REGISTRATION STATEMENT PURSUANT TO SECTION 12(b) OR (g) OF THE SECURITIES EXCHANGE ACT OF 1934 |
ANNUAL REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 |
TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 |
SHELL COMPANY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 |
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* | Not for trading, but only in connection with the registration of the American Depositary Shares. |
Large accelerated filer | ☐ | Accelerated filer | ☐ | |||
☒ | Emerging growth company |
International Financial Reporting Standards as issued | Other ☐ | |||||||
by the International Accounting Standards Board | ☐ |
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• | the timing, progress and results of preclinical studies and clinical trials for our product candidates, including our product development plans and strategies; |
• | the timing, scope and likelihood of regulatory filings and approvals, including final regulatory approval of our product candidates; |
• | the potential benefits and market opportunity for our product candidates and technologies; |
• | expectations regarding the size, scope and design of clinical trials; |
• | our manufacturing, commercialization, and marketing plans and strategies; |
• | our plans to hire additional personnel and our ability to attract and retain such personnel; |
• | our estimates of the number of patients who suffer from the diseases we are targeting and potential growth in the patient populations; |
• | our expectations regarding the approval and use of our product candidates as first, second or subsequent lines of therapy or in combination with other drugs; |
• | our competitive position and the development and impact of competing therapies that are or may become available; |
• | expectations regarding future events under licensing and research and development agreements, including potential future payments, as well as our plans and strategies for entering into further licensing and research and development agreements; |
• | our intellectual property position, including the scope of protection we are able to establish and maintain for intellectual property rights covering product candidates we may develop, including the extensions of existing patent terms where available, the validity of intellectual property rights held by third parties, and our ability not to infringe, misappropriate or otherwise violate any third-party intellectual property rights; |
• | the rate and degree of market acceptance and clinical utility of our product candidates we may develop; |
• | our estimates regarding expenses, future revenue, capital requirements and needs for additional financing; |
• | our future financial performance; |
• | the period over which we estimate our existing cash and cash equivalents will be sufficient to fund our future operating expenses and capital expenditure requirements; |
• | the impact of laws and regulations; and |
• | the impact of the COVID-19 pandemic and actions to slow its spread. |
• | We have incurred net losses since our inception and anticipate that we will continue to incur significant losses for the foreseeable future. We may never generate any revenue or become profitable or, if we achieve profitability, may not be able to sustain it. |
• | We will need to obtain substantial additional funding to complete the development and commercialization of our product candidates. If we are unable to raise this capital when needed, we may be forced to delay, reduce or eliminate our product development programs or other operations. |
• | We are early in our development efforts and have a limited history of conducting clinical trials to test our product candidates in humans. |
• | Our business is highly dependent on our lead product candidate, ARX788, and we must complete additional clinical testing before we can seek regulatory approval and begin commercialization of ARX788 for any indication. If we are unable to obtain regulatory approval for, and successfully commercialize, ARX788, our business may be materially harmed and such failure may affect the viability of our other product candidates. |
• | Preclinical and clinical development is a lengthy, expensive and uncertain process. The results of preclinical studies and early clinical trials are not always predictive of future results. If our preclinical studies and clinical trials are not sufficient to support regulatory approval 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. |
• | Our product candidates are based on novel technologies, making it difficult to predict the timing, results and cost of product candidate development and likelihood of obtaining regulatory approval. |
• | We may encounter substantial delays in initiating or completing our clinical trials. |
• | Serious adverse events, undesirable side effects or other unexpected properties of our product candidates may be identified during development or after approval, which could lead to the discontinuation of our clinical development programs, refusal by regulatory authorities to approve our product candidates or, if discovered following marketing approval, revocation of marketing authorizations or limitations on the use of our product candidates thereby limiting the commercial potential of such product candidate. |
• | We rely on third parties to conduct, supervise, and monitor our clinical trials and perform some of our research and preclinical studies. If these third parties do not satisfactorily carry out their contractual duties or fail to meet expected deadlines, our development programs may be delayed or subject to increased costs, each of which may have an adverse effect on our business and prospects. |
• | We are currently party to several in-license agreements under which we acquired rights to use, develop, manufacture and/or commercialize certain of our platform technologies and resulting product candidates. If we breach our obligations under these agreements, we may be required to pay damages, lose our rights to these technologies or both, which would adversely affect our business and prospects. |
• | We are dependent on our license agreements and R&D Agreements with various partners to develop and commercialize products using our technologies in various fields and indications as well as certain of our product candidates in certain geographies. The failure to maintain our R&D Agreements with our collaboration partners or the failure of our partners to perform their obligations under our R&D Agreements with them, could negatively impact our business. |
• | We face substantial competition, which may result in others discovering, developing or commercializing products more quickly or marketing them more successfully than us. |
• | If we are unable to obtain and maintain sufficient intellectual property protection for our platform technologies and product candidates, or if the scope of the intellectual property protection is not sufficiently broad, our competitors could develop and commercialize products similar or identical to ours, and our ability to successfully commercialize our products may be adversely affected. |
A. |
[Reserved] |
B. |
Capitalization and indebtedness. |
C. |
Reasons for the offer and use of proceeds. |
D. |
Risk Factors. |
• | the initiation, trial design, progress, timing, costs and results of drug discovery, preclinical studies and clinical trials of our product candidates, and in particular the clinical trials for ARX788; |
• | the number and characteristics of product candidates that we pursue, as well as the indications for which we develop our product candidates; |
• | the length of our clinical trials, including, among other things, as a result of delays in enrollment, difficulties enrolling sufficient subjects or delays or difficulties in clinical trial site initiations; |
• | the outcome, timing and costs of seeking regulatory approvals for our product candidates; |
• | the costs of manufacturing our product candidates, in particular for clinical trials in preparation for marketing approval and in preparation for commercialization; |
• | the costs of any third-party products used in our combination clinical trials that are not covered by such third party or other sources; |
• | the costs associated with hiring additional personnel and consultants as our preclinical, manufacturing, regulatory and clinical activities increase; |
• | whether and when we receive marketing approvals and revenue from any commercial sales of any of our product candidates, if approved; |
• | the cost of commercialization activities for any of our product candidates, if approved, including marketing, sales and distribution costs; |
• | the emergence of competing therapies and other adverse market developments; |
• | the ability to establish and maintain strategic collaboration, licensing or other arrangements and whether and when we receive or are obligated to make payments under such arrangements; |
• | the extent to which we in-license or acquire other products and technologies and the terms of these transactions; |
• | the costs involved in preparing, filing, prosecuting, maintaining, expanding, defending and enforcing patent claims, including litigation costs and the outcome of such litigation; |
• | our need and ability to retain key management and hire scientific, technical, business, and medical personnel; |
• | our implementation of additional internal systems and infrastructure, including operational, financial and management information systems; |
• | the costs associated with expanding our facilities or building out our laboratory space; |
• | the extent of the impacts and duration of the COVID-19 pandemic; and |
• | the costs of operating as a public company. |
• | successful completion of preclinical studies; |
• | submission of Investigational New Drug (IND) or other regulatory applications to allow for initiation of our planned and future clinical trials and authorizations from regulators to initiate clinical trials; |
• | successful initiation, execution and completion of, planned and future clinical trials and achieving positive results from such trials; |
• | demonstrating a risk-benefit profile acceptable to regulatory authorities; |
• | clinical trial data that are sufficient to support marketing approvals from applicable regulatory authorities; |
• | and obtaining and maintaining patent, trade secret and other intellectual property protection and regulatory exclusivity for our product candidates and avoiding infringement of third party intellectual property rights. |
• | incur unplanned costs; |
• | be delayed in or prevented from continuing clinical development and obtaining marketing approval for our product candidates; |
• | obtain approval for indications or patient populations that are not as broad as intended or desired; |
• | obtain approval with labeling that includes significant use or distribution restrictions or safety warnings, including boxed warnings or contraindications; |
• | be subject to changes or limitations in the way the product is administered; |
• | be required to perform additional preclinical studies or clinical trials to support approval or be subject to additional post-marketing testing requirements; |
• | have regulatory authorities withdraw their approval of the product, if granted, or impose restrictions on its distribution in the form of a Risk Evaluation and Mitigation Strategy (REMS); |
• | become subject to litigation; or |
• | experience damage to our reputation. |
• | delays in reaching a consensus with regulatory authorities on trial design; |
• | delays in reaching agreement or failing to agree on acceptable terms with prospective contract research organizations (CROs) and clinical trial sites; |
• | delays in opening sites, including delays in obtaining required approvals from institutional review boards (IRBs) and recruiting suitable patients to participate in our clinical trials; |
• | delays in enrolling patients in our clinical trials; |
• | failure by our CROs, other third parties or us to adhere to the trial protocol or applicable regulatory requirements, including the FDA’s good clinical practices (GCPs) or applicable regulatory requirements in other countries; |
• | regulatory authorities finding deficiencies in the manufacturing processes or facilities of third-party manufacturers with which we or any of our potential future collaborators contract for clinical supplies; |
• | delays in the testing, validation, manufacturing and delivery of our product candidates to the treatment sites, including due to a facility manufacturing any of our product candidates or any of their components being ordered by the FDA, NMPA, EMA or comparable regulatory authorities to temporarily or permanently shut down due to violations of current good manufacturing practices (cGMP) regulations or other applicable requirements, or infections or cross-contaminations of product candidates in the manufacturing process; |
• | imposition of a clinical hold by institutional review boards (IRBs) or regulatory authorities as a result of a serious adverse event (SAE), concerns with a class of product candidates, after an inspection of our clinical trial operations or trial sites, or for other reasons; |
• | suspensions or terminations by us, the IRBs of the institutions at which such trials are being conducted, by the Safety Review Committee or Data Safety Monitoring Board, for such trial or by regulatory authorities due to a number of factors, including those described above; |
• | patients not completing participation in a trial, returning for post-treatment follow-up or otherwise failing to adhere to clinical trial protocols; |
• | lack of adequate funding; or |
• | changes in regulatory requirements and guidance that require amending or submitting new clinical protocols. |
• | the size and nature of the patient population; |
• | the severity of the disease under investigation; |
• | eligibility criteria for the trial; |
• | the proximity of patients to clinical sites; |
• | the design of the clinical protocol; |
• | the ability to obtain and maintain patient consents; |
• | the ability to recruit clinical trial investigators with the appropriate competencies and experience; |
• | the risk that patients enrolled in clinical trials will drop out of the trials before the administration of our product candidates or trial completion; |
• | reporting of the preliminary results of our clinical trials; |
• | the number of competing clinical trials; |
• | the availability of new drugs approved for the indication the clinical trial is investigating; |
• | clinicians’ and patients’ perceptions as to the potential advantages of the drug being studied in relation to other available therapies; and |
• | other factors we may not be able to control. |
• | regulatory authorities may suspend, withdraw or limit approvals of such product; |
• | regulatory authorities may require additional warnings on the label, including a “boxed” warning or contraindication, or issue safety alerts, Dear Healthcare Provider letters, press releases or other communications containing warnings or other safety information about the product; |
• | regulatory authorities may require a REMS plan to mitigate risks; |
• | we may be required to change the way a product is distributed or administered, conduct additional clinical trials, or change the labeling of the product; |
• | the product may become less competitive, and our reputation may suffer; |
• | we may decide to remove the product from the marketplace; and |
• | we may be subject to regulatory investigations and government enforcement actions, including fines, injunctions or the imposition of civil or criminal penalties. |
• | such authorities may disagree with the design or implementation of our clinical trials; |
• | negative or ambiguous results from our clinical trials or results may not meet the level of statistical significance required by the FDA, NMPA, EMA or comparable regulatory authorities for approval; |
• | serious and unexpected product-related side effects may be experienced by participants in our clinical trials or by individuals using biological products similar to our product candidates; |
• | the population studied in the clinical trial may not be sufficiently broad or representative to assure safety in the full population for which we seek approval; |
• | such authorities may not accept clinical data from trials which are conducted at clinical facilities or in countries where the standard of care is potentially different from that of the United States; |
• | we may be unable to demonstrate that a product candidate’s clinical and other benefits outweigh its safety risks or that a product candidate is safe and effective for its proposed indication; |
• | such authorities may disagree with our interpretation of data from preclinical studies or clinical trials; |
• | such authorities may not agree that the data collected from clinical trials of our product candidates are acceptable or sufficient to support the submission of an application for regulatory approval or other submissions or to obtain regulatory approval in the United States or elsewhere, including due to clinical trial issues encountered as a result of COVID-19 pandemic, and such authorities may impose requirements for additional preclinical studies or clinical trials; |
• | such authorities may disagree regarding the formulation, labeling and/or the specifications of our product candidates; |
• | approval may be granted only for indications that are significantly more limited than what we apply for and/or with other significant restrictions on distribution and use; |
• | such authorities may fail to approve any required companion diagnostics to be used with our product candidates; |
• | such authorities may find deficiencies in the manufacturing processes or facilities of our third-party manufacturers with which we or any of our potential future collaborators contract for clinical and commercial supplies; or |
• | the approval policies or regulations of such authorities may significantly change in a manner rendering our or any of our potential future collaborators’ clinical data insufficient for approval. |
• | issuing warning or untitled letters or holds on clinical trials; |
• | mandating modifications to promotional materials or require us to provide corrective information to healthcare practitioners, or require other restrictions on the labeling or marketing of such products; |
• | seeking an injunction or imposing civil or criminal penalties or monetary fines; |
• | suspension or imposition of restrictions on operations, including product manufacturing or marketing or withdrawal of the product from the market; |
• | seizure or detention of products, refusal to permit the import or export of products or voluntary or mandatory product recalls; |
• | suspension, modification or revocation of our marketing approvals; |
• | suspension of any ongoing clinical trials; |
• | refusal to approve pending applications or supplements to applications submitted by us; |
• | imposition of a REMS, which may include distribution or use restrictions; or |
• | requiring us to conduct additional post-market clinical trials, change our product labeling or submit additional applications for marketing authorization. |
• | our inability to design such product candidates with the properties that we desire; or |
• | potential product candidates may, on further study, be shown to have harmful side effects or other characteristics that indicate that they are unlikely to be products that will receive marketing approval and achieve market acceptance. |
• | inability to meet our product specifications and quality requirements consistently; |
• | an inability to initiate or continue clinical trials of our product candidates under development; |
• | delay in submitting regulatory applications, or receiving marketing approvals, for our product candidates, if at all; |
• | loss of the cooperation of future collaborators; |
• | subjecting third-party manufacturing facilities or our manufacturing facilities to additional inspections by regulatory authorities; |
• | requirements to cease development or to recall batches of our product candidates; and |
• | in the event of approval to market and commercialize our product candidates, an inability to meet commercial demands for our product or any other future product candidates. |
• | efficacy and potential advantages compared to alternative treatments; |
• | our ability to offer our products for sale at competitive prices; |
• | convenience and ease of administration compared to alternative treatments; |
• | the willingness of the target patient population to try new therapies and of physicians to prescribe these therapies; |
• | the availability of coverage and adequate reimbursement from government and commercial third-party payors, and the willingness of patients to pay out of pocket for our products, once approved, in the absence of adequate third party payor reimbursement; |
• | the strength of marketing and distribution support; and |
• | the prevalence and severity of any side effects. |
• | a covered benefit under its health plan; |
• | safe, effective and medically necessary; |
• | appropriate for the specific patient; |
• | cost-effective; and |
• | neither experimental nor investigational. |
• | our inability to recruit and retain adequate numbers of effective sales and marketing personnel; |
• | the inability of sales personnel to obtain access to physicians or educate adequate numbers of physicians on the benefits of prescribing any future products; |
• | the lack of complementary products to be offered by sales personnel, which may put us at a competitive disadvantage relative to companies with more extensive product portfolios; and |
• | unforeseen costs and expenses associated with creating an independent sales and marketing organization. |
• | litigation involving patients taking our products; |
• | restrictions on such products, manufacturers or manufacturing processes; |
• | restrictions on the labeling or marketing of a product; |
• | restrictions on product distribution or use; |
• | requirements to conduct post-marketing studies or clinical trials; |
• | warning or untitled letters; |
• | withdrawal of the products from the market; |
• | refusal to approve pending applications or supplements to approved applications that we submit; |
• | recall of products; |
• | fines, restitution or disgorgement of profits or revenue; |
• | suspension or withdrawal of marketing approvals; |
• | suspension of any ongoing clinical trials; |
• | damage to relationships with any potential collaborators; |
• | unfavorable press coverage and damage to our reputation; |
• | refusal to permit the import or export of our products; |
• | product seizure; or |
• | injunctions or the imposition of civil or criminal penalties. |
• | our collaboration partners may not comply with applicable regulatory requirements with respect to developing or commercializing products under our agreements with them, which could adversely impact development, regulatory approval and eventual commercialization of such products. For example, our collaboration partners’ failure to comply with existing or future laws and regulations related to the management of human genetic resources (including materials and information) in China could lead to government enforcement actions, which could include fines, suspension of related activities and confiscation of related human genetic resources and gains generated from conducting these activities, or breach liability. Compliance or the failure to comply with such laws could increase the costs of, limit and cause significant delay in their clinical studies and research and development activities, which could materially and adversely affect our business and prospects as well; |
• | we and our collaboration partners could disagree as to future development plans and our partners may delay initiation of or cease research efforts, preclinical studies or clinical trials; |
• | there may be disputes between us and our collaboration partners, including disagreements regarding the terms of the applicable agreement or scope of the license, that may result in the delay of or failure to |
achieve development, regulatory and commercial objectives that would result in milestone or royalty payments to us, the delay or termination of any future development or commercialization of our product candidates or other product candidates using our technology, and/or costly litigation or arbitration that diverts our management’s attention and resources; |
• | our collaboration partners may not provide us with timely and accurate information regarding development progress and activities under the applicable agreement, which could adversely impact our ability to report progress to our investors and otherwise plan our own development activities; |
• | business combinations or significant changes in our collaboration partners’ business strategy may adversely affect their ability or willingness to perform their obligations under the applicable agreement; |
• | collaborators have significant discretion in determining the efforts and resources that they will apply to a collaboration; |
• | a collaborator with marketing and distribution rights to one or more products may not commit sufficient resources to their marketing and distribution; |
• | 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; |
• | our collaboration partners may not properly maintain or defend our licensed intellectual property rights or may use our proprietary information in such a way as to invite litigation that could jeopardize or invalidate our intellectual property rights or expose us to potential litigation; and |
• | the royalties we are eligible to receive from our collaboration partners may be reduced or eliminated based upon their and our ability to maintain or defend our intellectual property rights. |
• | interruption or delays in our operations, which may impact our ability to conduct and produce preclinical results required for submission of an IND; |
• | delays in receiving authorizations from local regulatory authorities to initiate our planned clinical trials; |
• | delays or difficulties in enrolling patients in our clinical trials due to patients’ concerns of contracting COVID-19 while visiting hospitals, including patients with cancer who may be immunocompromised during the COVID-19 pandemic; |
• | delays or difficulties in clinical site initiation, including difficulties in recruiting clinical site investigators and clinical site staff; |
• | delays in clinical sites receiving the supplies and materials needed to conduct our clinical trials, including interruption in global shipping that may affect the transport of clinical trial materials; |
• | changes in local regulations as part of a response to COVID-19 which may require us to change the ways in which our clinical trials are conducted, which may result in unexpected costs, or to discontinue the clinical trials altogether; |
• | diversion of healthcare resources away from the conduct of clinical trials, including the diversion of hospitals serving as our clinical trial sites and hospital staff supporting the conduct of our clinical trials; |
• | interruption of key clinical trial activities, such as clinical trial site monitoring, due to limitations on travel imposed or recommended by federal or state governments, employers and others, or interruption of clinical trial subject visits and study procedures, the occurrence of which could affect the integrity of clinical trial data; |
• | interruption or delays in the operations of the FDA or other regulatory authorities, which may impact review and approval timelines; |
• | risk that participants enrolled in our clinical trials will contract COVID-19 while the clinical trial is ongoing, which could impact the results of the clinical trial, including by increasing the number of observed adverse events; and |
• | refusal of the FDA to accept data from clinical trials in affected geographies outside the United States. |
• | impairment of our business reputation; |
• | withdrawal of clinical trial participants; |
• | costs due to related litigation; |
• | distraction of management’s attention from our primary business; |
• | substantial monetary awards to patients or other claimants; |
• | the inability to commercialize our product candidates; and |
• | decreased demand for our product candidates, if approved for commercial sale. |
• | identify, recruit integrate, maintain and motivate additional qualified personnel; |
• | manage our development efforts effectively, including the initiation and conduct of clinical trials for our product candidates, both as monotherapy and in combination with other therapeutics; and |
• | improve our operational, financial and management controls, reporting systems and procedures. |
• | the U.S. federal Anti-Kickback Statute, which prohibits, among other things, persons or entities from knowingly and willfully soliciting, offering, receiving or paying any remuneration (including any kickback, bribe or certain rebates), directly or indirectly, overtly or covertly, in cash or in kind, to induce or reward either the referral of an individual for, or the purchase, lease, order or recommendation of, any good, facility, item or service, for which payment may be made, in whole or in part, under U.S. federal and state healthcare programs such as Medicare and Medicaid. The government may assert that a claim including items or services resulting from a violation of the federal Anti-Kickback Statute constitutes a false or fraudulent claim for purposes of the federal civil False Claims Act or federal civil money penalties statute. This statute has been interpreted to apply to arrangements between pharmaceutical manufacturers on the one hand, and prescribers, purchasers, and formulary managers on the other. Although there are several statutory exceptions and regulatory safe harbors protecting certain common activities from prosecution, they are drawn narrowly, and practices that involve remuneration intended to induce prescribing, purchasing or recommending may be subject to scrutiny if they do not qualify for an exception or safe harbor. A person or entity does not need to have actual knowledge of the statute or specific intent to violate it in order to have committed a violation; |
• | the U.S. federal false claims, including the False Claims Act, which can be enforced through whistleblower actions, and civil monetary penalties laws, which, among other things, impose criminal and civil penalties against individuals or entities for knowingly presenting, or causing to be presented, to the U.S. federal government, claims for payment or approval that are false or fraudulent, knowingly making, using or causing to be made or used, a false record or statement material to a false or fraudulent claim, or from knowingly making a false statement to avoid, decrease or conceal an obligation to pay money to the U.S. federal government. Manufacturers can be held liable under the False Claims Act even when they do not submit claims directly to government payors if they are deemed to “cause” the submission of false or fraudulent claims. Companies that submit claims directly to payors may also be liable under the False Claims Act for the direct submission of such claims. The False Claims Act also permits a private individual acting as a “whistleblower” to bring actions on behalf of the federal government alleging violations of the False Claims Act and to share in any monetary recovery. In addition, the government may assert that a claim including items and services resulting from a violation of the U.S. federal Anti-Kickback Statute constitutes a false or fraudulent claim for purposes of the False Claims Act; |
• | the U.S. federal Health Insurance Portability and Accountability Act of 1996 (HIPAA) which imposes criminal and civil liability for, among other things, knowingly and willfully executing, or attempting to execute, a scheme to defraud any healthcare benefit program, or knowingly and willfully falsifying, concealing or covering up a material fact or making any materially false statement, in connection with the delivery of, or payment for, healthcare benefits, items or services; similar to the U.S. federal Anti-Kickback Statute, a person or entity does not need to have actual knowledge of the statute or specific intent to violate it in order to have committed a violation; |
• | HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act of 2009, (HITECH), and their respective implementing regulations, impose requirements on certain covered healthcare providers, health plans, and healthcare clearinghouses and their respective business |
associates that perform services for them that involve the use, or disclosure of, individually identifiable health information as well as their covered subcontractors, relating to the privacy, security, and transmission of such individually identifiable health information. HITECH also created new tiers of civil monetary penalties, amended HIPAA to make civil and criminal penalties directly applicable to business associates, and gave state attorneys general new authority to file civil actions for damages or injunctions in federal courts to enforce the federal HIPAA laws and seek attorneys’ fees and costs associated with pursuing federal civil actions; |
• | the U.S. Federal Food, Drug and Cosmetic Act, which prohibits, among other things, the adulteration or misbranding of drugs, biologics and medical devices; |
• | the U.S. federal legislation commonly referred to as Physician Payments Sunshine Act, enacted as part of the ACA, and its implementing regulations, which requires certain manufacturers of drugs, devices, biologics and medical supplies that are reimbursable under Medicare, Medicaid or the Children’s Health Insurance Program to report annually to the CMS information related to certain payments and other transfers of value to physicians (defined to include doctors, dentists, optometrists, podiatrists and chiropractors), other healthcare professionals (such as physician assistants and nurse practitioners) and teaching hospitals, as well as ownership and investment interests held by the physicians described above and their immediate family members; |
• | analogous state laws and regulations, including: state anti-kickback and false claims laws, which may apply to our business practices, including, but not limited to, research, distribution, sales and marketing arrangements and claims involving healthcare items or services reimbursed by any third-party payor, including private insurers; state laws that require pharmaceutical companies to comply with the pharmaceutical industry’s voluntary compliance guidelines and the relevant compliance guidance promulgated by the U.S. federal government, or otherwise restrict payments that may be made to healthcare providers and other potential referral sources; state laws and regulations that require drug manufacturers to file reports relating to pricing and marketing information, which requires tracking gifts and other remuneration and items of value provided to healthcare professionals and entities; and state and local laws requiring the registration of pharmaceutical sales representatives; and |
• | European and other foreign law equivalents of each of the laws, including reporting requirements detailing interactions with and payments to healthcare providers. |
• | if and when patents may issue based on our patent applications; |
• | the scope of protection of any patent issuing based on our patent applications; |
• | whether the claims of any patent issuing based on our patent applications will provide protection against competitors; |
• | whether or not third parties will find ways to invalidate or circumvent our patent rights, including designing around our patents; |
• | whether or not others will obtain patents claiming aspects similar to those covered by our patents and patent applications; |
• | whether we will need to initiate litigation or administrative proceedings to enforce and/or defend our patent rights which will be costly whether we win or lose; and/or |
• | whether the patent applications that we own or in-license will result in issued patents with claims that cover our product candidates or uses thereof in the United States or in other foreign countries. |
• | others may be able to make product candidates that are similar to ours but that are not covered by the claims of the patents that we own or have exclusively licensed by designing around features of our product candidates; |
• | we or our licensors or future collaborators might not have been the first to make the inventions covered by the issued patent or pending patent application that we own or have exclusively licensed; |
• | we or our licensors or future collaborators might not have been the first to file patent applications covering certain of our inventions; |
• | others may independently develop similar or alternative technologies or duplicate any of our technologies without infringing our intellectual property rights; |
• | it is possible that noncompliance with the USPTO and foreign governmental patent agencies requirement for a number of procedural, documentary, fee payment and other provisions during the patent process can result in abandonment or lapse of a patent or patent application, and partial or complete loss of patent rights in the relevant jurisdiction; |
• | it is possible that our pending patent applications will not lead to issued patents; |
• | issued patents that we own or have exclusively licensed may be revoked, modified, or held invalid or unenforceable, as a result of legal challenges by our competitors; |
• | our competitors might conduct research and development activities in countries where we do not have patent rights and then use the information learned from such activities to develop competitive products for sale in our major commercial markets; |
• | we may not develop additional proprietary technologies that are patentable; |
• | we cannot predict the scope of protection of any patent issuing based on our patent applications, including whether the patent applications that we own or in-license will result in issued patents with claims that directed to our product candidates or uses thereof in the United States or in other foreign countries; |
• | there may be significant pressure on the U.S. government and international governmental bodies to limit the scope of patent protection both inside and outside the United States for disease treatments that prove successful, as a matter of public policy regarding worldwide health concerns; |
• | countries other than the United States may have patent laws less favorable to patentees than those upheld by U.S. courts, allowing foreign competitors a better opportunity to create, develop and market competing product candidates; |
• | the claims of any patent issuing based on our patent applications may not provide protection against competitors or any competitive advantages, or may be challenged by third parties; |
• | if enforced, a court may not hold that our patents are valid, enforceable and infringed; |
• | we may need to initiate litigation or administrative proceedings to enforce and/or defend our patent rights which will be costly whether we win or lose; |
• | we may choose not to file a patent application in order to maintain certain trade secrets or know-how, and a third party may subsequently file a patent application covering such intellectual property; |
• | we may fail to adequately protect and police our trademarks and trade secrets; and |
• | the patents of others may have an adverse effect on our business, including if others obtain patents claiming subject matter similar to or improving that covered by our patents and patent applications. |
• | the scope of rights granted under the license agreement and other interpretation-related issues; |
• | the extent to which our technology and processes infringe on intellectual property of the licensor that is not subject to the licensing agreement; |
• | the sublicensing of patent and other rights; |
• | our diligence obligations under the license agreement and what activities satisfy those diligence obligations; |
• | the ownership of inventions and know-how resulting from the creation or use of intellectual property by us alone or with our licensors and partners; |
• | the scope and duration of our payment obligations; and |
• | the priority of invention of patented technology. |
• | positive or negative results from preclinical studies and clinical trials by us, our collaborators or competitors; |
• | concerns regarding the safety of our product candidates or ADCs in general; |
• | the timing of commencing, enrolling and announcing results from clinical trials; |
• | decisions as to which product candidates, indications or discovery programs we chose to pursue; |
• | announcements regarding competitive products or technologies or the biologics industry in general; |
• | actions taken or guidance provided by regulatory agencies with respect to our clinical trials or regulatory submissions; |
• | changes or developments in laws or regulations applicable to our product candidates and our markets, including in the United States and China; |
• | changes to our relationships with collaborators, manufacturers or suppliers; |
• | the loss of any of our key scientific or management personnel; |
• | changes in the structure of healthcare payment systems; |
• | actual or anticipated fluctuations in our operating results; |
• | changes in financial estimates or recommendations by securities analysts; |
• | potential acquisitions, financing, collaborations or other corporate transactions; |
• | the loss of rights under license, strategic or other research and development agreements; |
• | the results of our efforts to discover, develop, acquire or in-license additional product candidates; |
• | the trading volume of our ADSs on the NYSE; |
• | sales of our ADSs or ordinary shares by us, members of our senior management and directors or our significant shareholders or the anticipation that such sales may occur in the future; |
• | general economic, geopolitical, and market conditions and overall fluctuations in the financial markets in the United States or China, including due to civil or political unrest (such as the ongoing conflict between Ukraine and Russia), terrorism, insurrection or war, man-made or natural disasters; |
• | stock market price and volume fluctuations of comparable companies and, in particular, those that operate in the biologics industry; |
• | investors’ general perception of us and our business; |
• | public health pandemics or epidemics, including the ongoing and future impact of the COVID-19 pandemic and actions taken to slow its spread; and |
• | other events and factors, many of which are beyond our control. |
• | only one of our three classes of directors will be elected each year; |
• | shareholders are entitled to remove directors only for cause; |
• | shareholders are not be permitted to take actions by written consent; and |
• | shareholders must give advance notice to nominate directors or submit proposals for consideration at annual general meetings. |
A. |
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