Summit Therapeutics Inc
For the period ended Dec 31, 2024. Filed Feb 24, 2025.
View on SEC.govAbout this filing
A company's yearly report to the SEC, with audited financial statements. It is the fullest account a company gives of its business, its finances and the risks it sees.
FY2024 · Filed Feb 24, 2025
SMMT$17.84+9.2%Stored close · as of Nov 9, 2026
What changed in Risk Factors?
Read the current filingPrevious report: 10-K
Period ended 2023-12-31; filed 2024-02-20.
0001599298-24-000031
Item 1A. Risk FactorsCurrent report: 10-K
Period ended 2024-12-31; filed 2025-02-24.
0001599298-25-000048
Item 1A. Risk FactorsThe baseline is this issuer’s latest earlier reporting period of the same form that was filed before the current report. A previous 10-Q is a different quarter, not a year-over-year comparison. Amendments are excluded.
Compared 404 previous paragraphs and 411 current paragraphs.
242 unchanged; 129 reworded; 38 added; 30 removed; 3 previous and 2 current paragraphs rearranged.
Tables are not compared: 0 previous and 0 current tables excluded. Dates, whitespace, punctuation and numbering changes are ignored; changes to financial figures remain significant.
A changed paragraph is not evidence that risk increased or decreased. An unchanged paragraph does not establish that risk stayed the same.
Added paragraphs (38)
Current report
•obtaining timely and adequate pricing and reimbursement from payors;
Current report
If ongoing Phase II or Phase III clinical trials conducted by Summit or Akeso involving ivonescimab, or future clinical trial results, are unfavorable, the size and scope, including the number of patients, primary and secondary endpoints, and population of patients, of ongoing and future clinical trials could be impacted. Further, we may incur additional product development costs, experience delays or become unable to obtain regulatory approval of ivonescimab for the whole clinical trial or the approved label may be restricted to one cohort or subgroup, thereby adversely affecting our business.
Current report
•in clinical trials that include multiple endpoints, unfavorable results in any individual endpoint may limit any regulatory approval or commercialization of the applicable product candidate;
Current report
•preclinical tests or clinical trials not beginning as planned, needing to be restructured or not being completed on schedule, or at all.
Current report
For those patients EGFR mutations, there are several targeted therapies that have also been approved in the front-line setting, including, but not limited to, osimertinib (AstraZeneca) with or without chemotherapy and amivantamab and lazertinib (both from Johnson & Johnson). The proposed indication for ivonescimab in the HARMONi clinical trial setting, post third-generation EGFR-TKIs such as osimertinib or lazertinib, may face competition from amivantamab plus chemotherapy, as well as clinical candidates such as as datopotamab deruxetecan (AstraZeneca and Daiichi Sankyo) and patritumab deruxtecan (Merck and Daiichi Sankyo).
Current report
There are several PD-(L)1/VEGF(R2) bispecific antibodies in development or with planned development globally. These include, but are not limited to BNT327, which is owned by BioNTech SE, which has begun conducting Phase III clinical studies globally, and LM-299, which was licensed globally by Merck & Co., Inc. in November 2024.
Current report
Multiple in-class and related competitors for our product candidates are and can be developed, our competitive position could be compromised because it may be more difficult for us to obtain marketing approval for that product candidate and market acceptance of that product candidate due to a similar competitor. In addition, any product that competes with another approved product typically must demonstrate compelling advantages in efficacy, convenience, tolerability or safety, or some combination of these factors, to gain regulatory approvals, overcome price competition and be commercially successful.
Current report
If we fail to plan, execute and manage our growth effectively, our ability to develop and commercialize products could suffer.
Current report
We expect that if our clinical product candidates continue to progress in development, and we continue to build our clinical operations and invest in our commercial operations, we will require significant additional investment in personnel, infrastructure and resources, Our ability to achieve our research, development and commercialization objectives depends on our ability to respond timely and effectively to these demands and expand our internal organization, systems and controls to accommodate additional anticipated growth. The expansion of our operations may lead to significant costs and may divert our management and business resources. Failure to effectively manage our growth may impact our ability to successfully develop and commercialize our product candidates.
Current report
Risks Related to our Dependencies on Third Parties
Current report
We are exposed to the possibility of product supply disruption and increased costs in the event of changes in the policies of the U.S. or Chinese governments, political unrest or unstable economic conditions in China. New legislation, regulations or court decisions may impede, delay, limit, or increase the cost of manufacturing our therapeutic candidates. Such events could result in our clinical or commercial supply of drug being interrupted or limited, which could harm our business.
Current report
The U.S. Department of the Treasury and the IRS have released proposed and final regulations and other interpretive guidance
Current report
relating to the TCJA and the IRA. Any significant variance from our current interpretation of such regulations and interpretive
Current report
guidance could result in a change in our analysis of the application of the TCJA and the IRA to us and its impact on our
Current report
Furthermore, we are subject to various complex and evolving U.S. federal, state, local and non-U.S. tax laws. U.S. federal,
Current report
state, local and non-U.S. tax laws, policies, statutes, rules, regulations or ordinances could be interpreted, changed, modified or applied adversely to us, in each case, possibly with retroactive effect. Any significant variance in our interpretation of current tax laws, including as result of the release of final Treasury Regulations or other interpretive guidance implementing, or a successful challenge of one or more of our tax positions by the IRS or other state, local or non-U.S. tax authorities could increase our future tax liabilities and adversely affect our operating results and cash flows.
Current report
In the event that our NOL carryforwards or other tax attributes are subject to future limitation (including due to an ownership change under Sections 382 and 383 of the Code), deductions are not generated as expected, or if one or more of our tax positions are successfully challenged by the IRS or other tax authorities (in a tax audit or otherwise), our future tax liabilities may be greater than expected, which could adversely affect our operating results and cash flows.
Current report
In the U.S., the ACA substantially changed the way healthcare is financed by both governmental and private insurers, and significantly impacts the pharmaceutical industry. The ACA was intended to broaden access to health insurance, reduce or constrain the growth of healthcare spending, enhance remedies against healthcare fraud and abuse, add new transparency requirements for healthcare and health insurance industries, impose new taxes and fees on pharmaceutical and medical device manufacturers, and impose additional health policy reforms. Since its passage, there have been significant ongoing efforts to modify or eliminate the ACA and potential future legislative, judicial or regulatory actions related to the ACA, and any effects on us, are uncertain.
Current report
Other legislative changes have been proposed and adopted since passage of the ACA. These have, among other things, reduced Medicare payments to several types of providers, including hospitals, imaging centers and cancer treatment centers, and increased the statute of limitations period for the government to recover overpayments to providers.
Current report
It is unknown what form any future changes or any law would take under the Trump Administration and how or whether it may affect our business in the future. We expect that changes or additions to the ACA, the Medicare and Medicaid programs, changes allowing the federal government to directly negotiate drug prices and changes stemming from other healthcare reform measures, especially with regard to healthcare access, financing or other legislation in individual states, could have a material adverse effect on the healthcare industry. In addition, the ACA has also been subject to challenges in the courts, which remain ongoing.
Current report
The Company’s reputation or relationships with its stakeholders and other third parties could also be adversely impacted as a result of, among other things, (i) stakeholder or third-party perceptions of statements, if any, made by the Company, its employees, agents, any industry trade associations, or other third parties; or (ii) public pressure from investors or policy groups to change the Company's policies. Such statements or initiatives with respect to ESG matters are increasingly subject to heightened scrutiny from the public and governmental authorities, as well as other parties. Certain regulators, such as the SEC and various state agencies, as well as nongovernmental organizations and other private actors have filed lawsuits under various securities and consumer protection laws alleging that certain ESG statements, goals or standards were misleading, false or otherwise deceptive. On the other hand, the Company could face criticism from certain “anti-ESG” parties if it were to make environmental or social commitments or pursue certain environmental or social initiatives that are alleged to be inherently political or polarizing in nature and could subject the Company to pressure in the media or through other means, which could adversely affect our reputation, business, financial performance, market access and growth.
Current report
Our success depends in large part on our ability to obtain and maintain patent protection in the United States and other countries for our proprietary technology and products. We seek to protect our proprietary position by filing patent applications in strategic jurisdictions, including the United States, Europe and other key markets. However, this process is inherently costly, time-consuming, and uncertain. We may not successfully identify patentable aspects of our research in a timely manner, potentially missing opportunities to secure meaningful protection. Additionally, challenges such as high costs, delays in prosecution, and changes in the law could compromise our ability to file and prosecute all necessary or desirable applications. These factors may limit the scope of protection we achieve, increasing our vulnerability to competition and undermining the commercial potential of our products.
Current report
Moreover, if we license technology or product candidates from third parties in the future, we may have limited control over the preparation, filing, prosecution, or enforcement of the associated patents, leaving us vulnerable to decisions that may not align with our goals or interests. For example, under our License Agreement with Akeso, patent prosecution and enforcement in the Licensed Territory are subject to consultation and cooperation with Akeso. If we cannot align on our patent strategy, this could impact the patentability or enforcement of the licensed intellectual property. Actions or statements during patent prosecution outside of the Licensed Territory could significantly influence the validity of any patent obtained within the Licensed Territory, potentially undermining our competitive position. Additionally, Akeso owned patents and patent applications, which are non-exclusively licensed to Summit under the License Agreement, are under the control of Akeso. Akeso’s prosecution, enforcement, and licensing strategies with regard to their owned patents and patent applications may conflict with our objectives.
Current report
Even if we are successful in defending against intellectual property claims, litigation or related legal proceedings can still impose significant financial and operational burdens. These disputes often require us to allocate substantial resources, including legal fees and other expenses, which can strain our finances and reduce funds available for critical business functions like development, sales, and marketing. Moreover, these proceedings can pull key technical and management personnel away from their normal responsibilities, disrupting our operations and slowing our progress.
Current report
In addition, public announcements of the outcomes of hearings, motions or other interim proceedings or developments could have far reaching consequences. If securities analysts or investors interpret these developments negatively, it could have a substantial adverse effect on the price of our shares of common stock. Beyond the reputational impact, such litigation or proceedings could severely impact our business by diverting critical resources away from development, sales, marketing, and distribution efforts. Our ability to manage these legal challenges effectively may be constrained by limited financial and operational resources, especially when compared to competitors with deeper financial reserves who may weather such disputes more effectively. As a result, the cumulative costs, management distraction, and lingering uncertainties stemming from patent litigation or similar proceedings could substantially impair our ability to compete and succeed in the marketplace.
Current report
The risk of cybersecurity incidents may be heightened as a result of our some of our employees utilizing a remote working environment, which may be less secure and more susceptible to cybersecurity incidents. Additionally, the prevalent use of mobile devices that access our sensitive data increases the risk of data breaches. Advances in computer capabilities, discoveries in the field of artificial intelligence, cryptography, inadequate facility security or other developments may result in a compromise or breach of the technology we use to safeguard sensitive information.
Current report
Further, there are regulations related to data privacy and security that are specific to our industry. For example, the U.S. Department of Health and Human Services has issued rules governing the use, disclosure, and security of protected health information, and the FDA has issued further guidance concerning cybersecurity for medical devices. HIPAA, as amended by HITECH, and their respective implementing regulations impose significant obligations on covered entities and business associates to safeguard the privacy, security, and integrity of individually identifiable health information, also known as protected health information.
Current report
We or the third parties we rely on may be adversely affected by social unrest or terrorism.
Current report
Social instability, disruption, or widespread destruction in areas where we operate or in significant markets could have a negative impact on our business. Events, including war, terrorism, riot, civil insurrection or social unrest, regardless of cause, could result in material adverse effects on our ability to operate, the ability of our suppliers to operate, and macroeconomic conditions. Such negative impacts may adversely affect the Company’s business, results of operations and financial condition.
Current report
•slowed enrollment in and delayed execution of clinical trials due to hospital closures to clinical trials or patient hesitation to enroll in clinical trials;
Current report
•impact of infection of patients on the outcomes of clinical trials; and
Current report
•the acquisition activity and licensing and collaboration efforts of our competitors and large biopharmaceutical companies;
Current report
We are a “large accelerated filer” and the reduced disclosure requirements applicable to “non-accelerated filers,” and, starting in the first fiscal quarter of 2025, "smaller reporting companies" previously available to us no longer apply.
Current report
As of June 30, 2024, the market value of our common stock that was held by non-affiliates exceeded $700 million, and as a result, we now qualify as a “large accelerated filer.” As such, we incur significant additional expenses in complying with the Sarbanes-Oxley Act of 2002 and rules implemented by the SEC.
Current report
Additionally, if we or our independent registered public accounting firm identifies deficiencies in our internal control over financial reporting that are deemed to be material weaknesses, the market price of our stock could decline and we could be subject to sanctions or investigations by the SEC or other regulatory authorities, which would require additional financial and management resources. Additionally, we expect that our loss of “non-accelerated filer” and “smaller reporting company” status will require additional attention from management and will result in increased costs to us, which could include higher legal fees, accounting fees and fees associated with investor relations activities, among others.
Removed paragraphs (30)
Previous report
We do not currently have sufficient working capital to fund our planned operations, including fulfilling our debt obligations, for the next twelve months. There is uncertainty regarding our ability to raise additional capital and as such, there is substantial doubt regarding our ability to continue as a going concern.
Previous report
Our financial statements have been prepared under the assumption that we would continue as a going concern. However, we have concluded that there is substantial doubt about our ability to continue as a going concern, because without additional sources of funding, our cash and cash equivalents at December 31, 2023 is not sufficient for us to fund our working capital needs for the next twelve months after the date that the financial statements included in this Annual Report on Form 10-K are issued. Management’s plans concerning these matters, including raising additional capital, are described in Item 2 – Liquidity and Capital Resources – Sources of Liquidity of our financial statements included within this Annual Report on Form 10-K. However, we cannot guarantee that we will be able to obtain any or sufficient additional funding or that such funding, if available, will be obtainable on terms satisfactory to us. If we cannot continue as a going concern, our stockholders would likely lose most or all of their investment in us.
Previous report
•obtaining adequate pricing and a reimbursement profile;
Previous report
We have substantial indebtedness and may require additional indebtedness in the future, which may require us to use a substantial portion of our cash flow to service debt and limit our financial and operating flexibility.
Previous report
We have substantial indebtedness and may require additional indebtedness in the future. As of February 19, 2024, we had a total of $100 million of indebtedness outstanding under the Note Purchase Agreement. Further, the License Agreement calls for certain additional future payment obligations and we may require additional indebtedness to fund those obligations. Our existing and future indebtedness will require interest payments and need to be repaid or refinanced and could require us to divert funds identified for other purposes to service our debt. Our debt obligations could also result in cash demands and impair our liquidity position, causing financial risk for us. Diverting funds identified for other purposes for debt service may adversely affect our growth prospects. If we cannot generate sufficient cash flow from operations to service our debt, we will need to refinance our debt, dispose of assets, or issue equity to obtain necessary funds. We do not know whether we would be able to take any of these actions on a timely basis, on terms satisfactory to us, or at all.
Previous report
The Company’s failure to comply with the terms and obligations of the Note Purchase Agreement, including as a result of events beyond our control, may result in an event of default.
Previous report
The Note Purchase Agreement requires us to comply with certain repayment obligations, representations and covenants. A breach of any of these obligations, representations or covenants or the occurrence of certain other specified events could result in an event of default under the Note Purchase Agreement. Upon the occurrence of any event of default under the Note Purchase Agreement, the outstanding balance on the corresponding Note will, at the option of such lender, become immediately and automatically due and payable in cash and a default interest rate of an additional 2% per annum will apply on all outstanding obligations during the occurrence and continuance of an event of default.
Previous report
We may not be able to maintain compliance with these repayment obligations and covenants in the future and, if we fail to do so, we may not be able to obtain waivers from the lender and/or amend the covenants. Our failure to comply with the repayment obligations and covenants described above could result in an event of default, which, if not cured or waived, and if the lender accelerates, would result in us being required to repay these borrowings before their due date. If we are forced to refinance these borrowings on less favorable terms or if we are unable to refinance these borrowings, our business, financial condition, and results of operations could be materially adversely affected.
Previous report
Our product development costs will increase as we experience delays in testing or marketing approvals. We do not know whether any preclinical tests or clinical trials will begin as planned, will need to be restructured or will be completed on schedule, or at all. Significant preclinical or clinical trial delays also could shorten any periods during which we may have the
Previous report
exclusive right to commercialize our product candidates or allow our competitors to bring products to market before we do and impair our ability to successfully commercialize our product candidates and may harm our business and results of operations.
Previous report
Global economic uncertainty, changes in geopolitical conditions and political instability, changes in trade agreements and disputes, such as the conflict between Russia and Ukraine, conflict in the Middle East and other macroeconomic factors, could adversely affect our business and results of operations.
Previous report
Risks Related to our Financial and Intellectual Property Dependencies on Third Parties
Previous report
We rely on third parties to manufacture our product candidates. If our third party manufacturers divert their capacity and/or supply of materials needed for our product candidates, our ability to complete our clinical trials or eventually bring our product candidates to market may be compromised.
Previous report
NSCLC in 2023, such as Daiichi Sankyo and AstraZeneca’s datopotamab deruxetecan and Johnson & Johnson’s amivantamab and lazertinib. Finally, there are candidates in various stages of ongoing clinical trials for NSCLC, including Daiichi Sankyo and Merck with patritumab deruxtecan and AstraZeneca’s volrustomig, each currently enrolling in Phase III clinical trials.
Previous report
Our ability to use our U.S. federal, U.S. state and foreign net operating losses and other tax attributes may be limited.
Previous report
Unused U.S. federal tax losses for tax years beginning before January 1, 2018 and prior tax years will carry forward to offset future taxable income, if any, until such unused losses expire. Unused U.S. federal tax losses generated for tax year beginning after December 31, 2017 will not expire and may be carried forward indefinitely, and generally may not be carried back to prior taxable years, except that, under the CARES Act, net operating losses generated in 2018, 2019 and 2020 may be carried back to each of the five tax years preceding the tax years of such losses. Additionally, for taxable years beginning after December 31, 2020, the deductibility of such U.S. federal net operating losses is limited to 80% of our taxable income in any future taxable year. In addition, both our current and our future unused U.S. federal and state tax losses and unused U.S. federal and state research and development tax credits may be subject to limitation under Sections 382 and 383 of the Internal Revenue Code (“IRC” or “the Code”) of 1986, as amended, if we undergo an “ownership change,” generally defined as a greater than 50 percentage point change (by value) in its equity ownership by certain stockholders over a rolling three-year period. We may have experienced such ownership changes in the past, and we may experience ownership changes in the future as a result of shifts in our stock ownership, some of which are outside our control. As of December 31, 2023 and 2022, we reported U.S. federal and state gross operating loss carryforwards of approximately $53.4 million and $18.9 million, respectively, and federal research and development tax credit carryforwards of $5.3 million and $1.7 million, respectively. Our ability to utilize those net operating loss carryforwards could be limited by an “ownership change” as described above, which could result in increased tax liability to us.
Previous report
As of December 31, 2023, we reported foreign gross operating loss carryforwards of $194.5 million. Our ability to utilize those net operating loss carryforwards are dependent upon our generation of future taxable income.
Previous report
The Committee on Foreign Investment in the United States (“CFIUS”) or other regulatory agencies may modify, delay or prevent the transactions contemplated by the License Agreement.
Previous report
The Committee on Foreign Investment in the United States (“CFIUS”) has authority to review direct or indirect foreign investments in U.S. companies. Among other things, CFIUS is empowered to require certain foreign investors to make mandatory filings, to charge filing fees related to such filings and to self-initiate national security reviews of foreign direct and indirect investments in U.S. companies if the parties to that investment choose not to file voluntarily. In the case that CFIUS determines an investment to be a threat to national security, CFIUS has the power to unwind or place restrictions on the investment. Whether CFIUS has jurisdiction to review an acquisition or investment transaction depends on, among other factors, the nature and structure of the transaction, including the level of beneficial ownership interest and the nature of any information or governance rights involved. For example, investments that result in “control” of a U.S. business by a foreign person always are subject to CFIUS jurisdiction. CFIUS’s expanded jurisdiction under the Foreign Investment Risk Review Modernization Act of 2018 and implementing regulations that became effective on February 13, 2020 further includes investments that do not result in control of a U.S. business by a foreign person but afford certain foreign investors certain information or governance rights in a U.S. business that has a nexus to “critical technologies,” “critical infrastructure” and/or “sensitive personal data”.
Previous report
We believe that no mandatory filing was required in connection with the License Agreement but we have not yet determined whether we will make a voluntary filing. CFIUS may decide to modify or delay our proposed business combination, impose conditions with respect to such business combination, request the President of the United States to order us to divest all or a portion of the assets we acquired without first obtaining CFIUS approval or prohibit the License Agreement entirely. If it is determined that a mandatory filing was required to be made, it is possible that a material penalty could be assessed against the Company.
Previous report
Our success depends in large part on our ability to obtain and maintain patent protection in the United States and other countries with respect to our proprietary technology and products. We seek to protect our proprietary position by filing patent applications in the United States, in Europe and in certain additional foreign jurisdictions related to our novel technologies and product candidates that are important to our business. This process is expensive and time-consuming, and we may not be able to file and prosecute all necessary or desirable patent applications at a reasonable cost or in a timely manner. It is also possible that we will fail to identify patentable aspects of our research and development output before it is too late to obtain patent protection. Moreover, if we license technology or product candidates from third parties in the future, these license agreements may not permit us to control the preparation, filing and prosecution of patent applications, or to maintain or enforce the patents, covering the licensed technology or product candidates. These agreements could also give our licensors the right to enforce the licensed patents without our involvement, or to decide not to enforce the patents at all. Therefore, in these circumstances, these patents and applications may not be prosecuted or enforced in a manner consistent with the best interests of our business. For example, while under the collaboration and license agreement with Akeso for ivonescimab, we have the right, after a set period of time, to take control of the prosecution, maintenance and enforcement of certain patent applications licensed under the agreement in the Licensed Territory, prosecution is subject to consultation and cooperation with Akeso, except with regard to patent extension. If the parties cannot align this could impact patentability of the licensed intellectual property. Additionally, as actions or statements during prosecution in other territories (i.e., the non-Licensed Territory) can impact the validity of any patent obtained in the Licensed Territory, Akeso prosecution of its patent applications in the non-Licensed Territory, can have an impact on patent prosecution and validity of applications/patents that we are prosecuting, maintaining or enforcing in the Licensed Territory. Additionally, Akeso owned patents and patent applications, non-exclusively licensed to Summit under the agreement, are under the control of Akeso, Akeso’s prosecution and/or licensing strategies with regard to these patents and/or patent application may impact our business.
Previous report
Even if resolved in our favor, litigation or other legal proceedings relating to intellectual property claims may cause us to incur significant expenses, and could distract our technical and management personnel from their normal responsibilities. In addition, there could be public announcements of the results of hearings, motions or other interim proceedings or developments. If securities analysts or investors perceive these results to be negative, it could have a substantial adverse effect on the price of our shares of common stock. Such litigation or proceedings could substantially increase our operating losses and reduce the resources available for development, sales, marketing or distribution activities. We may not have sufficient financial or other resources to adequately conduct such litigation or proceedings. Some of our competitors may be able to sustain the costs of such litigation or proceedings more effectively than we can because of their greater financial resources. Accordingly, costs and lost management time, as well as uncertainties resulting from the initiation and continuation of patent litigation or other proceedings, could have a material adverse effect on our ability to compete in the marketplace.
Previous report
Risks Related to Corporate Governance and Employee Relations
Previous report
We are a “smaller reporting company” and the reduced disclosure requirements applicable to smaller reporting companies may make our shares of common stock less attractive to investors.
Previous report
We are a “smaller reporting company”, as defined in Rule 12b-2 under the Securities Exchange Act of 1934, as amended. We would cease to be a smaller reporting company if we have a public float in excess of $250 million or have annual revenues in excess of $100 million and a public float in excess of $700 million, determined on an annual basis.
Previous report
We expect to continue to take advantage of some or all of the exemptions available to us as a smaller reporting company. We cannot predict whether investors will find our shares of common stock less attractive if we rely on these exemptions. If some investors find our shares of common stock less attractive as a result, there may be a less active trading market for the shares and the market price of the shares may be more volatile.
Previous report
We incur increased costs as a result of operating as a company with shares of common stock that are publicly traded in the United States, and our management is required to devote substantial time to compliance initiatives.
Previous report
However, for as long as we remain a smaller reporting company, we may take advantage of certain exemptions from various reporting requirements that are applicable to other public companies that are not smaller reporting companies as described in the preceding risk factor.
Reworded paragraphs (129)
Previous wording
This section describes certain risks we face in our business. Additional risks we do not yet know of or that we currently believe are immaterial may also impair our business. If any of the events or circumstances described in this section actually occurs, our business, financial condition or operating results could suffer, and the market price of our common stock could decline. In assessing these risks, investors should also refer to the other information contained or incorporated by reference in this report and our other filings with the Securities and Exchange Commission.
Current wording
This section describes certain risks we face in our business. Additional risks we do not yet know of or that we currently believe are immaterial may also impair our business. If any of the events or circumstances described in this section actually occurs, our business, financial condition or operating results could suffer, and the market price of our common stock could decline. In assessing these risks, investors should also refer to the other information contained or incorporated by reference in this Annual Report on Form 10-K and our other filings with the SEC.
Previous wording
We are a development-stage company and have incurred significant losses since our inception. We expect to incur losses for at least the next several years and may never generate profits from operations or maintain profitability.
Current wording
We are a development-stage company and have incurred significant losses since our inception. We expect to incur losses for at least the next several years and may never generate or maintain profits.
Previous wording
We are a development-stage company and we cannot assure profitability. We expect to continue to generate operating losses for the foreseeable future. Until we can generate substantial revenue and achieve profitability, we will need to raise additional capital to fund ongoing operations and capital needs. Since inception, we have incurred significant operating losses. During the year ended December 31, 2023, we incurred a net loss of $614.9 million, and cash flows used in operating activities was $76.8 million. As of December 31, 2023 we had an accumulated deficit of $993.3 million, cash and cash equivalents of $71.4 million, short-term investments in U.S. treasury securities of $114.8 million, and current and long-term research and development tax credits receivable of $1.8 million. These losses could continue for the next several years as we invest in clinical development of ivonescimab. We expect to continue to generate operating losses for the foreseeable future. Until we can generate substantial revenue and achieve profitability, we will need to raise additional capital to fund ongoing operations and capital needs.
Current wording
We are a development-stage company and we cannot assure profitability. We expect to continue to generate operating losses for the foreseeable future. Until we can generate substantial revenue and achieve profitability, we will need to raise additional capital to fund ongoing operations and capital needs. Since inception, we have incurred significant operating losses. During the year ended December 31, 2024, we incurred a net loss of $221.3 million, and cash flows used in operating activities was $142.1 million. As of December 31, 2024 we had an accumulated deficit of $1,214.6 million, cash and cash equivalents of $104.9 million, short-term investments in U.S. treasury securities of $307.5 million, and current and long-term research and development tax credits receivable of $1.3 million. These losses could continue for the next several years as we invest in clinical development of ivonescimab. We expect to continue to generate operating losses for the foreseeable future. Until we can generate substantial revenue and achieve profitability, we will need to raise additional capital to fund ongoing operations and capital needs.
Previous wording
To become and remain profitable, we must succeed in developing and eventually either commercializing or partnering with other organizations to commercialize products that generate significant revenue. This will require us to be successful in a range of challenging activities, including completing preclinical testing and clinical trials of our product candidates, discovering additional product candidates, obtaining regulatory approval for these product candidates and manufacturing, marketing, and selling any products for which we may obtain regulatory approval. We are in the preliminary stages of many of these activities. We may never succeed in these activities and, even if we do, may never generate revenue that is significant enough to achieve profitability.
Current wording
To become and remain profitable, we must succeed in developing and eventually either commercializing or partnering with other organizations to commercialize products that generate significant revenue. This will require us to be successful in a range of challenging activities, including but not limited to completing preclinical testing and clinical trials of our product candidates, discovering additional product candidates, obtaining regulatory approval for these product candidates, and manufacturing, marketing, and selling any products for which we may obtain regulatory approval. We are in the preliminary stages of many of these activities. We may never succeed in these activities and, even if we do, may never generate revenue that is significant enough to achieve profitability.
Previous wording
We have not yet demonstrated our ability to successfully complete development of any product candidates which may make it difficult for you to evaluate the success of our business to date and to assess our future viability.
Current wording
We have not yet demonstrated an ability to successfully complete development of any product candidates, which may make it difficult for you to evaluate our success and future viability.
Previous wording
We have not yet demonstrated our ability to successfully complete development of any product candidates, obtain marketing approvals, manufacture a commercial scale product, or arrange for a third party to do so on our behalf, or conduct sales and marketing activities or otherwise obtain a partner to do so as is necessary for successful product commercialization. Consequently, any predictions you make about our future success or viability may not be as accurate as they could be if we had a longer operating history.
Current wording
We have not yet demonstrated an ability to successfully complete development of any product candidates, obtain marketing approvals, manufacture a commercial scale product, or arrange for a third party to do so on our behalf, or conduct sales and marketing activities or otherwise obtain a partner to do so, as is necessary for successful product commercialization. Consequently, any predictions you make about our future success or viability may not be as accurate as they could be if we had a longer operating history.
Previous wording
We will need substantial additional capital to fund our operations and to make payments under the License Agreement and the Note Purchase Agreement and if we fail to obtain necessary financing, we could be forced to delay, reduce or eliminate the development and commercialization of our product candidates.
Current wording
We will need substantial additional capital to fund our operations and to make payments under the License Agreement, and if we fail to obtain necessary financing, we could be forced to delay, reduce or eliminate the development and commercialization of our product candidates.
Previous wording
Conducting preclinical testing and clinical trials is a time-consuming, expensive and uncertain process that takes years to complete, and we may never generate the necessary data or results required to obtain marketing approval achieve product sales. In addition, our product candidates, if approved, may not achieve commercial success. Our commercial revenues, if any, will be derived from sales of products that we are not planning to have commercially available for several years, if at all. Accordingly, we will need to continue to rely on additional financing to achieve our business objectives. In addition, we may seek additional capital due to favorable market conditions or strategic considerations, even if we believe that we have sufficient funds for our current or future operating plans. Additional financing may not be available to us on acceptable terms, or at all.
Current wording
Conducting preclinical testing and clinical trials is a time-consuming, expensive and uncertain process that takes years to complete, and we may never generate the necessary data or results required to obtain marketing approval or achieve product sales. In addition, our product candidates, if approved, may not achieve commercial success. Our commercial revenues, if any, will be derived from sales of products that we are not planning to have commercially available for several years, if at all. Additional financing may not be available to us on acceptable terms, or at all.
Previous wording
We expect our research and development expenses to increase substantially in connection with our ongoing activities, particularly in connection with the License Agreement. In addition, if we obtain marketing approval for our potential future product candidates where we retain commercial rights or any other product candidates we develop, we expect to incur significant commercialization expenses related to product sales, marketing, distribution and manufacturing. Accordingly, we will need to obtain substantial additional funding in connection with our continuing operations. If we are unable to raise capital when needed or on attractive terms, we may be required to delay, limit, reduce or terminate our product development or future commercialization efforts or grant rights to develop and market product candidates that we would otherwise prefer to develop and market ourselves.
Current wording
We expect our research and development expenses to increase substantially in connection with our ongoing activities, particularly in connection with the License Agreement. In addition, if we obtain marketing approval for our potential future product candidates where we retain commercial rights or any other product candidates we develop, we expect to incur significant commercialization expenses related to product sales, marketing, distribution and manufacturing.
Previous wording
Our primary future capital requirements will be related to our obligations under the License Agreement.
Current wording
We expect to continue to generate operating losses for the foreseeable future. Our primary future capital requirements will be related to our obligations under the License Agreement and funding research and development efforts.
Previous wording
We expect to continue to generate operating losses for the foreseeable future. The License Agreement calls for initial consideration payments of $500 million (which have been paid), as well as total contingent payments by the Company of up to $5.0 billion, as Akeso will be eligible to receive regulatory milestones of up to $1.05 billion and commercial milestones of up to $3.45 billion, many of which will be due before the Company anticipates generating any revenue from the License Agreement. We entered into the Note Purchase Agreement to fund the initial consideration payments and we will need additional capital to fund our operations and payments under the License Agreement and the Note Purchase Agreement. We may anticipate the need for further capital raises to repay the remaining $100 million principal balance under the Note Purchase Agreement. We therefore expect to raise additional capital via issuances of equity or debt.
Current wording
The License Agreement, as amended, calls for initial consideration payments of $515 million (of which $500 million was paid in 2023 and $15 million was paid in 2024), as well as total contingent payments by the Company of up to $4.56 billion, as Akeso will be eligible to receive regulatory milestones of up to $1.05 billion and commercial milestones of up to $3.51 billion, many of which will be due before the Company anticipates generating any revenue from the License Agreement. We will need additional capital to fund our operations and payments under the License Agreement, which we may do via issuances of equity or debt or through global or regional partnerships in the Licensed Territory.
Previous wording
Raising additional capital may cause dilution to our investors, restrict our operations or require us to relinquish rights to our technologies or product candidates.
Current wording
Raising additional capital may cause dilution to our investors, restrict our operations or require us to relinquish rights to our product candidates.
Previous wording
Worldwide economic social, and geopolitical instability could adversely affect our operations, revenue, financial condition, or results of operations.
Current wording
Worldwide economic, social and geopolitical instability could adversely affect our operations, revenue, financial condition, results of operations or ability to raise capital.
Previous wording
Generally, worldwide economic conditions remain uncertain, particularly due to the effects of the conflict between Russia and Ukraine and the conflicts in the Middle East, including those in Gaza and Yemen, and disruptions in the banking system and financial markets, lingering COVID-19 pandemic, increased inflation and rising interest rates. The general economic and capital market conditions, both in the U.S. and worldwide, have been volatile in the past and at times have adversely affected the Company’s access to capital and increased the cost of capital. The capital and credit markets may not be available to support future capital raising activity on favorable terms. If economic conditions decline, the Company’s future cost of equity or debt capital and access to the capital markets could be adversely affected. In addition, adverse economic conditions, such as recent supply chain disruptions and labor shortages and persistent inflation, may negatively impact our business. These economic conditions make it more difficult for us to accurately forecast and plan our future business activities.
Current wording
Generally, worldwide economic conditions remain uncertain, particularly due to the effects of the conflict between Russia and Ukraine and the conflicts in the Middle East, including those in Gaza, Lebanon and Yemen, and disruptions in the banking system and financial markets, increased inflation and rising interest rates. The general economic and capital market conditions, both in the U.S. and worldwide, have been volatile in the past and at times have adversely affected the Company’s access to capital and increased the cost of capital. The ongoing geopolitical conflicts in various parts of the world, including but not limited to Russia, Ukraine and Middle East, are difficult to predict and could adversely affect our business in the Licensed Territory as well as our ability to enroll patients and supply ivonescimab to various clinical sites in the world, resulting in adverse effects on our business and financial condition.
Previous wording
We depend heavily on the success of ivonescimab. If we are unable to successfully develop or commercialize ivonescimab, or experience significant delays in doing so, we may extend the period in which we will incur significant financial losses as an organization.
Current wording
We depend heavily on the success of ivonescimab. If we are unable to successfully develop or commercialize ivonescimab, or experience significant delays in doing so, we may continue to incur significant financial losses.
Previous wording
We plan to invest a significant portion of our efforts and financial resources in the development of ivonescimab, which is still in clinical development. Our ability to generate product revenues, which may not occur for several years, if ever, will depend heavily on the successful development and commercialization of ivonescimab. The success of this product candidate will depend on a number of factors, including the following:
Current wording
We have and plan to continue investing a significant portion of our efforts and financial resources in the development of ivonescimab, which is still in clinical development. Our ability to generate product revenues, which may not occur for several years, if ever, will depend heavily on the successful development and commercialization of ivonescimab. The success of this product candidate depends on a number of factors, including, but not limited to, the following:
Previous wording
•Ability to use preclinical data and data of patients from Akeso’s clinical trials in China supporting registration studies and regulatory approval;
Current wording
•our ability to use preclinical data and data of patients from Akeso’s clinical trials in China supporting registration studies and regulatory approval;
Previous wording
•receipt of clinical trial approvals and future marketing approvals from applicable regulatory authorities in all the countries where we intend to conduct clinical trials and/or seek marketing approval;
Current wording
•receipt of clinical trial approvals and future marketing approvals from applicable regulatory authorities in all the countries where we intend to conduct clinical trials or seek marketing approval; the costs of post-marketing studies, if any, that could be required by regulatory authorities in jurisdictions where approval is obtained;
Previous wording
If we do not achieve one or more of these factors in a timely manner or at all, we could experience significant delays or an inability to successfully commercialize ivonescimab, which would materially harm our business.
Current wording
Risks and uncertainties related to these factors could cause us to experience significant delays or an inability to successfully commercialize ivonescimab, which would materially harm our business.
Previous wording
Clinical development involves a lengthy and expensive process with an uncertain outcome, and results of earlier studies and trials, as well any interim results, may not be predictive of future trial results.
Current wording
Clinical development is a lengthy process with an uncertain outcome, and results of earlier studies and trials, conducted by us or Akeso, as well any interim results thereof, may not be predictive of future trial results and may negatively impact the size and scope of our ongoing or future Phase III clinical trials.
Previous wording
Clinical development can take several years to complete and is an expensive process with inherent uncertainty in outcomes. Failure can occur at any time during the clinical trial process. The results of preclinical studies and early clinical trials of ivonescimab may not be predictive of the results of our later-stage clinical trials. Similarly, initial or interim results of a clinical trial may not be predictive of the final results and results for one indication may not be predictive of the success in additional indications. Drug candidates in later stages of clinical trials may fail to show the desired safety and efficacy traits despite having progressed through preclinical studies and initial clinical trials. Several factors can lead to significant variability in safety and/or efficacy results between different trials of the same drug candidate, including changes in trial procedures set forth in protocols, differences in the size and type of the patient populations, including genetic differences, patient adherence to the dosing regimen and other trial protocol elements and the rate of dropout among clinical trial participants. In the case of any trials we conduct, results may differ from earlier trials due to the larger number of clinical trial sites and additional countries involved in such later trials. In multi-regional trials results may differ across regions and countries, Our future clinical trial results may not be favorable. If future clinical trial results prove unfavorable, we may incur additional product development costs, experience delays and/or become unable to obtain regulatory approval of ivonescimab, thereby adversely affecting our business.
Current wording
Clinical development can take several years to complete and is an expensive process with inherent uncertainty in outcomes. Failure can occur at any time during the clinical development process. The results of preclinical studies and early clinical trials of ivonescimab, conducted by us or Akeso, may not be predictive of the results of our later-stage clinical trials. Similarly, initial or interim results of a clinical trial may not be predictive of the final results and results for one indication, in one cohort, or in one of the primary endpoints or secondary endpoints, may not be predictive of the success in additional indications, with different cohorts or in additional primary or secondary endpoints. Drug candidates in later stages of clinical trials may fail to show the desired safety and efficacy traits despite having progressed through preclinical studies and initial clinical trials. Several factors can lead to significant variability in safety and/or efficacy results between different trials of the same drug candidate, including changes in trial procedures set forth in protocols, differences in the size, type and geographic location of the patient populations, including genetic differences, patient adherence to the dosing regimen, and other trial protocol elements and the rate of dropout among clinical trial participants. In the case of any trials we conduct, results may differ from earlier trials due to the larger number of clinical trial sites and additional countries involved in such later trials. Results may differ materially in clinical trials held across multiple cohorts or subgroups, which could lead to unfavorable regulatory or health authority decisions.
Previous wording
If clinical trials of our product candidates fail to demonstrate safety and efficacy to the satisfaction of the U.S. Food and Drug Administration, or the FDA, or the European Medicines Agency, or the EMA, or do not otherwise produce favorable results, we may incur additional costs or experience delays in completing, or ultimately be unable to complete, the development and commercialization of ivonescimab or any other product candidate.
Current wording
If clinical trials of our product candidates fail to demonstrate safety and efficacy to the satisfaction of regulatory authorities, or do not otherwise produce favorable results, we may incur additional costs or experience delays, or ultimately be unable to, develop and commercialize any product candidate.
Previous wording
In connection with obtaining marketing approval from regulatory authorities for the sale of ivonescimab, or any other product candidate, we must complete preclinical development and then conduct extensive clinical trials to demonstrate the safety and efficacy of our product candidates in humans. Clinical testing is expensive, difficult to design and implement, can take many years to complete and is inherently uncertain as to outcome. A failure of one or more clinical trials can occur at any stage of testing. The outcome of preclinical testing and early clinical trials may not be predictive of the success of later clinical trials, and interim results of a clinical trial do not necessarily predict final results. In particular, due to the small number of patients in our early clinical trials, results from such trials may not be predictive of the outcome of later clinical trials. The design of a clinical trial can determine whether its results will support approval of a product, and flaws in the design of a clinical trial may not become apparent until the clinical trial is well advanced or completed. We have limited experience in designing clinical trials and may be unable to design and execute a clinical trial to support marketing approval. Moreover, preclinical and clinical data are often susceptible to varying interpretations and analyses, and many companies that have believed their product candidates performed satisfactorily in preclinical studies and clinical trials have nonetheless failed to obtain marketing approval of their products. To date, we have not conducted a clinical trial for ivonescimab and cannot predict the results of such trials.
Current wording
In connection with obtaining marketing approval from regulatory authorities (including the FDA, EMA, PMDA or any other regulatory authority in the Licensed Territory) for the sale of ivonescimab, or any other product candidate, we must complete preclinical development and then conduct extensive clinical trials to demonstrate the safety and efficacy of our product candidates in humans. Clinical testing is expensive, difficult to design and implement, can take many years to complete and is inherently uncertain as to outcome. A failure of one or more clinical trials can occur at any stage of testing. The outcome of preclinical testing and early clinical trials may not be predictive of the success of later clinical trials, and interim results of a clinical trial do not necessarily predict final results. In particular, due to the small number of patients in our early clinical trials, results from such trials may not be predictive of the outcome of later clinical trials. The design of a clinical trial can determine whether its results will support approval of a product, and flaws in the design of a clinical trial may not become apparent until the clinical trial is well advanced or completed. We have limited experience in designing clinical trials and may be unable to design and execute a clinical trial to support marketing approval. Moreover, preclinical and clinical data are often susceptible to varying interpretations and analyses, and many companies that have believed their product candidates performed satisfactorily in preclinical studies and clinical trials have nonetheless failed to obtain marketing approval of their products. To date, we have not completed a clinical trial for ivonescimab in the Licensed Territory and cannot predict the results of such trials.
Previous wording
As we expand into additional countries and sites for our current and/or additional clinical trials, we are required to obtain the regulatory approval of the applicable clinical trial applications with the respective regulatory authorities and approvals from central or local institutional review boards. We may decide to modify our plans to enter certain regions or countries based on the timelines and requirements from the respective regulatory regions. If the process to obtain regulatory approvals in a given region or country places onerous requirements on the Company or if the Company cannot reasonably obtain such approvals without material delays to its plans, we may choose not to enter certain regions or countries for our clinical trials, which may delay the development of our product in those countries and/or impact the scope of our dataset and market for our products.
Current wording
As we expand into additional countries and sites for our current and additional clinical trials, we are required to obtain the regulatory approval of the applicable clinical trial applications with the respective regulatory authorities and approvals from central or local institutional review boards. We may decide to modify our plans to enter certain regions or countries based on the timelines and requirements from the respective regulatory regions. If the process to obtain regulatory approvals in a given region or country places onerous requirements on the Company or if the Company cannot reasonably obtain such approvals without material delays to its plans, we may choose not to enter certain regions or countries for our clinical trials, which may delay the development of our product in those countries and impact the scope of our dataset and market for our products.
Previous wording
•the number of patients required for clinical trials of our product candidates may be larger than we anticipate, enrollment in these clinical trials may be slower than we anticipate or participants may drop out of these clinical trials at a higher rate than we anticipate for various reasons, including due to contagious diseases or illnesses;
Current wording
•the number of patients required for clinical trials of our product candidates may be larger, and the diversity of the patient population required for our clinical trials may be higher, than we anticipate or participants may drop out of these clinical trials at a higher rate than we anticipate for various reasons, including due to contagious diseases or illnesses;
Previous wording
•our ability to combine data from different regions and countries may be limited due to lack of consistency in data in these regions and/or countries, potentially delaying or preventing marketing approval for our product
Current wording
•our ability to combine data from different regions and countries may be limited due to lack of consistency in data in these regions and countries, potentially delaying or preventing marketing approval for our product in some or all of the Licensed Territory;
Previous wording
•In our multi-regional trials, we may experience delays in enrollment across one or more countries and/or regions, which may lead to variability in data and/or trial missing the required endpoints resulting in lack of approval from regulatory authorities
Current wording
•in our multi-regional trials, we may experience delays in enrollment across one or more countries and/or regions that could lead to variability in data or the trial missing the required endpoints resulting in lack of approval from regulatory authorities in some or all of the Licensed Territory;
Previous wording
•our third-party contractors may fail to comply with regulatory requirements or meet their contractual obligations to us in a timely manner, or at all;
Current wording
•we or our third-party contractors may fail to comply with regulatory requirements or meet their contractual obligations to us in a timely manner, or at all;
Previous wording
•we may have delays in reaching or fail to reach agreement on acceptable clinical trial contracts or clinical trial protocols with prospective trial sites;
Current wording
•we may have delays in reaching or fail to reach agreement on acceptable clinical trial contracts or clinical trial protocols with multiple prospective trial sites;
Previous wording
•the supply or quality of our product candidates, comparator drugs or other materials necessary to conduct clinical trials of our product candidates in adolescent patients may be insufficient or inadequate, which may occur if, for example, enrollment for our clinical trial programs are delayed and the clinical supply of ivonescimab or related comparator drug manufactured for such trials was not utilized prior to its expiration and needed to be replaced, or if there were disruptions in our supply chain due to weather conditions, natural disasters or contagious diseases or illnesses, such as the novel coronavirus; and
Current wording
•the supply or quality of our product candidates, comparator drugs or other materials necessary to conduct clinical trials of our product candidates in adolescent patients may be insufficient or inadequate, which may occur if, for example, enrollment for our clinical trial programs are delayed and the clinical supply of ivonescimab or related comparator drug manufactured for such trials was not utilized prior to its expiration and needed to be replaced, or if there were disruptions in our supply chain due to weather conditions, natural disasters or contagious diseases or illnesses, or pandemics or epidemics;
Previous wording
•our product candidates may have undesirable side effects or other unexpected characteristics, causing us or our investigators, regulators, institutional review boards or independent ethics committees to suspend or terminate the clinical trials.
Current wording
•our product candidates may have undesirable side effects or other unexpected characteristics, causing us or our investigators, regulators, institutional review boards or independent ethics committees to suspend or terminate the clinical trials; and
Previous wording
If serious adverse or inappropriate side effects are identified during the development of ivonescimab or any other product candidate, we may need to abandon or limit our development of that product candidate.
Current wording
If serious adverse or inappropriate side effects are identified during the development of any product candidate, we may need to abandon or limit our development of that product candidate.
Previous wording
Even if ivonescimab or any other product candidate receives marketing approval, it may fail to achieve the degree of market acceptance by physicians, patients, third-party payors and others in the medical community necessary for commercial success.
Current wording
Even if a product candidate receives marketing approval, it may fail to achieve the degree of market acceptance by physicians, patients, third-party payors and others in the medical community necessary for commercial success.
Previous wording
The ability to negotiate, secure and maintain third-party coverage and reimbursement may be affected by political, economic and regulatory developments in the United States, the European Union and other jurisdictions.
Current wording
The ability to negotiate, secure and maintain third-party coverage and reimbursement may be affected by political, economic and regulatory developments in the United States, the E.U., Japan and other jurisdictions in the Licensed Territory.
Previous wording
Governments continue to impose cost containment measures, and third-party payors are increasingly challenging prices charged for medicines and examining their cost effectiveness, in addition to their safety and efficacy. These and other similar developments could significantly limit the degree of market acceptance of ivonescimab or any of our other product candidates that receive marketing approval.
Current wording
Governments continue to impose cost containment measures, and third-party payors are increasingly challenging prices charged for medicines and examining their cost effectiveness, in addition to their safety and efficacy. These and other similar developments could significantly limit the degree of payor acceptance of ivonescimab or any of our other product candidates that receive marketing approval.
Previous wording
Biologics, such as ivonescimab, carry unique risks and uncertainties, which could have a negative impact on our business.
Current wording
Biologics, such as ivonescimab, carry unique risks and uncertainties that could negatively impact our business.
Previous wording
The successful development, manufacturing and sale of biologics is a long, expensive and uncertain process. There are unique risks and uncertainties with biologics. For example, access to and supply of necessary biological materials, such as cell lines, may be limited and governmental regulations restrict access to and regulate the transport and use of such materials. In addition, the development, manufacturing and sale of biologics is subject to regulations that are often more complex and extensive than the regulations applicable to other pharmaceutical products. Manufacturing biologic, especially in large quantities, is often complex and may require the use of innovative technologies. Such manufacturing also requires facilities specifically designed and validated for this purpose and sophisticated quality assurance and quality control procedures. Biologics are also frequently costly to manufacture. Failure to successfully, develop, manufacture and sell ivonescimab could adversely affect our business.
Current wording
The successful development, manufacturing and sale of biologics is a long, expensive and uncertain process. There are unique risks and uncertainties with biologics. For example, access to and supply of necessary biological materials, such as cell lines, may be limited and governmental regulations restrict access to and regulate the transport and use of such materials. In addition, the development, manufacturing and sale of biologics is subject to regulations that are often more complex and extensive than the regulations applicable to other pharmaceutical products. Manufacturing biologics, especially in large quantities, is often complex and may require the use of innovative technologies. Such manufacturing also requires facilities specifically designed and validated for this purpose and sophisticated quality assurance and quality control procedures. Biologics are also frequently costly to manufacture. Failure to successfully, develop, manufacture and sell ivonescimab could adversely affect our business.
Previous wording
Several pharmaceutical and biotechnology companies have established themselves in the market for the treatment of non-small cell lung cancer (“NSCLC”), and several additional companies are developing products for the treatment of NSCLC. Currently, the most commonly used treatments for NSCLC are several immuno-oncology drugs and chemotherapies, administered either as monotherapy or in combination with other approved therapeutics. NSCLC treatment regimens vary due to several factors, including genetic mutations and progression of disease. Several medications have been approved by FDA for these treatments, including, but not limited to pembrolizumab, atezolizumab, nivolumab, durvalumab and ipilmumab. There are anti-angiogenic therapies which are approved for the treatment of certain lung cancers, including bevacizumab and ramucirumab. In addition, there are several targeted therapies that have also been approved, including, but not limited to, osimertinib, adagrasib, and alectinib. Beyond currently approved therapies, several potential therapeutics are in various stages of development and clinical trials for the treatment of NSCLC, including late-stage candidates which have recently released Phase III clinical trial data in
Current wording
Several pharmaceutical and biotechnology companies have established themselves in the market for the treatment of NSCLC, and several additional companies are developing products for the treatment of NSCLC. Currently, the most commonly used treatments for first-line NSCLC without genomic alterations are several immuno-oncology drugs and chemotherapies, administered either individually as monotherapy, in combination with each other, or in combination with other approved therapeutics. In addition to various chemotherapies, several immunotherapies have been approved by the FDA for these treatments, including, but not limited to pembrolizumab, atezolizumab, nivolumab, durvalumab, cemiplimab and ipilimumab. There are anti-angiogenic therapies which are approved for the treatment of certain lung cancers, including bevacizumab in front-line non-squamous NSCLC as well as ramucirumab for patients who have progressed after platinum-based chemotherapy. The proposed indications for ivonescimab in the HARMONi-3 and HARMONi-7 clinical trial settings in first-line NSCLC may face competition from clinical candidates such as novel immunotherapy targets including various clinical candidates targeting T-cell immunoreceptors with Ig and ITIM domains (TIGIT) and lymphocyte activation gene 3 (LAG-3) each of which have various developers for different candidates as either monoclonal antibodies or multispecific antibodies, a bispecific antibody, volrustomig (AstraZeneca), and antibody drug conjugates (ADCs) with novel targets such as datopotamab deruxetecan (AstraZeneca and Daiichi Sankyo), sacituzumab tirumotecan (Merck), and sigvotatug vedotin (Pfizer), each having announced, are currently enrolling in, or having completed enrollment in Phase III clinical trials.
Previous wording
Many of our competitors may have significantly greater financial resources and expertise in research and development, manufacturing, preclinical testing, conducting clinical trials, obtaining approvals from regulatory authorities and marketing approved products than we do. Mergers and acquisitions in the pharmaceutical and biotechnology industries may result in even more resources being concentrated among a smaller number of our competitors. Smaller and other early-stage companies may also prove to be significant competitors, particularly through collaborative arrangements with large and established companies. These third parties compete with us in recruiting and retaining qualified scientific and management personnel, establishing clinical trial sites and patient registration for clinical trials, as well as in acquiring technologies complementary to or necessary for our programs.
Current wording
Many of our competitors may have significantly greater financial and operational resources and expertise in research and development, manufacturing, preclinical testing, conducting clinical trials, obtaining approvals from regulatory authorities and marketing approved products than we do. Mergers and acquisitions in the pharmaceutical and biotechnology industries may result in even more resources being concentrated among a smaller number of our competitors. Smaller and other early-stage companies may also prove to be significant competitors, particularly through collaborative arrangements with large and established companies. These third parties compete with us in recruiting and retaining qualified scientific and management personnel, establishing clinical trial sites and patient registration for clinical trials, as well as in acquiring technologies complementary to or necessary for our programs.
Previous wording
•our right to sublicense patent and other rights to third parties under collaborative development relationships;
Current wording
•our right to sublicense patent and other intellectual property rights to third parties under collaborative development relationships;
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Rearranged current paragraphs (2)
Current report — wording carried from elsewhere
Accordingly, we will need to continue to rely on additional financing in connection with our continuing operations. Additional financing may not be available to us on acceptable terms, or at all. If we are unable to raise capital when needed or on attractive terms, we may be required to delay, limit, reduce or terminate our product development or future commercialization efforts or grant rights to develop and market product candidates that we would otherwise prefer to develop and market ourselves.
Current report — wording carried from elsewhere
The capital and credit markets may not be available to support future capital raising activity on favorable terms. If economic conditions decline, the Company’s future cost of equity or debt capital and access to the capital markets could be adversely affected. In addition, adverse economic conditions, such as recent supply chain disruptions and labor shortages and persistent inflation, may negatively impact our business. These economic conditions make it more difficult for us to accurately forecast and plan our future business activities.
Rearranged previous paragraphs (3)
Previous report — wording carried elsewhere
Our operations and performance depend on ongoing stability of global, regional and U.S. economic and geopolitical conditions. General worldwide economic conditions have experienced significant instability in recent years, including due to recent global economic uncertainty and turbulent financial market conditions. The ongoing geopolitical conflicts in various parts of the world, including but not limited to Russia, Ukraine and Middle East, are difficult to predict and could adversely affect our business in our licensed territories as well as our ability to enroll patients and supply ivonescimab to various clinical sites in the world, resulting in adverse effects on our business and financial condition.
Previous report — wording carried elsewhere
Risks Related to Our Industry and Market
Previous report — wording carried elsewhere
UK are expected to be restricted going forward with further changes anticipated following a government consultation being launched with the intention of merging the SME and RDEC schemes.