What the changes say
- Capital needs and an accumulated deficit of $1.1 billion remain central risks as Spyre funds development of its programs.
- FDA disruption, healthcare-policy changes, compliance obligations, and AI regulation receive substantially greater emphasis.
- Risks increasingly cover licensed technology, foreign patents, engineered-antibody litigation, cybersecurity, and the SPY001/SPY002/SPY072/SPY003 portfolio.
What changed since the prior 10-K
New
- NewRisks Related to Our Financial Condition and Capital Requirements
accumulated deficit of $1.1 billion. We will need to raise substantial additional capital to continue to fund our operations in the future
Spyre may exhaust capital sooner than expected and need dilutive financing, debt, collaborations, or program cuts to continue operations.
- NewRisks Related to Government Regulation
We may be negatively impacted by changes in law or other policy, including healthcare reform initiatives
Healthcare reform, new laws, and current-administration policies could delay approvals, increase costs, or prevent commercialization.
- NewRisks Related to Government Regulation
See the section titled “Business – Government Regulation – Other Healthcare Laws and Compliance Requirements” in this Annual Report for a more detailed description of certain laws that may affect our ability to operate
Violations of healthcare laws could trigger fines, criminal penalties, exclusion from Medicare or Medicaid, and operational restructuring.
- NewRisks Related to Government Regulation
Disruptions at the FDA and other government agencies, including as a result of the government shutdown, could negatively affect the review of our regulatory submissions, which could negatively impact our business
FDA shutdowns, layoffs, funding constraints, leadership changes, or policy uncertainty could delay regulatory-submission reviews.
- NewRisks Related to Our Intellectual Property
Our technology licensed from various third parties may be subject to retained rights or may be affected by our failure to comply with obligations under license agreements or other disruptions to business relationships with licensors resulting in loss of license rights that are important to our business
Licensors may retain technology rights, while missed development milestones, infringement actions, or relationship disruptions could cause Spyre to lose important licenses.
- NewRisks Related to Our Intellectual Property
We have limited foreign intellectual property rights and may not be able to protect our intellectual property and proprietary rights throughout the world
Limited patent protection outside the United States may let competitors use Spyre technology or export competing products into difficult-to-enforce jurisdictions.
- NewRisks Related to Our Intellectual Property
their intellectual property rights, the outcome of which would be uncertain and may prevent, delay or otherwise interfere with our product discovery and development efforts
Unsettled engineered-antibody intellectual-property rights could produce litigation that blocks, delays, or interferes with product development.
- NewRisks Related to Employee Matters, Managing Growth and Other Risks Related to Our Business
access to, use of, or destruction of proprietary, confidential, employee, or personal data, which could result in additional costs, loss of revenue, significant liabilities, harm to our brand, and material disruption to our business
Cyberattacks or data loss affecting Spyre, CROs, clinical sites, suppliers, or other vendors could disrupt operations and expose confidential or personal information.
- NewRisks Related to Employee Matters, Managing Growth and Other Risks Related to Our Business
Our expanding use of AI exposes us to operational, regulatory, legal, and ethical risks that could adversely affect our business, reputation, financial condition, and results of operations
Increasing use of AI and machine learning could create bias, validation, cybersecurity, privacy, intellectual-property, liability, and clinical-quality problems.
- NewRisks Related to Employee Matters, Managing Growth and Other Risks Related to Our Business
to adjust business practices to comply with developing laws. Several governmental authorities have already proposed or enacted laws and other guidance governing AI
FDA and European AI requirements, including validation, traceability, explainability, and privacy rules, could increase costs, delay reviews, or create liability.
- NewRisks Related to Our Common Stock
interest in any shares of our capital stock shall be deemed to have notice of and to have consented to this provision of our Certificate of Incorporation and Bylaws
Spyre’s federal forum provision requires Securities Act claims to be brought in federal court rather than state court.
Dropped
- DroppedRisks Related to Discovery, Development and Commercialization
collaborator must conduct extensive nonclinical tests and clinical trials to demonstrate the safety and efficacy in humans of our programs and future product candidates
- DroppedRisks Related to Discovery, Development and Commercialization
permitted to market or promote these programs, or any other programs, before we receive marketing approval from the FDA and comparable foreign regulatory authorities, and we may never receive such marketing approvals
- DroppedRisks Related to Discovery, Development and Commercialization
the general patient population and by medical personnel. Any of these occurrences could harm our business, financial condition, results of operations and prospects significantly
- DroppedRisks Related to Government Regulation
We may face difficulties from healthcare legislative reform measures and other changes in law
- DroppedRisks Related to Our Intellectual Property
Our technology licensed from various third parties may be subject to retained rights
- DroppedRisks Related to Our Common Stock
Moreover, the capital markets in general have experienced substantial volatility that has often been unrelated to the operating performance of individual companies. These broad market fluctuations may also adversely affect the trading price of our common stock
- DroppedRisks Related to Our Common Stock
delisting proceedings by the stock exchange on which our common shares are listed, or sanctions or investigations by the SEC or other regulatory authorities, which would require additional financial and management resources
Delays or unforeseen events in collaborator-run nonclinical studies and clinical trials.
- DroppedRisks Related to Our Common Stock
If we fail to maintain proper and effective internal controls, our ability to produce accurate financial statements on a timely basis could be impaired, investors may lose confidence in the accuracy and completeness of our financial reports and the market price of our common stock may be negatively affected
- DroppedRisks Related to Our Common Stock
As a public company, we incur significant legal, accounting, insurance, and other expenses, and our management and other personnel have and will need to continue to devote a substantial amount of time to compliance initiatives resulting from operating as a public company
Uncertainty over obtaining FDA approval and limitations on marketing programs before approval.
Reworded
- 97% rewrittenRisks Related to Our Financial Condition and Capital Requirements
We have historically incurred losses, have a limited operating history on which to assess our business, and anticipate that we will continue to incur significant losses for the foreseeable future
Loss figures moved to 2025, 2024, and 2023, with 2025 net loss of $155.2 million replacing the prior-year period.
- 91% rewrittenRisks Related to Government Regulation
Our business operations and current and future arrangements with investigators, healthcare professionals, consultants, third-party payors, patient organizations, patients and others will be subject to applicable healthcare regulatory laws, which could expose us to penalties
The healthcare-law warning omits the prior explicit statement that compliance with these requirements would involve substantial costs.
Was: Our business operations and current and future arrangements with investigators, healthcare professionals, consultants, third-party payors, patient organizations and customers will be subject to applicable healthcare regulatory laws, which could expose us to penalties
- 91% rewrittenRisks Related to Our Common Stock
If equity research analysts do not publish research or reports, or publish unfavorable research or reports, about us, our business, or our market, our stock price and trading volume could decline
No substantive change; the warning still concerns analyst coverage, unfavorable research, stock price, and trading-volume declines.
- 89% rewrittenRisks Related to Employee Matters, Managing Growth and Other Risks Related to Our Business
Our employees, independent contractors, consultants, commercial collaborators, principal investigators, CROs, CMOs, suppliers and vendors may engage in misconduct or other improper activities, including noncompliance with regulatory standards and requirements
No substantive change; the warning still covers misconduct by employees, CROs, CMOs, collaborators, suppliers, and other representatives.
- 81% rewrittenRisks Related to Discovery, Development and Commercialization
We are substantially dependent on the success of our SPY001, SPY002, SPY072 and SPY003 programs, alone or in combination, and our current and planned clinical trials of such programs may not be successful
SPY072 was added to the key portfolio, and the risk now highlights majority resource allocation and the Phase 2 IBD platform trial.
Was: We are substantially dependent on the success of our three most advanced programs, SPY001, SPY002 and SPY003, alone or in combination, and our current and planned clinical trials of such programs may not be successful
- 76% rewrittenRisks Related to Discovery, Development and Commercialization
If we encounter difficulties enrolling participants in our current and future clinical trials, our clinical development activities could be delayed or otherwise adversely affected
Enrollment risks now specifically identify disease prevalence, eligibility criteria, site proximity, trial design, and recruiting qualified investigators.
- 73% rewrittenRisks Related to Government Regulation
We may not be able to meet requirements for the chemistry, manufacturing and control of our programs
The manufacturing warning is substantively unchanged and continues to cover FDA, foreign-regulator, formulation, device, validation, stability, and quality requirements.
- 72% rewrittenRisks Related to Discovery, Development and Commercialization
We are conducting and may conduct future clinical trials for our programs at sites in the United States and various other jurisdictions, and the FDA and comparable foreign regulatory authorities may not accept data from such trials
The warning now covers trials in various countries and states that regulators may reject foreign data entirely, with detailed U.S.-applicability conditions.
Was: We are conducting and may conduct future clinical trials for our programs at sites outside the United States, and the FDA may not accept data from trials conducted in such locations
- 70% rewrittenRisks Related to Discovery, Development and Commercialization
We face competition from entities that have developed or may develop programs for the diseases and/or mechanisms of action targeted by our product candidates
Was: We face competition from entities that have developed or may develop programs for the diseases addressed by our product candidates
- 64% rewrittenRisks Related to Employee Matters, Managing Growth and Other Risks Related to Our Business
Our ability to use our net operating loss carryforwards and certain other tax attributes may be limited
- 50% rewrittenRisks Related to Employee Matters, Managing Growth and Other Risks Related to Our Business
In order to successfully implement our plans and strategies, we will need to grow the size of our organization and we may experience difficulties in managing this growth
- 46% rewrittenRisks Related to Government Regulation
A breakthrough therapy, fast track, or other expedited designation for our product candidates may not lead to a faster development or regulatory review or approval process, and it does not increase the likelihood that those product candidates will receive marketing approval
- 45% rewrittenRisks Related to Discovery, Development and Commercialization
Some of our programs may compete with our other programs, which could negatively impact our business and reduce our future revenue
- 42% rewrittenRisks Related to Discovery, Development and Commercialization
Preliminary, “topline” or interim data from our clinical trials that we announce or publish from time to time may change as more participant data become available and are subject to audit and verification procedures
- 41% rewrittenRisks Related to Our Common Stock
Anti-takeover provisions in our charter documents and under Delaware law and the terms of some of our contracts could make an acquisition of us more difficult and may prevent attempts by our stockholders to replace or remove our management
- 37% rewrittenRisks Related to Our Common Stock
The market price of our common stock has historically been volatile, and the market price of our common stock may decline in the future
- 34% rewrittenRisks Related to Discovery, Development and Commercialization
Our approach to the discovery and development of our programs is unproven, and we may not be successful in our efforts to build a pipeline of programs with commercial value
- 30% rewrittenRisks Related to Government Regulation
Even if we are able to commercialize any product candidates, due to unfavorable pricing regulations and/or third-party coverage and reimbursement policies, we may not be able to offer such product candidates at competitive prices, which would seriously harm our business
- 29% rewrittenRisks Related to Employee Matters, Managing Growth and Other Risks Related to Our Business
We may be subject to adverse legislative or regulatory tax changes that could negatively impact our financial condition
- 27% rewrittenRisks Related to Employee Matters, Managing Growth and Other Risks Related to Our Business
Our future growth may depend, in part, on our ability to operate in foreign markets, where we would be subject to additional regulatory burdens and other risks and uncertainties
- 22% rewrittenRisks Related to Our Reliance on Third Parties
We currently rely on our collaborations and licensing arrangements with third parties, including Paragon, for a substantial portion of our discovery capabilities and in-licenses
- 22% rewrittenRisks Related to Our Common Stock
We are no longer a “smaller reporting company” within the meaning of the Securities Act and as a result we are or will be subject to certain enhanced disclosure requirements which will require us to incur significant expenses and expend time and resources
- 21% rewrittenRisks Related to Discovery, Development and Commercialization
If we do not achieve our projected development goals in the time frames we announce and expect, the commercialization of our product candidates may be delayed and our expenses may increase and, as a result, our stock price may decline
- 20% rewrittenRisks Related to Employee Matters, Managing Growth and Other Risks Related to Our Business
We maintain our cash at financial institutions, often in balances that exceed federally-insured limits. The failure of financial institutions could adversely affect our ability to pay our operational expenses or make other payments
All 64 risk factors
Headings as the filing states them, in filing order.
Risks Related to Our Financial Condition and Capital Requirements
- 01We will need to raise additional capital, and if we are unable to do so when needed, we will not be able to continue as a going concern
- 02Any of these events could have a material adverse effect on our business, operating results and prospects. Even if successful in raising new capital, we could be limited in the amount of capital we raise due to investor demand restrictions placed on the amount of capital we raise or other reasons
- 03We have never generated any revenue from product sales and may never be profitable
- 04We have historically incurred losses, have a limited operating history on which to assess our business, and anticipate that we will continue to incur significant losses for the foreseeable future97% rewritten
- 05accumulated deficit of $1.1 billion. We will need to raise substantial additional capital to continue to fund our operations in the futureNew
- 06Raising additional capital may cause dilution to our stockholders, restrict our operations, or require us to relinquish rights
Risks Related to Discovery, Development and Commercialization
- 07We face competition from entities that have developed or may develop programs for the diseases and/or mechanisms of action targeted by our product candidates70% rewritten
- 08We are substantially dependent on the success of our SPY001, SPY002, SPY072 and SPY003 programs, alone or in combination, and our current and planned clinical trials of such programs may not be successful81% rewritten
- 09If we do not achieve our projected development goals in the time frames we announce and expect, the commercialization of our product candidates may be delayed and our expenses may increase and, as a result, our stock price may decline21% rewritten
- 10Any drug delivery device that we potentially use to deliver our product candidates may have its own regulatory, development, supply and other risks
- 11Our approach to the discovery and development of our programs is unproven, and we may not be successful in our efforts to build a pipeline of programs with commercial value34% rewritten
- 12Development of combination therapies may present more or different challenges than development of monotherapies
- 13If we encounter difficulties enrolling participants in our current and future clinical trials, our clinical development activities could be delayed or otherwise adversely affected76% rewritten
- 14Preliminary, “topline” or interim data from our clinical trials that we announce or publish from time to time may change as more participant data become available and are subject to audit and verification procedures42% rewritten
- 15We may expend our limited resources to pursue a particular program and fail to capitalize on programs that may be more profitable or for which there is a greater likelihood of success
- 16Some of our programs may compete with our other programs, which could negatively impact our business and reduce our future revenue45% rewritten
- 17We are conducting and may conduct future clinical trials for our programs at sites in the United States and various other jurisdictions, and the FDA and comparable foreign regulatory authorities may not accept data from such trials72% rewritten
Risks Related to Government Regulation
- 18We may not be able to meet requirements for the chemistry, manufacturing and control of our programs73% rewritten
- 19Our product candidates for which we intend to seek approval as biologics may face competition sooner than anticipated
- 20We may be negatively impacted by changes in law or other policy, including healthcare reform initiativesNew
- 21Our business operations and current and future arrangements with investigators, healthcare professionals, consultants, third-party payors, patient organizations, patients and others will be subject to applicable healthcare regulatory laws, which could expose us to penalties91% rewritten
- 22See the section titled “Business – Government Regulation – Other Healthcare Laws and Compliance Requirements” in this Annual Report for a more detailed description of certain laws that may affect our ability to operateNew
- 23Even if we are able to commercialize any product candidates, due to unfavorable pricing regulations and/or third-party coverage and reimbursement policies, we may not be able to offer such product candidates at competitive prices, which would seriously harm our business30% rewritten
- 24Governments outside the United States tend to impose strict price controls, which may adversely affect our revenue, if any
- 25A breakthrough therapy, fast track, or other expedited designation for our product candidates may not lead to a faster development or regulatory review or approval process, and it does not increase the likelihood that those product candidates will receive marketing approval46% rewritten
- 26Disruptions at the FDA and other government agencies, including as a result of the government shutdown, could negatively affect the review of our regulatory submissions, which could negatively impact our businessNew
Risks Related to Our Intellectual Property
- 27Our ability to obtain and protect our patents and other proprietary rights is uncertain, exposing us to the possible loss of competitive advantage
- 28We may not be successful in obtaining or maintaining necessary rights to our programs through acquisitions and in-licenses
- 29We may be subject to patent infringement claims or may need to file claims to protect our intellectual property, which could result in substantial costs and liability and prevent us from commercializing our potential products
- 30We may be subject to claims that we have wrongfully hired an employee from a competitor or that our employees, consultants or independent contractors have wrongfully used or disclosed confidential information of third parties
- 31Changes to patent laws in the United States and other jurisdictions could diminish the value of patents in general, thereby impairing our ability to protect our products
- 32Obtaining and maintaining patent protection depends on compliance with various procedural, document submissions, fee payment and other requirements imposed by governmental patent agencies, and our patent protection could be reduced or eliminated for non-compliance with these requirements
- 33We may not identify relevant third-party patents or may incorrectly interpret the relevance, scope or expiration of a third-party patent, which might adversely affect our ability to develop and market our products
- 34We may become subject to claims challenging the inventorship or ownership of our patents and other intellectual property
- 35Patent terms may be inadequate to protect the competitive position of our product candidates for an adequate amount of time
- 36Our technology licensed from various third parties may be subject to retained rights or may be affected by our failure to comply with obligations under license agreements or other disruptions to business relationships with licensors resulting in loss of license rights that are important to our businessNew
- 37We have limited foreign intellectual property rights and may not be able to protect our intellectual property and proprietary rights throughout the worldNew
- 38their intellectual property rights, the outcome of which would be uncertain and may prevent, delay or otherwise interfere with our product discovery and development effortsNew
Risks Related to Our Reliance on Third Parties
- 39We currently rely on our collaborations and licensing arrangements with third parties, including Paragon, for a substantial portion of our discovery capabilities and in-licenses22% rewritten
Risks Related to Employee Matters, Managing Growth and Other Risks Related to Our Business
- 40In order to successfully implement our plans and strategies, we will need to grow the size of our organization and we may experience difficulties in managing this growth50% rewritten
- 41We are highly dependent on our key personnel and anticipate hiring new key personnel. If we are not successful in attracting and retaining highly qualified personnel, we may not be able to successfully implement our business strategy
- 42Our future growth may depend, in part, on our ability to operate in foreign markets, where we would be subject to additional regulatory burdens and other risks and uncertainties27% rewritten
- 43Our estimates of market opportunity and forecasts of market growth may prove to be inaccurate, and even if the markets in which we compete achieve the forecasted growth, our business may not grow at similar rates, or at all
- 44Our employees, independent contractors, consultants, commercial collaborators, principal investigators, CROs, CMOs, suppliers and vendors may engage in misconduct or other improper activities, including noncompliance with regulatory standards and requirements89% rewritten
- 45access to, use of, or destruction of proprietary, confidential, employee, or personal data, which could result in additional costs, loss of revenue, significant liabilities, harm to our brand, and material disruption to our businessNew
- 46Our expanding use of AI exposes us to operational, regulatory, legal, and ethical risks that could adversely affect our business, reputation, financial condition, and results of operationsNew
- 47to adjust business practices to comply with developing laws. Several governmental authorities have already proposed or enacted laws and other guidance governing AINew
- 48Our ability to use our net operating loss carryforwards and certain other tax attributes may be limited64% rewritten
- 49If we fail to comply with environmental, health and safety laws and regulations, we could become subject to fines or penalties or incur costs that could have a material adverse effect on the success of our business
- 50We may be subject to adverse legislative or regulatory tax changes that could negatively impact our financial condition29% rewritten
- 51We may acquire businesses or products, or form strategic alliances, in the future, and may not realize the benefits of such acquisitions
- 52We maintain our cash at financial institutions, often in balances that exceed federally-insured limits. The failure of financial institutions could adversely affect our ability to pay our operational expenses or make other payments20% rewritten
Risks Related to Our Common Stock
- 53The market price of our common stock has historically been volatile, and the market price of our common stock may decline in the future37% rewritten
- 54Anti-takeover provisions in our charter documents and under Delaware law and the terms of some of our contracts could make an acquisition of us more difficult and may prevent attempts by our stockholders to replace or remove our management41% rewritten
- 55interest in any shares of our capital stock shall be deemed to have notice of and to have consented to this provision of our Certificate of Incorporation and BylawsNew
- 56We do not anticipate that we will pay any cash dividends in the foreseeable future
- 57Future sales of shares by existing stockholders could cause our stock price to decline
- 58Future sales and issuances of equity and debt could result in additional dilution to our stockholders
- 59Our principal stockholders own a significant percentage of our stock and are able to exert significant control over matters subject to stockholder approval
- 60We may become exposed to costly and damaging liability claims, either when testing our programs in the clinic or at the commercial stage, and our product liability insurance may not cover all damages from such claims
- 61Litigation costs and the outcome of litigation could have a material adverse effect on our business
- 62We continue to incur significant costs and demands upon management as a result of complying with the laws and regulations regulating public companies
- 63We are no longer a “smaller reporting company” within the meaning of the Securities Act and as a result we are or will be subject to certain enhanced disclosure requirements which will require us to incur significant expenses and expend time and resources22% rewritten
- 64If equity research analysts do not publish research or reports, or publish unfavorable research or reports, about us, our business, or our market, our stock price and trading volume could decline91% rewritten
Other Spyre Therapeutics 10-Ks
- FY2024 10-K risk factors62 risks
This company has no prior year filing and is dominated by risks of capital requirements, clinical trials, and intellectual property protection.
Filed Feb 27, 2025
About this page
The headings are the filing's own. The one-line readings and the overview are automated and can be wrong: read Item 1A of the 10-K for the exact wording.