16 unchanged sentences
• If manufacturers obtain approval for generic versions of our products, or of products with which we compete, our business may be harmed.
−Removed: ● Unforeseen safety issues could emerge with our products that could require us to change the prescribing information to add warnings, limit use of the product, and/or result in litigation.
+Added: • Unforeseen safety issues could emerge with our products that could require us to change the prescribing information, including to add new or more significant warnings (including boxed warnings, the FDA's most prominent safety warning), limit use of the product, and/or result in litigation.
Any of these events could have a negative impact on our business.
15 unchanged sentences
We may need to continue to increase the size of our organization and we may encounter difficulties with managing our growth, which could adversely affect our business and results of operations.
−Removed: While we have substantially increased the size of our organization particularly in our sales force in 2021, we also implemented reductions in workforce particularly in our research and development group in 2021 and 2022.
We may need to add additional qualified personnel and resources to support our commercial activities and expected growth.
−Removed: Our current infrastructure may be inadequate to support our development and commercialization efforts and expected
+Added: Our current infrastructure may be inadequate to support our development and commercialization efforts and expected growth.
Future growth will impose significant added responsibilities on members of management, including the need to identify, recruit, maintain and integrate additional employees, and may take time away from running other aspects of our business, including commercialization of our products and development of our other product candidates.
16 unchanged sentences
This strategy is dependent on our ability to successfully identify and acquire or in-license relevant product candidates.
−Removed: In July 2022, we entered into a license and transition services agreement with Forma for an exclusive license to develop, manufacture and commercialize olutasidenib, a proprietary inhibitor of mIDH1, for any uses worldwide, including for the treatment of AML and other malignancies.
+Added: In July 2022, we entered into a license and transition services agreement with Forma for an exclusive license to develop, manufacture and commercialize olutasidenib, a proprietary inhibitor of m IDH1 , for any uses worldwide, including for the treatment of AML and other malignancies.
In December 2022, the FDA approved REZLIDHIA capsules for the treatment of adult patients with R/R AML with a susceptible IDH1 mutations as detected by an FDA-approved test.
4 unchanged sentences
The in-licensing and acquisition of a product is a highly competitive area, and many other companies are pursuing the same or similar product candidates to those that we may consider attractive.
−Removed: particular, larger companies with more well-established and diverse revenue streams may have a competitive advantage over us due to their size, financial resources and more extensive clinical development and commercialization capabilities.
+Added: In particular, larger companies with more well-established and diverse revenue streams may have a competitive advantage over us due to their size, financial resources and more extensive clinical development and commercialization capabilities.
Furthermore, companies that perceive us to be a competitor may be unwilling to assign or license rights to us.
5 unchanged sentences
In addition, acquisitions and in-licensing may entail numerous operational, financial and legal risks, including:
−Removed: ● potential failure of the due diligence process to identify significant problems, liabilities or other shortcomings or challenges of an acquired or licensed product candidate or technology, including problems, liabilities or other shortcomings or challenges with respect to intellectual property, product quality, partner disputes or issues and other legal and financial contingencies and known and unknown liabilities;
+Added: • potential failure of the due diligence process to identify significant problems, liabilities or other shortcomings or challenges of an acquired or licensed product candidate or technology, including problems, liabilities or
+Added: other shortcomings or challenges with respect to intellectual property, product quality, partner disputes or issues and other legal and financial contingencies and known and unknown liabilities;
• inability to integrate the target company or in-licensed asset successfully into our existing business and inability to maintain the key business relationships of the target;
7 unchanged sentences
There is a high risk that drug discovery and development efforts might not generate successful product candidates.
−Removed: We currently have product candidates in the clinical testing stage and may further pursue to expand our clinical testing efforts.
+Added: We currently have product candidates in the clinical development and testing stage and may further pursue to expand our development and clinical testing efforts.
In our industry, it is statistically unlikely that the limited number of compounds that we have identified as potential product candidates will actually lead to successful product development efforts.
8 unchanged sentences
The letter advises healthcare providers to apply certain measures to protect patient safety, including enhanced ongoing monitoring for signs and symptoms of infection as well as guidance for withholding treatment to patients in the presence of active infection.
+Added: On December 22, 2025, the FDA notified us of the approval of a Prior Approval supplemental NDA for GAVRETO, which updated the US Prescribing Information to add a boxed warning regarding serious infections, including opportunistic infections.
With respect to our own compounds in development, we have established anticipated timelines with respect to the initiation of clinical trials based on existing knowledge of the compounds.
1 unchanged sentence
Additionally, the initial results of a completed earlier clinical trial of a product candidate do not necessarily predict final results and the results may not be repeated in later clinical trials.
−Removed: Because of the uncertainty of whether the accumulated preclinical evidence (pharmacokinetic, pharmacodynamic, safety and/or other factors) or early clinical results will be observed in later clinical trials, we can make no assurances regarding the likely results from our future clinical trials or the impact of those results on our business.
+Added: Because of the uncertainty of whether the preclinical evidence (pharmacokinetic, pharmacodynamic, safety and toxicity, and/or other factors) or early clinical results will be observed in later clinical trials, we can make no assurances regarding the success of our clinical trials.
+Added: The impact of those preclinical and clinical results may require us to conduct additional studies, delay, limit or modify clinical trials, or result in more restrictive labeling or other regulatory actions.
For example, we conducted a Phase 3 pivotal trial of fostamatinib in patients with warm auto immune hemolytic anemia (wAIHA) initiated in March 2019 and completed in April 2022.
In June 2022, we announced top-line efficacy and safety data results of the trial, and the results did not demonstrate statistical significance in the primary efficacy endpoint of durable hemoglobin response in the overall study population .
−Removed: We conducted an in-depth analysis of these data to better understand differences in patient characteristics and outcomes and submitted these findings to the FDA.
−Removed: In October 2022, we announced that we received guidance from the FDA’s review of these findings.
−Removed: Based on the result of the trial and the guidance from the FDA, we did not file an sNDA for this indication.
+Added: Based on the result of the trial and the guidance from the FDA, we did not file an Supplemental New Drug Application (sNDA) for this indication.
Further, we may experience errors, data capture discrepancies at initial data analysis and final study results, or other technical issues in the analysis of our clinical trial results.
For example, we conducted our Phase 3 clinical trial to evaluate safety and efficacy of fostamatinib in hospitalized COVID-19 patients launched in November 2020 and completed enrollment in July 2022.
−Removed: We previously announced in November 2022 the top-line results did not meet statistical significance in the primary efficacy endpoint.
−Removed: Upon further analysis, we discovered an error by the biostatistical contract research organization in the application of a statistical stratification factor.
+Added: We announced in November 2022 that the top-line results did not meet statistical significance in the primary efficacy endpoint.
+Added: Upon further analysis, we discovered an error by the biostatistical CRO in the application of a statistical stratification factor.
After correcting for this statistical error, the primary endpoint of the study was met.
6 unchanged sentences
Foreign regulatory requirements governing clinical trials may diverge and impose additional regulatory burdens, which may result in delays.
−Removed: For instance, the new EU Clinical Trials Regulation (EU) No 536/2014 (CTR) has amended the system of approval for clinical trials in the EU and has established a new clinical trials portal and database for application for authorizations, called the Clinical Trials Information System (CTIS).
+Added: For instance, the new EU Clinical Trials Regulation No 536/2014 (CTR) has amended the system of approval for clinical trials in the EU and has established a new clinical trials portal and database for application for authorizations, called the Clinical Trials Information System (CTIS).
All ongoing clinical trials in the EU will be subject to the provisions of the CTR as of January 31, 2025.
5 unchanged sentences
Our employees, independent contractors, consultants, principal investigators, CROs, commercial partners and vendors may engage in misconduct or other improper activities, including noncompliance with regulatory standards and requirements.
−Removed: Our business operations and current and future arrangements with investigators, healthcare professionals, consultants, third-party payors and customers, may expose us to broadly applicable federal, state and foreign fraud and abuse and other healthcare laws and regulations including anti-kickback and false claims laws, data privacy and security laws, and transparency reporting laws.
+Added: Our business operations and current and future arrangements with investigators, healthcare professionals, consultants, third-party payors, vendors and customers, may expose us to broadly applicable federal, state and foreign fraud and abuse and other healthcare laws and regulations including anti-kickback and false claims laws, data privacy and security laws, and transparency reporting laws.
These laws may constrain the business or financial arrangements and relationships through which we conduct our operations, including how we research, market, sell and distribute any product for which we have obtained regulatory approval, or for which we may obtain regulatory approval in the future.
1 unchanged sentence
These laws and regulations may restrict or prohibit a wide range of pricing, discounting, marketing and promotion, including promoting off-label uses of our products, certain commission compensation, certain customer incentive programs, certain patient support offerings, and other business arrangements generally.
−Removed: Activities subject to these laws also involve the improper use or misrepresentation of information obtained in the course of patient recruitment for clinical trials, creating fraudulent data in our preclinical studies or clinical trials or illegal misappropriation of drug product, which could result in regulatory sanctions and cause serious harm to our reputation.
+Added: Activities subject to these laws also involve the improper use or misrepresentation of information
+Added: obtained in the course of patient recruitment for clinical trials, creating fraudulent data in our preclinical studies or clinical trials or illegal misappropriation of drug product, which could result in regulatory sanctions and cause serious harm to our reputation.
See “Business – Government Regulation – Healthcare and Privacy Law and Regulation and Healthcare Reform” contained in Part I, Item 1 of our Annual Report on Form 10-K for the year ended December 31, 2025 , for more information on the healthcare laws and regulations that may affect our ability to operate.
10 unchanged sentences
It is possible that governmental and enforcement authorities will conclude that our business practices may not comply with current or future statutes, regulations or case law interpreting applicable fraud and abuse or other healthcare laws and regulations.
−Removed: If any such actions are instituted against us, and we are not successful in defending ourselves or asserting our rights, those actions could have a significant impact on our business, including the imposition of significant civil, criminal and administrative penalties, damages, disgorgement, monetary fines, imprisonment, additional reporting obligations and oversight if we become subject to a corporate integrity agreement or other agreement to resolve allegations of non-compliance with these laws, possible exclusion from
−Removed: participation in Medicare, Medicaid and other federal healthcare programs, contractual damages, reputational harm, diminished profits and future earnings, and curtailment or restructuring of our operations, any of which could adversely affect our ability to operate our business and our results of operations.
+Added: If any such actions are instituted against us, and we are not successful in defending ourselves or asserting our rights, those actions could have a significant impact on our business, including the imposition of significant civil, criminal and administrative penalties, damages, disgorgement, monetary fines, imprisonment, additional reporting obligations and oversight if we become subject to a corporate integrity agreement or other agreement to resolve allegations of non-compliance with these laws, possible exclusion from participation in Medicare, Medicaid and other federal healthcare programs, contractual damages, reputational harm, diminished profits and future earnings, and curtailment or restructuring of our operations, any of which could adversely affect our ability to operate our business and our results of operations.
We are subject to stringent and evolving privacy and information security laws, regulations, rules, policies, and contractual obligations, and changes in such laws, regulations, rules, policies, contractual obligations and our actual or perceived failure to comply with such requirements could subject us to significant investigations, fines, penalties and claims, any of which may have a material adverse effect on our business, financial condition, results of operations or prospects.*
−Removed: We are subject to, or affected by, various federal, state and foreign laws, rules, directives, and regulations, as well as regulatory guidance, policies and contractual obligations relating to privacy and information security, governing the acquisition, collection, access, use, disclosure, processing, modification, retention, storage, transfer, destruction, protection, and security (collectively, “processing”) of personal information and other sensitive information about individuals.
−Removed: The global privacy and information security landscape is evolving rapidly, and implementation standards and enforcement practices are likely to continue to develop for the foreseeable future and may result in conflicting or inconsistent compliance obligations.
−Removed: Legislators and regulators are increasingly adopting or amending privacy and information security laws, rules, directives, and regulations that may create uncertainty in our business, affect our or our collaborators’, service providers’ and contractors’ ability to operate in certain jurisdictions or to process personal information, transfer data internationally, necessitate the acceptance of more onerous obligations in our contracts, result in enforcement actions, litigation or other liability or impose additional costs on us.
−Removed: The cost of compliance with these laws, regulations and standards is high and is likely to increase in the future.
−Removed: Any failure or perceived failure by us or our collaborators, service providers and contractors to comply with federal, state or foreign laws or regulations, our internal policies and procedures or our contracts governing the processing of personal information could result in negative publicity, diversion of management time and effort and proceedings against us by governmental entities or others.
−Removed: In many jurisdictions, enforcement actions, litigation, and other consequences for noncompliance with privacy and information security laws and regulations are rising.
−Removed: Compliance with applicable privacy and information security laws and regulations, as well as regulatory guidance, policies and contractual obligations, is a rigorous and time-intensive process, and we may be required to put in place additional mechanisms to ensure compliance with the new privacy and information security requirements.
−Removed: If we fail to comply with any such obligations, we may face significant investigations, fines, penalties and claims that could materially and adversely affect our business, financial condition, results of operations, ability to process personal information and income from certain business initiatives.
−Removed: We, like many companies in our industry, are evaluating and selectively using artificial intelligence (AI), including large language models and other emerging technologies, to enhance certain business processes, research initiatives, and operational efficiency.
−Removed: Although our current use of AI is limited, we expect that our reliance on these technologies may increase over time.
−Removed: As we incorporate AI and machine learning technologies in our business processes, evolving AI-specific regulation may impose additional obligations and liability for bias, transparency, or data handling, which could affect our ability to innovate efficiently.
−Removed: The performance of AI systems depends on the quality of the underlying data and algorithms.
−Removed: Errors, bias, or lack of transparency in AI outputs could lead to inaccurate analyses, unintended disclosures of confidential information, or flawed internal decisions.
−Removed: The use of third-party AI tools, including those hosted on external platforms, may also create risks relating to data privacy, cybersecurity, and intellectual property ownership, especially if proprietary or personal information is input into such systems.
−Removed: Because the laws, regulations, and ethical standards applicable to AI continue to develop, and public expectations surrounding responsible use of AI are increasing, we may face additional compliance burdens or reputational risks in the future.
−Removed: Any actual or perceived misuse of AI technologies, failure to comply with evolving requirements, or unanticipated consequences of AI-assisted activities could negatively impact our operations, reputation, or financial performance.
−Removed: In the US, these obligations include various federal, state, and local statutes, rules, and regulations relating to privacy and data security.
−Removed: The Federal Trade Commission (FTC) has authority under Section 5 of the FTC Act to regulate unfair or deceptive or practices, and has used this authority to initiate enforcement actions against companies that implement inadequate controls around privacy and information security in violation of their externally facing policies.
−Removed: The FTC has brought several cases alleging violations of Section 5 of the FTC Act with respect to health information, and has proposed rulemaking on a variety of privacy and data security topics.
−Removed: Additionally, the FTC published an advance notice of proposed rulemaking in 2022 on commercial surveillance and data security, and may
−Removed: propose regulation concerning the ways in which companies collect, aggregate, protect, use, analyze, and retain consumer data, as well as transfer, share, sell, or otherwise monetize that data in the coming years.
−Removed: The FTC has also been active with respect to enforcement of its Health Breach Notification Rule and in scrutinizing the use and disclosure of sensitive personal information.
−Removed: The FTC finalized changes to the Health Breach Notification Rule in April 2024.
−Removed: Moreover, the US federal government has also enacted statutes to address privacy and information security issues impacting particular industries or activities, including the following laws and regulations, including, but not limited to:
−Removed: the Electronic Communications Privacy Act, the Computer Fraud and Abuse Act, the Health Insurance Portability and Accountability Act (HIPAA), the Health Information Technology for Economic and Clinical Health Act, the Telephone Consumer Protection Act, the CAN-SPAM Act, and other laws and regulations, and continues to consider comprehensive federal privacy legislation.
−Removed: In addition, state legislatures have enacted statutes to address privacy and information security issues, including the California Consumer Privacy Act of 2018 (the CCPA).
−Removed: For example, the CCPA, as amended by the California Privacy Rights Act (CPRA), establishes a privacy framework applicable to for-profit entities that are doing business in California, including an expansive definition of personal information and data privacy rights for California residents (as consumers, business contacts and employees), and authorizes potentially severe statutory damages and creates a private right of action for certain data security breaches.
−Removed: The CCPA also requires businesses subject to the law to provide disclosures to California residents and to provide them with rights with respect to their personal information, including the right to opt out of the sale of such information.
−Removed: Moreover, the CPRA, among other things, imposes requirements relating to data minimization and correction, and gives California residents additional rights over their personal information, including the right to opt-out of the use of their personal information in online behavioral advertising and to opt-out of certain types of consumer profiling.
−Removed: The CPRA also provides for penalties for CPRA violations concerning California residents under the age of 16, and established the California Privacy Protection Agency to implement and enforce the law.
−Removed: Although there are exemptions for protected health information, clinical trial and other research-related data under the CCPA, the CCPA could impact our business depending on how it is interpreted by the California Privacy Protection Agency, as well from new regulations issued by the Agency to further implement the law.
−Removed: Compliance with the CCPA may increase our compliance costs and potential liability.
−Removed: Multiple other states have followed California and enacted comprehensive privacy laws, or are considering similar legislation.
−Removed: While these new laws and proposals generally include exemptions for HIPAA-covered protected health information and clinical trial data, they add layers of complexity to compliance in the US market, and could increase our compliance costs and adversely affect our business.
−Removed: Moreover, some states have enacted laws specific to health data privacy, which may cause additional compliance costs such as the Washington My Health My Data Act and Nevada’s Consumer Health Data Privacy Law.
−Removed: For example, the Washington My Health My Data Act regulates “consumer health data” which is defined as “personal information that is linked or reasonably linkable to a consumer and that identifies a consumer’s past, present, or future physical or mental health.” However, the My Health My Data Act provides exemptions for personal data used or shared in research, including data subject to 45 C.F.R.
−Removed: Parts 46, 50, and 56.
−Removed: States, such as Colorado, Utah and California, have passed or are considering legislation or regulation governing the development or use of AI technologies, supplementing the existing consumer protection, FDA and other regulatory guidance that may apply to the use of AI technologies in our business, and which may impact our use of technology.
−Removed: Moreover, many states also have in place data security laws requiring companies to maintain certain safeguards with respect to the processing of personal information, and all states require companies to notify individuals or government regulators in the event of a data breach impacting such information.
−Removed: Laws and regulations relating to privacy, data protection, consumer protection, AI and information security are evolving and subject to potentially differing interpretations.
−Removed: These requirements may be interpreted and applied in a manner that varies from one jurisdiction to another and/or may conflict with other laws or regulations.
−Removed: New laws and regulations add additional complexity, requirements, restrictions and potential legal risk.
−Removed: Accordingly, compliance programs may require additional investment in resources, and could impact availability of previously useful data.
−Removed: Internationally, our operations abroad may also be subject to increased scrutiny or attention from foreign data protection authorities.
−Removed: For example, our clinical trial programs and research collaborations outside the US may implicate foreign data protection laws, including those in the European Economic Area, Switzerland, and/or the UK (collectively, Europe).
−Removed: Many jurisdictions have established or are in the process of establishing privacy and data security legal frameworks with which we, our collaborators, service providers, including our CROs, and contractors must comply.
−Removed: example, in the EU, the collection, use, disclosure, transfer and other processing of personal data (i.e., data which identifies an individual or from which an individual is identifiable) is governed by the EU General Data Protection Regulation 2016/679 (the EU GDPR), which came into direct effect in all EU Member States on and from May 25, 2018.
−Removed: The UK has implemented the EU GDPR as the UK GDPR which sits alongside the UK Data Protection Act 2018 (the UK GDPR, and together with the EU GDPR, the GDPR).
−Removed: In October 2024, the UK government introduced to Parliament the Data (Use and Access) Bill (the DUA Bill) which is set to introduce reforms to the UK GDPR.
−Removed: The DUA Bill is currently progressing through the legislative process and is expected to be finalized during 2025.
−Removed: The GDPR has direct effect where an entity is established in the European Economic Area (EEA) or the UK (as applicable) and has extraterritorial effect, including where an entity established outside of the EEA or the UK processes personal data in relation to the offering of goods or services to individuals in the EEA and/or the UK or the monitoring of their behavior.
−Removed: The GDPR imposes obligations on controllers, including, among others:
−Removed: ● accountability and transparency requirements, requiring controllers to demonstrate and record compliance with the GDPR and to provide more detailed information to data subjects regarding the processing of their personal data;
−Removed: ● requirements to process personal data lawfully including specific requirements for obtaining valid consent where consent is the lawful basis for processing;
−Removed: ● obligations to consider data protection when any new products or services are developed and designed (including e.g., to limit the amount of personal data processed);
−Removed: ● obligations to comply with data protection rights of data subjects including a right:
−Removed: (i) of access to, erasure of, or rectification of personal data, (ii) to restriction of processing or to withdraw consent to processing, (iii) to object to processing or to ask for a copy of personal data to be provided to a third party, and (iv) not to be subject to solely automated decision-making;
−Removed: ● an obligation to report personal data breaches to:
−Removed: (i) the data protection supervisory authority without undue delay (and no later than 72 hours) after becoming aware of the personal data breach, where feasible, unless the personal data breach is unlikely to result in a risk to the data subjects’ rights and freedoms;
−Removed: and (ii) affected data subjects, where the personal data breach is likely to result in a high risk to their rights and freedoms.
−Removed: In addition, the EU GDPR prohibits the international transfer of personal data from the EEA to jurisdictions that the European Commission does not recognize as having an ‘adequate’ level of data protection unless a data transfer mechanism has been put in place or a derogation under the EU GDPR can be relied on.
−Removed: In certain cases (e.g., where transfers are made in reliance on EU SCCs) a company must also carry out a so-called transfer privacy impact assessment (TIA).
−Removed: A TIA, among other things, assesses laws governing access to personal data in the recipient country and considers whether supplementary measures that provide privacy protections additional to those provided under EU SCCs will need to be implemented to ensure an ‘essentially equivalent’ level of data protection to that afforded in the EEA.
−Removed: On July 10, 2023, the European Commission adopted its Final Implementing Decision granting the US adequacy (Adequacy Decision) for EU-US transfers of personal data for entities self-certified to the EU-US Data Privacy Framework (DPF).
−Removed: Entities relying on EU SCCs for transfers to the US.
−Removed: are also able to rely on the analysis in the Adequacy Decision as support for their TIA regarding the equivalence of US national security safeguards and redress.
−Removed: The UK GDPR also imposes similar restrictions on transfers of personal data from the UK to jurisdictions that the UK Government does not consider adequate, including the US.
−Removed: The UK Government has published its own form of the EU SCCs, known as the International Data Transfer Agreement and an International Data Transfer Addendum to the EU SCCs.
−Removed: The UK Information Commissioner’s Office (ICO) has also published its version of the TIA and guidance on international transfers, although entities may choose to adopt either the EU or UK style TIA.
−Removed: Further, on September 21, 2023, the UK Secretary of State for Science, Innovation and Technology established a UK-US data bridge (i.e., a UK
−Removed: adequacy decision) and adopted UK regulations to implement the UK-US data bridge (UK Adequacy Regulations).
−Removed: Personal data may be transferred from the UK under the UK-US data bridge through the UK extension to the DPF, from October 12, 2023, to organizations self-certified under the UK extension to the DPF.
−Removed: Data protection supervisory authorities have the power under the GDPR to (amongst other thing) impose fines for serious breaches of up to the higher of 4% of the organization’s annual worldwide turnover or €20 million (under the EU GDPR) or £17.5 million (under the UK GDPR).
−Removed: The GDPR identifies a list of points to consider when determining the level of fines for data supervisory authorities to impose (including the nature, gravity and duration of the infringement).
−Removed: Data subjects also have a right to compensation, as a result of an organization’s breach of the GDPR which has affected them, for financial or non-financial losses (e.g., distress).
−Removed: Privacy and data protection compliance has and may in the future require substantial amendments to our procedures and policies and the changes could adversely impact our business by increasing operational and compliance costs or impact business practices.
−Removed: Further, there is a risk that the amended policies and procedures will not be implemented correctly or that individuals within the business will not be fully compliant with the new procedures.
−Removed: If there are breaches of these measures, we could face significant litigation, government investigations, administrative and monetary sanctions as well as reputational damage which may have a material adverse effect on our operations, financial condition and prospects.
−Removed: There is a risk that we could be impacted by a cybersecurity incident that results in loss or unauthorized disclosure of personal data, potentially resulting in us facing harms similar to those described above.
−Removed: Additionally, other countries outside of Europe have enacted or are considering enacting similar cross-border data transfer restrictions and laws requiring local data residency, with strict requirements and limitations for processing personal information, which could increase the cost and complexity of delivering our services and operating our business.
−Removed: For example, Brazil enacted the General Data Protection Law, New Zealand enacted the New Zealand Privacy Act, China released its Personal Information Protection Law, which went into effect November 1, 2021, and Canada introduced the Digital Charter Implementation Act.
−Removed: As with the EU GDPR, these laws are broad and may increase our compliance burdens, including by mandating potentially burdensome documentation requirements and granting certain rights to individuals to control how we collect, use, disclose, retain, and process personal information about them.
−Removed: We publish privacy policies and other documentation regarding our collection, processing, use and disclosure of personal information and/or other confidential information.
−Removed: Although we endeavor to comply with our published policies and other documentation, we may at times fail to do so or may be perceived to have failed to do so.
−Removed: Moreover, despite our efforts, we may not be successful in achieving compliance if our employees, collaborators, contractors, service providers or vendors fail to act in accordance with our published policies and documentation.
−Removed: Such failures can subject us to potential foreign, local, state and federal action if they are found to be deceptive, unfair, or misrepresentative of our actual practices.
−Removed: Moreover, trial participants or research subjects about whom we or our partners obtain information, as well as the providers who share this information with us, may contractually limit our ability to use and disclose the information or exercise their right to do so under applicable privacy legislation.
−Removed: Claims that we have violated individuals’ privacy rights or failed to comply with data protection laws or applicable privacy policies and documentation, even if we are not found liable, could be expensive and time-consuming to defend and could result in adverse publicity that could harm our business.
−Removed: In addition to data privacy requirements, cybersecurity requirements are laid down in various laws in the EU and the UK, the key ones being:
−Removed: (i) the GDPR (as discussed above), which requires controllers and processors to implement appropriate technical and organizational measures to safeguard personal data to a level of security appropriate to the data protection risk;
−Removed: (ii) the UK Network and Information Systems Regulation 2018 (NIS Regulations), and (iii) the EU Network and Information Systems Security 2 Directive (NISD2).
−Removed: The GDPR does not provide for a specific set of cybersecurity requirements or measures to be implemented, but rather requires a controller or processor to implement appropriate cyber and data security measures in accordance with the then-current risk, the state of the art, the costs of implementation and the nature, scope, context and purposes of the processing.
−Removed: The GDPR however does explicitly require that controllers notify personal data breaches, within the meaning of the GDPR as described above.
−Removed: In the UK, the NIS Regulations apply to ‘operators of essential services’ (OES) and ‘relevant digital service providers’ (RDSP) and following the UK General Election in July 2024, the new UK Government has announced it intends to introduce a Cyber Security and Resilience Bill to the UK Parliament.
−Removed: The NIS Regulations require that appropriate and proportionate technical and organizational measures are implemented to manage the risk of network and information systems, and impose requirements related to incident handling and notification in relation to incidents with significant disruptive effect.
−Removed: Under the NIS Regulations, the ICO may issue fines of up to £17 million and take other action following non-compliance.
−Removed: In the EU, the NISD2 (and the implementing laws at a national EU Member State level) impose stringent cybersecurity and incident reporting requirements on ‘essential’ and ‘important’ entities, which include ICT managed service providers (MSP), cloud service providers as well as entities carrying out research and development activities of medicinal products, and certain specific medical device manufacturers.
−Removed: Our entities may be in scope of the NISD2 where they qualify as a MSP, cloud provider, R&D entity and/or medical device manufacturer within the meaning of NISD2 and offer those services in the EU.
−Removed: The NISD2 empowers the EU Member States to define all rules regarding penalties applicable to infringements, provided that they are effective, proportionate, and dissuasive.
−Removed: NISD2 states that any maximum fine which national implementing law provides for should at least be set at €10 million or 2% of total worldwide turnover, whichever is higher, where essential entities are concerned.
−Removed: Other sanctions may include (i) a temporary suspension to provide services in the EU (by suspending relevant authorizations/certifications);
−Removed: (ii) an order to make public certain elements of the infringement and/or inform customers;
−Removed: and (iii) injunctions to immediately cease infringing conduct.
−Removed: Importantly, NISD2 also provides that senior members of staff can be held personally liable, and face administrative fines or be temporarily suspended from exercising managerial functions at the legal representative or chief executive officer level.
−Removed: The NISD2 has not to date been transposed by all EU Member States despite the deadline for doing so having passed.
−Removed: In addition, the EU Critical Entities Resilience Directive (CER) is aimed at strengthening the resilience of ‘critical infrastructure’ against specific threats including cyber incidents, natural hazards, terrorist attacks, insider threats, and sabotage.
−Removed: The scope of CER includes entities designated as ‘critical’ under CER and includes (among other things) the health sector and the manufacturers of medical devices as ‘essential services.’ The CER imposes cybersecurity and resilience requirements in particular in relation to incidents with so-called ‘significant disruptive effects’ – which are incidents that are able to significantly impact the continuation of the critical infrastructure service offering in the EU.
−Removed: Requirements include to:
−Removed: (i) identify relevant risks that may significantly disrupt the provision of essential services (i.e., pursuant to a risk assessment);
−Removed: (ii) take appropriate and proportionate technical, security and organizational measures to ensure resilience (i.e., based on the outcome of the risk assessment);
−Removed: and (iii) notify disruptive incidents to the competent authorities within 24 hours after becoming aware of an incident.
−Removed: The CER is enforceable on a national EU Member State level by the competent authorities, and allows EU Member States to set penalties as long as they are effective, proportionate, and dissuasive.
−Removed: Our entities may be in scope of the CER where they qualify as critical entities within the meaning of CER.
−Removed: The CER has not to date been transposed by all EU Member States despite the deadline for doing so having passed.
−Removed: In the EU, a number of new laws related to digital data and AI have recently entered into force, are expected to enter into force in the foreseeable future, or have been proposed and are being considered.
−Removed: We are still assessing the scope of application, impact, and risk of these recent EU laws on our business, and will continue to assess this moving forward, including for example:
−Removed: (i) the EU’s Data Act, which – came into force on January 11, 2024 and which seeks to, among other things regulate the use of, and access to, data generated through connected (or Internet-of-Things) devices and introduces a new means for public sector bodies to access, use and re-use private sector data.
−Removed: EU Member State competent authorities are empowered to enforce the Data Act and determine the appropriate sanction provided penalties are “effective, proportionate and dissuasive” ;
−Removed: and (ii) the European Health Data Space Regulation (EHDS), which was formally adopted on January 8, 2025 and is expected to enter into force during 2025 and which seeks to, among other things, provide individuals with more control over their electronic health data (EHD), enable cross-border sharing of EHD between national EU healthcare systems and facilitate the sharing of EHD for secondary research purposes.
−Removed: The EU has developed a standalone law to govern the offering and use of AI systems in the EU (the “AI Act”) which entered into force on August 1, 2024 and will become applicable in a gradual manner between 2025-2027 depending on the requirement.
−Removed: The AI Act imposes regulatory requirements onto AI system providers, importers,
−Removed: distributors, and deployers, in accordance with the level of risk involved with the AI system (“unacceptable”, “high”, “limited”, and “minimal” risk).
−Removed: Unacceptable-risk AI systems are banned from being offered and used in the EU, and high-risk AI systems (which include AI used as part of medical devices in certain instances) are subject to a set of regulatory requirements under the AI Act including to establish quality and post-marketing monitoring and risk assessment systems, requirements related to the training of AI systems and training data, and requirements related to human oversight.
−Removed: Limited-risk AI systems are subject mainly to transparency requirements only and minimal-risk AI systems are not subject to obligations under the AI Act.
−Removed: General-purpose AI systems are subject to a number of requirements – mostly akin to the requirements that apply to high-risk AI systems under the AI Act.
−Removed: Non-compliance with the AI Act may be subject to regulatory fines of up to 7% of annual worldwide turnover.
−Removed: In parallel, on October 10, 2024, the EU adopted the EU Product Liability Directive to regulate non-contractual and non-fault based liability for defective products, including digital products and AI, and has introduced a new EU AI Liability Directive to facilitate claims for damages brought by EU users of AI systems.
−Removed: The UK to date has not adopted dedicated AI legislation, instead looking to rely on a principles-based, sector-specific approach to AI regulation.
−Removed: However, in July 2024 it was announced that new AI regulation would in fact be introduced.
−Removed: Further, many jurisdictions impose mandatory clinical trial information obligations on sponsors.
−Removed: In the EU, such obligations arise under the Transparency Regulation No 1049/ 2001, EMA Policy 0043, EMA Policy 0070 and the Clinical Trials Regulation No 536/2014 (which the UK has not implemented, as the law entered into force following the UK’s exit from the EU), all of which impose on sponsors the obligation to make publicly available certain information stemming from clinical studies.
−Removed: In the EU, the transparency framework provides EU-based parties the right to submit an access to documents request to the EMA for information included in the MAA dossier for approved medicinal products.
−Removed: Only very limited information is exempted from disclosure, i.e., commercially confidential information (which is construed increasingly narrowly) and protected personal data.
−Removed: It is possible for competitors to access and use this data in their own research and development programs anywhere in the world, once this data is in the public domain.
−Removed: Significant changes or developments in US laws or policies, including changes in US healthcare regulation, may have a material adverse effect on our business.*
+Added: We collect, use, store, process and transfer personal information and other sensitive data in connection with our clinical trials, research activities and business operations.
+Added: As a result, we are subject to a wide range of federal, state and foreign laws and regulations relating to privacy, data protection, cybersecurity and, increasingly, the use of artificial intelligence.
+Added: These requirements are rapidly evolving, may be interpreted and applied inconsistently across jurisdictions, and may conflict with one another, creating uncertainty and increasing the complexity and cost of compliance.
+Added: We are also subject to contractual obligations and internal policies governing the handling of personal information.
+Added: Any actual or perceived failure by us or by our collaborators, service providers or contractors to comply with applicable laws, regulations, contractual obligations or our policies could result in governmental investigations, enforcement actions, litigation, fines, penalties, or other liability, as well as reputational harm, negative publicity and diversion of management time and resources.
+Added: In addition, such failures could impair our ability to process personal information, conduct clinical trials, operate in certain jurisdictions, or pursue certain business initiatives.
+Added: In particular, our information technology systems and those of our contract research organizations, contract manufacturers, collaborators and other third-party service providers are vulnerable to damage or interruption from computer viruses, ransomware and other malicious code, unauthorized access by hackers or sophisticated nation-state and nation-state-supported actors, denial-of-service attacks, employee error or malfeasance, natural disasters and telecommunication and electrical failures.
+Added: The loss of clinical trial data from completed or ongoing clinical trials could result in delays in our regulatory approval efforts and significantly increase our costs to recover or reproduce the data.
+Added: Under SEC rules, we are required to disclose material cybersecurity incidents on Form 8-K within four business days of determining that an incident is material, and any failure to timely identify and disclose such an incident could result in SEC enforcement actions, litigation and reputational damage.
+Added: We may not have adequate insurance coverage for security
+Added: incidents or breaches, and the successful assertion of one or more large claims against us that exceeds our available insurance coverage could have an adverse effect on our business.
+Added: Compliance with these requirements is costly and time-consuming and may require us to implement additional safeguards, modify our data practices, or limit our use of data, which could adversely affect our operations.
+Added: Further, evolving laws governing international data transfers and data localization may restrict our ability to transfer personal information across borders or require us to incur additional costs to do so.
+Added: We also face risks related to cybersecurity incidents, including unauthorized access, loss or disclosure of personal or confidential information.
+Added: Any such incident, whether actual or perceived, could result in legal liability, regulatory scrutiny, operational disruption and reputational damage.
+Added: I n addition, our increasing use of artificial intelligence and other emerging technologies may subject us to new and developing regulatory requirements and increase risks related to data privacy, cybersecurity, intellectual property and the accuracy and reliability of outputs.
+Added: Any failure to comply with applicable requirements or to manage these risks could adversely affect our business, financial condition and results of operations.
+Added: Significant changes or developments in US laws or policies, including changes in US healthcare regulation, will affect our business and may have a material adverse effect on our business.
There is uncertainty surrounding potential changes to the regulatory environment in the US, particularly as it relates to healthcare regulation and related programs, which may have an adverse effect on our business.
−Removed: For example, the current administration issued an executive order establishing an agency to reform federal government processes and reduce expenditures and has committed to significantly reduce government spending through cuts to federal healthcare programs and reductions in the workforces of key government agencies, such as DHHS, FDA, and CMS.
+Added: For example, the current administration issued an executive order establishing an agency to reform federal government processes and reduce expenditures and has committed to significantly reduce government spending through cuts to federal healthcare programs and reductions in the workforces of key government agencies, such as the US Department of Health & Human Services (HHS), FDA, and CMS.
Pressures on and uncertainty surrounding the US federal government’s budget, and potential changes in budgetary priorities, could adversely affect the funding for individual programs, including Medicare and other government programs upon which our business depends.
−Removed: Moreover, further efforts by the current administration to limit federal agency budgets or personnel, including through potential reduction in force implemented in response to the recent US federal government shutdown may lead to slower response times, less guidance and longer review periods, inconsistencies in execution of federal policies, potentially affecting our ability to progress development of our product candidates or obtain regulatory approval for our product candidates.
−Removed: The recent US federal government shutdown may prevent the FDA or other regulatory authorities from conducting their regular inspections, reviews or other regulatory activities, and may 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: Moreover, further efforts by the current administration to limit federal agency budgets or personnel may lead to slower response times, less guidance and longer review periods, inconsistencies in execution of federal policies, potentially affecting our ability to progress development of our product candidates or obtain regulatory approval for our product candidates.
+Added: Additionally, in February 2025 HHS ended a longstanding commitment to voluntarily comply with notice-and-comment rulemaking procedures for public benefits rules, even when not required by statute, which could contribute to rapid changes in policy without opportunity for public input.
+Added: The continuing effects of the US federal government shutdown in late 2025 may delay inspections, reviews or other regulatory activities, and may 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.
Additionally, further changes in legislation and regulations (including those related to taxation, trade and importation), economic and monetary policies, geopolitical matters, among other potential impacts, could adversely impact the global economy and our operating results.
The potential impact of new policies that may be implemented as a result of the current administration is currently uncertain.
+Added: The biopharmaceutical industry is subject to extensive regulatory obligations and policies that are subject to significant and abrupt change, including due to judicial challenges, election cycles, and resulting regulatory updates and changes in policy priorities.
+Added: On June 28, 2024, the US Supreme Court issued an opinion in Loper Bright Enterprises v.
+Added: Raimondo holding that courts reviewing agency action pursuant to the Administrative Procedure Act (APA) “must exercise their independent judgment” and “may not defer to an agency interpretation of the law simply because a statute is ambiguous.” The decision has impacted how lower courts evaluate challenges to agency interpretations of law, including those by HHS, CMS, FDA and other agencies with significant oversight of the biopharmaceutical industry.
+Added: The new framework is likely to increase both the frequency of such challenges and their odds of success by eliminating one way in which the government previously prevailed in such cases.
+Added: As a result, significant regulatory policies are subject to increased prospects of litigation and judicial scrutiny.
+Added: In addition, federal agency activities, priorities, leadership, policies, rulemaking, communications, spending and staffing may be significantly impacted by election cycles and legislative developments.
+Added: For example, the current US presidential administration has committed to significantly reduce government spending through cuts to federal healthcare programs and reductions in the workforces of key government agencies, such as HHS, FDA, and CMS.
+Added: Further efforts by the current administration to reduce federal spending may result in reductions to agency budgets, employees, and
+Added: operations, which may lead to slower response times, less guidance and longer review periods, potentially affecting our ability to progress development of our product candidates or obtain regulatory approval for our product candidates.
+Added: The administration and agencies have also made abrupt announcements about new or changed regulatory policies, such as policies related to use of AI to review product applications.
+Added: These developments may lead to greater uncertainty regarding FDA policies, slower response times, longer review periods, unexpected delays, increased costs, or other negative impacts on our business that are difficult to predict.
+Added: These changes may potentially affect our ability to progress development of our product candidates or obtain regulatory approval for our product candidates.
Enhanced governmental and public scrutiny over, or investigations or litigation involving, pharmaceutical manufacturer donations to patient assistance programs may require us to modify our programs and could negatively impact our business practices, harm our reputation, divert the attention of management and increase our expenses.
−Removed: To help patients afford our products, we have a manufacturer-sponsored patient assistance program that helps eligible financially needy patients in the US access our therapies.
+Added: To help patients afford our products, we have a manufacturer-sponsored patient assistance program that helps eligible patients in the US access our therapies.
This type of program has become the subject of enforcement scrutiny in recent years.
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In addition, certain state and federal enforcement authorities continue to pursue investigations and enter into settlements related to manufacturers’ support of patient assistance programs, and members of Congress have also initiated inquiries on topics that include, for example, manufacturer-sponsored patient assistance programs, co-payment assistance programs, and manufacturer contributions to independent charitable patient assistance programs.
−Removed: Moreover, the DHHS, Office of the Inspector General continues to publish advisory opinions and other agency guidance on the topic of patient assistance, which reflects the government’s continued scrutiny of manufacturer sponsored or supported patient assistance programs.
+Added: Moreover, the HHS, Office of the Inspector General continues to publish advisory opinions and other agency guidance on the topic of patient assistance, which reflects the government’s continued scrutiny of manufacturer sponsored or supported patient assistance programs.
Numerous organizations, including pharmaceutical manufacturers, have been subject to ongoing litigation, enforcement activities and settlements related to their patient support programs and certain of these organizations have entered into, or have otherwise agreed to, significant civil settlements with applicable enforcement authorities.
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If manufacturers obtain approval for generic versions of our products, or of products with which we compete, our business may be harmed.
−Removed: Under the Federal Food, Drug and Cosmetic Act (FDCA), the FDA can approve an ANDA for a generic version of a branded drug without the ANDA applicant undertaking the clinical testing necessary to obtain approval to market a new drug.
+Added: Under the Federal Food, Drug and Cosmetic Act (FDCA), the FDA can approve an Abbreviated New Drug Application (ANDA) for a generic version of a branded drug without the ANDA applicant undertaking the clinical testing necessary to obtain approval to market a new drug.
Generally, in place of such clinical studies, an ANDA applicant usually needs only to submit data demonstrating that its product has the same active ingredient(s), strength, dosage form and route of administration and that it is bioequivalent to the branded product.
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The litigation resulted from submission by Annora of an ANDA to the FDA seeking approval to market a generic version of TAVALISSE in the US.
−Removed: For more information, see “Part II, Item 1, Legal Proceedings” of this Quarterly Report on Form 10-Q.
+Added: For more information, see “ Part I, Item 3, Legal Proceedings” of the Annual Report on Form 10-K for the year ended December 31, 2025 .
We intend to vigorously enforce and defend our intellectual property related to our products.
−Removed: We cannot be assured that we will prevent the introduction of a generic version of our product for any particular length of time, or at all.
+Added: We cannot be assured that we will prevent the introduction of a generic version of our products for any particular length of time, or at all.
If an ANDA from generic manufacturers is approved, and generic versions of our products are introduced, whether following the expiration of our patents, the invalidation of our patents as a result of any litigation, or the determination that the proposed generic product does not infringe on our patents, our sales of our products would be adversely affected.
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The letter advises healthcare providers to apply certain measures to protect patient safety, including enhanced ongoing monitoring for signs and symptoms of infection as well as guidance for withholding treatment to patients in the presence of active infection.
−Removed: This and other communications containing warnings or other safety information to physicians and pharmacies, or required updates to labeling statements, including specific warnings or contradictions, could limit the commercial success of GAVRETO or any of our other drug products.
+Added: On December 22, 2025, the FDA notified us of the approval of a Prior Approval supplemental NDA for GAVRETO, which updated the US Prescribing Information to add a boxed warning regarding serious infections, including opportunistic infections.
+Added: The addition of a boxed warning is the most prominent safety warning the FDA can require and could negatively affect prescribing rates, patient willingness to initiate or continue
+Added: therapy, and payer coverage and reimbursement for GAVRETO.
+Added: If the box warning causes healthcare providers to prescribe GAVRETO less frequently, or if payers impose additional restrictions on coverage results, the commercial success of GAVRETO or any of our other drug products could be limited.
Side effects and toxicities associated with our products, as well as the warnings, precautions and requirements listed in the prescribing information for our products, could affect the willingness of physicians to prescribe, and patients to utilize, our products and thus harm commercial sales of our products.
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These events could harm our business and results of operations and cause our stock price to decline.
−Removed: Our business could be materially and adversely affected by pandemics as a result of their potential impacts on our sales force and commercialization efforts, supply chain, regulatory, clinical development and corporate development activities and other business operations, in addition to the impact of a global economic slowdown.
−Removed: Pandemics may result in extended travel and other restrictions in order to reduce the spread of diseases.
−Removed: Government measures taken in response to pandemics could have a significant impact, both direct and indirect, on our business and commerce, as significant reductions in business related activities may occur, supply chains may be disrupted, and manufacturing and clinical development activities may be curtailed or suspended.
−Removed: For example, during the COVID-19 pandemic, we observed reduced patient-doctor interactions and our representatives had fewer visits with healthcare providers, which negatively affected our product sales.
−Removed: Physicians with practices severely impacted by the COVID-19 pandemic, or a pandemic occurring in the future, and who currently prescribe our products, may eventually decide to close their independent practices and join a larger medical organization with a practice that does not prescribe our products.
−Removed: Additionally, a pandemic, including COVID-19 or any resurgence thereof, may impact commercial-related activities, such as our marketing programs, speaker bureaus, and market access initiatives which may be required to be conducted virtually, delayed or cancelled, all of which occurred as a result of the COVID-19 pandemic.
−Removed: During the COVID-19 pandemic, w e had to deploy resources to enable our field-based employees to continue to engage with healthcare providers in hybrid virtual and in-person interactions, which may be required in the event a pandemic occurs in the future.
−Removed: With respect to clinical development, in response to the COVID-19 pandemic, we took measures to implement remote and virtual approaches, including remote patient monitoring where possible and working with our investigators for appropriate care of these patients in a safe manner.
−Removed: Due to the effects of COVID-19 pandemic, we experienced a
−Removed: number of our clinical trial investigators either paused, postponed or delayed new patient enrollment and restricted site visits of existing patients enrolled.
−Removed: In the event that a global pandemic, or a resurgence of the COVID-19 pandemic, occurs in the future, we may need to make decisions on a country-by-country basis to minimize risk to the patients and clinical trial sites.
−Removed: We may also rely heavily on our clinical trial investigators to inform us of the best course of action with respect to resuming enrollment/screening, considering the ability of sites to ensure patient safety or data integrity.
−Removed: We experienced slower than anticipated enrollment in some of our clinical trials due to adverse effects of COVID-19 pandemic, and in the future, we may experience adverse impacts of a global pandemic on our clinical trials, including the timing thereof, or our ability to continue to treat patients enrolled in our trials, enroll and assess new patients, supply study drugs and obtain complete data points in accordance with study protocol.
−Removed: Pandemics may cause significant disruption in the supply chain for our commercial products.
−Removed: We rely on third parties to, among other things, manufacture and ship our commercial product, raw materials and product supply for our clinical trials, perform quality testing and supply other goods and services to help manage our commercial activities, our clinical trials and our operations in the ordinary course of business.
−Removed: While we have engaged actively with various elements of our supply chain and distribution channel, including our customers, contract manufacturers, and logistics and transportation provider to meet demand for our products and to remain informed of any challenges within our supply chain, we may face disruptions to our supply chain and operations, and associated delays in the manufacturing and supply of our products.
−Removed: Such supply disruptions would adversely impact our ability to generate sales of and revenues from our products and our business, financial condition, results of operations and growth prospects could be adversely affected.
−Removed: Pandemics may affect our collaboration and licensing partners for the commercialization of our products globally, as well as our ability to advance our various clinical stage programs.
−Removed: We cannot predict the impact of s uch disruptions on our partners’ ability to advance commercialization of our products in the market and the timing of enrollment and completion of various clinical trials being conducted by our collaboration partners.
−Removed: Health regulatory agencies globally may experience prolonged disruptions in their operations as a result of pandemics.
−Removed: For example, in response to the COVID-19 pandemic, the FDA delayed inspections and evaluations of certain drug manufacturing facilities and clinical research sites We cannot predict whether, and when, health regulatory agencies will decide to pause or resume inspections due to pandemics.
−Removed: Any de-prioritization of our clinical trials or delay in regulatory review resulting from such disruptions could materially affect the completion of our clinical trials.
−Removed: In addition, as seen in the COVID-19 pandemic, pandemics could result in a significant disruption of global financial markets.
−Removed: We could experience an inability to access additional capital or an impact on liquidity, which could in the future negatively affect our capacity for certain corporate development transactions or our ability to make other important, opportunistic investments, or we may not be able to meet the requirements under our Credit and Security Agreement (Credit Agreement) with MidCap Financial Trust (MidCap).
−Removed: While we expect pandemics to adversely affect our business, financial condition, results of operations and growth prospects in the future periods, the extent of the impact on our ability to generate sales of and revenues from our approved products, our ability to continue to secure new collaborations and support existing collaboration efforts with our partners, our clinical development and regulatory efforts, our corporate development objectives and the value of and market for our common stock, will depend on future circumstances that are highly uncertain and cannot be predicted with confidence at this time, such as the ultimate duration and severity of pandemics, travel restrictions, quarantines, social distancing and business closure requirements in the US and other countries, and the effectiveness of actions taken globally to contain and treat diseases.
−Removed: To the extent pandemics adversely affect our business and results of operations, it may also have the effect of heightening many of the other risks and uncertainties described elsewhere in this “Risk Factors” section.
+Added: Our business could be materially and adversely affected by pandemics or other public health crises.*
+Added: Pandemics or similar public health events, and governmental responses thereto, may disrupt our commercialization efforts, clinical development activities, supply chain, regulatory interactions and overall operations.
+Added: These disruptions may reduce demand for our products, delay or impair clinical trials, interrupt the manufacture and supply of our products and clinical materials, and affect the ability of our collaborators and service providers to perform their obligations.
+Added: Pandemics may also delay regulatory review, inspections and approvals, and could negatively impact global economic conditions and our access to capital.
+Added: The extent of any such impacts is uncertain and beyond our control.
+Added: Any of these effects could materially and adversely affect our business, financial condition, results of operations and prospects, and may exacerbate other risks described in this section.
If we fail to comply with our reporting and payment obligations under the Medicaid Drug Rebate Program or other governmental pricing programs in the US, we could be subject to additional rebate or discount requirements, fines, sanctions and exposure under other laws which could have an adverse effect on our business, results of operations and financial condition.
−Removed: We participate in the Medicaid Drug Rebate Program, as administered by CMS, the 340B Drug Pricing Program, as administered by the Health Resources and Services Administration (HRSA), and other federal and state government drug pricing programs in the US, and we may participate in additional government pricing programs in the
+Added: We participate in the Medicaid Drug Rebate Program, as administered by CMS, the 340B Drug Pricing Program, as administered by the Health Resources and Services Administration (HRSA), and other federal and state government drug pricing programs in the US, and we may participate in additional government pricing programs in the future.
These programs generally require us to pay rebates or otherwise provide discounts to government payors and/or required covered entities in connection with drugs that are dispensed to beneficiaries/recipients of these programs.
−Removed: In some cases, such as with the Medicaid Drug Rebate Program, the rebates are based on pricing metrics that we report on a monthly and quarterly basis to the government agencies that administer the programs.
+Added: In some cases, such as
+Added: with the Medicaid Drug Rebate Program, the rebates are based on pricing metrics that we report on a monthly and quarterly basis to the government agencies that administer the programs.
Pricing requirements and rebate/discount calculations are complex, vary among products and programs, and are often subject to interpretation by governmental or regulatory agencies and the courts.
The requirements of these programs, including, by way of example, their respective terms and scope, change frequently.
−Removed: For example, in September 2024, CMS published a final rule that included significant revisions to certain Medicaid Drug Rebate Program provisions, including, but not limited to:
−Removed: (i) new definitions for key terms under the Medicaid Drug Rebate Program, such as “covered outpatient drug” and “market date”;
−Removed: (ii) revised processes for identifying drug misclassifications, as well as additional penalties that can be imposed against manufacturers in connection with such misclassifications;
−Removed: and (iii) a new 12-quarter time limit for manufacturers to initiate disputes, hearing requests, and audits for state-invoiced rebate amounts.
Responding to current and future changes may increase our costs, and ensuring compliance will be time consuming.
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Changes in estimates and assumptions may have an adverse effect on our business, results of operations and financial condition.
−Removed: In addition, the DHHS, Office of Inspector General and other governmental enforcement and administrative bodies have increased their focus, including through recent enforcement actions against manufacturers, on pricing requirements for products, including, but not limited to the methodologies used by manufacturers to calculate average manufacturer price and best price for compliance with reporting requirements under the Medicaid Drug Rebate Program.
+Added: In addition, the HHS, Office of Inspector General and other governmental enforcement and administrative bodies have increased their focus, including through recent enforcement actions against manufacturers, on pricing requirements for products, including, but not limited to the methodologies used by manufacturers to calculate average manufacturer price and best price for compliance with reporting requirements under the Medicaid Drug Rebate Program.
We are liable for errors associated with our submission of pricing data and for any overcharging of government payors.
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Finally, we may be affected by developments relating to the 340B Drug Pricing Program (340B Program).
−Removed: For example, since 2021, multiple manufacturers have implemented policies to reduce diversion and inappropriate claims for discounts by placing restrictions on 340B pricing for drugs dispensed through contract pharmacies.
−Removed: The DHHS sent several of these manufacturers’ letters claiming that the policies violate the 340B statute and referring the manufacturers for potential enforcement action.
−Removed: Manufacturers challenged these letters in federal court, and the US Court of Appeals for the Third Circuit and the District of Columbia Circuit have ruled in favor of several manufacturers, finding that the policies were consistent with the 340B statute.
−Removed: Multiple states have recently enacted laws that require manufacturers to ship 340B drugs to certain contract pharmacies and impose various civil and criminal penalties on manufacturers that do not comply.
+Added: Multiple states have recently enacted or are currently considering laws that require manufacturers to ship 340B drugs to certain contract pharmacies and impose various civil and criminal penalties on manufacturers that do not comply.
These laws have been challenged in federal court and many of the cases are pending.
In March 2024, the US Court of Appeals for the Eight Circuit upheld the Arkansas law prohibiting drug makers for restricting 340B drug discounts for providers using contract pharmacies.
−Removed: DHHS also issued a final rule on procedures for the 340B Program’s administrative dispute resolution process in April 2024.
+Added: HHS also issued a final rule on procedures for the 340B Program’s administrative dispute resolution process in April 2024.
Additionally, under the Trump administration, several changes to the 340B program have been considered, including a proposal in the President’s 2026 budget to shift oversight of the 340B program from the HRSA to CMS.
Additionally, on July 31, 2025, the HRSA announced that it will implement a 340B Rebate Model Pilot Program that will be open to a selected group of drugs and manufacturers.
−Removed: The 340B Rebate Model Pilot Program is intended to become effective January 1, 2026.
+Added: However, the HRSA withdrew this proposal in January 2026 following litigation that resulted in a federal court granting temporary restraining order to block the program and has since requested information from stakeholders as to alternative rebate models.
It is unclear how the other pending litigation, proposed legislation, or future administrative action relating to the 340B Program will impact our business.
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While we intend to opportunistically seek access to additional funds through public or private equity offerings or debt financings, we do not know whether additional financing will be available when needed, or that, if available, we will obtain financing on reasonable terms.
−Removed: Our ability to raise additional capital, including our ability to secure new collaborations and continue to support existing collaboration efforts with our partners, may also be adversely impacted by potential worsening global economic conditions and the recent disruptions to, and volatility in, the credit and financial markets in the US and worldwide resulting from a global pandemic and the global tensions arising from the Russia-Ukraine war and the Hamas-Israel war.
+Added: Our ability to raise additional capital, including our ability to secure new collaborations and continue to support existing collaboration efforts with our partners, may also be adversely impacted by potential worsening global economic conditions and the recent disruptions to, and volatility in, the credit and financial markets in the US and worldwide resulting from global geopolitical tensions.
Unless and until we are able to generate a sufficient amount of product, royalty or milestone revenue, which may never occur, we expect to finance future cash needs through public and/or private offerings of equity securities, debt financings or collaboration and licensing arrangements, as well as through proceeds from the exercise of stock options and interest income earned on the investment of our cash balances and short-term investments.
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The Credit Agreement provides for a $60.0 million term loan credit facility.
−Removed: As of September 30, 2025, the outstanding principal balance of the loan was $60.0 million, and no remaining funds were available under the term loan credit facility.
−Removed: Under the Credit Agreement, we are required to repay amounts due when there is an event of default for the term loans that results in the principal, premium, if any, and interest, if any, becoming due prior to the maturity date for the term loans.
+Added: As of March 31, 2026, the outstanding principal balance of the loan was $45.0 million.
+Added: Under the Credit Agreement, we
+Added: were required to repay amounts due when there is an event of default for the term loans that results in the principal, premium, if any, and interest, if any, becoming due prior to the maturity date for the term loans.
The Credit Agreement also contains a number of other affirmative and restrictive covenants.
−Removed: See “Note 10 – Debt” to our “Notes to Condensed Financial Statements” contained in Part I, Item 1, of this Quarterly Report on Form 10-Q for additional details of the Credit Agreement.
−Removed: These and other terms in the Credit Agreement have to be monitored closely for compliance and could restrict our ability to grow our business or enter into transactions that we believe would be beneficial to our business.
+Added: These and other terms had to be monitored closely for compliance and could have restricted our ability to grow our business or enter into transactions that we believe would be beneficial to our business.
+Added: On May 5, 2026, we terminated the term loan facility and entered into a new Credit Agreement with MidCap providing for a revolving credit facility with a maximum borrowing capacity of $40.0 million, with an option to increase to $60.0 million, subject to customary conditions.
+Added: As of the date of this filing, we had an outstanding borrowing of $8.0 million under the revolving credit facility.
+Added: Borrowings under the revolving credit facility are subject to availability and ongoing compliance with certain conditions, and we may not be able to access the full amount of the facility when needed.
+Added: Availability under the revolving credit facility is subject to a borrowing base based primarily on eligible accounts receivable and inventory.
+Added: While the revolving credit facility enhances our financial flexibility to support operations and working capital needs, our liquidity is dependent on the level of borrowing base availability.
+Added: In addition, the revolving credit facility may require us to seek additional financing over time to support our operations, and such financing may not be available on favorable terms, or at all.
+Added: The revolving credit facility bears interest at a variable rate based on SOFR, subject to a floor, which exposes us to the risk of increased interest expense in a rising interest rate environment.
+Added: The Credit Agreement contains affirmative and restrictive covenants, including financial covenants.
+Added: These and other terms must be monitored closely for compliance and could restrict our ability to grow our business or enter into transactions that we believe would be beneficial to our business.
Our business may not generate cash flow from operations in the future sufficient to service our debt and support our growth strategies.
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In addition, we cannot be sure that additional financing will be available when required or, if available, will be on terms satisfactory to us.
−Removed: Further, even if we are able to obtain additional financing, we may be required to use such proceeds to repay a portion of our debt.
+Added: Further, even if we are able to obtain additional financing, we may be required to use such proceeds to repay amounts outstanding under our Credit Agreement.
Our indebtedness may have other adverse effects, such as:
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• our inability to obtain additional financing in the future.
−Removed: Our Credit Agreement with MidCap contains a mandatory prepayment provision that gives MidCap and/or its agent the right to demand payment of the outstanding principal and additional interest and fees in the event of default.
−Removed: We may not have enough available cash or be able to obtain financing at the time we are required to repay the term loan with additional interest and fees prior to maturity.
+Added: The Credit Agreement contains provisions that could result in an event of default, including a mandatory prepayment provision that gives MidCap and/or its agent the right to demand payment of any outstanding borrowings, together with applicable interest and fees, upon the occurrence of an event of default.
+Added: If we fail to comply with the covenants or other requirements under the revolving credit facility, an event of default could occur, which could result in the acceleration of any outstanding borrowings and the exercise of remedies by the lender, including foreclosure on substantially all of our assets.
+Added: We may not have sufficient available cash or be able to obtain financing at the time we are required to repay amounts outstanding under the Credit Agreement.
We rely and may continue to rely on two distribution facilities for the sale of our products and potential sale of any of our product candidates.
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• uncertainty relating to when the drug may become commercially available to patients and rate of adoption in other territories.
−Removed: We expect that our revenues from sales of any of our products will continue to be based in part on estimates,
−Removed: judgment and accounting policies.
+Added: We expect that our revenues from sales of any of our products will continue to be based in part on estimates, judgment and accounting policies.
Any incorrect estimates or disagreements with regulators or others regarding such estimates or accounting policies may result in changes to our guidance, projections or previously reported results.
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We do not and will not have access to all information regarding our products and product candidates we licensed to our collaboration partners.
−Removed: We do not and will not have access to all information regarding our products and other product candidates, including potentially material information about commercialization plans, medical information strategies, clinical trial design and execution, safety reports from clinical trials, safety reports, regulatory affairs, process development, manufacturing and other areas known by our collaboration partners.
+Added: We do not and will not have access to all information regarding our products and other product candidates, including potentially material information about commercialization plans, medical information strategies, clinical trial design and execution, safety reports from clinical trials, safety reports, regulatory affairs, process development,
+Added: manufacturing and other areas known by our collaboration partners.
In addition, we have confidentiality obligations under our respective agreements with our collaboration partners.
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Insufficient funds may require us to delay, scale back or eliminate some or all of our commercial efforts and/or research and development programs, to reduce personnel and operating expenses, to lose rights under existing licenses or to relinquish greater or all rights to product candidates at an earlier stage of development or on less favorable terms than we would otherwise choose or may adversely affect our ability to operate as a going concern.
−Removed: Our success as a company is uncertain due to our history of operating losses and the uncertainty of any future profitability.*
−Removed: For the nine months ended September 30, 2025 and for the year ended December 31, 2024, we recognized income from operations primarily due to higher net product sales and collaboration revenues, partially offset by our operating expenses.
+Added: Our recent operating income may not be sustainable, and we may continue to incur significant losses.
+Added: For the three months ended March 31, 2026, in 2025 and 2024, we recognized income from operations primarily due to net product sales and collaboration revenues, partially offset by our operating expenses.
Historically, we have incurred losses from operations each year since we were incorporated in June 1996 other than in fiscal year 2010, due in large part to the significant research and development expenditures and costs of our ongoing commercial efforts.
−Removed: Although we recognized income from operations in 2024 and in the current period, there can be no assurance that we will generate annual operating income in the foreseeable future.
+Added: Although we are now recognizing income from operations, there can be no assurance that we will continue to generate annual
+Added: operating income in the foreseeable future.
Currently, our potential sources of revenues include sales of our products, as well as upfront, milestones and royalty payments pursuant to our collaboration arrangements, all of which may never materialize if sales of our products decline or if our collaboration partners do not achieve certain events or generate net sales to which these contingent payments are dependent on.
If our future drug candidates fail or do not gain regulatory approval, or if our drugs do not achieve sustainable market acceptance, we may not be profitable.
−Removed: As of September 30, 2025, we had an accumulated deficit of approximately $1.3 billion.
−Removed: The extent of our future losses or profitability, if any, is highly uncertain.
+Added: As of March 31, 2026, we had an accumulated deficit of approximately $1.0 billion.
+Added: The extent of our future losses or profitability, if any, is uncertain.
If our corporate collaborations or license agreements are unsuccessful, or if we fail to form new corporate collaborations or license agreements, our research and development efforts could be delayed.
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If these collaborations terminate or are not renewed, any resultant loss of revenues from these collaborations or loss of the resources and expertise of our collaborative partners could adversely affect our business.
−Removed: For example, on October 1, 2025, we received a notice from Lilly of its intent to terminate the CNS disease program under the Lilly Agreement, which will become effective sixty (60) days following notification.
−Removed: Following the termination of the CNS
−Removed: disease program, we do not believe we will be entitled to receive any future milestone and royalty payments associated with this program.
+Added: For example, in April 2026, we received written notice from Lilly of its election to terminate the Lilly Agreement, which will become effective June 15, 2026.
+Added: Following termination of the Lilly Agreement, including the prior termination of the CNS disease program effective in November 2025, we do not expect to receive future milestones or royalties under the Lilly Agreement.
Conflicts also might arise with collaborative partners concerning proprietary rights to particular compounds.
While our existing collaborative agreements typically provide that we retain milestone payments, royalty rights and/or revenue sharing with respect to drugs developed from certain compounds or derivative compounds, any such payments or royalty rights may be at reduced rates, and disputes may arise over the application of payment provisions or derivative payment provisions to such drugs, and we may not be successful in such disputes.
−Removed: For example, in September 2018, BerGenBio served us with a notice of arbitration seeking declaratory relief related to the interpretation of provisions under our June 2011 license agreement, particularly as they relate to the rights and obligations of the parties in the event of the license or sale of a product in the program by BerGenBio and/or the sale of BerGenBio to a third party.
−Removed: The arbitration panel dismissed four of the six declarations sought by BerGenBio, and we thereafter consented to one of the remaining declarations requested by BerGenBio.
−Removed: On February 27, 2019, the arbitration panel issued a determination granting the declaration sought by BerGenBio on the remaining issue, and held that in the event of a sale of shares by BerGenBio’s shareholders where there is no monetary benefit to BerGenBio, we would not be entitled to a portion of the proceeds from such a sale.
−Removed: In this circumstance where the revenue share provision is not triggered, the milestone and royalty payment provisions remain in effect.
−Removed: While we do not believe that the determination will have an adverse effect on our operations, cash flows or financial condition, we can make no assurance regarding any such impact.
Additionally, the management teams of our collaborators may change for various reasons including due to being acquired.
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Some of our corporate collaborators are conducting multiple product development efforts within each disease area that is the subject of the collaboration with us or may be acquired or merged with a company having a competing program.
−Removed: In some of our collaborations, we have agreed not to conduct, independently or with any third party, any research that is competitive with the research conducted under our collaborations.
+Added: In some of our collaborations, we have agreed not to conduct, independently or with any third party, any research that is competitive with the research conducted under our
+Added: collaborations.
Our collaborators, however, may develop, either alone or with others, products in related fields that are competitive with the products or potential products that are the subject of these collaborations.
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For example, in March 2025, we entered into a settlement agreement with Annora resolving patent litigation related to our product TAVALISSE.
−Removed: For more information, see “Part II, Item 1, Legal Proceedings” of this Quarterly Report on Form 10-Q.
+Added: For more information, see “Part I, Item 3, Legal Proceedings” of our Annual Report on Form 10-K for the year ended December 31, 2025.
We intend to vigorously enforce and defend our intellectual property rights related to our products.
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As a result, our effective tax rate is derived from a combination of applicable tax rates in the various places that we operate.
−Removed: In preparing our financial statements, we estimate the amount of tax that will become payable in each of such places.
+Added: In preparing our financial statements, we estimate the amount of tax that will become payable in each of such jurisdictions.
Nevertheless, our effective tax rate may be different than experienced in the past due to numerous factors, including passage of the newly enacted federal income tax law, changes in the mix of our profitability from state to state, the results of examinations and audits of our tax filings, our inability to secure or sustain acceptable agreements with tax authorities, changes in accounting for income taxes and changes in tax laws.
Any of these factors could cause us to experience an effective tax rate significantly different from previous periods or our current expectations and may result in tax obligations in excess of amounts accrued in our financial statements.
−Removed: In July 2025, the OBBBA was enacted, which includes a broad array of measures affecting corporations and other business entities, including locking in a key set of business tax provisions.
−Removed: These include incentives designed to promote innovation-driven investment, such as a permanent and immediate deduction for domestic research and development costs.
−Removed: The legislation also locks in 100% expensing for qualified equipment purchases and makes permanent the deduction of up to 20% for qualified business income.
+Added: In July 2025, the One Big Beautiful Bill Act (OBBBA) was signed into law.
+Added: The OBBBA includes a broad range of provisions affecting business entities, including the establishment of certain permanent business tax measures.
+Added: Among other changes, the legislation permits permanent and immediate deduction for domestic research and development expenditures and restoration of favorable tax treatment for certain business provisions.
+Added: The legislation contains multiple effective dates, with certain provisions effective beginning in 2025 and others phased through 2027.
+Added: In accordance with ASC 740, Income Taxes , the effects of changes in tax laws are recognized in the period of enactment.
+Added: Accordingly, we evaluated the provisions of the OBBBA and determined that the most significant impact to us relates to the capitalization requirements for research and experimental expenditures under Section 174 of the Internal Revenue Code (Section 174).
+Added: The effects of this provision have been reflected in our income tax provision in 2025.
+Added: The effects of the OBBBA on our financial statements were not material, other than the impact related to Section 174 as described above.
While we continue to evaluate the impact of these legislative changes as additional guidance becomes available, uncertainty remains regarding the timing and interpretation by tax authorities in affected jurisdictions.
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The legislation also limits the aggregate use of otherwise allowable business credits to $5.0 million for each tax year beginning on or after January 1, 2024 but before January 1, 2027 (except for certain credits not subject to the limitation).
−Removed: Although the TCJA required taxpayers to capitalize Research and Experimental (R&E) expenditures under Section 174 of the Internal Revenue Code, as amended (Code) for tax years beginning after December 31, 2022, the OBBBA restored and made permanent the ability for taxpayers to make immediate deductions for R&E expenditures generated in tax years beginning after December 31, 2024.
−Removed: In addition, utilization of NOLs to offset potential future taxable income and related income taxes that would otherwise be due is subject to annual limitations under the “ownership change” provisions of Sections 382 and 383 of the Code and similar state provisions, which may result in the expiration of NOLs before future utilization.
−Removed: In general, under the Code, if a corporation undergoes an “ownership change,” generally defined as a greater than 50% change (by value) in its equity ownership over a three-year period, the corporation’s ability to use its pre-change NOLs and other pre-change tax attributes (such as research and development credit carryforwards) to offset its post-change taxable income or taxes may be limited.
+Added: Although the TCJA required taxpayers to capitalize research and experimental expenditures under Section 174 for tax years beginning after December 31, 2022, the OBBBA restored and made permanent the ability for taxpayers to make immediate deductions for research and experimental expenditures generated in tax years beginning after December 31, 2024.
+Added: In addition, utilization of NOLs to offset potential future taxable income and related income taxes that would otherwise be due is subject to annual limitations under the “ownership change” provisions of Sections 382 and 383 of the Section 174 and similar state provisions, which may result in the expiration of NOLs before future utilization.
+Added: In general, under Section 174, if a corporation undergoes an “ownership change,” generally defined as a greater than 50% change (by value) in its equity ownership over a three-year period, the corporation’s ability to use its pre-change NOLs and other pre-change tax attributes (such as research and development credit carryforwards) to offset its post-change taxable income or taxes may be limited.
Our equity offerings and other changes in our stock ownership, some of which are outside of our control, may have resulted or could in the future result in an ownership change.
Although we have completed studies to provide reasonable assurance that an ownership change limitation would not apply, we cannot be certain that a taxing authority would reach the same conclusion.
−Removed: If, after a review or audit, an ownership change limitation were to apply, utilization of our domestic NOLs and tax credit carryforwards could be limited in future periods and a portion of the carryforwards could expire before being available to reduce future income tax liabilities.
+Added: If, after a review or audit, an ownership change limitation were to apply, utilization of our domestic NOLs and tax credit carryforwards could be limited in future periods and a portion of the
+Added: carryforwards could expire before being available to reduce future income tax liabilities.
Moreover, our ability to utilize our NOLs is conditioned upon us achieving profitability and generating US federal taxable income.
Changes in valuation allowance of deferred tax assets may affect our future operating results
−Removed: We continue to record a full valuation allowance on our deferred tax assets.
−Removed: In assessing the need for a valuation allowance, we consider historical levels of income, expectations and risks associated with estimates of future taxable income.
−Removed: We periodically evaluate our deferred tax asset balance for realizability.
−Removed: To the extent we believe it is more-likely-than-not that our deferred tax assets will not be realized, we will continue to maintain the valuation allowance against the deferred tax assets.
−Removed: Realization of our deferred tax assets is dependent primarily upon future taxable income.
−Removed: If our assumptions and consequently our estimates change in the future, the valuation allowances may be increased or decreased, resulting in a respective increase or decrease in income tax expense.
+Added: Our deferred tax assets are primarily from net operating loss carryforwards, tax credits and other deductible temporary differences.
+Added: Historically, we maintained a full valuation allowance on our outstanding deferred tax assets.
+Added: In the fourth quarter of 2025, based on our evaluation of all available positive and negative evidence, we concluded that it was more-likely-than not that a significant portion of our federal and state deferred tax assets would be realized.
+Added: Accordingly, we released the valuation allowance against these deferred tax assets, except for deferred tax assets associated with the portion of federal research and development credit carryforwards, C alifornia NOL and California research and development credit carryforwards.
+Added: The assessment of the realizability of deferred tax assets involved considerable management judgment and required evaluation of all available evidence, including cumulative recent financial performance, forecasts of future taxable income, and the reversal of taxable temporary differences.
+Added: As a result of this assessment, we recognized a deferred income tax benefit of $245.9 million in 2025.
+Added: Our evaluation process for deferred tax asset realizability incorporates multiple factors, including, historical earnings performance and trends, projections of future taxable income and associated risks, and strategic business developments and market conditions.
+Added: We conduct periodic reviews of our deferred tax asset balances to assess continued realizability.
+Added: When evidence suggests it is more-likely-than-not that deferred tax assets will not be realized, we maintain or establish appropriate valuation allowances.
+Added: The ultimate realization of our deferred tax assets depends principally on generating sufficient future taxable income during periods when temporary differences reverse.
+Added: Changes in our assessment can result in material adjustments to the valuation allowance, which directly affects our income tax provision and effective tax rate.
+Added: The release of a valuation allowance results in a tax benefit, while establishing additional allowances increases tax expense.
+Added: Changes in projected future performance or shifts in the weighting of positive versus negative evidence can lead to significant changes in the required valuation allowance, making this estimate particularly sensitive to management's judgments about future operations.
Because we expect to be dependent upon collaborative and license agreements, we might not meet our strategic objectives.
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Our receipt of revenues from collaborative arrangements is also significantly affected by the timing of efforts expended by us and our collaborators and the timing of lead compound identification.
−Removed: We have received payments from our current collaborations including Lilly, Grifols, Kissei, Medison, Knight, BerGenBio, and Daiichi.
+Added: We have received payments from our collaborations including Lilly, Grifols, Kissei, Medison, Knight, Dr.
+Added: Reddy's, BerGenBio, and Daiichi.
Under several agreements, future payments may not be earned until the collaborator has advanced product candidates into clinical testing, which may never occur or may not occur until sometime well into the future.
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It is possible that we could, in the future, incur judgments or enter into settlements of claims for monetary damages.
−Removed: A decision adverse to our interests on any such actions could result in the payment of substantial damages, or possibly fines, and could have an adverse effect on our
−Removed: cash flow, results of operations and financial position.
+Added: A decision adverse to our interests in any such actions could result in the payment of substantial damages, or possibly fines, and could have an adverse effect on our cash flow, results of operations and financial position.
If our competitors develop technologies that are more effective than ours, our commercial opportunity will be reduced or eliminated.
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In addition, academic institutions, government agencies and other public and private organizations conducting research may seek patent protection with respect to potentially competitive products or technologies and may establish exclusive collaborative or licensing relationships with our competitors.
−Removed: We believe that our ability to compete is dependent, in part, upon our ability to create, maintain and license scientifically-advanced technology and upon our and our collaborators’ ability to develop and commercialize pharmaceutical products based on this technology, as well as our ability to attract and retain qualified personnel, obtain patent protection or otherwise develop proprietary technology or processes, secure effective market access by ensuring competitive pricing and reimbursement in territories of interest, and secure sufficient capital resources for the expected substantial time period between technological conception and commercial sales of products based upon our technology.
+Added: We believe that our ability to compete is dependent, in part, upon our ability to create, maintain and license scientifically-advanced technology and upon our and our collaborators’ ability to develop and commercialize
+Added: pharmaceutical products based on this technology, as well as our ability to attract and retain qualified personnel, obtain patent protection or otherwise develop proprietary technology or processes, secure effective market access by ensuring competitive pricing and reimbursement in territories of interest, and secure sufficient capital resources for the expected substantial time period between technological conception and commercial sales of products based upon our technology.
The failure by any of our collaborators or us in any of those areas may prevent the successful commercialization of our potential drug targets.
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• obtain patent or other proprietary protection for our new drug compounds and technologies;
−Removed: ● obtain access to manufacturing resources of the sufficient standard and scale;
+Added: • obtain access to manufacturing resources of sufficient standard and scale;
• enter commercialization agreements for our new drug compounds;
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• period-to-period fluctuations in financial results.
−Removed: We completed a reverse stock split of our shares of common stock, which may reduce and may limit the market trading liquidity of the shares due to the reduced number of shares outstanding and may potentially have an anti-takeover effect.
−Removed: We completed a reverse stock split of our common stock by a ratio of 1-for-10 effective June 27, 2024.
−Removed: The primary objective of the reverse stock split was to attempt to raise the per share trading price of our common stock.
−Removed: We believe that a low per share market price of our common stock impairs our marketability to, and acceptance by, institutional investors and other members of the investing public and creates a negative impression of us.
−Removed: Among other benefits, the effectuation of the reverse stock split seeks to help us maintain compliance with the minimum bid continued listing requirement of $1.00 per share required to maintain continued listing on The Nasdaq Global Select Market (the Bid Price Requirement).
−Removed: Prior to us effecting a reverse stock split, the closing bid price of our common stock at certain periods fell below $1.00 per share for 30 consecutive trading days.
−Removed: We received deficiency letters from the Listing Qualifications Department of Nasdaq on November 22, 2022 and November 27, 2023, notifying us that, for 30 consecutive business days, the bid price for our common stock had closed below the Bid Price Requirement.
−Removed: We received notification from the Listing Department of Nasdaq on January 5, 2023 and December 12, 2023 that we had regained our compliance with the Bid Price Requirement because the closing price of our common stock closed at $1.00 or more for over 10 consecutive days.
−Removed: Although we regained compliance with the Nasdaq Bid Price Requirement, in the future, Nasdaq may initiate a delisting process with a notification letter if we were to again fall out of compliance.
−Removed: If we were to receive such a notification, we would be afforded a grace period of 180 calendar days to regain compliance with the Bid Price Requirement.
−Removed: In order to regain compliance, shares of our common stock would need to maintain a minimum closing bid price of at least $1.00 per share for a minimum of 10 consecutive trading days.
−Removed: Additionally, we may be unable to meet other applicable Nasdaq listing requirements, including maintaining minimum levels of stockholders’ equity or market values of our common stock in which case, our common stock could be delisted.
−Removed: common stock were to be delisted, the liquidity of our common stock would be adversely affected and the market price of our common stock could decrease.
−Removed: Reducing the number of outstanding shares of our common stock through the reverse stock split increased the per share trading price of our common stock.
−Removed: However, there is no assurance that:
−Removed: ● the market price per share of our common stock after the reverse stock split will rise in proportion to the reduction in the number of shares outstanding before the reverse stock split;
−Removed: ● the reverse stock split will result in a per-share price that would attract brokers and investors who do not trade in lower-priced stocks;
−Removed: ● the reverse stock split will result in a per-share price that will increase our ability to attract and retain employees and other service providers;
−Removed: ● the reverse stock split will promote greater liquidity for our stockholders with respect to their shares.
−Removed: In addition, the reverse stock split reduced the number of outstanding shares of our common stock without reducing the authorized number of shares of our common stock.
−Removed: Therefore, the number of shares of our common stock that are authorized and unissued has increased relative to the number of issued and outstanding shares of our common stock following the reverse stock split.
−Removed: Our Board of Directors may authorize the issuance of the remaining authorized and unissued shares without further stockholder action for a variety of purposes, except as such stockholder approval may be required in particular cases by our Amended and Restated Certificate of Incorporation, applicable law or the rules of any stock exchange on which our securities may then be listed.
−Removed: The issuance of additional shares would be dilutive to our existing stockholders and may cause a decline in the trading price of our common stock.
−Removed: The issuance of authorized but unissued shares of common stock could be used to deter a potential takeover of us that may otherwise be beneficial to stockholders by diluting the shares held by a potential suitor or issuing shares to a stockholder that will vote in accordance with our Board of Directors’ desires.
−Removed: A takeover may be beneficial to independent stockholders because, among other reasons, a potential suitor may offer such stockholders a premium for their shares of stock compared to the then-existing market price.
−Removed: We do not have any plans or proposals to adopt provisions or enter into agreements that may have material anti-takeover consequences.
−Removed: The market price of our common stock is based on our performance and other factors, some of which are unrelated to the number of shares outstanding.
−Removed: If the market price of our common stock declines, the percentage decline as an absolute number and as a percentage of our overall market capitalization may be greater than would occur in the absence of the reverse stock split.
−Removed: The withdrawal of the UK from the EU may adversely impact our ability to obtain regulatory approvals of our product candidates in the UK, result in restrictions or imposition of taxes and duties for importing our product candidates into the UK, and may require us to incur additional expenses in order to develop, manufacture and commercialize our product candidates in the UK.
−Removed: Following the result of a referendum in 2016, the UK left the EU on January 31, 2020, commonly referred to as Brexit.
−Removed: Pursuant to the formal withdrawal arrangements agreed between the UK and the EU, the UK was subject to a transition period until December 31, 2020, or the Transition Period, during which EU rules continued to apply.
−Removed: A trade and cooperation agreement (Trade Agreement) that outlines the future trading relationship between the UK and the EU was agreed to in December 2020 and has been approved by each EU member state and the UK.
−Removed: Since a significant proportion of the regulatory framework in the UK applicable to our business and our product candidates is derived from EU directives and regulations, Brexit has had, and will continue to have, a material impact upon the regulatory regime with respect to the development, manufacture, importation, approval and commercialization of our product candidates in the UK or the EU.
−Removed: Great Britain (made up of England, Scotland, and Wales) is no longer covered by the EEA’s procedures for the grant of marketing authorizations (Northern Ireland will be covered by such procedures).
−Removed: The UK Government and the EU recently adopted a new agreement, the “Windsor Framework” which will replace the Northern Ireland Protocol.
−Removed: According to the Windsor Framework, medicinal products intended for the UK
−Removed: market including Northern Ireland will be authorized by the MHRA, and will bear a “UK only” label.
−Removed: This means that Medicinal products placed on the market in Northern Ireland will no longer need to be compliant with EU law.
−Removed: These new measures will be implemented from January 1, 2025.
−Removed: A separate marketing authorization will be required to market drugs in Great Britain.
−Removed: The MHRA has launched the Innovative Licensing and Access Pathway (ILAP), a new accelerated assessment procedure for marketing authorization applications facilitating the interaction with pricing authorities and HTA bodies and aiming to enable companies to enter the UK market faster.
−Removed: On January 1, 2024, the MHRA launched a new International Recognition Procedure for Great Britain (England, Scotland and Wales) marketing authorization applications whereby the MHRA will, when considering such applications, recognize the approval of medicines by trusted reference regulators in Australia, Canada, Switzerland, Singapore, Japan, United States and EU following its own abbreviated assessment.
−Removed: Any delay in obtaining, or an inability to obtain, any marketing approvals would delay or prevent us from commercializing our product candidates in the UK or the EU and restrict our ability to generate revenue and achieve and sustain profitability.
−Removed: While the Trade Agreement provides for the tariff-free trade of medicinal products between the UK and the EU, there may be additional non-tariff costs to such trade which did not exist prior to the end of the Transition Period.
−Removed: Further, should the UK diverge from the EU from a regulatory perspective in relation to medicinal products, tariffs could be put into place in the future.
−Removed: We could therefore, both now and in the future, face significant additional expenses (when compared to the position prior to the end of the Transition Period) to operate our business, which could significantly and materially harm or delay our ability to generate revenues or achieve profitability of our business.
−Removed: Any further changes in international trade, tariff and import/export regulations as a result of Brexit or otherwise may impose unexpected duty costs or other non-tariff barriers on us.
−Removed: These developments, or the perception that any of them could occur, may significantly reduce global trade and, in particular, trade between the impacted nations and the UK.
−Removed: It is also possible that Brexit may negatively affect our ability to attract and retain employees, particularly those from the EU.
−Removed: Orphan designation in the UK following Brexit is granted on an essentially identical basis as in the EU but is based on the prevalence of the condition in the UK.
−Removed: It is therefore possible that conditions that are currently designated as orphan conditions in the UK will no longer be, and conditions that are not currently designated as orphan conditions in the EU will be designated as such in the UK.
−Removed: In April 2023, the European Commission adopted a wide ranging proposal for a new Directive and a new Regulation to revise and replace the existing general pharmaceutical legislation.
−Removed: This change will likely result in significant changes to the pharmaceutical industry.
−Removed: In particular, it is expected that the new Directive and Regulations will, if made into law, affect the duration of the period of regulatory protection afforded to medicinal products including regulatory data protection (also called “data exclusivity”), marketing exclusivity afforded to orphan medicinal products, as well as the conditions of eligibility to the orphan designation.
−Removed: The legislation is not expected to be adopted before 2026/2027.
+Added: The UK’s withdrawal from the EU could adversely affect our business.*
+Added: The UK’s exit from the EU has created, and may continue to create, regulatory, trade and operational uncertainty.
+Added: We may be required to obtain separate regulatory approvals in the UK and the EU, comply with differing regulatory requirements, and incur additional costs and administrative burdens in developing, manufacturing and commercializing our product candidates.
+Added: In addition, changes to trade arrangements between the UK and the EU may result in increased costs, delays or disruptions in the importation and exportation of our products and materials.
+Added: Regulatory divergence between the UK and the EU may further complicate our operations and increase compliance risk.
+Added: Any of these factors could delay or prevent our ability to obtain approvals, limit our ability to commercialize our products in the UK or the EU, increase our operating costs, or otherwise materially and adversely affect our business, financial condition, results of operations and prospects.
If product liability lawsuits are successfully brought against us, we may incur substantial liabilities and may be required to limit commercialization of our products.
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We rely on third-party vendors and their information technology systems.
−Removed: Despite the implementation of security measures, our recovery systems, security protocols, network protection mechanisms and other security measures and those of our CROs and other contractors and consultants are vulnerable to compromise from natural disasters;
+Added: Despite the implementation of security measures, our recovery systems, security protocols, network protection mechanisms and other security measures and those of our CROs and other contractors and consultants are vulnerable to
+Added: compromise from natural disasters;
telecommunication and electric failures;
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Any event that leads to unauthorized access, processing or disclosure of personal information, including personal information regarding our clinical trial participants or employees, could harm our reputation and business, compel us to comply with federal and/or state breach notification laws and foreign law equivalents, subject us to investigations and mandatory corrective action, and otherwise subject us to liability under laws, regulations or contracts that protect the privacy and security of personal information, which could disrupt our business, damage our reputation with our stakeholders, result in increased costs or loss of revenue, lead to negative publicity or result in significant financial exposure.
−Removed: The CCPA, in particular, includes a private right of action for California consumers whose personal information is impacted by a data security incident resulting from a company’s failure to maintain reasonable security procedures, and hence may result in civil litigation in the event of a security breach impacting such information.
+Added: The California Consumer Privacy Act of 2018 (CCPA), in particular, includes a private right of action for California consumers whose personal information is impacted by a data security incident resulting from a company’s failure to maintain reasonable security procedures, and hence may result in civil litigation in the event of a security breach impacting such information.
In addition, legislators and regulators in the US have enacted and are proposing new and more robust privacy and cybersecurity laws and regulations in response to increasing broad-based cyberattacks, including the CCPA and New York SHIELD Act.
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A security breach may cause us to breach our contracts with third parties.
−Removed: Our agreements with relevant stakeholders such as collaborators may require us to use legally required, industry-standard or reasonable measures to safeguard personal information.
+Added: Our agreements with relevant stakeholders such as collaborators may require us to use legally required, industry-standard or reasonable measures to
+Added: safeguard personal information.
A security breach could lead to claims by relevant stakeholders that we have failed to comply with such contractual obligations, or require us to cooperate with these stakeholders in their own compliance efforts related to the security breach.
3 unchanged sentences
We may not have adequate insurance coverage for security incidents or breaches.
−Removed: The successful assertion of one or more large claims against us that exceeds our available insurance coverage, or results in changes to our insurance policies (including premium increases or the imposition of large deductible or co-insurance requirements), could have an
−Removed: adverse effect on our business.
+Added: The successful assertion of one or more large claims against us that exceeds our available insurance coverage, or results in changes to our insurance policies (including premium increases or the imposition of large deductible or co-insurance requirements), could have an adverse effect on our business.
In addition, we cannot be sure that our existing insurance coverage will continue to be available on acceptable terms or that our insurers will not deny coverage as to any future claim.
Future equity issuances or a sale of a substantial number of shares of our common stock may cause the price of our common stock to decline.
−Removed: Because we may need additional capital in the future to continue to expand our business, we may conduct additional equity offerings.
−Removed: We have an Open Market Sale Agreement with Jefferies entered on August 4, 2020, and amended and restated on August 2, 2024, pursuant to which, we may sell from time to time, through Jefferies, shares of our common stock in sales deemed to be “at-the-market offerings” as defined in Rule 415 under the Securities Act, subject to conditions specified in the Open Market Sale Agreement, including maintaining an effective registration statement covering the sale of shares under the Open Market Sale Agreement.
−Removed: We had a shelf registration statement (the Prior Registration Statement) filed with the SEC that expired on August 3, 2024.
−Removed: The Prior Registration Statement included a base prospectus registering the offering, issuance, and sale by us of up to $250.0 million in the aggregate of the securities identified from time to time in one or more offerings, including the $100.0 million of shares of our common stock that may be offered, issued and sold under the Open Market Sale Agreement.
−Removed: On August 2, 2024, we filed a new shelf registration statement (the New Registration Statement) with the SEC to replace the Prior Registration Statement.
−Removed: The New Registration Statement was declared effective on August 9, 2024 by the SEC.
−Removed: The New Registration Statement includes a base prospectus to register the offering, issuance and sale by us of up to $250.0 million in the aggregate of securities identified from time to time in one or more offerings, including up to $100.0 million of shares of our common stock that may be offered, issued and sold under the Open Market Sale Agreement.
−Removed: As of September 30, 2025, we have not sold any shares of common stock under such Open Market Sale Agreement.
+Added: Because we will continue to need additional capital in the future to continue to expand our business, we may conduct additional equity offerings.
+Added: We have an Open Market Sale Agreement with Jefferies entered on August 4, 2020, and amended and restated on August 2, 2024, pursuant to which, we may sell from time to time, through Jefferies, shares of our common stock in sales deemed to be “at-the-market offerings” as defined in Rule 415 under the Securities Act, subject to conditions specified in the Open Market Sale Agreement.
+Added: On August 2, 2024, we filed a shelf registration statement with the SEC to register the offering, issuance and sale by us of up to $250.0 million in the aggregate of securities identified from time to time in one or more offerings, including up to $100.0 million of shares of our common stock that may be offered, issued and sold under the Open Market Sale Agreement.
+Added: As of March 31, 2026 , we have not sold any shares of common stock under the Open Market Sale Agreement.
We may also in the future enter into underwriting or sales agreements with financial institutions for the offer and sale of any combination of common stock, preferred stock, debt securities and warrants in one or more offerings.
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We cannot predict the initiatives that may be adopted in the future.
−Removed: The continuing efforts of the government, insurance companies, managed care organizations and other payors of healthcare services to contain or reduce the costs of
−Removed: healthcare and/or impose price controls may adversely affect, for example:
+Added: The continuing efforts of the government, insurance
+Added: companies, managed care organizations and other payors of healthcare services to contain or reduce the costs of healthcare and/or impose price controls may adversely affect, for example:
• the demand for our products, or our product candidates, if we obtain regulatory approval;
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In the US, there have been several Congressional inquiries and federal legislation designed to, among other things, bring more transparency to drug pricing, review the relationship between pricing and manufacturer-sponsored patient assistance programs, and reform government program reimbursement methodologies for drugs .
−Removed: On March 11, 2021, the American Rescue Plan Act of 2021 was signed into law, which, among other changes, eliminated the statutory Medicaid drug rebate cap, which was previously set at 100% of a drug’s average manufacture price, for single source and innovator multiple source drugs, as of January 1, 2024.
−Removed: The American Rescue Plan Act also temporarily increased premium tax credit assistance for individuals eligible for subsidies under the Affordable Care Act for 2021 and 2022 and removed the 400% federal poverty level limit that otherwise applies for purposes of eligibility to receive premium tax credits.
−Removed: The Inflation Reduction Act (IRA), signed into law on April 6, 2022, extended this increased tax credit assistance and removal of the 400% federal poverty limit through 2025.
−Removed: Additionally, beginning in April 2013, the Budget Control Act of 2011 created an automatic reduction of Medicare payments to providers of up to 2%.
−Removed: As a result of the COVID-19 pandemic, this reduction was temporarily suspended from May 1, 2020 through March 31, 2022, with subsequent reductions to 1% from April 1, 2022 through June 30, 2022.
−Removed: The 2% reduction was then reinstated and has been in effect since July 1, 2022, and will remain in effect through the first ten months in which the fiscal year 2032 sequestration order is in effect, unless additional Congressional action is taken.
−Removed: Additionally, the IRA implements substantial changes to the Medicare program, including drug pricing reforms and changes to the Medicare Part D benefit design.
−Removed: Among other reforms, the IRA allows Medicare to:
−Removed: beginning in 2026, establish a “maximum fair price” for a fixed number of pharmaceutical and biological products covered under Medicare Parts B and D following a price negotiation with CMS;
−Removed: beginning in 2023, penalize drug companies that raise prices for products covered under Medicare Parts B and D faster than inflation;
−Removed: and beginning in 2025, cap beneficiary annual out-of-pocket spending at $2,000, while imposing new discount obligations on pharmaceutical and biological manufacturers for products covered under Medicare Part D.
−Removed: CMS continues to take steps to implement the IRA, including:
−Removed: releasing the negotiated maximum prices, which will be effective in 2026, for the first ten drugs that were subject to the IRA’s negotiation process;
−Removed: releasing quarterly lists of Medicare Part B products that are subject to adjusted coinsurance rates based on the inflationary rebate provisions of the IRA;
−Removed: and announcing a list of fifteen additional drugs that will be subject to price negotiations during 2025.
−Removed: While it remains to be seen how the drug pricing provisions imposed by the IRA will affect the broader pharmaceutical industry, several pharmaceutical manufacturers and other industry stakeholders have challenged the law, including through lawsuits brought against the DHHS, the Secretary of the DHHS, CMS, and the CMS Administrator challenging the constitutionality and administrative implementation of the IRA’s drug price negotiation provisions.
−Removed: Additionally, when originally enacted, the IRA explicitly excluded from price negotiation orphan drugs designated for only one rare disease or condition and for which the only active approved indication is for such disease or condition.
−Removed: However, the OBBBA amended the applicable statute to broaden the orphan drug exclusion such that products with more than one orphan designation and more than one approved indication will remain exempt from price negotiation, so long as each approved indication is for a rare disease or condition.
−Removed: The OBBBA also postpones the start of price negotiation requirements for drugs and biologics with orphan designations until the product receives approval for a non-orphan indication.
+Added: Recent healthcare reform measures, including the Inflation Reduction Act and changes to government healthcare programs, could adversely affect our business.
+Added: federal and state healthcare reforms have resulted in, and are expected to continue to result in, significant changes to the pricing, reimbursement and coverage of pharmaceutical products.
+Added: For example, the Inflation Reduction Act (IRA) allows Medicare to negotiate prices for certain drugs, imposes inflation-based rebates for products covered under Medicare Parts B and D, and redesigns the Medicare Part D benefit in ways that increase financial obligations for manufacturers, while the elimination of the Medicaid drug rebate cap may increase our rebate liability.
+Added: Additionally, OBBBA broadened the scope of IRA’s exclusion of certain orphan drugs from price negotiations.
+Added: These and other reforms may reduce the prices we can charge for our products, increase our rebate and discount obligations, and negatively affect reimbursement, which could adversely impact our revenues, margins and operations.
+Added: The full impact of these measures, as well as potential future legislative, regulatory or judicial developments, remains uncertain and could materially and adversely affect our business, financial condition, results of operations and prospects.
Other proposed administrative actions may affect our government pricing responsibilities.
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It remains to be seen how these drug pricing initiatives will affect the broader pharmaceutical industry.
+Added: Although none of our products are currently subject to Medicare price negotiation under the IRA, the program is expected to expand to additional drugs in the future years.
+Added: If any of our products were selected for negotiation, the negotiated prices could significantly lower than the prices we currently receive, which could materially reduce our revenues and profitability.
The current presidential administration has also signaled its intent to pursue healthcare reform measures, including those aimed at reducing prescription drug prices.
For example, President Trump has signed multiple executive orders addressing prescription drug pricing and access, including:
−Removed: on April 15, 2025, outlining several actions the Secretary of the DHHS must take to optimize healthcare regulations that will provide access to prescription drugs at
−Removed: on May 5, 2025, aiming to promote domestic production of critical medicines;
−Removed: and on May 12, 2025, aiming
−Removed: to establish a most favored nation (MFN) drug pricing policy that would tie US drug prices to the prices paid for drugs in other countries.
−Removed: Since the May 12, 2025 MFN executive order, the Trump administration has continued to exert pressure on drug manufacturers to implement MFN pricing, and in early October 2025 announced two agreements with Pfizer and AstraZeneca.
−Removed: The Trump administration also announced that both manufacturers would make products available at significant discounts on a new direct-to-consumer website that will be launched in January 2026.
−Removed: Further, the current administration has suggested that it may impose tariffs on pharmaceuticals if similar MFN agreements are not reached with other drug manufacturers.
−Removed: In addition, on June 28, 2024, the US Supreme Court issued an opinion holding that courts reviewing agency action pursuant to the Administrative Procedure Act (APA) “must exercise their independent judgment” and “may not defer to an agency interpretation of the law simply because a statute is ambiguous.” The decision will have a significant impact on how lower courts evaluate challenges to agency interpretations of law, including those by CMS and other agencies with significant oversight of the healthcare industry.
−Removed: The new framework is likely to increase both the frequency of such challenges and their odds of success by eliminating one way in which the government previously prevailed in such cases.
−Removed: As a result, significant regulatory policies may be subject to increased litigation and judicial scrutiny.
−Removed: Any resulting changes in regulation may result in unexpected delays, increased costs, or other negative impacts that are difficult to predict but could have a material adverse effect on our business and financial condition.
−Removed: For example, certain of these changes could impose additional limitations on the rates we will be able to charge for our future products or the amounts of reimbursement available for our future products from governmental agencies or third-party payors.
+Added: an order on May 12, 2025 aiming to establish a most favored nation (MFN) drug pricing policy that would tie US drug prices to the prices paid for drugs in other countries.
+Added: Since the May 12, 2025 MFN executive order, the Trump administration has continued to exert pressure on drug manufacturers to implement MFN pricing.
+Added: Over a dozen large pharmaceutical manufacturers have entered into agreements with the Trump Administration to offer lower prices for their drugs.
+Added: Additionally, CMS has taken action to implement the administration’s MFN pricing policy, including by announcing a new voluntary payment model where drug manufacturers may offer supplemental rebates to participating state Medicaid programs to provide such Medicaid programs with a “most favored nation” price for participating manufacturers’ products, as well proposing mandatory payment models where, if finalized, manufacturers of certain Medicare Part B and Medicare Part D drugs would be assessed rebates if the prices for such products exceed those paid in economically comparable countries.
+Added: The Trump administration also announced the launch of a new direct-to-consumer website in February 2026 that is intended to make certain drugs available to consumers at significant discounts.
+Added: It remains to be seen how these drug pricing initiatives will affect the broader pharmaceutical industry.
At the state level, individual states are increasingly aggressive in passing legislation and implementing regulations designed to control pharmaceutical and biological product pricing.
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Given the lack of clarity in the laws and their implementation, our reporting actions could be subject to the penalty provisions of the pertinent state laws and regulations.
−Removed: Another emerging trend at the state level is the establishment of prescription drug affordability boards, some of which will prospectively permit certain states to establish upper payment limits for drugs that the state has determined to be “high-cost.” Prescription drug affordability boards in several states, including Colorado, Maryland, Oregon, and Washington, have begun identifying products for affordability reviews and issuing information request to manufacturers to determine whether upper payment limits may be justified.
+Added: Another emerging trend at the state level is the establishment of prescription drug affordability boards, some of which will prospectively permit certain states to establish upper payment limits for drugs that the state has determined to be “high-cost.” Prescription drug affordability boards in several states have begun identifying products for affordability reviews and issuing information requests to manufacturers to determine whether upper payment limits may be justified.
Furthermore, the increased emphasis on managed healthcare in the US and on country and regional pricing and reimbursement controls in the EU and the UK will put additional pressure on product pricing, reimbursement and usage, which may adversely affect our sales and results of operations.
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If we or any third parties we may engage are slow or unable to adapt to changes in existing requirements or the adoption of new requirements or policies, or if we or such third parties are not able to maintain regulatory compliance, our product candidates may lose any regulatory approval that may have been obtained and we may not achieve or sustain profitability.
−Removed: See “Business – Government Regulation – Healthcare Reform” contained in Part I, Item 1 of tour Annual Report on Form 10-K for the year ended December 31, 2024, for additional information.
+Added: See “Business – Government Regulation – Healthcare Reform” contained in Part I, Item 1 of our Annual Report on Form 10-K for the year ended December 31, 2025 , for additional information.
Regulatory approval for any approved product is limited by the FDA, the EC and other regulators to those specific indications and conditions for which clinical safety and efficacy have been demonstrated, and we may incur significant liability if it is determined that we are promoting the “off-label” use of our products or any of our future product candidates if approved.
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Delays in clinical testing could result in increased costs to us.
−Removed: We may not be able to initiate or continue clinical studies or trials for our product candidates if we are unable to locate and enroll a sufficient number of eligible patients to participate in these clinical trials as required by the FDA or other regulatory authorities, whether due to the impacts of a global pandemic, global tensions arising from the Russian-Ukrainian war and Hamas-Israel war or otherwise.
+Added: We may not be able to initiate or continue clinical studies or trials for our product candidates if we are unable to locate and enroll a sufficient number of eligible patients to participate in these clinical trials as required by the FDA or other regulatory authorities, whether due to the impacts of a global pandemic, global geopolitical tensions or otherwise.
Even if we are able to enroll a sufficient number of patients in our clinical trials, if the pace of enrollment is slower than we expect, the development costs for our product candidates may increase and the completion of our clinical trials may be delayed, or our clinical trials could become too expensive to complete.
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The clinical investigators are not our employees, and we cannot control the amount or timing of resources that they devote to our programs.
−Removed: Failure of the third-party organizations to meet their obligations, whether due to the potential future impacts of a global pandemic, the global tensions arising from the Russian-Ukrainian war and Hamas-Israel war or otherwise, could adversely affect clinical development of our products.
+Added: Failure of the third-party organizations to meet their obligations, whether due to the potential future impacts of a global pandemic, or global geopolitical tensions, could adversely affect clinical development of our products.
As a result, we may face additional delaying factors outside our control if these parties do not perform their obligations in a timely fashion.
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If these third-party investigators and organizations assist our competitors at our expense, it could harm our competitive position.
−Removed: Due to the effects of the COVID-19 pandemic, for several of our development programs, we experienced disruption or delay in our ability to enroll and assess patients, maintain patient enrollment, supply study drugs, report trial results, or interact with regulators, ethics committees or other important agencies due to limitations in employee resources or otherwise.
−Removed: In addition, in the event that a global pandemic occurs in the future, some patients in our clinical trial may not be able or willing to comply with clinical trial protocols if quarantines impede patient movement or interrupt healthcare services.
−Removed: Similarly, our ability to recruit and retain patients and principal investigators and site staff may be adversely affected if a global pandemic continues and persists for an extended period of time, and we may experience significant disruptions to our clinical development timelines, which would adversely affect our business, financial condition, results of operations and growth prospects in the future.
We have conducted in the past and are currently conducting or may conduct in the future clinical trials in the US and outside the US.
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Recent actions taken by the Russian Federation in Ukraine and surrounding areas have destabilized the region and caused the adoption of comprehensive sanctions by, among others, the EU, the US and the UK, which restrict a wide range of trade and financial dealings with Russia and Russian persons, as well as certain regions in Ukraine.
−Removed: Also, the recent global tensions arising from the Hamas-Israel war may result in disruptions in the broader global economic environment.
+Added: Also, recent global tensions, conflicts, and wars may result in disruptions in the broader global economic environment.
Further, some patients may not be able to comply with clinical trial protocols if the conflict impedes patient movement or interrupts healthcare services.
−Removed: In addition, clinical trial site initiation and patient enrollment may be delayed, and we may not be able to access sites for initiation and monitoring in regions affected by the Russian-Ukrainian war or the Hamas-Israel war including due to the prioritization of hospital resources away from clinical trials or as a result of warfare, violence, government-imposed curfews, or events or other governmental actions that restrict
+Added: In addition, clinical trial site initiation and patient enrollment may be delayed, and we may not be able to access sites for initiation and monitoring in regions affected by the global geopolitical tensions, including due to the prioritization of hospital resources away from clinical trials or as a result of warfare, violence, government-imposed
+Added: curfews, or events or other governmental actions that restrict movement.
We could also experience disruptions in our supply chain or limits our ability to obtain sufficient materials for our drug products in certain regions.
+Added: A Fast Track designation by the FDA may not lead to a faster development or regulatory review and does not increase the likelihood that our product candidates will receive approval.
+Added: We may seek fast track designation for our product candidates.
+Added: If a product is intended for the treatment of a serious or life-threatening disease or condition and it demonstrates the potential to address unmet medical needs for such a disease or condition, the sponsor may apply for FDA fast track designation for a particular indication.
+Added: We may seek fast track designation for our product candidates, but there is no assurance that the FDA will grant this designation to any of our proposed product candidates, even if such a designation has been granted to similar products.
+Added: Marketing applications submitted by sponsors of products in fast track development may qualify for priority review under the policies and procedures offered by the FDA, but the fast track designation does not assure any such qualification or ultimate marketing approval by the FDA.
+Added: The FDA has broad discretion whether or not to grant fast track designation, so even if we believe a particular product candidate is eligible for this designation, there can be no assurance that the FDA would decide to grant it.
+Added: Even if we do receive fast track designation, we may not experience a faster development process, review or approval compared to conventional FDA procedures or pathways and receiving a fast track designation does not provide assurance of ultimate FDA approval.
+Added: In addition, the FDA may withdraw fast track designation at any time, including if it believes that the designation is no longer supported by data from our clinical development program.
Public perception of the risk-benefit balance for our product candidates may be affected by adverse events in clinical trials involving our product candidate or other treatments.
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We do not currently have, nor do we plan to acquire the infrastructure or capability to supply, manufacture or distribute preclinical, clinical or commercial quantities of drug substances or products.
−Removed: For each clinical trial of our unpartnered product candidates, we rely on third-party manufacturers for the API, as well as various manufacturers to manufacture starting components, excipients and formulated drug products.
−Removed: Our ability to develop our product candidates, and our ability to commercially supply our products will depend, in part, on our ability to successfully obtain the API and other substances and materials used in our product candidates from third parties and to have finished products manufactured by third parties in accordance with regulatory requirements and in sufficient quantities for preclinical and clinical testing and commercialization.
+Added: For each clinical trial of our unpartnered product candidates, we rely on third-party manufacturers for the APIs, as well as various manufacturers to manufacture starting components, excipients and formulated drug products.
+Added: Our ability to develop our product candidates, and our ability to commercially supply our products will depend, in part, on our ability to successfully obtain the APIs and other substances and materials used in our product candidates from third parties and to have finished products manufactured by third parties in accordance with regulatory requirements and in sufficient
+Added: quantities for preclinical and clinical testing and commercialization.
If we fail to develop and maintain supply relationships with these third parties, we may be unable to continue to develop or commercialize our product candidates.
−Removed: We rely and will continue to rely on certain third parties, including those located outside the US, as our limited source of the materials they supply or the finished products they manufacture.
+Added: Since our commercialization, we have sold inventory quantities that were acquired or produced before FDA approval and therefore did not reflect full production costs, as pre-approval manufacturing costs were previously expensed to research and development.
+Added: Specifically, we utilized zero-cost API inventory for TAVALISSE, which reduced cost of product sales in those periods.
+Added: As post-approval inventory is acquired or produced, inventory and cost of product sales reflect the full manufacturing cost.
+Added: Further, the imposition or threat of imposition of trade policies, tariffs (including retaliatory tariffs), taxes and other cross-border operations could also result in higher cost of product sales.
+Added: We rely and will continue to rely on certain third parties, including those located outside the US, as our limited source suppliers of certain materials and finished products.
In the ordinary course of business, we enter into agreements with contract manufacturers to manufacture our inventory products.
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Any of these existing suppliers or manufacturers may:
−Removed: ● fail to supply us with product on a timely basis or in the requested amount due to unexpected damage to or
−Removed: destruction of facilities or equipment or otherwise;
+Added: • fail to supply us with product on a timely basis or in the requested amount due to unexpected damage to or destruction of facilities or equipment or otherwise;
• fail to increase manufacturing capacity and produce drug product and components in larger quantities and at higher yields in a timely or cost-effective manner, or at all, to sufficiently meet our commercial needs;
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Our third-party manufacturers could terminate or decline to renew our manufacturing arrangements based on their own business priorities, at a time that is costly or inconvenient for us.
−Removed: If we are unable to contract for the production of materials in sufficient quantity and of sufficient quality on acceptable terms, our planned clinical trials may be significantly delayed.
+Added: If we are unable to
+Added: contract for the production of materials in sufficient quantity and of sufficient quality on acceptable terms, our planned clinical trials may be significantly delayed.
Manufacturing delays could postpone the filing of our investigational new drug (IND) applications and/or the initiation or completion of clinical trials that we have currently planned or may plan in the future.
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Additionally, if we are required to enter into new supply arrangements, we may not be able to obtain approval from the FDA of any alternate supplier in a timely manner, or at all, which could delay or prevent the clinical development and commercialization of any related product candidates.
−Removed: Failure of our third-party manufacturers or us to comply with applicable regulations, whether due to the impacts of a global pandemic or otherwise, could result in sanctions being imposed on us, including fines, civil penalties, delays in or failure to grant marketing approval of our product candidates, injunctions, delays, suspension or withdrawal of approvals, license
−Removed: revocation, seizures or recalls of products and compounds, operating restrictions and criminal prosecutions, warning or similar letters or civil, criminal or administrative sanctions against us, any of which could adversely affect our business.
+Added: Failure of our third-party manufacturers or us to comply with applicable regulations, whether due to the impacts of a global pandemic or otherwise, could result in sanctions being imposed on us, including fines, civil penalties, delays in or failure to grant marketing approval of our product candidates, injunctions, delays, suspension or withdrawal of approvals, license revocation, seizures or recalls of products and compounds, operating restrictions and criminal prosecutions, warning or similar letters or civil, criminal or administrative sanctions against us, any of which could adversely affect our business.
Any product for which we have obtained regulatory approval, or for which we obtain approval in the future, is subject to, or will be subject to, extensive ongoing regulatory requirements by the FDA, EMA, MHRA and other comparable regulatory authorities, and if we fail to comply with regulatory requirements or if we experience unanticipated problems with our products, we may be subject to penalties, we may be unable to generate revenue from the sale of such products, our potential for generating positive cash flow will be diminished, and the capital necessary to fund our operations will be increased.*
We commercialize our products in the US and we have entered into commercialization agreements with third parties to commercialize our products outside the US.
−Removed: Any product for which we have obtained regulatory approval, or for which we obtain regulatory approval in the future, along with the manufacturing processes and practices, post-approval clinical research, product labeling, advertising and promotional activities for such product, are subject to continual requirements of, and review by, the FDA, the EMA and other comparable international regulatory authorities.
+Added: Any product for which we have obtained regulatory approval, or for which we obtain regulatory approval in the future, along with the manufacturing processes and practices, post-approval clinical research, product labeling, advertising and promotional activities for such product, are subject to continual requirements of, and review by, the FDA, the European Medicines Agency (EMA) and other comparable international regulatory authorities.
These requirements include submissions of safety and other post-marketing information and reports, registration and listing requirements, cGMP requirements relating to manufacturing, quality control, quality assurance and corresponding maintenance of records and documents, requirements regarding the distribution of samples to physicians, import and export requirements and recordkeeping.
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A REMS may be required to include various elements, such as a medication guide or patient package insert, a communication plan to educate healthcare providers of the drug’s risks, limitations on who may prescribe or dispense the drug, requirements that patients enroll in a registry or undergo certain health evaluations or other measures that the FDA deems necessary to ensure the safe use of the drug.
+Added: Additionally, approval of a drug under an accelerated drug approval program may be withdrawn or the labeled indication of the drug changed if trials fail to verify clinical benefit or do not demonstrate sufficient clinical benefit to justify the risks associated with the drug.
+Added: For example, GAVRETO is approved under accelerated approval for the treatment of adult and pediatric patients 12 years of age and older with advanced or metastatic RET fusion-positive thyroid cancer.
+Added: We have satisfied our post-marketing commitment with respect to the AcceleRET-Lung study for the NSCLC indication;
+Added: however, discussions with the FDA regarding confirmatory requirements for the thyroid cancer indication remain ongoing.
+Added: The FDA has demonstrated an increased
+Added: willingness to withdraw accelerated approvals where confirmatory trials have not been completed or have failed to verify clinical benefit.
+Added: If we are unable to satisfy the FDA’s confirmatory requirements for the thyroid cancer indication, the FDA could withdraw approval for that indication, which would reduce the addressable patient population for GAVRETO and could adversely affect our revenues and commercial strategy.
Discovery after approval of previously unknown problems with any of our products, manufacturers or manufacturing processes, or failure to comply with regulatory requirements, may result in actions such as:
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Outside the US, our ability, or that of our collaborative partners, to market a product is contingent upon receiving a marketing authorization from the appropriate regulatory authorities.
−Removed: This foreign regulatory approval process typically includes all of the risks and costs associated with FDA approval described above and may also include additional risks and costs, such as the risk that such foreign regulatory authorities, which often have different regulatory and clinical trial requirements, interpretations and guidance from the FDA, may require additional clinical trials or results for approval of a product candidate, any of which could result in delays, significant additional costs or failure to obtain such regulatory approval.
+Added: This foreign regulatory approval process typically includes all of the risks and costs associated with FDA approval described above and may also include additional risks and costs, such as the risk that such foreign regulatory authorities, which often have different regulatory and clinical trial requirements, interpretations and guidance from the FDA, may require additional clinical trials or results for approval of a product candidate, any of which could result in delays, significant additional costs or failure to obtain such regulatory
There can be no assurance, however, that we or our collaborative partners will not have to provide additional information or analysis, or conduct additional clinical trials, before receiving approval to market product candidates.
We have orphan drug designations from the FDA but we may not be able to obtain additional orphan drug designations in the future, or maintain the orphan drug designations or exclusivity for the approved drugs for the treatment of respective indications, or we may be unable to maintain the benefits associated with orphan drug designations, including the potential for market exclusivity.
−Removed: We have an orphan drug designation in the US for fostamatinib for the treatment of ITP and wAIHA, and for olutasidenib for the treatment of AML.
+Added: We have an orphan drug designation in the US for fostamatinib for the treatment of ITP and warm auto immune hemolytic anemia (wAIHA), and for olutasidenib for the treatment of AML.
Also, pralsetinib has an orphan drug designation in the US for the treatment of adult patients with metastatic RET fusion-positive NSCLC, for the treatment of advanced or metastatic RET fusion-positive thyroid cancer, and for the treatment of advanced or metastatic RET -mutant medullary thyroid carcinoma.
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We may also seek orphan drug designation for other product candidates in the future.
−Removed: Under the Orphan Drug Act, the FDA may grant orphan drug designation to a drug or biologic intended to treat a rare disease or condition, which is defined as one occurring in a patient population of fewer than 200,000 in the US, or a patient population greater than 200,000 in the US
−Removed: where there is no reasonable expectation that the cost of developing the drug will be recovered from sales in the US.
+Added: Under the Orphan Drug Act, the FDA may grant orphan drug designation to a drug or biologic intended to treat a rare disease or condition, which is defined as one occurring in a patient population of fewer than 200,000 in the US, or a patient population greater than 200,000 in the US where there is no reasonable expectation that the cost of developing the drug will be recovered from sales in the US.
In the US, orphan drug designation entitles a party to financial incentives such as opportunities for grant funding towards clinical trial costs, tax advantages and user-fee waivers.
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We are focusing a significant portion of our activities and resources on our products, and we believe our prospects are highly dependent on, and a significant portion of the value of our company relates to, our ability to sustain successful commercialization of our products in the US.
−Removed: We have also entered into exclusive commercialization agreements with third parties to commercialize our products outside the US, and we plan to further enter partnership with existing or other third parties to commercialize our products outside the US in the future.
+Added: We have also entered into exclusive commercialization agreements with third
+Added: parties to commercialize our products outside the US, and we plan to further enter partnership with existing or other third parties to commercialize our products outside the US in the future.
Sustained successful commercialization of our products is subject to many risks and uncertainties, including the impact of a global pandemic on the successful commercialization in the US, as well as the successful commercialization efforts for our products through our collaborative partners.
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We also do not know how physicians, patients and payors will respond to our future price increases of our products.
−Removed: Physicians may not prescribe our products
−Removed: and patients may be unwilling to use our products if coverage is not provided or reimbursement is inadequate to cover a significant portion of the cost.
+Added: Physicians may not prescribe our products and patients may be unwilling to use our products if coverage is not provided or reimbursement is inadequate to cover a significant portion of the cost.
Our products compete, and may in the future compete, with currently existing therapies, including generic drugs, and products currently under development.
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• acceptance by physicians, the medical community and patients of the product as a safe and effective treatment;
−Removed: ● potential future impacts, if any, due to the effects of a global pandemic and the global tensions arising from the Russian-Ukrainian war and Hamas-Israel war;
+Added: • potential future impacts, if any, due to the effects of a global pandemic and the global tensions arising from geopolitical conflicts, including the ongoing Russia-Ukraine war and the Hamas-Israel and Iran conflicts, as well as other conflicts in the Middle East;
• the ability to distinguish safety and efficacy from existing, less expensive generic alternative therapies, if any;
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• the cost of treatment in relation to alternative treatments, including any similar generic treatments;
−Removed: ● pricing and the availability of coverage and adequate reimbursement by third-party payors and government authorities;
+Added: • pricing and the availability and timing of coverage and adequate reimbursement by third-party payors and government authorities and the process for obtaining or re-obtaining such coverage;
• a positive HTA concluding that the product is cost-effective and the HTA bodies issuing a positive recommendation for the use of the product as a first or second line of treatment for the granted therapeutic indication;
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• the effectiveness of sales and marketing efforts.
−Removed: If we are unable to sustain anticipated level of sales growth from our products, or if we fail to achieve anticipated product royalties and collaboration milestones, we may need to reduce our operating expenses, access other sources of cash or otherwise modify our business plans, which could have a negative impact on our business, financial condition and results of operations.
−Removed: For example, during 2021, we experienced lower than anticipated sales of our products due to continuing impacts of physician and patient access issues created by the COVID-19 pandemic.
+Added: If we are unable to sustain anticipated level of sales growth from our products, or if we fail to achieve anticipated product royalties and collaboration milestones, we may need to reduce our operating expenses, access other sources of cash or otherwise modify our business plans, which could have a negative impact on our business, financial condition and
+Added: results of operations.
From time to time, our net product sales are negatively impacted by the decrease in level of inventories remaining at our distribution channels.
+Added: Our product revenues are subject to seasonal variability, including in the first quarter of each year, due to changes in patient out-of-pocket costs and access dynamics.
+Added: At the beginning of the year, patients enrolled in commercial and government insurance plans may experience deductible and co-payment resets, and Medicare beneficiaries may re-enter cost-sharing phases, which can increase out-of-pocket costs and adversely affect patient demand, initiation of therapy and adherence.
+Added: In addition, annual re-enrollment processes, prior authorization renewals and coverage re-verification may result in temporary delays or interruptions in patient access to our products.
+Added: These factors have caused and may continue to cause variability in our revenues between reporting periods, including lower net product sales in the first quarter relative to subsequent quarters.
+Added: We depend on a limited number of wholesale distributors for the distribution of our products, and the loss of, or significant disruption at, any of these distributors could adversely affect our business.
+Added: The loss of any of these distributors, or a material reduction in their purchases, could materially and adversely affect our product sales and results of operations.
+Added: In addition, consolidation among wholesale distributors could increase their bargaining power and reduce our margins.
We also may not be successful entering into arrangements with third parties to sell and market one or more of our product candidates or may be unable to do so on terms that are favorable to us.
−Removed: We likely will have little control over such third parties, including development and commercialization of fostamatinib in Kissei, Grifols, Medison and Knight’s territories, and of olutasidenib in Kissei and Dr.
+Added: We have limited control over such third parties, including development and commercialization of fostamatinib in Kissei, Grifols, Medison and Knight’s territories, and of olutasidenib in Kissei and Dr.
Reddy’s territories.
−Removed: As a consequence of our license
−Removed: agreements with our collaboration partners, we rely heavily upon their regulatory, commercial, medical affairs, market access and other expertise and resources for commercialization of our products in their respective territories outside of the US.
+Added: As a consequence of our license agreements with our collaboration partners, we rely heavily upon their regulatory, commercial, medical affairs, market access and other expertise and resources for commercialization of our products in their respective territories outside of the US.
We cannot control the amount of resources that our partners dedicate to the commercialization of our products, and our ability to generate revenues from the commercialization of our products by our partners depends on their ability to achieve market acceptance of our products in its approved indications in their respective territories.
−Removed: Furthermore, foreign sales of our products by our partners could be adversely affected by the imposition of governmental controls, political and economic instability, outbreaks of pandemic diseases, such as the COVID-19 pandemic, trade restrictions or barriers and changes in tariffs and escalating global trade and political tensions.
−Removed: If our collaborators are unable to successfully complete clinical trials, delay commercialization of our products or do not invest the resources necessary to successfully commercialize our products in international territories where it has been approved, this could reduce the amount of revenue we are due to receive under these license agreements, resulting in harm to our business and operations.
+Added: Furthermore, foreign sales of our products by our partners could be adversely affected by the imposition of governmental controls, political and economic instability, outbreaks of pandemic diseases, trade restrictions or barriers and changes in tariffs and escalating global trade and political tensions.
+Added: If our collaborators are unable to successfully complete clinical trials, delay commercialization of our products or do not invest the resources necessary to successfully commercialize our products in international territories where they have been approved, this could reduce the amount of revenue we are due to receive under these license agreements, resulting in harm to our business and operations.
If we do not establish and maintain sales and marketing capabilities successfully, either on our own or in collaboration with third parties, we will not be successful in commercializing our product candidates.
17 unchanged sentences
On January 12, 2025, the new HTA Regulation, Regulation No 2021/2282 on Health Technology Assessment (HTA Regulation) started applying to new cancer medicines and advanced therapy medicinal products, and imposes a new procedure for the assessment of the pricing and reimbursement of medicinal products.
−Removed: The HTA Regulation intends to foster cooperation among EU member states in assessing health technologies and provide a procedure for joint clinical assessments of medicinal products at a centralized level.
+Added: The HTA Regulation intends to foster cooperation among EU member states in assessing health technologies and provides a procedure for joint clinical assessments of medicinal products at a centralized level.
It requires companies applying for products in scope to make relevant submissions for the joint clinical assessment, in line with a number of prespecified criteria.
−Removed: By 2030 it will
−Removed: apply to all medicinal products.
+Added: By 2030 it will apply to all medicinal products.
In some foreign markets, prescription pharmaceutical pricing remains subject to continuing governmental control even after initial approval is granted.
17 unchanged sentences
Maintaining our sales, marketing, market access and product distribution capabilities requires significant resources, and there are numerous risks involved with managing our commercial team, including our potential inability to successfully train, retain and incentivize adequate numbers of qualified and effective sales and marketing personnel.
−Removed: We are also competing for talent with numerous commercial and pre-commercial-stage oncology-focused biotechnology companies seeking to build out their commercial organizations, as well as other large pharmaceutical organizations that have extensive, well-funded and more experienced sales and marketing operations, and we may be unable to maintain or
−Removed: adequately scale our commercial organization as a result of such competition.
+Added: We are also competing for talent with numerous commercial and pre-commercial-stage oncology-focused biotechnology companies seeking to build out their commercial organizations, as well as other large pharmaceutical organizations that have extensive, well-funded and more experienced sales and marketing operations, and we may be unable to maintain or adequately scale our commercial organization as a result of such competition.
If we cannot maintain effective sales, marketing, market access, and product distribution capabilities, we may be unable to realize the commercial potential of our products.
8 unchanged sentences
For example, in June 2022, we announced that the top-line results from our Phase 3 trial in wAIHA did not demonstrate statistical significance in the primary efficacy endpoint of durable hemoglobin response in the overall study population.
−Removed: While we conducted an in-depth analysis of these data to better understand differences in patient characteristics and outcomes and submitted these findings to the FDA, in October 2022, we announced that we received guidance from the FDA of these findings.
Based on the result of the trial and the guidance from the FDA, we did not file an sNDA for wAIHA.
18 unchanged sentences
Further, evolving FDA standards may cause additional setbacks.
−Removed: In 2023, FDA published guidance documents and a final rule which all concern clinical trial requirements.
−Removed: In June 2023, FDA published a draft guidance, E6(R3) Good Clinical Practice, which seeks to unify standards for clinical trial data for the International Council for Harmonisation of Technical Requirements of Pharmaceuticals for Human Use member countries and regions.
−Removed: In August 2023, FDA published a guidance document, Informed Consent, Guidance for IRBs, Clinical Investigators, and Sponsors, which supersedes past guidance and finalizes draft guidance on informed consent.
−Removed: Further, in December 2023, FDA published a final rule, Institutional Review Board Waiver or Alteration of Informed Consent for Minimal Risk Clinical Investigations, which allows exceptions from informed consent requirements when a clinical investigation poses no more than minimal risk to the human subject and includes appropriate safeguards to protect the rights, safety, and welfare of human subjects.
Alterations to clinical trial requirements, including due to judicial challenges, may affect recruitment and retention of patients and may hinder or delay a clinical trial.
6 unchanged sentences
Any significant deterioration in the US economy would likely affect the operation of our business and ability to raise capital.
−Removed: In addition, US debt ceiling and budget deficit concerns have increased the possibility of additional credit-rating downgrades and economic slowdowns, or a recession in the US.
+Added: In addition, concerns regarding the US federal debt ceiling and budget deficit have increased the risk of credit-rating downgrades and economic slowdowns, or a recession in the US.
Although US lawmakers passed legislation to raise the federal debt ceiling on multiple occasions, ratings agencies have lowered or threatened to lower the long-term sovereign credit rating on the US.
The impact of this or any further downgrades to the US government’s sovereign credit rating or its perceived creditworthiness could adversely affect the US and global financial markets and economic conditions.
−Removed: The global financial markets and economy may also be adversely affected by the current or anticipated impact of military conflict, including the ongoing Russian-Ukrainian war, and the Hamas-Israel war, terrorism or other geopolitical events.
−Removed: Sanctions imposed by the US and other countries in response to such conflicts, including the Russian-Ukrainian war and the Hamas-Israel war, may also adversely impact the financial markets and the global economy, and any economic countermeasures by the affected countries or others could exacerbate market and economic instability.
+Added: The global financial markets and economy may also be adversely affected by the current or anticipated impact of geopolitical conflict, including the ongoing Russian-Ukrainian war, and the Hamas-Israel conflict, which is currently subject to a fragile ceasefire with ongoing hostilities and risk of renewed escalation, as well as the conflict involving Iran and other actors in the Middle East and the potential for those conflicts to escalate even further.
+Added: The conflict involving Iran, including military actions by the US and Israel and retaliatory responses across the region has contributed to significant volatility in global energy markets, disruptions to key shipping routes such as the Strait of Hormuz, and broader instability in commodity prices and supply chains.
+Added: These developments have led to increased oil and gas prices, heightened inflationary pressures, and volatility in global equity and debt markets, and may continue to affect global economic growth.
+Added: Continued or increased disruptions to critical infrastructure and trade routes, as well as the potential for further regional escalation, could exacerbate these impacts and contribute to prolonged economic uncertainty, including risks of stagflation or recession in certain markets.
+Added: Sanctions imposed by the US and other countries in response to such conflicts, including those targeting Iran, Russia, and other affected regions, may further adversely impact the financial markets and the global
+Added: In addition, any retaliatory actions, countermeasures, or expansion of hostilities, whether through direct military engagement, cyber activity, or disruption of global trade and energy supplies, could intensify market volatility and economic instability.
The US government has indicated its intent to alter its approach to international trade policy and in some cases to renegotiate, or potentially terminate, certain existing bilateral or multi-lateral trade agreements and treaties with foreign countries.
1 unchanged sentence
Related to this action, certain foreign governments have instituted tariffs on certain US goods.
+Added: Recently imposed US tariffs on patented pharmaceutical products and their ingredients could increase our costs and adversely affect our business.
+Added: On April 2, 2026, President Trump issued a Proclamation under Section 232 of the Trade Expansion Act of 1962 imposing a 100% ad valorem tariff on imports of patented pharmaceutical products and associated pharmaceutical ingredients.
+Added: For the 17 large pharmaceutical companies identified in Annex III of the Proclamation, the tariffs become effective on July 31, 2026;
+Added: for all other importers, including smaller pharmaceutical companies that rely on contract manufacturers, the tariffs become effective on September 29, 2026.
+Added: The Proclamation provides for reduced tariff rates in certain circumstances.
+Added: The Proclamation also provides for a 0% tariff rate on certain specialty pharmaceutical products, including drugs for which all approved indications carry orphan drug designation under the Orphan Drug Act, subject to certain conditions, including that the products are from countries that have entered into trade agreements with the US or meet an urgent public health need.
+Added: Each of our three commercial products has received orphan drug designation from the FDA for its approved indications.
+Added: However, we cannot provide assurance that our products will qualify for the orphan drug exemption, as the exemption is subject to US government determinations that have not yet been made, and the scope and application of the exemption remain uncertain.
+Added: We rely on third-party contract manufacturers, certain of which are located outside the United States or source raw materials, including active pharmaceutical ingredients and excipients, from foreign countries that may be subject to tariffs under the Proclamation.
+Added: To the extent the tariffs apply to our products or their inputs, they could significantly increase our cost of product sales, reduce our gross margins, and adversely affect our results of operations.
+Added: We may be unable to pass increased costs on to our customers or patients, and we may not be able to identify alternative suppliers or manufacturing arrangements on acceptable terms or in a timely manner.
+Added: In addition, the tariffs could increase the cost of our research and development activities to the extent we rely on imported materials for clinical supply manufacturing.
+Added: The Proclamation may also affect our collaboration partners outside the US.
+Added: Certain of our partners import and commercialize our products in territories that may be subject to retaliatory trade measures, which could adversely affect their ability to commercialize our products and reduce the royalty and milestone revenues we receive under our collaboration agreements.
+Added: The full impact of the Proclamation on our business will depend on factors including the final determinations regarding orphan drug and other exemptions, the outcome of any legal challenges to the Proclamation, and whether additional tariff actions are taken.
It remains unclear what the US Administration or foreign governments will or will not do with respect to tariffs or other international trade agreements and policies.
−Removed: A trade war or other governmental action related to tariffs or international trade agreements or policies has the potential to disrupt our research activities, affect our suppliers and/or the US or global economy or certain sectors thereof and, thus, could adversely impact our businesses.
−Removed: Bank failures or other events affecting financial institutions could adversely impact our liquidity and other business.
−Removed: Financial institutions have recently experienced, and may experience in the future, industry instability and failures which have led to disruptions in access to bank deposits or lending commitments.
−Removed: In 2023, the closures of Silicon Valley Bank (SVB) and Signature Bank and their placement into receivership with the Federal Deposit Insurance Corporation (FDIC), as well as the FDIC’s seizure and sale of First Republic Bank, created bank-specific and broader financial institution liquidity risk and concerns.
−Removed: On March 12, 2023, federal regulators announced that the FDIC would complete its resolution of SVB in a manner that fully protects all depositors.
−Removed: On March 27, 2023, First Citizens Bank (FCB) announced that it has entered into an agreement with FDIC to purchase all of the asset and liabilities of SVB.
−Removed: Customers of SVB automatically become customers of FCB following the acquisition.
−Removed: We maintain a depository relationship with SVB/FCB and other banking institutions.
−Removed: All of our cash deposits are accessible to us, and we do not anticipate any losses with respect to such funds.
−Removed: Since the March 2023 financial institution failure, there has been a heightened risk and greater focus on the potential failures of other banks in the future.
−Removed: If these banks fail in the future, we may not be able to immediately (or ever) recover our cash in excess of the FDIC insured limits which would adversely impact our operating liquidity and could negatively impact our operations, results of operations and financial performance.
−Removed: Although we believe our exposure is limited, if in the future any of the financial institutions that we maintain depository or lending relationships were to be placed into receivership, we may be unable to access such funds to meet our working capital requirements.
−Removed: In addition, if any of our customers, suppliers or other parties with whom we conduct business are unable to access funds, 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: Although we assess our banking and customer 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 impacted by factors that affect us, the financial institutions with which we have credit agreement or arrangements directly, or the financial services industry or economy in general.
+Added: A trade war or further governmental action related to tariffs or international trade agreements or policies has the potential to disrupt our research activities, affect our suppliers and/or the US or global economy or certain sectors thereof and, thus, could adversely impact our businesses.
Shareholder activism and private securities-related litigation could cause material disruption to our business.
1 unchanged sentence
Responding to proxy contests and other actions by such activist investors or others in the future could be costly and time-consuming, disrupt our operations and divert the attention of our Board of Directors and senior management from the pursuit of our business strategies, which could adversely affect our results of operations and financial condition.
−Removed: There is a growing emphasis from select investors, regulators, and other stakeholders on corporate responsibility, particularly regarding ESG factors.
−Removed: Some investors and advocacy groups utilize these factors to shape investment strategies, potentially opting out of investing in our company if they perceive our corporate responsibility policies as insufficient.
−Removed: Third-party providers offering corporate responsibility ratings and reports have surged to meet rising investor demand, with numerous organizations evaluating companies on ESG matters, and these evaluations receive widespread attention.
−Removed: A low ESG or sustainability rating from such providers could lead certain investors to overlook our common stock in favor of competitors.
−Removed: Institutional investors, in particular, use these ratings to compare companies, and any perceived lag in our ESG efforts might prompt voting decisions or other actions to hold our Board of Directors accountable.
−Removed: Furthermore, evolving assessment criteria for corporate responsibility practices may raise expectations, compelling us to undertake costly initiatives to meet new standards.
−Removed: Failure to meet these evolving criteria
−Removed: could reinforce the perception of inadequate corporate responsibility policies.
−Removed: Non-compliance could also lead to reputational damage if our procedures or standards fall short of stakeholder expectations.
+Added: There is increasing focus from investors, regulators and other stakeholders on corporate responsibility, including ESG factors, which could adversely affect our business.
+Added: Certain investors and advocacy groups use ESG criteria to inform investment and voting decisions, and may choose not to invest in, or take actions against, companies they perceive as having inadequate ESG practices.
+Added: In addition, third-party ESG ratings are widely used to evaluate companies, and a low or declining rating could negatively impact investor interest in our common stock.
+Added: Evolving ESG standards and expectations may also require us to incur additional costs to implement new policies, procedures or initiatives.
+Added: At the same time, there is increasing political and regulatory scrutiny of ESG practices, including actions by the US federal government, state officials and courts that seek to limit or challenge ESG-related initiatives.
+Added: These developments have contributed to a fragmented and rapidly evolving regulatory and litigation landscape, and may expose us to additional legal, compliance and reputational risks regardless of our approach to ESG.
+Added: Any of these factors could adversely affect our reputation, investor
+Added: base and access to capital, and could materially and adversely affect our business, financial condition and results of operations.
Securities-related class action lawsuits and/or derivative lawsuits have often been brought against companies, including biotechnology and biopharmaceutical companies, that experience volatility in the market price of their securities.
16 unchanged sentences
Our Bylaws provide that, unless we consent in writing to the selection of an alternative forum, the Court of Chancery of the State of Delaware shall be the sole and exclusive forum for (i) any derivative action or proceeding brought on behalf of us under Delaware law, (ii) any action asserting a claim of breach of a fiduciary duty by any current or former director, officer, or other employee of ours that is owed to us or our stockholders, (iii) any action asserting a claim against us or any of our directors, officers, or other employees arising pursuant to any provision of the DGCL or our Amended and Restated Certificate of Incorporation and our Bylaws (as either may be amended from time to time), (iv) any action asserting a claim against us governed by the internal affairs doctrine, or (v) any other action asserting an “internal corporate claim,” as defined under Section 115 of the DGCL.
−Removed: The forgoing provisions do not apply to any claims arising under the Securities Act and, unless we consent in writing to the selection of an alternative forum, the federal district courts of the United States will be the sole and exclusive forum for resolving any action asserting a claim
−Removed: arising under the Securities Act.
−Removed: These choice of forum provisions may limit a stockholder’s ability to bring a claim in a judicial forum that it finds favorable for disputes with us or any of our current or former directors, officers, or other employees, which may discourage lawsuits with respect to such claims.
+Added: The forgoing provisions do not apply to any claims arising under the Securities Act and, unless we consent in writing to the selection of an alternative forum, the federal district courts of the United States will be the sole and exclusive forum for resolving any action asserting a claim arising under the Securities Act.
+Added: These choice of forum provisions may limit a stockholder’s ability to bring a claim in a judicial forum that it finds favorable for disputes with us or any of our current or former directors, officers, or other employees, which may discourage
+Added: lawsuits with respect to such claims.
There is uncertainty as to whether a court would enforce such provisions, and the enforceability of similar choice of forum provisions in other companies’ charter documents has been challenged in legal proceedings.
19 unchanged sentences
The insurance we maintain may not be adequate to cover our losses resulting from disasters or other business interruptions.
−Removed: Unregistered Sales of Equity Securities and Use of Proceeds
−Removed: Defaults Upon Senior Securities
−Removed: Mine Safety Disclosures
−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.