5 unchanged sentences
Risks Related to Our Business Operations
−Removed: We face risks related to health epidemics and other widespread outbreaks of contagious disease, including the novel coronavirus pandemic, or COVID-19, which has delayed our ability to complete our ongoing clinical trials, disrupted our business operations and may further delay our clinical trials, interrupt our supply chain, disrupt regulatory activities, or have other adverse effects on our business and operations.
+Added: We face risks related to health epidemics and other widespread outbreaks of contagious disease, including COVID-19, which has delayed our ability to complete our ongoing clinical trials, disrupted our business operations and may further delay our clinical trials, interrupt our supply chain, disrupt regulatory activities or have other adverse effects on our business and operations.
In addition, this pandemic has caused substantial disruption in the financial markets and economies worldwide, which could result in adverse effects on our business and operations.
−Removed: Significant outbreaks of contagious diseases, such as the COVID-19 pandemic, and other adverse public health developments, could have a material impact on our business operations and operating results.
+Added: Significant outbreaks of contagious diseases, such as COVID-19 and other adverse public health developments, could have a material impact on our business operations and operating results.
The COVID-19 pandemic and government measures taken in response thereto have also had a significant impact, both direct and indirect, on segments of the global economy and have interrupted our clinical trial activities, disrupted our business operations and have the potential to interrupt our supply chain.
We have experienced restrictions and delays at our existing clinical sites.
−Removed: For example, in our ongoing Phase 2b/3 trial of Haduvio for the treatment of pruritus associated with prurigo nodularis, which we refer to as our Phase 2b/3 PRISM trial, new patient screening and most enrollment was temporarily halted in March 2020 due to the COVID-19 pandemic.
−Removed: After resuming screening and enrollment, multiple sites in the Phase 2b/3 PRISM trial have begun requiring remote monitoring of patient data.
−Removed: We also experienced slower recruitment activities in the Phase 2b/3 PRISM trial worldwide through the latter part of 2020 and the beginning of 2021 due to the resurgence of the COVID-19 pandemic.
−Removed: In addition, the clinical sites in our ongoing Phase 2 trial for chronic cough in patients with idiopathic pulmonary fibrosis, or IPF, which we refer to as the Phase 2 CANAL trial, suspended enrollment and treatment of patients in the trial due to the vulnerability of IPF patients to COVID-19 and as a result, we amended the protocol for the trial to reduce the number of in-person patient visits and procedures.
−Removed: While patient screening and enrollment for our Phase 2 CANAL trial resumed at certain clinical trial sites in the fourth quarter of 2020, all sites in the trial paused screening again in December 2020 in response to a shelter in place directive from the U.K.
−Removed: This directive expired in March 2021 and we expect the other COVID-19 related restrictions will continue to be lifted through June 2021, assuming the pandemic does not worsen in the United Kingdom.
+Added: For example, in our ongoing Phase 2b/3 PRISM trial, new subject screening and most enrollment was temporarily halted in March 2020 due to COVID-19.
+Added: After resuming screening and enrollment, multiple sites in the Phase 2b/3 PRISM trial have begun requiring remote monitoring of subject data.
+Added: We also experienced slower recruitment activities in the Phase 2b/3 PRISM trial worldwide through the latter part of 2020 and the beginning of 2021 due to the resurgence of COVID-19.
+Added: In addition, the clinical sites in our ongoing Phase 2 trial for chronic cough in patients with IPF, which we refer to as the Phase 2 CANAL trial, suspended enrollment and treatment of subjects in the trial due to the vulnerability of IPF patients to COVID-19 and as a result, we amended the protocol for the trial to reduce the number of in-person subject visits and procedures.
+Added: While subject screening and enrollment for our Phase 2 CANAL trial resumed at certain clinical trial sites in the fourth quarter of 2020, all sites in the trial paused screening again in December 2020 in response to a shelter-in-place directive from the U.K.
+Added: This shelter-in-place directive expired in March 2021 and the remaining COVID-19 related restrictions were lifted in July 2021.
+Added: government may choose to reinstate any and/or all of the restrictions in the future depending on COVID-19 infection rates.
Initial screening activity has resumed at certain sites following the lifting of the shelter-in-place directive.
−Removed: However, we expect that some sites may take longer to resume their trial activity due to increased COVID-19 infection rates in the areas where they are located and that other sites may cease to participate in the trial entirely.
−Removed: We have decided not to pursue opening new clinical sites in Germany due to the estimated timing and cost to add these additional sites.
−Removed: Instead, in light of the easing of pandemic restrictions in the United Kingdom, we are focusing our efforts on the completion of enrollment in the Phase 2 CANAL trial in the United Kingdom.
−Removed: The COVID-19 pandemic may also adversely affect our ability to recruit and retain principal investigators and site staff who, as healthcare providers, may have heightened exposure to COVID-19, and may result in further disruptions to our clinical trials due to prioritization of hospital and medical resources toward the outbreak, restrictions on travel of patients and healthcare providers, potential unwillingness of patients to enroll in trials at this time, or the inability of patients to comply with clinical trial protocols if quarantines or travel restrictions impede patient movement or interrupt healthcare services.
−Removed: The response to the COVID-19 pandemic may also redirect resources of regulators in a way that could adversely impact our ability to progress regulatory approvals and we may face impediments to regulatory meetings and approvals relating to our clinical trials due to measures intended to limit in-person interactions.
−Removed: The COVID-19 pandemic may also affect employees of third-party contract research organizations located in affected geographies that we rely upon to carry out our clinical trials.
+Added: However, we expect that some sites may take longer to resume their trial activity as the clinical research related infrastructure was disrupted by COVID-19 and that other sites may cease to participate in the trial entirely.
+Added: COVID-19 may also adversely affect our ability to recruit and retain principal investigators and site staff who, as healthcare providers, may have heightened exposure to COVID-19 and may result in further disruptions to our clinical trials due to prioritization of hospital and medical resources toward the outbreak, restrictions on travel of patients and healthcare providers, potential unwillingness of subjects to enroll in trials at this time or the inability of subjects to comply with clinical trial protocols if quarantines or travel restrictions impede subject movement or interrupt healthcare services.
+Added: The response to COVID-19 may also redirect resources of regulators in a way that could adversely impact our ability to progress regulatory approvals and we may face impediments to regulatory meetings and approvals relating to our clinical trials due to measures intended to limit in-person interactions.
+Added: COVID-19 may also affect employees of third-party contract research organizations located in affected geographies that we rely upon to carry out our clinical trials.
The spread of COVID-19 or another infectious disease, could also negatively affect the operations at our third-party suppliers, which could result in delays or disruptions in the supply of drug product used in our clinical trials.
−Removed: In addition, we have taken temporary precautionary measures intended to help minimize the risk of the virus to our employees, including allowing employees to work remotely, suspending all non-essential travel worldwide for our employees and discouraging employee attendance at industry events, each of which could negatively affect our business.
−Removed: We cannot presently predict the scope and severity of the disruptions we may experience or continue to experience as a result of the COVID-19 pandemic.
+Added: In addition, we have taken temporary precautionary measures intended to help minimize the risk of the virus to our employees, including allowing employees to work remotely part of the week and suspending non-essential travel worldwide for our employees, each of which could negatively affect our business.
+Added: We cannot presently predict the scope and severity of the disruptions we may experience or continue to experience as a result of COVID-19.
If we or any of the third parties with whom we engage experience business disruptions, our ability to conduct our business in the manner and on the timelines presently planned could be materially and negatively affected.
−Removed: Additionally, the pandemic has already caused significant disruptions in the financial markets, and may continue to cause such disruptions, which could impact our ability to raise additional funds and has also impacted, and may continue to impact, the volatility of our stock price and trading in our stock.
+Added: Additionally, the pandemic has already caused significant disruptions in the financial markets and may continue to cause such disruptions, which could impact our
+Added: ability to raise additional funds and has also impacted and may continue to impact, the volatility of our stock price and trading in our stock.
Risks Related to Our Financial Position and Need for Additional Capital
2 unchanged sentences
We expect to continue to incur significant and increasing net losses for at least the next several years.
−Removed: Our net losses were $8.4 million and $32.8 million for the three months ended March 31, 2021 and for the year ended December 31, 2020, respectively.
−Removed: As of March 31, 2021, we had an accumulated deficit of $155.3 million.
+Added: Our net losses were $18.2 million and $32.8 million for the six months ended June 30, 2021 and for the year ended December 31, 2020, respectively.
+Added: As of June 30, 2021, we had an accumulated deficit of $165.1 million.
We have not generated any revenues from product sales, have not completed the development of any product candidate and may never have a product candidate approved for commercialization.
−Removed: We have financed our operations to date primarily through private placements of our convertible preferred stock and convertible notes prior to our initial public offering, borrowings under our prior term loan facility, proceeds from our initial public offering and concurrent private placement completed in May 2019, sales of our common stock pursuant to the ATM Sales Agreement we entered into in June 2020, which we refer to as the ATM Sales Agreement, and the term loan facility with Silicon Valley Bank that we entered into in August 2020, which we refer to as the SVB Term Loan.
+Added: We have financed our operations to date primarily through private placements of our convertible preferred stock and convertible notes prior to our IPO, borrowings under our prior term loan facility, proceeds from our IPO and concurrent private placement completed in May 2019, sales of our common stock pursuant to the ATM Sales Agreement and the SVB Term Loan.
We have devoted substantially all of our financial resources and efforts to the clinical development of our product candidate Haduvio and related activities.
4 unchanged sentences
continue to develop and conduct clinical trials of Haduvio, including our ongoing Phase 2b/3 PRISM trial and our ongoing Phase 2 CANAL trial;
−Removed: significantly increase the number of subjects in the Phase 2b/3 PRISM trial to a total of 360 patients based on the sample size re-estimation, or SSRE, analysis;
−Removed: complete other development work required for the filing of a new drug application, or NDA, with the U.S.
−Removed: Food and Drug Administration, or FDA, and the filing of a marketing authorization application, or MAA, with the European Medicines Agency, or EMA, for Haduvio for the treatment of pruritus associated with prurigo nodularis, including completing our Phase 2b/3 PRISM trial and at least one additional Phase 3 clinical trial in this indication;
+Added: significantly increase the number of subjects in the Phase 2b/3 PRISM trial to a total of 360 subjects based on the SSRE analysis;
+Added: complete other development work required for the filing of a NDA with the FDA and the filing of a MAA with the EMA for Haduvio for the treatment of pruritus associated with prurigo nodularis, including completing our Phase 2b/3 PRISM trial and at least one additional Phase 3 clinical trial in this indication;
seek regulatory and marketing approvals for Haduvio for the treatment of pruritus associated with prurigo nodularis or for other serious neurologically mediated conditions or for any future product candidate that successfully completes clinical trials, if any;
8 unchanged sentences
add equipment and physical infrastructure to support our development program for Haduvio and for any future product candidates.
−Removed: In addition, we may incur additional expenses as a result of the COVID-19 pandemic and resulting clinical trial delays and interruptions.
+Added: In addition, we may incur additional expenses as a result of COVID-19 and resulting clinical trial delays and interruptions.
Our ability to become and remain profitable depends on our ability to generate revenue.
13 unchanged sentences
We may encounter unforeseen expenses, difficulties, complications, delays and other known or unknown factors in achieving our business objectives.
−Removed: If we are able to obtain marketing approval for Haduvio or any future product candidate, we will need to transition from a company focused on clinical development to a company capable of supporting commercial activities.
+Added: If we obtain marketing approval for Haduvio or any future product candidate, we will need to transition from a company focused on clinical development to a company capable of supporting commercial activities.
We may not be successful in effectuating such a transition.
3 unchanged sentences
We believe there is substantial doubt about our ability to continue as a going concern as of the date of this Quarterly Report on Form 10-Q without additional capital.
−Removed: See Note 1 to our financial statements appearing elsewhere in this Quarterly Report on Form 10-Q for additional information on our assessment.
+Added: See Note 1 to the Condensed Consolidated Financial Statements appearing elsewhere in this Quarterly Report on Form 10-Q for additional information on our assessment.
We plan to address this condition through the sale of common stock in public offerings and/or private placements, debt financings or other capital sources, including collaborations with other companies or other strategic transactions.
−Removed: If we are unable to obtain such funding and continue as a going concern, we might have to liquidate our assets and the values we receive for our assets in liquidation or dissolution could be significantly lower than the values reflected in our financial statements.
+Added: If we are unable to obtain such funding and continue as a going concern, we might have to liquidate our assets and the values we receive for our assets in liquidation or dissolution could be significantly lower than the values reflected in our Condensed Consolidated Financial Statements .
Our lack of cash resources and our conclusion that we may be unable to continue as a going concern may materially adversely affect our share price and our ability to raise new capital or to enter into critical contractual relationships with third parties.
2 unchanged sentences
We have consumed substantial amounts of cash since our inception.
−Removed: For example, in the three months ended March 31, 2021 and the year ended December 31, 2020, we used net cash of $7.6 million and $29.0 million, respectively, in our operating activities, substantially all of which related to development activities for Haduvio.
−Removed: As of March 31, 2021, our cash and cash equivalents were $41.6 million.
+Added: For example, in the six months ended June 30, 2021 and the year ended December 31, 2020, we used net cash of $15.5 million and $29.0 million, respectively, in our operating activities, substantially all of which related to development activities for Haduvio.
+Added: As of June 30, 2021, our cash and cash equivalents were $36.4 million.
We expect our expenses to increase substantially in connection with our ongoing activities, particularly as we continue to develop and conduct clinical trials of Haduvio, including our ongoing Phase 2b/3 PRISM trial and the additional Phase 3 clinical trial we believe we will need to conduct for Haduvio for the
treatment of pruritus associated with prurigo nodularis and our other ongoing clinical trials, acquire or in-license rights to other potential product candidates or technologies and seek regulatory and marketing approvals for Haduvio or any future product candidate that successfully completes clinical trials, if any.
−Removed: In addition, we may incur additional expenses as a result of the COVID-19 pandemic and resulting clinical trial delays and interruptions.
+Added: In addition, we may incur additional expenses as a result of COVID-19 and resulting clinical trial delays and interruptions.
In addition, if we obtain marketing approval for Haduvio or any future product candidate, we may incur significant commercialization expenses related to product sales, marketing, manufacturing and distribution.
−Removed: For instance, we currently intend to commercialize Haduvio in the United States ourselves by developing a focused, specialty sales, marketing and distribution organization.
+Added: For instance, we currently intend to commercialize Haduvio in the U.S.
+Added: ourselves by developing a focused, specialty sales, marketing and distribution organization.
Furthermore, we expect to incur significant costs associated with operating as a public company.
1 unchanged sentence
If we are unable to raise sufficient capital when needed on acceptable terms or at all, we may be forced to delay, reduce or abandon our development programs or any future commercialization efforts.
−Removed: We plan to use our existing cash and cash equivalents to fund the development of Haduvio for the treatment of pruritus associated with prurigo nodularis and the treatment of chronic cough in patients with IPF and for working capital and other general corporate purposes.
−Removed: We will be required to expend significant funds in order to advance the development of Haduvio in multiple indications, as well as any future product candidates we may seek to develop.
+Added: We plan to use our existing cash and cash equivalents to fund the development of Haduvio for the treatment of pruritus associated with prurigo nodularis, for the treatment of chronic cough in patients with IPF and for working capital and other general corporate purposes.
+Added: We will be required to expend significant funds to advance the development of Haduvio in multiple indications, as well as any future product candidates we may seek to develop.
Our existing cash and cash equivalents will not be sufficient to complete development of Haduvio for the treatment of pruritus associated with prurigo nodularis or for any other condition or of any future product candidate.
−Removed: We do not have any committed external source of funds.
+Added: Other than our right to cause Lincoln Park to purchase shares of our common stock under the LPC Purchase Agreement, which is subject to certain limitations and conditions, w e do not have any committed external source of funds.
Accordingly, we will be required to obtain further funding through public or private equity offerings, debt financings, collaborations and licensing arrangements or other sources to achieve our business objectives.
1 unchanged sentence
Our failure to raise capital, as and when needed, would have a negative impact on our financial condition and our ability to pursue our business strategy.
−Removed: We believe that our existing cash and cash equivalents will enable us to fund our operating expenses and capital expenditure requirements into the second quarter of 2022.
−Removed: Our estimate as to how long we expect our existing cash and cash equivalents to continue to fund our operations is based on assumptions that may prove to be wrong, and we could use our available capital resources sooner than we currently expect.
+Added: We believe that our existing cash and cash equivalents will enable us to fund our operating expenses and capital expenditure requirements into the second quarter of 2022, without giving effect to the rights of SVB under the SVB Loan Agreement if we fail to achieve any of the Milestone Conditions or to the impact of any equity financing that we may conduct to satisfy the equity raise requirements of the SVB Loan Agreement.
+Added: If we fail to achieve any of the Milestone Conditions and SVB cash collateralizes the amounts then owed to SVB under the SVB Loan Agreement or uses such amounts to prepay the SVB Term Loan, the period for which we will be able to fund our operating expenses and capital expenditure requirements will be significantly shorter.
+Added: We have based our estimates as to how long we expect we will be able to fund our operations on assumptions that may prove to be wrong and we could use our available capital resources sooner than we currently expect, in which case we would be required to obtain additional financing.
+Added: We are required under the SVB Loan Agreement to raise in an equity financing of at least $15 million in net proceeds by October 31, 2021.
+Added: However, such a financing may not be available to us on acceptable terms, on a timely basis or at all.
+Added: Our failure to raise capital as and when needed would have a negative impact on our financial condition and our ability to pursue our business strategy.
Further, changing circumstances, some of which may be beyond our control, could cause us to consume capital significantly faster than we currently anticipate and we may need to seek additional funds sooner than planned.
1 unchanged sentence
the scope, progress, timing, costs and results of clinical trials of Haduvio for the treatment of pruritus associated with prurigo nodularis, as well as the scope, progress, timing, costs and results of clinical trials of Haduvio for other serious neurologically mediated conditions, including our ongoing Phase 2 CANAL trial, as well as any future product candidates;
−Removed: the impacts of the COVID-19 pandemic on the scope, progress, timing, costs and results of our ongoing and planned clinical trials of Haduvio;
+Added: the impacts of COVID-19 on the scope, progress, timing, costs and results of our ongoing and planned clinical trials of Haduvio;
the number and characteristics of indications for which we seek to develop Haduvio or any future product candidates and their respective development requirements;
−Removed: the outcome, timing and costs of clinical and nonclinical trials and of seeking regulatory approvals, including the costs of supportive clinical studies such as our planned human abuse liability, or HAL, study and a potential Thorough QT, or TQT, study;
+Added: the outcome, timing and costs of clinical and nonclinical trials and of seeking regulatory approvals, including the costs of supportive clinical studies such as our planned HAL study and a potential TQT study;
the costs associated with the manufacture of necessary quantities of Haduvio or any future product candidate for clinical development in connection with regulatory submissions;
10 unchanged sentences
Our indebtedness could adversely affect our financial condition or restrict our future operations.
−Removed: On August 13, 2020, we entered into a Loan and Security Agreement, or the SVB Loan Agreement, with Silicon Valley Bank, or SVB, pursuant to which SVB provided a term loan to us in the original principal amount of $14.0 million.
+Added: On August 13, 2020, we entered into the SVB Loan Agreement with SVB, pursuant to which SVB provided the SVB Term Loan to us.
+Added: In July 2021, we entered into the Loan Amendment.
The SVB Term Loan bears interest at a floating rate per annum equal to the greater of (A) the prime rate plus 1.00% and (B) 4.25%.
−Removed: If SVB receives evidence satisfactory to it that the Company has (i) received positive data for the Phase 2b/3 PRISM trial sufficient to advance Haduvio into a second Phase 3 clinical trial for prurigo nodularis, and (ii) raised sufficient financing to fund such Phase 3 clinical trial and the Company’s operations, the interest rate under the SVB Term Loan will be adjusted to a floating rate equal to the greater of (A) the prime rate plus 3.00% and (B) 6.25%.
+Added: If SVB receives evidence satisfactory to it that we have (i) received positive data for the Phase 2b/3 PRISM trial sufficient to advance Haduvio into a second Phase 3 clinical trial for prurigo nodularis and (ii) raised sufficient financing to fund such Phase 3 clinical trial and our operations, the interest rate under the SVB Term Loan will be adjusted to a floating rate equal to the greater of (A) the prime rate plus 3.00% and (B) 6.25%.
On the first business day of each month, we are required to make monthly interest payments and commencing on March 1, 2022, we will be required to repay the SVB Term Loan in 24 consecutive installments of principal plus monthly payments of accrued interest.
2 unchanged sentences
The SVB Loan Agreement also includes customary affirmative and negative covenants, including a requirement to maintain our bank accounts with SVB or bank accounts that are subject to SVB’s control and limitations on transferring all or any part of our business or property, changing our business, liquidating or dissolving, permitting a change in control, adding new offices or business locations, changing jurisdiction of organization, organizational structure or legal name, merging with or acquiring another entity, incurring additional indebtedness, creating any lien on our property, paying dividends or redeeming stock, entering into material transactions with an affiliate or making payments on subordinated debt.
−Removed: Additionally, if we fail to meet certain equity raise requirements under the SVB Loan Agreement, including raising $12.0 million by June 30, 2021, we will be required to deposit unrestricted and unencumbered cash equal to 100% of the principal amount of the SVB Term Loan then outstanding in a cash collateral account with SVB, which can be used by SVB to prepay the SVB Term Loan at any time.
+Added: Additionally, under the Loan Amendment, if we fail to receive positive data in our Phase 2b/3 PRISM trial or to meet certain equity raise requirements, including raising at least $15.0 million in net proceeds from the sale of equity securities during the period from June 1, 2021 through October 31, 2021 and raising by June 30, 2022 sufficient additional net proceeds from the sale of equity securities to finance our planned second Phase 3 clinical trial of Haduvio for prurigo nodularis and our ongoing operations or the Milestone Conditions, we will be required to deposit unrestricted and unencumbered cash equal to 100% of the principal amount of the SVB Term Loan then outstanding in a cash collateral account with SVB, which can be used by SVB to prepay the SVB Term Loan at any time.
+Added: In addition, if we fail to maintain at least $20.0 million in unrestricted and unencumbered cash in our accounts with SVB at any time prior to the satisfaction of all the Milestone Conditions, we will be required to cash collateralize all outstanding amounts owed to SVB under the SVB Loan Agreement.
Our debt combined with our other financial obligations and contractual commitments could have significant adverse consequences, including:
5 unchanged sentences
Funds from external sources may not be available on acceptable terms, if at all.
−Removed: In addition, a failure to comply with certain equity raise requirements in the SVB Loan Agreement could result in us having to deposit unrestricted and unencumbered cash equal to 100% of the principal amount of the SVB Term Loan then outstanding in a cash collateral account with SVB, which can be used by SVB to prepay the SVB Term Loan at any time.
+Added: In addition, as discussed above, a failure to satisfy any Milestone Condition or to maintain at least $20.0 million in unrestricted and unencumbered cash in our accounts with SVB at any time prior to satisfaction of all of the Milestone Conditions could result in us having to deposit unrestricted and unencumbered cash equal to 100% of the principal amount of the SVB Term Loan then outstanding in a cash collateral account with SVB, which can be used by SVB to prepay the SVB Term Loan at any time.
Failure to pay any amount due under the SVB Loan Agreement, to comply with covenants under the SVB Loan Agreement or the occurrence of an event that would reasonably be expected to have a material adverse effect on our business, operations or condition (financial or otherwise) would result in an event of default.
The occurrence and continuation of an event of default could cause interest to be charged at the rate that is otherwise applicable plus 5.00% (unless SVB elects to impose a smaller increase) and would provide SVB with the right to accelerate all obligations under the SVB Loan Agreement and exercise remedies against us and the collateral securing the SVB Term Loan and other obligations under the SVB Loan Agreement, including foreclosure against assets securing the SVB Term Loan and other obligations under the SVB Loan Agreement, including our cash.
−Removed: In addition, the covenants under the SVB Loan
−Removed: Agreement and the pledge of substantially all of our assets, excluding our intellectual property (which is subject to a negative pledge under the SVB Loan Agreement), as collateral on the SVB Term Loan may limit our ability to obtain additional debt financing.
+Added: In addition, the covenants under the SVB Loan Agreement and the pledge of substantially all our assets, excluding our intellectual property (which is subject to a negative pledge under the SVB Loan Agreement), as collateral on the SVB Term Loan may limit our ability to obtain additional debt financing.
Raising additional capital may cause dilution to our stockholders, restrict our operations or require us to relinquish rights to our product candidates.
1 unchanged sentence
To the extent that we raise additional capital through the sale of common stock, convertible securities or other equity securities, your ownership interest may be diluted, and the terms of these securities could include liquidation or other preferences and anti-dilution protections that could adversely affect your rights as a common stockholder.
−Removed: Our ability to obtain further debt financing may be limited by the covenants under the SVB Loan Agreement, which include a covenant not to incur additional indebtedness as well as the pledge of substantially all of our assets, excluding our intellectual property (which is subject to a negative pledge under the SVB Loan Agreement), as collateral on the SVB Term Loan.
+Added: Our ability to obtain further debt financing may be limited by the covenants under the SVB Loan Agreement, which include a covenant not to incur additional indebtedness as well as the pledge of substantially all our assets, excluding our intellectual property (which is subject to a negative pledge under the SVB Loan Agreement), as collateral on the SVB Term Loan.
In addition, further debt financing, if available, would result in additional fixed payment obligations and may involve agreements that include grants of additional security interests on our assets and additional restrictive covenants that limit our ability to take specific actions, such as incurring additional debt, making capital expenditures, granting liens over our assets, redeeming stock or declaring dividends, that could adversely impact our ability to conduct our business, which covenants may be more restrictive than the covenants to which we are subject under the SVB Loan Agreement.
4 unchanged sentences
If we are unable to complete the clinical development of, obtain marketing approval for or successfully commercialize Haduvio or if we experience significant delays in doing so, our business would be substantially harmed.
−Removed: We currently have no products approved for sale and are investing substantially all of our efforts and financial resources to fund the development of Haduvio for multiple serious neurologically mediated conditions.
+Added: We currently have no products approved for sale and are investing substantially all our efforts and financial resources to fund the development of Haduvio for multiple serious neurologically mediated conditions.
Our prospects are dependent on our ability to develop, obtain marketing approval for and successfully commercialize Haduvio in one or more indications as we currently have no other product candidates under development.
3 unchanged sentences
The success of Haduvio for the treatment of pruritus associated with prurigo nodularis, as well as for other serious neurologically mediated conditions, will depend on several factors, including the following:
−Removed: successfully recruiting, enrolling and retaining patients in and completing our Phase 2b/3 PRISM trial, including the additional 120 patients we intend to enroll based on the SSRE analysis;
−Removed: initiating and successfully recruiting, enrolling and retaining patients in and completing additional clinical and nonclinical trials, including the additional Phase 3 clinical trial we believe we will need to conduct for Haduvio for the treatment of pruritus associated with prurigo nodularis and other supportive clinical studies such as our planned HAL study and a potential TQT study;
+Added: successfully recruiting, enrolling and retaining subjects in and completing our Phase 2b/3 PRISM trial;
+Added: initiating and successfully recruiting, enrolling and retaining subjects in and completing additional clinical and nonclinical trials, including the additional Phase 3 clinical trial we believe we will need to conduct for Haduvio for the treatment of pruritus associated with prurigo nodularis and other supportive clinical studies such as our planned HAL study, a potential physical dependence study and a potential TQT study;
demonstrating safety, tolerability and efficacy profiles that are satisfactory to the FDA, EMA and other comparable regulatory authorities for marketing approval;
3 unchanged sentences
establishing and maintaining arrangements with third-party manufacturers of Haduvio, including developing, validating and maintaining a commercially viable manufacturing process that is compliant with current good manufacturing practices, or cGMPs;
−Removed: obtaining, maintaining and protecting our patents, trade secrets and regulatory exclusivity in the United States and other countries;
−Removed: establishing a focused, specialty sales organization in the United States and successfully launching commercial sales following any marketing approval;
+Added: obtaining, maintaining and protecting our patents, trade secrets and regulatory exclusivity in the U.S.
+Added: and other countries;
+Added: establishing a focused, specialty sales organization in the U.S.
+Added: and successfully launching commercial sales following any marketing approval;
obtaining commercial acceptance of our products, if approved, by patients, the medical community and third-party payors and obtaining and maintaining healthcare coverage and adequate reimbursement;
7 unchanged sentences
We are currently focused on the development and commercialization of Haduvio to treat serious neurologically mediated conditions.
−Removed: Haduvio is an oral extended release formulation of nalbuphine, the active drug ingredient in Haduvio, which is a mixed κ-opioid receptor agonist and μ-opioid receptor antagonist that has been approved and marketed as an injectable for pain indications for more than 20 years in the United States and Europe.
+Added: Haduvio is an oral extended-release formulation of nalbuphine, the active drug ingredient in Haduvio, which is a mixed κ-opioid receptor agonist and μ-opioid receptor antagonist that has been approved and marketed as an injectable for pain indications for more than 20 years in the U.S.
Nalbuphine is currently not commercially available in an oral dosage form, such as Haduvio.
1 unchanged sentence
Additionally, Haduvio has not been approved in any indication, including the treatment of pruritus associated with prurigo nodularis, the lead indication for which we are pursuing clinical development of Haduvio.
−Removed: No therapies have been approved in the United States or Europe for the treatment of moderate to severe pruritus, and we can provide no assurance that either Haduvio or any other future product candidate that we may seek to develop for this indication or for any other serious neurologically mediated condition will be effective or safe, obtain regulatory approval or be commercially successful.
+Added: No therapies have been approved in the U.S.
+Added: or Europe for the treatment of moderate to severe pruritus and we can provide no assurance that either Haduvio or any other future product candidate that we may seek to develop for this indication or for any other serious neurologically mediated condition
+Added: will be effective or safe, obtain regulatory approval or be commercially successful.
Clinical drug development involves a lengthy and expensive process with an uncertain outcome.
−Removed: We are not permitted to commercialize, market, promote or sell any product candidate in the United States without obtaining marketing approval from the FDA.
+Added: We are not permitted to commercialize, market, promote or sell any product candidate in the U.S.
+Added: without obtaining marketing approval from the FDA.
Foreign regulatory authorities, such as the EMA, impose similar requirements.
5 unchanged sentences
we may decide or regulators may require us, to restructure clinical trials, conduct additional clinical and nonclinical trials or abandon product development programs;
−Removed: the number of patients required for clinical trials may be larger than we anticipate, such as with the increase of the target number of enrolled patients for our Phase 2b/3 PRISM trial from 240 to 360 subjects as a result of the SSRE analysis;
−Removed: patient enrollment in these clinical trials may be slower than we anticipate, whether as a result of the COVID-19 pandemic or otherwise, or participants may discontinue their participation in these clinical trials at a higher rate than we anticipate, as we experienced in our Phase 2 clinical trial of Haduvio for the treatment of pruritus associated with prurigo nodularis;
−Removed: the cost of planned clinical trials may be greater than we anticipate, as we have experienced in our Phase 2b/3 PRISM trial as we added additional sites, increased the target number of enrolled patients as a result of the SSRE analysis, enrollment has taken longer than expected and we have used and expect to continue to use additional incentive strategies to address site activation and enrollment;
+Added: the number of subjects required for clinical trials may be larger than we anticipate, such as with the increase of the target number of enrolled subjects for our Phase 2b/3 PRISM trial from 240 to 360 subjects as a result of the SSRE analysis;
+Added: subject enrollment in these clinical trials may be slower than we anticipate, whether as a result of COVID-19 or otherwise or participants may discontinue their participation in these clinical trials at a higher rate than we anticipate, as we experienced in our Phase 2 clinical trial of Haduvio for the treatment of pruritus associated with prurigo nodularis;
+Added: the cost of planned clinical trials may be greater than we anticipate, as we have experienced in our Phase 2b/3 PRISM trial as we added additional sites, increased the target number of enrolled subjects as a result of the SSRE analysis, enrollment has taken longer than expected and we have used and expect to continue to use additional incentive strategies to address site activation and enrollment;
our clinical trials sites may not have adequate staff and resources to support our trials on a timely basis;
2 unchanged sentences
we may experience delays in reaching or fail to reach agreement on acceptable clinical trial contracts or clinical trial protocols with prospective trial sites;
−Removed: patients who enroll in a clinical trial may misrepresent their eligibility to do so or may otherwise not comply with applicable clinical trial protocols, resulting in the need to drop the patients from the clinical trial, increase the needed enrollment size for the clinical trial or extend the clinical trial’s duration;
+Added: subjects who enroll in a clinical trial may misrepresent their eligibility to do so or may otherwise not comply with applicable clinical trial protocols, resulting in the need to drop the subjects from the clinical trial, increase the needed enrollment size for the clinical trial or extend the clinical trial’s duration;
we may have to delay, suspend or terminate clinical trials for various reasons, including a finding that the participants are being exposed to unacceptable health risks, undesirable side effects or other unexpected characteristics of a product candidate;
6 unchanged sentences
In addition to the above, the continued spread of COVID-19 globally could adversely affect our clinical trial operations worldwide, including our ability to recruit and retain principal investigators and site staff who, as healthcare providers, may have heightened exposure to COVID-19 if an outbreak occurs in their geography and result in further delays in our clinical trials due to prioritization of hospital and medical resources toward the outbreak, restrictions in travel, potential unwillingness of patients to enroll in trials at this time or the inability of patients to comply with clinical trial protocols if quarantines or travel restrictions impede patient movement or interrupt healthcare services.
−Removed: Furthermore, the response to the COVID-19 pandemic may redirect resources of regulators in a way that would adversely impact our ability to progress regulatory approvals.
+Added: Furthermore, the response to COVID-19 may redirect resources of regulators in a way that would adversely impact our ability to progress regulatory approvals.
In addition, we may face impediments to regulatory meetings and approvals relating to our clinical trials due to measures intended to limit in-person interactions.
12 unchanged sentences
It is possible that even if Haduvio or any future product candidate has a beneficial effect, that effect will not be detected during clinical evaluation as a result of one or more of a variety of factors, including the size, duration, design, measurements, conduct or analysis of our clinical trials.
−Removed: For example, our Phase 2 clinical trial of Haduvio for the treatment of pruritus associated with prurigo nodularis failed to meet its primary endpoint, and the number of patients who discontinued treatment prior to the end of the trial had a substantial impact on the results.
+Added: For example, our Phase 2 clinical trial of Haduvio for the treatment of pruritus associated with prurigo nodularis failed to meet its primary endpoint and the number of subjects who discontinued treatment prior to the end of the trial had a substantial impact on the results.
Conversely, as a result of the same factors, our clinical trials may indicate an apparent positive effect of Haduvio or any future product candidate that is greater than the actual positive effect, if any.
4 unchanged sentences
For example, patients with prurigo nodularis may have pruritus that is caused by dermatological conditions other than prurigo nodularis and at a meeting with the FDA following the completion of our Phase 2 clinical trial of Haduvio for the treatment of pruritus associated with prurigo nodularis, the FDA raised the need to adequately isolate a patient population with pruritus associated with prurigo nodularis for our planned Phase 3 clinical trials.
−Removed: While the inclusion criteria in our Phase 2b/3 PRISM trial require that enrolled patients not be suffering from any active, uncontrolled dermatoses other than prurigo nodularis, it is possible that the FDA could conclude that this is not sufficient to identify patients suffering from pruritus associated with prurigo nodularis, in which case the FDA could question the overall validity of the results of the trial.
+Added: While the inclusion criteria in our Phase 2b/3 PRISM trial require that enrolled subjects not be suffering from any active, uncontrolled dermatoses other than prurigo nodularis, it is possible that the FDA could conclude that this is not sufficient to identify patients suffering from pruritus associated with prurigo nodularis, in which case the FDA could question the overall validity of the results of the trial.
To the extent that the results of our clinical trials are not satisfactory to the FDA or foreign regulatory authorities for support of a marketing application, approval of product candidates may be significantly delayed or we may be required to expend significant additional resources, which may not be available to us, to conduct additional trials in support of potential approval of product candidates.
14 unchanged sentences
The FDA could also require changes in the PROs we are currently using or indicate that the PROs we are using are insufficient for demonstrating efficacy in pruritus, potentially delaying clinical development of Haduvio, increasing our costs and making additional clinical trials necessary.
−Removed: If we experience delays or difficulties in the enrollment of patients in clinical trials, our receipt of necessary regulatory approvals could be delayed or prevented.
−Removed: We may not be able to initiate or continue clinical trials for Haduvio or any future product candidate if we are unable to locate and enroll a sufficient number of eligible patients to participate in clinical trials as required by the FDA or comparable foreign regulatory authorities.
+Added: If we experience delays or difficulties in the enrollment of subjects in clinical trials, our receipt of necessary regulatory approvals could be delayed or prevented.
+Added: We may not be able to initiate or continue clinical trials for Haduvio or any future product candidate if we are unable to locate and enroll a sufficient number of eligible subjects to participate in clinical trials as required by the FDA or comparable foreign regulatory authorities.
Patient enrollment is a significant factor in the timing of our clinical trials and is affected by many factors, including:
−Removed: the impact of the COVID-19 pandemic;
+Added: the impact of COVID-19;
the size and nature of the eligible patient population;
7 unchanged sentences
clinicians’ and patients’ perceptions as to the potential advantages and risks of the product candidate being studied in relation to other available therapies, including any new drugs that may be approved for the indications under investigation.
−Removed: In particular, the successful completion of our clinical development program for Haduvio for the treatment of pruritus associated with prurigo nodularis is dependent upon our ability to enroll a sufficient number of patients with this severe condition.
−Removed: We have experienced delays and difficulties in the enrollment of patients in our clinical trials, including our Phase 2b/3 PRISM trial and our Phase 2 CANAL trial, which have delayed the completion of our trials.
+Added: In particular, the successful completion of our clinical development program for Haduvio for the treatment of pruritus associated with prurigo nodularis is dependent upon our ability to enroll a sufficient number of subjects with this severe condition.
+Added: We have experienced delays and difficulties in the enrollment of subjects in our clinical trials, including our Phase 2b/3 PRISM trial and our Phase 2 CANAL trial, which have delayed the completion of our trials.
We have taken actions to increase enrollment, including increasing the number of clinical sites, expanding our clinical trials into additional countries, providing sites with additional trial management staff and closing underperforming sites.
However, these actions may not be successful.
−Removed: In addition, as a result of the COVID-19 pandemic, clinical sites for our Phase 2b/3 PRISM trial temporarily halted new patient screening and most patient enrollment.
−Removed: After resuming screening and enrollment, multiple sites in the Phase 2b/3 PRISM trial have begun requiring remote
−Removed: monitoring of patient data.
−Removed: In addition, the clinical sites in our ongoing Phase 2 CANAL trial temporarily suspended enrollment and treatment of patients in the trial due to the vulnerability of IPF patients to COVID-19 and we amended the protocol for the trial to reduce the number of in-person patient visits and procedures.
−Removed: While patient screening and enrollment for our Phase 2 CANAL trial resumed at certain clinical trial sites in the fourth quarter of 2020, all sites in the trial paused screening again in December 2020 in response to a shelter in place directive from the U.K.
−Removed: This directive expired in March 2021 and we expect the other COVID-19 related restrictions will continue to be lifted through June 2021, assuming the pandemic does not worsen in the United Kingdom .
−Removed: I nitial screening activity has resumed at certain sites following the lifting of the shelter in place directive .
−Removed: However, we expect that some sites may take longer to resume their trial activity due to increased COVID-19 infection rates in the areas where they are located that other sites may cease to participate in the trial entirely.
−Removed: We have decided not to pursue opening new clinical sites in Germany due to the estimated timing and cost to add these additional sites.
−Removed: Instead, in light of the easing of pandemic restrictions in the United Kingdom, we are focusing our efforts on the completion of enrollment in the Phase 2 CANAL trial in the United Kingdom.
−Removed: Furthermore, a s a result of the SSRE analysis, we have increased the target number of enrolled patients for our Phase 2b/3 PRISM trial from 240 to 360 subjects, which has also resulted in delays to our expected completion of enrollment for the trial and our anticipated timing for reporting top-line data for the trial.
+Added: In addition, as a result of COVID-19, clinical sites for our Phase 2b/3 PRISM trial temporarily halted new subject screening and most subject enrollment.
+Added: After resuming screening and enrollment, multiple sites in the Phase 2b/3 PRISM trial have begun requiring remote monitoring of subject data.
+Added: In addition, the clinical sites in our ongoing Phase 2 CANAL trial temporarily suspended enrollment and treatment of subjects in the trial due to the vulnerability of IPF patients to COVID-19 and we amended the protocol for the trial to reduce the number of in-person subject visits and procedures.
+Added: While subject screening and enrollment for our Phase 2 CANAL trial resumed at certain clinical trial sites in the fourth quarter of 2020, all sites in the trial paused screening again in December 2020 in response to a shelter-in-place directive from the U.K.
+Added: This shelter-in-place directive expired in March 2021 and other COVID-19 related restrictions were lifted in July 2021.
+Added: government may choose to reinstate any and/or all of the restrictions in the future depending on COVID-19 rates.
+Added: Initial screening activity has resumed at certain sites following the lifting of the shelter-in-place directive.
+Added: However, we expect that some sites may take longer to resume their trial activity as the clinical research related infrastructure was disrupted by COVID-19 and that other sites may cease to participate in the trial entirely.
+Added: Furthermore, as a result of the SSRE analysis, we have increased the target number of enrolled subjects for our Phase 2b/3 PRISM trial from 240 to 360 subjects, which has also resulted in delays to our expected completion of enrollment for the trial and our anticipated timing for reporting top-line data for the trial.
Other companies are conducting clinical trials or have announced plans for future clinical trials that are seeking or are likely to seek to enroll patients with prurigo nodularis in the case of our Phase 2b/3 PRISM trial and patients with IPF in the case of our Phase 2 CANAL trial and patients are generally only able to enroll in a single trial at a time.
−Removed: In addition, although there are no drugs approved in the United States or Europe for the treatment of pruritus associated with prurigo nodularis, many patients use various treatments off-label, such as antihistamines or gabapentin, and these patients and their physicians may be reluctant to forgo, discontinue or otherwise alter their use of such off-label therapeutic approaches to participate in our clinical trials.
−Removed: Our inability to enroll a sufficient number of patients for our clinical trials could result in significant delays or may require us to abandon one or more clinical trials altogether.
+Added: In addition, although there are no drugs approved in the U.S.
+Added: or Europe for the treatment of pruritus associated with prurigo nodularis, many patients use various treatments off-label, such as antihistamines or gabapentin and these patients and their physicians may be reluctant to forgo, discontinue or otherwise alter their use of such off-label therapeutic approaches to participate in our clinical trials.
+Added: Our inability to enroll a sufficient number of subjects for our clinical trials could result in significant delays or may require us to abandon one or more clinical trials altogether.
Enrollment delays in our clinical trials may result in increased development costs for Haduvio or any future product candidate, delay or halt the development of and approval processes for such product candidate and jeopardize our ability to commence sales of and generate revenues from such product candidate, any of which could cause the value of our company to decline and limit our ability to obtain additional financing, if needed.
7 unchanged sentences
The drug label for nalbuphine, the active ingredient in Haduvio, carries an opioid class label warning for serious, life-threatening or fatal respiratory depression and Haduvio, if approved for marketing in any indication, will likely carry a similar opioid class label.
−Removed: To support our planned submission of an NDA to the FDA for Haduvio, we may be required to conduct a clinical trial of Haduvio to assess cardiac risk and, due to the association of opioids with endocrine dysfunction, a clinical trial to evaluate potential endocrine side effects.
+Added: To support our planned submission of an NDA to the FDA for Haduvio, we may be required to conduct a clinical trial of Haduvio to assess cardiac risk and, due to the association of opioids with endocrine dysfunction, a clinical trial to
+Added: evaluate potential endocrine side effects.
We cannot be certain that any of these side effects often associated with opioids, or other side effects, will not be observed or observed at more severe levels in the future or that the FDA will not require additional trials or impose more severe labeling restrictions due to these side effects or other concerns.
−Removed: Such drug-related side effects could also affect patient recruitment or the ability of enrolled patients to complete a trial or result in potential product liability claims.
+Added: Such drug-related side effects could also affect patient recruitment or the ability of enrolled subjects to complete a trial or result in potential product liability claims.
In our Phase 2 clinical trial of Haduvio for the treatment of pruritus associated with prurigo nodularis, the most frequently reported adverse events associated with Haduvio were nausea, dizziness and headache.
In the open label extension of the trial, nausea, dizziness and fatigue were reported.
−Removed: Across both the Phase 2 clinical trial of Haduvio for the treatment of pruritus associated with prurigo nodularis and the open label extension, a total of four patients reported SAEs, but none of these events was attributed to Haduvio.
+Added: Across both the Phase 2 clinical trial of Haduvio for the treatment of pruritus associated with prurigo nodularis and the open label extension, a total of four subjects reported SAEs, but none of these events was attributed to Haduvio.
In our Phase 2b/3 trial of Haduvio in patients with uremic pruritus, the most frequently reported adverse events attributed to Haduvio were nausea, vomiting, somnolence and dizziness.
12 unchanged sentences
Furthermore, risks of Haduvio that are not adequately addressed through a proposed REMS program for Haduvio may also prevent or delay any approval for commercialization.
−Removed: In addition, while the intravenous formulation of nalbuphine is currently not classified as a controlled substance under the federal Controlled Substances Act of 1970, or the CSA, or the regulations of the U.S.
−Removed: Drug Enforcement Agency, or the DEA, it is the only opioid analgesic that is approved for marketing in the United States that is not classified as a controlled substance.
+Added: In addition, the parenteral formulation of nalbuphine is currently not classified as a controlled substance under the federal Controlled Substances Act of 1970 or the regulations of the U.S.
+Added: Drug Enforcement Agency, or the DEA, in the U.S.
It is possible that, based on the results of our HAL study, adverse events in our clinical trials or for other reasons, the DEA could determine that Haduvio, which is an oral, extended-release formulation, should be classified as a controlled substance.
The DEA regulates controlled substances as Schedule I, II, III, IV or V substances.
−Removed: Schedule I substances by definition have no established medicinal use and may not be marketed or sold in the United States.
+Added: Schedule I substances by definition have no established medicinal use and may not be marketed or sold in the U.S.
A pharmaceutical product may be listed as Schedule II, III, IV or V, with Schedule II substances considered to present the highest risk of abuse and carrying the greater level of regulatory control and Schedule V substances considered to present the lowest relative risk of abuse among such substances and, accordingly, the lowest level of regulatory control.
4 unchanged sentences
If Haduvio is classified as a controlled substance, the level of regulation would depend on how it is scheduled and we and our suppliers, manufacturers, contractors, distributors and any future customers would be required to obtain and maintain any applicable registrations from state, federal and foreign law enforcement and regulatory agencies and comply with any applicable state, federal and foreign laws and regulations regarding the manufacture, use, sale, importation, exportation and distribution of controlled substances.
−Removed: Also, if Haduvio is classified as a controlled substance, there is a risk that such regulations could limit its supply for use in clinical trials and, in the future, limit our ability to produce and distribute Haduvio in the volume needed to meet potential commercial demand.
+Added: Also, if Haduvio is classified as a controlled substance, there is a risk that such regulations could limit its supply for use in
+Added: clinical trials and, in the future, limit our ability to produce and distribute Haduvio in the volume needed to meet potential commercial demand.
Regulations associated with controlled substances govern manufacturing, labeling, packaging, testing, dispensing, production and procurement quotas, record keeping, reporting, handling, shipment and disposal.
3 unchanged sentences
The DEA may seek civil penalties, refuse to renew necessary registrations or initiate proceedings to revoke those registrations.
−Removed: In some circumstances,
−Removed: violations could lead to criminal proceedings.
+Added: In some circumstances, violations could lead to criminal proceedings.
Because of the restrictive nature of these regulations, if Haduvio is classified as a controlled substance, depending on how it is scheduled, its commercial prospects could be limited.
5 unchanged sentences
At a meeting with the FDA following the completion of our Phase 2 clinical trial of Haduvio for the treatment of pruritus associated with prurigo nodularis, the FDA advised us that the findings of the Phase 2 clinical trial may not be reliable and recommended that we conduct an additional Phase 2 dose ranging trial to identify the optimal dose and obtain reliable estimates of treatment effect for the recommended primary efficacy endpoint so as to better design and power our planned Phase 3 clinical trials.
−Removed: In providing such advice, the FDA noted the small number of patients in each arm of the Phase 2 clinical trial and the large differential discontinuation rate among the three treatment arms, as well as our plan to increase the fixed-dose treatment duration from eight weeks in the Phase 2 clinical trial to 12 weeks in our Phase 2b/3 PRISM trial.
+Added: In providing such advice, the FDA noted the small number of subjects in each arm of the Phase 2 clinical trial and the large differential discontinuation rate among the three treatment arms, as well as our plan to increase the fixed-dose treatment duration from eight weeks in the Phase 2 clinical trial to 12 weeks in our Phase 2b/3 PRISM trial.
We have limited experience in designing pivotal clinical trials and flaws in the design of a clinical trial could result in significant delays in completing the clinical trial or may require us to abandon the clinical trial altogether or conduct additional clinical trials.
For example, we have designed our Phase 2b/3 PRISM trial based on an assumed discontinuation rate that takes into account observed discontinuation rates in our Phase 2 clinical trial of Haduvio for the treatment of pruritus associated with prurigo nodularis.
−Removed: If enrolled patients withdraw from our Phase 2b/3 PRISM trial at a rate that is higher than expected, as occurred in our Phase 2 clinical trial of Haduvio for the treatment of pruritus associated with prurigo nodularis, or at rates that are inconsistent across clinical sites and treatment arms, we may not achieve the primary endpoint of the trial, the validity or statistical significance of the trial could be impaired and regulatory authorities may not view the trial as supportive of an application for marketing approval.
+Added: If enrolled subjects withdraw from our Phase 2b/3 PRISM trial at a rate that is higher than expected, as occurred in our Phase 2 clinical trial of Haduvio for the treatment of pruritus associated with prurigo nodularis or at rates that are inconsistent across clinical sites and treatment arms, we may not achieve the primary endpoint of the trial, the validity or statistical significance of the trial could be impaired and regulatory authorities may not view the trial as supportive of an application for marketing approval.
Preclinical and clinical data are also often susceptible to varying interpretations and analyses.
54 unchanged sentences
To achieve commercial success for any approved product, we must either develop a sales and marketing organization or outsource these functions to third parties.
−Removed: If Haduvio receives marketing approval from the FDA in any of our target indications, we believe we will have the opportunity to commercialize it in the United States directly through our own focused, specialty sales organization.
−Removed: If Haduvio receives marketing approval outside the United States, we may develop a variety of collaboration, distribution and other marketing arrangements with one or more third parties to commercialize the product in those markets.
+Added: If Haduvio receives marketing approval from the FDA in any of our target indications, we believe we will have the opportunity to commercialize it in the U.S.
+Added: directly through our own focused, specialty sales organization.
+Added: If Haduvio receives marketing approval outside the U.S., we may develop a variety of collaboration, distribution and other marketing arrangements with one or more third parties to commercialize the product in those markets.
We plan to build focused capabilities to commercialize development programs for certain indications where we believe that medical specialists are sufficiently concentrated to allow us to effectively promote products with a specialty sales team.
2 unchanged sentences
This may be costly and our business and financial prospects could be significantly affected if we could not retain or reposition our sales and marketing personnel.
−Removed: In addition, we may not be able to hire or retain a sales force in the United States that is sufficient in size or has adequate expertise in the medical markets that we plan to target.
+Added: In addition, we may not be able to hire or retain a sales force in the U.S.
+Added: that is sufficient in size or has adequate expertise in the medical markets that we plan to target.
If we are unable to establish or retain an adequate sales force and marketing and distribution capabilities, our operating results may be adversely affected.
3 unchanged sentences
As a result of entering into arrangements with third parties to perform sales, marketing and distribution services, our product revenues or the profitability of these product revenues may be substantially lower than if we were to directly market and sell products in those markets.
−Removed: Furthermore, we may be unsuccessful in entering into the necessary arrangements with third parties or may be unable to do so on terms that are favorable to us.
+Added: Furthermore, we may be unsuccessful in
+Added: entering into the necessary arrangements with third parties or may be unable to do so on terms that are favorable to us.
In addition, we may have little or no control over such third parties and any of them may fail to devote the necessary resources and attention to sell and market our products effectively.
6 unchanged sentences
If Haduvio is approved for the treatment of pruritus associated with prurigo nodularis, we expect that it would compete with a number of therapeutics that are used off-label to treat prurigo nodularis, including anti-itch creams and emollients, oral or injectable antihistamines, Dupixent (dupilumab), which is an injectable prescription medicine approved for atopic dermatitis that is in clinical development for the treatment of pruritus associated with prurigo nodularis, gabapentin and Lyrica (pregabalin), which are prescription medicines approved for the treatment of seizures and neuropathic pain, naltrexone and UVB light therapy.
−Removed: We also expect that Haduvio might compete with product candidates currently in clinical development in this indication, including nemolizumab, an anti-interleuk in-31 receptor A humanized monoclonal antibody being developed by Galderma;
+Added: We also expect that Haduvio might compete with product candidates currently in clinical development in this indication, including nemolizumab, an anti-interleukin-31 receptor A humanized monoclonal antibody being developed by Galderma;
KPL-716, a monoclonal antibody targeting oncostatin M receptor beta being developed by Kiniksa Pharmaceuticals;
3 unchanged sentences
In addition, it is possible that product candidates currently in development for the treatment of IPF could, if approved, reduce the need for therapies to treat chronic cough associated with IPF.
−Removed: If Haduvio is approved for the treatment of levodopa-induced dyskinesia, or LID, in patients with Parkinson’s disease, we expect that it would compete with Gocovri and Osmolex, which are extended release capsule formulations of amantadine marketed by Adamas Pharmaceuticals and expect that it might also compete with other product candidates currently in development for the treatment of LID by companies including Addex Therapeutics and IRLAB Therapeutics.
+Added: If Haduvio is approved for the treatment of LID in patients with Parkinson’s disease, we expect that it would compete with Gocovri and Osmolex, which are extended-release capsule formulations of amantadine marketed by Adamas Pharmaceuticals and expect that it might also compete with other product candidates currently in development for the treatment of LID by companies including Addex Therapeutics and IRLAB Therapeutics.
In addition, it is possible that product candidates currently in development for the treatment of Parkinson’s disease by companies could, if approved, reduce the need for therapies to treat LID.
5 unchanged sentences
Once an NDA is approved, the product covered thereby becomes a “reference-listed drug” in the FDA’s publication, “Approved Drug Products with Therapeutic Equivalence Evaluations,” or the Orange Book.
−Removed: Manufacturers may seek approval of generic versions of reference-listed drugs through submission of abbreviated new drug applications, or ANDAs, in the United States.
−Removed: In support of an ANDA, a generic manufacturer need not conduct clinical trials.
+Added: Manufacturers may seek approval of generic versions of reference-listed drugs through submission of abbreviated new drug applications, or ANDAs, in the U.S.
+Added: In support of an ANDA, a
+Added: generic manufacturer need not conduct clinical trials.
Rather, the applicant generally must show that its product has the same active ingredient(s), dosage form, strength, route of administration and conditions of use or labeling as the reference-listed drug and that the generic version is bioequivalent to the reference-listed drug, meaning it is absorbed in the body at the same rate and to the same extent.
9 unchanged sentences
Even if we are able to commercialize a product candidate, the product may become subject to unfavorable pricing regulations, third-party payor reimbursement practices or healthcare reform initiatives, any of which could harm our business.
−Removed: The commercial success of any product we develop will depend substantially, both in the United States and other countries, on the extent to which the costs of the product will be paid by third-party payors, including government health administration authorities and private health coverage insurers.
+Added: The commercial success of any product we develop will depend substantially, both in the U.S.
+Added: and other countries, on the extent to which the costs of the product will be paid by third-party payors, including government health administration authorities and private health coverage insurers.
If coverage and reimbursement are not available or reimbursement is available only to limited levels, we may not be able to successfully commercialize that product.
Even if coverage is provided for the product, the approved reimbursement amount may not be high enough to allow us to establish or maintain pricing sufficient to realize a return on our investments.
−Removed: In the United States, no uniform policy of coverage and reimbursement for products exists among third-party payors and coverage and reimbursement for products can differ significantly from payor to payor.
+Added: In the U.S., no uniform policy of coverage and reimbursement for products exists among third-party payors and coverage and reimbursement for products can differ significantly from payor to payor.
As a result, the coverage determination process is often a time-consuming and costly process that will require us to provide scientific and clinical support for the use of any product we commercialize to each payor separately, with no assurance that coverage and adequate reimbursement will be applied consistently or obtained in the first instance.
9 unchanged sentences
Third-party payors decide which medications they will cover and establish reimbursement levels.
−Removed: The healthcare industry is acutely focused on cost containment, both in the United States and other countries.
+Added: The healthcare industry is acutely focused on cost containment, both in the U.S.
+Added: and other countries.
Government authorities and other third-party payors have attempted to control costs by limiting coverage and the amount of reimbursement for particular medications, which could affect our ability to sell products profitably.
3 unchanged sentences
The commercial potential of any products we are able to commercialize depends in part on reimbursement by government health administration authorities, private health insurers and other organizations.
−Removed: If we are unable to obtain coverage or reimbursement for those products at the levels anticipated, our financial condition could be harmed.
+Added: If we are unable to obtain coverage or reimbursement for
+Added: those products at the levels anticipated, our financial condition could be harmed.
Additionally, if new compounds currently in development by potential competitors obtain marketing approval, there may be downward pressure on reimbursement levels for therapies in our target indications, which could have a negative impact on our ability to achieve and maintain profitability.
There may also be delays in obtaining coverage and reimbursement for newly approved drugs and coverage may be more limited than the indications for which the drug is approved by the FDA or comparable foreign regulatory authorities.
−Removed: eligibility for reimbursement does not imply that any drug will be paid for in all cases or at a rate that covers our costs, including development, manufacture, sale and distribution.
+Added: Moreover, eligibility for reimbursement does not imply that any drug will be paid for in all cases or at a rate that covers our costs, including development, manufacture, sale and distribution.
Reimbursement rates may vary, by way of example, according to the use of the product and the clinical setting in which it is used.
2 unchanged sentences
We cannot be sure that coverage will be available for any product candidate that we commercialize and, if available, that the reimbursement rates will be adequate.
−Removed: Further, the net reimbursement for drug products may be subject to additional reductions if there are changes to laws that presently restrict imports of drugs from countries where they may be sold at lower prices than in the United States.
+Added: Further, the net reimbursement for drug products may be subject to additional reductions if there are changes to laws that presently restrict imports of drugs from countries where they may be sold at lower prices than in the U.S.
An inability to promptly obtain coverage and adequate payment rates from both government-funded and private payors for any of our product candidates for which we obtain marketing approval could significantly harm our operating results, our ability to raise capital needed to commercialize products and our overall financial condition.
23 unchanged sentences
We do not independently conduct clinical trials of our product candidate.
−Removed: We rely, and expect to continue to rely, on third parties, such as clinical research organizations, or CROs, clinical data management organizations, medical institutions and clinical investigators, to conduct our clinical trials of Haduvio and any future product candidate that we may develop.
+Added: We rely and expect to continue to rely, on third parties, such as CROs, clinical data management organizations, medical institutions and clinical investigators, to conduct our clinical trials of Haduvio and any future product candidate that we may develop.
These third parties may terminate their engagements with us under certain circumstances.
We may not be able to enter into alternative arrangements or do so on commercially reasonable terms.
−Removed: In addition, there is a natural transition period when a new CRO begins work on a clinical trial.
+Added: addition, there is a natural transition period when a new CRO begins work on a clinical trial.
As a result, delays would likely occur, which could negatively impact our ability to meet our expected clinical development timelines and harm our business, financial condition and prospects.
4 unchanged sentences
We cannot be certain that, upon inspection, the FDA will determine that any of our clinical trials complies with cGCPs.
−Removed: Similar regulatory requirements apply outside the United States, including the International Council for Harmonisation of Technical Requirements for the Registration of Pharmaceuticals for Human Use, or ICH.
+Added: Similar regulatory requirements apply outside the U.S., including the International Council for Harmonisation of Technical Requirements for the Registration of Pharmaceuticals for Human Use, or ICH.
We are also required to register clinical trials and post the results of completed clinical trials on a government-sponsored database, ClinicalTrials.gov, within certain timeframes.
1 unchanged sentence
Furthermore, the third parties conducting clinical trials on our behalf are not our employees and except for remedies available to us under our agreements with our contractors, we cannot control whether they devote sufficient time, skill and resources to our ongoing development programs.
−Removed: These third parties may be also impacted by developments in the COVID-19 pandemic or government measures taken in response to the pandemic in ways that negatively impact their ability to fulfill their contractual obligations to us in connection with our clinical trials, even if we are not otherwise directly affected by such developments or measures.
+Added: These third parties may be also impacted by developments in COVID-19 or government measures taken in response to the pandemic in ways that negatively impact their ability to fulfill their contractual obligations to us in connection with our clinical trials, even if we are not otherwise directly affected by such developments or measures.
Additionally, these third parties may have relationships with other commercial entities, including potential competitors, for which they may also be conducting clinical trials or other drug development activities, which could impede their ability to devote appropriate time to our clinical programs.
17 unchanged sentences
We do not have long-term supply agreements with any of our contract manufacturers.
−Removed: If any of our existing manufacturers should become unavailable to us for any reason, or fail to supply us with the ordered quantities, including as a result of the COVID-19 pandemic or government measures taken in response to the pandemic, we may incur delays in identifying or qualifying replacement
−Removed: manufacturers or in obtaining replacement supply.
+Added: If any of our existing manufacturers should become unavailable to us for any reason or fail to supply us with the ordered quantities, including as a result of COVID-19 or government measures taken in response to the pandemic, we may incur delays in identifying or qualifying replacement manufacturers or in obtaining replacement supply.
Any performance failure on the part of our contract manufacturers or the other third-party contractors that we use to store and distribute drug substance and drug product could be disruptive to our operations and delay clinical development or marketing approval of Haduvio or any future product candidates of ours or commercialization of any resulting products, producing additional losses and depriving us of potential product revenue.
9 unchanged sentences
Consequently, we may not be able to reach agreement with third-party manufacturers on satisfactory terms, in a timely manner or at all, which could delay our commercialization efforts.
−Removed: Third-party manufacturers are required to comply with cGMPs and similar regulatory requirements outside the United States, such as the ICH.
+Added: Third-party manufacturers are required to comply with cGMPs and similar regulatory requirements outside the U.S., such as the ICH.
Facilities used by our third-party manufacturers must be approved by the FDA after we submit an NDA and before potential approval of the applicable product candidate.
11 unchanged sentences
Potential collaborators may include large and mid-size pharmaceutical companies, regional and national pharmaceutical companies, biotechnology companies and academic research institutions.
−Removed: In addition, if we are able to obtain marketing approval for any product candidates from foreign regulatory authorities, we intend to enter into strategic relationships with international biotechnology or pharmaceutical companies for the commercialization of those product candidates outside of the United States.
+Added: In addition, if we are able to obtain marketing approval for any product candidates from foreign regulatory authorities, we intend to enter into strategic relationships with international biotechnology or pharmaceutical companies for the commercialization of those product candidates outside of the U.S.
We face significant competition in seeking appropriate collaborators.
There have been a significant number of recent business combinations among large pharmaceutical companies that have resulted in a reduced number of potential future collaborators.
−Removed: Whether we reach a definitive agreement for a collaboration will depend, among other things, upon our assessment of the collaborator’s resources and expertise, the terms and conditions of the proposed collaboration and the proposed collaborator’s
−Removed: evaluation of a number of factors.
+Added: Whether we reach a definitive agreement for a collaboration will depend, among other things, upon our assessment of the collaborator’s resources and expertise, the terms and conditions of the proposed collaboration and the proposed collaborator’s evaluation of a number of factors.
Those factors may include the potential differentiation of our product candidates from competing product candidates, design or results of clinical trials, the likelihood of approval by the FDA or comparable foreign regulatory authorities and the regulatory pathway for any such approval, the potential market for the product candidate, the costs and complexities of manufacturing and delivering the product to patients and existing or potential competing products.
5 unchanged sentences
If we do not have sufficient funds, we may not be able to further develop our product candidates or bring them to market and generate product revenue.
−Removed: If we establish one or more collaborations, all of the risks relating to product development, regulatory approval and commercialization described in this Quarterly Report on Form 10-Q would also apply to the activities of any such future collaborators.
+Added: If we establish one or more collaborations, all the risks relating to product development, regulatory approval and commercialization described in this Quarterly Report on Form 10-Q would also apply to the activities of any such future collaborators.
If we enter into collaborations with third parties for the development or commercialization of Haduvio or any future product candidate, our prospects with respect to those product candidates will depend in significant part on the success of those collaborations.
28 unchanged sentences
If we fail to comply with our material obligations under these agreements or if we are subject to a bankruptcy event, the licensor may have the right to terminate the license or convert the license to a non-exclusive license, in which event we may be required to negotiate a new or reinstated license with less favorable terms or would not be able to exclusively market or market at all, products covered by the license.
−Removed: For instance, Rutgers University has asserted that we are not in compliance with our diligence obligations under our license agreement with Rutgers University and could seek to terminate the license agreement if we are unable to resolve the matter.
Any termination of our license agreements could have a material adverse impact on our business.
8 unchanged sentences
If we are unable to obtain and maintain sufficient patent protection for Haduvio or any future product candidate and the disease indications for which we are developing or may in the future develop , Haduvio or if the scope of the patent protection is not sufficiently broad, competitors could develop and commercialize products similar or identical to such product candidate and our ability to successfully commercialize such product candidate may be adversely affected.
−Removed: Our success depends in large part on our ability to obtain and maintain patent protection in the United States and other countries with respect to Haduvio and any future product candidates, and their use for indications for which we are developing, or may develop, them in the future.
+Added: Our success depends in large part on our ability to obtain and maintain patent protection in the U.S.
+Added: and other countries with respect to Haduvio and any future product candidates and their use for indications for which we are developing or may develop, them in the future.
If we do not adequately protect our intellectual property rights, competitors may erode or negate any competitive advantage we may have, which could harm our business and ability to achieve profitability.
−Removed: To protect our proprietary position, we have licensed exclusive rights under patents, prosecuted additional patents and filed patent applications in the United States and other countries related to methods of use and formulations of Haduvio.
+Added: To protect our proprietary position, we have licensed exclusive rights under patents, prosecuted additional patents and filed patent applications in the U.S.
+Added: and other countries related to methods of use and formulations of Haduvio.
The patent application and approval process is expensive and time-consuming.
10 unchanged sentences
The patent position of biotechnology and pharmaceutical companies generally is highly uncertain.
−Removed: No consistent policy regarding the breadth of claims allowed in biotechnology and pharmaceutical patents has emerged to date in the United States or in many foreign jurisdictions.
+Added: No consistent policy regarding the breadth of claims allowed in biotechnology and pharmaceutical patents has emerged to date in the U.S.
+Added: or in many foreign jurisdictions.
In addition, the determination of patent rights with respect to pharmaceutical compounds commonly involves complex legal and factual questions, which in recent years have been the subject of much litigation.
2 unchanged sentences
Assuming the other requirements for patentability are met, currently, the first to file a patent application is generally entitled to the patent.
−Removed: However, prior to March 16, 2013, in the United States, the first to invent was entitled to the patent.
−Removed: Publications of discoveries in the scientific literature often lag behind the actual discoveries, and patent applications in the United States and other jurisdictions are typically not published until 18 months after filing, or in some cases not at all.
+Added: However, prior to March 16, 2013, in the U.S., the first to invent was entitled to the patent.
+Added: Publications of discoveries in the scientific literature often lag behind the actual discoveries and patent applications in the U.S.
+Added: and other jurisdictions are typically not published until 18 months after filing or in some cases not at all.
Therefore, we cannot be certain that we were the first to make the inventions claimed in our patents or pending patent applications or that we were the first to file for patent protection of such inventions.
Similarly, we cannot be certain that parties from whom we do or may license or purchase patent rights were the first to make relevant claimed inventions or were the first to file for patent protection for them.
−Removed: If third parties have filed patent applications on inventions claimed in our patents or applications on or before March 15, 2013, an interference proceeding in the United States can be initiated by such third parties to determine who was the first to invent any of the subject matter covered by the patent claims of our applications.
−Removed: If third parties have filed such applications after March 15, 2013, a derivation proceeding in the United States can be initiated by such third parties to determine whether our invention was derived from theirs.
−Removed: Moreover, because the issuance of a patent is not conclusive as to its inventorship, scope, validity or enforceability, our patents or pending patent applications may be challenged in the courts or patent offices in the United States and other countries.
+Added: If third parties have filed patent applications on inventions claimed in our patents or applications on or before March 15, 2013, an interference proceeding in the U.S.
+Added: can be initiated by such third parties to determine who was the first to invent any of the subject matter covered by the patent claims of our applications.
+Added: If third parties have filed such applications after March 15, 2013, a derivation proceeding in the U.S.
+Added: can be initiated by such third parties to determine whether our invention was derived from theirs.
+Added: Moreover, because the issuance of a patent is not conclusive as to its inventorship, scope, validity or enforceability, our patents or pending patent applications may be challenged in the courts or patent offices in the U.S.
+Added: and other countries.
There is no assurance that all of the potentially relevant prior art relating to our patents and patent applications has been found.
2 unchanged sentences
Patent and Trademark Office, or USPTO, or to other patent offices around the world.
−Removed: Alternatively or additionally, we may become involved in post-grant review procedures, oppositions, derivation proceedings, reexaminations, inter partes review or interference proceedings, in the United States or other countries, challenging patents or patent applications in which we have rights, including patents on which we rely to protect our business.
−Removed: An adverse determination in any such challenge may result in loss of exclusivity or in patent claims being narrowed,
−Removed: invalidated or held unenforceable, in whole or in part, which could limit our ability to stop others from using or commercializing similar or identical products or product candidates, or limit the duration of the patent protection of Haduvio or any future product candidates of ours.
+Added: Alternatively or additionally, we may become involved in post-grant review procedures, oppositions, derivation proceedings, reexaminations, inter partes review or interference proceedings, in the U.S.
+Added: or other countries, challenging patents or patent applications in which we have rights, including patents on which we rely to protect our business.
+Added: An adverse determination in any such challenge may result in loss of exclusivity or in patent claims being narrowed, invalidated or held unenforceable, in whole or in part, which could limit our ability to stop others from using or commercializing similar or identical
+Added: products or product candidates or limit the duration of the patent protection of Haduvio or any future product candidates of ours.
In addition, given the amount of time required for the development, testing and regulatory review of new product candidates, patents protecting such candidates might expire before or shortly after such candidates are commercialized.
1 unchanged sentence
As a result, the inventorship or ownership of our intellectual property may be challenged in the future.
−Removed: Changes in either the patent laws or interpretation of the patent laws in the United States and other countries may diminish the value of our patents or narrow the scope of our patent protection.
−Removed: In addition, the laws of foreign countries may not protect our rights to the same extent or in the same manner as the laws of the United States.
−Removed: For example, patent laws in various jurisdictions, including significant commercial markets such as Europe, restrict the patentability of methods of treatment of the human body more than United States law does.
−Removed: Issued patents that we have or may obtain or license may not provide us with any meaningful protection, prevent competitors from competing with us or otherwise provide us with any competitive advantage.
+Added: Changes in either the patent laws or interpretation of the patent laws in the U.S.
+Added: and other countries may diminish the value of our patents or narrow the scope of our patent protection.
+Added: In addition, the laws of foreign countries may not protect our rights to the same extent or in the same manner as the laws of the U.S.
+Added: For example, patent laws in various jurisdictions, including significant commercial markets such as Europe, restrict the patentability of methods of treatment of the human body more than U.S.
+Added: Issued patents that we have, may obtain or license may not provide us with any meaningful protection, prevent competitors from competing with us or otherwise provide us with any competitive advantage.
Our competitors may be able to circumvent patents by developing similar or alternative technologies or products in a non-infringing manner.
22 unchanged sentences
In any patent infringement proceeding, there is a risk that a court will decide that one of our patents is invalid or unenforceable, in whole or in part and that we do not have the right to stop the other party from using the invention at issue.
−Removed: There is also a risk that, even if the validity of such patents is upheld, the court will construe the patent’s claims narrowly or decide
−Removed: that we do not have the right to stop the other party from using the invention at issue on the grounds that our patent claims do not cover the invention.
−Removed: An adverse outcome in a litigation or proceeding involving one or more of our patents could limit our ability to assert those patents against those parties or other competitors, and may curtail or preclude our ability to exclude third parties from making and selling similar or competitive products.
+Added: There is also a risk that, even if the validity of such patents is upheld, the court will construe the patent’s claims narrowly or decide that we do not have the right to stop the other party from using the invention at issue on the grounds that our patent claims do not cover the invention.
+Added: An adverse outcome in a litigation or proceeding involving one or more of our patents could limit our ability to assert those patents against those parties or other competitors and may curtail or preclude our ability to exclude third parties from
+Added: making and selling similar or competitive products.
Similarly, if we assert trademark infringement claims, a court may determine that the marks we have asserted are invalid or unenforceable or that the party against whom we have asserted trademark infringement has superior rights to the marks in question.
19 unchanged sentences
Proving invalidity is difficult.
−Removed: For example, in the United States, proving invalidity requires a showing of clear and convincing evidence to overcome the presumption of validity enjoyed by issued patents.
+Added: For example, in the U.S., proving invalidity requires a showing of clear and convincing evidence to overcome the presumption of validity enjoyed by issued patents.
Even if we are successful in these proceedings, we may incur substantial costs and the time and attention of our management and scientific personnel could be diverted in pursuing these proceedings, which could significantly harm our business and operating results.
8 unchanged sentences
Claims that we have misappropriated the confidential information or trade secrets of third parties could have a similar negative impact on our business.
−Removed: Changes to the patent law in the United States and other jurisdictions could diminish the value of patents in general, thereby impairing our ability to protect our products.
+Added: Changes to the patent law in the U.S.
+Added: and other jurisdictions could diminish the value of patents in general, thereby impairing our ability to protect our products.
As is the case with other biopharmaceutical companies, our success is heavily dependent on intellectual property, particularly patents.
Obtaining and enforcing patents in the biopharmaceutical industry involves both technological and legal complexity and is therefore costly, time consuming and inherently uncertain.
−Removed: Recent patent reform legislation in the United States, including the Leahy-Smith America Invents Act, or the America Invents Act, could increase those uncertainties and costs.
+Added: Recent patent reform legislation in the U.S., including the Leahy-Smith America Invents Act, or the America Invents Act, could increase those uncertainties and costs.
The America Invents Act was signed into law on September 16, 2011 and many of the substantive changes became effective on March 16, 2013.
−Removed: The America Invents Act reformed United States patent law in part by changing the U.S.
−Removed: patent system from a “first to invent” system to a “first inventor to file” system, expanding the definition of prior art, and developing a post-grant review system.
−Removed: This legislation changes United States patent law in a way that may weaken our ability to obtain patent protection in the United States for those applications filed after March 16, 2013.
−Removed: Further, the America Invents Act created new procedures to challenge the validity of issued patents in the United States, including post-grant review and inter partes review proceedings, which some third parties have been using to cause the cancellation of selected or all claims of issued patents of competitors.
+Added: The America Invents Act reformed U.S.
+Added: patent law in part by changing the U.S.
+Added: patent system from a “first to invent” system to a “first inventor to file” system,
+Added: expanding the definition of prior art and developing a post-grant review system.
+Added: This legislation changes U.S.
+Added: patent law in a way that may weaken our ability to obtain patent protection in the U.S.
+Added: for those applications filed after March 16, 2013.
+Added: Further, the America Invents Act created new procedures to challenge the validity of issued patents in the U.S., including post-grant review and inter partes review proceedings, which some third parties have been using to cause the cancellation of selected or all claims of issued patents of competitors.
For a patent with an effective filing date of March 16, 2013 or later, a petition for post-grant review can be filed by a third party in a nine-month window from issuance of the patent.
11 unchanged sentences
Supreme Court has ruled on several patent cases in recent years, either narrowing the scope of patent protection available in certain circumstances or weakening the rights of patent owners in certain situations.
−Removed: Additionally, there have been recent proposals for additional changes to the patent laws of the United States and other countries that, if adopted, could impact our ability to enforce our patents.
+Added: Additionally, there have been recent proposals for additional changes to the patent laws of the U.S.
+Added: and other countries that, if adopted, could impact our ability to enforce our patents.
In addition to increasing uncertainty with regard to our ability to obtain patents in the future, this combination of events has created uncertainty with respect to the value of patents once obtained.
3 unchanged sentences
We may not be able to enforce our intellectual property rights throughout the world.
−Removed: Filing, prosecuting and defending patents on our product candidates in all countries throughout the world would be prohibitively expensive, and our intellectual property rights in some countries outside the United States are less extensive than those in the United States.
+Added: Filing, prosecuting and defending patents on our product candidates in all countries throughout the world would be prohibitively expensive and our intellectual property rights in some countries outside the U.S.
+Added: are less extensive than those in the U.S.
The requirements for patentability may differ in certain countries, particularly in developing countries;
thus, even in countries where we do pursue patent protection, there can be no assurance that any patents will issue with claims that cover our products.
−Removed: Our competitors may export otherwise infringing products to territories where we have no patent protection or where we may obtain patent protection, but where patent enforcement is not as strong as that in the United States, and our issued or licensed patents and any future patent claims or other intellectual property rights may not be effective or sufficient to prevent them from so competing.
+Added: Our competitors may export otherwise infringing products to territories where we have no patent protection or where we may obtain patent protection, but where patent enforcement is not as strong as that in the U.S.
+Added: and our issued or licensed patents and any future patent claims or other intellectual property rights may not be effective or sufficient to prevent them from so competing.
Moreover, our ability to protect and enforce our intellectual property rights may be adversely affected by unforeseen changes in foreign intellectual property laws.
−Removed: Additionally, laws of some countries outside of the United States and Europe do not afford intellectual property protection to the same extent as the laws of the United States and Europe.
+Added: Additionally, laws of some countries outside of the U.S.
+Added: and Europe do not afford intellectual property protection to the same extent as the laws of the U.S.
Many companies have encountered significant problems in protecting and defending intellectual property rights in certain foreign jurisdictions.
2 unchanged sentences
For example, many foreign countries have compulsory licensing laws under which a patent owner must grant licenses to third parties.
−Removed: Consequently, we may not be able to prevent third parties from practicing our inventions in certain countries outside the United States and Europe.
+Added: Consequently, we may not be able to prevent third parties from practicing our inventions in certain countries outside the U.S.
Agreements through which we license patent rights may not give us sufficient rights to permit us to pursue enforcement of our licensed patents or defense of any claims asserting the invalidity of these patents (or control of enforcement or defense) of such patent rights in all relevant jurisdictions as requirements may vary.
17 unchanged sentences
Obtaining and maintaining patent protection depends on compliance with various procedural, document submission, fee payment and other requirements imposed by governmental patent agencies and our patent protection could be reduced or eliminated for non-compliance with these requirements.
−Removed: Periodic maintenance fees, renewal fees, annuity fees and various other governmental fees on patents and applications are required to be paid to the USPTO and various governmental patent agencies outside of the United States in several stages over the lifetime of the patents and applications.
+Added: Periodic maintenance fees, renewal fees, annuity fees and various other governmental fees on patents and applications are required to be paid to the USPTO and various governmental patent agencies outside of the U.S.
+Added: in several stages over the lifetime of the patents and applications.
The USPTO and various non-U.S.
12 unchanged sentences
The Drug Price Competition and Patent Term Restoration Act of 1984 or the Hatch-Waxman Act, added Section 505(b)(2) to the FDCA.
−Removed: Section 505(b)(2) permits the filing of an NDA where at least some of the information required for approval comes from studies that were not conducted by or for the applicant, and for which the applicant has not received a right of reference, which could expedite the development program for Haduvio for the treatment of pruritus associated with prurigo nodularis and any future product candidates by potentially decreasing the amount of preclinical and clinical data that we would need to generate in order to obtain FDA approval.
−Removed: However, while we believe that Haduvio is a reformulation of an existing drug and, therefore, its active moiety will not be treated as a new chemical entity, or NCE, the submission of an NDA under the Section 505(b)(2) regulatory pathway does not preclude the FDA from determining that Haduvio contains an active moiety that is an NCE and, therefore, is not eligible for review under such regulatory pathway.
+Added: Section 505(b)(2) permits the filing of an NDA where at least some of the information required for approval comes from studies that were not conducted by or for the applicant and for which the applicant has not received a right of reference, which could expedite the development program for Haduvio for the treatment of
+Added: pruritus associated with prurigo nodularis and any future product candidates by potentially decreasing the amount of preclinical and clinical data that we would need to generate in order to obtain FDA approval.
+Added: However, while we believe that Haduvio is a reformulation of an existing drug and, therefore, its active moiety will not be treated as a NCE, the submission of an NDA under the Section 505(b)(2) regulatory pathway does not preclude the FDA from determining that Haduvio contains an active moiety that is an NCE and, therefore, is not eligible for review under such regulatory pathway.
If the FDA does not allow us to pursue the Section 505(b)(2) or similar regulatory pathway as anticipated, we may need to conduct additional preclinical experiments and clinical trials, provide additional data and information and meet additional standards for regulatory approval.
14 unchanged sentences
The research, testing, manufacturing, labeling, approval, selling, marketing, promotion and distribution of products are subject to extensive regulation by the FDA and comparable foreign regulatory authorities.
−Removed: We are not permitted to market Haduvio or any other product candidate in the United States until we receive approval of an NDA from the FDA or in other countries until we receive marketing approval from the applicable regulatory authorities outside the United States.
−Removed: We have not submitted an application for or received marketing approval for any product candidate in the United States or in any other jurisdiction.
+Added: We are not permitted to market Haduvio or any other product candidate in the U.S.
+Added: until we receive approval of an NDA from the FDA or in other countries until we receive marketing approval from the applicable regulatory authorities outside the U.S.
+Added: We have not submitted an application for or received marketing approval for any product candidate in the U.S.
+Added: or in any other jurisdiction.
We have limited experience in conducting and managing the clinical trials necessary to obtain marketing approvals, including FDA approval of an NDA.
−Removed: The process of obtaining marketing approvals, both in the United States and other countries, is lengthy, expensive and uncertain.
+Added: The process of obtaining marketing approvals, both in the U.S.
+Added: and other countries, is lengthy, expensive and uncertain.
It may take many years, if approval is obtained at all and can vary substantially based upon a variety of factors, including the type, complexity and novelty of the product candidates involved.
5 unchanged sentences
Regulatory authorities have substantial discretion in the approval process and may refuse to accept any application or may decide that our data are insufficient for approval and require additional preclinical, clinical or other studies.
−Removed: In addition, varying interpretations of the data obtained from preclinical and clinical testing could delay, limit or prevent marketing approval of a product candidate.
+Added: In addition, varying interpretations of the data obtained from preclinical and clinical testing could delay, limit
+Added: or prevent marketing approval of a product candidate.
Any marketing approval we ultimately obtain may be limited or subject to restrictions or post-approval commitments that render the approved product not commercially viable.
3 unchanged sentences
If a prolonged government shutdown occurs, it could significantly impact the ability of the FDA to timely review and process our regulatory submissions, which could have a material adverse effect on our business.
−Removed: In response to the COVID-19 pandemic, on March 10, 2020, the FDA announced its intention to postpone most inspections of foreign manufacturing facilities, and on March 18, 2020, the FDA temporarily postponed routine surveillance inspections of domestic manufacturing facilities.
+Added: In response to COVID-19, on March 10, 2020, the FDA announced its intention to postpone most inspections of foreign manufacturing facilities and on March 18, 2020, the FDA temporarily postponed routine surveillance inspections of domestic manufacturing facilities.
Subsequently, on July 10, 2020, the FDA announced its intention to resume certain on-site inspections of domestic manufacturing facilities subject to a risk-based prioritization system.
The FDA intends to use this risk-based assessment system to identify the categories of regulatory activity that can occur within a given geographic area, ranging from mission critical inspections to resumption of all regulatory activities.
+Added: In May 2021, the FDA issued a report in which it outlined its priorities for inspections moving forward given the ongoing uncertainties stemming from the pandemic.
+Added: The agency indicated that inspections considered critical to the FDA’s mission will remain the primary focus.
+Added: When planning routine surveillance inspections, the agency will prioritize higher-risk establishments.
+Added: Therefore, a longer interval between inspections will occur for the less high-risk facilities as the FDA adjusts to the impact of COVID-19.
+Added: This means that postponed inspections will be prioritized based on risk and conducted over a longer period of time, ultimately increasing the amount of time between inspections of certain lower-risk facilities.
Regulatory authorities outside the United States may also impose similar restrictions or other policy measures in response to the COVID-19 pandemic.
1 unchanged sentence
Any delay in obtaining or failure to obtain required approvals and clearances could negatively impact our ability to generate revenue from the particular product candidate, which likely would result in significant harm to our financial position and adversely impact our stock price.
−Removed: We have conducted, are conducting and intend in the future to conduct clinical trials for Haduvio, and may conduct clinical trials for any future product candidates, at sites outside the United States.
−Removed: The FDA may not accept data from trials conducted in such locations and the conduct of trials outside the United States could subject us to additional delays and expense.
−Removed: We have conducted, are conducting and intend in the future to conduct clinical trials for Haduvio, and may conduct clinical trials for any future product candidates, at trial sites that are located outside the United States.
−Removed: Although the FDA may accept data from clinical trials conducted outside the United States, acceptance of these data is subject to certain conditions imposed by the FDA.
+Added: We have conducted, are conducting and intend in the future to conduct clinical trials for Haduvio and may conduct clinical trials for any future product candidates, at sites outside the U.S.
+Added: The FDA may not accept data from trials conducted in such locations and the conduct of trials outside the U.S.
+Added: could subject us to additional delays and expense.
+Added: We have conducted, are conducting and intend in the future to conduct clinical trials for Haduvio, and may conduct clinical trials for any future product candidates, at trial sites that are located outside the U.S.
+Added: Although the FDA may accept data from clinical trials conducted outside the U.S., acceptance of these data is subject to certain conditions imposed by the FDA.
For example, the clinical trial must be well designed and conducted and performed by qualified investigators in accordance with cGCPs.
3 unchanged sentences
population and U.S.
−Removed: medical practice in ways that the FDA deems clinically meaningful, except to the extent the disease being studied does not typically occur in the United States.
+Added: medical practice in ways that the FDA deems clinically meaningful, except to the extent the disease being studied does not typically occur in the U.S.
In addition, while these clinical trials are subject to the applicable local laws, FDA acceptance of the data will be dependent upon its determination that the trials also complied with all applicable U.S.
laws and regulations.
−Removed: There can be no assurance that the FDA will accept data from trials conducted outside of the United States.
−Removed: If the FDA does not accept the data from any trial that we conduct outside the United States, it would likely result in the need for additional trials, which would be costly and time-consuming and delay or permanently halt our development of Haduvio or the applicable future product candidate.
−Removed: In addition, the conduct of clinical trials outside the United States could have a significant adverse impact on us.
+Added: There can be no assurance that the FDA will accept data from trials conducted outside of the U.S.
+Added: If the FDA does not accept the data from any trial that we conduct outside the U.S., it would likely result in the need for additional trials, which would be costly and time-consuming and delay or permanently halt our development of Haduvio or the applicable future product candidate.
+Added: In addition, the conduct of clinical trials outside the U.S.
+Added: could have a significant adverse impact on us.
Risks inherent in conducting international clinical trials include:
6 unchanged sentences
Failure to obtain marketing approval in foreign jurisdictions would prevent Haduvio or any future product candidate from being marketed in other countries.
−Removed: Any marketing approval we are granted in the United States would not assure marketing approval in foreign jurisdictions.
−Removed: In order to market and sell products in the European Union and other foreign jurisdictions, we must obtain separate marketing approvals and comply with numerous and varying regulatory requirements.
+Added: Any marketing approval we are granted in the U.S.
+Added: would not assure marketing approval in foreign jurisdictions.
+Added: In order to market and sell products in the European Union, or E.U., and other foreign jurisdictions, we must obtain separate marketing approvals and comply with numerous and varying regulatory requirements.
The approval procedure varies among countries and can involve additional testing.
The time required to obtain approval may differ substantially from that required to obtain FDA approval.
−Removed: The marketing approval process outside the United States generally includes all of the risks associated with obtaining FDA approval.
−Removed: In addition, in many countries outside the United States, a product must be approved for reimbursement before the product can be approved for sale in that country.
−Removed: We may not obtain approvals from regulatory authorities outside the United States on a timely basis, if at all.
−Removed: Approval by the FDA does not ensure approval by regulatory authorities in other countries or jurisdictions, and approval by one regulatory authority outside the United States does not ensure approval by regulatory authorities in other countries or jurisdictions or by the FDA.
+Added: The marketing approval process outside the U.S.
+Added: generally includes all of the risks associated with obtaining FDA approval.
+Added: In addition, in many countries outside the U.S., a product must be approved for reimbursement before the product can be approved for sale in that country.
+Added: We may not obtain approvals from regulatory authorities outside the U.S.
+Added: on a timely basis, if at all.
+Added: Approval by the FDA does not ensure approval by regulatory authorities in other countries or jurisdictions and approval by one regulatory authority outside the U.S.
+Added: does not ensure approval by regulatory authorities in other countries or jurisdictions or by the FDA.
We may file for marketing approvals but not receive necessary approvals to commercialize any products in any market.
3 unchanged sentences
In addition, if we fail to obtain the non-U.S.
−Removed: approvals required to market products outside the United States or if we fail to comply with applicable non-U.S.
+Added: approvals required to market products outside the U.S.
+Added: or if we fail to comply with applicable non-U.S.
regulatory requirements, our target markets will be reduced and our ability to realize the full market potential of Haduvio or any future product candidate will be harmed and our business, financial condition, results of operations and prospects may be adversely affected.
−Removed: Additionally, we could face heightened risks with respect to seeking marketing approval in the United Kingdom as a result of the recent withdrawal of the United Kingdom from the European Union, commonly referred to as Brexit.
−Removed: The United Kingdom and European Union entered into a Trade and Cooperation Agreement in connection with Brexit that sets out certain procedures for approval and recognition of medical products in each jurisdiction.
−Removed: Since the regulatory framework for pharmaceutical products in the United Kingdom covering the quality, safety, and efficacy of pharmaceutical products, clinical trials, marketing authorization, commercial sales, and distribution of pharmaceutical products is derived from European Union directives and regulations, Brexit could materially impact the future regulatory regime that applies to products and the approval of product candidates in the United Kingdom.
−Removed: Any delay in obtaining, or an inability to obtain, any marketing approvals, as a result of the Trade and Cooperation Agreement would prevent us from commercializing any product candidates in the United Kingdom and/or the European Union and restrict our ability to generate revenue and achieve and sustain profitability.
−Removed: If any of these outcomes occur, we may be forced to restrict or delay efforts to seek regulatory approval in the United Kingdom and/or European Union for any product candidates, or incur additional costs, which could significantly and materially harm our business.
−Removed: We expect that we will be subject to additional risks in commercializing any of our product candidates that receive marketing approval outside the United States, including tariffs, trade barriers and regulatory requirements;
+Added: Additionally, we could face heightened risks with respect to seeking marketing approval in the U.K.
+Added: as a result of the recent withdrawal of the U.K.
+Added: from the E.U., commonly referred to as Brexit.
+Added: entered into a Trade and Cooperation Agreement in connection with Brexit that sets out certain procedures for approval and recognition of medical products in each jurisdiction.
+Added: Since the regulatory framework for pharmaceutical products in the U.K.
+Added: covering the quality, safety and efficacy of pharmaceutical products, clinical trials, marketing authorization, commercial sales and distribution of pharmaceutical products is derived from E.U.
+Added: directives and regulations, Brexit could materially impact the future regulatory regime that applies to products and the approval of product candidates in the U.K.
+Added: Any delay in obtaining or an inability to obtain, any marketing approvals, as a result of the Trade and Cooperation Agreement would prevent us from commercializing any product candidates in the U.K.
+Added: and/or the E.U.
+Added: and restrict our ability to generate revenue and achieve and sustain profitability.
+Added: If any of these outcomes occur, we may be forced to restrict or delay efforts to seek regulatory approval in the U.K.
+Added: for any product candidates or incur additional costs, which could significantly and materially harm our business.
+Added: We expect that we will be subject to additional risks in commercializing any of our product candidates that receive marketing approval outside the U.S., including tariffs, trade barriers and regulatory requirements;
economic weakness, including inflation or political instability in particular foreign economies and markets;
1 unchanged sentence
foreign currency fluctuations, which could result in increased operating expenses and reduced revenue and other obligations incident to doing business in another country;
−Removed: and workforce uncertainty in countries where labor unrest is more common than in the United States.
+Added: and workforce uncertainty in countries where labor unrest is more common than in the U.S.
A fast track designation, grant of priority review status or breakthrough therapy status by the FDA is not assured and, in any event, may not actually lead to a faster development or regulatory review or approval process and, moreover, would not assure FDA approval of Haduvio or any future product candidate.
−Removed: We may be eligible for fast track designation, priority review or breakthrough therapy status for product candidates we may develop.
+Added: We may be eligible for fast track designation, priority review or breakthrough therapy status for specific indications for the product candidates we may develop.
If a product candidate is intended for the treatment of a serious or life-threatening disease or condition and the product candidate demonstrates the potential to address unmet medical needs for this disease or condition, the product candidate sponsor may apply for FDA fast track designation.
2 unchanged sentences
The FDA has broad discretion whether or not to grant these designations, so even if we believe a particular product candidate is eligible for such designation or status, the FDA could decide not to grant it.
−Removed: We have received fast track designation for Haduvio for the proposed indication of reduction of moderate to severe pruritus in patients with prurigo nodularis, however this designation, or any future fast track, priority review or breakthrough therapy status designation, may not result in our experiencing a faster development process, review or approval compared to conventional FDA procedures and there is no assurance that the product candidate will be approved by the FDA.
+Added: We have received fast track designation for Haduvio for the proposed indication of reduction of moderate to severe pruritus in patients with prurigo nodularis, however this designation or any future fast track designation for a different indication, priority review or breakthrough therapy status designation, may not result in our experiencing a faster development process, review or approval compared to conventional FDA procedures and there is no assurance that the product candidate will be approved by the FDA.
Even if we obtain marketing approvals for a product, the terms of approvals and ongoing regulation of such product may limit how we manufacture and market the product, which could impair our ability to generate revenue.
6 unchanged sentences
Accordingly, assuming we receive marketing approval for one or more products, we and our contract manufacturers will continue to expend time, money and effort in a number of areas of regulatory compliance, including manufacturing, production, product surveillance and quality control.
−Removed: We expect that any regulatory approval to market Haduvio in the United States will be limited by indication.
+Added: Any regulatory approval to market Haduvio in the U.S.
+Added: will be limited by indication.
If we fail to comply or are found to be in violation of FDA and other regulations restricting the promotion of Haduvio for unapproved uses, we could be subject to criminal penalties, substantial fines or other sanctions and damage awards.
9 unchanged sentences
In recent years, a significant number of pharmaceutical and biotechnology companies have been the target of inquiries and investigations by various federal and state regulatory, investigative, prosecutorial and administrative entities in connection with the promotion of products for unapproved uses and other sales practices, including the Department of Justice and various U.S.
−Removed: Attorneys’ Offices, the Office of Inspector General of the Department of Health and Human Services, the FDA, the Federal Trade Commission
−Removed: and various state Attorneys General offices.
+Added: Attorneys’ Offices, the Office of Inspector General of the Department of Health and Human Services, the FDA, the Federal Trade Commission and various state Attorneys General offices.
These investigations have alleged violations of various federal and state laws and regulations, including claims asserting antitrust violations, violations of the FDCA, the False Claims Act, the Prescription Drug Marketing Act and anti-kickback laws and other alleged violations in connection with the promotion of products for unapproved uses, pricing and Medicare and/or Medicaid reimbursement.
13 unchanged sentences
The FDA and other agencies, including the Department of Justice, closely regulate and monitor the post-approval marketing and promotion of products to ensure that they are manufactured, marketed and distributed only for the approved indications and in accordance with the provisions of the approved labeling.
−Removed: The FDA imposes stringent restrictions on manufacturers’ communications regarding off-label use and if we market any product for an indication that is not approved, we may be subject to
−Removed: warnings or enforcement action for off-label marketing.
+Added: The FDA imposes stringent restrictions on manufacturers’ communications regarding off-label use and if we market any product for an indication that is not approved, we may be subject to warnings or enforcement action for off-label marketing.
Violation of the FDCA and other statutes, including the False Claims Act, relating to the promotion and advertising of prescription drugs may lead to investigations or allegations of violations of federal and state health care fraud and abuse laws and state consumer protection laws.
15 unchanged sentences
Current and future legislation may increase the difficulty and cost for us to obtain marketing approval of and commercialize Haduvio or any future product candidate and may affect the prices we may obtain.
−Removed: In the United States and some foreign jurisdictions, there have been and continue to be a number of legislative and regulatory changes and proposed changes regarding the healthcare system that could, among other things, prevent or delay marketing approval of Haduvio or any future product candidate, restrict or regulate post-approval activities and affect our ability to profitably sell any products for which we obtain marketing approval.
+Added: and some foreign jurisdictions, there have been and continue to be a number of legislative and regulatory changes and proposed changes regarding the healthcare system that could, among other things, prevent or delay marketing approval of Haduvio or any future product candidate, restrict or regulate post-approval activities and affect our ability to profitably sell any products for which we obtain marketing approval.
We expect that current laws, as well as other healthcare reform measures that may be adopted in the future, may result in more rigorous coverage criteria and in additional downward pressure on the price that we may receive for any approved products.
9 unchanged sentences
For example, with enactment of the Tax Cuts for Jobs Act, or TCJA, in 2017, Congress repealed the “individual mandate.” The repeal of this provision, which requires most Americans to carry a minimal level of health insurance, became effective in 2019.
−Removed: Further, on December 14, 2018, a United States District Court judge in the Northern District of Texas ruled that the individual mandate portion of the ACA is an essential and inseverable feature of the ACA, and therefore because the mandate was repealed as part of the TCJA, the remaining provisions of the ACA are invalid as well.
−Removed: The United States Supreme Court heard this case on November 10, 2020, and a ruling by the Court is expected sometime this year.
−Removed: Pending resolution of the litigation, all of the provisions in the ACA but the individual mandate to buy health insurance remains in effect.
+Added: Further, on December 14, 2018, a U.S.
+Added: District Court judge in the Northern District of Texas ruled that the individual mandate portion of the ACA is an essential and inseverable feature of the ACA and therefore because the mandate was repealed as part of the TCJA, the remaining provisions of the ACA are invalid as well.
+Added: Supreme Court heard this case on November 10, 2020 and on June 17, 2021, dismissed this action after finding that the plaintiffs do not have standing to challenge the constitutionality of the ACA.
Litigation and legislation over the ACA are likely to continue, with unpredictable and uncertain results.
12 unchanged sentences
Current and future legislative efforts may limit the prices for our products, if and when they are licensed for marketing and that could materially impact our ability to generate revenues.
−Removed: The prices of prescription pharmaceuticals have also been the subject of considerable discussion in the United States.
+Added: The prices of prescription pharmaceuticals have also been the subject of considerable discussion in the U.S.
To date, there have been several recent U.S.
−Removed: congressional inquiries, as well as proposed and enacted state and federal legislation designed to, among other things, bring more transparency to drug pricing, review the relationship between pricing and manufacturer patient programs, reduce the costs of drugs under Medicare and reform government program reimbursement methodologies for products.
+Added: congressional inquiries, as well as proposed and enacted state and federal legislation designed to, among
+Added: other things, bring more transparency to drug pricing, review the relationship between pricing and manufacturer patient programs, reduce the costs of drugs under Medicare and reform government program reimbursement methodologies for products .
For example, on September 24, 2020, the Trump Administration finalized a rulemaking allowing states or certain other non-federal government entities to submit importation program proposals to the FDA for review and approval.
11 unchanged sentences
We expect that additional state and federal healthcare reform measures will be adopted in the future, any of which could limit the amounts that federal and state governments will pay for healthcare products and services, which could result in reduced demand for our product candidates or additional pricing pressures.
−Removed: In the European Union, similar political, economic and regulatory developments may affect our ability to profitably commercialize our product candidates, if approved.
−Removed: In markets outside of the United States and the European Union, reimbursement and healthcare payment systems vary significantly by country, and many countries have instituted price ceilings on specific products and therapies.
−Removed: In many countries, including those of the European Union, the pricing of prescription pharmaceuticals is subject to governmental control and access.
+Added: In the E.U., similar political, economic and regulatory developments may affect our ability to profitably commercialize our product candidates, if approved.
+Added: In markets outside of the U.S.
+Added: and the E.U., reimbursement and healthcare payment systems vary significantly by country and many countries have instituted price ceilings on specific products and therapies.
+Added: In many countries, including those of the E.U., the pricing of prescription pharmaceuticals is subject to governmental control and access.
In these countries, pricing negotiations with governmental authorities can take considerable time after the receipt of marketing approval for a product.
9 unchanged sentences
False Claims Laws.
−Removed: The federal false claims and civil monetary penalties laws, including the federal civil False Claims Act, impose criminal and civil penalties, including through civil whistleblower or qui tam actions against individuals or entities for, among other things, knowingly presenting or causing to be presented false or fraudulent claims for payment by a federal healthcare program or making a false statement or record material to payment of a false claim or avoiding, decreasing or concealing an obligation to pay money to the federal government, with potential liability including mandatory treble damages and significant per-claim penalties.
+Added: The federal false claims and civil monetary penalties laws, including the federal civil False Claims Act, impose criminal and civil penalties, including through civil whistleblower or qui tam actions against individuals or entities for, among other things, knowingly presenting or causing to be presented false or fraudulent claims for payment by a federal healthcare program
+Added: or making a false statement or record material to payment of a false claim or avoiding, decreasing or concealing an obligation to pay money to the federal government, with potential liability including mandatory treble damages and significant per-claim penalties.
The federal Health Insurance Portability and Accountability Act of 1996, or HIPAA, imposes criminal and civil liability for, among other things, executing a scheme or making materially false statements in connection with the delivery of or payment for health care benefits, items or services.
12 unchanged sentences
Further, if any of the physicians or other healthcare providers or entities with whom we expect to do business is found to be not in compliance with applicable laws, they may be subject to criminal, civil or administrative sanctions, including exclusions from government funded healthcare programs.
−Removed: The provision of benefits or advantages to physicians to induce or encourage the prescription, recommendation, endorsement, purchase, supply, order or use of medicinal products is also prohibited in the European Union.
−Removed: The provision of benefits or advantages to physicians is governed by the national anti-bribery laws of European Union Member States, such as the U.K.
+Added: The provision of benefits or advantages to physicians to induce or encourage the prescription, recommendation, endorsement, purchase, supply, order or use of medicinal products is also prohibited in the E.U.
+Added: The provision of benefits or advantages to physicians is governed by the national anti-bribery laws of E.U.
+Added: Member States, such as the U.K.
Bribery Act 2010.
Infringement of these laws could result in substantial fines and imprisonment.
−Removed: Payments made to physicians in certain European Union Member States must be publicly disclosed.
−Removed: Moreover, agreements with physicians often must be the subject of prior notification and approval by the physician’s employer, his or her competent professional organization and/or the regulatory authorities of the individual European Union Member States.
−Removed: These requirements are provided in the national laws, industry codes or professional codes of conduct, applicable in the European Union Member States.
+Added: Payments made to physicians in certain E.U.
+Added: Member States must be publicly disclosed.
+Added: Moreover, agreements with physicians often must be the subject of prior notification and approval by the physician’s employer, his or her competent professional organization and/or the regulatory authorities of the individual E.U.
+Added: Member States.
+Added: These requirements are provided in the national laws, industry codes or professional codes of conduct, applicable in the E.U.
+Added: Member States.
Failure to comply with these requirements could result in reputational risk, public reprimands, administrative penalties, fines or imprisonment.
Compliance with global privacy and data security requirements could result in additional costs and liabilities to us or inhibit our ability to collect and process data globally and the failure to comply with such requirements could have a material adverse effect on our business, financial condition or results of operations .
−Removed: The collection, use, disclosure, transfer or other processing of personal data, including personal health data, of individuals in the European Union is governed by the General Data Protection Regulation, or GDPR.
+Added: The collection, use, disclosure, transfer or other processing of personal data, including personal health data, of individuals in the E.U.
+Added: is governed by the General Data Protection Regulation, or GDPR.
The GDPR became effective on May 25, 2018.
6 unchanged sentences
and implementing safeguards to protect the security and confidentiality of personal data.
−Removed: The GDPR imposes strict rules on the transfer of personal data to countries outside the European Union, including the United States.
+Added: The GDPR imposes strict rules on
+Added: the transfer of personal data to countries outside the E.U.
+Added: , including the U.S.
Failure to comply with the requirements of the GDPR may result in fines of up to 20 million euros or four percent of annual global revenues, whichever is greater.
2 unchanged sentences
This may be onerous and adversely affect our business, financial condition, results of operations and prospects and despite our efforts, there is a risk that we may be subject to fines, litigation and reputational harm in connection with our European activities.
−Removed: Similar actions are either in place or under way in the United States.
+Added: Similar actions are either in place or under way in the U.S.
There are a broad variety of data protection laws that are applicable to our activities and a wide range of enforcement agencies at both the state and federal levels that can review companies for privacy and data security concerns based on general consumer protection laws.
7 unchanged sentences
Even if we are not determined to have violated these laws, government investigations into these issues typically require the expenditure of significant resources and generate negative publicity, which could harm our reputation and our business.
−Removed: Laws and regulations governing any international operations we may have in the future may preclude us from developing, manufacturing and selling certain products outside of the United States and require us to develop and implement costly compliance programs.
−Removed: If we further expand our operations outside the United States, we will need to dedicate additional resources to comply with U.S.
+Added: Laws and regulations governing any international operations we may have in the future may preclude us from developing, manufacturing and selling certain products outside of the U.S.
+Added: and require us to develop and implement costly compliance programs.
+Added: If we further expand our operations outside the U.S., we will need to dedicate additional resources to comply with U.S.
laws regarding international operations and the laws and regulations in each jurisdiction in which we operate and plan to operate.
1 unchanged sentence
individual or business from paying, offering or authorizing payment or offering of anything of value, directly or indirectly, to any foreign official, political party or candidate for the purpose of influencing any act or decision of the foreign entity in order to assist the individual or business in obtaining or retaining business.
−Removed: The FCPA also obligates companies whose securities are listed in the United States to comply with certain accounting provisions requiring the company to maintain books and records that accurately and fairly reflect all transactions of the company, including international subsidiaries, and to devise and maintain an adequate system of internal accounting controls for international operations.
+Added: The FCPA also obligates companies whose securities are listed in the U.S.
+Added: to comply with certain accounting provisions requiring the company to maintain books and records that accurately and fairly reflect all transactions of the company, including international subsidiaries and to devise and maintain an adequate system of internal accounting controls for international operations.
Compliance with the FCPA is expensive and difficult, particularly in countries in which corruption is a recognized problem.
1 unchanged sentence
Certain payments to hospitals in connection with clinical trials and other work have been deemed to be improper payments to government officials and have led to FCPA enforcement actions.
−Removed: Various laws, regulations and executive orders also restrict the use and dissemination outside of the United States, or the sharing with certain non-U.S.
+Added: Various laws, regulations and executive orders also restrict the use and dissemination outside of the U.S.
+Added: or the sharing with certain non-U.S.
nationals, of information classified for national security purposes, as well as certain products and technical data relating to those products.
−Removed: Further, the provision of benefits or advantages to physicians to induce or encourage the prescription, recommendation, endorsement, purchase, supply, order, or use of medicinal products is prohibited in the European Union.
−Removed: The provision of benefits or advantages to physicians is also governed by the national anti-bribery laws of European Union Member States, such as the U.K.
+Added: Further, the provision of benefits or advantages to physicians to induce or encourage the prescription, recommendation, endorsement, purchase, supply, order or use of medicinal products is prohibited in the E.U.
+Added: The provision of benefits or advantages to physicians is also governed by the national anti-bribery laws of E.U.
+Added: Member States, such as the U.K.
Bribery Act 2010.
Infringement of these laws could result in substantial fines and imprisonment.
−Removed: Payments made to physicians in certain European Union Member States must be publicly disclosed.
−Removed: Moreover, agreements with physicians often must be the subject of prior notification and approval by the physician’s employer, his or her competent professional organization, and/or the regulatory authorities of the individual European Union Member States.
−Removed: These requirements are provided in the national laws,
−Removed: industry codes, or professional codes of conduct applicable in the European Union Member States.
+Added: Payments made to physicians in certain E.U.
+Added: Member States must be publicly disclosed.
+Added: Moreover, agreements with physicians often must be the subject of prior notification and approval by the physician’s employer, his or her competent professional organization and/or the regulatory authorities of the individual E.U.
+Added: Member States.
+Added: These requirements are provided in the national laws, industry codes or professional codes of conduct applicable in the E.U.
+Added: Member States.
Failure to comply with these requirements could result in reputational risk, public reprimands, administrative penalties, fines or imprisonment.
−Removed: If we expand our presence outside of the United States, it will require us to dedicate additional resources to comply with these laws, and these laws may preclude us from developing, manufacturing or selling certain products and product candidates outside of the United States, which could limit our growth potential and increase our development costs.
+Added: If we expand our presence outside of the U.S., it will require us to dedicate additional resources to comply with these laws and these laws may preclude us from developing, manufacturing or selling certain products and product candidates outside of the U.S., which could limit our growth potential and increase our development costs.
The failure to comply with laws governing international business practices may result in substantial civil and criminal penalties and suspension or debarment from government contracting.
−Removed: The Securities and Exchange Commission, or SEC, also may suspend or bar issuers from trading securities on U.S.
+Added: The SEC also may suspend or bar issuers from trading securities on U.S.
exchanges for violations of the FCPA’s accounting provisions.
15 unchanged sentences
To the extent 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 also incur liability and the development of Haduvio or any future product candidate could be significantly delayed.
−Removed: In the ordinary course of our business, we directly or indirectly collect and store sensitive data, including intellectual property, confidential information, preclinical and clinical trial data, proprietary business information, personal data and personally identifiable health information of our clinical trial patients and employees, in our data centers and on our networks, or on those of third parties.
+Added: In the ordinary course of our business, we directly or indirectly collect and store sensitive data, including intellectual property, confidential information, preclinical and clinical trial data, proprietary business information, personal data and personally identifiable health information of our clinical trial subjects and employees, in our data centers and on our networks or on those of third parties.
The secure processing, maintenance and transmission of this information is critical to our operations.
11 unchanged sentences
Sciascia, these agreements do not prevent them from terminating their employment with us at any time.
−Removed: Except as otherwise required by law, all of
−Removed: the members of our executive team are employed “at will,” meaning that they may terminate their employment with us at any time with or without notice and for any reason or no reason.
+Added: Except as otherwise required by law, all members of our executive team are employed “at will,” meaning that they may terminate their employment with us at any time with or without notice and for any reason or no reason.
The loss of the services of any of these persons could impede the achievement of our research, development and commercialization objectives.
9 unchanged sentences
We expect to expand our organization and as a result, we may encounter difficulties in managing our growth, which could disrupt our operations.
−Removed: As of March 31, 2021, we had 23 employees.
+Added: As of June 30, 2021, we had 23 employees.
We expect to experience significant growth in the number of our employees and the scope of our operations.
4 unchanged sentences
Our expected growth could also require significant capital expenditures and may divert financial resources from other projects, such as the development of Haduvio for additional indications or the development of additional product candidates.
−Removed: If we are unable to effectively manage our expected growth, our expenses may increase more than expected, our ability to generate revenues could be reduced and we may not be able to implement our business strategy, including the successful commercialization of any product candidate.
+Added: If we are unable to effectively manage our expected growth, our expenses may increase more than expected, our ability to generate revenues could be reduced and we may be unable to implement our business strategy, including the successful commercialization of any product candidate.
Our employees, independent contractors and consultants may engage in misconduct or other improper activities, including non-compliance with regulatory standards and requirements, which could cause significant liability for us and harm our reputation.
22 unchanged sentences
results of clinical trials of product candidates of our competitors;
−Removed: regulatory or legal developments in the United States and other countries;
+Added: regulatory or legal developments in the U.S.
+Added: and other countries;
developments or disputes concerning patent applications, issued patents or other intellectual property rights;
8 unchanged sentences
recommendations and changes in estimates or recommendations by securities analysts, if any, that cover our stock;
−Removed: changes in the structure of healthcare payment systems in the United States and other countries;
+Added: changes in the structure of healthcare payment systems in the U.S.
+Added: and other countries;
market conditions in the pharmaceutical and biotechnology sectors;
−Removed: general economic, industry and market conditions, including recent adverse changes in the domestic and international financial markets, and the impacts of the COVID-19 pandemic;
+Added: general economic, industry and market conditions, including recent adverse changes in the domestic and international financial markets and the impacts of COVID-19;
+Added: our obligations in connection with the SVB Term Loan;
our ability to continue as a going concern;
other factors and considerations described in this “Risk Factors” section.
−Removed: In addition, the COVID-19 pandemic has negatively affected the stock market and investor sentiment.
+Added: In addition, COVID-19 has negatively affected the stock market and investor sentiment.
The price and volatility of our common stock may be disproportionately affected as investors may favor traditional profit-making industries and companies during the times of market uncertainty and instability.
19 unchanged sentences
In June 2020, we entered into the ATM Sales Agreement, pursuant to which, from time to time, we may offer and sell under the ATM Sales Agreement up to $12.0 million of the common stock registered under the Shelf Registration Statement pursuant to one or more “at the market” offerings.
−Removed: As of March 31, 2021, we had sold 2,055,497 shares of common stock for an aggregate purchase price of $7.6 million pursuant to the ATM Sales Agreement.
+Added: As of June 30, 2021, we had sold 3,421,368 shares of common stock for an aggregate purchase price of $10.6 million, before deducting estimated commissions and allocated fees of $0.8 million, pursuant to the ATM Sales Agreement.
The extent to which we utilize the ATM Sales Agreement as a source of funding will depend on a number of factors, including the prevailing market price of our common stock, general market conditions and the extent to which we are able to secure funds from other sources.
−Removed: Sales of substantial amounts of shares of our common stock or other securities by our stockholders, by us under the Shelf Registration Statement, whether pursuant to the ATM Sales Agreement or otherwise, or through any other means could also lower the market price of our common stock and impair our ability to raise capital through the sale of equity or equity-related securities.
+Added: In addition, on June 18, 2021, we entered into the LPC Purchase Agreement with Lincoln Park pursuant to which Lincoln Park has committed to purchase up to $15.0 million of shares of our common stock.
+Added: We filed a registration statement on Form S-1, or the Form S-1, covering the resale of shares of common stock that are issued to Lincoln Park under the LPC Purchase Agreement, which was declared effective on July 14, 2021.
+Added: We generally have the right to control the timing and amount of any future sales of shares of our common stock to Lincoln Park.
+Added: Sales of shares of our common stock, if any, to Lincoln Park will depend upon market conditions and other factors to be determined by us.
+Added: We may ultimately decide to sell to Lincoln Park all, some or none of the additional shares of our common stock that may be available for us to sell pursuant to the LPC Purchase Agreement.
+Added: If and when we do sell shares of our common stock to Lincoln Park, after Lincoln Park has acquired the shares of common stock, Lincoln Park may resell all, some or none of those shares of common stock at any time or in its discretion.
+Added: The sale by Lincoln Park of a substantial number of shares of our common stock issued by us to Lincoln Park under the LPC Purchase Agreement or the anticipation of such sales, could make it more difficult for us to sell equity or equity-related securities in the future at a time and at a price that we might otherwise wish to effect sales.
+Added: Sales of substantial amounts of shares of our common stock or other securities by our stockholders, by us under the Shelf Registration Statement, whether pursuant to the ATM Sales Agreement or otherwise or by Lincoln Park pursuant to the Form S-1 or through any other means could also lower the market price of our common stock and impair our ability to raise capital through the sale of equity or equity-related securities.
Ownership of our common stock is concentrated among our executive officers and directors and their affiliates and our significant stockholders, who have significant influence over our business, which may prevent new investors from influencing significant corporate decisions.
−Removed: Our executive officers and directors and their affiliates and our significant stockholders in the aggregate, beneficially own shares representing approximately 60.0% of our common stock as of May 12, 2021.
−Removed: As a result, our executive officers and directors and their affiliates and our significant stockholders acting together would be able to control all matters submitted to our stockholders for approval, as well as our management and affairs.
+Added: Our executive officers and directors and their affiliates and our significant stockholders in the aggregate, beneficially own shares representing approximately 61.0% of our common stock as of August 12, 2021.
+Added: As a result, our executive officers and directors and their
+Added: affiliates and our significant stockholders acting together would be able to control all matters submitted to our stockholders for approval, as well as our management and affairs.
This concentration of ownership control may:
3 unchanged sentences
Some of these persons or entities may have interests different than yours.
−Removed: For example, because many of these stockholders purchased their shares at prices substantially below our initial public offering price and have held their shares for a longer period, they may be more interested in selling our company to an acquirer than other investors or they may want us to pursue strategies that deviate from the interests of other stockholders.
+Added: For example, because many of these stockholders purchased their shares at prices substantially below our IPO price and have held their shares for a longer period, they may be more interested in selling our company to an acquirer than other investors or they may want us to pursue strategies that deviate from the interests of other stockholders.
We do not anticipate paying any cash dividends on our capital stock in the foreseeable future.
11 unchanged sentences
If some investors find our common stock less attractive as a result of our reliance on these exemptions, the trading market for our common stock may be less active and our stock price may be more volatile.
−Removed: We will incur increased costs as a result of operating as a public company, and our management will be required to devote substantial time to new compliance initiatives and corporate governance practices.
−Removed: As a public company, and particularly after we are no longer an “emerging growth company” or a “smaller reporting company,” we will incur significant legal, accounting, investor relations and other expenses that we did not incur as a private company.
+Added: We incur increased costs as a result of operating as a public company and our management is required to devote substantial time to compliance initiatives and corporate governance practices.
+Added: As a public company and particularly after we are no longer an “emerging growth company” or a “smaller reporting company,” we incur and will continue to incur, significant legal, accounting, investor relations and other expenses that we did not incur as a private company.
The Sarbanes-Oxley Act of 2002, the Dodd-Frank Wall Street Reform and Consumer Protection Act, the listing requirements of the Nasdaq Stock Market and other applicable securities rules and regulations impose various requirements on public companies, including establishment and maintenance of effective disclosure and financial controls and corporate governance practices.
−Removed: We may need to hire additional accounting, finance and other personnel in connection with our efforts to comply with the requirements of being a public company and our management and other personnel will need to devote a substantial amount of time in complying with these requirements, which could negatively impact our financial results.
+Added: We may need to hire additional accounting, finance and other personnel in connection with our efforts to comply with the requirements of being a public company and our management and other personnel devote a substantial amount of time in complying with these requirements, which could negatively impact our financial results.
Current and changing laws, rules and regulations relating to corporate governance and public disclosure may increase our legal and financial compliance costs and make some activities more time-consuming and costly.
3 unchanged sentences
This could result in continuing uncertainty regarding compliance matters and higher costs necessitated by ongoing revisions to disclosure and governance practices.
−Removed: We intend to invest resources to comply with evolving laws, rules and regulations, and this investment may result in increased general and administrative expenses and a diversion of management’s time and attention from revenue-generating activities to compliance activities.
+Added: We have invested in and intend to continue to invest in, resources to comply with evolving laws, rules and
+Added: regulations and this investment may result in increased general and administrative expenses and a diversion of management’s time and attention from revenue-generating activities to compliance activities.
If, notwithstanding our efforts to comply with new laws, rules and regulations, we fail to comply, regulatory authorities may initiate legal proceedings against us and our business may be harmed.
12 unchanged sentences
These net operating loss and tax credit carryforwards could expire unused and be unavailable to offset future income tax liabilities.
−Removed: In general, under Section 382 of the Internal Revenue Code of 1986, as amended, or the Code, and corresponding provisions of state law, a corporation that undergoes an “ownership change,” generally defined as a greater than 50 percentage point change (by value) in its equity ownership by certain stockholders over a three year period, is subject to limitations on its ability to utilize its pre-change net operating losses and research and development tax credit carryforwards to offset future taxable income.
−Removed: Due to our Series A convertible preferred stock financing in December 2012 and the shares issued in connection with our IPO in May 2019, an “ownership change” under Section 382 of the Code occurred.
+Added: In general, under Section 382 of the Internal Revenue Code of 1986, as amended, or the IRC, and corresponding provisions of state law, a corporation that undergoes an “ownership change,” generally defined as a greater than 50 percentage point change (by value) in its equity ownership by certain stockholders over a three year period, is subject to limitations on its ability to utilize its pre-change net operating losses and research and development tax credit carryforwards to offset future taxable income.
+Added: Due to our Series A convertible preferred stock financing in December 2012 and the shares issued in connection with our IPO in May 2019, an “ownership change” under Section 382 of the IRC occurred.
As a result, our ability to use approximately $91.3 million of our net operating loss carryforwards and approximately $3.0 million of our research and development tax credits is limited.
12 unchanged sentences
On December 22, 2017, the U.S.
−Removed: government enacted the Tax Act, which significantly reformed the Code.
−Removed: The Tax Act, among other things, contained significant changes to corporate taxation, including a reduction of the corporate tax rate from a top marginal rate of 35% to a flat rate of 21%, the limitation of the tax deduction for net interest expense to 30% of adjusted taxable income (except for certain small businesses), the limitation of the deduction for net operating losses arising in taxable years beginning after December 31, 2017 to 80% of current year taxable income and elimination of net operating loss carrybacks for losses arising in taxable years ending after December 31, 2017 (though any such NOLs may be carried forward indefinitely), the imposition of a one-time taxation of offshore earnings at reduced
−Removed: rates regardless of whether they are repatriated, the elimination of U.S.
+Added: government enacted the Tax Act, which significantly reformed the IRC.
+Added: The Tax Act, among other things, contained significant changes to corporate taxation, including a reduction of the corporate tax rate from a top marginal rate of 35% to a flat rate of 21%, the limitation of the tax deduction for net interest expense to 30% of adjusted taxable income (except for certain small businesses), the limitation of the deduction for net operating losses arising in taxable years beginning after December 31, 2017 to 80% of current year
+Added: taxable income and elimination of net operating loss carrybacks for losses arising in taxable years ending after December 31, 2017 (though any such NOLs may be carried forward indefinitely), the imposition of a one-time taxation of offshore earnings at reduced rates regardless of whether they are repatriated, the elimination of U.S.
tax on foreign earnings (subject to certain important exceptions), the allowance of immediate deductions for certain new investments instead of deductions for depreciation expense over time and the modification or repeal of many business deductions and credits.
−Removed: As part of Congress’s response to the COVID-19 pandemic, the Families First Coronavirus Response Act, or FFCR Act, was enacted on March 18, 2020, and the CARES Act was enacted on March 27, 2020.
+Added: As part of Congress’s response to COVID-19, the Families First Coronavirus Response Act, or FFCR Act, was enacted on March 18, 2020 and the CARES Act was enacted on March 27, 2020.
Both contain numerous tax provisions.
3 unchanged sentences
Regulatory guidance under the Tax Act, the FFCR Act and the CARES Act is and continues to be forthcoming and such guidance could ultimately increase or lessen impact of these laws on our business and financial condition.
−Removed: It is also likely that Congress will enact additional legislation in connection with the COVID-19 pandemic, some of which could have an impact on our company.
+Added: It is also likely that Congress will enact additional legislation in connection with COVID-19, some of which could have an impact on our company.
In addition, it is uncertain if and to what extent various states will conform to the Tax Act, the FFCR Act or the CARES Act.
16 unchanged sentences
These provisions may also prevent changes in our management or limit the price that investors are willing to pay for our stock.
−Removed: Our certificate of incorporation provides that the Court of Chancery of the State of Delaware will be the exclusive forum for substantially all disputes between us and our stockholders and that the federal district courts of the United States of America are the sole and exclusive forum for the resolution of any complaint asserting a cause of action arising under the Securities Act.
+Added: Our certificate of incorporation provides that the Court of Chancery of the State of Delaware will be the exclusive forum for substantially all disputes between us and our stockholders and that the federal district courts of the U.S.
+Added: are the sole and exclusive forum for the resolution of any complaint asserting a cause of action arising under the Securities Act.
These choice of forum provisions could limit our stockholders’ ability to obtain a favorable judicial forum for disputes with us or our directors, officers or employees.
Our certificate of incorporation provides that the Court of Chancery of the State of Delaware (or, if the Court of Chancery of the State of Delaware does not have jurisdiction, the federal district court for the District of Delaware) shall, to the fullest extent permitted by law, be the sole and exclusive forum for (1) any derivative action or proceeding brought on behalf of our company, (2) any action asserting a claim of breach of fiduciary duty owed by any director, officer, other employee or stockholder of our company to us or our stockholders, (3) any action asserting a claim arising pursuant to any provision of the Delaware General Corporation Law or as to which the Delaware General Corporation Law confers jurisdiction on the Court of Chancery or (4) any action asserting a claim arising pursuant to any provision of our certificate of incorporation or by-laws or governed by the internal affairs doctrine.
−Removed: Our certificate of incorporation further provides that, unless we consent in writing to the selection of an alternative forum, the federal district courts of the United States of America shall, to the fullest extent permitted by law, be the sole and exclusive forum for the resolution of any complaint asserting a cause of action arising under the Securities Act.
−Removed: Neither of these choice of forum provisions would affect suits brought to enforce any liability or duty created by the Exchange Act or the rules and regulations thereunder, jurisdiction over which is exclusively vested by statute in the United States federal courts or any other claim for which United States federal courts have exclusive jurisdiction.
+Added: Our certificate of incorporation further provides that, unless we consent in writing to the selection of an alternative forum, the federal district courts of the U.S.
+Added: shall, to the fullest extent permitted by law, be the sole and exclusive forum for the resolution of any complaint asserting a cause of action arising under the Securities Act.
+Added: Neither of these choice of forum provisions would affect suits brought to enforce any liability or duty created by the Exchange Act or the rules and regulations thereunder, jurisdiction over which is exclusively vested by statute in the U.S.
+Added: federal courts or any other claim for which U.S.
+Added: federal courts have exclusive jurisdiction.
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 our directors, officers or other employees, which may discourage such lawsuits against us and our directors, officers and other employees.
1 unchanged sentence
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.