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Item 1A. Risk Factors

2025-02-24 compared with 2024-02-20 · 473 added, 452 removed, 568 unchanged (62% of the section changed)

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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.

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.

Risks Related to our Financial Position and Need for Additional Capital

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.

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.

Worldwide economic social, and geopolitical instability could adversely affect our operations, revenue, financial condition, or results of operations.

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.

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.

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:

• Ability to use preclinical data and data of patients from Akeso’s clinical trials in China supporting registration studies and regulatory approval;

• successful completion of global clinical development;

• 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;

• establishing supply chain and commercial manufacturing arrangements with third-party manufacturers;

• obtaining and maintaining patent and trade secret protection and regulatory exclusivity;

• protecting our rights in our intellectual property portfolio;

• establishing sales, marketing and distribution capabilities;

• launching commercial sales of ivonescimab if and when approved, whether alone or in collaboration with others;

• acceptance of ivonescimab, if and when approved, by patients, the medical community and third-party payors;

• obtaining adequate pricing and a reimbursement profile;

• ensuring no disruption in supply or lack of sufficient quantities of ivonescimab;

• effectively competing with other therapies;

• maintaining an acceptable safety profile of ivonescimab during development and following approval.

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.

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.

We expect to incur losses for at least the next several years and may never generate or maintain profits.

We are a development-stage company and we cannot assure profitability.

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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.

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.

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Our failure to become and remain profitable would depress our value and could impair our ability to raise capital, expand our business, maintain our research and development efforts, diversify our product offerings or even continue our operations.

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.

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.

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.

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.

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We may encounter unforeseen expenses, difficulties, complications and delays, and may not be successful in such a transition.

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.

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.

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.

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.

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.

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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.

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.

Our primary future capital requirements will be related to our obligations under the License Agreement.

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.

Raising additional capital may cause dilution to our investors, restrict our operations or require us to relinquish rights to our technologies or product candidates.

Our primary future capital requirements will be related to our obligations under the License Agreement and funding research and development efforts.

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.

Raising additional capital may cause dilution to our investors, restrict our operations or require us to relinquish rights to our product candidates.

Until such time, if ever, as we can generate substantial product revenues, we expect to finance our cash needs through a combination of equity offerings, collaborations, strategic alliances, grants and clinical trial support from government entities, philanthropic, non-government and not-for-profit organizations and patient advocacy groups, debt financings, and marketing, distribution or licensing arrangements.

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If we are unable to raise additional funds through equity or debt financings, or other arrangements when needed based on our liquidity needs, 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.

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.

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.

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.

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.

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.

Worldwide economic, social and geopolitical instability could adversely affect our operations, revenue, financial condition, results of operations or ability to raise capital.

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.

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.

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.

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:

• our ability to use preclinical data and data of patients from Akeso’s clinical trials in China supporting registration studies and regulatory approval;

• successful completion of global clinical development;

• 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;

• establishing supply chain and commercial manufacturing arrangements with third-party manufacturers;

• obtaining and maintaining patent and trade secret protection and regulatory exclusivity;

• protecting our rights in our intellectual property portfolio;

• establishing sales, marketing and distribution capabilities;

• launching commercial sales of ivonescimab if and when approved, whether alone or in collaboration with others;

• acceptance of ivonescimab, if and when approved, by patients, the medical community and third-party payors;

• obtaining timely and adequate pricing and reimbursement from payors;

• ensuring no disruption in supply or lack of sufficient quantities of ivonescimab;

• effectively competing with other therapies;

• maintaining an acceptable safety profile of ivonescimab during development and following approval.

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.

Risks Related to the Development and Commercialization of our Product Candidates

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.

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.

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.

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 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.

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.

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.

Results may differ materially in clinical trials held across multiple cohorts or subgroups, which could lead to unfavorable regulatory or health authority decisions.

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.

If we experience delays or difficulties in the enrollment of patients in our clinical trials, our receipt of necessary marketing approvals could be delayed or prevented.

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Our inability to enroll a sufficient number of patients in our planned clinical trials of ivonescimab or any other planned clinical trials would result in significant delays, may generate a limited data set from which no meaningful conclusions could be made, or may require us to abandon one or more clinical trials altogether.

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.

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.

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.

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.

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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.

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.

To date, we have not completed a clinical trial for ivonescimab in the Licensed Territory and cannot predict the results of such trials.

Regulatory requirements and timelines may affect the scope and timeline of our trials and the potential market for our product candidates.

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.

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/or impact the scope of our dataset and market for our products.

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.

If we experience any number of possible unforeseen events in connection with our clinical trials, potential marketing approval or commercialization of our product candidates could be delayed or prevented.

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• clinical trials of our product candidates may produce negative or inconclusive results, and we may decide, or regulators may require us, to conduct additional clinical trials or abandon product development programs;

• 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;

• 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

• 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

• 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;

• 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;

• 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;

• 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;

• we may be unable to enroll a sufficient number of patients in our clinical trials to ensure adequate statistical power to detect any statistically significant treatment effects;

• 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;

• 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;

• regulators, institutional review boards or independent ethics committees may not authorize us or our investigators to commence a clinical trial or conduct a clinical trial at a prospective trial site;

• we may have delays in reaching or fail to reach agreement on acceptable clinical trial contracts or clinical trial protocols with prospective trial sites;

• 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;

• we may have to suspend or terminate clinical trials of our product candidates for various reasons, including a finding that the participants are being exposed to unacceptable health risks;

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• regulators, institutional review boards or independent ethics committees may require that we or our investigators suspend or terminate clinical research for various reasons, including noncompliance with regulatory requirements or a finding that the participants are being exposed to unacceptable health risks;

• the cost of clinical trials of our product candidates may be greater than we anticipate;

• 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;

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;

• 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;

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

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.

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.

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.

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.

• preclinical tests or clinical trials not beginning as planned, needing to be restructured or not being completed on schedule, or at all.

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.

All of our product candidates are in clinical or early-stage development and their risk of failure is high.

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Any of these occurrences could materially harm our business.

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.

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.

If ivonescimab or any of our other product candidates receive marketing approval, such products may nonetheless fail to gain sufficient market acceptance by physicians, patients, third-party payors and others in the medical community.

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• any restrictions on concomitant use of other medications.

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.

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.

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.

If we are unable to establish sales and marketing capabilities or enter into agreements with third parties to market and sell our product candidates, we may not be successful in commercializing a product candidate if and when such product candidates are approved.

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In addition, we may not be successful in entering into arrangements with third parties to sell and market our product candidates or may be unable to do so on terms that are acceptable to us.

We likely will have little control over such third parties, and any of them may fail to devote the necessary resources and attention to sell and market our products

We likely will have little control over such third parties, and any of them may fail to devote the necessary resources and attention to sell and market our products effectively.

If we do not establish sales and marketing capabilities successfully, either on our own or in collaboration with third parties, we will not be successful in commercializing our product candidates.

Biologics, such as ivonescimab, carry unique risks and uncertainties, which could have a negative impact on our business.

Biologics, such as ivonescimab, carry unique risks and uncertainties that could negatively impact our business.

The successful development, manufacturing and sale of biologics is a long, expensive and uncertain process.

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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.

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.

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If we do not accurately evaluate the commercial potential or target market for a particular product candidate, we may relinquish valuable rights to that product candidate through collaboration, licensing or other royalty arrangements in cases in which it would have been more advantageous for us to retain sole development and commercialization rights to such product candidate.

Risks Related to our Financial and Intellectual Property Dependencies on Third Parties

We face substantial competition, which may result in others discovering, developing or commercializing products before us or more successfully than we do.

The development and commercialization of new drug products is highly competitive.

We face competition with respect to our current product candidates and any products we may seek to develop or commercialize whether ourselves or through third-party partners, in the future from major pharmaceutical companies, specialty pharmaceutical companies and biotechnology companies worldwide.

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.

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).

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.

Potential competitors also include academic institutions, government agencies and other public and private research organizations that conduct research, seek patent protection and establish collaborative arrangements for research, development, manufacturing and commercialization.

Our commercial opportunity could be reduced or eliminated if our competitors develop and commercialize products that are more effective, safer, have fewer or less severe side effects, are approved for broader indications or patient populations, or are more convenient or less expensive than any products that we develop and commercialize.

Our competitors may also obtain marketing approval for their products more rapidly than we may obtain approval for ours, which could result in our competitors establishing a strong market position before we are able to enter the market.

We believe that many competitors are attempting to develop therapeutics for the target indications of our product candidates, including academic institutions, government agencies, public and private research organizations, large pharmaceutical companies and smaller more focused companies.

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.

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.

If we fail to plan, execute and manage our growth effectively, our ability to develop and commercialize products could suffer.

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.

Risks Related to our Dependencies on Third Parties

We depend on our relationship with, and the comprehensiveness of the intellectual property licensed from, Akeso, and termination of the License Agreement, or issues related to intellectual property could have a material adverse effect on our business.

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• whether third parties are entitled to compensation or equitable relief, such as an injunction, for our use of intellectual property without their authorization;

• our right to sublicense patent and other rights to third parties under collaborative development relationships;

• our right to sublicense patent and other intellectual property rights to third parties under collaborative development relationships;

• our compliance with our obligations with respect to the use of the licensed technology in relation to our development and commercialization of product candidates;

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These issues, if they arise, could narrow what we believe to be the scope of our rights to the relevant intellectual property or technology, increase what we believe to be our financial or other obligations under the relevant agreement, or increase our costs to develop, manufacture and commercialize products under the License Agreement.

We will be reliant on Akeso for knowledge transfer relating to manufacturing of our product candidate.

The loss of any of the knowledge transferred relating to ivonescimab from Akeso may cause us to incur additional transition costs or result in delays in the manufacturing and delivery of the ivonescimab product candidate.

We have entered into the License Agreement and will enter into a Supply Agreement with Akeso for manufacturing of drug substance and or drug product that we will rely on to be used in our product candidate, and the termination or Akeso’s breach of these agreements could have a material adverse effect on our business.

Akeso’s drug substance and/or drug product may not comply with FDA quality requirements and/or have sufficient stability for commercialization which may require additional investment and delay our development, approval and commercialization plans

Further, failure of Akeso to adequately transfer knowledge to Summit to produce ivonescimab could have a material adverse effect on our business.

We may be reliant on Akeso for knowledge transfer relating to any improvements in manufacturing of ivonescimab.

The loss of any of the knowledge transferred relating to ivonescimab from Akeso may cause us to incur additional transition costs or result in delays in the manufacturing and delivery of ivonescimab.

We have entered into the License Agreement pursuant to which we agreed to purchase a certain portion of drug substance and/or drug product for clinical and commercial supply, and the termination or Akeso’s breach of these agreements could have a material adverse effect on our business.

Akeso’s drug substance and drug product may not comply with regulatory authority quality requirements or have sufficient stability for commercialization which may require additional investment and delay our development, approval and commercialization plans.

Further, failure of Akeso to adequately transfer knowledge to Summit relating to any improvements in producing ivonescimab could have a material adverse effect on our business.

Manufacturing of biological compounds is inherently complex and establishing new manufacturing relationships with a third-party manufacturer may take longer, resulting in higher costs and potential inventory issues.

Manufacturing processes may use materials which Summit may not be able to secure, requiring Summit to have to develop alternative processes and delay manufacturing.

The product may not comply with the FDA quality requirements and/or have sufficient stability for commercialization, which may require additional manufacturing development and delays.

Manufacturing processes may use materials which Summit may not be able to secure, requiring Summit to develop alternative processes and delay manufacturing.

The product may not comply with regulatory authority quality requirements or have sufficient stability for commercialization, which may require additional manufacturing development and delays.

As Summit is relying initially on supply from Akeso, any delays in obtaining import or export licenses may delay development.

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If a collaborator of ours were to be involved in a business combination, the continued pursuit and emphasis on our product development or commercialization program could be delayed, diminished or terminated.

Use of third parties, including Akeso, to manufacture our product candidates may increase the risk that we will not have sufficient quantities of our product candidates or products or such quantities at an acceptable time and cost, which could delay, prevent or impair our development or commercialization efforts.

We rely on the use of third parties, including Akeso, to manufacture our product candidate, which may increase the risk that we will not have sufficient quantities of our product candidates or products or such quantities at an acceptable time and cost, which could delay, prevent or impair our development or commercialization efforts.

We do not own or operate manufacturing facilities for the production of clinical or commercial supplies of our product candidates.

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We are in the process of setting up agreements with third party manufacturers for the long-term clinical and commercial supply of ivonescimab.

We may be unable to conclude agreements for commercial supply with third-party manufacturers, or may be unable to do so on acceptable terms The third-party manufacturers may not successfully carry out their contractual duties or obligations, the occurrence of which could substantially increase our costs and limit our supply of such product candidates.

We may be unable to conclude agreements for commercial supply with third-party manufacturers, or may be unable to do so on acceptable terms.

The third-party manufacturers may not successfully carry out their contractual duties or obligations, the occurrence of which could substantially increase our costs and limit our supply of such product candidates.

The demand for third-party manufacturer’s services is very high, and such manufacturers could be subject to market transactions including mergers, acquisitions and other market consolidation transactions that limit their ability to provide products and services to us thereby increasing the time and cost it could take us to manufacture our product.

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Third-party manufacturers, including Akeso, may not be able to comply with current good manufacturing practice (“cGMP”), regulations or similar regulatory requirements outside the United States.

Our failure, or the failure of our third-party manufacturers, including Akeso,, to comply with applicable regulations could result in sanctions being imposed on us,

including fines, injunctions, civil penalties, delays, suspension or withdrawal of approvals, license revocation, seizures or recalls of product candidates or products, operating restrictions and criminal prosecutions, any of which could significantly and adversely affect supplies of our product candidates.

Our failure, or the failure of our third-party manufacturers, including Akeso, to comply with applicable regulations could result in sanctions being imposed on us, including fines, injunctions, civil penalties, delays, suspension or withdrawal of approvals, license revocation, seizures or recalls of product candidates or products, operating restrictions and criminal prosecutions, any of which could significantly and adversely affect supplies of our product candidates.

Our product candidates and any products that we may develop may compete with other product candidates and products for access to manufacturing facilities.

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In addition, if we are not able to obtain adequate supplies of our product candidates or the drug substances used to manufacture them, it will be more difficult for us to develop our product candidates and compete effectively.

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.

We rely on third-party manufacturers for the capability to manufacture ivonescimab and/or other product candidates.

Large pharmaceutical companies with greater resources, either through acquisitions, market consolidation or otherwise, may be able to obtain privileged access to manufacturing capacity and/or supply of material needed for the manufacture of ivonescimab or other similar competing drugs.

Large pharmaceutical companies with greater resources, either through acquisitions, market consolidation or otherwise, may be able to obtain privileged access to manufacturing capacity and supply of material needed for the manufacture of ivonescimab or other similar competing drugs.

If our competitors are able to use their resources to secure preferential access to the supply capacity of third party manufacturers, or if third party manufacturers elect to terminate their contracts with us in favor of exclusive contracts with other larger pharmaceutical companies, our ability to obtain a supply of ivonescimab or any other future product candidates may be impacted resulting in significant delays and higher costs for development and commercialization of our products.

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For example, we remain responsible for ensuring that each of our clinical trials is conducted in accordance with the general investigational plan and protocols for the clinical trial.

Moreover, the FDA requires us to comply with standards, commonly referred to as Good Clinical Practice (GCP), for conducting, recording and reporting the results of clinical trials to assure that data and reported results are credible and accurate and that the rights, integrity of data and confidentiality of clinical trial participants are protected.

The European Medicines Agency (EMA) and Pharmaceutical and Medical Devices agency (PDMA) impose similar requirements on us for products that are the subject of clinical trials in the European Union, including the United Kingdom, and Japan.

Moreover, the FDA requires us to comply with standards, commonly referred to as GCP, for conducting, recording and reporting the results of clinical trials to assure that data and reported results are credible and accurate and that the rights, integrity of data and confidentiality of clinical trial participants are protected.

The EMA and PDMA impose similar requirements on us for products that are the subject of clinical trials in the E.U., including the U.K., and Japan.

Furthermore, third parties that we rely on for our clinical development activities may also have relationships with other entities, some of which may be our competitors.

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If we do not have sufficient funds, we may not be able to further develop our product candidates or bring them to market and generate product revenue.

Risks Related to Our Industry and Market

We face substantial competition, which may result in others discovering, developing or commercializing products before us or more successfully than we do.

The development and commercialization of new drug products is highly competitive.

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

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.

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.

Inadequate funding for the FDA, the SEC, and other government agencies, including from government shutdowns, or other disruptions to these agencies’ operations, could hinder their ability to hire and retain key leadership and other personnel, prevent new products and services from being developed or commercialized in a timely manner or otherwise prevent those agencies from performing normal business functions on which the operation of our business may rely, which could negatively impact our business.

The ability of the FDA to review and approve new products can be affected by a variety of factors, including government budget and funding levels, the ability to hire and retain key personnel and the acceptance of user fees payments, and statutory, regulatory, and policy changes.

Average review times at the agency have fluctuated in recent years as a result.

If a prolonged government shutdown occurs, if the FDA is required to furlough review staff or necessary employees, or if the agency operations are otherwise impacted, it could significantly affect the ability of the FDA to timely review and process our regulatory submissions, which could have a material adverse effect on our ability to successfully develop and commercialize ivonescimab or any other product candidate in our pipeline.

Further, future government shutdowns could impact our ability to access the public markets and obtain necessary capital in order to properly capitalize and continue our operations.

We may complete a future acquisition that may not achieve intended results or could increase the number of our outstanding shares or amount of outstanding debt or result in a change of control.

In addition to the License Agreement and the transactions contemplated thereby, we may pursue business development opportunities to expand or enhance our pipeline of drug candidates, including without limitation, through potential acquisitions of and/or collaborations with other entities.

Any such transaction could happen at any time, could be material to our business and could take any number of forms, including, for example, an acquisition, merger or a collaboration with other entities.

Evaluating potential transactions and integrating completed ones may divert the attention of our management from ordinary operating matters.

The success of these potential transactions will depend, in part, on our ability to realize the anticipated growth opportunities through the successful integration of the businesses we acquire with our existing business, as well as the success of the underlying business or intellectual property that we acquire or otherwise obtain rights to.

Even if we are successful in integrating the acquired businesses, these integrations may not result in the realization of the full benefit of any anticipated growth opportunities or these benefits may not be realized within the expected time frames.

In addition, acquired businesses may have unanticipated liabilities or contingencies.

If we complete an acquisition, investment or other strategic transaction, we may require additional financing that could result in an increase in the number of our outstanding shares or the aggregate amount of our debt.

Legal, Tax, Regulatory, and Compliance Risks

Even if we are able to commercialize ivonescimab or any other product candidate that we develop, the product may become subject to unfavorable pricing regulations, third-party reimbursement practices or healthcare reform initiatives, which would harm our business.

Even if we are able to commercialize a product candidate, it may become subject to unfavorable pricing regulations, third-party reimbursement practices or healthcare reform initiatives, which could harm our business.

The regulations that govern marketing approvals, pricing, coverage and reimbursement for new drug products vary widely from country to country.

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There may be significant delays in obtaining coverage and reimbursement for newly approved drugs, and coverage may be more limited than the purposes for which the drug is approved by the applicable regulatory authority.

Moreover, eligibility for coverage and reimbursement does not imply that any drug will be paid for in all cases or at a rate that covers our costs, including research, development, intellectual property, manufacture, sale and distribution expenses.

Moreover, eligibility for coverage and reimbursement does not imply that any drug will be paid for in all cases or at a rate that covers our costs,

including, but not limited to, research, development, intellectual property, manufacture, sale and distribution expenses.

Interim reimbursement levels for new drugs, if applicable, may also not be sufficient to cover our costs and may not be made permanent.

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In the United States, third-party payors often rely upon Medicare coverage policy and payment limitations in setting their own reimbursement policies.

In the European Union, reference pricing systems and other measures may lead to cost containment and reduced prices.

In the E.U., reference pricing systems and other measures may lead to cost containment and reduced prices.

Our inability to promptly obtain coverage and adequate reimbursement rates from both government-funded and private payors for any approved products that we develop could have a material adverse effect on our operating results, our ability to raise capital needed to commercialize products and our overall financial condition.

Governments outside the United States tend to impose strict price controls, which may adversely affect our revenues, if any.

In some countries, particularly the member states of the European Union, the pricing of prescription pharmaceuticals is subject to governmental control.

In some countries, particularly the E.U.

Member States, the pricing of prescription pharmaceuticals is subject to governmental control.

In these countries, pricing negotiations with governmental authorities can take considerable time after the receipt of marketing approval for a product.

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Political, economic and regulatory developments may further complicate pricing negotiations, and pricing negotiations may continue after reimbursement has been obtained.

Reference pricing used by various European Union member states and parallel distribution,

or arbitrage between low-priced and high-priced member states, can further reduce prices.

Reference pricing used by various E.U.

Member States and parallel distribution, or arbitrage between low-priced and high-priced E.U.

Member States, can further reduce prices.

In some countries, we may be required to conduct a clinical trial or other studies that compare the cost-effectiveness of our product candidate to other available therapies in order to obtain or maintain reimbursement or pricing approval.

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• difficulties in managing foreign relationships and operations generally.

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.

U.S.-China trade relations may adversely impact our supply chain operations and business.

and Chinese governments have taken certain actions that change trade policies, including tariffs that affect certain products which are manufactured in China and mutual exchange of certain types of data.

and Chinese governments have taken certain actions that change trade policies, including tariffs and threats of additional tariffs that affect certain products which are manufactured in China and mutual exchange of certain types of data.

Due to our collaboration with Akeso, we are reliant on collaborating with a company with significant operations in China.

It is unknown whether and to what extent new tariffs, laws or regulations will be adopted that increase the cost or feasibility of importing and/or exporting products, components and information from China to the United States and vice versa.

We do not know whether and to what extent the Trump administration will implement or alter any tariffs, laws or regulations that may increase the cost or feasibility of importing and exporting products, components and information from China to the United States and vice versa.

Further, the effect of any such new tariffs or actions on our industry and customers is unknown and difficult to predict.

As additional new tariffs, legislation and/or regulations are implemented, or if existing trade agreements are renegotiated or if China or other affected countries take retaliatory trade actions, such changes could have a material adverse effect on our clinical development plans, business, financial condition, results of operations or cash flows.

As additional tariffs, legislation and regulations are implemented, or if existing trade agreements are renegotiated, or if China or other affected countries take retaliatory trade actions, such changes could have a material adverse effect on our clinical development plans, business, financial condition, results of operations or cash flows.

Product liability lawsuits against us could cause us to incur substantial liabilities and to limit commercialization of any products that we may develop.

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Recent and potential future changes to U.S.

tax laws could materially adversely affect our company and holders of our shares of common stock.

We are unable to predict what tax changes may be enacted in the future or what effect such changes would have on our business, but such changes could affect our effective tax rates in countries where we have operations and could have an adverse effect on our overall tax position in the future, along with increasing the complexity, burden and cost of tax compliance.

tax laws or the interpretation thereof or the imposition of new or increased taxes or fees could increase our future tax liabilities and adversely affect our operating results and cash flows.

From time to time, U.S.

federal, state and non-U.S.

legislation has been proposed that would, if enacted into law, make significant changes to tax laws, including certain key U.S.

federal, state and non-U.S.

income tax provisions currently applicable to companies like us.

It is unclear whether these or similar changes will be enacted and, if enacted, how soon any such changes could take effect.

The passage of any legislation as a result of these proposals and other changes in tax laws or the imposition of new or increased taxes or fees could affect our effective tax rates in countries where we have operations and could have an adverse effect on our overall tax position in the future, along with increasing the complexity, burden and cost of tax compliance, in each case potentially increasing our future tax liabilities and adversely affect our operating results and cash flows.

United States

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On December 22, 2017, the U.S.

government enacted the Tax Cuts and Jobs Act, or the TCJA, which significantly reformed the U.S.

Internal Revenue Code of 1986, as amended, or the Code.

The TCJA, among other things, contained significant changes to corporate taxation, including the limitation of the tax deduction for net interest expense to 30% of adjusted taxable income (except for certain small businesses), the limitation of the deduction for net operating losses arising in taxable years beginning after December 31, 2017 to 80% of current year taxable income, the allowance of net operating losses arising in taxable years beginning after December 31, 2017 to be carried forward indefinitely, the allowance of immediate deductions for certain new investments instead of deductions for depreciation expense over time, and the modification or repeal of many business deductions and credits.

Beginning with costs incurred in 2022, the TCJA also eliminated the option to deduct research and development expenditures currently and requires taxpayers to capitalize and amortize them over five or fifteen years pursuant to Internal Revenue Code Section 174.

This does not increase our effective tax rate or our cash tax payable in 2022 or 2023.

However, if the requirement to capitalize Section 174 expenditures is not modified, it may also impact our effective tax rate and our cash tax liability in future years.

United Kingdom

Recent announcements of changes in the UK R&D regime are likely to impact the level of cash benefit that the Company will be able to receive in respect of the R&D activity.

As a result of a reduction in rates applied in the SME regime, the cash credit that the Company will be able to obtain is likely to reduce if the qualified spending remains consistent.

This will be partly offset by an increase in the RDEC regime.

In addition, there is a refocus of relief towards UK activity and therefore costs outside the

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.

Our ability to use our U.S.

federal, U.S.

state and foreign net operating losses and other tax attributes may be limited.

Our ability to use our U.S.

federal, U.S.

state and foreign net operating losses to offset potential future taxable income and related income taxes that would otherwise be due is dependent upon our generation of future taxable income, and we cannot predict with certainty when, or whether, we will generate sufficient taxable income to use all of our net operating losses.

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.

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.

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.

Laws and regulations affecting government contracts, such as BARDA and CARB-X , make it more costly and difficult for us to successfully conduct our business.

government enacted the Tax Cuts and Jobs Act (the “TCJA”), which significantly reformed the Code.

The TCJA, among other things, contained significant changes to corporate taxation, including certain limitations on interest deductions, limitations of the deduction for certain net operating losses, and the modification or repeal of many business deductions and credits.

Beginning with costs incurred in 2022, the TCJA also eliminated the option to deduct research and development expenditures and requires taxpayers to capitalize and amortize them over five or fifteen years.

If this requirement is not modified, it may impact our effective tax rate and our cash tax liability in future years.

More recently, the IRA contained, among other things, a corporate alternative minimum tax, which imposes a 15% minimum tax will be imposed on certain financial statement income of “applicable corporations” in taxable years beginning after December 31, 2022.

The IRA also imposes a 1% non-deductible excise tax on the fair market value of any stock repurchased by a publicly traded domestic corporation during any taxable year, with the fair market value of such repurchased stock reduced by the fair market value of certain stock issued by such corporation during such taxable year.

Department of the Treasury and the IRS have released proposed and final regulations and other interpretive guidance

relating to the TCJA and the IRA.

Any significant variance from our current interpretation of such regulations and interpretive

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

operations and cash flows.

Recent announcements of changes in the U.K.

research and development (“R&D”) regime are likely to impact the level of cash benefit that the Company will be able to receive in respect of the R&D activity.

As a result of a reduction in rates applied in the Small and Medium Enterprise (“SME”) regime, the cash credit that the Company will be able to obtain is likely to reduce if the qualified spending remains consistent.

This will be partly offset by an increase in the Research and Development Expenditure Credit (“RDEC”) regime.

In addition, there is a refocus of relief towards U.K.

activity and therefore costs outside the U.K.

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.

Our future tax liabilities may be greater than expected if our net operating loss carryforwards and other tax attributes are limited, we do not generate expected deductions, or tax authorities challenge our tax positions.

As of December 31, 2024, we have U.S.

federal and state net operating loss (“NOL”) carryforwards of approximately $44.3 million and $7.0 million, respectively, U.S.

federal research and development tax credit carryforwards of approximately $7.0 million, and U.K.

NOL carryforwards of approximately $198.7 million.

Our ability to utilize these tax attributes to offset potential future taxable income and related income taxes that would otherwise be due is dependent upon our generation of future taxable income, which cannot be assured.

In addition, our ability to use NOL carryforwards and other tax attributes may be subject to significant limitations under Sections 382 and 383 of the Code.

Under those sections of the Code, if a corporation undergoes an “ownership change” (as defined in Section 382 of the Code), the corporation’s ability to use its pre-change NOL carryforwards and other tax attributes may be substantially limited.

An ownership change generally occurs if one or more stockholders (or groups of stockholders) who are each deemed to own at least 5% of such corporation’s stock change their ownership by more than 50 percentage points over their lowest ownership percentage within a rolling three-year period.

In the event that we were to undergo an ownership change, utilization of our NOL carryforwards and other tax attributes would be subject to an annual limitation under Section 382 of the Code and Section 383 of the Code (as applicable), determined by

multiplying the value of our stock at the time of the ownership change by the applicable long-term tax-exempt rate in effect during the month in which the ownership change occurs, subject to certain adjustments, which could result in a portion of our tax attributes expiring prior to their utilization.

Any unused annual limitation may be carried over to later years.

Any limitation on our ability to utilize our NOL carryforwards or other tax attributes against income or gain we generate in the future could increase our future tax liabilities and adversely affect our operating results and cash flows.

Furthermore, we are subject to various complex and evolving U.S.

federal, state, local and non-U.S.

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.

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.

Laws and regulations affecting government contracts make it more costly and difficult for us to successfully conduct our business.

Failure to comply with these laws and regulations could result in significant civil and criminal penalties and adversely affect our business.

W e must comply during the term of such government contracts and upon expiration/termination of such contracts, as to continuing obligations, with numerous laws and regulations.

We must comply during the term of such government contracts and upon expiration/termination of such contracts, as to continuing obligations, with numerous laws and regulations.

These laws, regulations and obligations include, for example, the Federal Acquisition Regulation, compliance regulations, business ethics and public integrity obligations, export and import laws and regulations, etc.

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In addition, we could suffer serious reputational harm if allegations of impropriety were made against us, which could jeopardize our other research programs, deter research institutions from engaging with us, and cause our stock price to decrease.

Even if we complete the necessary clinical trials, the marketing approval process is expensive, time-consuming and uncertain and may prevent us from obtaining approvals for the commercialization of some or all of our product candidates.

If we are not able to obtain, or if there are delays in obtaining, required regulatory approvals, we will not be able to commercialize our product candidates, and our ability to generate revenue will be materially impaired.

The marketing approval process is expensive, time-consuming and uncertain, and may prevent us from obtaining approvals for the commercialization of some or all of our product candidates.

If we are unsuccessful or delayed in obtaining required regulatory approvals, we will not be able to commercialize our product candidates, and our ability to generate revenue will be materially impaired.

Our product candidates, including ivonescimab, and the activities associated with their development and commercialization, including their design, testing, manufacture, safety, efficacy, recordkeeping, labeling, storage, approval, advertising, promotion, sale and distribution, are subject to comprehensive regulation by the FDA and by comparable authorities in other countries.

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Securing marketing approval requires the submission of extensive preclinical and clinical data and supporting information to regulatory authorities for each therapeutic indication to establish the product candidate’s safety and efficacy.

Securing marketing approval also requires the submission of information about the product manufacturing process to, and inspection of manufacturing facilities

by, the regulatory authorities.

Securing marketing approval also requires the submission of information about the product manufacturing process to, and inspection of manufacturing facilities by, the regulatory authorities.

Regulatory authorities may determine that ivonescimab or any of our other product candidates are not effective or only moderately effective, or have undesirable or unintended side effects, toxicities, safety profiles or other characteristics that preclude us from obtaining marketing approval or that prevent or limit commercial use.

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Regulatory authorities have substantial discretion in the approval process and may refuse to accept any application or may decide that our data are insufficient for approval and require additional preclinical, clinical or other studies.

In addition, varying interpretations of the data obtained from preclinical and clinical testing could delay, limit or prevent marketing approval of a product candidate.

In addition, varying interpretations of the data obtained from preclinical and clinical testing could delay, limit or

prevent marketing approval of a product candidate.

Any marketing approval we ultimately obtain may be limited or subject to restrictions or post-approval commitments that render the approved product not commercially viable.

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Failure to comply would violate federal requirements and could result in fines and/or civil and criminal sanctions, which would delay the regulatory approval process and result in adverse publicity.

Our failure to obtain marketing approval in foreign jurisdictions would prevent our product candidates from being marketed in these other jurisdictions, and any approval we are granted for our product candidates in the United States and Europe would not assure approval of our product candidates in other jurisdictions.

Our failure to obtain marketing approval in a jurisdiction would prevent our product candidates from being marketed in such jurisdiction, and any approval we are granted for our product candidates in one jurisdiction would not assure approval of our product candidates in any other jurisdictions.

In order to market and sell ivonescimab and our other product candidates in foreign jurisdictions, we must obtain separate marketing approvals and comply with numerous and varying regulatory requirements in those jurisdictions.

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Marketing approvals in countries outside the United States and Europe do not ensure pricing approvals in those countries or in any other countries, and marketing approvals and pricing approvals do not ensure that reimbursement will be obtained.

Our ability to obtain and maintain conditional marketing authorizations in the European Union is limited to specific circumstances and subject to several conditions and obligations.

Our ability to obtain and maintain conditional marketing authorizations in the E.U.

is limited to specific circumstances and subject to several conditions and obligations.

A failure to renew any conditional approval that we obtain prior to full approval for the applicable indication would prevent us from continuing to market our products.

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Thus, neither we nor our collaborators will be able to promote any products we develop for indications or uses for which they are not approved.

In addition, manufacturers of approved products and those manufacturers’ facilities are required to ensure that quality control and manufacturing procedures conform to cGMP, which include requirements relating to quality control and quality assurance as well as the corresponding maintenance of records and documentation and reporting requirements.

requirements.

We and our contract manufacturers could be subject to periodic unannounced inspections by the FDA to monitor and ensure compliance with cGMP.

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These requirements include, but are not limited to, restrictions governing promotion of an approved product, submissions of safety and other post-marketing information and reports, registration and listing requirements, cGMP requirements relating to manufacturing, quality control, quality assurance and corresponding maintenance of records and documents, and requirements regarding the distribution of samples to physicians and recordkeeping.

The FDA and other federal and state agencies, including the Department of Justice, or DOJ, closely regulate compliance with all requirements governing prescription drug products, including requirements pertaining to marketing and promotion of drugs in accordance with the provisions of the approved labeling and manufacturing of products in accordance with cGMP requirements.

The FDA and other federal and state agencies, including the DOJ, closely regulate compliance with all requirements governing prescription drug products, including requirements pertaining to marketing and promotion of drugs in accordance with the provisions of the approved labeling and manufacturing of products in accordance with cGMP requirements.

The FDA and DOJ impose stringent restrictions on manufacturers’ communications regarding off-label use, and if we do not market our products for their approved indications, we may be subject to enforcement action for off-label marketing.

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requirements regarding safety monitoring or pharmacovigilance, and with requirements related to the development of products for the pediatric population, can also result in significant financial penalties.

Similarly, failure to comply with the European Union’s requirements regarding the protection of personal information can also lead to significant penalties and sanctions.

Similarly, failure to comply with the E.U.’s requirements regarding the protection of personal information can also lead to significant penalties and sanctions.

Our relationships with customers, healthcare providers and professionals and third-party payors will be subject to applicable anti-kickback, fraud and abuse and other healthcare laws and regulations, which could expose us to criminal sanctions, civil penalties, contractual damages, reputational harm and diminished profits and future earnings.

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This statute has been broadly interpreted to apply to manufacturer arrangements with prescribers, purchasers and formulary managers, among others.

Several other countries, including the United Kingdom, have enacted similar anti-kickback, fraud and abuse, and healthcare laws and regulations.

Several other countries, including the U.K., have enacted similar anti-kickback, fraud and abuse, and healthcare laws and regulations.

• The federal False Claims Act imposes civil penalties, including civil whistleblower or qui tam actions, against individuals or entities for knowingly presenting, or causing to be presented, to the federal government, claims for payment that are false or fraudulent or making a false statement to avoid, decrease or conceal an obligation to pay money to the federal government.

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There is also a separate false claims provision imposing criminal penalties.

• The federal Health Insurance Portability and Accountability Act of 1996, or HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act, imposes criminal and civil liability for executing a scheme to defraud any healthcare benefit program and also imposes obligations, including mandatory contractual terms, with respect to safeguarding the privacy, security and transmission of individually identifiable health information.

• HIPAA, as amended by the HITECH, imposes criminal and civil liability for executing a scheme to defraud any healthcare benefit program and also imposes obligations, including mandatory contractual terms, with respect to safeguarding the privacy, security and transmission of individually identifiable health information.

• HIPAA also imposes criminal liability for knowingly and willfully falsifying, concealing or covering up a material fact or making any materially false statement in connection with the delivery of or payment for healthcare benefits, items or services.

• The federal Physician Sunshine Act requirements under the Patient Protection and Affordable Care Act of 2010, as amended by the Health Care and Education Reconciliation Act of 2010, referred to together as the Affordable Care Act, require manufacturers of drugs, devices, biologics and medical supplies to report to the Department of Health and Human Services information related to payments and other transfers of value made to or at the request of covered recipients, such as physicians and teaching hospitals, and physician ownership and investment interests in such manufacturers.

• The federal Physician Sunshine Act requirements under the ACA require manufacturers of drugs, devices, biologics and medical supplies to report to the Department of Health and Human Services information related to payments and other transfers of value made to or at the request of covered recipients, such as physicians and teaching hospitals, and physician ownership and investment interests in such manufacturers.

Payments made to physicians and research institutions for clinical trials are included within the ambit of this law.

Failure to submit timely, accurate and required information for all payments, transfers of value and ownership or investment interests may result in civil monetary penalties.

pharmaceutical industry’s voluntary compliance guidelines and the relevant compliance guidance promulgated by the federal government in addition to requiring drug manufacturers to report information related to payments to physicians and other health care providers or marketing expenditures.

• Analogous state laws and regulations, such as state anti-kickback and false claims laws, may apply to sales or marketing arrangements and claims involving healthcare items or services reimbursed by non-governmental third-party payors, including private insurers, and some state laws require pharmaceutical companies to comply with the pharmaceutical industry’s voluntary compliance guidelines and the relevant compliance guidance promulgated by the federal government in addition to requiring drug manufacturers to report information related to payments to physicians and other health care providers or marketing expenditures.

Additionally, some state and local laws require the registration of pharmaceutical sales representatives in the jurisdiction.

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Exclusion, suspension and debarment from government funded healthcare programs would significantly impact our ability to commercialize, sell or distribute any drug.

If any of the physicians or other providers or entities with whom we expect to do business are found to be not in compliance with applicable laws, they may be subject to criminal, civil or administrative sanctions, including exclusions from government funded healthcare programs.

Current and future legislation may increase the difficulty and cost for us and any future collaborators to obtain marketing approval of and commercialize our product candidates and affect the prices we, or they, may obtain.

If any of the physicians or other providers or entities with whom we expect

to do business are found to be not in compliance with applicable laws, they may be subject to criminal, civil or administrative sanctions, including exclusions from government funded healthcare programs.

Inadequate funding for or other disruptions to government agencies could hinder or otherwise prevent those agencies from performing normal business functions on which the operation of our business may rely, which could negatively impact our business.

The ability of reviewing regulatory agencies, including the FDA, to review and approve new products can be affected by a variety of factors, including government budget and funding levels, the ability to hire and retain key leadership and other personnel and the acceptance of user fees payments, and statutory, regulatory, and policy changes.

Average review times at the agency have fluctuated in recent years as a result.

If funding is inadequate, a prolonged government shutdown occurs, the FDA is required to furlough review staff or necessary employees, or if the agency operations are otherwise disrupted, it could significantly affect the ability of the FDA to timely review and process our regulatory submissions, which could have a material adverse effect on our ability to successfully develop and commercialize ivonescimab or any other product candidate in our pipeline.

Further, future government shutdowns could impact our ability to access the public markets and obtain necessary capital in order to properly capitalize and continue our operations.

Current and future legislation may increase the difficulty and cost to obtain marketing approval of and commercialize our product candidates and could affect the prices we may obtain.

In the United States and some foreign jurisdictions, there have been and continue to be a number of legislative and regulatory changes and proposed changes regarding the healthcare system that could, among other things, prevent or delay marketing approval of our product candidates, restrict or regulate post-approval activities and affect our ability, or the ability of any future collaborators, to profitably sell any products for which we, or they, obtain marketing approval.

We expect that current laws, as well as other healthcare reform measures that may be adopted in the future, may result in more rigorous coverage criteria and in additional downward pressure on the price that we, or any future collaborators, may receive for any approved products.

We expect that recently enacted healthcare reforms, as well as other healthcare reform measures that may be adopted in the future, may result in additional reductions in Medicare and other healthcare funding, more rigorous coverage criteria, new payment methodologies and additional downward pressure on the price that we receive for any approved product and/or the level of reimbursement physicians receive for administering any approved product we might bring to market.

Reductions in reimbursement levels may negatively impact the prices we receive or the frequency with which our products are prescribed or administered.

We expect that current laws, as well as other healthcare reform measures that may be adopted in the future, may result in more limits on reimbursement and additional downward pressure on the price that we, or any future collaborators, may receive for any approved products.

We expect that recently enacted healthcare reforms, as well as other healthcare reform measures that may be adopted in the future, may result in additional reductions in Medicare and other healthcare funding, more rigorous coverage criteria, new payment methodologies and additional downward pressure on the price that we receive for any approved product as well as impact reimbursement to stakeholders that administer any approved product we might bring to market.

Any reductions in reimbursement may negatively impact physicians, hospitals and other provider's ability to purchase and appropriately prescribe our products.

Any reduction in reimbursement from Medicare or other government programs may result in a similar reduction in payments from private payors.

The costs of prescription pharmaceuticals has also been the subject of considerable discussion in the United States.

The costs of prescription pharmaceuticals have also been the subject of considerable discussion in the United States.

To date, there have been several U.S.

congressional inquiries and proposed and enacted state and federal legislation designed to, among other things, bring more transparency to drug pricing, review the relationship between pricing and manufacturer patient programs, reduce the costs of drugs under Medicare and reform government program reimbursement methodologies for drug products.

More recently, in August 2022, President Biden signed into law the Inflation Reduction Act of 2022 (the “IRA”).

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.

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.

Further legislative, regulatory and other legal changes remain possible.

President Biden signed into law the Inflation Reduction Act of 2022 (the “IRA”) on August 16, 2022, which includes several provisions to lower prescription drug costs for Medicare patients and reduce drug spending by the federal government.

Among other things, the IRA has multiple provisions that may impact the prices of drug products that are both sold into the Medicare program and throughout the United States.

Starting in 2023, a manufacturer of a drug or biological product covered by Medicare Parts B or D must pay a rebate to the federal government if the drug product’s price increases faster than the rate of inflation.

This calculation is made on a drug product by drug product basis and the amount of the rebate owed to the federal government is directly dependent on the volume of a drug product that is paid for by Medicare Parts B or D.

This calculation is made on a drug product by

drug product basis and the amount of the rebate owed to the federal government is directly dependent on the volume of a drug product that is paid for by Medicare Parts B or D.

Additionally, starting in payment year 2026, the U.S.

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CMS will also negotiate drug prices for a select number of Part B drugs starting for payment year 2028.

Negotiations will occur for products that have been on the market for seven years for Part D drugs and for eleven years for Part B drugs.

Revised prices will take effect two years after these negotiations occur.

If a drug product is selected by CMS for negotiation, it is expected that the revenue generated from such drug will decrease.

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.

At the state level, individual states are increasingly aggressive in passing legislation and implementing regulations designed to control pharmaceutical and biological product pricing, including price or patient reimbursement constraints, discounts, restrictions on certain product access and marketing cost disclosure and transparency measures, and, in some cases, designed to encourage importation from other countries and bulk purchasing.

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These measures could reduce the ultimate demand for our products, once approved, or put pressure on our product pricing.

We expect that additional state and federal healthcare reform

measures will be adopted in the future, any of which could limit the amounts that federal and state governments will pay for healthcare products and services, which could result in reduced demand for our product candidates or additional pricing pressures.

We expect that additional state and federal healthcare reform measures will be adopted in the future, any of which could limit the amounts that federal and state governments will pay for healthcare products and services, which could result in reduced demand for our product candidates or additional pricing pressures.

Legislative and regulatory proposals have also been made to expand post-approval requirements and restrict sales and promotional activities for pharmaceutical products.

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Congress of the FDA’s approval process may significantly delay or prevent marketing approval, as well as subject us and any future collaborators to more stringent product labeling and post-marketing testing and other requirements.

In the European Union, similar political, economic and regulatory developments may affect our ability to profitably commercialize our products.

In addition to continuing pressure on prices and cost containment measures, legislative developments at the European Union or member state level may result in significant additional requirements or obstacles that may increase our operating costs.

In the E.U., similar political, economic and regulatory developments may affect our ability to profitably commercialize our products.

In addition to continuing pressure on prices and cost containment measures, legislative developments at the E.U.

or Member State level may result in significant additional requirements or obstacles that may increase our operating costs.

We are subject to anti-corruption laws, as well as export control laws, customs laws, sanctions laws and other laws governing our operations.

If we fail to comply with these laws, we could be subject to civil or criminal penalties, other remedial measures and legal expenses, which could adversely affect our business, results of operations and financial condition.

Our operations are subject to anti-corruption laws, including the U.S.

Foreign Corrupt Practices Act, or FCPA, the U.K.

Bribery Act 2010, or Bribery Act, and other anti-corruption laws that apply in countries where we do business and may do business in the future.

Our operations are subject to anti-corruption laws, including the FCPA, the U.K.

Bribery Act 2010 (the “Bribery Act”), and other anti-corruption laws that apply in countries where we do business and may do business in the future.

The FCPA, Bribery Act and these other laws generally prohibit us, our officers, and our employees and intermediaries from bribing, being bribed or making other prohibited payments to government officials or other persons to obtain or retain business or gain some other business advantage.

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In addition, we cannot predict the nature, scope or effect of future regulatory requirements to which our international operations might be subject or the manner in which existing laws might be administered or interpreted.

We are also subject to other laws and regulations governing our international operations, including regulations administered by the governments of the United States and the United Kingdom, and authorities in the European Union, including applicable export control regulations, economic sanctions on countries and persons, customs requirements and currency exchange regulations, collectively referred to as the Trade Control laws.

We are also subject to other laws and regulations governing our international operations, including regulations administered by the governments of the U.S.

and the U.K., and authorities in the E.U., including applicable export control regulations, economic sanctions on countries and persons, customs requirements and currency exchange regulations, collectively referred to as the "Trade Control laws".

There is no assurance that we will be completely effective in ensuring our compliance with all applicable anti-corruption laws, including the FCPA, the Bribery Act or other legal requirements, including Trade Control laws.

If we are not in compliance with the FCPA, the Bribery Act and other anti-corruption laws or Trade Control laws, we may be subject to criminal and civil penalties, disgorgement and other sanctions and remedial measures, and legal expenses, which could have an adverse impact on our business, financial condition, results of operations and liquidity.

If we are not in compliance

with the FCPA, the Bribery Act and other anti-corruption laws or Trade Control laws, we may be subject to criminal and civil penalties, disgorgement and other sanctions and remedial measures, and legal expenses, which could have an adverse impact on our business, financial condition, results of operations and liquidity.

Likewise, any investigation of any potential violations of the FCPA, the Bribery Act, other anti-corruption laws or Trade Control laws by U.S., U.K.

or other authorities could also have an adverse impact on our reputation, our business, results of operations and financial condition.

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.

The Committee on Foreign Investment in the United States (“CFIUS”) has authority to review direct or indirect foreign investments in U.S.

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”.

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.

Environmental, social and governance matters may impact our business and reputation.

Governmental authorities, non-governmental organizations, customers, investors, external stakeholders and employees are increasingly sensitive to environmental, social and governance, or ESG, concerns, such as diversity and inclusion, climate change, water use, recyclability or recoverability of packaging, and plastic waste.

This focus on ESG concerns may lead to new requirements that could result in increased costs associated with developing, manufacturing and distributing our products.

Our ability to compete could also be affected by changing customer preferences and requirements, such as growing demand for more environmentally friendly products, packaging or supplier practices, or by failure to meet such customer expectations or demand.

We risk negative stockholder reaction, including from proxy advisory services, as well as damage to our brand and reputation, if we do not act responsibly, or if we are perceived to not be acting responsibly in key ESG areas, including equitable access to medicines, product quality and safety, diversity and inclusion, environmental stewardship, support for local communities, corporate governance and transparency, and addressing human capital factors in our operations.

If we do not meet the ESG expectations of our investors, customers and other stakeholders, we could experience reduced demand for our products, loss of customers, and other negative impacts on our business and results of operations.

Environmental, social and governance ( “ ESG ” ) matters may impact our business and reputation.

Governmental authorities, non-governmental organizations, customers, investors, external stakeholders and employees are increasingly aware of ESG concerns, such as climate change, water use, recyclability or recoverability of packaging, and plastic waste.

The ESG landscape is uncertain and constantly evolving due to changes in executive action, legislation, regulations and court orders.

ESG concerns may lead to new requirements that could result in increased costs associated with developing, manufacturing and distributing our products.

Our ability to compete could also be affected by changing customer preferences and requirements or by failure to meet such customer expectations or demand.

If we do not meet the ESG expectations of government agencies, our investors, customers and other stakeholders, we could experience reduced demand for our products, loss of customers, and other negative impacts on our business and results of operations.

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.

Risks Related to Our Intellectual Property, Cybersecurity and Data Privacy

If we are unable to obtain and maintain patent protection for our technology and product candidates, or if the scope of our patent protection is not sufficiently broad, our competitors could develop and commercialize technology and drug products similar or identical to ours, and our ability to successfully commercialize our technology and drug product candidates may be impaired.

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.

The patent position of biotechnology and pharmaceutical companies generally is highly uncertain, involves complex legal and factual questions and has in recent years been the subject of much litigation.

As a result, the issuance, scope, validity, enforceability and commercial value of our patent rights are highly uncertain.

Our pending and future patent applications may not result in patents being issued which protect our technology or products, in whole or in part, or which effectively prevent others from commercializing competitive technologies and products.

Changes in either the patent laws or interpretation of the

patent laws in the United States and other countries may diminish the value of our patents, narrow the scope of our patent protection or make enforcement more difficult or uncertain.

The laws of foreign countries may not protect our patent rights to the same extent as the laws of the United States.

For example, European patent law restricts the patentability of methods of treatment of the human body more than U.S.

In addition, for the foregoing reasons, we may not pursue or obtain patent protection in all major markets or may not obtain protection that enables us to prevent the entry of third parties into the market.

Assuming the other requirements for patentability are met, currently, the first to file a patent application is generally entitled to the patent.

However, prior to March 16, 2013, in the United States, the first to invent was entitled to the patent.

Publications of discoveries in the scientific literature often lag behind the actual discoveries, and patent applications in the United States and other jurisdictions are typically not published until 18 months after filing, or in some cases not at all.

Therefore, we cannot know with certainty whether we were the first to make the inventions claimed in our U.S.

If we are unable to obtain and maintain patent protection for our technology and product candidates, our competitors could develop and commercialize technology and drug products similar or identical to ours, and our ability to successfully commercialize our technology and drug product candidates may be impaired.

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.

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.

The patent position of biotechnology and pharmaceutical companies generally is highly uncertain, involves complex legal and factual questions, and is currently the focus of extensive litigation.

This unpredictability makes the issuance, scope, validity, enforceability and commercial value of our patent rights highly uncertain.

While we strive to secure patents that protect our technology and products, our pending and future patent applications may not yield issued patents that provide meaningful protection.

Even when patents are granted, they may fail to effectively prevent competitors from developing and commercializing similar or identical technologies and products.

Furthermore, ongoing changes in patent laws or their interpretation due to changing administrations, specifically in the United States and internationally, may diminish the value of our patents, restrict the scope of our patent protection, or complicate our enforcement efforts.

The laws of foreign countries may offer less robust protection for patent rights compared to those in the United States, potentially exposing us to heightened competition.

For example, European patent law imposes stricter limitations on the patentability of methods of treatment for the human body when compared with U.S.

law, which may leave aspects of our technology and products vulnerable in certain markets.

Additionally, differences in national patent laws and enforcement mechanisms may make it more difficult to obtain and maintain comprehensive protection across all major markets.

This patchwork of international protection may hinder our ability to prevent the entry of third parties into the market.

Assuming the other requirements for patentability are met, under current U.S.

law, the first to file a patent application is generally entitled to the patent.

This framework, implemented after March 16, 2013, replaced the previous “first to invent” system which granted rights to the original inventor regardless of the filing date.

Unfortunately, publications of discoveries in the scientific literature often lag behind the actual discoveries, and patent applications in the United States and other jurisdictions are typically not published until 18 months after filing, or in some cases not at all.

This lack of clarity makes it difficult to ascertain whether we were the first to make the inventions claimed in our U.S.

patents or pending U.S.

patent applications, or that we were the first to file for patent protection of such inventions outside the United States or, since March 16, 2013, within the United States.

Moreover, we may be subject to a third party pre-issuance submission of prior art to the USPTO or become involved in opposition, derivation, reexamination, reissue, inter parties review, post grant review, interference proceedings or other patent office proceedings, court litigation or International Trade Commission proceedings, in the United States or elsewhere, challenging our patent rights or the patent rights of others.

An adverse determination in any such submission, proceeding or litigation concerning our patent rights could reduce the scope of or prevent the enforceability of, or invalidate, our patent rights, allowing third parties to commercialize our technology or products, or equivalent or similar technology or products, and so to compete directly with us, without payment to us, or, where such proceedings involve third-party patents, result in our inability to manufacture or commercialize products without infringing third-party patent rights.

patent applications.

We face similar uncertainties when seeking patent protection outside of the United States, where filing dates are critical to determining patent rights.

Moreover, we may be subject to third-party pre-issuance submissions of prior art to the USPTO or become involved in opposition, derivation, reexamination, reissue, inter parties review, post grant review, interference proceedings or other patent office proceedings, court litigation or International Trade Commission proceedings, in the United States or elsewhere, challenging our patent rights or the patent rights of others.

Adverse determinations in any of these proceedings could severely restrict or invalidate our patents, reducing their enforceability and allowing third parties to commercialize similar or identical technologies without compensation to us.

Furthermore, when third-party patents are involved, such disputes may result in our inability to manufacture, market, or commercialize our products without infringing on third-party rights.

In addition, if the breadth or strength of protection provided by our patents and patent applications is threatened or narrowed by operation of any of the foregoing, such an event could dissuade companies from collaborating with us to license, develop or commercialize current or future product candidates.

Third parties may have filed patent applications or received patents and may obtain additional patents and proprietary rights that block or compete with our patents.

Resolving an intellectual property infringement claim can be costly and time consuming and may require Summit to design around the claims of patents covering our products that may have been issued by third parties or to obtain a license, either of which could cause us to incur additional expenses.

Summit cannot guarantee that it would be able to obtain license agreements on commercially reasonable terms.

A successful claim of patent or other intellectual property infringement could subject Summit to significant damages or an injunction preventing the manufacture, sale, or use of the affected product.

We may choose not to file a patent in order to maintain certain trade secrets or know-how, and a third party may subsequently file a patent covering such intellectual property.

Even if our patent applications issue as patents, they may not issue in a form that will provide us with adequate protection to prevent competitors from competing with us or otherwise to provide us with any competitive advantage.

Our competitors may be able to circumvent our owned or licensed patents by developing similar, improved or alternative technologies or products in a non-infringing manner.

Resolving intellectual property disputes, such as infringement claims, can be costly and time consuming.

Such disputes may force us to design around third-party patents, incurring additional expenses, or seek licenses on terms that may not be commercially reasonable, favorable, or even obtainable.

A successful claim of patent or other intellectual property infringement could result in substantial damages, disrupt our operations, or lead to an injunction preventing the manufacture, sale, or use of the affected product.

We may choose not to file patents for certain intellectual property to maintain trade secrets or know-how, leaving a risk that third parties may subsequently patent those innovations.

Even if our patent applications issue as patents, they may not issue in a form that would provide us with adequate protection against competition.

Our competitors may circumvent our owned or licensed patents by developing similar, improved or alternative technologies or products in a non-infringing manner, eroding our competitive advantage.

In addition, other companies may attempt to circumvent any regulatory data protection or market exclusivity, such as orphan drug exclusivity in the United States, which we obtain under applicable legislation, which may require us to allocate significant resources to preventing such circumvention.

Legal and regulatory developments in the European Union and elsewhere may also result in clinical trial data submitted as part of a marketing authorization application becoming publicly available.

Such developments could enable other companies to use our clinical trial data to assist in their own product development and to obtain marketing authorizations in the European Union and in other jurisdictions.

These efforts can divert attention and financial resources away from other critical business activities, potentially slowing our overall progress.

Legal and regulatory developments in the E.U.

and elsewhere may also result in clinical trial data submitted as part of a marketing authorization application becoming publicly available.

Such developments could enable other companies to use our clinical trial data to assist in their own product development and to obtain marketing authorizations in the E.U.

and in other jurisdictions.

Loss of market exclusivity, particularly through the entry of generic or biosimilar competitors, could significantly reduce our revenue and market share.

Such developments may also require us to allocate significant resources to prevent other companies from circumventing or violating our intellectual property rights.

Our attempts to prevent third parties from circumventing our intellectual property and other rights may ultimately be unsuccessful.

We may also fail to take the required actions or pay the necessary fees to maintain our patents.

Despite our best efforts, our attempts to prevent third parties from circumventing our intellectual property and other rights may ultimately be unsuccessful.

Additionally, any failure to take the required actions, such as paying necessary

maintenance fees or addressing administrative formalities, could jeopardize the longevity and enforceability of our patents, further exposing us to risks of market erosion and reduced exclusivity.

The issuance of a patent is not conclusive as to its inventorship, scope, validity or enforceability, and our owned and licensed patents may be challenged in the courts or patent offices in the United States and abroad.

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Given the amount of time required for the development, testing and regulatory review of new product candidates, patents protecting such candidates might expire before or shortly after such candidates are commercialized.

This could be the case even after giving effect to patent term extensions and data exclusivity provisions preventing third parties from relying on clinical trial data filed by us for regulatory approval in support of their own applications

for such approval.

As a result, our patent portfolio may not provide us with sufficient rights to exclude others from commercializing products similar or identical to ours.

We may become involved in lawsuits or other enforcement proceedings to protect or enforce our patents or other intellectual property, which could be expensive, time-consuming and potentially unsuccessful.

Competitors may infringe our patents, trademarks, copyrights or other intellectual property.

To counter infringement or unauthorized use, we may be required to file claims, which can be expensive and time-consuming.

Any claims we assert against perceived infringers could provoke these parties to assert counterclaims against us alleging that we infringe their intellectual property or that our patent and other intellectual property rights are invalid or unenforceable, including for anti-trust reasons.

As a result, in a patent infringement proceeding, a court or administrative body may decide that a patent of ours is invalid or unenforceable, in whole or in part, or may construe the patent’s claims narrowly and so refuse to stop the other party from using the technology at issue on the grounds that our patents do not cover the competitor technology in question.

Even if we are successful in a patent infringement action, the unsuccessful party may subsequently raise antitrust issues and bring a follow-on action thereon.

Antitrust issues may also provide a bar to settlement or constrain the permissible settlement terms.

Further, settlement agreements in the pharmaceutical sector are the subject of ongoing review by the antitrust authorities in the European Union.

Third parties may initiate legal proceedings alleging that we are infringing their intellectual property rights, the outcome of which would be uncertain and could have a material adverse effect on the success of our business.

Competitors may infringe our patents, trademarks, copyrights or other intellectual property rights.

To counter infringement or unauthorized use, we may be required to initial legal claims or enforcement actions, which can be expensive and time-consuming.

Such actions are not always successful.

Any claims we assert against perceived infringers may prompt these parties to assert counterclaims against us, alleging that we infringe their intellectual property or that our patent and other intellectual property rights are invalid or unenforceable, including counterclaims based on antitrust or other legal theories.

In a patent infringement proceeding, a court or administrative body may decide that a patent of ours is invalid or unenforceable, in whole or in part, or may construe the patent’s claims narrowly.

Such rulings could allow the other party to continue using the disputed technology at issue on the grounds that our patents do not cover the competitor's activities or products.

Antitrust considerations may also hinder our ability to settle such matters on favorable terms, as certain types of settlement agreements, particularly in the pharmaceutical sector, are subject to heightened scrutiny by antitrust authorities.

In the E.U., for instance, antitrust regulators closely monitor settlement agreements for compliance with competition laws, adding another layer of complexity and potential risk to these proceedings.

Our commercial success depends upon our ability and the ability of our collaborators to develop, manufacture, market and sell our product candidates and use our proprietary technologies, including our in-licensed drug candidate ivonescimab, without infringing the intellectual property and other proprietary rights of third parties.

There is considerable intellectual property litigation in the biotechnology and pharmaceutical industries, and we may become party to, or threatened with, future adversarial proceedings or litigation regarding intellectual property rights with respect to our products and technology, including interference, derivation, inter parties review, reexamination, reissue or post-grant review proceedings before the USPTO.

The risks of being involved in such litigation and office proceedings may also increase as our product candidates approach commercialization, and as we gain greater visibility as a publicly traded company in the United States.

Third parties may assert infringement claims against us based on existing or future intellectual property rights and so restrict our freedom to operate.

Third parties may also seek injunctive relief against us, whereby they would attempt to prevent us from practicing our technologies altogether pending outcome of any litigation against us.

If we are found to infringe a third party’s intellectual property rights, or in order to avoid or settle litigation, we could be required to obtain a license to enable us to continue developing and marketing our products and technology.

However, we may not be able to obtain any required license on commercially reasonable terms or at all.

Even if we were able to obtain a license, it could be non-exclusive, thereby giving our competitors access to the same technologies as are licensed to us, and could require us to make substantial payments.

Absent a license, we could be forced, including by court order, to cease commercializing the infringing technology or product.

In addition, we could be found liable for monetary damages, including treble damages and attorneys’ fees if we are found to have willfully infringed a patent or other intellectual property right.

The risks of being involved in such disputes may increase as our product candidates approach commercialization, and as we gain greater visibility as a publicly traded company in the United States.

Third parties may assert infringement claims against us based on their existing or future intellectual property rights, potentially restricting our freedom to operate or delaying our progress.

Moreover, they may seek injunctive relief to bar us from practicing our technologies altogether while litigation against us is pending, potentially causing significant disruptions to our operations.

If we are found to infringe third party’s intellectual property rights, or if we choose to settle a dispute to avoid prolonged litigation, we may be required to obtain a license to enable us to continue developing and marketing our products and technology.

However, obtaining such licenses may be challenging or unattainable on commercially reasonable terms.

Even if we were able to obtain a license, it could be non-exclusive, which would enable our competitors access to the same technologies and we may be required to pay substantial upfront or ongoing royalties.

Absent a license, we could be forced, including by court order, to cease commercializing the infringing technology or product entirely.

In addition, we could be found liable for monetary damages, including treble damages and attorneys’ fees, particularly if we are found to have willfully infringed a patent or other intellectual property right.

A finding of infringement could prevent us from commercializing our product candidates or force us to cease some of our business operations, which could materially harm our business.

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We may be subject to claims by third parties asserting that we or our employees have misappropriated their intellectual property, or claiming ownership of what we regard as our own intellectual property.

Many of our employees were previously employed at universities or other biotechnology or pharmaceutical companies, including our competitors or potential competitors.

Although we try to ensure that our employees do not use the proprietary or otherwise confidential information or know-how of others in their work for us, we may be subject to claims that we or these employees have without authorization used or disclosed intellectual property, including trade secrets or other proprietary or confidential information, of any such employee’s former employer.

Many of our employees were previously employed at universities, research institutions or other biotechnology or pharmaceutical companies, including competitors or potential competitors.

Although we take measures to ensure that our employees do not use the proprietary or otherwise confidential information or know-how from former employers, we may be subject to claims that we or our employees have, without authorization, misappropriated intellectual property, trade secrets or other proprietary or confidential information.

Litigation may be necessary to defend against these claims.

In addition, while we typically require our employees and contractors who may be involved in the development of intellectual property to execute agreements assigning such intellectual property to us and agreeing to cooperate and assist us with securing and defending our intellectual property, we may be unsuccessful in executing such an agreement with each party who in fact develops intellectual property that we regard as our own.

Our and their assignment agreements may not be self-executing or may be breached, and we may be forced to bring claims against third parties, or defend claims they may bring against us, to determine the ownership of what we regard as our intellectual property.

We may be unsuccessful in executing such an agreement from all relevant parties who develop intellectual property for us, and certain agreements may not be enforceable under applicable laws or may be subject to challenges from third parties.

Furthermore, assignment agreements may not be self-executing or may be breached, and we may be forced to bring claims against third parties, or defend claims third parties may bring against us, to determine the ownership of what we regard as our intellectual property.

If we fail in prosecuting or defending any such claims, in addition to paying monetary damages, we may lose valuable intellectual property rights or personnel.

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Intellectual property litigation could cause us to spend substantial resources and could distract our personnel from their normal responsibilities.

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.

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.

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.

If we are unable to protect the confidentiality of our trade secrets, our business and competitive position would be harmed.

In addition to seeking patents for some of our technology and products, we also rely on trade secrets, including unpatented know-how, technology and other proprietary and confidential information, to maintain our competitive position.

We seek to protect these trade secrets, in part, by entering into non-disclosure and confidentiality agreements with parties who have access to them, such as our employees, corporate collaborators, outside scientific collaborators, contract manufacturers, consultants, advisors and other third parties.

However, we cannot guarantee that we have executed these agreements with each party that may have or have had access to our trade secrets or that the agreements we have executed will provide adequate protection.

Any party with whom we have executed such an agreement may breach that agreement and disclose our proprietary or confidential information, including our trade secrets, and we may not be able to obtain adequate remedies for such breaches.

To safeguard these trade secrets, we employ non-disclosure and confidentiality agreements with parties who have access to them, such as our employees, corporate collaborators, outside scientific collaborators, contract manufacturers, consultants, advisors and other third parties.

However, despite these measures, we cannot guarantee that we have executed these agreements with each party that may have or have had access to our trade secrets or that the agreements we have executed will provide adequate protection.

Even with these protections, any party with whom we have executed such an agreement may breach their obligations and disclose our proprietary or confidential information, including our trade secrets unlawfully.

We may not be able to obtain adequate remedies for such breaches.

Enforcing a claim that a party illegally disclosed or misappropriated a trade secret is difficult, expensive and time-consuming, and the outcome is unpredictable.

If any of our trade secrets were to be lawfully obtained or independently developed by a competitor, we would have no right to prevent them, or those to whom they communicate it, from using that technology or information to compete with us.

Additionally, if any of our trade secrets were to be lawfully obtained or independently developed by a competitor, we would have no legal recourse to prevent them from using this information to compete with us.

If any of our trade secrets, particularly unpatented know-how, were to be obtained or independently developed by a competitor, our competitive position would be harmed.

We operate in the biotechnology sector and rely heavily on information technology.

Any interruption or lapse related to that technology, including any cyber security incidents, could harm our ability to operate our business effectively.

Despite our security measures, our information technology and infrastructure are subject to attacks or breaches.

Any such breach could result in a material compromise of our systems or these systems of our third party vendors, and the information stored there could be accessed, publicly disclosed, lost, stolen, or rendered, permanently or temporarily, inaccessible.

Furthermore, we may not promptly discover a system intrusion.

Attacks could have a material impact on our business, operations or financial results.

Any such access, disclosure or other loss of information, including our data being breached at third party providers, could result in legal claims or proceedings, liability under laws that protect the privacy of personal information, disrupt our operations and damage our reputation, which could adversely affect our business.

We also may need to pay “ransomware” to re-access our systems.

If our information technology systems or data, or those of third parties upon whom we rely, are or were compromised, we could experience adverse consequences resulting from such compromise, including, but not limited to, regulatory investigations and actions;

litigation (including class claims);

fines and penalties;

a disruption of our business operations such as our clinical trials;

reputational harm;

loss of revenue and profits;

and other adverse consequences.

In the ordinary course of our business, we (and third parties upon whom we rely) may collect, receive, store, use, transfer, make accessible, protect, secure, dispose of, transmit, disclose or otherwise process proprietary, confidential and sensitive information (including personal data (such as health-related data and participant study related data), intellectual property, and trade secrets (collectively, sensitive data).

In addition, we rely on service providers to establish and maintain appropriate information technology and data security protections over the information technology systems they provide to us to operate our critical business systems (such as cloud-based infrastructure and systems, personnel email, as well as data storage and management systems).

However, except for contractual protections, we have limited ability to control their safeguards and actions related to

such matters and these service providers may not maintain adequate information security measures.

Any interruption, malfunction, or lapse related to that technology, including any cybersecurity incidents, could harm our ability to operate our business effectively.

We rely on both internal information technology systems and those of third parties to process and store sensitive data, including confidential research, business plans, financial information, intellectual property and personal data that may be subject to legal protection, and ensure the continuity of the Company's operations.

As of the date of this Annual Report on Form 10-K, though the Company and our service providers have experienced certain cybersecurity incidents, we are not aware of any previous cybersecurity incidents that have materially affected or are reasonably likely to materially affect the Company.

Any such cybersecurity incidents could result in a material compromise of our systems or the systems of our third-party vendors, and the information stored there could be accessed, publicly disclosed, lost, stolen, corrupted or rendered, permanently or temporarily, inaccessible.

Furthermore, the Company or its service providers may not promptly discover a system intrusion.

Cybersecurity incidents could have a material impact on our business, operations or financial results.

Any access, disclosure or other loss of information, including Company data being compromised within the systems of our third-party providers, could result in legal claims or proceedings, liability under laws that protect the privacy of personal information or personal health information, disrupt our operations and damage our reputation, which could adversely affect our business.

We also may need to make a material ransom payment to unencrypt, re-access, or preserve the confidentiality of our data or systems.

We could be required to spend significant financial and other resources to respond to and remedy the damage caused by such an incident, including the costs to recover data or to repair or replace networks and information technology systems, increased cybersecurity protection costs and increased insurance premiums.

If our information technology systems or data, or those of third parties upon whom we rely or interact, are or were compromised, we could experience material adverse consequences resulting from such compromise.

In the ordinary course of our business, we and the third parties we rely on collect, receive, store, use, transfer, make accessible, dispose of, transmit, disclose or otherwise process proprietary, confidential and sensitive information, personal information, personal health information, participant-study-health-related data, proprietary information, intellectual property, and trade secrets (collectively, "sensitive data").

In addition, we rely on service providers to establish and maintain appropriate information technology and data security protections to operate critical business systems (such as cloud-based infrastructure and systems, personnel email, as well as data storage and management systems).

However, except for contractual protections, which may prove ineffective, we have limited ability to control the safeguards implemented and actions taken by such third parties.

These service providers may not maintain adequate information security measures.

We may share or receive sensitive data with or from third parties whose information security measures may not be adequate.

In particular, the COVID-19 pandemic has caused us to modify our information technology practices including that our employees may work remotely which increases the risk of data breaches.

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.

Our information technology systems, including in our remote work environment, and those of parties upon which we rely, are vulnerable to evolving threats.

These threats are prevalent, continue to increase and come from a variety of sources such as “hackers;” external or internal bad actors;

personnel (such as through theft, error and/or misuse);

These threats are prevalent, continue to increase and come from a variety of sources such as hackers;

external or internal bad actors;

personnel (such as through theft, error and misuse);

sophisticated nation-states and nation-state-supported actors;

These threats include, but are not limited to, social-engineering attacks, malicious code or intrusions, malware, denial-of-service attacks, personnel misconduct or errors, ransomware attacks, supply-chain attacks, software bugs, computer viruses, server malfunctions, software and hardware failures, theft or loss of data and other information technology assets, adware, natural disasters, terrorism, war, as well as telecommunication and electrical failures.

These threats include, but are not limited to, outages, social-engineering attacks, malicious code or intrusions, malware, denial-of-service attacks, personnel misconduct or errors, ransomware attacks, supply-chain attacks, software bugs, computer viruses, server malfunctions, software and hardware failures, misdirected wire transfers, theft or loss of data and other information technology assets, adware, natural disasters, terrorism, war, as well as telecommunication and electrical failures.

In particular, ransomware attacks are becoming increasingly prevalent and severe and can lead to significant disruptions to operations, loss of data and income, reputational harm and diversion of funds.

If we were to experience such an attack, extortion payments might alleviate some of the negative impacts of a ransomware attack but we might be unwilling or unable to make such payments due to, for example, applicable laws or regulations prohibiting such payments.

Any of these threats may result in unauthorized, unlawful or accidental loss, corruption, access, modification, destruction, alteration, acquisition or disclosure of sensitive data (such as clinical trial data).

The costs to us to attempt to protect against such breaches is significant and could potentially require us to modify our business (including non-clinical and clinical trial activities).

If we were to experience such an attack, ransom payments might alleviate some of the negative impacts of a ransomware attack but we might be unwilling or unable to make such payments due to, for example, applicable laws or regulations prohibiting such payments.

The costs to us to attempt to protect against such cybersecurity incidents and breaches are significant and could potentially require us to modify our business (including without limitation non-clinical and clinical trial activities).

While we have implemented security measures designed to protect our information technology systems and to identify and remediate potential vulnerabilities, such measures may not be successful.

We may not be able to detect vulnerabilities in our information technology systems because such threats and techniques used by threat actors change frequently, are sophisticated in nature and may not be detected until after a security incident has occurred.

In addition, we may not have adequate insurance coverage to provide compensation for any losses associated with such events.

If we or others upon whom we rely experience or are perceived to have experienced a breach, we may experience adverse consequences.

In addition, we may not have adequate insurance coverage to remediate or provide compensation for any losses associated with such events.

If we or our third-party partners upon whom we rely experience or are perceived to have experienced a breach, we may experience adverse consequences.

These consequences may include:

government enforcement actions (for example, investigations, fines, penalties, audits and inspections), interruptions in our operations (including disruptions to our clinical trials), interruptions or restrictions on processing sensitive data (which could result in delays in obtaining, or our inability to obtain, regulatory approvals and significantly increase our costs to recover or reproduce the sensitive data), reputational harm, litigation (including class-action claims), indemnification obligations, monetary fund diversions, financial loss and other harms.

In addition, such a breach may require notification of the breach to relevant stakeholders.

In addition, such a breach may require notification of the breach to relevant stakeholders, certain state agencies or the media.

Such disclosures are costly and the disclosure or the failure to comply with such requirements could lead to adverse consequences.

Many of our contracts with relevant stakeholders include obligations relating to the safeguarding of sensitive data and a breach could lead to claims against us by such stakeholders.

There can be no assurance that the limitations of liability in our contracts would be enforceable or adequate or would otherwise protect us from liabilities, damages or claims relating to our data privacy and security obligations.

Many of our contracts with relevant stakeholders include obligations relating to safeguarding sensitive data and a breach or other cybersecurity incident could lead to claims against us by such stakeholders.

There can be no assurance that the limitations of liability or other protections in our contracts would be enforceable or adequate or would otherwise protect us from liabilities, damages or claims relating to our data privacy and security obligations.

In addition, failure to maintain effective internal accounting controls related to data security breaches and cybersecurity in general could impact our ability to produce timely and accurate financial statements and could subject us to regulatory and private party scrutiny.

We are subject to stringent and changing obligations related to data privacy and security.

Our actual or perceived failure to comply with such obligations could lead to regulatory investigations and actions;

fines and penalties;

disruptions to our business operations;

reputational harm;

loss of revenue and profits;

and other adverse business impacts.

Our actual or perceived failure to comply with such obligations could lead to material adverse consequences.

In the ordinary course of business, we process personal data and other sensitive data (including proprietary and confidential business information, trade secrets, intellectual property, clinical trial data, and other sensitive third-party data).

We are subject to or affected by numerous data privacy and security obligations such as various federal, state, local and foreign laws, regulations, and guidances;

We are subject to or affected by numerous data privacy and security obligations such as various federal, state, local and foreign laws, regulations, and guidance;

industry standards;

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and other obligations governing the processing of personal data by us and on our behalf.

These obligations may change, are subject to differing interpretations and may be inconsistent among jurisdictions.

These obligations may change, are subject to differing interpretations and may be inconsistent across jurisdictions.

The global data protection landscape is rapidly evolving and implementation standards and enforcement practices are likely to remain uncertain for the foreseeable future.

This evolution may create uncertainty in our business, affect us or our collaborators’, service providers’ and others’ ability to operate in certain jurisdictions or to collect, store, transfer, use, share, and otherwise process personal data, necessitate the acceptance of more onerous obligations in our contracts, result in liability or impose additional costs on us.

This evolution may create uncertainty in our business, affect us or our collaborators’, service providers’ and others’ ability to operate in certain jurisdictions or to collect, store, transfer (including across jurisdictional borders), use, share, and otherwise process personal data, necessitate the acceptance of more onerous obligations in our contracts, result in liability or impose additional costs on us.

The cost of compliance with these obligations is high and is likely to increase in the future.

These obligations may necessitate changes to our information

technologies, systems and practices and to those of any service providers that process personal data on our behalf.

These obligations may necessitate changes to our information technologies, systems and practices and to those of any service providers that process personal data on our behalf.

In addition, these obligations may require us to change our business plans.

Outside the U.S., an increasing number of laws, regulations and industry standards apply to data privacy and security.

For example, the European Union’s General Data Protection Regulation (GDPR) (EU) 2016/679, or the EU GDPR, imposes strict requirements on the processing of personal data.

Under the EU GDPR, government regulators may impose temporary or definitive bans on personal data processing as well as fines of up to 20 million Euros or 4% of the annual global revenues of the noncompliant company, whichever is greater.

For example, the E.U.’s GDPR, imposes strict requirements on the processing of personal data.

Under the E.U.

GDPR, government regulators may impose temporary or definitive bans on personal data processing as well as fines of up to 20 million Euros or 4% of the annual global revenues of the noncompliant company, whichever is greater.

Additionally, the Personal Information Protection Law (“PIPL”) of the People’s Republic of China may apply to certain personal data processed by us, our collaborators or others on our behalf.

Similar to the EU GDPR, PIPL imposes strict requirements on the processing of personal data and allows for statutory fines and penalties.

Certain jurisdictions, including the United Kingdom, EU, and China have enacted data localization laws and cross-border personal data transfer laws which make it more difficult to transfer information across jurisdictions (such as transferring or receiving personal data that originates in the UK or in other foreign jurisdictions).

Similar to the E.U.

GDPR, PIPL imposes strict requirements on the processing of personal data and allows for statutory fines and penalties.

Certain jurisdictions, including the U.K., E.U., and China have enacted data localization laws and cross-border personal data transfer laws which make it more difficult to transfer information across jurisdictions (such as transferring or receiving personal data that originates in the U.K.

or in other foreign jurisdictions).

Existing mechanisms that facilitate cross-border personal data transfers may change or be invalidated.

The processing of sensitive personal data, such as physical health conditions, is a topic of active interest among regulators.

As we expand into countries and jurisdictions outside the U.S., we may be subject to additional laws and regulations that may affect how we conduct business in relation to the personal data we process.

For example, in relation to these cross-border personal data laws, if we cannot maintain a valid compliance mechanism for cross-border personal data transfers, we may face increased exposure to regulatory actions, fines and injunctions against the transferring of personal data from the UK, Europe, China and elsewhere.

As we expand into countries and jurisdictions outside the U.S., we will be subject to additional laws and regulations that may affect how we conduct business in relation to the personal data or personal health information we or our third-party partners process.

For example, in relation to cross-border personal data laws, if we cannot maintain a valid compliance mechanism for cross-border personal data transfers, we may face increased exposure to regulatory actions, fines and injunctions against the transferring of personal data from the U.K., Europe, China and elsewhere.

We may have to increase our personal data processing capabilities and infrastructure in foreign jurisdictions at significant expense.

Likewise, we expect that there will continue to be new proposed laws, regulations and industry standards relating to data privacy and security in the U.S.

For example, the California Consumer Privacy Act, as amended, imposes obligations on business to which it applies.

Likewise, we expect that there will continue to be new laws, regulations and industry standards relating to data privacy and security in the U.S.

For example, the California Consumer Privacy Act, as amended by the California Privacy Rights Act (the "CCPA"), imposes obligations on business to which it applies.

These obligations include, but are not limited to, providing specific disclosures in privacy notices and affording California residents certain rights related to their personal data.

The CCPA allows for statutory fines for noncompliance (up to $7,500 per violation).

allows for statutory fines for noncompliance (up to $7,500 per violation).

While the CCPA contains limited exceptions for clinical trial data, the CCPA’s implementation standards and enforcement practices are likely to remain uncertain for the foreseeable future.

In addition, the CCPA, as amended, establishes a new California Privacy Protection Agency to implement and enforce the CCPA which could increase the risk of an enforcement action.

Other states (such as Colorado and Virginia) have also enacted data privacy laws.

If we become subject to new data privacy laws, at the state level, the risk of enforcement action against us could increase because we may become subject to additional obligations and the number of individuals or entities that can initiate actions against us may increase (including individuals, via a private right of action, and state actors).

In addition, the CCPA establishes a new California Privacy Protection Agency to implement and enforce the CCPA which could increase the risk of an enforcement action.

Other states (such as Colorado, Virginia, Delaware, Texas and others) have also enacted data privacy laws.

If we become subject to new data privacy laws, the risk of enforcement actions or class-action litigation brought against us could increase because we may become subject to additional obligations and the number of individuals or entities that can initiate actions against us may increase (including individuals, via a private right of action, and state agencies).

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.

Although we endeavor to comply with all applicable data privacy and security obligations, we may at times fail to do so or may be perceived to have failed to do so.

Moreover, despite our efforts, we may not be successful in achieving compliance if our personnel or third parties upon whom we rely fail to comply with such obligations, which could negatively impact our business operations and compliance posture.

Moreover, despite our efforts, we may not be successful in achieving compliance if our personnel or third parties we rely on fail to comply with such obligations, which could negatively impact our business operations and compliance posture.

For example, any failure by a service provider to comply with applicable data privacy and security obligations could result in adverse effects, including inability to operate our business and proceedings against us by governmental entities or others.

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litigation (including class-related claims);

additional reporting requirements and/or oversight;

additional reporting requirements and oversight;

bans on processing personal data;

orders to destroy or not use personal data;

individual, media or agency notifications, including without limitation notice to the Department of Health and Human Services;

and imprisonment of company officials.

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or revision or restructuring of our operations.

Moreover, trial participants or research subjects as well as the providers who share their information with us, may contractually limit our ability to use and disclose the information.

We or the third parties upon whom we depend may be adversely affected by natural disasters and/or terrorism attacks, and our business continuity and disaster recovery plans may not adequately protect us from a serious disaster.

Natural disasters could severely disrupt our operations, and have a material adverse effect on our business, results of operations, financial condition and prospects.

If a natural disaster, power outage, terrorism attack or other event occurred that prevented us from using all or a significant portion of our office, manufacturing and/or lab spaces, that damaged critical infrastructure, such as the manufacturing facilities of our third-party contract manufacturers, or that otherwise disrupted operations, it may be difficult or, in certain cases, impossible for us to continue our business for a substantial period of time.

The Company may incur

substantial expenses as a result of the limited nature of our disaster recovery and business continuity plans, which could have a material adverse effect on our business.

Risks Related to Corporate Governance and Employee Relations

Our future success depends on our ability to retain our Chief Executive Offices and other key executives and to attract, retain and motivate qualified personnel.

Moreover, trial participants or research subjects as well as the providers who share their information with us, may contractually limit our ability to use and disclose the information, and we may face significant liability for failing to abide by such limitations.

Risks Related to Operations

Our future success depends on our ability to retain our Co-Chief Executive Officers, Chief Operating Officer and other key executives .

We are highly dependent on the principal members of our executive and scientific teams, including Mr.

Duggan and and Dr.

Mahkam Zanganeh, our Chief Executive Officers,, and Mr.

Manmeet Soni, our Chief Operating Officer, all of whom are at-will employees.

Duggan and Dr.

Mahkam Zanganeh, our Co-Chief Executive Officers, and Mr.

Manmeet Soni, our Chief Operating Officer and Chief Financial Officer, all of whom are at-will employees.

They may terminate their employment with us at any time.

Duggan and Dr.

Zanganeh have also been married since December 18, 2024.

We do not maintain “key person” insurance on any of our executive officers.

The unplanned loss of the services of any of these persons could materially impact the achievement of our research, development and commercialization objectives.

Recruiting and retaining qualified scientific, clinical, manufacturing and sales and marketing personnel, including in the United States where we plan to continue to expand our physical presence, will also be critical to our success.

We may not be able to attract and retain these personnel on acceptable terms given the competition among numerous biotechnology and pharmaceutical companies for similar personnel.

We also experience competition for the hiring of scientific and clinical personnel from universities and research institutions.

In addition, we rely on consultants and advisors, including scientific and clinical advisors, to assist us in formulating our research and development and commercialization strategy.

We or the third parties we rely on may be adversely affected by social unrest or terrorism.

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.

We or the third parties we rely on may be adversely affected by natural disasters and our business continuity and disaster recovery plans may not adequately protect us from a serious disaster.

The changing nature, frequency, and severity of natural disasters and extreme weather events such as tornadoes, hurricanes flooding, extreme heat, and wildfires pose a risk to Company facilities, assets, and programs, as well as those of third parties on

whom we rely.

Natural disasters could severely disrupt our operations and have a material adverse effect on our business, results of operations, financial condition and prospects.

If a natural disaster, power outage, or other event occurred that prevented us from using all or a significant portion of our offices or prevented a third party on whom we rely from using its facilities, or if a disaster damaged critical infrastructure that we and third parties rely upon, or if a disaster otherwise disrupted operations, it may be difficult or, in certain cases, impossible, for us to continue our business for extended periods period of time.

In addition to operational impacts, natural disasters could significantly affect clinical trial participants, institutions, doctors, and supporting staff.

For participants, a disruption in trial operations could delay access to investigational therapies, compromise ongoing treatment regimens, or create uncertainty about trial continuity.

Institutions and medical personnel and staff could face logistical challenges, including damage to clinical trial sites, limited availability of resources, and interrupted communication channels.

Key staff may be unable to perform their duties due to displacement, injury, or other disaster-related issues, leading to trial delays and operational challenges.

Such disruptions may result in increased costs, delays in regulatory submissions, and reputational harm.

Our existing disaster recovery and business continuity plans may not fully mitigate these risks, and unanticipated gaps in communication during emergencies may hinder our decision making and response efforts.

We may incur substantial expenses to address and recover from such disruptions, which could further strain our financial and operational resources.

Widespread health concerns, pandemics or epidemics, and other outbreaks of illness may negatively affect the Company’s ability to maintain operations and execute its business plan.

Widespread health concerns, pandemics, epidemics and other outbreaks of illness can have evolving and uncertain impacts on our business.

As a result of any widespread health concern, pandemic, or other outbreaks of illness, including the COVID-19 pandemic, the Company has in the past and may experience disruptions that severely impact our business, commercialization, third party vendor operations, including foreign and domestic supply chains, or delays in clinical trial activities, including:

• delays or difficulties in initiating clinical trial sites;

• disruption to and delays in preclinical research and analysis activities due to an extended temporary closure of contract lab facilities;

• disruptions in supply, logistics or other activities related to the procurement of materials, which could have a negative impact on the Company’s ability to conduct preclinical studies, initiate or complete clinical trials or commercialize product candidates;

• diversion of healthcare resources away from conducting clinical trials;

• interruption of key preclinical studies and clinical trial activities, due to limitations on travel imposed or recommended by federal, state, provincial or municipal governments, employers and others;

• limitations in resources that would otherwise be focused on the conduct of the Company’s business or current or planned preclinical studies or clinical trials, including due to sickness, restrictions on travel, prolonged stay-at-home or shelter-in-place orders and other pandemic related concerns;

• slowed enrollment in and delayed execution of clinical trials due to hospital closures to clinical trials or patient hesitation to enroll in clinical trials;

• impact of infection of patients on the outcomes of clinical trials;

• changes in regulations as part of a response to the future pandemic or epidemic may require the Company to change the ways in which the preclinical studies and clinical trials are conducted and incur unexpected costs, or requires the Company to discontinue our preclinical research or clinical trials altogether.

Our employees may engage in misconduct or other improper activities, including non-compliance with regulatory standards and requirements, which could cause significant liability for us and harm our reputation.

We may be exposed to the risk of employee fraud or other misconduct, including intentional failures to comply with FDA or Office of Inspector General regulations or similar regulations of comparable non-U.S.

regulatory authorities, provide accurate information to the FDA or comparable non-U.S.

regulatory authorities, comply with manufacturing standards we have established, comply with federal and state healthcare fraud and abuse laws and regulations and similar laws and regulations established and enforced by comparable non-U.S.

regulatory authorities, report financial information or data accurately or disclose unauthorized activities to us.

Employee misconduct could also involve the improper use of information obtained in the course of clinical trials, which could result in regulatory sanctions and serious harm to our reputation, or a request for the reimbursement of expenses that were not incurred.

It is not always possible to identify and deter employee misconduct, and the precautions we take to detect and prevent this activity may not be effective in controlling unknown or unmanaged risks or losses or in protecting us from governmental investigations or other actions or lawsuits stemming from a failure to be in compliance with such laws, standards or regulations.

If any such actions are instituted against us, and we are not successful in

defending ourselves or asserting our rights, those actions could have a significant impact on our business and results of operations, including the imposition of significant fines and other sanctions.

Key personnel have been, and may continue to be, difficult to attract and retain.

Our ability to maintain and grow our business is directly related to the service of our employees in each area of our business, as we consider talent to be a key asset.

Our performance is directly tied to our ability to hire, train, motivate and retain qualified personnel, including highly skilled technical, operational and program managerial, clinical, medical, analytical and legal or financial personnel.

There is significant competition for personnel in the clinical sciences marketplace, particularly in certain geographies where we are located, including but not limited to the United States, where we plan to expand our physical presence, as well as Europe.

Also, employees in our industry are increasingly able to work remotely, which could increase employee mobility and turnover, making it more difficult for us to attract and retain employees.

In addition, many of our clinical development, operational and program management positions, require deep technical expertise, and it can be particularly challenging to identify and attract candidates and retain employees possessing such expertise.

We have experienced, and may continue to experience, attrition in certain key positions.

If we are unable to hire sufficient numbers of qualified employees or retain and motivate existing employees, our business and operating results would be harmed.

Additionally, we rely on consultants and advisors, including scientific and clinical advisors, to assist us in formulating our research and development, and commercialization strategy.

Our consultants and advisors may be employed by employers other than us and may have commitments under consulting or advisory contracts with other entities that may limit their availability to us.

Our principal stockholder and Chief Executive Officer maintains the ability to control or significantly influence all matters submitted to stockholders for approval.

Risks Related to Owning Our Common Stock

Our principal stockholder and Co-Chief Executive Officer maintains the ability to control or significantly influence all matters submitted to stockholders for approval.

As of December 31, 2024, Mr.

Duggan beneficially owned, in the aggregate, shares of common stock representing approximately 78.3% of our outstanding capital stock.

Duggan beneficially owned, in the aggregate, shares of common stock representing over 70% of our outstanding capital stock.

Duggan is able to control or significantly influence all matters submitted to our stockholders for approval, as well as our management and affairs.

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Accordingly, during the period we remain a controlled company and during any transition period following a time when we are no longer a controlled company, you may not have the same protections afforded to stockholders of companies that are subject to all of the corporate governance requirements of the Nasdaq Stock Market.

We are exposed to the risk of employee fraud or other misconduct, including intentional failures to comply with FDA or Office of Inspector General regulations or similar regulations of comparable non-U.S.

regulatory authorities, provide accurate information to the FDA or comparable non-U.S.

regulatory authorities, report financial information or data accurately or disclose unauthorized activities to us.

It is not always possible to identify and deter employee misconduct, and the

precautions we take to detect and prevent this activity may not be effective in controlling unknown or unmanaged risks or losses or in protecting us from governmental investigations or other actions or lawsuits stemming from a failure to be in compliance with such laws, standards or regulations.

If any such actions are instituted against us, and we are not successful in defending ourselves or asserting our rights, those actions could have a significant impact on our business and results of operations, including the imposition of significant fines or other sanctions.

Key personnel have been, and may continue to be, difficult to attract and retain.

Our ability to maintain and grow our business is directly related to the service of our employees in each area of our business, as we consider talent to be a significant asset.

There is significant competition for personnel in the clinical sciences marketplace, particularly in certain geographies where we are located, including but not limited to Miami, the San Francisco Bay area and Europe.

Also, employees in our industry are increasingly able to work remotely, which could increase employee mobility and turnover, making it more difficult for us to attract and retain employees.

We have experienced, and may continue to experience, attrition in certain key positions.

If we are unable to hire sufficient numbers of qualified employees or retain and motivate existing employees, our business and operating results would be harmed.

Risks Related to Owning Our Common Stock

The prices of our shares of common stock may be volatile and fluctuate substantially, which could result in substantial losses for our stockholders.

The market prices of our shares of common stock on the Nasdaq Global Market may be volatile and fluctuate substantially.

The price of our shares of common stock have in the past, and may continue to be volatile and fluctuate substantially, which could result in substantial losses for our stockholders.

The market prices of our shares of common stock on the Nasdaq Global Market have in the past and may continue to be volatile and fluctuate substantially.

The stock market in general and the market for smaller pharmaceutical and biotechnology companies in particular have experienced extreme volatility that has often been unrelated to the operating performance of particular companies.

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• results of clinical trials of product candidates of our competitors;

• the acquisition activity and licensing and collaboration efforts of our competitors and large biopharmaceutical companies;

• changes or developments in laws or regulations applicable to ivonescimab and any other product candidates that we develop;

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• regulatory or legal developments in the United States and other countries;

• the societal and economic impact of public health epidemics, such as the ongoing COVID-19 pandemic, and government efforts to slow their spread;

• the societal and economic impact of public health epidemics and pandemics, and government efforts to slow their spread;

• general economic, industry and market conditions;

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These fluctuations are often unrelated to the operating performance of particular companies.

These broad market fluctuations, such as those caused by the COVID-19 pandemic, may cause declines in the trading price and market value of our common stock.

These broad market fluctuations may cause declines in the trading price and market value of our common stock.

Substantial future sales of our shares of common stock in the public market, or the perception that these sales could occur, could cause the price of the shares to decline significantly, even if our business is doing well.

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Following the domestication, all of our outstanding shares of common stock were freely tradeable in the public market without restriction, unless held by our affiliates.

Our principal stockholder and chief executive officer, Mr.

Our principal stockholder and Co-Chief Executive Officer, Mr.

Duggan, holds a substantial number of shares.

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If he sells, or indicates an intention to sell, substantial amounts of shares in the public market, the trading price of our shares could decline.

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.

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.

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.

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.

As a company with shares of common stock that are publicly traded in the United States, and particularly after we are no longer a “smaller reporting company”, we have incurred and will continue to incur significant legal, accounting and other expenses that we did not previously incur.

In addition, the Sarbanes-Oxley Act, the Dodd-Frank Act, the listing requirements of the Nasdaq Stock Market and other applicable securities rules and regulations impose various requirements on public companies, including establishment and maintenance of effective disclosure and financial controls and corporate governance practices.

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.

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.

As a large accelerated filer, we are subject to certain disclosure requirements that are applicable to other public companies that were not applicable to us as a “non-accelerated filer” and “smaller reporting company.” We have incurred and will continue to incur significant legal, accounting and other expenses that we did not previously incur.

In addition, the Sarbanes-Oxley Act, the Dodd-Frank Act, the listing requirements of the Nasdaq Stock Market and other applicable securities rules and regulations impose various requirements on public companies, including the establishment and maintenance of effective disclosure and financial controls and corporate governance practices.

Our management and other personnel devote a substantial amount of time to these compliance initiatives.

Moreover, these rules and regulations increase our legal and financial compliance costs and make some activities more time-consuming and costly.

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.

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.

If we fail to maintain an effective system of internal control over financial reporting, we may not be able to accurately report our financial results or prevent fraud.

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We are required to disclose changes made in our internal controls and procedures on a quarterly basis, and our management is required to assess the effectiveness of these controls annually.

However, for as long as we are a “smaller reporting company”, our independent registered public accounting firm will not be required to attest to the effectiveness of our internal control over

financial reporting pursuant to Section 404.

Now that we have transitioned from a “ non-accelerated filer ” and “smaller reporting company” to a “large accelerated filer, ” our independent registered public accounting firm is required to attest to the effectiveness of our internal control over financial reporting pursuant to Section 404.

Pursuant to Section 404(a) of the Sarbanes-Oxley Act, we are required to furnish a report by our management on our internal controls over financial reporting.

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This could result in an adverse reaction in the financial markets due to a loss of confidence in the reliability of our financial statements.

Our restated certificate of incorporation designates the Court of Chancery of the State of Delaware and the federal district courts of the United States of America as the sole and exclusive forum for certain types of actions and proceedings that may be initiated by our stockholders, which could limit our stockholders’ ability to obtain a favorable judicial forum for disputes with us or our directors, officers and employees.

Our restated certificate of incorporation designates the Court of Chancery of the State of Delaware and the federal district courts of the U.S.

as the sole and exclusive forum for certain types of actions and proceedings that may be initiated by our stockholders, which could limit our stockholders’ ability to obtain a favorable judicial forum for disputes with us or our directors, officers and employees.

Our restated certificate of incorporation provides that, unless we consent in writing to the selection of an alternative forum, the Court of Chancery of the State of Delaware (or, if the Court of Chancery of the State of Delaware does not have jurisdiction, the federal district court for the District of Delaware) will be the sole and exclusive forum for the following types of actions or proceedings under Delaware statutory or common law:

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• any action asserting a claim of breach of a fiduciary duty owed by any of our directors, officers, employees or stockholders to our company or our stockholders;

• any action asserting a claim arising pursuant to any provision of the DGCL or as to which the DGCL confers jurisdiction on the Court of Chancery of the State of Delaware;

• any action asserting a claim arising pursuant to any provision of the Delaware General Corporation Law ("DGCL") or as to which the DGCL confers jurisdiction on the Court of Chancery of the State of Delaware;

• any action asserting a claim arising pursuant to any provision of our certificate of incorporation or bylaws (in each case, as they may be amended from time to time) or governed by the internal affairs doctrine.

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Accordingly, both state and federal courts have jurisdiction to entertain such claims.

To prevent having to litigate claims in multiple jurisdictions and the threat of inconsistent or contrary rulings by different courts, among other considerations, our restated certificate of incorporation provides that, unless we consent in writing to the selection of an alternative forum, the federal district courts of the United States of America shall, to the fullest extent permitted by law, be the sole and exclusive forum for the resolution of any claims arising under the Securities Act.

To prevent having to litigate claims in multiple jurisdictions and the threat of inconsistent or contrary rulings by different courts, among other

considerations, our restated certificate of incorporation provides that, unless we consent in writing to the selection of an alternative forum, the federal district courts of the U.S.

shall, to the fullest extent permitted by law, be the sole and exclusive forum for the resolution of any claims arising under the Securities Act.

While the Delaware courts have determined that such choice of forum provisions are facially valid, a stockholder may nevertheless seek to bring a claim in a venue other than those designated in the exclusive forum provisions.

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Because we do not anticipate paying any cash dividends on our shares of common stock in the foreseeable future, capital appreciation, if any, will be the sole source of gain for our stockholders.

We have never declared or paid cash dividends on our shares of common stock or on Summit Therapeutics plc’s ordinary shares.

We have never declared or paid cash dividends on our shares of common stock.

We currently intend to retain all of our future earnings to fund the development and expansion of our business.

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We are exposed to risks related to currency exchange rates.

We conduct a portion of our operations in the United Kingdom.

Because our financial statements are presented in U.S.

dollars, changes in currency exchange rates have had and could have a significant effect on our operating results when our operating results are translated into pounds sterling.

We conduct a portion of our operations in the U.K and rely on third parties across the globe.

Exchange rate fluctuations between local currencies and the U.S.

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The failure by our management to apply these funds effectively could result in financial losses that could have a material adverse effect on our business, cause the market price of our shares of common stock to decline and delay the development of our product candidates.

Risks Related to Widespread Health Concerns

Widespread health concerns, pandemics or epidemics, and other outbreaks of illness may negatively affect the Company’s ability to maintain operations and execute its business plan.

Widespread health concerns, pandemics, epidemics and other outbreaks of illness, particularly in North America but also globally, can have evolving and uncertain impacts on our business.

We continue to monitor our operations and applicable government recommendations, and we have made modifications to our normal operations because of the COVID-19 pandemic, including flexible working arrangements.

Changes in flexible working arrangements could impact employee retention, employees’ productivity and morale, strain our technology resources and introduce operational risks.

Additionally, the risk of cyber-attacks or other privacy or data security incidents may be heightened as a result of our moving increasingly towards a remote working environment, which may be less secure and more susceptible to hacking attacks.

As a result of any widespread health concern, pandemic, or other outbreaks of illness, including the COVID-19 pandemic, the Company may experience disruptions that severely impact our business, commercialization, third party vendor operations, including foreign and domestic supply chains, or delays in clinical trial activities, including:

◦ delays or difficulties in initiating clinical trial sites;

◦ disruption to and delays in preclinical research and analysis activities due to an extended temporary closure of contract lab facilities;

◦ disruptions in supply, logistics or other activities related to the procurement of materials, which could have a negative impact on the Company’s ability to conduct preclinical studies, initiate or complete clinical trials or commercialize product candidates;

◦ diversion of healthcare resources away from conducting clinical trials;

◦ interruption of key preclinical studies and clinical trial activities, due to limitations on travel imposed or recommended by federal, state, provincial or municipal governments, employers and others;

◦ limitations in resources that would otherwise be focused on the conduct of the Company’s business or current or planned preclinical studies or clinical trials, including due to sickness, restrictions on travel, prolonged stay-at-home or shelter-in-place orders and other pandemic related concerns;

◦ changes in regulations as part of a response to the future pandemic and/or epidemic may require the Company to change the ways in which the preclinical studies and clinical trials are conducted and incur unexpected costs, or requires the Company to discontinue our preclinical research or clinical trials altogether.

We may complete a future acquisition that may not achieve intended results or could increase the number of our outstanding shares or amount of outstanding debt or result in a change of control.

Evaluating potential transactions and integrating completed ones may divert the attention of our management from ordinary operating matters.

In addition, acquired businesses may have unanticipated liabilities or contingencies.

Compared sentence by sentence after normalising whitespace, quotation marks, case and digits, so re-formatting and restated figures do not read as changed language. Wording changes appear as one removal and one addition. The current filing and the prior one are authoritative.

What changed 10-K

Item 1A. Risk Factors