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Risk Factor Summary
−Removed: ● Our prospects are highly dependent on our first commercial product, TAVALISSE ® (fostamatinib disodium hexahydrate) and our recently launched second commercial product, REZLIDHIA ™ (olutasidenib).
−Removed: To the extent that the commercial success of our products in the US and respective territories outside of the US is diminished or is not commercially successful, our business, financial condition and results of operations may be adversely affected, and the price of our common stock may decline.
−Removed: ● We may not be able to successfully develop or commercialize our product candidates if problems arise in the clinical testing and approval process.
+Added: ● Our prospects are highly dependent on our commercial products, TAVALISSE ® (fostamatinib disodium hexahydrate) and REZLIDHIA ™ (olutasidenib).
+Added: To the extent that the commercial success of our products in the US and respective territories outside of the US is diminished or halted, our business, financial condition and results of operations may be adversely affected, and the price of our common stock may decline.
+Added: ● We may not be able to successfully develop or commercialize our product candidates if problems arise in the clinical testing and/or approval process.
There is a high risk that drug discovery and development efforts might not generate successful product candidates.
−Removed: If the results of our clinical trials do not meet the primary efficacy endpoints, or if the top-line data from the results of our clinical trials may not ultimately meet the requirements for an NDA approval by the FDA and other national regulatory authorities, the commercial prospects of our business may be harmed, and our ability to generate product revenues may be delayed or eliminated.
−Removed: ● Even if we, or any of our collaborative partners, are able to continue to commercialize our products or any product candidate that we, or they, develop, the product may become subject to unfavorable pricing regulations, unfavorable health technology assessments (HTA) assessment, third-party payor reimbursement practices or labeling restrictions, all of which may vary from country to country and any of which could harm our business.
+Added: If the results of our clinical trials do not meet the primary efficacy endpoints, or if the top-line data from the results of our clinical trials may not ultimately meet the requirements for an NDA approval by the FDA and other regulatory authorities, the commercial prospects of our business may be harmed, and our ability to generate product revenues may be delayed or eliminated.
+Added: ● Even if we, or any of our collaborative partners, are able to continue to commercialize our products or any product candidate that we, or they, develop, the product may become subject to unfavorable pricing regulations, unfavorable health technology assessments (HTA) , third-party payor reimbursement practices or labeling restrictions, all of which may vary from country to country and any of which could harm our business.
● If we are unable to successfully market and distribute our products and retain experienced commercial personnel, our business will be substantially harmed.
−Removed: ● Our business was adversely affected and could be materially and adversely affected in the future by the evolving effects of the COVID-19 pandemic as a result of the potential future impacts on our 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: ● 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.
+Added: ● We are subject to stringent and evolving healthcare regulatory, 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, audits, fines, penalties, and claims, any of which may have a material adverse effect on our business, financial condition, results of operations or prospects.
● If manufacturers obtain approval for generic versions of our products, or of products with which we compete, our business may be harmed.
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● We rely and may continue to rely on third party distribution facilities for the sale of our products and potential sale of any of our product candidates.
−Removed: If any or all of them become subject to adverse findings from inspections or face other difficulties to operate, then the distribution of our products may be interrupted or otherwise
−Removed: adversely affected.
+Added: If any or all of them become subject to adverse findings from inspections or face other difficulties to operate, then the distribution of our products may be interrupted or otherwise adversely affected.
● We lack the capability to manufacture compounds for clinical development and we intend to rely on third parties for commercial supply, manufacturing and distribution, if any, of our product candidates which receive regulatory approval and we may be unable to obtain required material or product in a timely manner, at an acceptable cost or at a quality level required to receive regulatory approval.
−Removed: ● 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 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 will 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.
+Added: ● 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 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 may be diminished, and the capital necessary to fund our operations will be increased.
● 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.
−Removed: ● Our success is dependent on intellectual property rights held by us and third parties, and our interest in such rights is complex and uncertain.
+Added: ● Our success is dependent on intellectual property and data exclusivity and similar regulatory rights held by us and third parties, and our interest in such rights is complex and uncertain.
● If a dispute arises regarding the infringement or misappropriation of the proprietary rights of others, such dispute could be costly and result in delays in our research and development activities, partnering and commercialization activities.
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We may not be able to accomplish these tasks or successfully manage our operations and, accordingly, may not achieve our research, development, and commercialization goals.
−Removed: Our failure to accomplish any of these goals, including as a result of business or other interruptions resulting from the potential future impacts of the COVID-19 pandemic, if any, could adversely affect our business and operations.
+Added: Our failure to accomplish any of these goals, including as a result of business or other interruptions resulting from, if any, potential future impacts of a pandemic or global economic slowdown, could adversely affect our business and operations.
There is a high risk that drug discovery and development efforts might not generate successful product candidates.
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Based on the result of the trial and the guidance from the FDA, we did not file an sNDA for this indication.
−Removed: Further, we have our Phase 3 clinical trial to evaluate safety and efficacy of fostamatinib in hospitalized COVID-19 patients which we launched in November 2020.
−Removed: In July 2022, we completed the enrollment on this trial, and on November 1, 2022, we announced the top-line results of the clinical trial.
−Removed: The trial approached but did not meet statistical significance in the primary efficacy endpoint.
−Removed: All prespecified secondary endpoints in the trial numerically favored fostamatinib over placebo, including mortality, time to sustained recovery, change in ordinal scale assessment, and number of days in the ICU.
−Removed: We are evaluating the opportunity and discussing next steps with the FDA and in collaboration with our partner, the US Department of Defense.
+Added: Further, we may experience errors in the analysis of our clinical trial results.
+Added: For example, we conducted our Phase 3 clinical trial to evaluate safety and efficacy of fostamatinib in hospitalized COVID-19 patients which we launched in November 2020 and completed the enrollment on this trial in July 2022.
+Added: We previously announced in November 2022 the top-line results did not meet statistical significance in the primary efficacy endpoint.
+Added: Upon further analysis, we discovered an error by the CRO in the application of a statistical stratification factor.
+Added: After correcting for this statistical error, the primary endpoint of the study was met.
+Added: However, given the end of the federal COVID-19 PHE in May 2023, and based on feedback from the FDA, US Department of Defense and other advisors regarding the program’s regulatory requirements, costs, timeline and potential for success, we decided not to submit an EUA or sNDA.
If the results of our clinical trials fail to meet the primary efficacy endpoints, or otherwise do not ultimately meet the requirements for an NDA approval by the FDA, the commercial prospects of our business may be harmed, our ability to generate product revenues may be delayed or eliminated or we may be forced to undertake other strategic alternatives that are in our shareholders’ best interests, including cost reduction measures.
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In particular, the promotion, sales and marketing of healthcare items and services, as well as certain business arrangements in the healthcare industry, are subject to extensive laws and regulations intended to prevent fraud, misconduct, bribery kickbacks, self-dealing and other abusive or inappropriate practices.
−Removed: 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, commission compensation, certain customer incentive programs, certain patient support offerings, and other business
−Removed: arrangements generally.
+Added: These laws and regulations may restrict or prohibit
+Added: a wide range of pricing, discounting, marketing and promotion, including promoting off-label uses of our products, commission compensation, certain customer incentive programs, certain patient support offerings, and other business arrangements generally.
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.
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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
−Removed: process, and we may be required to put in place additional mechanisms to ensure compliance with the new privacy and information security requirements.
+Added: In many jurisdictions, enforcement actions, litigation, and other consequences for noncompliance with privacy and
+Added: information security laws and regulations are rising.
+Added: 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.
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.
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In the event of non-compliance, the EU GDPR provides for robust regulatory enforcement and fines of up to €20 million or 4% of the annual global revenue, whichever is greater.
−Removed: In addition, the EU GDPR confers a private right of action on data subjects and consumer associations to lodge complaints with supervisory authorities, seek judicial remedies and obtain compensation for damages resulting from violations of the EU GDPR.
+Added: In addition, the EU GDPR confers a private right of action on data subjects and consumer associations to lodge complaints with supervisory authorities, seek judicial remedies and obtain compensation for
+Added: damages resulting from violations of the EU GDPR.
European data protection laws, including the EU GDPR, generally also restrict the transfer of personal information from Europe to the US and most other countries that are not recognized as having “adequate” data protection laws unless the parties to the transfer have implemented specific safeguards to protect the transferred personal information.
One of the primary safeguards allowing US companies to import personal information from Europe has been certification to the EU-US Privacy Shield and Swiss-US Privacy Shield frameworks administered by the US Department of Commerce.
−Removed: However, the Court of Justice of the European Union (CJEU) issued a decision in July 2020 invalidating the EU-US Privacy Shield framework as a data transfer mechanism ( Schrems II ) and imposing further restrictions on the use of standard contractual clauses (SCCs), including a requirement for companies to carry out a transfer privacy impact assessment, which, among other things, assesses laws governing access to personal information in the recipient country and considers whether supplementary measures that provide privacy protections additional to those provided under the SCCs will need to be implemented to ensure an essentially equivalent level of data protection to that afforded in Europe.
−Removed: Following that decision, the Swiss Federal Data Protection and Information Commissioner (FDPIC) took a similar view and considered that data transfers based on the Swiss-US Privacy Shield framework are no longer lawful (despite the fact that Schrems II is not directly applicable in Switzerland (unless the Swiss based company is subject to the EU GDPR) and the Swiss-US Privacy Shield has not been officially invalidated).
−Removed: Further, the EC published new EU SCCs in June 2022, which place onerous obligations on the contracting parties.
−Removed: At present, there are few, if any, viable alternatives to the SCCs.
−Removed: However, on October 7, 2022, the US President introduced an Executive Order to facilitate a new Trans-Atlantic Data Privacy Framework which will act as a successor to the invalidated Privacy Shield.
−Removed: On December 13, 2022, the EC also published its draft adequacy decision to reflect its view that the new executive order and Trans-Atlantic Data Privacy Framework, is able to meet the concerns raised in Schrems II .
−Removed: If the draft adequacy decision is approved and implemented, the agreement will facilitate the transatlantic flow of personal data and provide additional safeguards to data transfer mechanisms (including EU SCCs and Binding Corporate Rules) for companies transferring personal data from the EU to the US.
−Removed: However, before parties rely on the new framework, there are still legislative and regulatory steps that must be undertaken both in the US and in the EU.
−Removed: As such, any transfers by us or our third-party vendors, collaborators or others of personal information from Europe to the US or elsewhere may not comply with European data protection laws, may increase our exposure to European data protection laws’ heightened sanctions for cross-border data transfer restrictions may restrict our clinical trial activities in Europe and may limit our ability to collaborate with CROs, service providers, contractors and other companies subject to European data protection laws.
+Added: However, the Court of Justice of the European Union (CJEU) issued a decision in July 2020 invalidating the EU-US Privacy Shield framework as a data transfer mechanism ( Schrems II ) and imposing further restrictions on the use of standard contractual clauses (SCCs).
+Added: The SCCs were subsequently updated by the EC and these now place a contractual obligation on the parties, to carry out a transfer privacy impact assessment, which, among other things, assesses laws governing access to personal information in the recipient country and considers whether supplementary measures that provide privacy protections additional to those provided under the SCCs will need to be implemented to ensure an essentially equivalent level of data protection to that afforded in Europe.
+Added: Following that decision, the Swiss Federal Data Protection and Information Commissioner (FDPIC) took a similar view and considered that data transfers based on the Swiss-US Privacy Shield framework are no longer lawful.
+Added: On October 7, 2022, the US President introduced an Executive Order to facilitate a new Trans-Atlantic Data Privacy Framework (DPF) and on July 10, 2023, the EC also adopted its adequacy decision to reflect its view that the new Executive Order and DPF, is able to meet the concerns raised in Schrems II .
+Added: In turn, entities relying on SCCs for transfers to the US are able to rely on the analysis in the EC’s adequacy decision as support for their transfer impact assessments.
+Added: Importantly, the US Department of Commerce has also announced that companies will also immediately be able to self-certify to the UK and Swiss extensions of the DPF, but that the UK component will not be live until the finalization of the separate and ongoing UK-U.S.
+Added: adequacy process.
+Added: Given the above, any transfers by us or our third-party vendors, collaborators or others of personal information from Europe to the US or elsewhere may not comply with European data protection laws, may increase our exposure to European data protection laws’ heightened sanctions for cross-border data transfer restrictions may restrict our clinical trial activities in Europe and may limit our ability to collaborate with CROs, service providers, contractors and other companies subject to European data protection laws.
Loss of our ability to transfer personal information from Europe may also require us to increase our data processing capabilities in those jurisdictions at significant expense.
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The UK Information Commissioner’s Office (ICO) has also published its version of the transfer impact assessment and revised guidance on international transfers, although entities may choose to adopt either the EU or UK style transfer impact assessment.
−Removed: In terms of international data transfers between the UK and US, it is understood that the UK and the US are negotiating an adequacy agreement.
+Added: In terms of international data transfers between the UK and US, as outlined above, there is an ongoing UK-US adequacy process which, once finalized, will extend the DPF to apply also to transfers from the UK.
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.
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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, 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 marketing authorization application dossier for approved medicinal products.
−Removed: Only very limited information is exempted from disclosure, i.e.
−Removed: commercially confidential information (which is construed increasingly narrowly) and protected personal data.
+Added: 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.
+Added: Only very limited information is exempted from disclosure, i.e., commercially confidential information (which is construed increasingly narrowly) and protected personal data.
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.
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We had to deploy resources to enable our field-based employees to continue to engage with health care providers in hybrid virtual and in-person interactions.
−Removed: With respect to clinical development, in response to the COVID-19 pandemic, we have taken, and may continue to take, 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 number of our clinical trial investigators have paused, postponed or delayed new patient enrollment and restricted site visits of existing patients enrolled.
−Removed: Although some sites have resumed patient
−Removed: screening, and we may continue to experience delays in new patient enrollment in the future.
−Removed: We are continuing to make decisions country-by-country to minimize risk to the patients and clinical trial sites.
−Removed: We 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: Patients already enrolled in our studies continue to receive study drugs, and we remain focused on supporting our sites in providing care for these patients and providing continued investigational drug supply.
−Removed: We experienced slower than anticipated enrollment in some of our clinical trials, and in the future, we may experience adverse impact that the COVID-19 pandemic may have 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.
+Added: With respect to clinical development, in response to the COVID-19 pandemic, we had taken, and may continue to take, 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.
+Added: Due to the effects of COVID-19 pandemic, we had experienced a number of our clinical trial investigators either paused, postponed or delayed new patient enrollment and restricted site visits of existing patients enrolled.
+Added: In the event that a global pandemic occurs in the
+Added: future, we may need to make decisions on a country-by-country basis to minimize risk to the patients and clinical trial sites.
+Added: 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.
+Added: 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 impact 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.
Pandemics may cause significant disruption in the supply chain for our commercial products.
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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 financially needy patients.
+Added: To help patients afford our products, we have a manufacturer-sponsored patient assistance program that helps financially needy patients in the US.
This type of program has become the subject of enforcement scrutiny in recent years.
For example, some pharmaceutical manufacturers have been named in class action lawsuits challenging the legality of their patient assistance programs under a variety of federal and state laws.
−Removed: In addition, certain state and federal enforcement
−Removed: authorities have pursued investigations and settlements and members of Congress have initiated inquiries about manufacturer-sponsored patient support programs, including, for example, manufacturer-sponsored patient assistance programs, co-payment assistance programs, and manufacturer contributions to independent charitable patient assistance programs.
+Added: In addition, certain state and federal enforcement authorities have pursued investigations and settlements and members of Congress have initiated inquiries about manufacturer-sponsored patient support programs, including, for example, manufacturer-sponsored patient
+Added: assistance programs, co-payment assistance programs, and manufacturer contributions to independent charitable patient assistance programs.
Moreover, the Department of Health and Human Services, 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.
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On July 25, 2022, we filed a lawsuit in the US District Court for the District of New Jersey against Annora and its affiliates, Hetero Labs Ltd., and Hetero USA, Inc., for infringement of our US patents identified in Annora’s Paragraph IV certification.
−Removed: On September 21, 2022, Annora and its affiliates answered and counterclaimed for
−Removed: declaratory judgment of non-infringement and invalidity of the ’458, ’122, ’492, ’648, and ’504 patents.
+Added: On September 21, 2022, Annora and its affiliates answered and counterclaimed for declaratory judgment of non-infringement and invalidity of the ’458, ’122, ’492, ’648, and ’504 patents.
We filed an answer to Annora’s counterclaims on October 12, 2022.
−Removed: Annora served invalidity and non-infringement contentions on December 31, 2022.
+Added: Annora served invalidity and non-infringement contentions on
+Added: December 31, 2022.
We filed an answer to Annora’s invalidity and non-infringement contentions in March 2023.
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● regulatory authorities may require the addition of labeling statements, specific warnings, contraindications, or field alerts to physicians and pharmacies;
−Removed: ● regulatory authorities may withdraw their approval of the product and require us to take our approved drugs off the market;
+Added: ● regulatory authorities may withdraw their approval of the product and require us to take our approved drugs off the market or suspend their commercialization until the identified issues have been satisfactorily addressed;
● we may be required to change the way the product is administered, conduct additional clinical trials, change the labeling of the product, or implement a Risk Evaluation and Mitigation Strategy (REMS);
−Removed: ● we may have limitations on how we promote our drugs;
+Added: ● we may have additional limitations on how we promote our drugs;
● third-party payors may limit coverage or reimbursement for our products;
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● the willingness of physicians to change their current treatment practices;
+Added: ● any additional support that may be required to administer the treatment to patients;
● the willingness of hospitals and hospital systems to include our product candidates as treatment options;
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We will continue to need additional capital and the amount of future capital needed will depend largely on the success of our commercialization of our products, and the success of our internally developed programs as they proceed in later and more expensive clinical trials, including any additional clinical trials that we may decide to conduct with respect to fostamatinib.
−Removed: 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
−Removed: 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 the COVID-19 pandemic and the conflict in Russia and Ukraine.
+Added: 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,
+Added: if available, we will obtain financing on reasonable terms.
+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 the COVID-19 pandemic and the conflict in Russia and Ukraine.
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 March 31, 2023, the outstanding principal balance of the loan was $60.0 million, and no remaining funds available under the term loan credit facility.
+Added: As of June 30, 2023, the outstanding principal balance of the loan was $60.0 million, and no remaining funds were available under the term loan credit facility.
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.
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Further, climate change may increase both the frequency and severity of extreme weather conditions and natural disasters, which may affect our business operations.
−Removed: If we encounter difficulties with any of our distribution facilities, whether due to the potential future impacts of the COVID-19 pandemic (including as a result of disruptions of global shipping and the transport of products) or otherwise, or other problems or disasters arise, we cannot ensure that critical systems and operations will be restored in a timely manner or at all, and this would have an adverse effect on our business.
+Added: If we encounter difficulties with any of our distribution facilities, whether due to the potential future impacts of a global pandemic (including as a result of disruptions of global shipping and the transport of products) or otherwise, or other problems or disasters arise, we cannot ensure that critical systems and operations will be restored in a timely manner or at all, and this would have an adverse effect on our business.
In addition, growth could require us to further expand our current facility, which could affect us adversely in ways that we cannot predict.
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● the rate of adoption in the particular market, including fluctuations in demand for various reasons;
−Removed: ● potential future impacts, if any, due to the COVID-19 pandemic;
+Added: ● potential future impacts, if any, due to a global pandemic;
● lack of patient and physician familiarity with the drug;
6 unchanged sentences
We make estimates for provisions for sales discounts, returns and allowances.
−Removed: Our estimates are based on available customer and payer data receceived from the specialty pharmacies and distributors, as well as third party market research data.
+Added: Our estimates are based on available customer and payer data received from the specialty pharmacies and distributors, as well as third party market research data.
In part, our estimates are dependent on our distribution channel and payer mix.
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● the progress and success of our clinical trials and preclinical activities (including studies and manufacture of materials) of our product candidates conducted by us;
−Removed: ● potential future impacts, if any, of the evolving COVID-19 pandemic;
+Added: ● potential future impacts, if any, of a global pandemic;
● the costs and timing of regulatory filings and approvals by us and our collaborators;
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Our success as a company is uncertain due to our history of operating losses and the uncertainty of any future profitability.*
−Removed: For the three months ended March 31, 2023, we recognized loss from operations of $12.7 million primarily due to higher operating and non-operating expenses, partly offset by our net product sales and collaboration revenues.
+Added: For the six months ended June 30, 2023, we recognized loss from operations of $18.0 million primarily due to higher operating and non-operating expenses, partly offset by our net product sales and collaboration revenues.
We have historically 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 required to identify and validate new product candidates and pursue our development efforts, and the costs of our ongoing commercial efforts for our products.
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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 March 31, 2023, we had an accumulated deficit of approximately $1.4 billion.
−Removed: The extent of our future losses or profitability, if any, especially due to the COVID-19 pandemic, is highly uncertain.
+Added: As of June 30, 2023, we had an accumulated deficit of approximately $1.4 billion.
+Added: The extent of our future losses or profitability, if any, is highly 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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● obtain patent or other proprietary protection for our new drug compounds and technologies;
+Added: ● obtain access to manufacturing resources of the sufficient standard and scale;
● enter commercialization agreements for our new drug compounds;
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On January 5, 2023, we received notification from the Listing Qualifications Department of the Nasdaq Stock Market LLC that we have regained compliance with the Bid Price Requirement because the closing bid price of our common stock closed at $1.00 or more for over 10 consecutive business days from December 13, 2022 to January 4, 2023.
−Removed: While we have regained compliance, the Nasdaq Stock Market LLC may in the future initiate the delisting process with a notification letter if we were to again fall out of compliance.
+Added: Although we have regained compliance, the Nasdaq Stock Market LLC may in the future initiate the delisting process with a notification letter if we were to again fall out of compliance.
If we were to receive such a notification, we would be afforded a grace period of 180 calendar days to regain compliance with the minimum bid price requirement.
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however, we may be unable to obtain product liability insurance on commercially reasonable terms or in adequate amounts.
−Removed: Our inability to obtain sufficient product liability insurance at an acceptable cost to protect against potential product liability claims could prevent or inhibit the commercialization of pharmaceutical products we develop, alone or with corporate collaborators.
−Removed: We, or our corporate collaborators, might not be able to obtain insurance
−Removed: at a reasonable cost, if at all.
+Added: Our inability to obtain sufficient product liability insurance at an acceptable cost to protect against potential product liability claims could prevent or inhibit the commercialization of pharmaceutical products we
+Added: develop, alone or with corporate collaborators.
+Added: We, or our corporate collaborators, might not be able to obtain insurance at a reasonable cost, if at all.
While under various circumstances we are entitled to be indemnified against losses by our corporate collaborators, indemnification may not be available or adequate should any claim arise.
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We receive, generate and store significant and increasing volumes of personal (including health), confidential and proprietary information.
−Removed: There can be no assurance that we, or our collaborators, CROs, third-party vendors, contractors and consultants will be successful in efforts to detect, prevent, protect against or fully recover systems or data from all break-downs, service interruptions, attacks or breaches.
+Added: There can be no assurance that we, or our collaborators, CROs, third-party vendors, contractors and consultants will be successful in efforts to detect, prevent, protect against or fully recover systems or data from all breakdowns, service interruptions, attacks or breaches.
Any breakdown, cyber-attack or information security breach could result in a disruption of our drug development programs or other aspects of our business.
For example, the loss of clinical trial data from completed or ongoing clinical trials for a product candidate could result in delays in our regulatory approval efforts and significantly increase our costs to recover or reproduce the data.
−Removed: To the extent that any disruption or security breach were to result in a loss of or damage to our data or applications, or inappropriate disclosure of personal, confidential or proprietary information, we could incur liability, incur significant remediation or litigation costs, result in product development delays, disrupt key business operations, cause loss of
−Removed: revenue and divert attention of management and key information technology resources.
+Added: To the extent that any disruption or security breach were to result in a loss of or damage to our data or applications, or inappropriate disclosure of personal, confidential or proprietary information, we could incur liability, incur significant
+Added: remediation or litigation costs, result in product development delays, disrupt key business operations, cause loss of revenue and divert attention of management and key information technology resources.
Hackers and data thieves are increasingly sophisticated and operate large-scale and complex automated attacks, including on companies within the healthcare industry.
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Moreover, on June 16, 2022, the Federal Trade Commission issued a policy statement stating its intension to increase enforcement scrutiny of “exclusionary rebates” to PBMs and other intermediaries that “foreclose competition.” On August 16, 2022, President Biden signed into law the IRA, which, among other reforms, allows Medicare to:
−Removed: beginning in 2026, establish a “maximum fair price” for certain pharmaceutical and biological products covered under Medicare Parts B and D;
+Added: 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;
beginning in 2023, penalize drug companies that raise prices for products covered under Medicare Parts B and D faster than inflation;
and beginning in 2025 impose new discounts obligations on pharmaceutical and biological manufacturers for products covered under Medicare Part D.
+Added: On June 9, 2023, CMS released a list of 43 Medicare Part B products that had an adjusted coinsurance rate based on the inflationary rebate provisions of the IRA for the time period of July 1, 2023 to September 30, 2023.
+Added: Additionally, on June 30, 2023, CMS issued guidance detailing the requirements and parameters of the first round of price negotiations for products subject to the “maximum fair price” provision.
+Added: This negotiation process will occur during 2023 and 2024 and result in maximum prices that will be effective beginning in 2026.
+Added: It is unclear how future regulatory actions to implement the IRA may affect our products and future profitability.
The Biden administration has also taken executive action to address drug pricing and other healthcare policy changes .
−Removed: For example, in response to a July 9, 2021 Executive Order from President Biden that included several prescription drug initiatives, on September 9, 2021, the Department of Health and Human Services issued a Comprehensive Plan for Addressing High Drug Prices that identified potential legislative policies and administrative tools that Congress and the agency can pursue in order to make drug prices more affordable and equitable, improve and promote competition throughout the prescription drug industry, and foster scientific innovation.
−Removed: Additionally, on September 12, 2022, President Biden issued an Executive Order to promote biotechnology and biomanufacturing innovation.
+Added: For example, on September 12, 2022, President Biden issued an Executive Order to promote biotechnology and biomanufacturing innovation.
The Order noted several methods through which the Biden Administration would support the advancement of biotechnology and biomanufacturing in healthcare, and instructed the Department of Health and Human Service to submit, within 180 days of the Order, a report assessing how to use biotechnology and biomanufacturing to achieve medical breakthroughs, reduce the overall burden of disease, and improve health outcomes.
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The Executive Order further directed the Secretary of the Department of Health and Human Services to submit, within 90 days after the date of the Executive Order, a report regarding any models that may lead to lower cost-sharing for commonly used drugs and support value-based payment that promotes high-quality care.
−Removed: On February 14, 2023, the Department of Health and Human Services issued a report in response to the October 14, 2022, Executive Order, which, among other things, selects three potential drug affordability and accessibility models to be tested by the CMS Innovation Center.
+Added: On February 14, 2023, the Department of Health and Human Services issued a report in response to the October 14, 2022, Executive Order, which, among other things,
+Added: selects three potential drug affordability and accessibility models to be tested by the CMS Innovation Center.
Specifically, the report addresses:
−Removed: (1) a model that would allow Part D Sponsors to
−Removed: establish a “high-value drug list” setting the maximum co-payment amount for certain common generic drugs at $2;
+Added: (1) a model that would allow Part D Sponsors to establish a “high-value drug list” setting the maximum co-payment amount for certain common generic drugs at $2;
(2) a Medicaid-focused model that would establish a partnership between CMS, manufacturers, and state Medicaid agencies that would result in multi-state outcomes-based agreements for certain cell and gene therapy drugs;
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If we are not able to obtain FDA approval for any desired future indications for our products and product candidates, our ability to effectively market and sell our products may be reduced and our business may be adversely affected.
−Removed: While physicians may choose to prescribe drugs for uses that are not described in the product’s labeling and for uses that differ from those tested in clinical studies and approved by the regulatory authorities, our ability to promote the products is limited to those indications and patient populations that are specifically approved by the FDA.
−Removed: label” uses are common across medical specialties and may constitute an appropriate treatment for some patients in varied circumstances.
+Added: While physicians may choose to prescribe drugs for uses that are not described in the product’s labeling and for
+Added: uses that differ from those tested in clinical studies and approved by the regulatory authorities, our ability to promote the products is limited to those indications and patient populations that are specifically approved by the FDA.
+Added: These “off-label” uses are common across medical specialties and may constitute an appropriate treatment for some patients in varied circumstances.
We have implemented compliance and monitoring policies and procedures, including a process for internal review of promotional materials, to deter the promotion of our products for off-label uses.
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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 the COVID-19 pandemic, the Russian-Ukrainian conflict 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, the Russian-Ukrainian conflict 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 the COVID-19 pandemic, the Russian-Ukrainian conflict 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, the Russian-Ukrainian conflict or otherwise, 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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Moreover, these third-party investigators and organizations may also have relationships with other commercial entities, some of which may compete with us.
−Removed: If these third-party investigators and organizations assist our competitors at our expense, it could harm our competitive position.
−Removed: Due to the evolving effects of the COVID-19 pandemic, for several of our development programs, we had experienced and may continue to experience disruption or delay in our ability to enroll and assess patients, maintain patient enrollment, supply study drug, report trial results, or interact with regulators, ethics committees or other important agencies due to limitations in employee resources or otherwise.
−Removed: In addition, some patients 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 who, as healthcare providers, may have heightened exposure to COVID-19 may adversely impact our clinical trial operations.
−Removed: In light of the evolving effects of the COVID-19 pandemic, we had taken measures to implement remote and virtual approaches to clinical development, including remote patient monitoring where possible, and if the COVID-19 pandemic continues and persists for an extended period of time, we could experience significant disruptions to our clinical development timelines, which would adversely affect our business, financial condition, results of operations and growth prospects.
−Removed: We have conducted in the past and are currently conducting clinical trials in the US and outside US including Ukraine and Russia.
+Added: third-party investigators and organizations assist our competitors at our expense, it could harm our competitive position.
+Added: Due to the effects of the COVID-19 pandemic, for several of our development programs, we had experienced disruption or delay in our ability to enroll and assess patients, maintain patient enrollment, supply study drug, report trial results, or interact with regulators, ethics committees or other important agencies due to limitations in employee resources or otherwise.
+Added: 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.
+Added: 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.
+Added: We have conducted in the past and are currently conducting or may conduct in the future clinical trials in the US and outside US including Ukraine and Russia.
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.
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We could also experience disruptions in our supply chain or limits our ability to obtain sufficient materials for our drug products in certain regions.
−Removed: We may not be able to obtain an EUA for fostamatinib for the treatment of hospitalized patients with COVID-19, and, even if we do, absent sNDA approval for that indication, such EUA would be revoked when the COVID-19 emergency terminates.
−Removed: Based on the results of the NIH/NHLBI-sponsored Phase 2 trial, in May 2021, we filed an EUA for the use of fostamatinib for the treatment of hospitalized patients with COVID-19.
−Removed: In August 2021, the FDA informed us that the clinical data submitted from the NIH/NHLBI-sponsored Phase 2 trial of fostamatinib to treat hospitalized patients suffering from COVID-19 was insufficient for EUA.
−Removed: In July 2022, we completed enrollment with 280 patients in our pivotal FOCUS Phase 3 clinical trial evaluating fostamatinib in high-risk patients hospitalized with COVID-19.
−Removed: The trial had originally targeted a total of 308 patients;
−Removed: however, we determined the trial would be sufficiently powered with 280 patients to potentially provide a clinically meaningful result and determine the efficacy and safety of fostamatinib in hospitalized COVID-19 patients.
−Removed: On November 1, 2022, we announced the top-line results of the clinical trial.
−Removed: The trial approached but did not meet statistical significance in the primary efficacy endpoint.
−Removed: All prespecified secondary endpoints in the trial numerically favored fostamatinib over placebo, including mortality, time to sustained recovery, change in ordinal scale assessment, and number of days in the ICU.
−Removed: We are evaluating the opportunity and discussing next steps with the FDA and in collaboration with our partner, the US Department of Defense.
−Removed: Section 564 of the FDCA (21 U.S.C.
−Removed: § 360bbb-3) allows the FDA to authorize the shipment of drugs, biological products, or medical devices that either lack required approval, licensure, or clearance (unapproved products), or are approved but are to be used for unapproved ways to diagnose, treat, or prevent serious diseases or conditions in the event of an emergency declaration by the HHS Secretary.
−Removed: On February 4, 2020, then-HHS Secretary Alex M.
−Removed: Azar II determined that a public health emergency exists for COVID-19 and declared that it justifies the authorization of emergency use of in vitro diagnostics for COVID-19, pursuant to Section 564 of the FDCA.
−Removed: On March 2, 2020, March 24, 2020, and March 27, 2020, Secretary Azar issued corresponding declarations for personal respiratory protective devices;
−Removed: for medical devices, including alternative products used as medical devices;
−Removed: and, for drugs and biological products .
−Removed: The determination and these declarations were published in the Federal Register on February 7, 2020, March 10, 2020, March 27, 2020, and April 1, 2020, respectively.
−Removed: While the emergency determination and declarations are effective, the FDA may authorize the use of an unapproved product or an unapproved use of an approved product if it concludes that:
−Removed: an agent referred to in the emergency declaration could cause a serious or life-threatening disease or condition;
−Removed: it is reasonable to believe that the authorized product may be effective in diagnosing, treating, or preventing that disease or condition or a serious or life-threatening disease or condition caused by an approved product or a product marketed under an EUA;
−Removed: the known and potential benefits of the authorized product, when used for that disease or condition, outweigh known and potential risks, taking into consideration the material threat of agents identified in the emergency declaration;
−Removed: there is no adequate, approved, and available alternative to the authorized product for diagnosing, preventing, or treating the relevant disease or condition;
−Removed: any other criteria prescribed by the FDA is satisfied.
−Removed: Medical products that are granted an EUA are only permitted to commercialize their products under the terms and conditions provided in the authorization.
−Removed: The FDCA authorizes FDA to impose such conditions on an EUA as may be necessary to protect the public health.
−Removed: Consequently, postmarketing requirements will vary across EUAs.
−Removed: In addition, FDA has, on occasion, waived requirements for drugs marketed under an EUA.
−Removed: Generally, EUAs for unapproved products or unapproved uses of approved products require that manufacturers distribute factsheets for healthcare providers, addressing significant known and potential benefits and risk, and the extent to which benefits and risks are unknown, and the fact that FDA has authorized emergency use;
−Removed: and, distribution of factsheets for recipients of the product, addressing significant known and potential benefits and risk, and the extent to which benefits and risks are unknown, the option to accept or refuse the product, the consequences of refusing, available alternatives and the fact that FDA has authorized emergency use.
−Removed: Generally, EUAs for unapproved products and, per FDA’s discretion, EUAs for unapproved uses of approved products, include requirements for adverse event monitoring and reporting, and other recordkeeping and reporting requirements.
−Removed: Note, however, that approved products are already subject to equivalent requirements.
−Removed: In addition, the FDA may include various requirements in an EUA as a matter of discretion as deemed necessary to protect the public health, including restrictions on which entities may distribute the product, and how to perform distribution (including requiring that distribution be limited to government entities), restrictions on who may administer the product, requirements for collection and analysis of safety and effectiveness data, waivers of current good manufacturing practices (cGMP), and restrictions applicable to prescription drugs or restricted devices (including advertising and promotion restrictions).
−Removed: The FDA may revoke an EUA when it is determined that the underlying health emergency no longer exists or warrants such authorization, if the conditions for the issuance of the EUA are no longer met, or if other circumstances make revocation appropriate to protect the public health or safety.
−Removed: We cannot predict how long, if ever, an EUA would remain in place.
−Removed: It is difficult to predict when the determination and declaration will be revoked or ended, which will impact the marketing of products under existing EUAs and the availability of new EUAs based on the determination and declaration.
−Removed: For example, in January 2023, Congress proposed legislation that would end other COVID-19-related emergency declarations, if passed, and the White House has issued a statement that those declarations will end on May 11, 2023.
−Removed: FDA officials have stated that this will not impact FDA’s ability to authorize treatments for emergency use, such that existing EUAs will remain in effect and the agency may continue to issue new EUAs going forward when criteria for issuance are met.
−Removed: This is nonetheless subject to change.
−Removed: We cannot predict with certainty whether the result of our trial will be sufficient for submission of a second application for an EUA for fostamatinib, and we cannot predict whether FDA will grant an EUA for fostamatinib based on the trial data.
−Removed: We also cannot predict how long, if ever, an EUA would remain in place.
−Removed: Our COVID-19 product candidate may not successfully protect against variants of the SARS-CoV-2 virus.
−Removed: As the SARS-CoV-2 virus continues to evolve, new strains of the virus or those that are already in circulation may prove more transmissible or cause more severe forms of COVID-19 disease than the predominant strains to date.
−Removed: There is a risk that any product candidates we develop will not be as effective against variant strains of the SARS-CoV-2 virus expressing variants of the spike protein, particularly strains with mutations in the receptor binding domain and N-terminal domain.
−Removed: Such failure could lead to significant reputational harm, in addition to adversely affecting our financial results.
Public perception of the risk-benefit balance for our COVID-19 product candidates may be affected by adverse events in clinical trials involving our product candidate or other COVID-19 treatments.
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We currently use one active pharmaceutical ingredient manufacturer and one finished goods manufacturer for each of our products.
−Removed: 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.
+Added: We do not currently have, nor do we plan to acquire the infrastructure or capability to supply, manufacture or
+Added: distribute preclinical, clinical or commercial quantities of drug substances or products.
For each clinical trial of our unpartnered product candidates, we rely on third-party manufacturers for the active pharmaceutical ingredients, as well as various manufacturers to manufacture starting components, excipients and formulated drug products.
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Moreover, we may not be able to transfer processes that are proprietary to the manufacturer, if any.
−Removed: These manufacturers may not be able to produce material on a timely basis or manufacture material at the quality level or in the quantity required to meet our development timelines and applicable regulatory requirements and may also experience a shortage in qualified personnel, including due to the impacts of the COVID-19 pandemic.
+Added: These manufacturers may not be able to produce material on a timely basis or manufacture material at the quality level or in the quantity required to meet our development timelines and applicable regulatory requirements and may also experience a shortage in qualified personnel.
Our third-party manufacturers import certain materials from China to produce our products.
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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.
−Removed: Drug manufacturers are subject to ongoing periodic unannounced inspection by the FDA, the Drug Enforcement Administration, the European Medicines Agency, national competent authorities in the EU and UK and other federal and state government and regulatory agencies to ensure strict compliance with cGMP and other government regulations and corresponding foreign standards.
+Added: Drug manufacturers are subject to ongoing periodic unannounced inspection by the FDA, the Drug
+Added: Enforcement Administration, the European Medicines Agency, national competent authorities in the EU and UK and other federal and state government and regulatory agencies to ensure strict compliance with cGMP and other government regulations and corresponding foreign standards.
We do not have control over third-party manufacturers’ compliance with these regulations and standards and they may not be able to comply.
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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 the COVID-19 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.
+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 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.
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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.
−Removed: If we or our suppliers encounter manufacturing, quality or compliance difficulties with respect to our products or any of our product candidates, when and if approved, whether due to the impacts of the COVID-19 pandemic (including as a result of disruptions of global shipping and the transport of products) or otherwise, we may be unable to obtain or maintain regulatory approval or meet commercial demand for such products, which could adversely affect our business, financial conditions, results of operations and growth prospects.
+Added: If we or our suppliers encounter manufacturing, quality or compliance difficulties with respect to our products or any of our product candidates, when and if approved, whether due to the impacts of a global pandemic (including as a result of disruptions of global shipping and the transport of products) or otherwise, we may be unable to obtain or maintain regulatory approval or meet commercial demand for such products, which could adversely affect our business, financial conditions, results of operations and growth prospects.
Promotional communications with respect to prescription drugs are subject to a variety of legal and regulatory restrictions and must be consistent with the information in the product’s approved labeling.
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For example, sales and medical science liaison or MSL personnel, including contractors, must comply with FDA requirements for the advertisement and promotion of products.
−Removed: Fast track designation by the FDA may not actually lead to a faster development or regulatory review or approval process and does not assure FDA approval of our product candidates.
−Removed: If a product candidate is intended for the treatment of a serious or life-threatening condition and the product candidate demonstrates the potential to address unmet medical need for this condition, the sponsor may apply for FDA fast track designation.
−Removed: Fast track designation applies to the combination of the product and the specific indication for which it is being studied.
−Removed: The sponsor of a fast track product has opportunities for more frequent interactions with the review team during product development, and the FDA may consider for review sections of the NDA on a rolling basis before the complete application is submitted, if the sponsor provides a schedule for the submission of the sections of the NDA, the FDA agrees to accept sections of the NDA and determines that the schedule is acceptable, and the sponsor pays any required user fees upon submission of the first section of the NDA.
−Removed: However, fast track designation does not change the standards for approval and does not ensure that the product candidate will receive marketing approval or that approval will be granted within any particular timeframe.
−Removed: As a result, while the FDA has granted fast track designation to fostamatinib for the treatment of wAIHA and/or we may seek and receive fast track designation for our future product candidates, we may not experience a faster development process, review or approval compared to conventional FDA procedures.
−Removed: In addition, the FDA may withdraw fast track designation if it believes that the designation is no longer supported by data from our clinical development program.
−Removed: Fast track designation alone does not guarantee qualification for the FDA’s priority review procedures.
If we are unable to obtain regulatory approval to market products in the US and foreign jurisdictions, we will not be permitted to commercialize products we or our collaborative partners may develop.
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Satisfaction of regulatory requirements typically takes many years, is dependent upon the type, complexity and novelty of the product and requires the expenditure of substantial resources.
−Removed: Of particular significance to us are the requirements relating to research and development and testing.
+Added: Of particular
+Added: significance to us are the requirements relating to research and development and testing.
Before commencing clinical trials in humans in the US, we, or our collaborative partners, will need to submit and receive approval from the FDA of an IND application.
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Apart from our internal discovery efforts, our strategy to expand our development pipeline is also 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, Forma’s proprietary inhibitor of mIDH1, for any uses worldwide, including for the treatment of AML and other malignancies.
−Removed: Forma submitted an NDA for olutasidenib to the FDA with PDUFA action date for the application of February 15, 2023.
+Added: In July 2022, we entered into a license and transition services agreement with Forma (now Novo Nordisk) 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.
On December 1, 2022, the FDA approved REZLIDHIA capsules for the treatment of adult patients with R/R AML with a susceptible IDH1 mutations as detected by and FDA-approved test.
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We may also be unable to in-license or acquire additional relevant product candidates on acceptable terms that would allow us to realize an appropriate return on our investment.
−Removed: If we are unable to develop suitable product candidates through internal discovery efforts, whether due to the impacts of the COVID-19 pandemic or otherwise, or if we are unable to successfully obtain rights to additional suitable product candidates, our business and prospects for growth could suffer.
+Added: If we are unable to develop suitable product candidates through internal discovery efforts, whether due to the impacts of a global pandemic or otherwise, or if we are unable to successfully obtain rights to additional suitable product candidates, our business and prospects for growth could suffer.
Even if we succeed in our efforts to obtain rights to suitable product candidates, the competitive business environment may result in higher acquisition or licensing costs, and our investment in these potential products will remain subject to the inherent risks associated with the development and commercialization of new medicines.
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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.
−Removed: In addition, if a product that has orphan drug designation subsequently receives the first FDA approval for the disease for which it has such designation, the product is entitled to
−Removed: orphan drug exclusivity, which means that the FDA may not approve any other applications, including a full NDA, to market the same drug for the same indication for seven years, except in limited circumstances, such as a showing of clinical superiority to the product with orphan drug exclusivity or where the manufacturer is unable to assure sufficient product quantity.
+Added: In addition, if a product that has orphan drug designation subsequently receives the first FDA approval for the disease for which it has such designation, the product is entitled to orphan drug exclusivity, which means that the FDA may not approve any other applications, including a full NDA, to
+Added: market the same drug for the same indication for seven years, except in limited circumstances, such as a showing of clinical superiority to the product with orphan drug exclusivity or where the manufacturer is unable to assure sufficient product quantity.
At this time, we do not have nor will we seek to apply for orphan drug designation in the EU or the UK in the foreseeable future.
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We have also entered into exclusive commercialization agreements with third parties to commercialize fostamatinib outside the US, and we plan to further enter partnership with existing or other third parties to commercialize fostamatinib and olutasidenib outside the US in the future.
−Removed: Sustained successful commercialization of our products is subject to many risks and uncertainties, including the impact of the COVID-19 pandemic on the successful commercialization in the US, as well as the successful commercialization efforts for our products through our collaborative partners.
+Added: 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.
There are numerous examples of unsuccessful product launches and failures to meet high expectations of market potential, including by pharmaceutical companies with more experience and resources than us.
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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 and patients may be unwilling to use our products if coverage is not
−Removed: provided or reimbursement is inadequate to cover a significant portion of the cost.
−Removed: Our products compete, and may in the future compete, with currently existing therapies, including generic drugs, and products currently under development.
+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.
+Added: Our products compete, and may in the
+Added: future compete, with currently existing therapies, including generic drugs, and products currently under development.
Our competitors, particularly large pharmaceutical companies, may deploy more resources to market, sell and distribute their products.
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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 evolving effects of the COVID-19 pandemic and the Russian-Ukrainian conflict;
+Added: ● potential future impacts, if any, due to the effects of a global pandemic and the Russian-Ukrainian conflict;
● the ability to distinguish safety and efficacy from existing, less expensive generic alternative therapies, if any;
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● pricing and the availability of coverage and adequate reimbursement by third-party payors and government authorities;
−Removed: ● a positive HTA assessment 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;
+Added: ● 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;
● the prevalence and severity of adverse side effects;
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We likely will have little control over such third parties, including Kissei’s development and commercialization of fostamatinib in all indications in Japan, China, Taiwan, and the Republic of Korea, Grifols’ commercialization of fostamatinib in Europe and Turkey, Medison for future commercialization of fostamatinib in Canada and Israel, and Knight for commercialization of fostamatinib in Latin America.
−Removed: As a consequence of our license agreements with Kissei, Grifols, Medison and Knight, we rely heavily upon their regulatory, commercial, medical affairs, market access and other expertise and resources for
−Removed: commercialization of fostamatinib in their respective territories outside of the US.
−Removed: We cannot control the amount of resources that our partners dedicate to the commercialization of fostamatinib, and our ability to generate revenues from the commercialization of fostamatinib by our partners depends on their ability to achieve market acceptance of fostamatinib in its approved indications in their respective territories.
+Added: As a consequence of our license agreements with Kissei, Grifols, Medison and Knight, we rely heavily upon their regulatory, commercial, medical affairs, market access and other expertise and resources for commercialization of fostamatinib in their respective territories outside of the US.
+Added: We cannot control the amount of resources that our partners dedicate to the commercialization of fostamatinib, and our ability to generate revenues from
+Added: the commercialization of fostamatinib by our partners depends on their ability to achieve market acceptance of fostamatinib in its approved indications in their respective territories.
Furthermore, foreign sales of fostamatinib 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.
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As a result, we, or any of our collaborative partners, might obtain marketing approval for a product in a particular country, but then be subject to price regulations that delay commercial launch of the product, possibly for lengthy time periods, which may negatively impact the revenues we are able to generate from the sale of the product in that country.
−Removed: In particular, we cannot predict to what extent the evolving effects of the COVID-19 pandemic, depending on its scale and duration, may continue to disrupt global healthcare systems and access to our products or result in a widespread loss of individual health insurance coverage due to unemployment, a shift from commercial payor coverage to government payor coverage, or an increase in demand for patient assistance and/or free
−Removed: drug programs, any of which would adversely affect access to and demand for our products and our net sales.
−Removed: Adverse pricing limitations may also hinder our ability or the ability of any future collaborators to recoup our or their investment in one or more product candidates, even if our product candidates obtain marketing approval.
+Added: In particular, we cannot predict to what extent the effects of a global pandemic, depending on its scale and duration, may continue to disrupt global healthcare systems and access to our products or result in a widespread loss of individual health insurance coverage due to unemployment, a shift from commercial payor coverage to government payor coverage, or an increase in demand for patient assistance and/or free drug programs, any of which would adversely affect access to and demand for our products and our net sales.
+Added: Adverse pricing limitations may also hinder our ability or the ability of any future collaborators to recoup our or their investment in one or more
+Added: product candidates, even if our product candidates obtain marketing approval.
Further, even if favorable coverage and reimbursement status is attained for one or more products for which we or our collaborative partners receive regulatory approval, less favorable coverage policies and reimbursement rates may be implemented in the future.
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If they are unable to perform effectively or if they do not provide efficient distribution of the medicine to patients, our business may be harmed.
−Removed: In addition, we actively participate in medical conferences and exhibits, such as the ASCO and ASH Annual Meeting & Exposition that are significant opportunities for us to educate physicians and key opinion leaders about our products.
−Removed: ASCO was held in Chicago, Illinois as well as virtually in June 2022, and ASH was held in New Orleans, Louisiana as well as virtually in December 2022.
−Removed: In the future, other key conferences may be held live, virtually, postponed or cancelled.
−Removed: Such disruptions may prevent us from effectively educating the prescribing physicians and key opinion leaders about our products which would negatively impact utilization of our products and our results of operations and growth prospects could be adversely affected.
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.
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.
−Removed: If we cannot maintain effective sales, marketing, market access and product distribution capabilities, whether as a result of the COVID-19 pandemic or otherwise, we may be unable to realize the commercial potential of our products.
−Removed: Also, to the extent that the commercial opportunities for our products grow over time, we may not properly judge the requisite size and experience of our
−Removed: current commercialization teams or the level of distribution necessary to market and sell our products, which could have an adverse impact on our business, financial condition and results of operations.
+Added: If we cannot maintain effective sales, marketing, market access and product distribution capabilities, whether as a result of a global pandemic or otherwise, we may be unable to realize the commercial potential of our products.
+Added: Also, to the extent that the commercial opportunities for our products grow over time, we may not properly judge the requisite size and experience of our current commercialization teams or the level of distribution necessary to market and sell our products, which could have an adverse impact on our business, financial condition and results of operations.
We may not be able to successfully develop or commercialize our product candidates if problems arise in the clinical testing and approval process.
−Removed: The activities associated with the research, development and commercialization of fostamatinib and other product candidates in our pipeline must undergo extensive clinical trials, which can take many years and require substantial expenditures, subject to extensive regulation by the FDA and other regulatory agencies in the US and by comparable authorities in other countries.
+Added: The activities associated with the research, development and commercialization of fostamatinib and other product candidates in our pipeline must undergo extensive clinical trials, which can take many years and require substantial expenditures, subject to extensive regulation by the FDA and other regulatory agencies in the US and by
+Added: comparable authorities in other countries.
The process of obtaining regulatory approvals in the US and other foreign jurisdictions is expensive, and lengthy, if approval is obtained at all.
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Based on the result of the trial and the guidance from the FDA , we did not file an sNDA for wAIHA.
−Removed: Due to the evolving effects of COVID-19 pandemic, it is also possible that we could experience delays in the timing of our interactions with regulatory authorities due to absenteeism by governmental employees or the diversion of regulatory authority efforts and attention to approval of other therapeutics or other activities related to COVID-19 or other public health emergencies, which could delay or limit our ability to make planned regulatory submissions or develop and commercialize our product candidates on anticipated timelines.
+Added: Due to the effects of a global pandemic, it is also possible that we could experience delays in the timing of our interactions with regulatory authorities due to absenteeism by governmental employees or the diversion of regulatory authority efforts and attention to approval of other therapeutics or other activities related to COVID-19 or other public health emergencies, which could delay or limit our ability to make planned regulatory submissions or develop and commercialize our product candidates on anticipated timelines.
In addition, delays or rejections may be encountered based upon changes in regulatory policy for product approval during the period of product development and regulatory agency review, which may cause delays in the approval or rejection of an application for fostamatinib or for our other product candidates.
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● the clinical results may not replicate the results of earlier, smaller trials;
−Removed: ● we or third parties with whom we collaborate, may be significantly impacted by the evolving impacts of the COVID-19 pandemic;
+Added: ● we or third parties with whom we collaborate, may be significantly impacted by force majeure events;
● we, or the FDA or similar foreign regulatory authorities, may delay, terminate or suspend the trials;
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The global credit and financial markets are currently, and have from time to time experienced extreme volatility and disruptions, including severely diminished liquidity and credit availability, rising interest and inflation rates, declines in consumer confidence, declines in economic growth, increases in unemployment rates and uncertainty about economic stability.
−Removed: More recently, the closures of SVB and Signature Bank and their placement into receivership with the FDIC created bank-specific and broader financial institution liquidity risk and concerns.
+Added: More recently, the closures of Silicon Valley Bank (SVB) and Signature Bank and their placement into receivership with the Federal Deposit Insurance Corporation (FDIC) created bank-specific and broader financial institution liquidity risk and concerns.
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, FCB announced that it has entered into an agreement with FDIC to purchase all of the asset and liabilities of SVB.
+Added: 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.
Customers of SVB automatically become customers of FCB following the acquisition.
We maintain a depository relationship with SVB/FCB.
−Removed: To date and as of March 31, 2023, the amount of our cash held on deposit with SVB/FCB was not material with respect our total cash, cash equivalents and short-term investments.
+Added: The amount of our cash held on deposit with SVB/FCB was not material with respect our total cash, cash equivalents and short-term investments.
All of our cash deposits with SVB/FCB are accessible to us, and we do not anticipate any losses with respect to such funds.
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In addition, the US government has initiated or is considering imposing tariffs on certain foreign goods.
−Removed: Related to this action, certain foreign governments, including China, have instituted or are considering imposing
−Removed: tariffs on certain US goods.
+Added: Related to this action, certain foreign governments, including China, have instituted or are considering imposing tariffs on certain US goods.
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.
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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 owed by any current or former director, officer, or other employee of the Company 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 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
−Removed: courts of the United States will be the sole and exclusive forum for resolving any action asserting a claim 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
+Added: discourage 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.
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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.