, an improvement from $38.8 million in Q2 2024. This was influenced by increased R&D expenses, a $10.0 million gain on the sale of an in-process R&D asset, and stable G&A and other income. For the six months ended June 30, 2025, the net loss was $81.5 million, slightly better than $82.7 million in the prior year period Consolidated Statements of Operations (Three Months Ended June 30, in thousands) | Item | 2025 (in thousands) | 2024 (in thousands) | YoY Change | | :------------------------------------------ | :------ | :------ | :--------- | | Research and development | $40,145 | $32,636 | +22.9% | | General and administrative | $11,790 | $11,511 | +2.4% | | Gain on sale of in-process R&D asset | $(10,000) | $0 | N/A | | Total operating expenses | $41,935 | $44,147 | -5.1% | | Loss from operations | $(41,935) | $(44,147) | -5.0% | | Total other income | $5,218 | $5,310 | -1.7% | | Net loss | $(36,717) | $(38,837) | -5.5% | | Net loss per share, common (basic and diluted) | $(0.49) | $(0.59) | -16.9% | Consolidated Statements of Operations (Six Months Ended June 30, in thousands) | Item | 2025 (in thousands) | 2024 (in thousands) | YoY Change | | :------------------------------------------ | :------ | :------ | :--------- | | Research and development | $81,768 | $67,564 | +21.0% | | General and administrative | $23,734 | $24,357 | -2.6% | | Gain on sale of in-process R&D asset | $(10,000) | $0 | N/A | | Total operating expenses | $95,502 | $91,921 | +3.9% | | Loss from operations | $(95,502) | $(91,921) | +3.9% | | Total other income | $13,997 | $9,259 | +51.2% | | Net loss | $(81,490) | $(82,694) | -1.5% | | Net loss per share, common (basic and diluted) | $(1.09) | $(1.31) | -16.8% | - R&D expenses increased by 22.9% for Q2 2025 and 21.0% for the six months ended June 30, 2025, reflecting increased clinical trial activities[13][28] - A $10.0 million gain from the sale of an in-process R&D asset positively impacted the net loss for both the three and six-month periods in 2025[14][28]