−Removed: Investing in our American Depositary Shares, or ADSs, involves a high degree of risk.
+Added: Investing in our American Depositary Shares ("ADSs") involves a high degree of risk.
You should carefully consider the following risks and uncertainties, together with all other information in this report, including our consolidated financial statements and related notes and “Management’s Discussion and Analysis of Financial Condition and Results of Operations,” as well as our other filings with the Securities and Exchange Commission.
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We have incurred net losses each year since inception through to December 31, 2021.
−Removed: For the year ended December 31, 2022, we reported a net income of $5.3 million, and net loss of $51.1 million for the year ended December 31, 2021.
−Removed: As of December 31, 2022, we had an accumulated deficit of $103.2 million.
−Removed: Notwithstanding that we were profitable in 2022, we do not expect profits or positive cash flows from operations in the foreseeable future.
+Added: For the year ended December 31, 2022, we generated net income of $5.3 million, primarily as a result of revenues arising from AstraZeneca sales of Vaxzevria and our agreement with OUI.
+Added: For the year ended December 31, 2023, we incurred net losses of $73.4 million.
+Added: As of December 31, 2023 and 2022, we had an accumulated deficit of $176.6 million and $103.2 million, respectively, and we do not currently expect profits or positive cash flows from operations in the foreseeable future.
We anticipate that our expenses will increase substantially if, and as we:
• seek marketing authorizations for product candidates that successfully complete clinical trials, if any;
−Removed: ● conduct preclinical studies and clinical trials for our current and future product candidates based on our proprietary biologic and synthetic platforms, including the Chimpanzee Adenovirus Oxford, or ChAdOx, and Modified vaccinia Ankara, or MVA, vectors, SNAPvax and our other technologies;
+Added: • conduct preclinical studies and clinical trials for our current and future product candidates based on our proprietary biologic and synthetic platforms, including the Chimpanzee Adenovirus Oxford ("ChAdOx") and Modified vaccinia Ankara ("MVA"), vectors, SNAP-TI, SNAP-CI and our other technologies;
• expand our operational, financial and management systems and increase personnel, including personnel to support our clinical development, manufacturing and commercialization efforts and our operations as a public company;
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The size of our future net losses will depend, in part, on the rate of future growth of our expenses and our ability to generate revenue.
−Removed: Our prior losses and expected future losses have had and will continue to have an adverse effect on our shareholders’ equity and working capital.
+Added: Our prior losses and expected future losses have had and will continue to have an adverse effect on our stockholders’ equity and working capital.
If we do achieve profitability, we may not be able to sustain or increase profitability on a quarterly or annual basis.
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A decline in the value of our company also could cause you to lose all or part of your investment.
−Removed: Actual payments we may receive in connection with certain milestones or net sales under the AstraZeneca License Agreement may differ materially from those described in this Annual Report, and there can be no assurance that we will receive any such payments at all.
−Removed: While we currently receive a share of certain milestones and royalties on net sales of certain vaccines under the research collaboration and exclusive worldwide license agreement, or the AstraZeneca License Agreement, between Oxford University Innovation Limited, or OUI, and AstraZeneca UK Limited, or AstraZeneca, there can be no assurance as to the timing or amount of any such milestones or royalties on net sales.
−Removed: In particular, we are not party to the AstraZeneca License Agreement, and we do not have any direct claim against AstraZeneca to receive a share of any milestones or net sales, or any other payments under the AstraZeneca License Agreement.
−Removed: Instead, we are party to the amendment, assignment and revenue share agreement, or the OUI License Agreement Amendment, with OUI, to the license agreement we entered into with OUI in March 2016, pursuant to which OUI agreed to pay us approximately 24% of payments, including royalties and milestones, received by OUI in connection with the commercialization of any ChAdOx1 vector-based or ChAdOx2 vector-based vaccine in the field of SARS-CoV2 covered by or disclosed in the assigned patent application.
−Removed: As a result, we will only receive a share of any milestones or royalties paid on net sales of any such vaccine under the AstraZeneca License Agreement if, and to the extent that, OUI receives a share of any such milestones or royalties pursuant to that agreement.
−Removed: Moreover, our understanding is that, under the AstraZeneca License Agreement, OUI agreed to forego its share of any royalties from the commercialization of AZD1222 until after the pandemic period.
−Removed: In April 2022, we announced the commencement of royalty payments relating to commercial sales of Vaxzevria (formerly AZD1222).
−Removed: Our understanding of the terms of the AstraZeneca License Agreement is based solely on an extract of the agreement provided by the parties to that agreement.
−Removed: We are not a party to the AstraZeneca License Agreement and do not have access to a copy of that agreement to verify such extract.
−Removed: In addition, no party to the AstraZeneca License Agreement has confirmed that there are no material terms in that agreement that could adversely impact the economic and other terms of the AstraZeneca License Agreement.
−Removed: Moreover, there can be no assurance that the AstraZeneca License Agreement is an enforceable agreement, that the parties thereto will comply with their obligations under the agreement (including any obligations of AstraZeneca to make milestone or royalty payments to OUI), that the agreement will not be terminated pursuant to its terms or otherwise, or that the terms of the agreement (including royalty rates and other economic terms) will not be modified by the parties in the future.
−Removed: Accordingly, these and other factors could cause amounts received by OUI pursuant to the AstraZeneca License Agreement, and accordingly any share of the revenue under that agreement that we may receive, to fluctuate.
−Removed: Any such fluctuations could be material.
−Removed: Additionally, our understanding of the terms of the AstraZeneca License Agreement is that AstraZeneca is required to notify OUI of OUI’s shares of milestone and royalty payments within 30 days following the close of a fiscal quarter.
−Removed: OUI is then required to notify us of our share of the payments within 30 days after the end of a quarter when OUI received such milestone or royalty payments from AstraZeneca.
−Removed: If the required notifications are not made in accordance with the terms of the agreements, we may not be able to recognize revenue in the period in which it is earned.
−Removed: In addition, the announcement of adverse events observed in individuals who receive Vaxzevria and any negative impact on the perceptions of Vaxzevria safety may reduce sales of the vaccine and therefore the potential payments that we would receive from royalties paid on net sales of Vaxzevria.
−Removed: Further, if Vaxzevria is found to be less effective against certain variants of COVID-19, then that may also reduce sales of the vaccine.
−Removed: Any association of Vaxzevria with adverse events, or the perception of such association, or any findings that Vaxzevria is less effective against certain variants of COVID-19, may prevent or reduce sales of Vaxzevria and therefore the potential payments that we may receive from net sales of the vaccine, and may otherwise adversely impact the development of, and our ability to commercialize, any of our product candidates.
We have not yet generated any material revenue from our product candidates.
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Certain of our product candidates are in the preclinical stages of development and will require additional preclinical studies, and all of our product candidates will require additional clinical development, regulatory review and approval, substantial investment, access to sufficient commercial manufacturing capacity and significant marketing efforts before we can generate any revenue from product sales.
−Removed: We have not yet administered certain of our product candidates to humans and, as such, we face significant translational risk as our product candidates advance into and through the clinical stage, as promising results in preclinical studies may not be replicated in subsequent clinical trials, and testing on animals may not accurately predict human experience.
+Added: We have not yet administered certain of our product candidates to humans
+Added: and, as such, we face significant translational risk as our product candidates advance into and through the clinical stage, as promising results in preclinical studies may not be replicated in subsequent clinical trials, and testing on animals may not accurately predict human experience.
Our ability to generate revenue depends on a number of factors, including, but not limited to:
• timely completion of our manufacturing, preclinical studies and clinical trials, which may be significantly slower or cost more than we currently anticipate and will depend substantially upon the performance of third-party contractors;
−Removed: ● delays out of our control, such as those currently experienced with the unforeseen pandemic effect on clinical trial progress and participant willingness to enroll;
−Removed: ● our ability to complete investigational new drug application, or IND, enabling trials and successfully submit INDs or comparable applications, for our product candidates;
−Removed: ● whether we are required by the U.S.
−Removed: Food and Drug Administration, or the FDA, the European Medicines Agency, or the EMA, or the United Kingdom Medicines and Healthcare products Regulatory Agency, or the MHRA, or similar foreign regulatory authorities, to conduct additional clinical trials or other studies beyond those planned to support the approval and commercialization of our product candidates or any future product candidates;
+Added: • delays out of our control, such as participant willingness to enroll;
+Added: • our ability to complete IND, enabling trials and successfully submit INDs or comparable applications, for our product candidates;
+Added: • whether we are required by the FDA, the EMA, or the MHRA or similar foreign regulatory authorities, to conduct additional clinical trials or other studies beyond those planned to support the approval and commercialization of our product candidates or any future product candidates;
• our ability to demonstrate to the satisfaction of the FDA and similar foreign regulatory authorities the safety, potency, purity, efficacy and acceptable risk to benefit profile of our product candidates or any future product candidates and such regulatory authorities’ acceptance of our development strategy;
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• the actual and perceived availability, cost, risk profile and side effects and efficacy of our product candidates, if approved, relative to existing and future alternative immunotherapies, therapeutic and prophylactic vaccines and competitive product candidates and technologies;
−Removed: our ability and the ability of third parties with whom we contract to manufacture adequate clinical and commercial supplies of our product candidates or any future product candidates, remain in good standing with regulatory authorities and develop, validate and maintain commercially viable manufacturing processes that are compliant with current good manufacturing practices, or cGMP;
+Added: our ability and the ability of third parties with whom we contract to manufacture adequate clinical and commercial supplies of our product candidates or any future product candidates, remain in good standing with regulatory authorities and develop, validate and maintain commercially viable manufacturing processes that are compliant with cGMP;
• our ability to successfully develop a commercial strategy and thereafter commercialize our product candidates or any future product candidates in the United States and internationally, if approved for marketing, reimbursement, sale and distribution in such countries and territories, whether alone or in collaboration with others;
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• the ability of our licensees and collaborators to develop and commercialize our products effectively;
−Removed: ● the risk that some or all of the patients that receive Vaxzevria develop neutralizing antibodies against ChAdOx, which could limit the immunogenicity from subsequent dosing with one of our product candidates;
+Added: • the risk that some or all of the patients that receive Vaxzevria develop neutralizing antibodies against ChAdOx, which could limit the immunological response from subsequent dosing with one of our product candidates;
• the possibility that immunogenicity may not translate into clinical benefit;
−Removed: ● the increased costs and complexities associated with manufacturing both the prime and boost elements, ChAdOx, MVA and SNAPvax, of our immunotherapeutics.
+Added: • the increased costs and complexities associated with manufacturing and
+Added: • funding for the development of product candidates contributed by third parties, such as CRUK, CEPI and CanSino, whether spent directly by them or by grant or other funding into our company.
Many of the factors listed above are beyond our control and could cause us to experience significant delays or prevent us from obtaining marketing authorizations for, or commercializing, our product candidates.
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If we are unable to generate sufficient revenue through the sale of our product candidates or any future product candidates, we may be unable to continue operations without continued funding.
−Removed: If we engage in further acquisitions or future strategic partnerships, this may increase our capital requirements, dilute our shareholders, cause us to incur debt or assume contingent liabilities, and subject us to other risks.
−Removed: We engaged in an acquisition and may evaluate additional acquisitions and strategic partnerships in the future, including licensing or acquiring complementary product candidates, intellectual property rights, technologies or businesses.
+Added: If we engage in acquisitions or future strategic partnerships, this may increase our capital requirements, dilute our shareholders, cause us to incur debt or assume contingent liabilities, and subject us to other risks.
+Added: We may evaluate acquisitions and strategic partnerships in the future, including licensing or acquiring complementary product candidates, intellectual property rights, technologies or businesses.
Any acquisition or strategic partnership may entail numerous risks, including:
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Failure to obtain this necessary capital when needed may force us to delay, limit or terminate our product development efforts or other operations.
−Removed: We are currently advancing current and future product candidates based on our proprietary biologic and synthetic platforms, including the Chimpanzee Adenovirus Oxford, or ChAdOx, and Modified vaccinia Ankara, or MVA, vectors, SNAPvax and our other technologies through clinical development.
+Added: We are currently advancing current and future product candidates based on our proprietary biologic and synthetic platforms, including the ChAdOx and MVA vectors, SNAP-TI, SNAP-CI and our other technologies through clinical development.
Developing and commercializing products for therapeutic indications is expensive, and we do not expect to generate meaningful product revenues in the foreseeable future.
As of December 31, 2023, our cash and cash equivalents were $142.1 million.
−Removed: Based on our current business plan, our management believes that we have sufficient cash to support our operations in to the first quarter of 2025, without additional financing.
+Added: Based on our current business plan, our management believes that we have sufficient cash to support our operations into the fourth quarter of 2025, without additional financing.
Our fundraising efforts to raise additional capital may divert our management from their day-to-day activities, which may adversely affect our ability to develop our platforms.
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Moreover, the terms of any financing may adversely affect the holdings or the rights of our shareholders and the issuance of additional securities, whether equity or debt, by us, or the possibility of such issuance, may cause the market price of our shares to decline.
−Removed: The sale of additional equity or convertible securities would dilute all of our stockholders.
−Removed: The incurrence of indebtedness would result in increased fixed payment obligations and we may be required to agree to certain restrictive covenants, such as limitations on our ability to incur additional debt, limitations on our ability to acquire, sell or license intellectual property rights and other operating restrictions that could adversely impact our ability to conduct our business.
+Added: The sale of additional equity or convertible securities would dilute our stockholders.
+Added: The incurrence of indebtedness would result in increased fixed payment obligations and we may be required to agree to certain restrictive covenants, such as limitations on our ability to incur additional debt, limitations on our ability to acquire, sell or license intellectual property rights and other
+Added: operating restrictions that could adversely impact our ability to conduct our business.
We could also be required to seek funds through arrangements with collaborative partners or otherwise at an earlier stage than otherwise would be desirable and we may be required to relinquish rights to some of our technologies or product candidates or otherwise agree to terms unfavorable to us, any of which may have a material adverse effect on our business, operating results and prospects.
−Removed: If we are unable to obtain funding on a timely basis, we may be required to revise our business plan and strategy, which may result in us significantly curtailing, delaying or discontinuing one or more of our clinical trials or may result in our being unable to expand our operations or otherwise capitalize on our business opportunities.
+Added: If we are unable to obtain funding on a timely basis, we may be required to revise our business plan and strategy, which may result in us significantly curtailing, delaying or discontinuing one or more of our clinical trials, decreasing headcount or may result in our being unable to expand our operations or otherwise capitalize on our business opportunities.
As a result, our business, financial condition and results of operations could be materially affected.
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• the costs, timing and outcome of regulatory review of our product candidates;
−Removed: ● the success of the COVID-19 vaccine program for which we licensed certain of our licensed intellectual property rights to OUI/AstraZeneca;
• the costs of future commercialization activities, including product sales, marketing, manufacturing and distribution, for any of our product candidates for which we receive marketing approval;
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Actual events involving limited liquidity, defaults, non-performance or other adverse developments that affect financial institutions, transactional counterparties or other companies in the financial services industry or the financial services industry generally, or concerns or rumors about any events of these kinds or other similar risks, have in the past and may in the future lead to market-wide liquidity problems.
−Removed: For example, on March 10, 2023, Silicon Valley Bank (“SVB US”), was closed by the California Department of Financial Protection and Innovation, which appointed the Federal Deposit Insurance Corporation, or FDIC, as receiver.
+Added: For example, on March 10, 2023, Silicon Valley Bank was closed by the California Department of Financial Protection and Innovation, which appointed the Federal Deposit Insurance Corporation ("FDIC") as receiver.
Similarly, on March 12, 2023, Signature Bank was swept into receivership.
−Removed: Although a statement by the Department of the Treasury, the Federal Reserve and the FDIC indicated that all depositors of SVB US would have access to all of their money after only one business day of closure, including funds held in uninsured deposit accounts, borrowers under credit agreements, letters of credit and certain other financial instruments with SVB US, Signature Bank or any other financial institution that is placed into receivership by the FDIC may be unable to access undrawn amounts thereunder.
−Removed: In addition, on March 10, 2023, The Bank of England announced that, absent any meaningful further information, it intends to apply to the Court to place Silicon Valley Bank UK Limited (“SVB UK”) into a Bank Insolvency Procedure.
−Removed: On March 13, 2023, The Bank of England announced that, in consultation with the Prudential Regulation Authority (“PRA”) HM Treasury (“HMT”), and the Financial Conduct Authority (“FCA”) it has taken the decision to sell SVB UK to HSBC UK Bank Plc, (“HSBC”).
−Removed: The Bank of England stated that all depositors’ money with SVB UK is safe and secure as a result of this transaction.
−Removed: The Bank of England further stated that SVB UK’s business will continue to be operated normally by SVB UK and that all services will continue to operate as normal and customers should not notice any changes.
−Removed: As of March 10, 2023, we believe that we had limited exposure to SVB US, and had less than 1% of our cash on deposit with SVB US through our subsidiary, Vaccitech North America Inc.
−Removed: Additionally, we have a $0.2 million letter of credit held with SVB US related to a lease.
−Removed: As of March 10, 2023, a substantial amount of our cash was on deposit with SVB UK.
−Removed: Although we are not a borrower or party to any other such instruments with Signature or any other financial institution currently in receivership or a similar proceeding, if any of our counterparties to any such instruments were to be placed into receivership, we may be unable to access such funds.
−Removed: In addition, if any of our suppliers or other parties with whom we conduct business are unable to access funds pursuant to such instruments or lending arrangements with such a financial institution, such parties’ ability to pay their obligations to us or to enter into new commercial arrangements requiring additional payments to us could be adversely affected.
−Removed: In this regard, counterparties to SVB US or SVB UK credit agreements and arrangements, and third parties such as beneficiaries of letters of credit (among others), may experience direct impacts from the closure of SVB US and SVB UK and uncertainty remains over liquidity concerns in the broader financial services industry.
−Removed: Similar impacts have occurred in the past, such as during the 2008-2010 financial crisis.
−Removed: Inflation and rapid increases in interest rates have led to a decline in the trading value of previously issued government securities with interest rates below current market interest rates.
−Removed: Although the U.S.
−Removed: Department of Treasury, FDIC and Federal Reserve Board have announced a program to provide up to $25 billion of loans to financial institutions secured by certain of such government securities held by financial institutions to mitigate the risk of potential losses on the sale of such instruments, widespread demands for customer withdrawals or other liquidity needs of financial institutions for immediately liquidity may exceed the capacity of such program.
−Removed: Additionally, there is no guarantee that the U.S.
−Removed: Department of Treasury, FDIC and Federal Reserve Board will provide access to uninsured funds in the future in the event of the closure of other banks or financial institutions, or that they would do so in a timely fashion.
Although we assess our banking relationships as we believe necessary or appropriate, our access to funding sources and other credit arrangements in amounts adequate to finance or capitalize our current and projected future business operations could be significantly impaired by factors that affect us, the financial institutions with which we have financial arrangements directly, or the financial services industry or economy in general.
These factors could include, among others, events such as liquidity constraints or failures, the ability to perform obligations under various types of financial, credit or liquidity agreements or arrangements, disruptions or instability in the financial services industry or financial markets, or concerns or negative expectations about the prospects for companies in the financial services industry.
−Removed: These factors could involve financial institutions or financial services industry companies with which we have financial or business relationships, but could also include factors involving financial markets or the financial services industry generally.
+Added: These factors could
+Added: involve financial institutions or financial services industry companies with which we have financial or business relationships, but could also include factors involving financial markets or the financial services industry generally.
The results of events or concerns that involve one or more of these factors could include a variety of material and adverse impacts on our current and projected business operations and our financial condition and results of operations.
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Any third-party manufacturer or supplier bankruptcy or insolvency, or any breach or default by a third-party manufacturer or supplier, or the loss of any significant third-party manufacturer or supplier relationships, could result in material losses to us and may have a material adverse impact on our business.
+Added: Actual payments we may receive in connection with certain milestones or net sales under the AstraZeneca License Agreement may differ from those described in this Annual Report, and there can be no assurance that we will receive any such payments at all.
+Added: We received a share of certain milestones and royalties on net sales of certain vaccines under the research collaboration and exclusive worldwide license agreement (the "AstraZeneca License Agreement"), between Oxford University Innovation Limited ("OUI") and AstraZeneca UK Limited ("AstraZeneca"), through to the second quarter of 2023, however there can be no assurance as to the timing or amount of any such milestones or royalties on future net sales.
+Added: In particular, we are not party to the AstraZeneca License Agreement, and we do not have any direct claim against AstraZeneca to receive a share of any milestones or net sales, or any other payments under the AstraZeneca License Agreement.
+Added: Instead, we are party to the amendment, assignment and revenue share agreement, or the OUI License Agreement Amendment, with OUI, to the license agreement we entered into with OUI in March 2016, pursuant to which OUI agreed to pay us approximately 24% of payments, including royalties and milestones, received by OUI in connection with the commercialization of any ChAdOx1 vector-based or ChAdOx2 vector-based vaccine in the field of SARS-CoV2 covered by or disclosed in the assigned patent application.
+Added: As a result, we will only receive a share of any milestones or royalties paid on net sales of any such vaccine under the AstraZeneca License Agreement if, and to the extent that, OUI receives a share of any such milestones or royalties pursuant to that agreement.
+Added: Our understanding of the terms of the AstraZeneca License Agreement is based solely on an extract of the agreement provided by the parties to that agreement.
+Added: We are not a party to the AstraZeneca License Agreement and do not have access to a copy of that agreement to verify such extract.
+Added: In addition, no party to the AstraZeneca License Agreement has confirmed that there are no material terms in that agreement that could adversely impact the economic and other terms of the AstraZeneca License Agreement.
+Added: Moreover, there can be no assurance that the AstraZeneca License Agreement is an enforceable agreement, that the parties thereto will comply with their obligations under the agreement (including any obligations of AstraZeneca to make milestone or royalty payments to OUI), that the agreement will not be terminated pursuant to its terms or otherwise, or that the terms of the agreement (including royalty rates and other economic terms) will not be modified by the parties in the future.
+Added: Accordingly, these and other factors could cause amounts received by OUI pursuant to the AstraZeneca License Agreement, and accordingly any share of the revenue under that agreement that we may receive, to fluctuate.
+Added: Any such fluctuations could be material.
+Added: Additionally, our understanding of the terms of the AstraZeneca License Agreement is that AstraZeneca is required to notify OUI of OUI’s shares of milestone and royalty payments within 30 days following the close of a fiscal quarter.
+Added: OUI is then required to notify us of our share of the payments within 30 days after the end of a quarter when OUI received such milestone or royalty payments from AstraZeneca.
+Added: If the required notifications are not made in accordance with the terms of the agreements, we may not be able to recognize revenue in the period in which it is earned.
+Added: In addition, the announcement of adverse events observed in individuals who receive Vaxzevria and any negative impact on the perceptions of Vaxzevria safety may reduce sales of the vaccine and AstraZeneca may decide not to market Vaxzevria, and therefore reduce the potential payments that we would receive from royalties paid on net sales of Vaxzevria.
+Added: Any association of Vaxzevria with adverse events, or the perception of such association, may otherwise adversely impact the development of, and our ability to commercialize, any of our product candidates.
Risks Related to Our Business and Industry and Risks Related to Clinical Development
If we are unable to advance our current or future product candidates into and through clinical trials, obtain marketing approval or reimbursement and ultimately commercialize any product candidates we develop, or experience significant delays in doing so, our business will be materially harmed.
−Removed: All of our product candidates are in early stages of development, including our lead product candidates, VTP-300, VTP-200, VTP-850, VTP-600, VTP-1100 and VTP-1000, and as such will require extensive preclinical and clinical testing, as applicable.
−Removed: Product candidates may not meet targeted clinical or safety endpoints during clinical trials such as the MVA-based influenza prophylactic, VTP-100, which did not meet defined primary clinical endpoints in two concurrent Phase 2b trials and we subsequently discontinued further development of this program.
+Added: All of our product candidates are in early stages of development, including our lead product candidates VTP-300 and VTP-200, and as such will require extensive preclinical and clinical testing, as applicable.
+Added: Product candidates may not meet targeted clinical or safety endpoints during clinical trials such as the MVA-based influenza vaccine candidate, VTP-100, which did not meet defined primary clinical endpoints in two concurrent Phase 2b trials and we subsequently discontinued further development of this program.
+Added: Our product candidate VTP-1100 in HPV cancer was paused in January 2024 to prioritize the other pipeline candidates already in the clinic, and the advancement of VTP-1100 may depend on our ability to fund or how we prioritize our pipeline.
Our ability to generate product revenues, which we do not expect to occur for several years, if ever, will depend heavily on the successful development and eventual commercialization or out-license of the product candidates we develop, which may never occur.
−Removed: Before we are able to generate any revenues from product sales, our current product candidates, and any future product candidates we develop, will require additional preclinical and clinical development, management of clinical, preclinical and manufacturing activities, marketing approval in the United States and other markets, demonstrating effectiveness to pricing and reimbursement authorities, obtaining sufficient manufacturing supply for both clinical development and commercial production, building of a commercial organization, and substantial investment and significant marketing efforts.
+Added: Before we are able to generate any revenues from product sales, our current product candidates, and any future product candidates we develop, will require additional preclinical and clinical development, management of preclinical, clinical, and manufacturing activities, marketing approval in the United States and other markets, demonstrating effectiveness to pricing and reimbursement authorities, obtaining sufficient manufacturing supply for both clinical development and commercial production, building of a commercial organization, and substantial investment and significant marketing efforts.
The success of our current and future product candidates will depend on several factors, including the following:
−Removed: ● successful completion, with sufficient efficacy and safety profiles, of preclinical studies and clinical trials;
+Added: • successful completion, with sufficient safety and efficacy profiles, of preclinical studies and clinical trials;
• sufficiency of our financial and other resources to complete the necessary preclinical studies and clinical trials;
• acceptance of INDs or equivalent clinical trial authorizations in other regions for our planned clinical trials or future clinical trials;
−Removed: ● successful enrollment and completion of our ongoing and future clinical trials, including any delays in enrollment or completed due to the evolving COVID-19 pandemic;
+Added: • successful enrollment and completion of our ongoing and future clinical trials;
• sufficient data from our clinical program that support an acceptable risk-benefit profile of our product candidates in the intended populations;
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• establishing our own manufacturing capabilities or agreements with third-party manufacturers for clinical supply for our clinical trials and commercial manufacturing, if our product candidate is approved;
−Removed: ● ability to develop product candidate formulations that provide sufficient genetic and thermal stability for long term storage and shipment to meet market requirements;
+Added: • ability to develop product candidate designs and formulations that provide sufficient genetic and thermal stability for long term storage and shipment to meet market requirements;
• entry into collaborations, where needed, to further the development of our product candidates;
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• the risk that foreign regulatory authorities may not authorize our clinical trial protocols and other clinical trial documentation, including manufacturing documentation, even when previously authorized by the FDA, EMA or MHRA, which could lead to a delay in starting such clinical trials.
−Removed: For example, we are conducting our HBV002 clinical trial in South Korea and have experienced delays due to additional regulatory review of our clinical protocol.
+Added: For example, our HBV002 clinical trial conducted in South Korea experienced delays due to additional regulatory review of our clinical protocol.
We have limited experience obtaining such approvals in foreign jurisdictions and therefore may need more time to navigate the regulatory process as a result.
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If our preclinical studies and clinical trials are not sufficient to support marketing authorization of any of our product candidates, we may incur additional costs or experience delays in completing, or ultimately be unable to complete, the development of such product candidate.
−Removed: We may experience delays in obtaining the FDA’s authorization to initiate clinical trials under future INDs, completing ongoing preclinical studies of our other product candidates, and initiating our planned preclinical studies and clinical trials.
+Added: We may experience delays in obtaining the FDA’s or other regulatory agencies authorization to initiate clinical trials under future INDs, completing ongoing preclinical studies of our other product candidates, and initiating our planned preclinical studies and clinical trials.
Additionally, we cannot be certain that preclinical studies or clinical trials for our product candidates will begin on time, not require redesign, enroll an adequate number of participants on time, or be completed on schedule, if at all.
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• future collaborators may conduct clinical trials in ways they view as advantageous to them but that are suboptimal for us.
−Removed: In addition, the ChAdOx vectors are currently being evaluated in clinical trials outside of our licensed fields conducted by the University of Oxford and other third parties to which OUI has granted licenses, including trials conducted by AstraZeneca for Vaxzevria.
−Removed: We have no control over these other clinical trials and any adverse results in these clinical trials could impact public perception and regulatory
−Removed: approval of our product candidates.
+Added: In addition, the ChAdOx vectors are currently being evaluated in clinical trials outside of our licensed fields conducted by Oxford and other third parties to which OUI has granted licenses.
+Added: We have no control over these other clinical trials and any adverse results in these clinical trials could impact public perception and regulatory approval of our product candidates.
Even after any of our product candidates obtain regulatory marketing authorization, the announcement of adverse events observed in individuals who receive these products may impact public perception and may result in increased regulatory scrutiny across our platform.
For example, in March 2021, several countries announced plans to either temporarily suspend the use of a particular batch of Vaxzevria or the use of Vaxzevria altogether following reports of very rare thromboembolic events in people following vaccination.
−Removed: While the European Medicines Agency, or the EMA, subsequently issued an update confirming the overall risk-benefit profile of Vaxzevria remains positive, and Vaxzevria later received full marketing authorization in the EU in November 2022, the applicable regulatory authorities continue to assess available safety data as Vaxzevria continues to be administered and have made recommendations regarding updates to the vaccine’s labeling and use in certain populations.
+Added: While the EMA subsequently issued an update confirming the overall risk-benefit profile of Vaxzevria remains positive, and Vaxzevria later received full marketing authorization in the EU in November 2022, the applicable regulatory authorities continue to assess available safety data as Vaxzevria continues to be administered and have made recommendations regarding updates to the vaccine’s labeling and use in certain populations.
These recommendations may continue to evolve, and these types of announcements may affect public perception of the safety of Vaxzevria, which may extend to product candidates we are developing.
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If we are required to conduct additional clinical trials or other testing of our product candidates beyond those that we currently contemplate, if we are unable to successfully complete clinical trials of our product candidates or other testing, if the results of these trials or tests are not positive or are only moderately positive or if there are safety concerns, our business and results of operations may be adversely affected and we may incur significant additional costs.
−Removed: We could also encounter delays if a clinical trial is suspended or terminated by us, by the Institutional Review Boards, or IRBs, or ethics committees of the institutions in which such clinical trials are being conducted, or by the FDA or other regulatory authorities, or suspended or terminated based on recommendations by the Data Safety Monitoring Board or equivalent for such clinical trial.
+Added: We could also encounter delays if a clinical trial is suspended or terminated by us, by the IRBs, or ethics committees of the institutions in which such clinical trials are being conducted, or by the FDA or other regulatory authorities, or suspended or terminated based on recommendations by the Data Safety Monitoring Board or equivalent for such clinical trial.
Such authorities may suspend or terminate a clinical trial due to a number of factors, including failure to conduct the clinical trial in accordance with regulatory requirements or our clinical trial protocols, inspection of the clinical trial operations or trial site by the FDA or other regulatory authorities resulting in the imposition of a clinical hold, unforeseen safety issues or adverse side effects, failure to demonstrate a benefit from the product candidates, changes in governmental regulations or administrative actions or lack of adequate funding to continue the clinical trial.
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From time to time, we may publicly disclose preliminary or topline data from our preclinical studies and clinical trials, which is based on a preliminary analysis of then-available data, and the results and related findings and conclusions are subject to change following a more comprehensive review of the more complete data related to the particular study or trial.
−Removed: We also make assumptions, estimations,
−Removed: calculations and conclusions as part of our analyses of data, and we may not have received or had the opportunity to fully and carefully evaluate all data.
+Added: We also make assumptions, estimations, calculations and conclusions as part of our analyses of data, and we may not have received or had the opportunity to fully and carefully evaluate all data.
As a result, the topline or preliminary results that we report may differ from future results of the same studies or clinical trials, or different conclusions or considerations may qualify such results, once additional data have been received and fully evaluated.
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Further, disclosure of interim data by us or by our competitors could result in volatility in the price of our ADSs.
−Removed: In addition, the ChAdOx vectors are currently being evaluated in clinical trials conducted by Oxford and other third parties to which the University of Oxford has granted licenses, including trials conducted by AstraZeneca for Vaxzevria.
+Added: In addition, the ChAdOx vectors are currently being evaluated in clinical trials conducted by Oxford and other third parties to which Oxford has granted licenses.
We have no control over these other clinical trials and any adverse results in these clinical trials could impact public perception and regulatory approval of our product candidates.
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If the interim, topline, or preliminary data that we report differ from more complete results, or if others, including regulatory authorities, disagree with the conclusions reached, our ability to obtain marketing authorization for, and commercialize, our product candidates may be harmed, which could harm our business, operating results, prospects or financial condition.
−Removed: Our product candidates are based on a novel approach to the treatment of cancer, which makes it difficult to predict the time and cost of product candidate development.
−Removed: We have concentrated our research and development efforts on our proprietary platform to develop product candidates that stimulate powerful, targeted immune responses against pathogens and tumor cells, which is a novel approach.
−Removed: Our future success depends on the successful development of this platform.
+Added: Our product candidates are based on a novel approach to the treatment of infectious disease, autoimmunity and cancer, which makes it difficult to predict the time and cost of product candidate development.
+Added: We have concentrated our research and development efforts on components of our proprietary platforms to develop product candidates that stimulate powerful, targeted immune responses against pathogens and tumor cells, which is a novel approach.
+Added: Our future success depends on the successful development of these platforms.
There can be no assurance that any development problems we experience in the future will not cause significant delays or unanticipated costs, or that such development problems can be solved.
Should we encounter development problems, including unfavorable preclinical or clinical trial results, the FDA or foreign regulatory authorities may refuse to approve our product candidates, or may require additional information, tests, or trials, which could significantly delay product development and significantly increase our development costs.
−Removed: Moreover, even if we are able to provide the requested information or trials to the FDA, there would be no guarantee that the FDA would accept them or approve our product candidates.
+Added: Moreover, even if we are able to provide the requested information or trials to the FDA,
+Added: there would be no guarantee that the FDA would accept them or approve our product candidates.
We may also experience delays in developing a sustainable, reproducible and scalable manufacturing process, or developing other testing and manufacturing methods, which may prevent us from completing our clinical trials or commercializing our product candidates on a timely or profitable basis, if at all.
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The timing of completion of our clinical trials depends in part on the speed at which we can recruit participants to participate in testing our product candidates, and we may experience delays in our clinical trials if we encounter difficulties in enrollment.
−Removed: We may not be able to initiate or continue clinical trials for our product candidates if we are unable to locate and enroll a sufficient number of eligible participants to
−Removed: participate in these trials as required by the FDA, the EMA or other foreign regulatory authorities.
−Removed: For example, randomized clinical controlled trials for Middle East respiratory syndrome, or MERS, are difficult due to the sporadic and low incidence of cases.
−Removed: Our ability to enroll participants may be significantly delayed by the COVID-19 pandemic due to local lockdowns, and government and site level policies in the countries we are performing our clinical trials.
−Removed: In addition, where potential participants for our clinical trials have had previous exposure to the ChAdOx1 vector, we may not be able to enroll these individuals in a clinical trial or their enrollment may be delayed due to the concern that neutralizing antibodies might be present for some time after ChAdOx exposure.
+Added: We may not be able to initiate or continue clinical trials for our product candidates if we are unable to locate and enroll a sufficient number of eligible participants to participate in these trials as required by the FDA, the EMA or other foreign regulatory authorities.
+Added: For example, randomized clinical controlled trials for MERS are difficult due to the sporadic and low incidence of cases.
+Added: Our ability to enroll participants may be significantly delayed when potential participants for our clinical trials have had previous exposure to the ChAdOx1 vector, as we may not be able to enroll these individuals in a clinical trial or their enrollment may be delayed due to the concern that neutralizing antibodies might be present for some time after ChAdOx exposure.
For example, we may not be able to enroll or may need to delay the enrollment of potential subjects who received the Vaxzevria vaccine.
Although we believe the presence and impact of such neutralizing antibodies is transient, we do not have full data on this yet and our assessment may change.
−Removed: Until the pandemic is over, we will not know the full extent and scope of such delays.
−Removed: The initiation of our Phase 1/2a clinical trial for VTP-200, our Phase 1b/2a clinical trial for VTP-300 and our Phase 1/2a clinical trial for VTP-600, which are being conducted across sites in various countries, was delayed due to COVID-19.
−Removed: Slow enrollment and further delays remain a risk.
+Added: The initiation of our Phase 1/2a clinical trial for VTP-200, our Phase 1b/2a clinical trial for VTP-300 and our Phase 1/2a clinical trial for VTP-600, were delayed due to COVID-19.
We cannot anticipate the next pandemic or how that may or may not impact future clinical trial enrollment.
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• the risk that participants enrolled in clinical trials will drop out of the clinical trials before clinical trial completion;
−Removed: ● factors we may not be able to control, such as current or potential pandemics that may limit participants, principal investigators or staff or clinical site availability ( e.g.
+Added: • factors we may not be able to control, such as potential pandemics that may limit participants, principal investigators or staff or clinical site availability ( e.g.
, the COVID-19 pandemic).
Since the number of qualified clinical investigators is limited, we expect to conduct some of our clinical trials at the same clinical trial sites that some of our competitors use, which will reduce the number of participants who are available for our clinical trials at such clinical trial sites.
−Removed: Moreover, because certain of our product candidates represent a departure from more commonly used methods for cancer treatment and because certain of our product candidates have not been tested in humans before, potential participants and their doctors may be inclined to use conventional therapies, such as chemotherapy, rather than enroll participants in any future clinical trial.
+Added: Moreover, because certain of our product candidates represent a departure from more commonly used methods for treatment of disease, particularly in cancer, and because certain of our product candidates have not been tested in humans before, potential participants and their doctors may be inclined to use conventional therapies, rather than enroll participants in a future clinical trial.
If we experience delays in the completion or termination of any clinical trial of our product candidates, the commercial prospects of our product candidates will be harmed, and our ability to generate product revenue from any of these product candidates could be delayed or prevented.
Our product candidates may cause serious adverse events, serious side effects or have other properties that could halt their clinical development, prevent their marketing authorization, require expansion of the trial size, limit their commercial potential or result in significant negative consequences.
−Removed: Serious side effects caused by our product candidates could cause us or regulatory authorities, including IRBs and ethics committees, to interrupt, delay or halt clinical trials and could result in a more restrictive label or the delay or denial of marketing authorization by the
−Removed: FDA, the EMA or other comparable foreign regulatory authorities.
+Added: Serious side effects caused by our product candidates could cause us or regulatory authorities, including IRBs and ethics committees, to interrupt, delay or halt clinical trials and could result in a more restrictive label or the delay or denial of marketing authorization by the FDA, the EMA or other comparable foreign regulatory authorities.
Further, clinical trials by their nature utilize a sample of the potential patient population.
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When cancer is detected early enough, first line therapy is sometimes adequate to cure the cancer or prolong life without a cure.
−Removed: Whenever first line therapy, usually chemotherapy, antibody drugs, tumor-targeted small molecules, hormone therapy, radiation therapy, surgery, or a combination of these, proves unsuccessful, second line therapy may be administered.
+Added: Whenever first line therapy, usually chemotherapy, antibody drugs, tumor-targeted small molecules, hormone
+Added: therapy, radiation therapy, surgery, or a combination of these, proves unsuccessful, second line therapy may be administered.
Second line therapies often consist of more chemotherapy, radiation, antibody drugs, tumor-targeted small molecules, or a combination of these.
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We expect to seek approval of VTP-600 as a component of first line therapy but we expect to seek approval of our other oncology product candidates initially as second or third line therapy, for use in patients with relapsed or refractory metastatic cancer.
−Removed: Subsequently, for those product candidates that prove to be sufficiently safe and beneficial as third line or second line therapies, if any, we would expect to seek approval
−Removed: as earlier line therapies, but there is no guarantee that our product candidates, even if approved as a second or third line of therapy, would be approved for an earlier line of therapy, and, prior to any such approvals, we may have to conduct additional clinical trials.
+Added: Subsequently, for those product candidates that prove to be sufficiently safe and beneficial as third line or second line therapies, if any, we would expect to seek approval as earlier line therapies, but there is no guarantee that our product candidates, even if approved as a second or third line of therapy, would be approved for an earlier line of therapy, and, prior to any such approvals, we may have to conduct additional clinical trials.
Our projections of both the number of people who have the infectious diseases and cancers we are targeting, as well as the subset of people with these infectious diseases and cancers in a position to receive a particular line of therapy and who have the potential to benefit from treatment with our product candidates, are based on our beliefs and estimates.
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Even if we obtain significant market share for our product candidates within our addressable patient population, because the potential target populations are small, we may never achieve profitability without obtaining marketing authorization for additional indications, including use as first or second line therapy.
−Removed: Negative developments in the field of infectious disease and immuno-oncology could damage public perception of any of our product candidates and negatively affect our business.
−Removed: The commercial success of our product candidates will depend in part on public acceptance of the use of immunotherapies and vector-based viral vaccines.
−Removed: Adverse events in clinical trials of VTP-300 and VTP-200, or in clinical trials of others developing similar products and the resulting publicity, as well as any other negative developments in the field of infectious disease and immuno-oncology that may occur in the future, including in connection with competitor therapies, could result in a decrease in demand for any product candidates that we may develop.
+Added: Negative developments in the fields of infectious disease and immuno-oncology could damage public perception of any of our product candidates and negatively affect our business.
+Added: The commercial success of our product candidates will depend in part on public acceptance of the use of immunotherapies and viral vector-based antigen-delivery platforms.
+Added: Adverse events in clinical trials of VTP-300 and VTP-200, or in clinical trials of similar products developed by others and the resulting publicity, as well as any other negative developments in the field of infectious disease and immuno-oncology that may occur in the future, including in connection with competitor therapies, could result in a decrease in demand for any product candidates that we may develop.
These events could also result in the suspension, discontinuation, or clinical hold of or modification to our clinical trials.
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Product candidates that we successfully develop and commercialize will compete with existing therapies and new therapies that may become available in the future.
−Removed: Specifically, we expect that our product candidates will compete against alternative or more conventional approaches, including antivirals, immune modulators, siRNA, CRISPR editing, capsid inhibitors, novel entry inhibitors, or other small molecules, RNA, DNA, nanoparticle, VLP, peptide, protein, whole-killed or other vaccine technologies.
+Added: Specifically, we expect that our product candidates will compete against alternative or more conventional approaches, including antivirals, immune modulators, antisense oligonucleotides, siRNA, CRISPR editing, capsid inhibitors, novel entry inhibitors, or other small molecules, RNA, DNA, nanoparticle, VLP, peptide, protein, whole-killed vaccines or other technologies.
If our product candidates are approved for the indications for which we are currently conducting or planning clinical trials, they will likely compete with the competitor products mentioned above and with other products that are currently in development.
−Removed: Key product features that would affect our ability to effectively compete with other therapeutics include the efficacy, safety, formulation, stability and convenience of our products.
+Added: Key product features that would affect our ability to effectively compete with other therapeutics include the safety, efficacy, formulation, stability, and convenience of our products.
Our competitors may obtain patent protection or other intellectual property rights that limit our ability to develop or commercialize our product candidates.
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In some instances, there can be significant variability in safety, potency, purity, or efficacy results between different preclinical studies and clinical trials of the same product candidate due to numerous factors, including changes in trial procedures set forth in protocols, differences in the size and type of the patient populations, changes in and adherence to the clinical trial protocols and the rate of dropout among clinical trial participants.
−Removed: While we have not yet initiated clinical trials for certain of our product candidates, VTP- 400, VTP-1100, VTP-1000 and VTP-600, and are in early stages of clinical trials for certain of our product candidates, VTP-300, VTP-500 and VTP-200, as is the case with all novel immunotherapeutics and viral-vector based vaccines, it is likely that there may be side effects associated with their use.
+Added: While we have not yet initiated clinical trials for certain of our product candidates, such as VTP-1000, and are in early stages of clinical trials for certain of our product candidates, VTP-300, VTP-500, VTP-200, VTP-400, VTP-850 and VTP-600, as is the case with all novel immunotherapeutics and viral-vector based antigen-delivery platforms, it is likely that there may be side effects associated with their use.
Results of our trials could reveal a high and unacceptable severity and prevalence of these side effects.
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Even if we obtain marketing authorization for our product candidates, the products may not gain market acceptance among physicians, patients, hospitals, cancer treatment centers and others in the medical community.
−Removed: The use of novel immunotherapeutics, nanoparticle and viral-vector based product candidates to target the treatment and prevention of infectious diseases, and cancer and autoimmuneimmune tolerance diseases is a recent development and may not become broadly accepted by physicians, patients, hospitals, cancer treatment centers and others in the medical community.
+Added: The use of novel immunotherapeutics, nanoparticle and viral-vector based product candidates to target the treatment and prevention of infectious diseases, and cancer and autoimmune diseases is a recent development and may not become
+Added: broadly accepted by physicians, patients, hospitals, cancer treatment centers and others in the medical community.
Various factors will influence whether our product candidates are accepted in the market, including:
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• the prevalence and severity of any side effects for other immunotherapeutics and public perception of other immunotherapeutics;
−Removed: ● the prevalence and severity of any side effects for other viral-vector based vaccines and/or therapeutics and public perception of other viral-vector based vaccines and/or therapeutics;
−Removed: ● The prevalence and severity of any side effects for other nanoparticle based vaccines and/or therapeutics and public perception of other nanoparticle based vaccines and/or therapeutics
+Added: • the prevalence and severity of any side effects for other viral-vector based antigen-delivery platforms and public perception of other viral-vector based antigen-delivery platforms;
+Added: • The prevalence and severity of any side effects for other nanoparticle-based therapeutics and public perception of other nanoparticle-based therapeutics
• product labeling or product insert requirements of the FDA or other regulatory authorities;
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If our product candidates are licensed but fail to achieve market acceptance among physicians, patients, hospitals, cancer treatment centers or others in the medical community, we will not be able to generate significant revenue.
−Removed: In addition, although our product candidates differ in certain ways from other immunotherapeutic and viral-vector based vaccine approaches, serious adverse events or deaths in other clinical trials involving immunotherapeutics and viral-vector based vaccines, even if not ultimately attributable to our product or product candidates, could result in increased government regulation, unfavorable public perception and publicity, potential regulatory delays in the testing or licensing of our product candidates, stricter labeling requirements for those product candidates that are licensed, and a decrease in demand for any such product candidates.
+Added: In addition, although our product candidates differ in certain ways from other immunotherapeutic and viral-vector based approaches, serious adverse events or deaths in other clinical trials involving immunotherapeutic and viral-vector based product candidates, even if not ultimately attributable to our product or product candidates, could result in increased government regulation, unfavorable public perception and publicity, potential regulatory delays in the testing or licensing of our product candidates, stricter labeling requirements for those product candidates that are licensed, and a decrease in demand for any such product candidates.
Even if our products achieve market acceptance, we may not be able to maintain that market acceptance over time if new products or technologies are introduced that are more favorably received than our products, are more cost effective or render our products obsolete.
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We will have to compete with other pharmaceutical and biotechnology companies to recruit, hire, train and retain marketing and sales personnel.
−Removed: There are risks involved with both establishing our own sales and marketing capabilities and entering into arrangements with third parties to perform these services.
+Added: There are risks involved with both establishing our own sales
+Added: and marketing capabilities and entering into arrangements with third parties to perform these services.
For example, recruiting and training a sales force is expensive and time-consuming and could delay any product launch.
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If these third parties do not properly and successfully carry out their contractual duties or meet expected deadlines, we may not be able to obtain marketing authorizations for, or commercialize, our product candidates and our business could be substantially harmed.
−Removed: We utilize and depend, and expect to continue to utilize and depend, upon independent investigators and collaborators, such as medical institutions, contract research organizations, or CROs, contract manufacturing organizations, or CMOs, and strategic partners to conduct and support certain of our preclinical studies and clinical trials under agreements with us.
+Added: We utilize and depend, and expect to continue to utilize and depend, upon independent investigators and collaborators, such as medical institutions, contract research organizations ("CROs"), contract manufacturing organizations ("CMOs"), and strategic partners to conduct and support certain of our preclinical studies and clinical trials under agreements with us.
For example, we are dependent on our regional partner, CanSino Biologics, to conduct a Phase 1 clinical trial of VTP-400 for herpes zoster prevention.
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Regulatory authorities enforce GCP through periodic inspections of trial sponsors, principal investigators and trial sites.
−Removed: If we, or any of these third parties fail to comply with applicable GCP regulations, the clinical data generated in our clinical trials may be deemed unreliable and the FDA or comparable foreign regulatory authorities may require us to perform additional clinical trials before approving our marketing authorization applications, or MAA.
+Added: If we, or any of these third parties fail to comply with applicable GCP regulations, the clinical data generated in our clinical trials may be deemed unreliable and the FDA or comparable foreign regulatory authorities may require us to perform additional clinical trials before approving our MMAs.
We cannot assure you that, upon inspection, such regulatory authorities will determine that any of our clinical trials comply with the GCP regulations.
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• disputes may arise between us and a collaborator that cause the delay or termination of the research, development or commercialization of our product candidates, or that result in costly litigation or arbitration that diverts management attention and resources;
−Removed: ● collaborations may be terminated and, if terminated, may result in a need for additional capital to pursue further development or commercialization of the applicable product candidates;
+Added: • collaboration and grant funding agreements may be terminated and, if terminated, may result in a need for additional capital to pursue further development or commercialization of the applicable product candidates;
• collaborators may own or co-own intellectual property covering our products that results from our collaborating with them, and in such cases, we would not have the exclusive right to commercialize such intellectual property.
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We have not yet manufactured our product candidates on a commercial scale and may not be able to do so for any of our product candidates.
−Removed: Manufacturing of biological drug products is complex and requires significant expertise and capital investment, including the development of advanced manufacturing techniques and process controls.
+Added: Manufacturing of biologic and synthetic products is complex and requires significant expertise and capital investment, including the development of advanced manufacturing techniques and process controls.
Manufacturers of biologic products often encounter difficulties in production, particularly in scaling up, validating the production process and assuring high reliability of the manufacturing process, including the absence of contamination.
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• our future contract manufacturers may not perform as agreed, may not devote sufficient resources to our product candidates or may not remain in the contract manufacturing business for the time required to supply our clinical trials or to successfully produce, store, and distribute our products, if any;
−Removed: ● manufacturers are subject to ongoing periodic unannounced inspection by the FDA and corresponding state agencies to ensure strict compliance with cGMP and other government regulations and corresponding foreign standards and we have no control over third-party manufacturers’ compliance with these regulations and standards;
+Added: • manufacturers are subject to ongoing periodic unannounced inspection by the FDA and corresponding state agencies to ensure strict compliance with cGMP and other government regulations and corresponding foreign
+Added: standards and we have no control over third-party manufacturers’ compliance with these regulations and standards;
• we may not own, or may have to share, the intellectual property rights to any improvements made by our third-party manufacturers in the manufacturing process for our product candidates;
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The marketing authorization processes of the FDA, the EMA, MHRA and other comparable foreign regulatory authorities are lengthy, time-consuming, and inherently unpredictable, and if we are ultimately unable to obtain marketing authorizations for our product candidates, or the marketing authorization is for a narrower indication than we seek, our business will be substantially harmed.
−Removed: The time required to obtain approval from the FDA, the EMA, MHRA and other comparable foreign regulatory authorities is unpredictable but typically takes many years following the commencement of clinical trials and depends upon numerous factors, including the substantial discretion of the regulatory authorities.
+Added: The time required to obtain marketing approval from the FDA, the EMA, MHRA and other comparable foreign regulatory authorities is unpredictable but typically takes many years following the commencement of clinical trials and depends upon numerous factors, including the substantial discretion of the regulatory authorities.
In addition, approval policies, regulations, or the type and amount of clinical data necessary to gain approval may change during the course of a product candidate’s clinical development and may vary among jurisdictions.
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• the FDA, the EMA, MHRA or other comparable foreign regulatory authorities may disagree with the design or implementation of our clinical trials;
−Removed: ● the data collected from clinical trials of our product candidates may not be sufficient to support the submission of a Biologics Licensing Application, or BLA, to the FDA, or an MAA to the EMA or other comparable submission to regulatory authorities in other regions, to obtain authorization in the United States, the European Union or elsewhere;
+Added: • the data collected from clinical trials of our product candidates may not be sufficient to support the submission of a Biologics Licensing Application ("BLA") to the FDA, or an MAA to the EMA or other comparable submission to regulatory authorities in other regions, to obtain authorization in the United States, the European Union, or elsewhere;
• we may be unable to demonstrate to the satisfaction of the FDA, the EMA, MHRA or regulatory authorities in other regions that a product candidate has an overall suitable benefit/risk profile for its proposed indication;
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• the risk that foreign regulatory authorities may not authorize our clinical trial protocols and other clinical trial documentation, including manufacturing documentation, even when previously authorized by the FDA, EMA or MHRA, which could lead to a delay in starting such clinical trials.
−Removed: For example, we intend to conduct our HBV002 clinical trial in South Korea and have experienced delays due to additional regulatory review of our clinical protocol.
+Added: For example, the conduct of our HBV002 clinical trial in South Korea experienced delays due to additional regulatory review of our clinical protocol.
We have limited experience obtaining such approvals in foreign jurisdictions and therefore may need more time to navigate the regulatory process as a result.
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We have conducted, and intend to conduct, clinical trials of certain of our product candidates outside the United States.
−Removed: Although the FDA may accept data from clinical trials conducted outside the United States, acceptance of these data are subject to certain conditions imposed by the FDA, including compliance with all applicable U.S.
+Added: Although the FDA may accept data from clinical trials conducted outside the United States, acceptance of these data are
+Added: subject to certain conditions imposed by the FDA, including compliance with all applicable U.S.
laws and regulations.
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Depending on what changes the FDA may make to its orphan drug regulations and policies, our business could be adversely impacted.
−Removed: While we may seek Orphan Drug Designation for applicable indications for our current and any future drug candidates, we may never receive such designations.
+Added: While we may seek Orphan Drug Designation for applicable indications for our current and any future drug candidates, we
+Added: may never receive such designations.
Even if we do receive such designations, there is no guarantee that we will enjoy the benefits of those designations.
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We may seek Breakthrough Therapy designation for certain of our current and future product candidates.
−Removed: A breakthrough therapy is defined as a drug or biologic that is intended, alone or in combination with one or more other drugs or biologics, to treat a serious or life-threatening disease or condition and preliminary clinical evidence indicates that the drug or biologic may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints, such as substantial treatment effects observed early in clinical development.
+Added: A breakthrough therapy is defined as a drug or biologic that is intended, alone or in combination with one or more other drugs or biologics, to treat a serious or life-threatening disease or condition and preliminary clinical evidence indicates that the drug or biologic may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints, defined as those that measure an effect on irreversible morbidity or mortality or on symptoms that represent serious consequences of the disease.
For product candidates that have been designated as breakthrough therapies, interaction and communication between the FDA and the sponsor of the trial can help to identify the most efficient path for clinical development while minimizing the number of patients placed in ineffective control regimens.
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Sponsors must also update FDA on the status of these studies, and under FDORA, the FDA has increased authority to withdraw approval of a drug granted accelerated approval on an expedited basis if the sponsor fails to conduct such studies in a timely manner, send the necessary updates to the FDA, or if such post-approval studies fail to verify the drug’s predicted clinical benefit.
−Removed: In addition, the FDA currently requires, unless otherwise informed by the agency, pre-approval of promotional materials for products receiving Accelerated Approval, which could adversely impact the timing of the commercial launch of the product.
+Added: In addition, the FDA currently requires sponsors, unless otherwise informed by the agency, to request pre-approval of promotional materials for products receiving Accelerated Approval, which could adversely impact the timing of the commercial launch of the product.
Even if we do receive accelerated approval, we may not experience a faster development or regulatory review or approval process, and receiving accelerated approval does not provide assurance of ultimate full FDA approval.
If approved, our investigational products regulated as biologics may face competition from biosimilars approved through an abbreviated regulatory pathway.
−Removed: The Patient Protection and Affordable Care Act, as amended by the Health Care and Education Reconciliation Act of 2010, or collectively the ACA, includes a subtitle called the Biologics Price Competition and Innovation Act of 2009, or BPCIA, which created an abbreviated approval pathway for biologic products that are biosimilar to or interchangeable with an FDA-licensed reference biologic product.
+Added: The Patient Protection and Affordable Care Act, as amended by the ACA, includes a subtitle called the BPCIA which created an abbreviated approval pathway for biologic products that are biosimilar to or interchangeable with an FDA-licensed reference biologic product.
Under the BPCIA, an application for a biosimilar product may not be submitted to the FDA until four years following the date that the reference product was first licensed by the FDA.
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We believe that any of our product candidates approved as a biologic product under a BLA should qualify for the 12 year period of exclusivity.
−Removed: However, there is a risk that this exclusivity could be shortened due to congressional action or otherwise, or that the FDA will not consider our investigational medicines to be reference products for competing products, potentially creating the opportunity for generic competition sooner than anticipated.
+Added: However, there is a risk that this exclusivity could be shortened due to congressional action or otherwise, or that the FDA will not consider our investigational medicines to be reference products for competing products, potentially creating the opportunity for biosimilar competition sooner than anticipated.
Moreover, the extent to which a biosimilar, once licensed, will be substituted for any one of our reference products in a way that is similar to traditional generic substitution for non-biologic products is not yet clear, and will depend on a number of marketplace and regulatory factors that are still developing.
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The foreign marketing authorization process may include all of the risks associated with obtaining FDA, EMA or MHRA approval, in addition to country-specific risks and challenges.
−Removed: For example, we are developing VTP-300 for HBV infection, which is most prevalent in China and other countries in Asia.
+Added: For example, we are developing VTP-300 for chronic hepatitis B, which is most prevalent in China and other countries in Asia.
We have limited development experience in this market and we may need to rely on a local, third-party partner to help us navigate the applicable regulatory requirements.
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Future changes to tax laws could materially adversely affect our financial condition and results of operations, and reduce net returns to our shareholders.
−Removed: We conduct business globally and file income tax returns in multiple jurisdictions.
+Added: We conduct business globally and file tax returns in multiple jurisdictions.
The tax treatment of the Company or any of the group companies could be materially adversely affected by several factors, including:
3 unchanged sentences
the resolution of issues arising from tax audits or examinations and any related interest or penalties.
−Removed: Such changes may include (but are not limited to) the taxation of operating income, investment income, dividends received or (in the specific context of withholding tax) dividends paid.
+Added: Such changes (which may be retroactive) may include (but are not limited to) the taxation of operating income, investment income, dividends received or (in the specific context of withholding tax) dividends paid.
We are unable to predict what tax reform may be proposed or enacted in the future or what effect such changes would have on our business, but such changes, to the extent they are brought into tax legislation, regulations, policies or practices in jurisdictions in which we operate, could affect our financial position, future results of operations, cash flows in a particular period and overall or effective tax rates in the future in countries where we have operations, reduce post-tax returns to our shareholders and increase the complexity, burden and cost of tax compliance.
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A tax authority may disagree with tax positions that we have taken, which could result in increased tax liabilities.
−Removed: For example, Her Majesty’s Revenue & Customs, or HMRC, the IRS or another tax authority could challenge our allocation of income by tax jurisdiction and the amounts paid between our affiliated companies pursuant to our intercompany arrangements and transfer pricing policies, including amounts paid with respect to our intellectual property development.
+Added: For example HMRC, the IRS or another tax authority could challenge our allocation of income by tax jurisdiction and the amounts paid between our affiliated companies pursuant to our intercompany arrangements and transfer pricing policies, including amounts paid with respect to our intellectual property development.
There can be no assurance that a taxing authority will not have a different interpretation of applicable law and assess us with additional taxes.
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If we are assessed with additional taxes, this may result in a material adverse effect on our results of operations and/or financial condition.
−Removed: We may be unable to use net operating loss and tax credit carryforwards and certain built-in losses or tax credits to reduce future tax payments or to benefit from favorable UK tax legislation.
−Removed: As a UK incorporated and tax resident entity, we are subject to UK corporate taxation.
−Removed: Due to the nature of our business, we have generated losses since inception and therefore have not paid any UK corporation tax.
+Added: We may be unable to use net operating loss and tax credit carryforwards and certain built-in losses or tax credits to reduce future tax payments or to benefit from favorable U.K.
+Added: tax legislation.
+Added: incorporated and tax resident entity, we are subject to U.K.
+Added: corporate taxation.
+Added: Due to the nature of our business, we have generated losses since inception and therefore have not paid any U.K.
+Added: corporation tax.
As of December 31, 2023, we had cumulative carryforward tax losses of approximately $92.7 million (December 31, 2022:
$39.6 million).
−Removed: Subject to any relevant criteria and restrictions (including those that limit the percentage of profits that can be reduced by carried forward losses and those that can restrict the use of carried forward losses where there is a change of ownership of more than half of our ordinary shares and a major change in the nature, conduct or scale of the trade), we expect these to be eligible for carry forward and utilization against future operating profits.
−Removed: The use of loss carryforwards in relation to UK profits incurred on or after April 1, 2017 is generally limited each year to £5.0 million plus an incremental 50% of UK taxable profits.
−Removed: In addition, if we were to have a major change in the nature of the conduct of our trade, loss carryforwards may be restricted or extinguished.
−Removed: As a company that carries out extensive research and development activities, we seek to benefit from the UK research and development tax relief programs, being the Small and Medium-sized Enterprises R&D tax relief program, or SME Program, and, to the extent that our projects are grant funded or relate to work subcontracted to us by third parties, the Research and Development Expenditure Credit program.
+Added: Subject to any relevant criteria and restrictions (including those that limit the percentage of profits that can be reduced by carried forward losses and those that can restrict the use of carried forward losses where there is a change of ownership of more than half of our ordinary shares and a major change in the nature, conduct or scale of the trade), we expect these to be eligible for carry forward and utilization against future operating profits, if any.
+Added: The use of loss carryforwards in relation to U.K.
+Added: profits incurred on or after April 1, 2017 is generally limited each year to £5.0 million plus an incremental 50% of U.K.
+Added: taxable profits.
+Added: As a company that carries out extensive research and development activities, we seek to benefit from the U.K.
+Added: research and development tax relief programs, being the Small and Medium-sized Enterprises R&D tax relief program, or SME Program, and, to the extent that our projects are grant funded or relate to work subcontracted to us by third parties, the Research and Development Expenditure Credit program.
Under the SME Program, where available, we may be able to surrender some of our trading losses that arise from our qualifying research and development activities for cash or carry forward such losses for potential offset against future profits (subject to relevant restrictions).
1 unchanged sentence
Our eligibility to claim payable research and development tax credits may be limited or eliminated because we may no longer qualify as a small or medium-sized company.
−Removed: In addition, the SME Program has been amended
−Removed: by the Finance Act 2021 which came into force in April 2021.
+Added: In addition, the SME Program has been amended by the Finance Act 2021 which came into force in April 2021.
This legislation introduced a cap on claims under the SME Program to a multiple of payroll taxes (broadly, to a maximum payable credit equal to £20,000 plus three times the total PAYE and NICs liability of the company) subject to an exception which prevents the cap from applying.
1 unchanged sentence
If such exception does not apply, this could restrict the amount of payable credit that we claim.
−Removed: Changes to the UK R&D tax relief legislation that have been recently enacted or proposed, and expected to take effect from April 2023, respectively reduce the R&D cash rebate rate under the SME Program, and may introduce restrictions on relief that may be claimed for expenditure on sub-contracted R&D activity, broadly requiring either that workers carrying on such activity are subject to UK PAYE or, where work is undertaken outside the UK, that this must be due to geographical, environmental, social or other conditions that:
−Removed: (i) are not present in the UK;
−Removed: and (ii) it would be wholly unreasonable to replicate in the UK.
−Removed: This rate reduction and such proposed restrictions may impact the quantum of R&D relief that we are able to claim in the future.
−Removed: In addition, the UK government is currently consulting on the potential replacement of the SME Program and RDEC Program with a single program, operating similarly to the RDEC Program, which may, inter alia, change the present treatment of sub-contracted R&D work and introduce different thresholds and caps on expenditure and relief.
+Added: Changes to the U.K.
+Added: R&D tax relief legislation that have been recently enacted or proposed, and which took effect from April 2023, reduce the R&D cash rebate rate under the SME Program, and may introduce restrictions on relief that may be claimed for expenditure on sub-contracted R&D activity, broadly requiring either that workers carrying on such activity are subject to U.K.
+Added: PAYE or, where work is undertaken outside the U.K., that this must be due to geographical, environmental, social or other conditions that:
+Added: (i) are not present in the U.K.;
+Added: and (ii) it would be wholly unreasonable to replicate in the U.K.
+Added: This rate reduction and any proposed restrictions may impact the quantum of R&D relief that we are able to claim in the future.
+Added: In addition, the U.K.
+Added: government is currently consulting on the potential replacement of the SME Program and RDEC Program with a single program, operating similarly to the RDEC Program, which may, inter alia, change the present treatment of sub-contracted R&D work and introduce different thresholds and caps on expenditure and relief.
If enacted, the new program would be expected to have effect for expenditure incurred from April 2024 onwards, and could have a material impact on the quantum of R&D relief that we are eligible to claim.
−Removed: We may benefit in the future from the UK’s “patent box” regime, which allows certain profits attributable to revenue from patented products (and other qualifying income) to be taxed at an effective rate of 10% by giving an additional tax deduction.
−Removed: When taken in combination with the enhanced relief available on our research and development expenditures, we expect a long-term rate of corporation tax lower than the statutory to apply to us.
−Removed: If, however, there are unexpected adverse changes to the UK research and development tax credit regime or the “patent box” regime, or for any reason we are unable to qualify for such advantageous tax legislation, or we are unable to use net operating loss and tax credit carryforwards and certain built-in losses to reduce future tax payments then our business, results of operations and financial condition may be adversely affected.
+Added: This announcement also saw the introduction of a higher rate of relief for loss-making R&D-intensive small and medium enterprises, the SME Intensive Scheme.
+Added: Companies claiming under the existing SME Intensive Scheme tax relief will be eligible for a higher payable credit rate if they meet the definition for R&D intensity.
+Added: We will assess if we can claim under the new loss-making R&D-intensive SME Intensive Scheme for the accounting period ending December 31, 2024 and future periods, which will provide benefits consistent with those claimed under the current SME Programs.
+Added: We may benefit in the future from the U.K.’s “patent box” regime, which allows certain profits attributable to revenue from patented products (and other qualifying income) to be taxed at an effective rate of 10% by giving an additional tax deduction.
+Added: When taken in combination with the enhanced relief available on our research and development expenditures, we expect a long-term effective rate of corporation tax lower than the statutory rate to apply to us.
+Added: If, however, there are unexpected adverse changes to the U.K.
+Added: R&D tax credit regime or the “patent box” regime, or for any reason we are unable to qualify for such advantageous tax legislation, or we are unable to use net operating loss and tax credit carryforwards and certain built-in losses to reduce future tax payments then our business, results of operations and financial condition may be adversely affected.
This may impact our ongoing requirement for investment and the timeframes within which additional investment is required.
+Added: For completeness, it should be noted that the UK tax authority, HMRC, currently has an increased focus on claims for R&D tax credits and so the Company may be subject to increased scrutiny in respect of any claims it makes.
+Added: In addition, the legislation on the UK R&D tax credits regime is updated and changed frequently, so there can be no guarantee of our ability of to make use of such credits as we might currently expect to in future.
Risks Related to Ongoing Regulatory Obligations
1 unchanged sentence
Any marketing authorizations that we receive for our product candidates will require surveillance to monitor the safety and efficacy of the product candidate.
−Removed: The FDA may also require a risk evaluation and mitigation strategy, or REMS, and the EMA may also require additional rapid microbiological method approvals or educational materials in order to approve our product candidates, which could entail requirements for a medication guide, physician communication plans or additional elements to ensure safe use, such as restricted distribution methods, patient registries and other risk minimization tools.
+Added: The FDA may also require a REMS and the EMA may also require additional rapid microbiological method approvals or educational materials in order to approve our product candidates, which could entail requirements for a medication guide, physician communication plans or additional elements to ensure safe use, such as restricted distribution methods, patient registries and other risk minimization tools.
In addition, if the FDA or a comparable foreign regulatory authority approves our product candidates, the manufacturing processes, labeling, packaging, distribution, adverse event reporting, storage, advertising, promotion, import, export and recordkeeping for our product candidates will be subject to extensive and ongoing regulatory requirements.
11 unchanged sentences
Additionally, under FDORA, sponsors of approved drugs and biologics must provide 6 months’ notice to the FDA of any changes in marketing status, such as the withdrawal of a drug, and failure to do so could result in the FDA placing the product on a list of discontinued products, which would revoke the product’s ability to be marketed.
−Removed: The FDA’s and other regulatory authorities’ policies may change and additional government regulations may be enacted that could prevent, limit or delay marketing authorization of our product candidates.
+Added: The FDA’s and other regulatory authorities’ policies may change and additional government regulations may be enacted that could prevent, limit
+Added: or delay marketing authorization of our product candidates.
We cannot predict the likelihood, nature or extent of government regulation that may arise from future legislation or administrative action, either in the United States or abroad.
23 unchanged sentences
We may not be able to provide data sufficient to gain acceptance with respect to coverage and reimbursement.
−Removed: If reimbursement
−Removed: is not available, or is available only at limited levels, we may not be able to successfully commercialize our product candidates, if approved.
+Added: If reimbursement is not available, or is available only at limited levels, we may not be able to successfully commercialize our product candidates, if approved.
Even if coverage is provided, the approved reimbursement amount may not be high enough to allow us to establish or maintain pricing sufficient to realize a sufficient return on our investment.
There is significant uncertainty related to the insurance coverage and reimbursement of newly approved products.
−Removed: In the United States, the principal decisions about reimbursement for new medicines are typically made by CMS, an agency within the U.S.
−Removed: Department of Health and Human Services, as CMS decides whether and to what extent a new medicine will be covered and reimbursed under Medicare.
+Added: In the United States, the principal decisions about reimbursement for new medicines are typically made by CMS, an agency within the HHS, as CMS decides whether and to what extent a new medicine will be covered and reimbursed under Medicare.
Private payors tend to follow CMS to a substantial degree.
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The downward pressure on healthcare costs in general, particularly prescription drugs and surgical procedures and other treatments, has become very intense.
−Removed: Many pharmaceutical manufacturers must calculate and report certain price reporting metrics to the government, such as average sales price, or ASP, and best price.
+Added: Many pharmaceutical manufacturers must calculate and report certain price reporting metrics to the government, such as average sales price and best price.
Penalties may apply in some cases when such metrics are not submitted accurately and timely.
14 unchanged sentences
The implementation of cost containment measures or other healthcare reforms may prevent us from being able to generate revenue, attain profitability, or commercialize our drugs, and could have a material adverse effect on our business, financial condition, and results of operations.
−Removed: Our business activities will be subject to the Foreign Corrupt Practices Act, or FCPA, and similar anti-bribery and anti- corruption laws in other jurisdictions.
+Added: Our business activities will be subject to the Foreign Corrupt Practices Act ("FCPA"), and similar anti-bribery and anti- corruption laws in other jurisdictions.
As we engage in and expand our business activities outside of the United States, including our clinical trial efforts, we will be subject to the FCPA and similar anti-bribery or anti-corruption laws, regulations or rules of other countries in which we operate.
15 unchanged sentences
government has shut down several times and certain regulatory authorities, such as the FDA and the SEC, have had to furlough critical FDA, SEC and other government employees and stop critical activities.
−Removed: If a prolonged
−Removed: government shutdown occurs, it could significantly impact the ability of the FDA to timely review and process our regulatory submissions, which could have a material adverse effect on our business.
+Added: If a prolonged government shutdown occurs, it could significantly impact the ability of the FDA to timely review and process our regulatory submissions, which could have a material adverse effect on our business.
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.
−Removed: Since March 2020 when foreign and domestic inspections of facilities were largely placed on hold, the FDA has been working to resume pre-pandemic levels of inspection activities, including routine surveillance, bioresearch monitoring and pre-approval inspections.
−Removed: Should FDA determine that an inspection is necessary for approval and an inspection cannot be completed during the review cycle due to restrictions on travel, and the FDA does not determine a remote interactive evaluation to be adequate, the agency has stated that it generally intends to issue, depending on the circumstances, a complete response letter or defer action on the application until an inspection can be completed.
−Removed: During the COVID-19 public health emergency, a number of companies announced receipt of complete response letters due to the FDA’s inability to complete required inspections for their applications.
−Removed: Regulatory authorities outside the U.S.
−Removed: may adopt similar restrictions or other policy measures in response to COVID-19 and may experience delays in their regulatory activities.
Our business operations and current and future relationships with principal investigators, healthcare providers, including physicians, consultants, third-party payors and customers may be subject, directly or indirectly, to U.S.
3 unchanged sentences
Our current and future arrangements with healthcare professionals, principal investigators, consultants, customers and third-party payors subject us to various U.S.
−Removed: federal and state fraud and abuse laws and other healthcare laws, including, without limitation, the federal Anti- Kickback Statute, or AKS, the federal civil and criminal false claims laws, and the law commonly referred to as the Physician Payments Sunshine Act, or Sunshine Act, along with regulations promulgated under such laws.
+Added: federal and state fraud and abuse laws and other healthcare laws, including, without limitation, the AKS, the federal civil and criminal false claims laws, and the law commonly referred to as the Sunshine Act, along with regulations promulgated under such laws.
These laws impact, among other things, our clinical research activities, proposed sales, marketing and educational programs, and other arrangements and relationships with third-party payors, healthcare professionals, and other parties through which we market, sell and distribute our product candidates for which we obtain marketing approval.
22 unchanged sentences
If we fail to comply with environmental, health and safety laws and regulations, we could become subject to fines or penalties or incur costs that could have a material adverse effect on the success of our business.
−Removed: We are subject to numerous environmental, health and safety laws and regulations, including those governing laboratory procedures and the handling, use, storage, treatment and disposal of hazardous materials and wastes.
−Removed: Our operations involve the use of hazardous and flammable materials, including chemicals and biological and radioactive materials.
−Removed: Our operations also produce hazardous waste products.
−Removed: We generally contract with third parties for the disposal of these materials and wastes.
−Removed: We cannot eliminate the risk of contamination or injury from these materials.
−Removed: In the event of contamination or injury resulting from our use of hazardous materials, we could be held liable for any resulting damages, and any liability could exceed our resources.
−Removed: We also could incur significant costs associated with civil or criminal fines and penalties.
−Removed: Although we maintain workers’ compensation insurance to cover us for costs and expenses we may incur due to injuries to our employees resulting from the use of hazardous materials, this insurance may not provide adequate coverage against potential liabilities.
−Removed: We do not maintain insurance for environmental liability or toxic tort claims that may be asserted against us in connection with our storage or disposal of biological, hazardous or radioactive materials.
−Removed: Failure to comply with current or future national, supranational, federal or state laws and regulations, regulatory guidance and industry standards relating to data protection, privacy and information security, including restrictive European regulations, could lead to government enforcement actions (which could include civil or criminal penalties), private litigation, and/or adverse publicity and could negatively affect our operating results and business.
We and our collaborators and third-party providers are subject to national, supranational, federal or state laws and regulations, regulatory guidance and industry standards relating to data protection, privacy and information security.
−Removed: This includes the EU General Data Protection Regulation, or GDPR, as well as other national data protection legislation in force in relevant EU member states (including the GDPR in such form as incorporated into the law of England and Wales, Scotland and Northern Ireland by virtue of the European Union (Withdrawal) Act 2018 and any regulations thereunder and the UK Data Protection Act 2018, or UK GDPR.
−Removed: The GDPR and UK GDPR are wide-ranging in scope and impose numerous additional requirements on companies that process personal data, including imposing special requirements in respect of the processing of health and other sensitive data, requiring that consent of individuals to whom the personal data relates is obtained in certain circumstances, requiring additional disclosures to individuals regarding data processing activities, requiring that safeguards are implemented to protect the security and confidentiality of personal data, creating mandatory data breach notification requirements in certain circumstances, requiring data protection impact assessments for high risk processing and requiring that certain measures (including contractual requirements) are put in place when engaging third-party processors.
−Removed: The GDPR and the UK GDPR also provide individuals with various rights in respect of their personal data, including rights of access, erasure, portability, rectification, restriction and objection.
−Removed: The GDPR and UK GDPR define personal data to include pseudonymized or coded data and requires different informed consent practices and more detailed notices for clinical trial participants and investigators than applies to clinical trials conducted in the United States.
−Removed: We are required to apply GDPR and UK GDPR standards to any clinical trials that our EU and UK established businesses carry out anywhere in the world.
−Removed: The GDPR and UK GDPR impose strict rules on the transfer of personal data to countries outside the European Economic Area, including the United States.
−Removed: The UK and Switzerland have adopted similar restrictions.
−Removed: Although the UK is regarded as a third country under the EU’s GDPR, the European Commission, or EC, has now issued a decision recognizing the UK as providing adequate protection under the EU GDPR and, therefore, transfers of personal data originating in the EU to the UK remain unrestricted.
−Removed: Like the EU GDPR, the UK GDPR restricts personal data transfers outside the UK to countries not regarded by the UK as providing adequate protection.
−Removed: The UK government has confirmed that personal data transfers from the UK to the EEA remain free flowing.
−Removed: To enable the transfer of personal data outside of the EEA or the UK, adequate safeguards must be implemented in compliance with European and UK data protection laws.
−Removed: On June 4, 2021, the EC issued new forms of standard contractual clauses for data transfers from controllers or processors in the EU/EEA (or otherwise subject to the GDPR) to controllers or processors established outside the EU/EEA (and not subject to the GDPR).
−Removed: The new standard contractual clauses replace the standard contractual clauses that were adopted previously under the EU Data Protection Directive.
−Removed: The UK is not subject to the EC’s new standard contractual clauses but has published a draft version of a UK-specific transfer mechanism, which, once finalized, will enable transfers from the UK.
−Removed: We will be required to implement these new safeguards when conducting restricted data transfers under the EU and UK GDPR and doing so will require significant effort and cost.
−Removed: The GDPR and UK GDPR may increase our responsibility and liability in relation to personal data that we process where such processing is subject to the GDPR and UK GDPR.
−Removed: While we have taken steps to comply with the GDPR and UK GDPR, and implementing legislation in applicable EU member states and the UK, including by seeking to establish appropriate lawful bases for the various processing activities we carry out as a controller or joint controller, reviewing our security procedures and those of our vendors and collaborators, and entering into data processing agreements with relevant vendors and collaborators, we cannot be certain that our efforts to achieve and remain in compliance have been, and/or will continue to be, fully successful.
−Removed: Given the breadth and depth of changes in data protection obligations, preparing for and complying with the GDPR and UK GDPR and similar laws’ requirements are rigorous and time intensive and require significant resources and a review of our technologies, systems and practices, as well as those of any third-party collaborators, service providers, contractors or consultants that process or transfer personal data.
+Added: With respect to Europe, the collection and processing of personal data regarding (i) individuals in the EEA and UK, and/or (ii) carried out in the context of the activities of our establishments in the EEA or UK, is subject to the GDPR, as well as other national data protection legislation in force in relevant EEA member states and the UK, (including the UK Data Protection Act 2018).
+Added: The GDPR is wide-ranging in scope and impose numerous obligations on companies that process personal data, including imposing special requirements in respect of the processing of health and other sensitive data, requiring that consent of individuals to whom the personal data relates is obtained in certain circumstances, requiring additional disclosures to individuals regarding data processing activities, requiring that safeguards are implemented to protect the security and confidentiality of personal data, creating mandatory data breach notification requirements in certain circumstances, requiring data protection impact assessments for high risk processing and requiring that certain measures (including contractual requirements) are put in place when engaging third-party processors.
+Added: The GDPR also provides individuals with various rights in respect of their personal data, including rights of access, erasure, portability, rectification, restriction and objection.
+Added: The GDPR defines personal data to include pseudonymized or coded data and require different informed consent practices and more detailed notices for clinical trial participants and investigators than applies to clinical trials conducted in the United States.
+Added: We are required to apply GDPR standards to any clinical trials that our EEA and UK established businesses carry out anywhere in the world.
+Added: The GDPR impose strict rules on the transfer of personal data to countries outside the EEA and UK, including the United States in certain circumstances, unless a derogation exists or we incorporate a GDPR transfer mechanism (such as the European Commission approved standard contractual clauses (“SCCs”) or the UK International Data Transfer Addendum
+Added: (“IDTA”)) into our agreements with third parties to govern such transfers of personal data and carry out transfer impact assessments to assess whether the data importer can ensure sufficient guarantees for safeguarding the personal information under the GDPR, including an analysis of the laws in the recipient’s country.
+Added: Carrying out such restricted transfers, therefore, comes with a significant compliance burden, requiring significant effort and expense to overcome.
+Added: Failure to implement valid mechanisms for personal data transfers from Europe may result in increased exposure to regulatory actions, substantial fines, and injunctions against processing personal data from Europe.
+Added: If we are unable to export personal data, this may also restrict our activities outside of Europe and require us to increase processing capabilities within Europe at significant expense or otherwise segregate our systems and operations.
+Added: Switzerland has adopted similar transfer restrictions as under the GDPR.
+Added: Although the UK is regarded as a third country under the EU GDPR, the European Commission issued a decision recognizing the UK as providing adequate protection under the EU GDPR and, therefore, transfers of personal data originating in the EEA to the UK remain unrestricted.
+Added: Personal data transfers from the UK to the EEA remain free flowing by virtue of a UK government adequacy decision.
+Added: The GDPR may increase our responsibility and liability in relation to personal data that we process where such processing is subject to the GDPR.
+Added: While we have taken steps to comply with the GDPR, and implementing legislation in applicable EEA member states and the UK, including by seeking to establish appropriate lawful bases for the various processing activities we carry out as a controller or joint controller, reviewing our security procedures and those of our vendors and collaborators, and entering into data processing agreements with relevant vendors and collaborators, we cannot be certain that our efforts to achieve and remain in compliance have been, and/or will continue to be, fully successful.
+Added: Given the breadth and depth of the applicable obligations, complying with the GDPR and similar data protection laws’ requirements are rigorous and time intensive and require significant resources and a review of our technologies, systems and practices, as well as those of any third-party collaborators, service providers, contractors or consultants that process or transfer personal data.
+Added: The UK’s data protection regime is independent from but aligned to the EU’s data protection regime.
+Added: However following the Brexit, there will be increasing scope for divergence in application, interpretation and enforcement of the data protection laws between these territories.
+Added: For example, the UK has recently introduced a new Data Protection & Digital Information (No.
+Added: 2) Bill, or the Data Reform Bill into the UK legislative process with the intention for this bill to reform the UK’s data protection regime following Brexit.
+Added: if passed, the Data Reform Bill could reshape the UK's data protection regime, distancing it from the EU’s data protection regime and threaten the UK’s adequacy decision from the EC.
+Added: This lack of clarity on future UK laws and regulations and their interaction with those of the EU could add legal risk, uncertainty, complexity, and cost to our handling of European personal data and our privacy and security compliance programs;
+Added: and any resulting divergence in laws could increase our risk profile and may require us to implement different compliance measures for the UK and EEA.
In the United States, numerous federal and state laws and regulations, including federal health information privacy laws, state data breach notification laws, state health information privacy laws and federal and state consumer protection laws ( e.g.
, Section 5 of the FTCA), that govern the collection, use, disclosure and protection of health-related and other personal information could apply to our operations or the operations of our collaborators and third-party providers.
−Removed: For example, California recently enacted the California Consumer Privacy Act, or the CCPA, which became effective on January 1, 2020.
+Added: For example, California recently enacted the CCPA which became effective on January 1, 2020.
The CCPA gives California residents expanded rights to access and delete their personal information, opt out of certain personal information sharing and receive detailed information about how their personal information is used.
2 unchanged sentences
At this time, we do not collect personal data on residents of California but should we begin to do so, and in the context of doing so, become subject to the CCPA, the CCPA will impose new and burdensome privacy compliance obligations on our business and will raise new risks for potential fines and class actions.
−Removed: In addition to the CCPA, a California ballot initiative, the California Privacy Rights Act, or CPRA, was passed in November 2020.
+Added: In addition to the CCPA, a California ballot initiative, the CPRA, was passed in November 2020.
Effective as of January 1, 2023, the CPRA imposes additional obligations on companies covered by the legislation and will significantly modify the CCPA, including by expanding consumers’ rights with respect to certain sensitive personal information.
2 unchanged sentences
Some observers have noted that the CCPA and CPRA could mark the beginning of a trend toward more stringent privacy legislation in the United States, which could increase our potential liability and adversely affect our business.
−Removed: For example, on January 1, 2023, the Virginia Consumer Data Protection Act, or the CDPA, became effective.
+Added: For example, on January 1, 2023, the CDPA became effective.
Further, many additional United States state privacy laws will go into effect throughout 2023:
−Removed: the Colorado Privacy Act, or the CPA (July 1, 2023);
−Removed: the Connecticut Data Privacy Act, or the CTDPA (July 1, 2023);
−Removed: and the Utah Consumer Privacy Act, or the UCPA (December 31, 2023).
+Added: the CPA (July 1, 2023);
+Added: the CTDPA (July 1, 2023);
+Added: and the UCPA (December 31, 2023).
The CDPA, CPA, CTDPA, and UCPA are substantially similar in scope and contain many of the same requirements and exceptions as the CCPA, including a general exemption for clinical trial data and information governed by HIPAA.
1 unchanged sentence
While the CDPA, CPA, CTDPA, and UCPA incorporate many similar concepts of the CCPA and CPRA, there are also several key differences in the scope, application, and enforcement of the laws that will change the operational practices of regulated businesses.
−Removed: The new laws will, among other things, impact how regulated businesses collect and process personal sensitive data, conduct data protection assessments, transfer personal data to affiliates, and respond to consumer rights requests.
+Added: The new laws will, among other things, impact how regulated
+Added: businesses collect and process personal sensitive data, conduct data protection assessments, transfer personal data to affiliates, and respond to consumer rights requests.
A number of other states have proposed new privacy laws, some of which are similar to the above discussed recently passed laws.
19 unchanged sentences
Moreover, clinical trial participants about whom we or our potential collaborators obtain information, as well as the providers who share this information with us, may contractually limit our ability to use and disclose the information.
−Removed: Claims that we have violated individuals’ privacy rights, failed to comply with data protection laws or breached our contractual obligations, even if we are not found
−Removed: liable, could be expensive and time-consuming to defend, could result in adverse publicity and could have a material adverse effect on our business, financial condition, results of operations and prospects.
+Added: Claims that we have violated individuals’ privacy rights, failed to comply with data protection laws or breached our contractual obligations, even if we are not found liable, could be expensive and time-consuming to defend, could result in adverse publicity and could have a material adverse effect on our business, financial condition, results of operations and prospects.
Risks Related to Our Intellectual Property
7 unchanged sentences
Changes in either the patent laws or their interpretation in the United States and other countries may diminish our ability to protect our inventions, obtain, maintain, and enforce our intellectual property rights and, more generally, could affect the value of our intellectual property or narrow the scope of our patents.
−Removed: In addition, it is uncertain whether the World Trade Organization, or WTO, will waive certain intellectual property protections now or in the future on certain technologies.
+Added: In addition, it is uncertain whether the World Trade Organization ("WTO") will waive certain intellectual property protections now or in the future on certain technologies.
It is unknown if such a waiver would be limited to patents, or would include other forms of intellectual property including trade secrets and confidential know-how.
12 unchanged sentences
The issuance of a patent is not conclusive as to its inventorship, scope, validity, or enforceability, and our patents may be challenged in the courts or patent offices in the United States and abroad.
−Removed: We or our licensors may become subject to a third party pre-issuance submission of prior art to the United States Patent and Trademark Office, or the USPTO, or opposition, derivation, revocation, reexamination, post-grant and inter partes review, or interference proceedings and other similar proceedings challenging our patent rights or the patent rights of others.
+Added: We or our licensors may become subject to a third party pre-issuance submission of prior art to the USPTO, or opposition, derivation, revocation, reexamination, post-grant and inter partes review, or interference proceedings and other similar proceedings challenging our patent rights or the patent rights of others.
An adverse determination in any such submission, proceeding or litigation could reduce the scope of, or invalidate, our patent rights, allow third parties to commercialize our technology or products and compete directly with us, without payment to us, or result in our inability to manufacture or commercialize products without infringing third-party patent rights.
33 unchanged sentences
As a result, we may encounter significant problems in protecting and defending our intellectual property both in the United States and abroad.
−Removed: If we are unable to prevent unauthorized material disclosure of our intellectual property to third parties, we will not be able to establish or maintain a competitive advantage in our market, which could materially adversely affect our business, financial condition, results of operations and prospects.
+Added: If we are unable to prevent unauthorized material disclosure of our intellectual property to third parties,
+Added: we will not be able to establish or maintain a competitive advantage in our market, which could materially adversely affect our business, financial condition, results of operations and prospects.
Enforcing a claim that a party illegally disclosed or misappropriated a trade secret is difficult, expensive and time-consuming, and the outcome is unpredictable.
1 unchanged sentence
These lawsuits may consume our time and other resources even if we are successful and could have a material adverse effect on our business, financial conditions, results of operations and prospects.
−Removed: The intellectual property landscape around immunotherapeutics, nanoparticles and viral-vector based vaccines is crowded and dynamic, and third parties may initiate legal proceedings alleging that we are infringing, misappropriating or otherwise violating their intellectual property rights and such claims may be costly and time-consuming and may prevent or delay our product discovery and development efforts.
−Removed: The intellectual property landscape around immunotherapeutics, nanoparticles and viral-vector based vaccines is crowded and dynamic, and third parties may initiate legal proceedings alleging that we are infringing, misappropriating, or otherwise violating their intellectual property rights, the outcome of which would be uncertain and could have a material adverse effect on the success of our business.
+Added: The intellectual property landscape around immunotherapeutic, nanoparticle and viral vector-based products is crowded and dynamic, and third parties may initiate legal proceedings alleging that we are infringing, misappropriating or otherwise violating their intellectual property rights and such claims may be costly and time-consuming and may prevent or delay our product discovery and development efforts.
+Added: The intellectual property landscape around immunotherapeutic, nanoparticle and viral vector-based products is crowded and dynamic, and third parties may initiate legal proceedings alleging that we are infringing, misappropriating, or otherwise violating their intellectual property rights, the outcome of which would be uncertain and could have a material adverse effect on the success of our business.
Our commercial success depends upon our ability to develop, manufacture, market and sell our current and future product candidates and use our proprietary technologies without infringing, misappropriating or otherwise violating the intellectual property rights of third parties.
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These proceedings are expensive and may consume our time or other resources.
−Removed: We may choose to challenge a third party’s patent in patent opposition proceedings in the European Patent Office, or EPO, or other foreign patent office.
+Added: We may choose to challenge a third party’s patent in patent opposition proceedings in the European Patent Office ("EPO") or other foreign patent office.
The costs of these opposition proceedings could be substantial, and may consume our time or other resources.
27 unchanged sentences
We currently have rights to intellectual property, through licenses from third parties, to develop and commercialize our product candidates.
−Removed: Many pharmaceutical companies, biotechnology companies, and academic institutions are competing with us in the field of infectious disease, immunotolerance and oncology and filing patent applications potentially relevant to our business.
+Added: Many pharmaceutical companies, biotechnology companies, and academic institutions are competing with us in the field of infectious disease, immune tolerance and oncology and filing patent applications potentially relevant
+Added: to our business.
Because our current and future product candidates may require the use of proprietary rights held by third parties, the growth of our business will likely depend in part on our ability to acquire, in-license or use these proprietary rights.
15 unchanged sentences
In addition, companies that perceive us to be a competitor may be unwilling to assign or license rights to us.
−Removed: We also may be unable to license or acquire third-party intellectual property rights on terms that would allow us to make an appropriate return on our investment or at all.
+Added: We also may be unable to license or acquire third-party intellectual property rights on terms that would enable us to make an appropriate return on our investment or at all.
There can be no assurance that we will be able to successfully complete such negotiations and ultimately acquire the rights to the intellectual property surrounding the additional product candidates that we may seek to acquire.
15 unchanged sentences
Post-grant proceedings provoked by third parties or brought by the USPTO may be necessary to determine the validity or priority of inventions with respect to our patent applications or any patents we may in-license or own in the future.
−Removed: These proceedings are expensive and an unfavorable outcome could result in a loss of our current patent rights and could require us to cease using the related technology or to attempt to license rights to it from the prevailing party.
+Added: These proceedings are expensive and an unfavorable outcome could result in a loss of our current patent rights and could require
+Added: us to cease using the related technology or to attempt to license rights to it from the prevailing party.
Our business could be harmed if the prevailing party does not offer us a license on commercially reasonable terms.
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Depending upon the timing, duration and specifics of any FDA marketing approval of any of our current or future product candidates we may develop, one or more U.S.
−Removed: patents we in-license or may own in the future may be eligible for limited patent term extension under the Drug Price Competition and Patent Term Restoration Act of 1984, or the Hatch-Waxman Amendments.
+Added: patents we in-license or may own in the future may be eligible for limited patent term extension under the Hatch-Waxman Amendments.
The Hatch- Waxman Amendments permit a patent term extension of up to five years as compensation for patent term lost during the FDA regulatory review process.
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The United States has enacted and implemented wide-ranging patent reform legislation.
−Removed: On September 16, 2011, the Leahy-Smith America Invents Act, or America Invents Act, was signed into law, which includes a number of significant changes to U.S.
+Added: On September 16, 2011, the Leahy-Smith America Invents Act ("America Invents Act"), was signed into law, which includes a number of significant changes to U.S.
These include provisions that affect the way patent applications are prosecuted, redefine prior art, may affect patent litigation, establish a new post-grant review system and switch the U.S.
13 unchanged sentences
A successful invalidity challenge to a European patent under the UPC would result in loss of patent protection in those European countries.
−Removed: Accordingly, a single proceeding under the UPC could result in the partial or complete loss of patent protection in numerous European countries, rather than in each validated European country separately as such patents always have been adjudicated.
+Added: Accordingly, a single proceeding under the UPC could result in the partial or complete loss of
+Added: patent protection in numerous European countries, rather than in each validated European country separately as such patents always have been adjudicated.
Such a loss of patent protection could have a material adverse impact on our business and our ability to commercialize our technology and product candidates and, resultantly, on our business, financial condition, prospects and results of operations.
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However, if such third party continues to assert its claims, we cannot provide any assurance whether we could reach a settlement relating to such claims or whether we would prevail in any litigation or action related to such claims.
−Removed: Regardless of its outcome, any litigation related to such claims may subject us to damages, impair our ability to use our “Vaccitech” trademark, and otherwise adversely affect our business, results of operations and financial condition.
Moreover, during the trademark registration process, we may receive Office Actions from the USPTO objecting to the registration of our trademarks.
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The loss of the services of any of our executive officers, other key employees and other scientific and medical advisors, and an inability to find suitable replacements could result in delays in product development and harm our business.
−Removed: We conduct our operations at our facilities in Harwell, United Kingdom and Baltimore, Maryland.
+Added: We conduct our operations at our facilities in Harwell, United Kingdom and Germantown, Maryland.
These regions are headquarters to many other biopharmaceutical companies and many academic and research institutions.
Competition for skilled personnel in these markets is intense and may limit our ability to hire and retain highly qualified personnel on acceptable terms, or at all.
−Removed: Changes to UK, U.S.
−Removed: or similar foreign immigration and work authorization laws and regulations, including those that restrain the flow of scientific and professional talent, can be significantly affected by political forces and levels of economic activity.
−Removed: Our business may be materially adversely affected if legislative or administrative changes to the UK (including, but not limited to, those that result as a direct or indirect consequence of Brexit), U.S.
+Added: Changes to U.K., U.S.
+Added: or similar foreign immigration and work authorization laws and regulations, including those that restrain the flow of scientific and professional talent, can be significantly affected by
+Added: political forces and levels of economic activity.
+Added: Our business may be materially adversely affected if legislative or administrative changes to the U.K.
+Added: (including, but not limited to, those that result as a direct or indirect consequence of Brexit), U.S.
or similar foreign immigration or visa laws and regulations impair our hiring processes and goals or projects involving personnel who are not U.S.
2 unchanged sentences
Despite our efforts to retain valuable employees, members of our management, scientific and development teams may terminate their employment with us on short notice.
−Removed: Although we have employment agreements with all our employees, these employment agreements with US employees provide for at-will employment, which means that any of our US employees could leave our employment at any time, by providing the required contractual notification of their intent to leave.
−Removed: The standard notice period for UK employed personnel is three calendar months or six calendar months for the senior executive team.
+Added: Although we have employment agreements with all our employees, these employment agreements with U.S.
+Added: employees provide for at-will employment, which means that any of our U.S.
+Added: employees could leave our employment at any time, by providing the required contractual notification of their intent to leave.
+Added: The standard notice period for U.K.
+Added: employed personnel is three calendar months or six calendar months for the senior executive team.
Our success also depends on our ability to continue to attract, retain and motivate highly skilled junior, mid-level and senior managers as well as junior, mid-level and senior scientific and medical personnel.
2 unchanged sentences
As of December 31, 2023, we had 130 full-time and part-time employees.
−Removed: As our development and commercialization plans and strategies develop, and as we continue to transition into operating as a public company, we expect to need additional managerial, operational, sales, marketing, financial and other personnel, as well as additional facilities to expand our operations.
+Added: As our development and commercialization plans and strategies develop, and as we continue to transition into operating as a public company, we expect to need additional managerial, operational, technical, sales, marketing, financial and other personnel, as well as additional facilities to expand our operations.
Future growth would impose significant added responsibilities on members of management, including:
1 unchanged sentence
• managing clinical trial sites in multiple countries;
−Removed: ● managing our internal development efforts effectively, including the clinical and FDA review process for our product candidates, while complying with our contractual obligations to contractors and other third parties;
+Added: • managing our internal development efforts effectively, including the clinical and regulatory review process for our product candidates, while complying with our contractual obligations to contractors and other third parties;
• improving our operational, financial and management controls, reporting systems and procedures.
8 unchanged sentences
The risk of a security breach or disruption, particularly through cyberattacks or cyber intrusion, including by computer hackers, foreign governments, and cyber terrorists, has generally increased as the number, intensity and sophistication of attempted attacks and intrusions from around the world have increased.
−Removed: Cyberattacks could include wrongful conduct by hostile foreign governments, industrial espionage, wire fraud and other forms of cyber fraud, the deployment of harmful malware, denial-of-service, social engineering fraud or other means to threaten data security, confidentiality, integrity and availability.
+Added: Cyberattacks could include wrongful conduct by hostile foreign governments, industrial espionage, wire fraud and other forms of cyber fraud, the deployment of harmful malware, denial-of-service, social engineering fraud or other means to threaten data security,
+Added: confidentiality, integrity and availability.
If such an event were to occur, it could result in the theft or destruction of intellectual property, data or other misappropriation of assets, or otherwise compromise our confidential or proprietary information and result in a material disruption of our development programs and our business operations, such as the loss of clinical trial data from completed or future clinical trials.
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• workforce uncertainty in countries where labor unrest is more common than in the United States;
−Removed: ● potential liability under the FCPA Office of Foreign Assets Control Anti-Money Laundering Program as required by the Bank Secrecy Act and its implementing regulations, or comparable foreign laws, including the UK Bribery Act 2010, or Bribery Act;
+Added: • potential liability under the FCPA Office of Foreign Assets Control Anti-Money Laundering Program as required by the Bank Secrecy Act and its implementing regulations, or comparable foreign laws, including the UK Bribery Act 2010 ("Bribery Act");
• challenges enforcing our contractual and intellectual property rights, especially in those foreign countries that do not respect and protect intellectual property rights to the same extent as the United States;
5 unchanged sentences
Accordingly, our future results could be harmed by a variety of factors, including the following:
−Removed: ● economic weakness, including inflation, political instability in particular in foreign economies and markets, and the potentially severe continued United States and global economic impact caused by the COVID-19 pandemic;
+Added: • economic weakness, including inflation, political instability in particular in foreign economies and markets;
• differing regulatory requirements for drug approvals;
31 unchanged sentences
If the courts of England and Wales give a judgment for the sum payable under a U.S.
−Removed: judgment, the English judgment will be enforceable by methods generally available for this purpose.
+Added: judgment, the English
+Added: judgment will be enforceable by methods generally available for this purpose.
These methods generally permit the courts of England and Wales discretion to prescribe the manner of enforcement.
18 unchanged sentences
See Note 3 in the notes to our annual financial statements appearing elsewhere in this Annual Report for a description of foreign exchange risks.
−Removed: The possible abandonment of the euro by one or more members of the European Union, or the EU, could materially affect our business in the future.
+Added: The possible abandonment of the euro by one or more members of the European Union could materially affect our business in the future.
Despite measures taken by the EU to provide funding to certain EU member states in financial difficulties and by a number of European countries to stabilize their economies and reduce their debt burdens, it is possible that the euro could be abandoned in the future as a currency by countries that have adopted its use.
3 unchanged sentences
dollar and the pound sterling, the U.S.
−Removed: dollar equivalent of the proceeds that a holder of ADSs would receive upon the sale in the UK of any ordinary shares withdrawn from the depositary and the U.S.
+Added: dollar equivalent of the proceeds that a holder of ADSs would receive upon the sale in the U.K.
+Added: of any ordinary shares withdrawn from the depositary and the U.S.
dollar equivalent of any cash dividends paid in euros on our ordinary shares represented by ADSs could also decline.
13 unchanged sentences
In addition to the factors discussed in this “Risk Factors” section and elsewhere in this Annual Report, these factors include:
−Removed: ● the results of our ongoing, planned or any future preclinical studies, clinical trials or clinical development programs and those of third parties, such as those of AstraZeneca’s with respect to Vaxzevria;
• the commencement, enrollment, or results of clinical trials of our product candidates or any future clinical trials we may conduct, or changes in the development status of our product candidates;
39 unchanged sentences
We cannot guarantee that ADS holders will receive the voting materials in time to ensure that they can instruct the depositary to vote the ordinary shares underlying their ADSs.
−Removed: Otherwise, ADS holders will not be able to exercise their right to vote, unless they withdraw the ordinary shares underlying the ADSs they hold to vote them in person or by proxy in accordance with applicable laws and regulations and our articles of association, or the Articles.
+Added: Otherwise, ADS holders will not be able to exercise their right to vote, unless they withdraw the ordinary shares underlying the ADSs they hold to vote them in person or by proxy in accordance with applicable laws and regulations and our articles of association.
However, ADS holders may not know about the meeting far enough in advance to withdraw those ordinary shares.
15 unchanged sentences
In determining whether to enforce a contractual pre-dispute jury trial waiver provision, courts will generally consider whether a party knowingly, intelligently and voluntarily waived the right to a jury trial.
−Removed: We believe that this is the case with respect to the deposit agreement and our ADSs.
+Added: We believe that this is the case with respect to the
+Added: deposit agreement and our ADSs.
It is advisable that you consult legal counsel regarding the jury waiver provision before entering into the deposit agreement.
9 unchanged sentences
We are an emerging growth company and a smaller reporting company, and we cannot be certain if the reduced reporting requirements applicable to emerging growth companies and smaller reporting companies will make our ADSs less attractive to investors.
−Removed: We are an emerging growth company, as defined in the Jumpstart Our Business Startups Act, or JOBS Act, enacted in April 2012.
−Removed: For as long as we continue to be an emerging growth company, we may take advantage of exemptions from various reporting requirements that are applicable to other public companies that are not emerging growth companies, including not being required to comply with the auditor attestation requirements of Section 404 of the Sarbanes-Oxley Act of 2002, as amended, or Sarbanes-Oxley Act, reduced disclosure obligations regarding executive compensation in our periodic reports and proxy statements, and exemptions from the requirements of holding nonbinding advisory votes on executive compensation and shareholder approval of any golden parachute payments not previously approved.
+Added: We are an emerging growth company, as defined in the JOBS Act enacted in April 2012.
+Added: For as long as we continue to be an emerging growth company, we may take advantage of exemptions from various reporting requirements that are applicable to other public companies that are not emerging growth companies, including not being required to comply with the auditor attestation requirements of Section 404 of the Sarbanes-Oxley Act reduced disclosure obligations regarding executive compensation in our periodic reports and proxy statements, and exemptions from the requirements of holding nonbinding advisory votes on executive compensation and shareholder approval of any golden parachute payments not previously approved.
We could be an emerging growth company for up to five years following the year in which we became a public company, although circumstances could cause us to lose that status earlier.
10 unchanged sentences
Moreover, these rules and regulations will increase our legal and financial compliance costs and will make some activities more time-consuming and costly.
−Removed: For example, we expect that these rules and regulations may make it more difficult and more expensive for us to obtain director and officer liability insurance, which in turn could make it more difficult for us to attract and retain qualified members of our board of directors.
+Added: For example, we expect that these
+Added: rules and regulations may make it more difficult and more expensive for us to obtain director and officer liability insurance, which in turn could make it more difficult for us to attract and retain qualified members of our board of directors.
However, these rules and regulations are often subject to varying interpretations, in many cases due to their lack of specificity, and, as a result, their application in practice may evolve over time as new guidance is provided by regulatory and governing bodies.
This could result in continuing uncertainty regarding compliance matters and higher costs necessitated by ongoing revisions to disclosure and governance practices.
−Removed: We are subject to the reporting requirements of the Securities Exchange Act of 1934, the Sarbanes-Oxley Act of 2002 and the rules and regulations of The Nasdaq Global Market.
−Removed: Pursuant to Section 404 of the Sarbanes-Oxley Act of 2002, we are required to perform system and process evaluation and testing of our internal control over financial reporting to allow our management to report on the effectiveness of our internal control over financial reporting.
+Added: We are subject to the reporting requirements of the Securities Exchange Act of 1934, the Sarbanes-Oxley Act and the rules and regulations of The Nasdaq Global Market.
+Added: Pursuant to Section 404 of the Sarbanes-Oxley Act, we are required to perform system and process evaluation and testing of our internal control over financial reporting to allow our management to report on the effectiveness of our internal control over financial reporting.
See section entitled “Controls and Procedures – Management’s Annual Report on Internal Controls Over Financial Reporting.” However, while we remain an emerging growth company, we will not be required to include an attestation report on internal control over financial reporting issued by our independent registered public accounting firm.
9 unchanged sentences
• the timing and outcomes of clinical trials for our current and any other future product candidates;
−Removed: ● the cost of manufacturing our current and any future product candidates, which may vary depending on FDA guidelines and requirements, the quantity of production and the terms of our agreements with manufacturers;
+Added: • the cost of manufacturing our current and any future product candidates, which may vary depending on regulatory guidelines and requirements, the quantity of production and the terms of our agreements with manufacturers;
• our ability to adequately support our future growth;
12 unchanged sentences
However, in accordance with the limitations set forth in the deposit agreement, it may be unlawful or impractical to make a distribution available to holders of ADSs.
−Removed: We have no obligation to take any other action to permit distribution on the ADSs, ordinary shares, rights or anything else to holders of the ADSs.
+Added: We have no obligation to take any other action to permit distribution on the ADSs, ordinary
+Added: shares, rights or anything else to holders of the ADSs.
This means that holders of our ADSs may not receive the distributions we make on our ordinary shares or any value from them if it is unlawful or impractical to make them available to holders of our ADSs.
21 unchanged sentences
Such approval may be for a maximum period of up to five years.
−Removed: Shareholder protections found in provisions under the UK City Code on Takeovers and Mergers, or the Takeover Code, will not apply if our place of central management and control is considered to be outside of the UK (or the Channel Islands or the Isle of Man).
+Added: Shareholder protections found in provisions under the UK City Code on Takeovers and Mergers (the "Takeover Code"), will not apply if our place of central management and control is considered to be outside of the UK (or the Channel Islands or the Isle of Man).
We believe that our place of central management and control is not in the United Kingdom (or the Channel Islands or the Isle of Man) for the purposes of the jurisdictional criteria of the Takeover Code.
Accordingly, we believe that we are not currently subject to the Takeover Code and, as a result, our shareholders are not currently entitled to the benefit of certain takeover offer protections provided under the Takeover Code, including the rules regarding mandatory takeover bids.
−Removed: In the event that this changes, or if the interpretation and application of the Takeover Code by the Panel on Takeovers and Mergers, or Takeover Panel, changes (including changes to the way in which the Takeover Panel assesses the application of the Takeover Code to English companies whose shares are listed outside of the United Kingdom), the Takeover Code may apply to us in the future.
+Added: In the event that this changes, or if the interpretation and application of the Takeover Code by the Panel on Takeovers and Mergers, (the "Takeover Panel"), changes (including changes to the way in which the Takeover Panel assesses the application of the Takeover Code to English companies whose shares are listed outside of the United Kingdom), the Takeover Code may apply to us in the future.
The Takeover Code provides a framework within which takeovers of companies which are subject to the Takeover Code are regulated and conducted.
The following is a brief summary of some of the most important rules of the Takeover Code:
−Removed: ● in connection with a potential offer, if following an approach by or on behalf of a potential bidder, the company is “the subject of rumor or speculation” or there is an “untoward movement” in the company’s share price, there is a requirement for the potential bidder to make a public announcement about a potential offer for the company, or for the company to make a public announcement about its review of a potential offer;
+Added: • in connection with a potential offer, if following an approach by or on behalf of a potential bidder, the company is “the subject of rumor or speculation” or there is an “untoward movement” in the company’s share price, there is a
+Added: requirement for the potential bidder to make a public announcement about a potential offer for the company, or for the company to make a public announcement about its review of a potential offer;
• when any person acquires, whether by a series of transactions over a period of time or not, an interest in shares which (taken together with shares already held by that person and an interest in shares held or acquired by persons acting in concert with him or her) carry 30% or more of the voting rights of a company that is subject to the Takeover Code, that person is generally required to make a mandatory offer to all the holders of any class of equity share capital or other class of transferable securities carrying voting rights in that company to acquire the balance of their interests in the company;
49 unchanged sentences
or (d) any action or proceeding asserting a claim or otherwise related to our affairs (the “England and Wales Forum Provision”.) The England and Wales Forum Provision will not apply to any causes of action arising under the Securities Act or the Exchange Act.
−Removed: Our Articles further provide that unless we consent by ordinary resolution to the selection of an alternative forum, the United States District Court for the Southern District of New York shall be the exclusive forum for resolving any complaint asserting a cause of action arising under the Securities Act or the Exchange Act (the “ U.S.
+Added: Our Articles further provide that unless we consent by ordinary resolution to the selection of an alternative forum, the United States District Court for the Southern District of New York shall be the exclusive forum for resolving any complaint
+Added: asserting a cause of action arising under the Securities Act or the Exchange Act (the “U.S.
Federal Forum Provision.”) In addition, our Articles provide that any person or entity purchasing or otherwise acquiring any interest in our shares is deemed to have notice of and consented to the England and Wales Forum Provision and the U.S.
23 unchanged sentences
federal income tax consequences to U.S.
−Removed: Under the Internal Revenue Code, or Code, we will be a passive foreign investment company, or PFIC, for any taxable year in which (i) 75% or more of our gross income consists of passive income or (ii) 50% or more of the average quarterly value of our assets consists of assets that produce, or are held for the production of, passive income.
+Added: Under the Internal Revenue Code (the "Code"), we will be a passive foreign investment company, or PFIC, for any taxable year in which (i) 75% or more of our gross income consists of passive income or (ii) 50% or more of the average quarterly value of our assets consists of assets that produce, or are held for the production of, passive income.
For purposes of these tests, passive income includes dividends, interest, gains from the sale or exchange of investment property and certain rents and royalties.
16 unchanged sentences
Treasury Regulations.
−Removed: Based on the current and expected composition of our income and the value of our assets, we believe we were not a PFIC for the year ended December 31, 2021.
−Removed: However, based on current projections of our income and volatility in the price of our shares, it is possible we may be a PFIC for our current taxable year.
+Added: Based on the current and expected composition of our income and the value of our assets, we were a PFIC for the year ended December 31, 2023 and expect to remain a PFIC for our current taxable year.
No assurances regarding our PFIC status can be provided for the current taxable year or any future taxable years.
38 unchanged sentences
Any failure to implement required new or improved controls, or difficulties encountered in their implementation could cause us to fail to meet our reporting obligations.
−Removed: In addition, testing required to be conducted by us in connection with Section 404, and subsequent testing by our independent registered public accounting firm, may reveal deficiencies in our internal controls over financial reporting that are deemed to be material weaknesses or that may require prospective or retroactive changes to our financial statements or identify other areas for further attention or improvement.
−Removed: Inferior internal controls could also cause investors to lose confidence in our reported financial information, which could have a negative effect on the trading price of our ADSs.
+Added: In addition, testing required to be conducted by us in connection with Section 404 of the Sarbanes-Oxley Act, and any subsequent testing by our independent registered public accounting firm, may reveal deficiencies in our internal controls over financial reporting that are deemed to be material weaknesses or that may require prospective or retroactive changes to our financial statements or identify other areas for further attention or improvement.
+Added: Deficient internal controls could also cause investors to lose confidence in our reported financial information, which could have a negative effect on the trading price of our ADSs.
If we fail to establish and maintain proper internal controls, our ability to produce accurate financial statements or comply with applicable regulations could be impaired.
As a result, shareholders could lose confidence in our financial and other public reporting, which would harm our business and the trading price of our ADSs.
−Removed: Implementing any appropriate changes to our internal controls, including compliance with the requirements of Section 404 of the Sarbanes-Oxley Act, may distract our officers and employees, entail substantial costs to modify our existing processes, and take significant time to complete.
+Added: Implementing any appropriate changes to our internal controls, including changes relating to our application of the requirements of Section 404 of the Sarbanes-Oxley Act, may distract our officers and employees, entail substantial costs to modify our existing processes, and take significant time to complete.
These changes may not, however, be effective in maintaining the adequacy of our internal controls, and any failure to maintain that adequacy, or consequent inability to produce accurate financial statements on a timely basis, could increase our operating costs and harm our business.
In addition, investors’ perceptions that our internal controls are inadequate or that we are unable to produce accurate financial statements on a timely basis may harm our stock price and make it more difficult for us to continue to discover and develop novel immunotherapeutics and vaccines for the treatment and prevention of infectious diseases, immunetolerance and cancer.
−Removed: We identified material weaknesses in connection with our internal control over financial reporting.
−Removed: Although we are taking steps to remediate these material weaknesses, we may not be successful in doing so in a timely manner, or at all, and we may identify other material weaknesses.
−Removed: For year ended December 31, 2022, pursuant to Section 404, we are required to furnish a report by our senior management on our internal control over financial reporting.
−Removed: However, while we remain an emerging growth company, we will not be required to include an attestation report on internal control over financial reporting issued by our independent registered public accounting firm.
−Removed: To achieve compliance with Section 404, we have been engaged in a process to document and evaluate our internal control over financial reporting, which is both costly and challenging.
−Removed: In this regard, we will need to continue to dedicate internal resources, potentially continue to engage outside consultants and adopt a detailed work plan to assess and document the adequacy of internal control over financial reporting, continue steps to improve control processes as appropriate, validate through testing that controls are functioning as documented and implement a continuous reporting and improvement process for internal control over financial reporting.
−Removed: Management previously reported, in our Annual Report on Form 10-K for the year ended December 31, 2021, material weaknesses in our internal control over financial reporting related to:
−Removed: (i) our IT general control environment has not been sufficiently designed to include appropriate user access rights and (ii) policies and procedures with respect to the review, supervision and monitoring of our accounting and reporting functions were either not designed and in place or not operating effectively.
−Removed: As of the year ended December 31, 2022, in addition to the above material weakness on IT general control user access rights, we also identified additional deficiencies related to the design and implementation of controls over program development, program changes, and computer operations.
−Removed: During fiscal year 2022, we undertook efforts to remediate previously disclosed material weaknesses, implement a company-wide formal control program, and strengthen our internal controls.
−Removed: Implementing section 404 within our environment has been a significant undertaking.
−Removed: Although we made substantial progress throughout the year, the design and operation of SOX-level controls remained ongoing as of December 31, 2022, due to a significant amount of progress occurring in the second half of the year, and therefore being unable to determine if a control had been formalized, operated and tested with enough instances to be embedded within the control environment for fiscal year 2022.
−Removed: Our internal control remediation efforts will continue into fiscal year 2023.
−Removed: See section entitled “Controls and Procedures.”
−Removed: Assessing our procedures to improve our internal control over financial reporting is an ongoing process.
−Removed: We may need to hire additional accounting and financial staff and consultants with appropriate experience and technical accounting knowledge, and compile the system and process documentation necessary to remediate the material weaknesses identified.
−Removed: We may not be able to complete our evaluation, testing and any required remediation in a timely fashion.
−Removed: We therefore can provide no assurance that our remediation efforts described
−Removed: herein will be successful and that we will not have material weaknesses in the future.
−Removed: Any other material weaknesses we identify could result in an adverse reaction in the financial markets due to a loss of confidence in the reliability of our consolidated financial statements.
+Added: We previously identified material weaknesses in connection with our internal control over financial reporting.
+Added: Although we have taken steps to remediate these material weaknesses, we may identify other material weaknesses in the future, which could have a significant adverse effect on our business and the trading price of our ADSs.
+Added: For the year ended December 31, 2023, pursuant to Section 404 of the Sarbanes-Oxley Act, we are required to furnish a report by our senior management on our internal control over financial reporting.
+Added: This report is required to include disclosure of any material weaknesses identified by our management in our internal control over financial reporting.
+Added: However, while we remain an non-accelerated filer, we will not be required to include an attestation report on internal control over financial reporting issued by our independent registered public accounting firm.
+Added: To achieve compliance with Section 404 of the Sarbanes-Oxley Act, we have been engaged in a process to document and evaluate our internal control over financial reporting, which is both costly and challenging.
+Added: In this regard, we will need to continue to dedicate internal resources, potentially continue to engage outside consultants and adopt a detailed work plan to assess and document the
+Added: adequacy of internal control over financial reporting, continue steps to improve control processes as appropriate, validate through testing that controls are functioning as documented and implement a continuous reporting and improvement process for internal control over financial reporting.
+Added: Management previously reported, in our Annual Report for the year ended December 31, 2022, material weaknesses in our internal control over financial reporting related to:
+Added: (i) our IT general control environment has not been sufficiently designed to include appropriate controls over program development, program changes, computer operations and user access rights and (ii) policies and procedures with respect to the review, supervision and monitoring of our accounting and reporting functions were either not designed and in place or not operating effectively.
+Added: During fiscal years 2022 and 2023, we undertook efforts to remediate previously disclosed material weaknesses, implement a company-wide formal control program, and strengthen our internal controls.
+Added: Implementing Section 404 of the Sarbanes-Oxley Act within our environment has been a significant undertaking.
+Added: Although management has concluded that the actions taken to strengthen our internal control over financial reporting, as well as the results of our testing over the design and operating effectiveness of these controls, remediated the previously identified material weaknesses as of December 31, 2023, there is no guarantee that our internal control over financial reporting will be effective in the future periods and the effectiveness of our internal controls are subject to the risk that controls may become inadequate because of changes in conditions, or that the degree of compliance with applicable policies, processes and documentation requirements may deteriorate.
+Added: Ineffective disclosure controls and procedures and internal control over financial reporting could also cause investors to lose confidence in our reported financial and other information, which would likely have a negative effect on the trading price of our ADSs.
We could be subject to securities class action litigation .
5 unchanged sentences
There was a transition period during which EU pharmaceutical laws continued to apply to the United Kingdom, which expired on December 31, 2020.
−Removed: However, the EU and the United Kingdom have concluded a trade and cooperation agreement, or TCA, which was provisionally applicable since January 1, 2021 and has been formally applicable since May 1, 2021.
+Added: However, the EU and the United Kingdom have concluded a TCA which was provisionally applicable since January 1, 2021 and has been formally applicable since May 1, 2021.
The TCA includes specific provisions concerning pharmaceuticals, which include the mutual recognition of GMP, inspections of manufacturing facilities for medicinal products and GMP documents issued, but does not foresee wholesale mutual recognition of the United Kingdom and European Union pharmaceutical regulations.
7 unchanged sentences
Given these possibilities and others we may not anticipate, as well as the absence of comparable precedent, it is unclear what financial, regulatory and legal implications the withdrawal of the United Kingdom from the European Union will have in the long-term and the full extent to which our business could be adversely affected.
−Removed: Unresolved Staff Comments
−Removed: Not Applicable.
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.