# EDGAR Filing Document

**Accession Number:** 0001636282
**File Stem:** 0001636282-25-000104
**Filing Date:** 2025-11
**Character Count:** 47771
**Document Hash:** fcf9eb6e17cd070d4430c335d48bf7b5
**Contains OCR:** False
**Source Format:** 

## Filing Content

## Filing Summary
**0001636282-25-000104.hdr.sgml**: 20251104

**ACCESSION NUMBER**: 0001636282-25-000104

**CONFORMED SUBMISSION TYPE**: 8-K

**PUBLIC DOCUMENT COUNT**: 16

**CONFORMED PERIOD OF REPORT**: 20251104

**ITEM INFORMATION**: Results of Operations and Financial Condition

**ITEM INFORMATION**: Regulation FD Disclosure

**ITEM INFORMATION**: Other Events

**ITEM INFORMATION**: Financial Statements and Exhibits

**FILED AS OF DATE**: 20251104

**DATE AS OF CHANGE**: 20251104

**FILER**: 

**COMPANY DATA:**
- **COMPANY CONFORMED NAME:** Spyre Therapeutics, Inc.
- **CENTRAL INDEX KEY:** 0001636282
- **STANDARD INDUSTRIAL CLASSIFICATION:** PHARMACEUTICAL PREPARATIONS [2834]
- **ORGANIZATION NAME:** 03 Life Sciences
- **EIN:** 464312787
- **STATE OF INCORPORATION:** DE
- **FISCAL YEAR END:** 1231

**FILING VALUES:**
- **FORM TYPE:** 8-K
- **SEC ACT:** 1934 Act
- **SEC FILE NUMBER:** 001-37722
- **FILM NUMBER:** 251449138

**BUSINESS ADDRESS:**
- **STREET 1:** 221 CRESCENT STREET
- **STREET 2:** BUILDING 23, SUITE 105
- **CITY:** WALTHAM
- **STATE:** MA
- **ZIP:** 02453
- **BUSINESS PHONE:** 6176515940

**MAIL ADDRESS:**
- **STREET 1:** 221 CRESCENT STREET
- **STREET 2:** BUILDING 23, SUITE 105
- **CITY:** WALTHAM
- **STATE:** MA
- **ZIP:** 02453

**FORMER COMPANY:**
- **FORMER CONFORMED NAME:** Aeglea BioTherapeutics, Inc.
- **DATE OF NAME CHANGE:** 20150311

?xml version='1.0' encoding='ASCII'? syre-20251104

**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): November 4, 2025** 

_______________________________________________________

**SPYRE THERAPEUTICS, INC.**

**(Exact name of Registrant as Specified in Its Charter)**

_______________________________________________________

---

| | | |
|:---|:---|:---|
| **Delaware** | **001-37722** | **46-4312787** |
| **(State or Other Jurisdiction<br>of Incorporation)** | **(Commission File Number)** | **(IRS Employer<br>Identification No.)** |
| **221 Crescent Street**<br>**Building 23**<br>**Suite 105** | | |
| **Waltham, MA** | | **02453** |
| **(Address of Principal Executive Offices)** | | **(Zip Code)** |

---

Registrant's Telephone Number, Including Area Code: 617 651-5940

**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<br>Symbol(s)** | **Name of each exchange on which registered** |
| Common Stock, $0.0001 Par Value Per Share | SYRE | The Nasdaq Stock Market LLC<br>(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 □

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. □

**Item 2.02 Results of Operations and Financial Condition.**

On November 4, 2025, Spyre Therapeutics, Inc. (the "Company") issued a press release announcing its financial results for the third quarter ended September 30, 2025. A copy of the press release is furnished as Exhibit 99.1 to this report.

The information in this Item 2.02, including Exhibit 99.1 to this report, shall not be deemed to be "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 into any filing under the Exchange Act or under the Securities Act of 1933, as amended, except as shall be expressly set forth by specific reference in such filing.

**Item 7.01 Regulation FD Disclosure.**

On November 4, 2025, Spyre Therapeutics, Inc. ("Spyre" or the "Company") issued a press release announcing positive interim Phase 1 results from its first-in-human trials of SPY003, an investigational, novel, extended half-life monoclonal antibody targeting IL-23.

A copy of the press release is attached hereto as Exhibit 99.2. The information in this Item 7.01 of this Current Report on Form 8-K, including Exhibit 99.2 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 November 4, 2025, the Company announced positive interim Phase 1 results from its first-in-human trial of SPY003, an investigational, extended half-life antibody targeting the p19 subunit of IL-23.

***Key Phase 1 Interim Findings***

The SPY003 Phase 1 trial was a first-in-human, randomized, double-blind, placebo-controlled study designed to evaluate safety and pharmacokinetic ("PK") in healthy volunteers. The trial enrolled 59 healthy adult participants into five single-ascending dose cohorts, a multiple dose cohort, and a Chinese ethnobridging single dose cohort. Doses of SPY003 evaluated included 200 mg IV, 600 mg SC (two formulations), 600 mg IV, and 1200 mg IV (as single and multiple doses). Interim findings from the trial as of September 19<sup>th</sup>, 2025 data cutoff include:

**Safety:** SPY003 was well tolerated at all dose levels, with a favorable safety profile consistent with the anti-IL-23 class. There were two Grade 2 or above treatment-emergent adverse events ("TEAEs"), both deemed not treatment-related, and no serious adverse events were observed in the study. The only TEAE to occur in two or more subjects was headache.

------

**PK:** SPY003 showed a half-life of approximately 85 days, more than 3-times that of risankizumab's published half-life with dose proportionality and limited intrasubject variability. This differentiated PK profile supports the potential for quarterly or twice annual maintenance dosing in a single SC injection.

**Immunogenicity:** No apparent impact of anti-drug-antibodies was observed on PK.

**Forward-Looking Statements**

This Current Report on Form 8-K contains "forward-looking" statements within the meaning of the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995. All statements contained in this Current Report on Form 8-K, other than statements of historical fact are forward-looking statements. These forward-looking statements include statements regarding the Company's ability to achieve the expected benefits or opportunities with respect to its pipeline of product candidates such as the potential efficacy, tolerability, convenience, commercial viability, dosing regimen and safety profile of SPY003 in humans, including the potential for a quarterly or twice yearly maintenance dosing profile that may set a new standard of care for inflammatory bowel disease ("IBD"); the potential for SPY003 to become a best-in-class therapy for IBD; its plans to advance the SPY003 program into the SKYLINE Phase 2 platform study; expectations regarding the drug delivery of SPY003, including in the form of a subcutaneous injection; its ongoing 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 data readouts and number of data readouts expected to be delivered in 2026; the potential consistency of the SPY003 Phase 2 trial final data readouts with interim Phase 1 results; the potential therapeutic benefits of its product candidates as monotherapies or in combinations and their extended half-life, including the expected duration of half-life in comparison to competitor products; the timing and results of clinical trials; and potential potency, efficacy, dosing regimen and convenience compared to today's standard of care; estimated market sizes and potential growth opportunities and that human PK data is not based on head-to-head clinical trials and differences exist between trial design and patient populations which could confound the results. The words "believe," "may," "will," "potentially," "estimate," "continue," "anticipate," "predict," "target," "intend," "could," "would," "should," "project," "plan," "expect," the negatives of these terms, and similar expressions that convey uncertainty of future events or outcomes are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. These forward-looking statements involve a number of risks, uncertainties (some of which are beyond the Company's control) or other assumptions that may cause actual results or performance, final clinical trial data readouts and clinical trial designs, to be materially different from those expressed or implied by these forward-looking statements. These risks and uncertainties include, but are not limited, to the final SPY003 Phase 1 trial data readouts not being consistent with or being different than the interim SPY003 Phase 1 trial results reported in this Current Report on Form 8-K; regulatory feedback including potential disagreement by regulatory authorities with the Company's interpretation of data and the Company's planned clinical trials for its product candidates; including our plans for and timing of cohort initiation for combination therapy arms for the ongoing SKYLINE Phase 2 platform trial across different jurisdictions; the potential for final data not being consistent with or different than the interim data reported for our programs; the potential impact of Trump Administration policies and changes in law on our business; impacts of adverse events or disappointing results in clinical trials of third parties, including our competitors developing product candidates that target similar mechanisms of action and/or indications as our product candidates; and those uncertainties and factors described under the heading "Risk Factors," "Risk Factor Summary" and "Note about Forward-Looking Statements" in Spyre's most recent Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission, as well as discussions of potential risks, uncertainties, and other important factors included in other filings by Spyre from time to time. Should one or more of these risks or uncertainties materialize, or should any of Spyre's assumptions prove incorrect, actual results may vary in material respects from those projected in these forward-looking statements. Nothing in this Current Report on Form 8-K should be regarded as a representation by any person that the forward-looking statements set forth therein will be achieved or that any of the contemplated results of such forward-looking statements will be achieved. You should not place undue reliance on forward-looking statements in this Current Report on Form 8-K, 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. This Current Report on Form 8-K does not purport to summarize all of the conditions, risks and other attributes of an investment in Spyre.

------

**Item 9.01 Financial Statements and Exhibits.**

(d)Exhibits

---

| | |
|:---|:---|
| Exhibit <u>Number</u> | <u>Description</u> |
| 99.1 | <u>[Press release issued by Spyre Therapeutics, Inc. regarding its financial results for the](spyre-20250930xexx991.htm)[third](spyre-20250930xexx991.htm)[quarter ended](spyre-20250930xexx991.htm)[September 30](spyre-20250930xexx991.htm)[, 2025](spyre-20250930xexx991.htm)[,](spyre-20250930xexx991.htm)[dated](spyre-20250930xexx991.htm)[November 4](spyre-20250930xexx991.htm)[, 2025.](spyre-20250930xexx991.htm)</u> |
| 99.2 | <u>[Press release issued by Spyre Therapeutics, Inc. regarding Data, dated November](spyre20250930-exx992.htm)[4](spyre20250930-exx992.htm)[, 2025.](spyre20250930-exx992.htm)</u> |
| 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: | November 4, 2025 | By: | /s/ Scott Burrows |
|  |  |  | Scott Burrows<br>Chief Financial Officer |

---

## Exhibit 99.1

**Exhibit 99.1**

![image_1.jpg](image_1.jpg)

**Spyre Therapeutics Reports Third Quarter 2025 Financial Results and Provides Corporate Update** 

*Reported positive interim Phase 1 results for SPY003, a next-generation anti-IL-23 antibody, demonstrating the molecule was well-tolerated and exhibited an ~85-day half-life supporting quarterly or twice annual maintenance dosing*

*Initiated Phase 2 SKYWAY basket study of SPY072 evaluating TL1A inhibition in rheumatoid arthritis ("RA"), psoriatic arthritis ("PsA"), and axial spondyloarthritis ("axSpA")*

*On track for 6 proof-of-concept readouts in 2026 across the SKYLINE and SKYWAY Phase 2 trials* 

*Further strengthened balance sheet with $316 million gross proceeds from an underwritten public offering of common stock* 

*$783 million of pro forma cash, cash equivalents, and marketable securities as of September 30, 2025, with expected runway into the second half of 2028*

**Waltham, Mass, November 4, 2025 (GLOBE NEWSWIRE) -** Spyre Therapeutics, Inc. ("Spyre" or the "Company") (NASDAQ:SYRE), a clinical-stage biotechnology company pioneering long-acting antibodies and antibody combinations to redefine the standard of care for inflammatory bowel disease ("IBD") and rheumatic diseases, today announced its third quarter 2025 financial results and provided program and corporate updates.

"We have now reported positive Phase 1 data for each of our four investigational antibodies, fully unlocking the breadth of our innovative Phase 2 trials evaluating product candidates with potential indication-leading profiles in diseases that together impact more than five million Americans," said Cameron Turtle, DPhil, Chief Executive Officer of Spyre. "With optimized monotherapies and uniquely differentiated combination therapies in IBD, and a potential first- and best-in-class anti-TL1A therapy in rheumatic diseases, our portfolio could redefine the standard of care in indications totaling over $60B in annual revenue. We anticipate 2026 will be a transformational year for the company as we expect to unveil six Phase 2 proof-of-concept readouts in these indications. With our world-class development organization, de-risked biology, and a recently-strengthened balance sheet, we are poised to deliver meaningful value for patients and shareholders alike."

**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 the United States, it is estimated that approximately 2.4 million individuals are diagnosed with IBD. RA, PsA, and axSpA are chronic inflammatory autoimmune conditions primarily characterized by pain, stiffness, and swelling of the joints, as well as impacts on the spine and skin. Together, these rheumatic conditions affect more than three million individuals in the U.S. Existing therapies for these diseases today generally offer incomplete efficacy, meaningful safety warnings, and inconvenient dosing profiles.

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.

**SPY001** – a highly potent and selective investigational monoclonal antibody targeting α4β7, 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 α4β7 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, which initiated in May 2025.

**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 recent medical meetings, 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, which initiated in September 2025.

**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 half-life of ~85 days, supporting potential Q3M or Q6M maintenance dosing.

• Based on these interim results, SPY003 is expected to advance 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 α4β7 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.

**SKYLINE Phase 2 Platform Trial -** in May 2025, the Company initiated a Phase 2 induction and maintenance platform trial of SPY001, SPY002, SPY003, as well as pairwise combinations thereof (six active investigational agents in total) in patients with moderately to severely active UC. The trial consists of two parts:

• <u>Part A:</u> Open-label assessment of the safety and preliminary efficacy of a single dose level of each investigational monotherapy, with induction data expected in 2026.

• <u>Part B:</u> 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 the SPY001 and SPY002 arms of Part A, with SPY003 expected to begin enrolling in the coming months. Part B is expected to begin enrolling after Part A completes enrollment.

**SKYWAY Phase 2 Basket Trial in Rheumatic Diseases (RA, PsA, axSpA) -** 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, each expected to provide proof-of-concept data in 2026:

• <u>RA sub-study:</u> Double-blind, placebo-controlled safety and efficacy study of two dose levels of SPY072 at Week 12.

• <u>PsA sub-study:</u> Double-blind, placebo-controlled safety and efficacy study of a single dose level of SPY072 at Week 16.

• <u>axSpA sub-study:</u> Double-blind, placebo-controlled safety and efficacy study of a single dose level of SPY072 at Week 16.

**Third Quarter 2025 Financial Results&nbsp;&nbsp;&nbsp;&nbsp;**

**Cash Position:** As of September 30, 2025, Spyre had cash, cash equivalents, and marketable securities of $486.2 million*.* Pro forma cash of $782.7 million at September 30, 2025 also reflects $296.5 million in net proceeds from the recently closed October 2025 underwritten public offering of common stock. Net cash used in operating activities was $37.1 million for the third quarter of 2025.

**Research and Development (R&D) expenses:** R&D expenses totaled $45.2 million for the third quarter of 2025 and $44.7 million for the third quarter of 2024. Higher clinical trial expenses and milestone payments were offset by lower early-stage R&D activities.

**General and Administrative (G&A) expenses:** G&A expenses totaled $11.6 million for the third quarter of 2025 and $10.6 million for the third quarter of 2024. The increase was primarily driven by higher headcount.

**Other income (expense), net:** Other income totaled $45.7 million for the third quarter of 2025 versus $13.6 million of expense for the third quarter of 2024 primarily driven by changes in the fair value of the contingent value right (CVR) liability.

**Net Loss:** Net loss totaled $11.2 million and $69.0 million for the third quarters of 2025 and 2024, respectively.

**About Spyre Therapeutics**

Spyre Therapeutics is a clinical-stage biotechnology company pioneering long-acting antibodies and antibody combinations to redefine the standard of care for inflammatory bowel disease ("IBD") and rheumatic diseases. Spyre's pipeline includes investigational extended half-life antibodies targeting α4β7, TL1A, and IL-23.

------

For more information, please visit http://spyre.com.

**Safe Harbor / Forward Looking Statements**

This press release contains "forward-looking" statements within the meaning of the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995. All statements contained in this press release, other than statements of historical fact, are forward-looking statements. These forward-looking statements include statements regarding the Company's future results of operations and financial position; its business strategy, including the Company's 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 our 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 interim Phase 1 results; 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 timing of data readouts for the ongoing SKYWAY-RD Phase 2 basket trial, plans for and timing of monotherapy/combination arm enrollment, cohort initiation and data readouts for the ongoing SKYLINE-UC Phase 2 platform trial and further clinical evaluation of therapeutic combinations, enrollment of clinical trials, number of data readouts expected to be delivered in 2026 and 2027 and the advancement of SPY003 to the SKYLINE-UC Phase 2 platform trial, and related regulatory feedback; further clinical evaluation of therapeutic combinations, including expectations regarding efficacy and dosing regime; the potential efficacy, tolerability, convenience, commercial viability and safety profile of its product candidates, including in combinations; the planned dosing regimen for SPY001, SPY002, SPY072 and our other product candidates, including the potential for a Q3M or Q6M dosing profile; and the potential therapeutic benefits and economic value of its product candidates as monotherapies or in combinations and their extended half-life. The words "believe," "may," "will," "potentially," "estimate," "continue," "anticipate," "predict," "target," "intend," "could," "would," "should," "project," "plan," "expect," the negatives of these terms, and similar expressions that convey uncertainty of future events or outcomes are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words.

These forward-looking statements are subject to a number of risks, uncertainties and assumptions, including those arising from regulatory feedback, including potential disagreement by regulatory authorities with our clinical trial design, interpretation of data and our ongoing or planned clinical trials for our product candidates, including our plans for and timing of cohort initiation for combination arms for the ongoing SKYLINE-UC Phase 2 platform trial across different jurisdictions; the potential for final clinical data not being consistent with or different than the previously disclosed interim data for our programs; the impacts of adverse events or disappointing results in clinical trials of third parties, including our competitors developing product candidates that target similar mechanisms of action and/or indications as our product candidates; the expected or potential impact of macroeconomic conditions, including inflationary pressures, rising interest rates, general economic slowdown or a recession, changes in tariff/trade and monetary policy, volatile market conditions, financial institution instability, as well as geopolitical instability, including the ongoing military conflicts between Ukraine and Russia, conflicts in the Middle East, and geopolitical tensions between the United States and other countries, including China, on the Company's operations; the implementation of changes in law, tariffs, sanctions, export or import controls, and other government measures that could impact our business operations, including restricting international trade by the United States, China or other countries and the BIOSECURE Act or similar act if passed into law; and those risks described in the Company's Quarterly Reports on Form 10-Q, Annual Reports on Form 10-K, as well as in other filings and reports that the Company makes from time to time with the Securities and Exchange Commission. Moreover, the Company operates in a very competitive and rapidly changing environment, and new risks emerge from time to time. It is not possible for the Company's management to predict all risks, nor can the Company assess the impact of all factors on the business or the extent to which any factor, or combination of factors, may cause actual results to differ

------

materially from those contained in any forward-looking statements it may make. In light of these risks, uncertainties, and assumptions, the forward-looking events and circumstances discussed in this press release may not occur and actual results could differ materially and adversely from those anticipated or implied in the forward-looking statements.

You should not rely upon forward-looking statements as predictions of future events. Although the Company believes that the expectations reflected in the forward-looking statements are reasonable, the Company cannot guarantee that the future results, levels of activity, performance or events and circumstances reflected in the forward-looking statements will be achieved or occur. The Company undertakes no obligation to update publicly any forward-looking statement for any reason after the date of this press release to conform these statements to actual results, to reflect changes in the Company's expectations, or otherwise, except as required by law. You should read press release with the understanding that the Company's actual results, levels of activity, performance, events, outcomes, and the timing of results and outcomes, and other circumstances may be materially different from what the Company expects.

**Contact Information:**

**Media Contact**

Josie Butler, 1AB

josie@1abmedia.com

**Investor Contact**

Eric McIntyre

eric.mcintyre@spyre.com

------

**Spyre Therapeutics, Inc.**

**Consolidated Balance Sheets**

**(Unaudited, in thousands, except share and per share amounts)**

---

| | | |
|:---|:---|:---|
| | **September 30,<br>2025** | **December 31,<br>2024** |
| **ASSETS** | | |
| CURRENT ASSETS |  |  |
| &nbsp;&nbsp;&nbsp;&nbsp;Cash and cash equivalents | $64897 | $89423 |
| &nbsp;&nbsp;&nbsp;&nbsp;Marketable securities | 421301 | 513665 |
| &nbsp;&nbsp;&nbsp;&nbsp;Prepaid expenses and other current assets | 18406 | 5386 |
| &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;Total current assets | 504604 | 608474 |
| Other non-current assets |  | 10 |
| TOTAL ASSETS | $504604 | $608484 |
| **LIABILITIES AND STOCKHOLDERS' EQUITY** |  |  |
| CURRENT LIABILITIES |  |  |
| &nbsp;&nbsp;&nbsp;&nbsp;Accounts payable | $7457 | $666 |
| &nbsp;&nbsp;&nbsp;&nbsp;CVR liability | 11020 | 25080 |
| &nbsp;&nbsp;&nbsp;&nbsp;Accrued and other current liabilities | 23827 | 27711 |
| &nbsp;&nbsp;&nbsp;&nbsp;Related party accounts payable | 3970 | 603 |
| &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;Total current liabilities | 46274 | 54060 |
| Non-current CVR liability | 3230 | 36620 |
| TOTAL LIABILITIES | 49504 | 90680 |
| Commitments and Contingencies |  |  |
| STOCKHOLDERS' EQUITY |  |  |
| &nbsp;&nbsp;&nbsp;Series A non-voting convertible preferred stock, $0.0001 par value; 1,086,341 shares authorized as of September 30, 2025 and December 31, 2024; 346,045 shares issued and outstanding as of September 30, 2025 and December 31, 2024. | 146425 | 146425 |
| &nbsp;&nbsp;&nbsp;Series B non-voting convertible preferred stock, $0.0001 par value; 271,625 shares authorized and 16,667 shares issued and outstanding as of September 30, 2025 and December 31, 2024. | 9395 | 9395 |
| &nbsp;&nbsp;&nbsp;Preferred stock, $0.0001 par value; 8,642,034 shares authorized as of September 30, 2025 and December 31, 2024; no shares issued and outstanding as of September 30, 2025 and December 31, 2024. |  |  |
| &nbsp;&nbsp;&nbsp;Common stock, $0.0001 par value; 400,000,000 shares authorized as of September 30, 2025 and December 31, 2024; 60,471,793 shares and 60,257,023 shares issued and outstanding as of September 30, 2025 and December 31, 2024, respectively. | 13 | 13 |
| &nbsp;&nbsp;&nbsp;&nbsp;Additional paid-in capital | 1363581 | 1334223 |
| &nbsp;&nbsp;&nbsp;&nbsp;Accumulated other comprehensive income | 791 | 180 |
| &nbsp;&nbsp;&nbsp;&nbsp;Accumulated deficit | (1065105) | (972432) |
| TOTAL STOCKHOLDERS' EQUITY | 455100 | 517804 |
| TOTAL LIABILITIES, CONVERTIBLE PREFERRED STOCK AND STOCKHOLDERS' EQUITY | $504604 | $608484 |

---

------

**Spyre Therapeutics, Inc.**

**Consolidated Statements of Operations**

**(Unaudited, in thousands, except share and per share amounts)**

---

| | | | | |
|:---|:---|:---|:---|:---|
| | **Three Months Ended<br>September 30,** | **Three Months Ended<br>September 30,** | **Nine Months Ended<br>September 30,** | **Nine Months Ended<br>September 30,** |
| | **2025** | **2024** | **2025** | **2024** |
| Operating expenses: |  |  |  |  |
| &nbsp;&nbsp;&nbsp;Research and development <sup>(1)</sup> | 45247 | 44744 | 127015 | 112308 |
| &nbsp;&nbsp;&nbsp;General and administrative <sup>(2)</sup> | 11641 | 10648 | 35375 | 35005 |
| &nbsp;&nbsp;&nbsp;&nbsp;Gain on sale of in-process research and development asset |  |  | (10000) |  |
| &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;Total operating expenses | 56888 | 55392 | 152390 | 147313 |
| Loss from operations | (56888) | (55392) | (152390) | (147313) |
| Other income (expense): |  |  |  |  |
| &nbsp;&nbsp;&nbsp;Interest income | 5379 | 5184 | 17746 | 15536 |
| &nbsp;&nbsp;&nbsp;Other income (expense), net | 40326 | (18802) | 41956 | (19895) |
| &nbsp;&nbsp;&nbsp;&nbsp;Total other income (expense) | 45705 | (13618) | 59702 | (4359) |
| Loss before income tax expense | (11183) | (69010) | (92688) | (151672) |
| &nbsp;&nbsp;&nbsp;Income tax (expense) benefit |  | (18) | 15 | (50) |
| Net loss | $(11183) | $(69028) | $(92673) | $(151722) |
| Net loss per share, basic and diluted, Series A Preferred Stock | $(5.97) | $(42.22) | $(49.53) | $(95.68) |
| Weighted-average Series A non-voting convertible preferred stock outstanding, basic and diluted | 346045 | 346045 | 346045 | 383903 |
| Net loss per share, basic and diluted, Series B Preferred Stock | $(5.97) | $(42.24) | $(49.53) | $(95.68) |
| Weighted-average Series B non-voting convertible preferred stock outstanding, basic and diluted | 16667 | 16667 | 16667 | 95158 |
| Net loss per share, basic and diluted, common | $(0.15) | $(1.06) | $(1.24) | $(2.39) |
| Weighted-average common stock outstanding, basic and diluted | 60414223 | 50889443 | 60338541 | 44263746 |

---

(1)Includes $7.0 million and $9.6 million in related party expenses for the three and nine months ended September 30, 2025, respectively, and $7.7 million and $34.2 million related party expenses for the three and nine months ended September 30, 2024, respectively.

(2)Includes related party expenses of $0.3 million for the three months ended September 30, 2025 and 2024, and $0.8 million for the nine months ended September 30, 2025 and 2024.

## Exhibit 99.2

**Exhibit 99.2**

![image_1.jpg](image_1.jpg)

**Spyre Therapeutics Announces Positive Interim Phase 1 Results for SPY003, Its Novel, Half-Life Extended anti-IL-23 Antibody**

*SPY003 was well tolerated and exhibited an ~85-day half-life, supporting potential quarterly or twice annual maintenance dosing*

*SPY003 positive interim results unlock development of SPY130 (α4β7 + IL-23) and SPY230 (TL1A + IL-23) investigational combination therapies for IBD with potential for indication-leading efficacy, safety, and dosing profiles*

*SPY003 expected to advance to the ongoing Part A of the SKYLINE Ph2 platform trial*

*SKYLINE and SKYWAY trials are expected to provide 6 proof-of-concept readouts in 2026*

WALTHAM, Mass., November 4, 2025 (GLOBE NEWSWIRE) – Spyre Therapeutics, Inc. (NASDAQ: SYRE), a clinical-stage biotechnology company pioneering long-acting antibodies and antibody combinations to redefine the standard of care for inflammatory bowel disease ("IBD") and rheumatic diseases, today announced positive interim Phase 1 results from its first-in-human trial of SPY003, an investigational, extended half-life antibody targeting the p19 subunit of IL-23.

"These encouraging Phase 1 data for SPY003 mark our fourth successful first-in-human trial in the past year, underscoring the strength of our antibody engineering platform and efficiency of our development organization," said Deanna Nguyen, M.D., SVP of Clinical Development at Spyre. "Advancing SPY003 into SKYLINE represents a pivotal step in realizing our vision for a comprehensive IBD portfolio that includes three optimized monotherapies and three uniquely differentiated combinations that have the potential to be dosed on a quarterly or twice annual basis."

**Key Phase 1 Interim Findings**

The SPY003 Phase 1 trial was a first-in-human, randomized, double-blind, placebo-controlled study designed to evaluate safety and pharmacokinetic (PK) in healthy volunteers. The trial enrolled 59 healthy adult participants into five single-ascending dose (SAD) cohorts, a multiple dose cohort (MD), and a Chinese ethnobridging (Ch Eb) single dose cohort. Doses of SPY003 evaluated included 200 mg IV, 600 mg SC (two formulations), 600 mg IV, and 1200 mg IV (as single and multiple doses). Interim findings from the trial as of September 19<sup>th</sup>, 2025 data cutoff include:

**Safety:** SPY003 was well tolerated at all dose levels, with a favorable safety profile consistent with the anti-IL-23 class. There were two Grade 2 or above treatment-

------

emergent adverse events (TEAEs), both deemed not treatment-related, and no serious adverse events were observed in the study. The only TEAE to occur in two or more subjects was headache. Blinded safety data are summarized as follows.

---

| | | | | | | | |
|:---|:---|:---|:---|:---|:---|:---|:---|
| Cohort | SAD 1 | SAD 2 | SAD 3 | SAD 4 | SAD 5 | MD1 | Ch Eb 1 |
| Dose | 200 mg IV | 600 mg SC | 600 mg IV | 1200 mg IV | 600 mg SC<sup>3</sup> | 1200 mg IV x 2 | 1200 mg IV |
| N= | 8 | 8 | 9 | 8 | 8 | 8 | 10 |
| At least one TEAE | 5 <br>(63%) | &nbsp;&nbsp;&nbsp;&nbsp;0<br>(0%) | 2<br>(22%) | 2<br>(25%) | 3<br>(38%) | 1<br>(13%) | 0<br>(0%) |
| At least one TESAE | 0<br>(0%) | 0<br>(0%) | 0<br>(0%) | 0<br>(0%) | 0<br>(0%) | 0<br>(0%) | 0<br>(0%) |
| At least one Treatment-related AE<sup>1</sup> | 0<br>(0%) | 0<br>(0%) | 1<br>(11%) | 1<br>(13%) | 0<br>(0%) | 0<br>(0%) | 0<br>(0%) |
| At least one ≥Grade 2 TEAE<sup>2</sup> | 1<br>(13%) | 0<br>(0%) | 0<br>(0%) | 1<br>(13%) | 0<br>(0%) | 0<br>(0%) | 0<br>(0%) |

---

<sup>1</sup>One case of infusion reaction and one case of pruritus, both Grade 1 and resolved without medication.

<sup>2</sup>One case of asymptomatic increased lipase, isolated to Day 43 post-dose (Grade 3); One case of bronchitis (Grade 2). Neither deemed treatment related.

<sup>3</sup>High concentration formulation.

**PK:** SPY003 showed a half-life of approximately 85 days, more than 3-times that of risankizumab's published half-life with dose proportionality and limited intrasubject variability. This differentiated PK profile supports the potential for quarterly or twice annual maintenance dosing in a single SC injection.

------

![spy003meanpkprofiles_small.jpg](spy003meanpkprofiles_small.jpg)

<sup>1</sup>SAD5 (600 mg SC high concentration formulation) and Ch Eb1 (1200 mg SC in volunteers of Chinese descent) not shown for visual clarity, results were consistent with other cohorts at similar doses.

**Immunogenicity:** No apparent impact of anti-drug-antibodies was observed on PK.

**About SPY003**

SPY003 is an investigational, extended half-life monoclonal antibody targeting IL-23, being developed for the treatment of IBD. IBD is a chronic condition characterized by inflammation in the gastrointestinal tract and encompasses two main disorders: ulcerative colitis and Crohn's disease. Together, it is estimated that more than 2.4 million individuals currently have IBD in the United States. In head-to-head preclinical studies, SPY003 demonstrated equivalent potency to risankizumab in inhibiting pSTAT signaling and IL-17 production. Interim data from a Phase 1 trial demonstrated that SPY003 was well tolerated and exhibited prolonged pharmacokinetics. Based on Phase 1 clinical data, the company plans to evaluate SPY003 in its SKYLINE Phase 2 platform study (NCT07012395).

**About Spyre Therapeutics**

Spyre Therapeutics is a clinical-stage biotechnology company pioneering long-acting antibodies and antibody combinations to redefine the standard of care for inflammatory bowel disease ("IBD") and rheumatic diseases. Spyre's pipeline includes investigational extended half-life antibodies targeting α4β7, TL1A, and IL-23.

For more information, please visit http://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, concerning Spyre and other matters. These forward-looking statements include, but are not limited to, express or implied statements relating to Spyre's management team's expectations, hopes, beliefs, intentions or strategies regarding the future including, without limitation, Spyre's ability to achieve the expected benefits or opportunities with respect to its pipeline of product candidates such as the potential efficacy, tolerability, convenience, commercial viability, dosing regimen and safety profile of SPY003 in humans, including the potential for a quarterly or twice yearly maintenance dosing profile that may set a new standard of care for IBD; the potential for SPY003 to become a best-in-class therapy for IBD; its plans to advance the SPY003 program into the SKYLINE Phase 2 platform study; expectations regarding the drug delivery of SPY003, including in the form of a subcutaneous injection; Spyre's ongoing 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 data readouts and number of data readouts expected to be delivered in 2026; the potential consistency of the SPY003 Phase 2 trial final data readouts with interim Phase 1 results; the potential therapeutic benefits of Spyre's product candidates as monotherapies or in combinations and their extended half-life, including the expected duration of half-life in comparison to competitor products and the potential potency, efficacy, dosing regimen and convenience compared to today's standard of care; estimated market sizes and potential growth opportunities and that human PK data is not based on head-to-head clinical trials and differences exist between trial design and patient populations which could confound the results. In addition, any statements that refer to projections, forecasts or other characterizations of future events or circumstances, including any underlying assumptions, are forward-looking statements. The words "opportunity," "potential," "milestones," "pipeline," "can," "goal," "aim," "strategy," "target," "seek," "anticipate," "achieve," "believe," "contemplate," "continue," "could," "estimate," "expect," "intends," "may," "might," "plan," "possible," "predict," "project," "should," "will," "would," and similar expressions (including the negatives of these terms or variations of them) 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 concerning future developments and their potential effects. There can be no assurance that future developments affecting Spyre will be those that have been anticipated. These forward-looking statements involve a number of risks, uncertainties (some of which are beyond Spyre's control) or 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, including our plans for

------

and timing of cohort initiation for combination therapy arms for the ongoing SKYLINE Phase 2 platform trial across different jurisdictions; the potential for final data not being consistent with or different than the interim data reported for our programs; the potential impact of Trump Administration policies and changes in law on our business; impacts of adverse events or disappointing results in clinical trials of third parties, including our competitors developing product candidates that target similar mechanisms of action and/or indications as our product candidates; and those uncertainties and factors described under the heading "Risk Factors," "Risk Factor Summary" and "Note about Forward-Looking Statements" in Spyre's most recent Annual Report on Form 10-K, as supplemented and updated by subsequent Quarterly Reports on Form 10-Q and Current Reports on Form 8-K that the Company has filed or will file with the SEC, as well as discussions of potential risks, uncertainties, and other important factors included in other filings by Spyre from time to time. Should one or more of these risks or uncertainties materialize, or should any of Spyre's assumptions prove incorrect, actual results may vary in material respects from those projected in these forward-looking statements. Nothing in this press release should be regarded as a representation by any person that the forward-looking statements set forth therein will be achieved or that any of the contemplated results of such forward-looking statements will be achieved. 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. This press release does not purport to summarize all of the conditions, risks and other attributes of an investment in Spyre.

**For Investors:** 

Eric McIntyre

VP of Finance and Investor Relations

Spyre Therapeutics

Eric.mcintyre@spyre.com

**For Media:** 

Josie Butler, 1AB

josie@1abmedia.com

<br>