SYRE Stock: Insider Activity, Filings & Research

Spyre Therapeutics, Inc. (SYRE) — Drillr’s hub for SYRE insider activity, SEC filings, earnings signals and AI research. Over the trailing 3 months, SYRE insiders filed 0 open-market buys and 30 sales (SEC Form 4).

Sentiment

0/100

Buys (3m)

Sells (3m)

Net (3m)

-$17.2M

Insider trades by month Buys Sells

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Context3-month price +78.9%Institutions accumulating (13F)

Date	Insider	Type	Shares	Price
Jun 3, 2026	Sloan Sheldonofficer: Chief Medical Officer	Option	8,333	$27.46
Jun 3, 2026	Burrows Scott Lofficer: Chief Financial Officer	Sell	1,801	$69.75
Jun 3, 2026	Burrows Scott Lofficer: Chief Financial Officer	Sell	3,100	$72.06
Jun 3, 2026	Burrows Scott Lofficer: Chief Financial Officer	Option	7,500	$14.50
Jun 3, 2026	Burrows Scott Lofficer: Chief Financial Officer	Sell	2,599	$70.77
Jun 3, 2026	Turtle Camerondirector, officer: Chief Executive Officer	Sell	3,294	$71.38
Jun 3, 2026	Turtle Camerondirector, officer: Chief Executive Officer	Sell	8,149	$70.50
Jun 3, 2026	Turtle Camerondirector, officer: Chief Executive Officer	Sell	3,557	$69.40
Jun 3, 2026	Sloan Sheldonofficer: Chief Medical Officer	Sell	8,333	$75.00
May 29, 2026	Albers Jeffrey W.director	Grant	8,026	$72.51
May 29, 2026	Milligan Sandradirector	Grant	8,026	$72.51
May 29, 2026	McKenna Mark C.director	Grant	8,026	$72.51
May 29, 2026	Stelzer Lauriedirector	Grant	8,026	$72.51
May 29, 2026	HENDERSON MICHAEL THOMASdirector	Grant	8,026	$72.51
May 29, 2026	Fairmount Funds Management LLCdirector	Grant	8,026	$72.51

Source: SYRE SEC Form 4 filings, latest Jun 3, 2026. For informational purposes only — not investment advice.

Overview

Spyre Therapeutics, Inc. (NASDAQ:SYRE) is a preclinical-stage biotechnology company founded in 2013 and headquartered in Waltham, Massachusetts. The company went public in April 2016 and underwent a significant strategic transformation in November 2023, when it changed its name from Aeglea BioTherapeutics to Spyre Therapeutics to reflect its new focus on inflammatory bowel disease treatments. This pivot marked a complete shift from the company's previous focus on rare genetic diseases to developing novel antibody therapies for patients suffering from inflammatory bowel disease.

Business

Spyre Therapeutics operates in the biotechnology sector, specifically focusing on developing therapeutic antibodies for inflammatory bowel disease (IBD), which includes ulcerative colitis and Crohn's disease. IBD represents a group of chronic inflammatory conditions affecting the digestive tract that cause severe symptoms including abdominal pain, diarrhea, and intestinal bleeding, significantly impacting patients' quality of life. The company's pipeline centers around several monoclonal antibody candidates designed to target specific proteins involved in the inflammatory cascade that drives IBD. Their lead program is SPY001, a human monoclonal antibody that selectively binds to the α4β7 integrin, a protein that helps inflammatory cells migrate to the gut. By blocking this integrin, SPY001 aims to prevent inflammatory cells from reaching and damaging intestinal tissue. Beyond SPY001, Spyre is developing SPY002, which targets tumor necrosis factor-like ligand 1A (TL1A), another key inflammatory protein. The company is also exploring combination therapies, including SPY120 (combining SPY001 and SPY002) and additional early-stage programs targeting interleukin-23 (IL-23) and other novel mechanisms. All of these programs are currently in preclinical development, meaning they are still being tested in laboratory and animal studies before advancing to human clinical trials.

Revenue model

As a preclinical-stage biotechnology company, Spyre Therapeutics currently generates no meaningful revenue from product sales. The company's financial statements show minimal revenue (under $1 million annually) likely from research collaborations or licensing activities. Instead, Spyre operates on a typical biotech development model where it burns cash to fund research and development activities while seeking to advance its drug candidates through clinical trials toward eventual commercialization. The company's future revenue model would be based on product sales of approved IBD therapies, with potential customers being IBD patients treated through gastroenterologists and specialty clinics. The IBD market is substantial, with existing therapies generating billions in annual revenue, suggesting significant commercial opportunity if Spyre's candidates prove successful. Several factors could impact Spyre's future profitability margins. Positive factors include the large and growing IBD patient population, high unmet medical need creating pricing power for effective therapies, and potential for combination therapies to command premium pricing. Negative factors include intense competition from established players like AbbVie (Humira), Johnson & Johnson (Stelara), and emerging biosimilars, the high cost and risk of clinical development, regulatory approval challenges, and the need for extensive manufacturing capabilities. The company's success will ultimately depend on demonstrating superior efficacy or safety compared to existing treatments while navigating the complex and expensive drug development process.

Competitive moat

Spyre Therapeutics currently operates with a relatively weak competitive moat, which is typical for early-stage biotechnology companies. The company's primary potential advantages lie in its novel antibody designs and combination therapy approach, particularly the selective targeting of α4β7 integrin and TL1A pathways. If successful, these could provide differentiated treatment options in the competitive IBD market. However, the company faces significant competitive threats. The IBD therapeutic market is dominated by well-established players with approved products and extensive resources, including AbbVie's anti-TNF therapies, Johnson & Johnson's IL-23 inhibitor Stelara, and Takeda's α4β7 integrin inhibitor Entyvio (vedolizumab). Spyre's SPY001 directly competes with Entyvio's mechanism of action, though the company claims improved selectivity. The biotechnology sector's inherent challenges further weaken Spyre's moat position. The company lacks intellectual property protection for approved products, faces substantial clinical development risks with no guarantee of success, and requires significant capital investment with uncertain returns. Additionally, larger pharmaceutical companies could potentially develop competing therapies or acquire promising competitors. Spyre's ultimate moat will depend on successfully demonstrating superior clinical outcomes, achieving regulatory approval, and establishing market presence - all of which remain highly uncertain at the preclinical stage.

Risks & safety

Spyre Therapeutics presents a mixed margin of safety profile typical of preclinical biotechnology companies, with strong liquidity but significant execution risks. **Cash Position and Burn Rate:** - Cash and short-term investments of $48.5 million as of Q1 2025, down from $89.4 million in Q4 2024 - Quarterly cash burn of approximately $41 million in Q1 2025, suggesting roughly 3-4 quarters of runway at current burn rate - No debt burden (debt-to-equity ratio of 0.0) provides financial flexibility - Strong current ratio of 8.1x indicates excellent short-term liquidity **Valuation Metrics:** - Trading at 11.6x price-to-book ratio, indicating premium valuation relative to tangible assets - Negative enterprise value-to-EBITDA due to losses, making traditional valuation metrics less meaningful - Graham net-net ratio of 1.38x suggests reasonable asset backing **Other Considerations:** - High cash burn rate creates urgency for clinical progress or additional financing - Preclinical stage means no revenue generation and high binary risk from clinical trial outcomes - Strong balance sheet provides time to execute on development plans but limited runway without additional capital

Recent development

Spyre Therapeutics underwent a dramatic strategic transformation in 2023, completely pivoting from rare genetic diseases to inflammatory bowel disease. This shift, formalized with the November 2023 name change from Aeglea BioTherapeutics, represents a fundamental repositioning of the company's entire research and development focus. The company has been advancing its lead IBD program SPY001 through preclinical development, with management focusing on demonstrating the antibody's selective binding to α4β7 integrin compared to existing treatments like vedolizumab. Simultaneously, Spyre has been developing its broader pipeline including SPY002 (anti-TL1A) and combination therapy approaches that could differentiate its offerings in the competitive IBD market. The strategic pivot required significant organizational changes, including likely restructuring of research teams and capabilities to focus on antibody development for inflammatory diseases rather than enzyme replacement therapies for rare genetic conditions. This transformation has been accompanied by substantial cash expenditures, as evidenced by the company's high burn rate exceeding $40 million per quarter, reflecting the costs of rebuilding research programs and advancing multiple preclinical candidates toward clinical development.

SYRE company profile · for informational purposes only — not investment advice.

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