−Removed: You should consider carefully the following risks and uncertainties when reading this Annual Report on Form 10-K, as well as the other information contained herein, including our audited consolidated financial statements and the related notes and the section titled “Management’s Discussion and Analysis of Financial Condition and Results of Operation.”
−Removed: If any of the following risks occur, our business, financial condition and results of operations could be materially and adversely affected.
+Added: You should consider carefully the following risks and uncertainties when reading this Annual Report on Form 10-K, as well as the other information contained herein, including our audited consolidated financial statements and the related notes and the section titled “Management’s Discussion and Analysis of Financial Condition and Results of Operation.” If any of the following risks occur, our business, financial condition and results of operations could be materially and adversely affected.
Although we believe that we have identified and discussed below the key risk factors affecting our business, there may be additional risks and uncertainties that are not presently known or that are not currently believed to be significant that may adversely affect our performance or financial condition.
2 unchanged sentences
We have incurred significant losses since our inception and anticipate that we will incur continued losses for the foreseeable future.
−Removed: Since our inception we have devoted substantially all of our resources to the development of CTI-1601.
+Added: Since our inception we have devoted substantially all of our resources to the development of nomlabofusp.
We have incurred significant losses in each year of operation since our inception in 2016.
1 unchanged sentence
We have devoted substantially all of our financial resources and efforts to research and development, including non-clinical studies, our clinical development program, the development of manufacturing processes as well as the manufacture of initial lots of clinical trial material.
−Removed: We expect to incur significant losses for the foreseeable future to further develop and commercialize our lead drug candidate, CTI-1601.
+Added: We expect to incur significant losses for the foreseeable future to further develop and commercialize our lead drug candidate, nomlabofusp.
We expect that our expenses will increase substantially if and as we:
−Removed: continue clinical development efforts for CTI-1601;
+Added: • continue clinical development efforts for nomlabofusp;
• seek regulatory and marketing approvals in the United States and in foreign jurisdictions for our product candidates that successfully complete clinical trials, if any;
3 unchanged sentences
• hire and retain additional personnel, such as clinical, manufacturing, quality control, regulatory and finance personnel;
−Removed: build out our sales, marketing and distribution infrastructure, assuming CT-1601 is approved for marketing;
• experience any delays or encounter issues with any of the above.
−Removed: We currently have no sales, marketing.
−Removed: medical affairs infrastructure and have no experience in the sales, marketing, or distribution of pharmaceutical products.
−Removed: Assuming CTI-1601 ultimately is approved for marketing in the US and elsewhere, we will need to establish sales and marketing capabilities as well as customer service and support, logistics, and other related functions, or make arrangements with third parties to perform these services;
+Added: We currently have no sales, marketing or medical affairs infrastructure and have no experience in the sales, marketing, or distribution of pharmaceutical products.
+Added: Assuming nomlabofusp ultimately is approved for marketing in the US and elsewhere, we will need to establish commercial capabilities as well as customer service and support, logistics, and other related functions, or make arrangements with third parties to perform these services.
Net losses and negative cash flows have had, and will continue to have, an adverse effect on our liquidity and potentially the ability for us to raise capital due to our unfavorable operating results.
1 unchanged sentence
To date, we have not generated any commercial revenue.
−Removed: Our ability to generate revenue and become profitable depends upon our ability to obtain regulatory approval for, and to successfully commercialize, CTI-1601 or other product candidates that we may develop, in-license or acquire in the future.
−Removed: This will require success in a range of challenging activities, including completing numerous clinical trials of CTI-1601 or any future product candidates, obtaining marketing approval for CTI-1601 and any future product candidates, manufacturing, marketing and selling those products for which we, or any future collaborators or partners, may obtain marketing approval, satisfying any post-marketing requirements and obtaining reimbursement for our products from private insurance and/or government payors.
−Removed: Even if we are able to successfully achieve the above, we do not know what the reimbursement status of CTI-1601 or any other future product candidates will be or when any of these products will generate revenue for us, if at all.
−Removed: We have not generated, and do not expect to generate, any product revenue for the foreseeable future, and expect to continue to incur significant operating losses for the foreseeable future due to the cost of research and development, non-clinical studies and clinical trials and the regulatory approval process for CTI-1601 and any future product candidates.
−Removed: Our ability to generate revenue from CTI-1601 or any future product candidates also depends on a number of additional factors, including our ability to:
+Added: Our ability to generate revenue and become profitable depends upon our ability to obtain regulatory approval for, and to successfully commercialize, nomlabofusp or other product candidates that we may develop, in-license or acquire in the future.
+Added: This will require success in a range of challenging activities, including completing numerous clinical trials of nomlabofusp or any future product candidates, obtaining marketing approval for nomlabofusp and any future product candidates, manufacturing, marketing and selling those products for which we, or any future collaborators
+Added: or partners, may obtain marketing approval, satisfying any post-marketing requirements and obtaining reimbursement for our products from private insurance and/or government payors.
+Added: Even if we are able to successfully achieve the above, we do not know what the reimbursement status of nomlabofusp or any other future product candidates will be or when any of these products will generate revenue for us, if at all.
+Added: We have not generated, and do not expect to generate, any product revenue for the foreseeable future, and expect to continue to incur significant operating losses for the foreseeable future due to the cost of research and development, non-clinical studies and clinical trials and the regulatory approval process for nomlabofusp and any future product candidates.
+Added: Our ability to generate revenue from nomlabofusp or any future product candidates also depends on a number of additional factors, including our ability to:
• successfully complete development activities, including the remaining non-clinical studies and planned clinical trials for our product candidates;
−Removed: complete and submit NDAs and BLAs to the FDA and MAAs to the EMA and obtain regulatory approval for indications for which there is a commercial market;
+Added: • complete and submit BLAs to the FDA and MAAs to the EMA and obtain regulatory approval for indications for which there is a commercial market;
• complete and submit applications to, and obtain regulatory approval from, other foreign regulatory authorities;
6 unchanged sentences
We and any future collaborators may never succeed in these activities and, even if we do, or any future collaborators do, we may never generate revenues that are large enough for us to achieve profitability.
−Removed: Even if we are able to complete the processes described above, we anticipate incurring significant costs associated with commercializing CTI-1601 or any of our future product candidates.
+Added: Even if we are able to complete the processes described above, we anticipate incurring significant costs associated with commercializing nomlabofusp or any of our future product candidates.
Even if we achieve profitability in the future, we may not be able to sustain profitability in subsequent periods.
1 unchanged sentence
A decline in the value of our business could also cause shareholders to lose all or part of their investment.
−Removed: We need to raise additional funding in order to continue our planned operations.
+Added: We may need to raise additional funding to complete the development and commercialization of nomlabofusp.
This funding may not be available on acceptable terms, or at all.
Failure to obtain this necessary capital when needed would force us to delay, limit or terminate our product development efforts or other operations.
−Removed: We expect to continue to spend substantial and increasing amounts to conduct clinical trials of CTI-1601 and further research and development activities for CTI-1601, and for any additional product candidates that we may develop, in-license or acquire in the future.
+Added: As of December 31, 2023, our existing cash, cash equivalents and marketable securities were $86.8 million, excluding restricted cash of $1.3 million.
+Added: In February 2024, we completed an underwritten public offering of 19,736,842 shares of our common stock at an offering price of $8.74 per share with net proceeds, after deducting underwriting commissions and offering costs, of approximately $161.6 million.
+Added: Together with our existing cash, cash equivalents and marketable securities, we have adequate resources to fund our operations into 2026.
+Added: We expect to continue to spend substantial and increasing amounts to conduct clinical trials of nomlabofusp and further research and development activities for nomlabofusp, and for any additional product candidates that we may develop, in-license or acquire in the future.
In addition, raising funds in the current economic environment may present substantial challenges, and our expenses will increase as we expand, through development, in-license or acquisition, our pipeline of product candidates.
1 unchanged sentence
Accordingly, we will need to obtain additional funding in connection with our continuing operations.
−Removed: As of December 31, 2022, our existing cash, cash equivalents and marketable securities were $118.4 million, excluding restricted cash of $1.3 million.
−Removed: This amount will not be sufficient to fund all of the efforts that we plan to
−Removed: undertake or to fund the completion of the development of CTI-1601.
−Removed: Accordingly, we will be required to obtain further funding through public or private equity offerings, debt financings, collaborations and licensing arrangements or other sources.
+Added: Our current cash, cash equivalents and marketable securities may not be sufficient to fund all of the
+Added: efforts that we plan to undertake or to fund the completion of the development and commercialization of nomlabofusp.
+Added: Accordingly, we may be required to obtain further funding through public or private equity offerings, debt financings, collaborations and licensing arrangements or other sources.
The incurrence of indebtedness would result in increased fixed payment obligations and we may be required to agree to certain restrictive covenants, such as limitations on our ability to incur additional debt, limitations on our ability to acquire, sell or license intellectual property rights and other operating restrictions that could adversely impact our ability to conduct our business.
Any additional fundraising efforts may divert our management from their day-to-day activities, which may adversely affect our ability to develop and commercialize our product candidates.
−Removed: There can be no assurance that we will be able to raise sufficient additional capital on acceptable terms or at all.
+Added: If additional capital is needed to complete the development and commercialization of nomlabofusp, there can be no assurance that we will be able to raise sufficient additional capital on acceptable terms or at all.
If such additional financing is not available on satisfactory terms, or is not available in sufficient amounts, or we do not have sufficient authorized shares, we may be required to delay, limit, or eliminate the development of business opportunities and our ability to achieve our business objectives, our competitiveness, and our business, financial condition, and results of operations will be materially adversely affected.
We could also be required to seek funds through arrangements with collaborative partners or otherwise at an earlier stage than otherwise would be desirable and we may be required to relinquish rights to some of our technologies or product candidates or otherwise agree to terms unfavorable to us, any of which may have a material adverse effect on our business, operating results, financial condition and prospects.
−Removed: In addition, geopolitical unrest including, for example, the broader impact of the Russian invasion of Ukraine, the possibility that the conflict could expand beyond eastern Europe, and the impact of a possible resurgence of vaccine resistant, more deadly or more contagious variant of COVID-19 or other health crisis or recent liquidity constraints, failures and instability in U.S.
+Added: In addition, geopolitical tension including, for example, the broader impact of the ongoing conflict between Russia and Ukraine and the current conflict in Israel and Gaza (including any escalation or expansion), and the impact of a future pandemic, epidemic or outbreak of an infectious disease, such as COVID-19, or recent liquidity constraints, failures and instability in U.S.
and international financial banking systems on the global financial markets may reduce our ability to access capital, which could negatively affect our liquidity.
−Removed: If we are unable to obtain funding when needed and/or on acceptable terms, we may be required to significantly curtail, delay or discontinue one or more of our research and development programs, the manufacture of clinical and commercial supplies, product portfolio expansion or pre commercialization efforts, which could adversely affect our business prospects, or we may be unable to continue operations.
−Removed: Raising additional capital may cause dilution to our existing stockholders, restrict our operations or require us to relinquish rights to our technologies, CTI-1601 or other product candidates that we may develop, in-license or acquire in the future.
+Added: If additional capital is needed to complete the development and commercialization of nomlabofusp, and if we are unable to obtain funding when needed and/or on acceptable terms, we may be required to significantly curtail, delay or discontinue one or more of our research and development programs, the manufacture of clinical and commercial supplies, product portfolio expansion or pre commercialization efforts, which could adversely affect our business prospects, or we may be unable to continue operations.
+Added: Raising additional capital may cause dilution to our existing stockholders, restrict our operations or require us to relinquish rights to our technologies, nomlabofusp or other product candidates that we may develop, in-license or acquire in the future.
We may seek additional capital through a combination of private or public equity offerings, debt financings, collaborations and licensing arrangements or other sources.
To the extent we raise additional capital through the sale of equity or convertible debt securities, existing ownership interests will be diluted and the terms of such financings may include liquidation or other preferences that adversely affect the rights of existing stockholders.
−Removed: Debt or equity financings may be coupled with an additional equity component, such as warrants to purchase shares, which could also result in dilution of our existing stockholder’s ownership.
−Removed: If we raise additional funds through strategic partnerships and alliances and licensing arrangements with third parties, we may have to relinquish valuable rights, including future revenue streams, to CTI-1601 or other product candidates that we may develop, in-license or acquire in the future, or grant licenses on terms that are not favorable to us.
+Added: Debt or equity financings may be coupled with an additional equity component, such as warrants to purchase shares, which could also result in dilution of our existing stockholder’s ownership.
+Added: If we raise additional funds through strategic partnerships and alliances and licensing arrangements with third parties, we may have to relinquish valuable rights, including future revenue streams, to nomlabofusp or other product candidates that we may develop, in-license or acquire in the future, or grant licenses on terms that are not favorable to us.
Our ability to use our NOLs and certain other tax attributes may be limited.
1 unchanged sentence
federal income tax purposes of $179.0 million, a portion of which begin to expire in 2026.
−Removed: Our net operating losses ("NOLs") could expire unused and be unavailable to offset future income tax liabilities because of their limited duration or because of restrictions under U.S.
+Added: Our NOLs could expire unused and be unavailable to offset future income tax liabilities because of their limited duration or because of restrictions under U.S.
NOLs generated in taxable years beginning before January 1, 2018 are permitted to be carried forward for 20 taxable years under applicable U.S.
4 unchanged sentences
As of December 31, 2023, the Company had federal net operating loss carryforwards that were generated after December 31, 2017 of $140.3 million that do not expire, however these carryforwards are limited to 80% of the taxable income in any one tax period.
−Removed: In general, under Section 382 of the Internal Revenue Code (the "Code") if a corporation undergoes an “ownership change,”
−Removed: generally defined as a greater than 50% change (by value) in its equity ownership over a three-year period, the corporation’s ability to use its pre-change NOLs and other pre-change tax attributes (such as
−Removed: capitalized research and development costs and research tax credits) to offset its post-change income may be limited.
+Added: In general, under Section 382 of the Internal Revenue Code (the "Code") if a corporation undergoes an “ownership change,” generally defined as a greater than 50% change (by value) in its equity ownership over a
+Added: three-year period, the corporation’s ability to use its pre-change NOLs and other pre-change tax attributes (such as capitalized research and development costs and research tax credits) to offset its post-change income may be limited.
We believe that as a result of our merger with Zafgen, our ability to utilize NOLs acquired in the transaction and our other NOLs is expected to be severely limited by Section 382 of the Code.
−Removed: Additionally, our July 2021 and September 2022 equity transactions could also limit our ability to utilize NOLs in the future.
+Added: Additionally, our July 2021, September 2022 and February 2024 equity transactions could also limit our ability to utilize NOLs in the future.
We may also experience ownership changes in the future as a result of subsequent shifts in our stock ownership.
13 unchanged sentences
Risks Related to Our Product Development and Regulatory Approvals
−Removed: The FDA has placed a partial clinical hold on CTI-1601 and there is uncertainty as to when, or if, the FDA will lift the partial clinical hold on our CTI-1601 program, if it will allow additional cohorts of the dose exploration study or if it will ever allow further clinical development of CTI-1601.
−Removed: In May 2021, the FDA placed a clinical hold on our CTI-1601 clinical program after we notified the agency of mortalities at the two highest dose levels of the 26-week NHP toxicology study that was designed to support extended dosing of patients with CTI-1601.
−Removed: This NHP study included four dose groups in addition to vehicle and the mortalities were seen in the two highest dose groups.
−Removed: At the time the hold was placed, we had no interventional clinical trials with patients enrolling or enrolled.
−Removed: In July 2021, we completed dosing in the NHP toxicology study.
−Removed: Data from the study were collected throughout the second half of 2021 and included in the complete response submitted to the FDA
−Removed: In February 2022, in response to our complete response to the clinical hold discussed above, the FDA stated that it was maintaining the clinical hold and that additional data were needed to resolve the clinical hold.
−Removed: We subsequently submitted a request to the FDA for a Type C meeting, which was granted and was held in July 2022.
−Removed: We submitted a complete response to the FDA incorporating additional information requested by the FDA at the meeting as well as information on a proposed dose exploration study in August 2022.
−Removed: In September 2022, following the Type C meeting and the submission of our complete response, the FDA allowed the 25 mg cohort of a Phase 2, four-week, placebo-controlled, dose exploration trial of CTI-1601 in FA patients to proceed.
−Removed: In connection with this decision, the FDA lifted its full clinical hold on the CTI-1601 clinical development program and imposed a partial hold.
−Removed: We have since initiated the 25 mg cohort of the Phase 2 dose exploration trial.
−Removed: Initiation of the second cohort and/or other clinical trials is contingent on the FDA’s agreement based on its review of the trial's 25 mg cohort data and on review by the trial’s independent data monitoring committee.
−Removed: We anticipate that we will provide an update that will outline the next steps for the clinical trial in the second quarter of 2023 and anticipate reporting top-line data in the second half of 2023
−Removed: Our business may be adversely affected if the FDA does not lift the partial clinical hold in a timely manner, if it places a full clinical hold on the development of CTI-1601, or, if additional non-clinical or clinical studies are required.
−Removed: This may cause significant delays or expense in developing CTI-1601.
−Removed: Our success is currently dependent upon the success of our lead product candidate, CTI-1601, for which we have completed two Phase 1 clinical trials in patients with FA and are currently conducting a Phase 2 dose exploration study.
−Removed: We cannot be certain that data from the first cohort of our current dose exploration study will provide the FDA with adequate data to allow the CTI-1601 development program to proceed as planned in part or in full, or that we will ultimately be successful with our clinical development or that we will be ever able to obtain regulatory approval for CTI-1601.
−Removed: We currently have no drug products for sale and our business is currently wholly dependent on our successful clinical development, regulatory approval and commercialization of CTI-1601, our lead product candidate and our only product candidate in clinical development, for which we have completed two Phase 1 clinical trials in patients with FA and are currently working to complete a Phase 2 dose exploration under an FDA partial clinical hold.
−Removed: The study’s first cohort (25 mg ) is proceeding in line with our planned timeline with dosing completed.
−Removed: Additional cohorts and/or other clinical trials are contingent on the review of the study’s 25 mg cohort data by the FDA and the data monitoring committee.
−Removed: We expect to provide an update on the study in the second quarter of 2023 and anticipate reporting top-line data in the second half of 2023.
−Removed: If our efforts to develop and commercialize CTI-1601 for the treatment of FA are unsuccessful, or we experience significant delays in doing so, our business could also be substantially harmed.
−Removed: The success of CTI-1601 will depend on several factors, including the following:
−Removed: maintaining our IND application with the FDA in order to continue to conduct clinical trials in the United States, including our ability to have the clinical hold lifted by the FDA on a timely basis, if at all;
+Added: The FDA has placed a partial clinical hold on nomlabofusp and there is uncertainty as to when, or if, the FDA will lift the partial clinical hold on our nomlabofusp program, or if it will ever allow further clinical development of nomlabofusp beyond our currently ongoing OLE study at the 25 mg dose level.
+Added: To support extended dosing of patients with nomlabofusp, we conducted a 26-week NHP toxicology study.
+Added: In May 2021, we notified the FDA of certain mortalities which occurred at the two highest dose levels in the then ongoing study.
+Added: On May 25, 2021, the FDA placed a clinical hold on the nomlabofusp clinical program.
+Added: In the clinical hold letter, the FDA stated that it needed to review a full study report from the then-ongoing NHP study and that we could not initiate additional interventional clinical trials until we submitted such report and received notification from the FDA that additional clinical trials could commence.
+Added: At the time of the FDA clinical hold, we had no interventional clinical trials with patients enrolling or enrolled.
+Added: In July 2021, we completed dosing in the 26-week NHP toxicology study.
+Added: The study included four dose groups in addition to vehicle.
+Added: Data from the study were collected throughout the second half of 2021 and included in the complete response to the clinical hold submitted to the FDA in January 2022.
+Added: In February 2022, in response to the complete response to clinical hold, we submitted to the FDA, the FDA stated that it was maintaining the clinical hold and that additional data were needed to resolve the clinical hold.
+Added: We subsequently submitted a request to the FDA for a Type C meeting, which was granted and held in July 2022.
+Added: We submitted a complete response to clinical hold incorporating additional information requested by the FDA at the meeting as well as information on the proposed study in August 2022.
+Added: In September 2022, following the Type C meeting and the submission of the complete response to clinical hold, the FDA allowed the 25 mg cohort of a Phase 2, four-week, placebo-controlled, dose exploration trial of nomlabofusp in FA patients discussed above to proceed.
+Added: In connection with this decision, the FDA lifted its full clinical hold on the nomlabofusp clinical development program and imposed a partial clinical hold.
+Added: In June 2023, we met with the FDA.
+Added: Following that meeting, we submitted a complete response to the FDA’s partial clinical hold that included unblinded safety, PK and frataxin data from the Phase 2 trial’s completed 25 mg cohort.
+Added: In July 2023, following the FDA’s review of our complete response to the partial clinical hold, the FDA cleared initiation of a second cohort (50 mg) in our four-week, placebo-controlled, Phase 2 dose exploration trial and the initiation of our OLE trial with daily dosing of 25 mg.
+Added: In January 2024, we initiated the OLE trial evaluating daily subcutaneous injections of 25 mg of nomlabofusp self-administered or administered by a caregiver, with the first patient dosed in March 2024.
+Added: Dose escalation in the OLE trial will be considered based on safety, tolerability, PK, and tissue FXN levels from the Phase 2 trial’s 50 mg cohort as well as available data from the 25 mg dose of nomlabofusp in the OLE trial, and is contingent on FDA review as part of the partial clinical hold.
+Added: Initial data from the OLE trial is expected in the fourth quarter of 2024.
+Added: In February 2024, we reported positive top-line data and successful completion of both the 25 mg cohort and the 50 mg cohort of our four-week, placebo-controlled Phase 2 dose exploration study of nomlabofusp in participants with FA.
+Added: Nomlabofusp was generally well tolerated and demonstrated dose dependent increases in FXN levels in all evaluated tissues (skin and buccal cells) after daily dosing of 14 days followed by every other day dosing until day 28 in the 25 mg and 50 mg cohorts.
+Added: Our business may be adversely affected if the FDA partial clinical hold does not enable the development program to proceed as planned, if the FDA places a full clinical hold on the development of nomlabofusp, or, if additional non-clinical or clinical studies are required.
+Added: This may cause significant delays or expense in developing nomlabofusp.
+Added: Our success is currently dependent upon the success of our lead product candidate, nomlabofusp.
+Added: We cannot be certain that data from both cohorts of our Phase 2 dose exploration study augmented by data from the OLE trial will provide the FDA with adequate data to remove the partial clinical hold on nomlabofusp, allow the nomlabofusp development program to proceed as planned in part or in full, or that we will ultimately be successful with our clinical development or that we will be ever able to obtain regulatory approval for nomlabofusp.
+Added: We currently have no drug products for sale and our business is currently wholly dependent on our successful clinical development, regulatory approval and commercialization of nomlabofusp, our lead product candidate and our only product candidate in clinical development, for which we have completed two Phase 1 studies and a four-week, placebo-controlled Phase 2 dose exploration study in patients with FA.
+Added: In January 2024, as permitted by the FDA, we initiated the OLE trial evaluating daily subcutaneous injections of 25 mg of nomlabofusp self-administered or administered by a caregiver, with the first patient dosed in March 2024.
+Added: Participants who completed treatment in the Phase 2 dose exploration trial, or who previously completed a prior clinical trial of nomlabofusp are potentially eligible for the OLE.
+Added: Dose escalation in the OLE trial will be considered based on safety, PK, and tissue FXN levels from the 25 mg dose of nomlabofusp in the OLE trial, as well as other data from the Phase 2 trial’s 50 mg cohort, and is contingent on FDA review as part of the partial clinical hold.
+Added: We cannot provide any assurance that the data from our Phase 1 and Phase 2 trials augmented by data from the OLE trial will prove the FDA with adequate data to remove the partial clinical hold, allow us to continue our development of nomlabofusp, or that we will ultimately be successful in our clinical development.
+Added: In addition to the regulatory and manufacturing hurdles faced by our product candidate, the administration of a protein such as nomlabofusp, may cause an immune response, resulting in the creation of antibodies directed against the protein.
+Added: These anti-drug antibodies can have no effect or can neutralize the effectiveness of the protein or require that higher doses be used to obtain a therapeutic effect.
+Added: Neutralizing antibodies may be detected at a later date or upon longer exposure periods and there can be no assurance that neutralizing antibodies will not be detected in the future.
+Added: If our efforts to develop and commercialize nomlabofusp for the treatment of FA are unsuccessful, or we experience significant delays in doing so, our business could also be substantially harmed.
+Added: The success of nomlabofusp will depend on several factors, including the following:
+Added: • maintaining our IND with the FDA in order to continue to conduct clinical trials in the United States, including our ability to expand to higher doses or have the partial clinical hold lifted by the FDA on a timely basis, if at all;
+Added: • successfully submitting a BLA for accelerated approval;
• successfully recruiting, enrolling and retaining patients in and completing any clinical trials, if allowed to continue, including trials in pediatric patients;
−Removed: demonstrating safety, tolerability and efficacy profiles that are satisfactory to the FDA, EMA and other comparable regulatory authorities for marketing approval;
−Removed: successfully completing all necessary toxicology studies to support clinical development and regulatory approval for CTI-1601;
+Added: • demonstrating long-term chronic daily dosing safety, tolerability and efficacy profiles that are satisfactory to the FDA, EMA and other comparable regulatory authorities for marketing approval;
+Added: • successfully completing all necessary toxicology studies to support clinical development and regulatory approval for nomlabofusp;
• receiving timely marketing approvals from applicable regulatory authorities;
• managing the extent and cost of any required post-marketing approval commitments to applicable regulatory authorities;
−Removed: establishing and maintaining arrangements with third-party manufacturers for CTI-1601, including developing, validating and maintaining a commercially viable manufacturing process that is compliant with cGMPs;
+Added: • establishing and maintaining arrangements with third-party manufacturers for nomlabofusp, including developing, validating and maintaining a commercially viable manufacturing process that is compliant with cGMPs;
• maintaining and growing an organization of scientists and business people who can develop our product candidates and technology;
6 unchanged sentences
The process of obtaining regulatory approval is expensive and time consuming.
−Removed: The FDA and foreign regulatory authorities may never approve CTI-1601 for sale and marketing, and even if CTI-1601 is ultimately approved, regulatory approval may be delayed or
−Removed: limited in the United States or in other jurisdictions.
−Removed: Even if we are authorized to sell and market CTI-1601 in one or more markets, there is no assurance that we will be able to successfully market CTI-1601 or that CTI-1601 will achieve market acceptance sufficient to generate profits.
−Removed: If we are unable to successfully develop and commercialize CTI-1601 due to failure to obtain regulatory approval for CTI-1601, to successfully market CTI-1601, to generate profits from the sale of CTI-1601, or due to other risk factors outlined in this report, it would have material adverse effects on our business, financial condition, and results of operations as CTI-1601 is currently our sole product candidate.
+Added: The FDA and foreign regulatory authorities may never approve nomlabofusp for sale and marketing, and even if nomlabofusp is ultimately approved, regulatory approval may be delayed or limited in the United States or in other jurisdictions.
+Added: Even if we are authorized to sell and market nomlabofusp in one or more markets, there is no assurance that we will be able to successfully market nomlabofusp or that nomlabofusp will achieve market acceptance sufficient to generate profits.
+Added: If we are unable to successfully develop and commercialize nomlabofusp due to failure to obtain regulatory approval for nomlabofusp, to successfully market nomlabofusp, to generate profits from the sale of nomlabofusp, or due to other risk factors outlined in this report, it would have material adverse effects on our business, financial condition, and results of operations as nomlabofusp is currently our sole product candidate.
Clinical development is a lengthy and expensive process with an uncertain outcome, and the results of non-clinical studies, toxicology studies or clinical trials may not be predictive of future non-clinical studies, toxicology studies or clinical trial results.
3 unchanged sentences
The historical failure rate for product candidates in our industry is high, especially for products in early stages of development.
−Removed: The results from non-clinical studies, toxicology studies or clinical trials of a product candidate may not predict the results of later non-clinical or clinical trials of the product candidate, or in clinical trials with different patient populations such as children and adolescents and interim results of a clinical trial are not necessarily indicative of final results.
+Added: The results from non-clinical studies, toxicology studies or clinical trials of a product candidate may not predict the results of later non-clinical or clinical trials of the product candidate, or in clinical trials with different patient populations such as children and adolescents and interim results of a clinical trial are not necessarily
+Added: indicative of final results.
Product candidates in later stages of clinical trials may fail to show the desired safety and efficacy characteristics despite having progressed through non-clinical studies and initial clinical trials.
4 unchanged sentences
Furthermore, we cannot provide assurance that we will be able to successfully progress any future non-clinical programs from candidate identification to Phase 1 clinical development.
−Removed: As is typical in candidate development, we have a program of ongoing toxicology studies in animals for CTI-1601 and cannot provide assurance that the findings from such studies or any ongoing or future clinical trials will not adversely affect the clinical development of CTI-1601.
−Removed: For the foregoing reasons, we cannot be certain that our ongoing and planned non-clinical studies and clinical trials will be successful.
−Removed: If non-clinical studies or clinical trials for CTI-1601 or any future product candidates or indications fail to demonstrate safety or efficacy to the satisfaction of the FDA or the equivalent regulatory authorities in other countries, the FDA or equivalent regulatory authority will not approve our product candidates in those and other indications, which could have a material adverse effect on our business, financial condition results of operations and prospects.
−Removed: We do not know whether any ongoing or future clinical trials for CTI-1601 will be completed on schedule, if at all, as the commencement and completion of clinical trials can be delayed, prevented or terminated for a number of reasons, including as a result of safety concerns, or ambiguous or negative interim results.
−Removed: In addition, a clinical trial may be suspended or terminated by us, the FDA, other regulatory authorities, institutional review boards (IRBs") or ethics committees, an independent data monitoring committee, or safety review committee, overseeing the clinical trial at issue or other regulatory authorities due to a number of factors, including, among others:
+Added: As is typical in candidate development, we have a program of toxicology studies in animals for nomlabofusp and cannot provide assurance that the findings from such studies or any ongoing or future clinical trials will not adversely affect the clinical development of nomlabofusp.
+Added: For the foregoing reasons, we cannot be certain that our non-clinical studies and clinical trials will be successful.
+Added: If non-clinical studies or clinical trials for nomlabofusp or any future product candidates or indications fail to demonstrate safety or efficacy to the satisfaction of the FDA or the equivalent regulatory authorities in other countries, the FDA or equivalent regulatory authority will not approve our product candidates in those and other indications, which could have a material adverse effect on our business, financial condition results of operations and prospects.
+Added: We do not know whether any ongoing or future clinical trials for nomlabofusp will be completed on schedule, if at all, as the commencement and completion of clinical trials can be delayed, prevented or terminated for a number of reasons, including as a result of safety concerns, or ambiguous or negative interim results.
+Added: In addition, a clinical trial may be suspended or terminated by us, the FDA, other regulatory authorities, IRBs or ethics committees, an independent data monitoring committee, or safety review committee, overseeing the clinical trial at issue or other regulatory authorities due to a number of factors, including, among others:
• failure to conduct the clinical trial in accordance with regulatory requirements or our clinical protocols;
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• severe, serious or unexpected drug-related adverse events experienced by patients in clinical trials;
+Added: • unanticipated negative effects of chronic long-term daily patient dosing;
• the FDA, the EMA, or other applicable regulatory authorities may disagree with our clinical trial designs, our interpretation of data from clinical trials, or may change the requirements for approval even after it has reviewed and commented on the design for our clinical trials;
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Failures or delays in the completion of our clinical trials could result in increased costs and could delay, prevent or limit our ability to generate revenue and continue our business.
−Removed: For our lead product candidate CTI-1601, we have completed two Phase 1 clinical trials in patients with FA and are currently conducting the first cohort of a Phase 2, four-week, placebo-controlled, dose exploration trial of CTI-1601 in FA patients.
−Removed: Additional cohorts and/or the initiation of other clinical trials are contingent on agreement by the FDA based on its review of the data from the 25 mg cohort and on review by the study's independent data monitoring committee.
−Removed: We expect to provide an update that will outline the next steps for the study in the second quarter of 2023 and anticipate reporting top-line data in the second half of 2023.
−Removed: We do not know if, or when, the FDA will lift the partial clinical hold on our CTI-1601 program, if it will allow additional cohorts of this dose exploration study or if it will ever allow further clinical development of CTI-1601.
+Added: For our lead product candidate nomlabofusp, we have completed two Phase 1 clinical trials in patients with FA and our four-week, placebo-controlled Phase 2 dose exploration study of nomlabofusp in FA patients.
+Added: The FDA has agreed that we may commence our OLE study in patients who previously participated in one of our previous nomlabofusp clinical trials at the 25 mg level.
+Added: We cannot be certain that data from both cohorts of our Phase 2 dose exploration study augmented by data from the OLE study will provide the FDA with adequate data to remove the current partial clinical hold on nomlabofusp.
Clinical trials may also be delayed or terminated as a result of safety issues in non-clinical or clinical trials, ambiguous or negative interim results or events outside of our control.
−Removed: If future clinical trials of CTI-1601 fail or further delays occur in the United States and or other countries, we may not be able to develop and commercialize CTI-1601 and could fail to realize the potential advantages of doing so, and it could materially adversely affect our business, financial condition and results of operations.
−Removed: In addition, disruptions caused by health crises, such as the recent COVID-19 pandemic may increase the likelihood that we encounter such difficulties or delays in initiating, enrolling, conducting or completing our planned and ongoing clinical trials.
+Added: If future clinical trials of nomlabofusp fail or further delays occur in the United States and or other countries, we may not be able to develop and commercialize nomlabofusp and could fail to realize the potential advantages of doing so, and it could materially adversely affect our business, financial condition and results of operations.
+Added: In addition, disruptions caused by future pandemic, epidemic or outbreak of an infectious disease, such as the COVID-19 pandemic may increase the likelihood that we encounter such difficulties or delays in initiating, enrolling, conducting or completing our planned and ongoing clinical trials.
Further, FA is a rare disease, there are a limited number of patients in close proximity to clinical trial sites and clinical trial patients may need to travel from other countries to the clinical trial sites in order to participate.
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We may not be successful in our efforts to identify, discover or acquire additional product candidates.
−Removed: We currently only have one product candidate CTI-1601 in clinical development, although we have other product candidates in pre-clinical development.
+Added: We currently only have one product candidate nomlabofusp in clinical development, although we have other product candidates in pre-clinical development.
Therefore, the success of our business largely depends upon our ability to identify, develop, in-license or acquire and commercialize products targeting rare diseases.
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If any of these events occur, we may be forced to abandon our development efforts for a program or programs, which would have a material adverse effect on our business, financial condition and results of operations.
−Removed: We have no marketed proprietary products and have not yet advanced a product candidate beyond Phase 2 clinical trials, which makes it difficult to assess our ability to develop CTI-1601 or any future product candidates and commercialize any resulting products independently.
−Removed: We have no experience in later stage clinical development, and related regulatory requirements or the commercialization of products.
−Removed: As a result, we have not yet demonstrated our ability to independently and repeatedly conduct clinical development after Phase 1, successfully conduct an international multi-center clinical trial, conduct a pivotal clinical trial, obtain regulatory approval, manufacture drug product on a commercial scale or arrange for a third party to do so on our behalf, and commercialize therapeutic products.
+Added: We have no marketed proprietary products and have not yet advanced a product candidate beyond Phase 2 clinical trials, which makes it difficult to assess our ability to develop nomlabofusp or any future product candidates and commercialize any resulting products independently.
+Added: We have little experience in later stage clinical development, and related regulatory requirements or the commercialization of products.
+Added: As a result, we have not yet demonstrated our ability to independently and repeatedly conduct clinical development after Phase 1, successfully conduct an international multi-center clinical trial, conduct a pivotal clinical trial, obtain regulatory approval, manufacture drug product on a commercial scale or
+Added: arrange for a third party to do so on our behalf, and commercialize therapeutic products.
We will need to develop such abilities if we are to execute on our business strategy to develop and independently commercialize product candidates for orphan and niche indications.
To execute on our business plan for the development of independent programs, we will need to successfully:
−Removed: obtain the FDA's permission to continue with the clinical development of CTI-1601;
+Added: • obtain the FDA's permission to continue with the clinical development of nomlabofusp beyond our currently ongoing OLE study at the 25 mg dose level;
• execute our clinical development plans for product candidates;
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If we are unsuccessful in accomplishing these objectives, we will not be able to develop and commercialize any product candidates independently and could fail to realize the potential advantages of doing so, and it would materially adversely affect our business, financial condition and results of operations.
−Removed: We cannot be certain that we will be able to successfully complete clinical trials for CTI-1601 or any other product candidates.
−Removed: We have advanced only one product candidate into clinical development, CTI-1601.
−Removed: Our business currently depends primarily on CTI-1601’s successful clinical development, regulatory approval and commercialization.
+Added: We cannot be certain that we will be able to successfully complete clinical trials for nomlabofusp or any other product candidates.
+Added: We have advanced only one product candidate into clinical development, nomlabofusp.
+Added: Our business currently depends primarily on nomlabofusp’s successful clinical development, regulatory approval and commercialization.
We submitted our IND and it was accepted, permitting the conduct of clinical trials.
−Removed: We completed two Phase 1 clinical trials but, as a result of certain mortalities in a non-clinical study of NHPs, the FDA issued a clinical hold.
−Removed: We responded to the clinical hold in January 2022.
−Removed: Following review of our response, the FDA maintained the clinical hold.
−Removed: In September 2022, following the Type C meeting and the submission of our complete response, the FDA allowed the 25 mg cohort of a Phase 2, four-week, placebo-controlled, dose exploration trial of CTI-1601 in FA patients to proceed.
−Removed: In connection with this decision, the FDA lifted its full clinical hold on the CTI-1601 clinical development program and imposed a partial hold.
−Removed: The dose exploration trial is designed to further characterize CTI-1601’s safety and PD and PK profiles to provide information about the preferred long-term dose and dose regimen.
−Removed: We have since initiated the 25 mg cohort of the Phase 2 dose exploration trial.
−Removed: Initiation of the second cohort and/or
−Removed: other clinical trials is contingent on the FDA’s agreement based on its review of the trial's 25 mg cohort data and on review by the trial’s independent data monitoring committee.
−Removed: We anticipate that we will provide an update that will outline the next steps for the clinical trial in the second quarter of 2023 and anticipate reporting top-line data in the second half of 2023.
−Removed: We do not know if, or when, the FDA will lift the partial clinical hold on our CTI-1601 program, if it will allow additional cohorts of the dose exploration study or if it will ever allow further clinical development of CTI-1601.
−Removed: If the FDA does not lift the clinical hold in a timely manner, or at all, our development timelines and our business may be adversely affected and our stock price may decline.
−Removed: Further, even if the FDA lifts the partial clinical hold, or if the FDA or other regulatory agencies continue to express safety concerns after the partial clinical hold is lifted, future CTI-1601 non-clinical or clinical studies may be required.
−Removed: In such instances, our progress in the development of CTI-1601 may be significantly slowed and the associated costs may be significantly increased, adversely affecting our business, which could impair our ability to ultimately obtain FDA or other regulatory approval for CTI-1601.
+Added: We completed two Phase 1 and our four-week, placebo-controlled Phase 2 dose exploration study.
+Added: As a result of certain mortalities in a non-clinical study of NHPs, the FDA issued a clinical hold in May 2021.
+Added: In September 2022, following a Type C meeting and the submission of our complete response to the partial clinical hold, the FDA allowed the 25 mg cohort of a Phase 2, four-week, placebo-controlled, dose exploration trial of nomlabofusp in FA patients to proceed.
+Added: In connection with this decision, the FDA lifted its full clinical hold on the nomlabofusp clinical development program and imposed a partial hold.
+Added: In June 2023, we met with the FDA.
+Added: Following that meeting, we submitted a complete response to the FDA’s partial clinical hold that included unblinded safety, PK and frataxin data from the Phase 2 trial’s completed 25 mg cohort.
+Added: In July 2023, following the FDA’s review of our complete response to the partial clinical hold, the FDA cleared initiation of a second cohort at 50 mg of our four-week, placebo-controlled, Phase 2 dose exploration trial and to initiate our OLE trial with daily dosing of 25 mg.
+Added: In February 2024, we reported positive top-line data and successful completion of our four-week, placebo-controlled Phase 2 dose exploration study of nomlabofusp in participants with FA.
+Added: Nomlabofusp was generally well tolerated and demonstrated dose dependent increases in FXN levels in all evaluated tissues (skin and buccal cells) after daily dosing of 14 days followed by every other day dosing until day 28 in the 25 mg and 50 mg cohorts.
+Added: Participants in the 25 mg (n=13) and 50 mg (n=15) cohorts were randomized 2:1 to receive subcutaneous injections of nomlabofusp or placebo.
+Added: The initiation of additional U.S.
+Added: clinical trials evaluating nomlabofusp are contingent on FDA review of data under the partial clinical hold.
+Added: The FDA has agreed that we may commence our OLE study in patients who previously participated in one of our previous nomlabofusp clinical trials at the 25 mg level dosed daily.
+Added: We cannot be certain that data from both cohorts of our Phase 2 dose exploration study augmented by data from the OLE study will provide the FDA with adequate data to remove the current partial clinical hold on nomlabofusp, allow the nomlabofusp development program to proceed as planned in part or in full, or that we will ultimately be successful with our clinical development or that we will be ever able to obtain regulatory approval for.
In clinical development of any product candidate, the outcome of toxicology studies and early clinical trials may not be positive and may not be predictive of the success of later non-clinical studies or clinical trials.
Adverse toxicology or safety results could lead to clinical holds or other developmental delays.
−Removed: Interim results of clinical trials do not necessarily predict success in those or future clinical trials.
+Added: Interim results of clinical
+Added: trials do not necessarily predict success in those or future clinical trials.
Success in adult clinical trials may not predict the outcome of pediatric clinical trials.
−Removed: Published clinical data or case reports from third parties or early clinical trial data of CTI-1601 or any future product candidates may not be predictive of the results of later-stage clinical trials.
+Added: Published clinical data or case reports from third parties or early clinical trial data of nomlabofusp or any future product candidates may not be predictive of the results of later-stage clinical trials.
Interpretation of results from early, usually smaller, studies that suggest a clinically meaningful response in some patients, requires caution.
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These uncertainties are enhanced where the diseases under study lack established clinical endpoints, validated measures of efficacy, as is often the case with orphan diseases for which no drugs have been developed previously and where the product candidates target novel mechanisms.
−Removed: For example, to our knowledge, CTI-1601 is the only protein replacement therapy being developed for the treatment of FA and therefore non-clinical studies may not be adequate to predict efficacy in a clinical trial due to our novel protein replacement therapy platform.
+Added: For example, to our knowledge, nomlabofusp is the only protein replacement therapy being developed for the treatment of FA and therefore non-clinical studies may not be adequate to predict efficacy in a clinical trial due to our novel protein replacement therapy platform.
In some instances, there can be significant variability in safety or efficacy results between different clinical trials of the same product candidate due to numerous factors, including changes in trial procedures set forth in protocols, differences in the size and type of the patient populations, such as pediatric patients, variability of the disease being studied, changes in and adherence to the dosing regimen and other clinical trial protocols and the rate of dropout among clinical trial participants.
−Removed: If we fail to ultimately receive positive results in clinical trials of CTI-1601, the development timeline and regulatory approval and commercialization prospects for CTI-1601, and, correspondingly, our business, financial prospects and results of operation would be negatively impacted.
−Removed: Further, CTI-1601 or any future product candidates may not be approved even if they achieve their primary endpoint in clinical trials.
+Added: If we fail to ultimately receive positive results in clinical trials of nomlabofusp, the development timeline and regulatory approval and commercialization prospects for nomlabofusp, and, correspondingly, our business, financial prospects and results of operation would be negatively impacted.
+Added: Further, nomlabofusp or any future product candidates may not be approved even if they achieve their primary endpoint in clinical trials.
The FDA, EMA or foreign regulatory authorities may disagree with our trial design and our interpretation of data from non-clinical studies and clinical trials.
−Removed: In addition, any of these regulatory authorities may change its requirements for the approval of a product candidate even after reviewing and providing comments or advice on a protocol for a pivotal clinical trial that, if successful, would potentially form the basis for an application for approval by the FDA, EMA or another regulatory authority.
−Removed: Furthermore, any of these regulatory authorities may also approve CTI-1601 or any future product candidates for a narrower indication than we may request or may grant approval contingent on the performance of costly post-marketing clinical trials.
−Removed: We may experience difficulties identifying and enrolling patients in our clinical trials given the limited number of patients who have the disease for which CTI-1601 is being studied or for any other product candidate we may study in the future.
−Removed: Difficulty in enrolling patients could delay or prevent clinical trials of CTI-1601 or any future product candidate.
−Removed: There are also competing FA therapeutics, other competing studies and potentially other FA therapeutics that could be approved that may also limit the availability of prospective participants in CTI-1601 clinical trials.
−Removed: Identifying and qualifying patients to participate in clinical trials of CTI-1601 is critical to our success.
−Removed: The timing of our clinical trials depends in part on the speed at which we can recruit patients to participate in testing CTI-1601, and we may experience delays in our clinical trials if we encounter difficulties in enrollment, such as difficulties with enrollment in pediatric clinical trials.
−Removed: The conditions for which we are planning to evaluate CTI-1601 and any product candidates we may evaluate in the future, are rare genetic diseases.
+Added: In addition, FDA, EMA or foreign regulatory authorities may disagree with the extent of population exposure to assess clinical safety.
+Added: Any of these regulatory authorities may change its requirements for the approval of a product candidate even after reviewing and providing comments or advice on a protocol for a pivotal clinical trial that, if successful, would potentially form the basis for an application for approval by the FDA, EMA or another regulatory authority.
+Added: Furthermore, any of these regulatory authorities may also approve nomlabofusp or any future product candidates for a narrower indication than we may request or may grant approval contingent on the performance of costly post-marketing clinical trials.
+Added: We may experience difficulties identifying and enrolling patients in our clinical trials given the limited number of patients who have the disease for which nomlabofusp is being studied or for any other product candidate we may study in the future.
+Added: Difficulty in enrolling patients could delay or prevent clinical trials of nomlabofusp or any future product candidate.
+Added: There are also competing FA therapeutics, other competing studies and potentially other FA therapeutics that could be approved that may also limit the availability of prospective participants in nomlabofusp clinical trials.
+Added: Identifying and qualifying patients to participate in clinical trials of nomlabofusp is critical to our success.
+Added: The timing of our clinical trials depends in part on the speed at which we can recruit patients to participate in testing nomlabofusp, and we may experience delays in our clinical trials if we encounter difficulties in enrollment, such as difficulties with enrollment in pediatric clinical trials.
+Added: The conditions for which we are planning to evaluate nomlabofusp and any product candidates we may evaluate in the future, are rare genetic diseases.
Accordingly, there are limited patient pools from which to draw for clinical trials.
Arranging for investigative sites and recruiting patients for clinical trials in this disease may be very difficult.
−Removed: The recent FDA approval of a product for the treatment of FA may impact our ability to enroll patients in our clinical trials as patients using other FA treatments may be excluded from participation in our CTI-1601 studies or may be less likely to participate in our CTI-1601 clinical trials due to the availability of another FA therapy.
−Removed: If other companies are studying their investigational products in Friedreich’s ataxia and/or if other companies have their products approved for the treatment of FA, it may be more difficult to enroll eligible patients into our clinical trials.
+Added: The recent FDA approval of a product for the treatment of FA may impact our ability to enroll patients in our clinical trials as patients using other FA treatments may be excluded from participation in our nomlabofusp studies or may be less likely to participate in our nomlabofusp clinical trials due to the availability of another FA therapy.
+Added: If other companies are studying their investigational products in Friedreich’s ataxia and/or if other companies have their products approved for the treatment of FA, it may be more difficult to enroll eligible patients into our clinical trials.
Competing priorities at sites and participation of subjects in other studies may limit our ability to execute clinical trials in a timely fashion, if at all.
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Furthermore, our inability to enroll a sufficient number of patients for our clinical trials, including pediatric clinical trials, could result in significant delays or may require us to abandon one or more clinical trials altogether.
−Removed: Enrollment delays in our clinical trials may result in increased development costs for CTI-1601 or any future product candidates, and jeopardize our ability to achieve our clinical development timeline and goals, including the dates by which we will commence, complete and receive results from clinical trials.
+Added: Enrollment delays in our clinical trials may result in increased development costs for nomlabofusp or any future product candidates, and jeopardize our ability to achieve our clinical development timeline and goals, including the dates by which we will commence, complete and receive results from clinical trials.
If patients are unwilling to participate in our trials for any reason, the timeline for recruiting patients, conducting trials, and obtaining regulatory approval of potential products may be delayed.
−Removed: Enrollment delays in our clinical trials may also jeopardize our ability to commence sales of and generate revenues from CTI-1601, which could cause the value of our company to decline and limit our ability to obtain additional financing, if needed.
+Added: Enrollment delays in our clinical trials may also jeopardize our ability to commence sales of and generate revenues from nomlabofusp, which could cause the value of our company to decline and limit our ability to obtain additional financing, if needed.
Any of these occurrences may harm our business, financial condition, and prospects significantly.
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The clinical trial requirements of the FDA and other comparable regulatory agencies and the criteria these regulators use to determine the safety and efficacy of any product candidate vary substantially according to the type, complexity, novelty and intended use and market of the potential product.
−Removed: Given the nature of FA, we may have to devise novel clinical endpoints to be tested in our clinical trials, which can lead to some subjectivity in interpreting trial results and could result in regulatory agencies not agreeing with the validity of our endpoints, or our interpretation of the clinical data, and therefore denying approval, which would materially adversely affect our business, financial condition and results of operations.
−Removed: As a result, the design and conduct of clinical trials for a therapeutic product candidate such as CTI-1601 that is intended to deliver FXN through a subcutaneously administered, recombinant fusion protein in FA patients are subject to unknown risks, and we may
−Removed: experience setbacks with our planned clinical trials of CTI-1601 in FA because of the limited clinical experience with our mechanism of action in these patients.
−Removed: In particular, regulatory authorities in the United States and the European Union have not issued definitive guidance as to how to measure and achieve efficacy in treatments for FA.
−Removed: As a result, the design and conduct of clinical trials of CTI-1601 may take longer, be more costly or be less effective as part of the novelty of development in FA.
−Removed: We may use new or novel endpoints or methodologies, and the FDA or other regulatory authorities may not consider the endpoints of our clinical trials to provide clinically meaningful results.
+Added: Recently, we had discussions with the FDA regarding the use of tissue FXN levels as a novel surrogate endpoint.
+Added: The FDA has acknowledged that frataxin deficiency appears to be critical to the pathogenic mechanism of FA, and that there continues to be an unmet need for treatments for FA patients that address the underlying disease pathophysiology.
+Added: We intend to pursue an accelerated approval using FXN levels, supportive PD and clinical information, and safety data from the OLE study, along with additional non-clinical pharmacology information needed to support the novel surrogate endpoint approach.
+Added: We are beginning to plan for a confirmatory study and are targeting a BLA submission in the second half of 2025.
+Added: The FDA or other regulatory authorities may not agree with this approach.
+Added: Regulatory authorities in the United States, the United Kingdom and the European Union have not issued definitive guidance as to how to measure and achieve efficacy in treatments for FA.
+Added: As a result, the design and conduct of clinical trials of nomlabofusp may take longer, be more costly or be less effective as part of the novelty of development in FA.
+Added: The FDA may not accept that the supportive PD and clinical information, and safety data from the OLE study, along with additional non-clinical pharmacology data we ultimately submit in our BLA, adequately supports the use of FXN levels as a novel surrogate endpoint.
+Added: Even if the FDA supports the use of FXN levels as a novel surrogate endpoint, the FDA may not agree with the adequacy of the design of clinical trials intended to assess this novel surrogate endpoint.
Even if applicable regulatory authorities do not object to our proposed endpoints in an earlier stage clinical trial, such regulatory authorities may require evaluation of additional or different clinical endpoints in later-stage clinical trials.
−Removed: CTI-1601 may cause adverse events or undesirable side effects in non-clinical or clinical trials that could delay or prevent its regulatory approval, limit the commercial profile of approved labeling, or result in significant negative consequences following regulatory approval, if any.
−Removed: Any adverse events or undesirable side effects caused by, or other unexpected properties of, CTI-1601 in non-clinical or clinical studies could cause us, any future collaborators, an IRB or ethics committee or regulatory authorities to interrupt, delay or halt clinical trials of our product candidate and could result in a more restrictive label or the delay or denial of regulatory approval by the FDA or other regulatory authorities.
−Removed: Should the FDA permit us to continue with the clinical development of CTI-1601, it is possible that as we progress CTI-1601 through clinical trials and toxicology studies, or as the use of CTI-1601 becomes more widespread if it receives regulatory approval, illnesses, injuries, discomforts and other adverse events that were not observed in earlier trials, as well as conditions that did not occur or went undetected in previous trials, may be reported by patients.
+Added: Nomlabofusp, including the effects of long-term daily patient dosing, may cause adverse events or undesirable side effects in clinical trials that could delay or prevent its regulatory approval, limit the commercial profile of approved labeling, or result in significant negative consequences following regulatory approval, if any.
+Added: Any adverse events or undesirable side effects caused by, or other unexpected properties of, nomlabofusp in non-clinical or clinical studies could cause us, any future collaborators, an IRB or ethics committee or regulatory authorities to interrupt, delay or halt clinical trials of our product candidate and could result in a more restrictive
+Added: label or the delay or denial of regulatory approval by the FDA or other regulatory authorities.
+Added: Should the FDA permit us to continue with the clinical development of nomlabofusp, it is possible that as we progress nomlabofusp through clinical trials and toxicology studies, or as the use of nomlabofusp becomes more widespread if it receives regulatory approval, illnesses, injuries, discomforts and other adverse events that were not observed in earlier trials, as well as conditions that did not occur or went undetected in previous trials, may be reported by patients.
If such side effects become known later in development or after approval, such findings may harm our business, financial condition and prospects significantly.
−Removed: Further, if a serious safety issue is identified in connection with the use of CTI-1601 commercially or in third-party clinical trials elsewhere, such issues may adversely affect the development potential of CTI-1601 elsewhere or result in regulatory authorities restricting our ability to develop or commercialize CTI-1601, if approved.
−Removed: Further, if CTI-1601 were to receive marketing approval and we or others identify undesirable side effects caused by the product (or any other product) after the approval, a number of potentially significant negative consequences could result, including:
+Added: Further, if a serious safety issue is identified in connection with the use of nomlabofusp commercially or in third-party clinical trials elsewhere, such issues may adversely affect the development potential of nomlabofusp elsewhere or result in regulatory authorities restricting our ability to develop or commercialize nomlabofusp, if approved.
+Added: Further, if nomlabofusp were to receive marketing approval and we or others identify undesirable side effects caused by the product (or any other product) after the approval, a number of potentially significant negative consequences could result, including:
• regulatory authorities may request that we recall or withdraw the product from the market or may limit the approval of the product through labeling or other means;
−Removed: regulatory authorities may require the addition of labeling statements, such as a “boxed”
−Removed: warning or a contraindication or a precaution, or labeling restrictions based on patient population;
+Added: • regulatory authorities may require the addition of labeling statements, such as a “boxed” warning or a contraindication or a precaution, or labeling restrictions based on patient population;
• we may be required to change the way the product is distributed or administered, conduct additional clinical trials or change the labeling of the product;
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• we could lose our commercial market opportunity and our revenues could decrease substantially;
−Removed: damage to the public perception of the safety of CTI-1601;
+Added: • damage to the public perception of the safety of nomlabofusp;
• our reputation may suffer and physicians or patients might be less likely to use our product or may refer patients to products produced by our competitors.
Any of these events could prevent us from achieving or maintaining market acceptance of the affected product candidate and could substantially increase the costs of commercializing our product candidates and significantly impact our ability to successfully commercialize our product candidates and generate revenues, all of which would materially adversely affect our business, financial condition and results of operations.
−Removed: Interim, “top-line,”
−Removed: and preliminary data from our clinical trials that we announce or publish from time to time may change as more patient data become available or as additional analyses are conducted, and as the data are subject to audit and verification procedures that could result in material changes in the final data.
−Removed: From time to time, we may publish interim, “top-line”
−Removed: or preliminary data from our clinical trials.
+Added: In addition, the patient populations under investigation with nomlabofusp have many co-morbidities that may cause severe illness or death unrelated to our product candidate, which may be attributed to nomlabofusp in a manner that negatively affects the safety profile of our product candidate.
+Added: Interim, “top-line,” and preliminary data from our clinical trials that we announce or publish from time to time may change as more patient data become available or as additional analyses are conducted, and as the data are subject to audit and verification procedures that could result in material changes in the final data.
+Added: From time to time, we may publish interim, preliminary or “top-line” data from our clinical trials.
Interim data from clinical trials that we may complete are subject to the risk that one or more of the clinical outcomes may materially change as patient enrollment continues and more patient data become available.
−Removed: Preliminary or “top-line”
−Removed: data also remain subject to audit and verification procedures that may result in the final data being materially different from the preliminary data we previously published.
+Added: Preliminary or “top-line” data also remain subject to audit and verification procedures that may result in the final data being materially different from the preliminary data we previously published.
As a result, interim and preliminary data should be viewed with caution until the final data are available.
−Removed: Material adverse changes between preliminary, “top-line”
−Removed: or interim data and final data could significantly harm our business, financial condition, results of operations and prospects.
+Added: Material adverse changes between interim, preliminary or “top-line” data and final data could significantly harm our business, financial condition, results of operations and prospects.
Our approach to discover and develop fusion proteins for delivering proteins is novel and may never lead to marketable products.
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The scientific discoveries that form the basis for our research are relatively new.
−Removed: CTI-1601 uses a novel and unproven approach and mechanism to treat FA and therefore its efficacy and safety are difficult to predict, and there is no guarantee that CTI-1601 will be approved by the FDA, the EMA, or any other regulatory authorities.
−Removed: If CTI-1601 proves to be ineffective, unsafe or commercially unviable, it is possible that our platform and pipeline would have little, if any, value, which would substantially harm our business, financial condition, results of operations and prospects.
+Added: Nomlabofusp uses a novel and unproven approach and mechanism to treat FA and therefore its efficacy and safety are difficult to predict, and there is no guarantee that nomlabofusp will be approved by the FDA, the EMA, or any other regulatory authorities.
+Added: If nomlabofusp proves to be ineffective, unsafe or commercially unviable, it is possible that our platform and pipeline would have little, if any, value, which would substantially harm our business, financial condition, results of operations and prospects.
In addition, our approach may expose us to additional financial risks and make it more difficult to raise additional capital than other, more advanced proven technologies, which would materially adversely affect our business, financial condition and results of operations.
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We could experience manufacturing problems that result in delays in the development or commercialization of our protein replacement therapy platform or product candidates or otherwise harm our business.
−Removed: The manufacture of fusion proteins, such as CTI-1601 and any fusion protein candidates, is technically complex and necessitates substantial expertise and capital investment.
−Removed: Production difficulties caused by unforeseen events may delay the availability of material for clinical trials and commercial products for CTI-1601 or any fusion protein product that may receive regulatory approval in the future.
+Added: The manufacture of fusion proteins, such as nomlabofusp and any fusion protein candidates, is technically complex and necessitates substantial expertise and capital investment.
+Added: Production difficulties caused by unforeseen events may delay the availability of material for clinical trials and commercial products for nomlabofusp or any fusion protein product that may receive regulatory approval in the future.
Additionally, because biologic products are complex, the manufacture of such products and product candidates is more difficult and costly.
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Any failure by us or our contract manufacturing organizations to adhere to or document compliance to such regulatory requirements could lead to a delay or interruption in the availability of our program materials for clinical trials or commercial use, among other consequences.
−Removed: If we or our manufacturers fail to comply with the FDA, EMA, or other regulatory authorities, it could result in sanctions being imposed on us, including fines, injunctions, civil penalties, delays, suspension or withdrawal of approvals, clinical holds or termination of clinical trials, Form 483s, warning or untitled letters, regulatory communications warning the public about safety issues with a product, import or export
−Removed: refusals, license revocation, seizures, detentions, or recalls of product candidates or product, operating restrictions, criminal prosecutions or debarment, suits under the civil False Claims Act, corporate integrity agreements, or consent decrees any of which could significantly and adversely affect supplies of our product candidates and our business, financial conditions and results of operations could be materially adversely affected.
+Added: If we or our manufacturers fail to comply with the FDA, EMA, or other regulatory authorities, it could result in sanctions being imposed on us, including fines, injunctions, civil penalties, delays, suspension or withdrawal of approvals, clinical holds or termination of clinical trials, Form 483s, warning or untitled letters, regulatory communications warning the public about safety issues with a product, import or export refusals, license revocation, seizures, detentions, or recalls of product candidates or product, operating restrictions, criminal prosecutions or debarment, suits under the civil False Claims Act, corporate integrity agreements, or consent decrees any of which could significantly and adversely affect supplies of our product candidates and our business, financial conditions and results of operations could be materially adversely affected.
Our current dependence upon others for the manufacture of our product candidates may also adversely affect our business, results of operations, financial condition, and our ability to commercialize any product candidates that receive regulatory approval on a timely and competitive basis.
−Removed: Fast track designation by the FDA or any future designations may not lead to a faster development, regulatory review or approval process and it does not increase the likelihood that any of our product candidates will receive marketing approval.
−Removed: We have received fast track therapy designation for CTI-1601 for the treatment of FA.
−Removed: We may, in the future, apply for other designations from the FDA (such as breakthrough therapy or accelerated approval) for CTI-1601 or future product candidates.
+Added: Fast track designation by the FDA or any future expedited program designations may not lead to a faster development, regulatory review or approval process and it does not increase the likelihood that any of our product candidates will receive marketing approval.
+Added: We have received fast track therapy designation for nomlabofusp for the treatment of FA.
+Added: We may, in the future, apply for other expedited program designations from the FDA (such as breakthrough therapy) for nomlabofusp or future product candidates.
Designation for these programs is within the discretion of the FDA.
−Removed: Accordingly, even if we believe CTI-1601 or a future product candidate meets the criteria for designation, the FDA may disagree.
−Removed: In any event, the receipt of a designation may not result in a faster development process, review or approval compared to products considered for approval under conventional FDA procedures and, in any event, does not assure ultimate approval by the FDA.
−Removed: In addition, even though CTI-1601 has obtained fast track designation, the FDA may later decide that it no longer meets the criteria for designation and revoke it.
−Removed: Approval of other therapies for the treatment Friedreich’s ataxia could negatively impact our continued fast track therapy designation for CTI-1601 for the treatment of FA.
−Removed: In addition, if we apply to the FDA for other designations for CTI-1601 or future product candidates, the FDA might not grant such designations.
−Removed: If we apply for any similar programs in foreign countries for CTI-1601 or future product candidates, those designations also might not be granted by the regulatory authorities of those countries.
+Added: Accordingly, even if we believe nomlabofusp or a future product candidate meets the criteria for designation, the
+Added: FDA may disagree.
+Added: The receipt of a designation may not result in a faster development process, review or approval compared to products considered for approval without these expedited program designations and, in any event, does not assure ultimate approval by the FDA.
+Added: In addition, even though nomlabofusp has obtained fast track designation, the FDA may later decide that it no longer meets the criteria for designation and revoke it.
+Added: Approval of other therapies for the treatment Friedreich’s ataxia could negatively impact our continued fast track therapy designation for nomlabofusp for the treatment of FA.
+Added: In addition, if we apply to the FDA for other designations for nomlabofusp or future product candidates, the FDA might not grant such designations.
+Added: If we apply for any similar programs in foreign countries for nomlabofusp or future product candidates, those designations also might not be granted by the regulatory authorities of those countries.
Any of the above could adversely affect our business, financial condition and results of operations.
−Removed: If we decide to pursue accelerated approval for any of our product candidates, it may not lead to a faster development or regulatory review or approval process and does not increase the likelihood that it will receive marketing approval.
+Added: We intend to pursue accelerated approval from FDA for nomlabofusp for the treatment of Friedreich’s ataxia, however this may not lead to a faster development or regulatory review or approval process and does not increase the likelihood that we will receive marketing approval.
If we are unable to obtain approval under an accelerated pathway, we may be required to conduct additional clinical trials beyond those that we contemplate, which could increase the expense of obtaining, reduce the likelihood of obtaining, and/or delay the timing of obtaining, necessary marketing approvals.
−Removed: In the future, we may decide to pursue accelerated approval for one or more of our product candidates.
−Removed: Under the FDA’s accelerated approval program, the FDA may approve a drug or biologic for a serious or life-threatening illness that provides meaningful therapeutic benefit to patients over existing treatments based upon a surrogate endpoint that is reasonably likely to predict clinical benefit, or on a clinical endpoint that can be measured earlier than irreversible morbidity or mortality, that is reasonably likely to predict an effect on irreversible morbidity or mortality or other clinical benefit, taking into account the severity, rarity, or prevalence of the condition and the availability or lack of alternative treatments.
−Removed: Approval of other therapies for the treatment Friedreich’s ataxia, including the recent approval of omaveloxolone for the treatment of FA, could negatively impact our ability to demonstrate a benefit over existing treatments and therefore utilize the accelerated approval pathway.
+Added: We intend to pursue an accelerated approval from FDA for nomlabofusp for the treatment of FA using FXN levels, supportive pharmacodynamic and clinical information and safety data from the OLE study, along with additional non-clinical pharmacology information needed to support our surrogate biomarker approach.
+Added: Under the FDA’s accelerated approval program, the FDA may approve a drug or biologic for a serious or life-threatening illness that provides meaningful therapeutic benefit to patients over existing treatments based upon a surrogate endpoint that is reasonably likely to predict clinical benefit, or on a clinical endpoint that can be measured earlier than irreversible morbidity or mortality, that is reasonably likely to predict an effect on irreversible morbidity or mortality or other clinical benefit, taking into account the severity, rarity, or prevalence of the condition and the availability or lack of alternative treatments.
+Added: Although we have initiated discussions with FDA concerning our surrogate biomarker approach, there can be no assurance that data we intend to generate will be successful in establishing that increases in FXN levels are reasonably likely to predict clinical benefit.
+Added: In addition, future nonclinical pharmacology and clinical studies may not provide adequate information or may fail to support the predictive value of increases in FXN and, therefore, its ability to serve as a surrogate endpoint.
+Added: Even if these evidentiary requirements are met, we may not be able to accrue adequate exposures to assess clinical safety or expedite the scale up of manufacturing or meet other CMC requirements in a timeframe commensurate with the expedited assessment of clinical efficacy.
+Added: Approval of other therapies for the treatment of FA, including the approval of omaveloxolone for the treatment of FA, could negatively impact our ability to utilize the accelerated approval pathway, and/or get approval for nomlabofusp.
For drugs or biologics granted accelerated approval, post-marketing confirmatory trials are required to describe the anticipated effect on irreversible morbidity or mortality or other clinical benefit.
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Moreover, the FDA may withdraw approval of any product candidate approved under the accelerated approval pathway if, for example:
−Removed: the trial or trials required to verify the predicted clinical benefit of the product candidate fails to verify such benefit or do not demonstrate sufficient clinical benefit to justify the risks associated with such product;
+Added: • the trial or trials required to verify the predicted clinical benefit of the product candidate fail to verify such benefit or do not demonstrate sufficient clinical benefit to justify the risks associated with such product;
• other evidence demonstrates that the product candidate is not shown to be safe or effective under the conditions of use;
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Changes to or termination of the accelerated approval program could prevent or limit our ability to obtain accelerated approval of any of our clinical development programs.
−Removed: Recently, the accelerated approval pathway has come under scrutiny within the FDA and by Congress.
+Added: Recently, the accelerated
+Added: approval pathway has come under scrutiny within the FDA and by Congress.
The FDA has put increased focus on ensuring that confirmatory studies are conducted with diligence and, ultimately, that such studies confirm the benefit.
−Removed: In addition, Congress recently enacted the Food and Drug Omnibus Reform Act (“FDORA”), which included provisions related to the accelerated approval pathway.
−Removed: Pursuant to FDORA, the FDA is authorized to require a post-approval study to be underway prior to approval or within a specified time period following approval.
+Added: In addition, the Food and Drug Omnibus Reform Act (“FDORA”), included provisions related to the accelerated approval pathway.
+Added: Pursuant to FDORA, the FDA is authorized to require, as appropriate, that a post-approval study to be underway prior to approval or within a specified time period following approval.
FDORA also requires the FDA to specify conditions of any required post-approval study and requires sponsors to submit progress reports for required post-approval studies and any conditions required by the FDA.
−Removed: FDORA enables the FDA to initiate enforcement action for the failure to conduct with due diligence a required post-approval study, including a failure to meet any required conditions specified by the FDA or to submit timely reports.
−Removed: If we fail to maintain orphan drug designation or other regulatory exclusivity for CTI-1601 or obtain such exclusivity for any of our other product candidates in the future, our competitive position would be harmed.
−Removed: We received orphan drug designation from the FDA for CTI-1601 for the treatment of FA in July 2017.
+Added: FDORA also gives the FDA increased authority to withdraw approval of a drug or biologic granted accelerated approval on an expedited basis if the sponsor fails to verify the drug or biologic’s predicted clinical benefit.
+Added: FDORA enables the FDA to initiate enforcement action for a sponsor's failure to conduct with due diligence a required post-approval study, including a failure to meet any required conditions specified by the FDA or to submit timely reports.
+Added: If we fail to maintain orphan drug designation or other regulatory exclusivity for nomlabofusp or obtain such exclusivity for any of our other product candidates in the future, our competitive position would be harmed.
+Added: We received orphan drug designation from the FDA for nomlabofusp for the treatment of FA in July 2017.
In the United States, orphan drug designation entitles a party to financial incentives such as tax advantages and user-fee waivers.
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Further, even after an orphan drug is approved, the FDA or comparable foreign regulatory authority can subsequently approve another drug for the same condition if such regulatory authority concludes that the later drug is clinically superior, if it is shown to be safer, more effective or makes a major contribution to patient care.
−Removed: We have also received orphan drug designation for CTI-1601 in the European Union.
−Removed: In the European Union, the European Medicines Agency, or EMA’s Committee for Orphan Medicinal Products grants orphan drug designation to promote the development of products that are intended for the diagnosis, prevention or treatment of life threatening or chronically debilitating conditions affecting not more than five in 10,000 persons in the European Union.
+Added: We have also received orphan drug designation for nomlabofusp in the European Union.
+Added: In the European Union, the European Medicines Agency, or EMA’s Committee for Orphan Medicinal Products grants orphan drug designation to promote the development of products that are intended for the diagnosis, prevention or treatment of life threatening or chronically debilitating conditions affecting not more than five in 10,000 persons in the European Union.
Additionally, designation is granted for products intended for the diagnosis, prevention or treatment of a life threatening, seriously debilitating or serious and chronic condition and when, without incentives, it is unlikely that sales of the drug in the European Union would be sufficient to justify the necessary investment in developing the drug.
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This period may be reduced to six years if the orphan drug designation criteria are no longer met, including where it is shown that the product is sufficiently profitable so that market exclusivity is no longer justified.
−Removed: Loss of orphan drug designation for CTI-1601 or the failure to obtain such designation in other countries or for any future product candidates could adversely affect our business, financial condition and results of operation.
+Added: Loss of orphan drug designation for nomlabofusp or the failure to obtain such designation in other countries or for any future product candidates could adversely affect our business, financial condition and results of operation.
If another product has received approval in the indications for which we have received orphan drug designation, we may still receive approval in that indication if we can demonstrate that our product candidate is clinically superior to the existing orphan product.
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Having to comply with these additional requirements to obtain orphan drug exclusivity could adversely affect our business, financial condition and results of operation.
−Removed: Although we have obtained rare pediatric disease designation for CTI-1601, we may not be eligible to receive a priority review voucher in the event the FDA determines we no longer meet the criteria for designation, revokes the designation or that FDA approval does not occur prior to September 30, 2026.
+Added: Although we have obtained rare pediatric disease designation for nomlabofusp, we may not be eligible to receive a priority review voucher in the event the FDA determines we no longer meet the criteria for designation, revokes the designation or FDA approval does not occur prior to September 30, 2026.
The sponsor of an application for a rare pediatric disease drug product may be eligible for a voucher that can be used or sold to obtain a priority review for a subsequent application submitted under section 505(b)(1) of the FDCA or section 351 of the PHS Act.
The rare pediatric disease priority review voucher program was most recently reauthorized by Congress through September 30, 2024, with the potential for priority review vouchers to be granted through September 30, 2026.
−Removed: We received rare pediatric disease designation from the FDA for CTI-1601 in 2019.
+Added: We received rare pediatric disease designation from the FDA for nomlabofusp in 2019.
We may, in the future, apply for rare pediatric disease designation from the FDA for future product candidates that may qualify for designation.
Vouchers for rare pediatric disease drugs are awarded for qualifying applications when the drug receives approval.
−Removed: Although CTI-1601 has received rare pediatric disease designation, CTI-1601 may not receive a priority review voucher for a number of reasons:
−Removed: CTI-1601 may not receive approval;
−Removed: CTI-1601 may receive approval in adults, but not pediatric patients;
−Removed: CTI-1601 may not meet the eligibility requirements for a priority voucher at the time we seek approval for CTI-1601;
+Added: Although nomlabofusp has received rare pediatric disease designation, nomlabofusp may not receive a priority review voucher for a number of reasons:
+Added: nomlabofusp may not receive approval;
+Added: nomlabofusp may receive approval in adults, but not pediatric patients;
+Added: nomlabofusp may not meet the eligibility requirements for a priority voucher at the time we seek approval for nomlabofusp;
or we may not meet the current deadline for receiving a priority review voucher (September 30, 2026), in which case we would not be able to obtain a voucher unless Congress further reauthorizes the program.
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If we apply for designation for future product candidates as drugs for rare pediatric diseases, the FDA may not grant the designation.
−Removed: The failure to maintain rare pediatric disease designation for CTI-1601 or if FDA approval does not occur prior to September 30, 2026 could result in the inability to receive a priority review voucher which could adversely affect our business, financial condition and results of operations.
−Removed: If we fail to maintain PRIME designation in the European Union for CTI-1601, our competitive position would be harmed.
+Added: The failure to maintain rare pediatric disease designation for nomlabofusp or if FDA approval does not occur prior to September 30, 2026 could result in the inability to receive a priority review voucher which could adversely affect our business, financial condition and results of operations.
+Added: If we fail to maintain PRIME designation in the European Union for nomlabofusp, our competitive position would be harmed.
The PRIME scheme is open to medicines under development and for which the applicant intends to apply for an initial MAA through the centralized procedure.
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Applicants will typically be at the exploratory clinical trial phase of development and will have preliminary clinical evidence in patients to demonstrate the promising activity of the medicine and its potential to address to a significant extent an unmet medical need.
−Removed: In exceptional cases, applicants from the academic sector or SMEs may submit an eligibility request at an earlier stage of development if compelling non-clinical data in a relevant model provide early evidence of promising activity, and first in man studies indicate adequate exposure for the desired pharmacotherapeutic effects and tolerability.
+Added: In exceptional cases, applicants from the academic sector or SMEs may submit an eligibility request at an earlier stage of development if compelling non-clinical data in a relevant model provide early evidence of promising activity to establish proof of principle, and first in man studies indicate adequate exposure for the desired pharmacotherapeutic effects and tolerability.
If a medicine is selected for the PRIME scheme, the EMA:
• appoints a rapporteur from the CHMP or from the CAT to provide continuous support and to build up knowledge of the medicine in advance of the filing of an MMA;
−Removed: issues guidance on the applicant’s overall development plan and regulatory strategy;
+Added: • issues guidance on the applicant’s overall development plan and regulatory strategy;
• organizes a kick-off meeting with the rapporteur and experts from relevant EMA committees and working groups;
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They are required to submit relevant data and justification as the product development reaches this stage.
−Removed: Medicines that are selected for the PRIME scheme are also expected to benefit from EMA’s accelerated assessment procedure at the time of application for marketing authorization.
−Removed: Where, during the course of
−Removed: development, a medicine no longer meets the eligibility criteria, or if a medicine granted early access to the PRIME scheme cannot later demonstrate proof of concept, support under the PRIME scheme may be withdrawn.
−Removed: Approval of other therapies for the treatment Friedreich’s ataxia, including the recent approval of omaveloxolone could negatively impact our continued access to this and similar programs.
−Removed: Loss of PRIME designation for CTI-1601 or the failure to obtain such designation for any future product candidates could adversely affect our business, financial condition and results of operation.
−Removed: Changes in regulatory requirements, FDA guidance, guidance from other regulatory authorities or unanticipated events during our non-clinical or clinical trials of CTI-1601 or future product candidates may result in changes to clinical trial protocols or additional non-clinical or clinical trial requirements, which could result in increased costs to us and could delay our development timeline.
+Added: Medicines that are selected for the PRIME scheme are also expected to benefit from EMA’s accelerated assessment procedure at the time of application for marketing authorization.
+Added: Where, during the course of development, a medicine no longer meets the eligibility criteria, or if a medicine granted early access to the PRIME scheme cannot later demonstrate proof of concept, support under the PRIME scheme may be withdrawn.
+Added: Approval of other therapies for the treatment Friedreich’s ataxia, including the recent approval of omaveloxolone could negatively impact our continued access to this and similar programs.
+Added: Loss of PRIME designation for nomlabofusp or
+Added: the failure to obtain such designation for any future product candidates could adversely affect our business, financial condition and results of operation.
+Added: Changes in regulatory requirements, FDA guidance, guidance from other regulatory authorities or unanticipated events during our non-clinical or clinical trials of nomlabofusp or future product candidates may result in changes to clinical trial protocols or additional non-clinical or clinical trial requirements, which could result in increased costs to us and could delay our development timeline.
Changes in regulatory requirements, FDA guidance or guidance from EMA or unanticipated events during our non-clinical or clinical trials may force us to terminate or adjust our clinical programs.
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Amendments to our clinical trial protocols would require resubmission to the FDA, or the applicable regulatory authorities as well as IRBs and ethics committees for review and approval, which may adversely impact the cost, timing or successful completion of a clinical trial.
−Removed: If we experience delays completing, or if we terminate, any of our clinical trials, or if we are required to conduct additional clinical trials, or non-clinical studies and/or post-market studies, the commercial prospects for CTI-1601 or any other potential product candidates may be harmed and our ability to generate product revenue will be delayed or eliminated, and it would materially adversely affect our business, financial condition and results of operations.
+Added: If we experience delays completing, or if we terminate, any of our clinical trials, or if we are required to conduct additional clinical trials, or non-clinical studies and/or post-market studies, the commercial prospects for nomlabofusp or any other potential product candidates may be harmed and our ability to generate product revenue will be delayed or eliminated, and it would materially adversely affect our business, financial condition and results of operations.
In order to market any product outside of the United States, we must comply with numerous and varying regulatory requirements of other countries regarding drug development and commercialization.
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Regulatory approval in one country does not ensure regulatory approval in another, but a failure or delay in obtaining regulatory approval in one country may negatively impact the regulatory process in others.
−Removed: Even if we receive marketing approval for CTI-1601 in the United States, we may never receive regulatory approval to market CTI-1601 outside of the United States.
+Added: Even if we receive marketing approval for nomlabofusp in the United States, we may never receive regulatory approval to market nomlabofusp outside of the United States.
Disruptions at the FDA and other government agencies caused by funding shortages or global health concerns could hinder their ability to hire, retain or deploy key leadership and other personnel, or otherwise prevent new or modified products from being developed, approved or commercialized in a timely manner or at all, which could negatively impact our business.
−Removed: The ability of the FDA to review and/or approve new products can be affected by a variety of factors, including government budget and funding levels, statutory, regulatory, and policy changes, the FDA’s ability to hire and retain key personnel, and accept the payment of user fees, and other events that may otherwise affect the FDA’s ability to perform routine functions.
+Added: The ability of the FDA to review and/or approve new products can be affected by a variety of factors, including government budget and funding levels, statutory, regulatory, and policy changes, the FDA’s ability to hire and retain key personnel, and accept the payment of user fees, and other events that may otherwise affect the FDA’s ability to perform routine functions.
In addition, government funding of other government agencies that fund research and development activities is subject to the political process, which is inherently fluid and unpredictable.
Disruptions at the FDA and other agencies may also slow the time necessary for new drugs to be reviewed and/or approved by necessary government agencies, which would adversely affect our business.
−Removed: For example, since March 2020 when foreign and domestic inspections of facilities were largely placed on hold, the FDA has been working to resume routine surveillance, bioresearch monitoring and pre-approval inspections on a prioritized basis.
−Removed: Since April 2021, the FDA has conducted limited inspections and employed remote interactive evaluations, using risk management methods, to meet user fee commitments and goal dates.
−Removed: Ongoing travel restrictions and other uncertainties continue to impact oversight operations both domestic and abroad and it is unclear when standard operational levels will resume.
−Removed: Regulatory authorities outside the United States may adopt similar restrictions or other policy measures in response to a resurgence of COVID-19, and/or other outbreaks of communicable diseases.
+Added: Furthermore, government shutdowns could also impact the ability of regulatory authorities and government agencies to function normally and support our operations.
+Added: For example, the U.S.
+Added: federal government has shut down repeatedly since 1980, including for a period of 35 days beginning on December 22, 2018.
+Added: During a shutdown, certain regulatory authorities and agencies, such as the FDA, have had to furlough key personnel and stop critical activities.
If a prolonged government shutdown occurs, or if global health concerns prevent the FDA or other regulatory authorities from conducting their regular inspections, reviews, or other regulatory activities, it could significantly impact the ability of the FDA or other regulatory authorities to timely review and process our regulatory submissions, which could have a material adverse effect on our business.
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Regulatory requirements governing biologic drug products are evolving and may continue to change in the future.
−Removed: As a result, it is difficult to determine how long it will take or how much it will cost to obtain regulatory approvals for CTI-1601 for the treatment of FA or any other future protein replacement therapy product candidates in any indication, if at all.
−Removed: Regulatory review agencies and the new requirements and guidelines they promulgate may lengthen the regulatory review process, require us to perform additional or larger studies, increase our development costs, lead to changes in regulatory positions and interpretations, delay or prevent approval and commercialization of our product candidates or lead to significant post-approval studies, limitations or restrictions.
+Added: As a result, it is difficult to determine how long it will take or how much it will cost to obtain regulatory approvals for nomlabofusp for the treatment of FA or any other future protein replacement therapy product candidates in any indication, if at all.
+Added: Regulatory review agencies and the new requirements and guidelines they promulgate may lengthen the regulatory review process, require us to perform additional or larger studies, increase
+Added: our development costs, lead to changes in regulatory positions and interpretations, delay or prevent approval and commercialization of our product candidates or lead to significant post-approval studies, limitations or restrictions.
+Added: Legislative and regulatory proposals have been made to expand post-approval requirements and restrict sales and promotional activities for pharmaceutical products.
+Added: We cannot be sure whether additional legislative changes will be enacted, or whether FDA regulations, guidance or interpretations will be changed, or what the impact of such changes on the marketing approvals of our product candidates, if any, may be.
+Added: In addition, increased scrutiny by the U.S.
+Added: Congress of the FDA’s approval process may significantly delay or prevent marketing approval, as well as subject us to more stringent product labeling and post-marketing testing and other requirements.
Delays, failure or unexpected costs in obtaining, the regulatory approval necessary to bring our product candidates to market could have a material adverse effect on our business, results of operations, financial condition and prospects.
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The regulatory approval process for novel product candidates such as ours can be more expensive and take longer than for other, better known or more extensively studied product candidates.
−Removed: The clinical trials of CTI-1601 and any future product candidates are, and the manufacturing and marketing of CTI-1601 and any future product candidates, will be subject to extensive and rigorous review and regulation by numerous government authorities in the United States and in other countries, such as within the European Union, where we intend to seek regulatory approval of, and market, any product candidates.
+Added: The clinical trials of nomlabofusp and any future product candidates are, and the manufacturing and marketing of nomlabofusp and any future product candidates, will be subject to extensive and rigorous review and regulation by numerous government authorities in the United States and in other countries, such as within the European Union, where we intend to seek regulatory approval of, and market, any product candidates.
Before obtaining regulatory approvals for the commercial sale of any product candidate, we must demonstrate through non-clinical testing and clinical trials that the product candidate is safe and effective for use in each target indication.
This process can take many years.
−Removed: In addition, approval policies, regulations, or the type and amount of clinical data necessary to gain approval may change during the course of a product candidate’s clinical development and may vary among jurisdictions, which may cause delays in the approval of or may result in the decision not to approve our product candidates.
−Removed: We have not obtained regulatory approval for CTI-1601, and it is possible that this product candidate or any product candidates we may seek to develop in the future will never obtain regulatory approval.
+Added: In addition, approval policies, regulations, or the type and amount of clinical data necessary to gain approval may change during the course of a product candidate’s clinical development and may vary among jurisdictions, which may cause delays in the approval of or may result in the decision not to approve our product candidates.
+Added: We have not obtained regulatory approval for nomlabofusp, and it is possible that this product candidate or any product candidates we may seek to develop in the future will never obtain regulatory approval.
If marketing approval is obtained, it will likely include post-marketing studies, and other post-marketing requirements, and surveillance such as REMS which will require the expenditure of substantial resources beyond the proceeds we currently have on hand.
−Removed: Furthermore, we are not permitted to market CTI-1601 in the United States or the European Union until we receive approval of a BLA from the FDA or a MAA from the EMA, or in any other foreign countries until we receive the requisite marketing approval from such countries.
+Added: Furthermore, we are not permitted to market nomlabofusp in the United States, or the European Union until we receive approval of a BLA from the FDA or a MAA from the EMA, or in any other foreign countries until we receive the requisite marketing approval from such countries.
The development of drugs for FA or other rare diseases may require initial non-clinical studies, early and usually smaller, clinical trials and randomized, double-blind placebo controlled long-term safety and efficacy trials in order to test the safety and efficacy of the drug.
−Removed: CTI-1601 requires substantial further clinical development before we can submit a BLA to the FDA.
−Removed: Development and/or regulatory programs for CTI-1601 in any countries other than the United States (such as a MAA to the EMA) are only in very preliminary stages and may require substantial further development in those countries prior to regulatory submissions seeking regulatory approval for marketing.
+Added: Nomlabofusp requires substantial further clinical development before we can submit a BLA to the FDA.
+Added: Development and/or regulatory programs for nomlabofusp in any countries other than the United States (such as a MAA to the EMA) are only in very preliminary stages and may require substantial further development in those countries prior to regulatory submissions seeking regulatory approval for marketing.
Even after successful completion of clinical trials, there is a risk that the FDA or other regulatory agencies may request further information from us, disagree with our findings or otherwise undertake a lengthy review of our submission.
−Removed: The FDA and certain European regulatory authorities may delay, limit or deny testing or approval of CTI-1601 for many reasons, including, among others:
−Removed: we may not be able to demonstrate that CTI-1601 is safe and effective to the satisfaction of the FDA or the EMA;
+Added: The FDA and certain European regulatory authorities may delay, limit or deny testing or approval of nomlabofusp for many reasons, including, among others:
+Added: • we may not be able to demonstrate that nomlabofusp is safe and effective to the satisfaction of the FDA or the EMA;
• the results of our clinical trials may not meet the level of statistical or clinical significance required by the FDA or the EMA for marketing approval;
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• the FDA or the EMA may require that we conduct additional non-clinical studies and/or clinical trials;
−Removed: the FDA or the EMA may not approve the formulation, manufacturing, labeling or specifications of CTI-1601;
−Removed: the CROs that we retain to conduct and/our clinical trials may take actions outside of our control that materially adversely impact our clinical trials;
−Removed: the FDA or the EMA may find the data from non-clinical studies and clinical trials insufficient to demonstrate that CTI-1601’s clinical and other benefits outweigh its safety risks;
+Added: • the FDA or the EMA may not approve the formulation, manufacturing, labeling or specifications of nomlabofusp;
+Added: • the CROs that we retain to conduct our clinical trials may take actions outside of our control that materially adversely impact our clinical trials;
+Added: • the FDA or the EMA may find the data from non-clinical studies and clinical trials insufficient to demonstrate that nomlabofusp’s clinical and other benefits outweigh its safety risks;
• the FDA or the EMA may disagree with our interpretation of data from our non-clinical studies or clinical trials;
1 unchanged sentence
• if and when our BLA is submitted, the FDA could require an FDA advisory committee assessment, or the advisory committee may recommend against approval of our application or may recommend that the FDA require, as a condition of approval, additional non-clinical studies or clinical trials, limitations on approved labeling or distribution and use restrictions;
−Removed: the FDA or the EMA could require development of a REMS as a condition of approval or post-approval, or may not agree with our proposed REMS, or may impose additional requirements, including requirements that limit the promotion, advertising, distribution, or sales of CTI-1601;
+Added: • the FDA or the EMA could require development of a REMS as a condition of approval or post-approval, or may not agree with our proposed REMS, or may impose additional requirements, including requirements that limit the promotion, advertising, distribution, or sales of nomlabofusp;
• the FDA or the EMA may find deficiencies with or not approve the manufacturing processes or facilities of third-party manufacturers with which we contract;
• the FDA or the EMA may change their approval policies or adopt new regulations rendering our clinical data insufficient for approval.
−Removed: Any of these factors, many of which are beyond our control, could jeopardize our ability to obtain and/or maintain regulatory approval for and successfully market CTI-1601.
+Added: Any of these factors, many of which are beyond our control, could jeopardize our ability to obtain and/or maintain regulatory approval for and successfully market nomlabofusp.
Any delay or failure in obtaining required approvals could have a material adverse effect on our business, financial condition and results of operations.
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It is possible that our product candidates may not obtain appropriate regulatory approvals necessary for us to commence clinical trials for our product candidates.
−Removed: Accordingly, even if we are able to obtain the requisite financing to continue to fund our development and clinical trials, we cannot ensure that CTI-1601, or any other of our potential product candidates will be successfully developed or commercialized.
+Added: Accordingly, even if we are able to obtain the requisite financing to continue to fund our development and clinical trials, we cannot ensure that nomlabofusp, or any other of our potential product candidates will be successfully developed or commercialized.
We are subject to healthcare laws and regulations, and health information privacy and security laws, which could expose us to criminal sanctions, civil penalties, contractual damages, reputational harm and diminished profits and future earnings.
−Removed: Healthcare providers, physicians and others will play a primary role in the recommendation and prescription of CTI-1601 or any potential product candidates, if approved.
−Removed: Our future arrangements with third-party payors will expose us broadly to applicable fraud and abuse and other healthcare laws and regulations that may constrain the business or financial arrangements and relationships through which we market, sell and distribute CTI-1601 or potential product candidates, if we obtain marketing approval.
+Added: Healthcare providers, physicians and others will play a primary role in the recommendation and prescription of nomlabofusp or any potential product candidates, if approved.
+Added: Our future arrangements with third-party payors will expose us broadly to applicable fraud and abuse and other healthcare laws and regulations that may constrain the business or financial arrangements and relationships through which we market, sell and distribute nomlabofusp or potential product candidates, if we obtain marketing approval.
In addition, we may be subject to patient privacy regulation by both the federal government and the states or other countries in which we conduct our business.
−Removed: Restrictions under applicable federal and state healthcare laws and regulations include the following:
−Removed: the federal Anti-Kickback Statute prohibits, among other things, persons from knowingly and willfully soliciting, offering, receiving or paying remuneration, directly or indirectly, in cash or in kind, to induce or reward either the referral of an individual for, or the purchase, order or recommendation of, any good or
−Removed: service, for which payment may be made under federal healthcare programs such as Medicare and Medicaid;
−Removed: the federal false claims laws impose criminal and civil penalties, including those from civil whistleblower or qui tam actions pursuant to the federal False Claims Act, against individuals or entities for knowingly presenting, or causing to be presented, to the federal government, claims for payment that are false or fraudulent or making a false statement to avoid, decrease, or conceal an obligation to pay money to the federal government;
−Removed: HITECH imposes criminal and civil liability for executing a scheme to defraud any healthcare benefit program and also imposes obligations, including mandatory contractual terms, with respect to safeguarding the privacy, security and transmission of individually identifiable health information;
−Removed: the federal false statements statute prohibits knowingly and willfully falsifying, concealing or covering up a material fact or making any materially false statement in connection with the delivery of or payment for healthcare benefits, items or services;
−Removed: the federal transparency requirements, sometimes referred to as the “Sunshine Act,”
−Removed: under the Affordable Care Act, require manufacturers of drugs, devices, biologics, and medical supplies to report to CMS information related to payments and other transfers of value provided to physicians (defined to include doctors, dentists, optometrists, podiatrists and chiropractors), physician assistants, nurse practitioners, clinical nurse specialists, certified nurse anesthetists, certified nurse-midwives and teaching hospitals, as well as ownership and investment interests held by physicians and their immediate family members;
−Removed: federal consumer protection and unfair competition laws, which broadly regulate marketplace activities and activities that potentially harm consumers;
−Removed: analogous state laws and regulations, such as state anti-kickback and false claims laws and transparency laws, may apply to sales or marketing arrangements and claims involving healthcare items or services reimbursed by non-governmental third-party payors, including private insurers.
−Removed: Some state laws require pharmaceutical companies to comply with the pharmaceutical industry’s voluntary compliance guidelines and the relevant compliance guidance promulgated by the federal government in addition to requiring drug manufacturers to report information related to payments to physicians and other healthcare providers or marketing expenditures and drug pricing.
+Added: For more information, see the section of this report titled “Business – Healthcare Laws and Regulations – Other Healthcare Laws.”
Ensuring that our future business arrangements with third parties comply with applicable healthcare laws and regulations could be costly.
It is possible that governmental authorities will conclude that our business practices do not comply with current or future statutes, regulations or case law involving applicable fraud and abuse or other healthcare laws and regulations.
−Removed: If our operations, including anticipated activities to be conducted by our sales team, were found to be in violation of any of these laws or any other governmental regulations that may apply to us, we may be subject to significant civil, criminal and administrative penalties, damages, fines and exclusion from government funded healthcare programs, such as Medicare and Medicaid, any of which could substantially disrupt our operations and would materially adversely affect our business, financial condition and results of operations.
+Added: If our operations, including anticipated activities to be conducted by our sales team, were found to be in violation of any of these laws or any other governmental regulations that may apply to us, we may be subject to significant civil, criminal and administrative penalties, damages, fines and exclusion from
+Added: government funded healthcare programs, such as Medicare and Medicaid, any of which could substantially disrupt our operations and would materially adversely affect our business, financial condition and results of operations.
If any of the physicians or other providers or entities with whom we expect to do business is found not to be in compliance with applicable laws, they may be subject to criminal, civil or administrative sanctions, including exclusions from government funded healthcare programs, which could have a material adverse effect on our business, results of operations, financial condition and prospects.
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The United States and many foreign jurisdictions have enacted or proposed legislative and regulatory changes affecting the healthcare system that may affect our ability to profitably sell our product and product candidates, if approved.
−Removed: The United States government, state legislatures and foreign governments also have shown significant interest in implementing cost-containment programs to limit the
−Removed: growth of government-paid healthcare costs, including price controls, restrictions on reimbursement and requirements for substitution of generic products for branded prescription drugs.
−Removed: The Affordable Care Act was intended to broaden access to health insurance, reduce or constrain the growth of healthcare spending, enhance remedies against fraud and abuse, add transparency requirements for the healthcare and health insurance industries, impose new taxes and fees on the health industry and impose additional health policy reforms.
−Removed: There have been significant ongoing administrative, executive and legislative efforts to modify or eliminate the Affordable Care Act.
−Removed: For example, the Tax Act enacted on December 22, 2017, repealed the shared responsibility payment for individuals who fail to maintain minimum essential coverage under section 5000A of the Internal Revenue Code, commonly referred to as the individual mandate.
−Removed: Other legislative changes have been proposed and adopted since the passage of the Affordable Care Act.
−Removed: The Budget Control Act of 2011,and subsequent legislation triggered reductions to Medicare payments to healthcare providers of up to 2.0% per fiscal year, which will remain in effect through 2031 unless additional Congressional action is taken.
−Removed: The American Taxpayer Relief Act was signed into law in 2013, which, among other things, reduced Medicare payments to several types of providers, including hospitals, imaging centers and cancer treatment centers, and increased the statute of limitations period for the government to recover overpayments to providers from three to five years.
−Removed: Most recently, the IRA includes several provisions that will impact our business to varying degrees, including provisions that reduce the out-of-pocket cap for Medicare Part D beneficiaries to $2,000 starting in 2025;
−Removed: impose new manufacturer financial liability on certain drugs in Medicare Part D, allow the U.S.
−Removed: government to negotiate Medicare Part B and Part D price caps for certain high-cost drugs and biologics without generic or biosimilar competition, require companies to pay rebates to Medicare B and Part D for certain drug prices that increase faster than inflation, and delay the rebate rule that would limit the fees that pharmacy benefit managers can charge.
−Removed: We expect that changes to the Affordable Care Act, the Medicare and Medicaid programs, changes allowing the federal government to directly negotiate drug prices and changes stemming from other healthcare reform measures, especially with regard to healthcare access, financing or other legislation in individual states, could have a material adverse effect on the healthcare industry.
−Removed: At the state level, legislatures have increasingly passed legislation and implemented regulations designed to control pharmaceutical product pricing, including price or patient reimbursement constraints, discounts, restrictions on certain product access and marketing cost disclosure and transparency measures, and, in some cases, designed to encourage importation from other countries and bulk purchasing.
+Added: The United States government, state legislatures and foreign governments also have shown significant interest in implementing cost-containment programs to limit the growth of government-paid healthcare costs, including price controls, restrictions on reimbursement and requirements for substitution of generic products for branded prescription drugs.
+Added: The pharmaceutical industry has been a particular focus of these efforts and has been significantly affected by major legislative initiatives.
+Added: Previously, in March 2010, the ACA was enacted, which was intended to broaden access to health insurance, reduce or constrain the growth of healthcare spending, enhance remedies against fraud and abuse, add new transparency requirements for health care and health insurance industries, impose new taxes and fees on the health industry and impose additional health policy reforms.
+Added: Healthcare reform initiatives recently culminated in the enactment of the IRA Inflation Reduction Act of 2022 or IRA, which, among other things, allow allows HHS to directly negotiate the ceiling price of a statutorily specified number of drugs and biologic each year that CMS reimburses under Medicare Part B and Part D, requires the payment of rebates on Medicare Part B and Part D drugs whose prices have increased at a rate faster than the rate of inflation, and redesign the Medicare Part D cost sharing structure, including revising manufacturer financial liability for covered products.
+Added: For more information, see the section of this report titled “Business – Healthcare Laws and Regulations – Healthcare Reform.”
We expect that additional federal, state and foreign 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 limited coverage and reimbursement and reduced demand for our products, once approved, or additional pricing pressures.
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Government authorities and these third-party payors have attempted to control costs by limiting coverage and the amount of reimbursement for particular medications.
−Removed: We cannot be sure that reimbursement will be available for CTI-1601, if approved, or future product candidates that we elect to sell on our own and, if reimbursement is available, the level of such reimbursement.
−Removed: Reimbursement may impact the demand for, or the price of, product candidates that we elect to.
+Added: We cannot be sure that reimbursement will be available for nomlabofusp, if approved, or future product candidates that we elect to sell on our own and, if reimbursement is available, the level of such reimbursement.
+Added: Reimbursement may impact the demand for, or the price of, product candidates that we elect to sell.
If reimbursement is not available or is available only at limited levels, we may not be able to successfully commercialize product candidates that we elect to sell.
+Added: For more information, see the section of this report titled “Business – Healthcare Laws and Regulations – Coverage and Reimbursement.”
In some foreign countries, particularly in Canada and European countries, the pricing of prescription pharmaceuticals is subject to strict governmental control.
In these countries, pricing negotiations with governmental authorities can take six to 12 months or longer after the receipt of regulatory approval and product launch.
−Removed: To obtain favorable reimbursement for the indications sought or pricing approval in some countries, we may be required to conduct a clinical trial that compares the cost-effectiveness of product candidates that we elect to sell on our own with other available therapies.
−Removed: If reimbursement for product candidates that we elect to sell on our own is
−Removed: unavailable in any country in which we seek reimbursement, if it is limited in scope or amount, if it is conditioned upon our completion of additional clinical trials, or if pricing is set at unsatisfactory levels, our business, financial conditions and results of operations could be materially adversely affected.
−Removed: Even if we obtain regulatory and marketing approval for a product candidate, our product candidates will remain subject to regulatory oversight.
−Removed: Even if we receive marketing and regulatory approval for CTI-1601 or a future product candidate, regulatory authorities may still impose significant restrictions on the indicated uses or marketing or impose ongoing requirements for potentially costly post-approval studies.
−Removed: CTI-1601 or future product candidates will also be subject to ongoing regulatory requirements for manufacturing, labeling, packaging, storage, advertising, promotion, sampling, record-keeping and submission of safety and other post-market information.
+Added: To obtain favorable reimbursement for the indications sought or pricing approval in some countries, we may be required to conduct a clinical trial that compares the cost-effectiveness of product candidates that we elect to sell on our own
+Added: with other available therapies.
+Added: If reimbursement for product candidates that we elect to sell on our own is unavailable in any country in which we seek reimbursement, if it is limited in scope or amount, if it is conditioned upon our completion of additional clinical trials, or if pricing is set at unsatisfactory levels, our business, financial conditions and results of operations could be materially adversely affected.
+Added: Even if we obtain marketing approval for a product candidate, our product candidates will remain subject to regulatory oversight.
+Added: Even if we receive marketing approval for nomlabofusp or a future product candidate, regulatory authorities may still impose significant restrictions on the indicated uses or marketing or impose ongoing requirements for potentially costly post-approval studies.
+Added: Nomlabofusp or future product candidates will also be subject to ongoing regulatory requirements for manufacturing, labeling, packaging, storage, advertising, promotion, sampling, record-keeping and submission of safety and other post-market information.
The FDA has significant post-market authority, including, for example, the authority to require labeling changes based on new safety information and to require post-market studies or clinical trials to evaluate serious safety risks related to the use of a drug.
An unsuccessful post-marketing study or failure to complete such a study could result in the withdrawal of marketing approval.
−Removed: Any regulatory approvals that we receive for CTI-1601 may also be subject to a REMS, limitations on the approved indicated uses for which the product may be marketed or to the conditions of approval, or contain requirements for potentially costly post-marketing testing, including post-approval clinical trials, and surveillance to monitor the quality, safety and efficacy of the product, all of which could lead to lower sales volume and revenue.
+Added: Any regulatory approvals that we receive for nomlabofusp may also be subject to a REMS, limitations on the approved indicated uses for which the product may be marketed or to the conditions of approval, or contain requirements for potentially costly post-marketing testing, including post-approval clinical trials, and surveillance to monitor the quality, safety and efficacy of the product, all of which could lead to lower sales volume and revenue.
For example, the holder of an approved BLA or NDA is obligated to monitor and report adverse events and any failure of a product to meet the specifications in the BLA or NDA.
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If we, or a regulatory authority, discover(s) previously unknown problems with a product, such as adverse events of unanticipated severity or frequency, or problems with the facility where the product is manufactured or if a regulatory authority disagrees with the promotion, marketing or labeling of that product, a regulatory authority may impose restrictions relative to that product, the manufacturing facility or us, including requiring recall or withdrawal of the product from the market or suspension of manufacturing.
−Removed: If we or our contractors fail to comply with applicable regulatory requirements following approval of CTI-1601, a regulatory authority may:
+Added: If we or our contractors fail to comply with applicable regulatory requirements following approval of nomlabofusp, a regulatory authority may:
• issue a warning letter, or untitled letter asserting that we are in violation of the law;
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Any government investigation of alleged violations of law could require us to expend significant time and resources in response and could generate negative publicity.
−Removed: The occurrence of any event or penalty described above
−Removed: may inhibit our ability to commercialize CTI-1601, if approved, and adversely affect our business, financial condition, results of operations and prospects.
−Removed: In addition, the FDA’s policies, and those of equivalent foreign regulatory agencies, may change and additional government regulations may be enacted that could prevent, limit or delay regulatory approval of CTI-1601.
+Added: The occurrence of any event or penalty described above may inhibit our ability to commercialize nomlabofusp, if approved, and adversely affect our business, financial condition, results of operations and prospects.
+Added: In addition, the FDA’s policies, and those of equivalent foreign regulatory agencies, may change and additional government regulations may be enacted that could prevent, limit or delay regulatory approval of nomlabofusp.
We cannot predict the likelihood, nature or extent of government regulation that may arise from future legislation or administrative action, either in the United States or abroad.
If we are slow or unable to adapt to changes in existing requirements or the adoption of new requirements or policies, or if we are not able to maintain regulatory compliance, we may lose any marketing approval that we may have obtained and we may not achieve or sustain profitability, which would materially and adversely affect our business, financial condition, results of operations and prospects.
−Removed: Even if we receive marketing approval for CTI-1601 in the United States, we may never receive regulatory approval to market CTI-1601 outside of the United States.
−Removed: We may pursue marketing approval for CTI-1601 in the United States, the European Union and in other jurisdictions worldwide.
+Added: Even if we receive marketing approval for nomlabofusp in the United States, we may never receive regulatory approval to market nomlabofusp outside of the United States.
+Added: We may pursue marketing approval for nomlabofusp in the United States, the European Union and in other jurisdictions worldwide.
In order to market any product outside of the United States, we must establish and comply with the numerous and varying safety, efficacy and other regulatory requirements of other jurisdictions, including potential additional clinical trials and/or non-clinical studies.
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Our future growth depends, in part, on our ability to penetrate foreign markets, where we would be subject to additional regulatory burdens and other risks and uncertainties.
−Removed: The prevalence of FA is estimated to be approximately three times greater in the European Union than in the United States, and, therefore, represents our largest potential market for CTI-1601.
−Removed: Our future profitability will depend, in part, on our ability to commercialize CTI-1601 and future product candidates in the European Union and other foreign markets for which we may rely on collaborations with third parties.
+Added: The prevalence of FA is estimated to be approximately three times greater in the European Union than in the United States, and, therefore, represents our largest potential market for nomlabofusp.
+Added: Our future profitability will depend, in part, on our ability to commercialize nomlabofusp and future product candidates in the European Union and other foreign markets for which we may rely on collaborations with third parties.
If we commercialize a product candidate in foreign markets, we would be subject to additional risks and uncertainties, including:
−Removed: our customers’
−Removed: ability to obtain reimbursement for a product candidate in foreign markets;
+Added: • our customers’ ability to obtain reimbursement for a product candidate in foreign markets;
• compliance with the FCPA;
10 unchanged sentences
Sales in the European Union and other foreign markets of a product candidate could also be adversely affected by the imposition of governmental controls, political and economic instability, trade restrictions and changes in tariffs.
−Removed: If we are unable to establish sales and marketing capabilities or enter into agreements with third parties to market and sell CTI-1601, if approved, we may not be able to generate any revenue.
+Added: If we are unable to establish sales and marketing capabilities or enter into agreements with third parties to market and sell nomlabofusp, if approved, we may not be able to generate any revenue.
We do not currently have an established infrastructure for the sales, marketing and distribution of biologic or drug products in the United States or foreign countries.
1 unchanged sentence
If we are unable to establish adequate sales, marketing and distribution capabilities, whether independently or with third parties, or if we are unable to do so on commercially reasonable terms, our business, results of operations, financial condition and prospects will be materially adversely affected.
−Removed: Even if we receive marketing approval for CTI-1601, we may not achieve broad market acceptance, which would limit the revenue that we generate from our sales.
−Removed: The commercial success of CTI-1601, if developed and approved for marketing by the FDA or EMA or other applicable regulatory authorities, will depend upon the market size for, and the awareness and acceptance of CTI-1601 among the medical community, including physicians, patients, advocacy groups and healthcare payors.
−Removed: Market acceptance of CTI-1601, if approved, will depend on a number of factors, including, among others:
+Added: Even if we receive marketing approval for nomlabofusp, we may not achieve broad market acceptance, which would limit the revenue that we generate from our sales.
+Added: The commercial success of nomlabofusp, if developed and approved for marketing by the FDA or EMA or other applicable regulatory authorities, will depend upon the market size for, and the awareness and acceptance of nomlabofusp among the medical community, including physicians, patients, advocacy groups and healthcare payors.
+Added: Market acceptance of nomlabofusp, if approved, will depend on a number of factors, including, among others:
• if the actual number of patients with FA is lower than we believe;
• the relative convenience and ease of subcutaneous injections as the necessary method of administration;
−Removed: the prevalence and severity of any adverse side effects associated with CTI-1601;
−Removed: limitations or warnings contained in the labeling approved for CTI-1601 by the FDA, EMA, or other regulatory authorities, such as a “boxed”
−Removed: warning or if any approval that we obtain is based on a narrower definition of possible patient populations;
−Removed: availability of alternative treatments, including any competitive FA therapies approved or in development that have been or could be approved or commercially launched prior to approval of CTI-1601;
+Added: • the prevalence and severity of any adverse side effects associated with nomlabofusp;
+Added: • limitations or warnings contained in the labeling approved for nomlabofusp by the FDA, EMA, or other regulatory authorities, such as a “boxed” warning or if any approval that we obtain is based on a narrower definition of possible patient populations;
+Added: • availability of alternative treatments, including any competitive FA therapies approved or in development that have been or could be approved or commercially launched prior to approval of nomlabofusp;
• the willingness of the target patient population to try new therapies and of physicians to prescribe these therapies;
1 unchanged sentence
• publicity concerning our products or competing products and treatments;
−Removed: patient acceptance of the cost and inconvenience associated with refrigerated storage for CTI-1601;
+Added: • patient acceptance of the cost and inconvenience associated with refrigerated storage for nomlabofusp;
• payor acceptance;
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• the effectiveness of our sales and marketing strategies;
−Removed: our ability to increase awareness of CTI-1601 through marketing efforts;
+Added: • our ability to increase awareness of nomlabofusp through marketing efforts;
• our ability to obtain sufficient third-party coverage or reimbursement;
1 unchanged sentence
• the likelihood that the FDA may require development of a REMS, as a condition of approval or post-approval or may not agree with our proposed REMS or may impose additional requirements that limit the promotion, advertising, distribution or sales of our product candidates.
−Removed: If CTI-1601 is approved but does not achieve an adequate level of acceptance by patients, advocacy groups, physicians and payors, we may not generate sufficient revenue from CTI-1601 to become or remain profitable and our business, financial condition and results of operations could be materially adversely affected.
−Removed: Our efforts to educate the medical community and third-party payors about the benefits of CTI-1601 may require significant resources and may never be successful.
+Added: If nomlabofusp is approved but does not achieve an adequate level of acceptance by patients, advocacy groups, physicians and payors, we may not generate sufficient revenue from nomlabofusp to become or remain profitable and our business, financial condition and results of operations could be materially adversely affected.
+Added: Our efforts to educate the medical community and third-party payors about the benefits of nomlabofusp may require significant resources and may never be successful.
The FDA and other regulatory agencies actively enforce the laws and regulations prohibiting the promotion of off-label uses.
If we are found to have improperly promoted off-label uses, we may become subject to significant liability.
−Removed: The FDA and other regulatory agencies strictly regulate the promotional claims that may be made about prescription products, such as CTI-1601 or any potential product candidates, if approved.
−Removed: If we receive marketing approval for CTI-1601, or any potential product candidates, physicians may prescribe our product candidates to their patients in a manner that is inconsistent with the approved label.
+Added: The FDA and other regulatory agencies strictly regulate the promotional claims that may be made about prescription products, such as nomlabofusp or any potential product candidates, if approved.
+Added: If we receive marketing approval for nomlabofusp, or any potential product candidates, physicians may prescribe our product candidates to their patients in a manner that is inconsistent with the approved label.
If we are found to have promoted such off-label uses, we may become subject to significant liability.
1 unchanged sentence
The FDA has also requested that companies enter into consent decrees or permanent injunctions under which specified promotional conduct is changed or curtailed.
−Removed: If we cannot successfully manage the promotion of CTI-1601 or any potential product candidates, if approved, we could become subject to significant liability, which would materially adversely affect our business, financial condition and results of operations.
−Removed: Additional competing technologies could emerge, adversely affecting our opportunity to generate revenue from the sale of CTI-1601, if approved.
+Added: If we cannot successfully manage the promotion of nomlabofusp or any potential product candidates, if approved, we could become subject to significant liability, which would materially adversely affect our business, financial condition and results of operations.
+Added: Additional competing technologies could emerge, adversely affecting our opportunity to generate revenue from the sale of nomlabofusp, if approved.
The biotechnology and pharmaceutical industries are intensely competitive and subject to rapid and significant technological change.
−Removed: For example, the FDA recently approved omaveloxolone for the treatment of FA in adults and adolescents aged 16 and older.
−Removed: CTI-1601 will compete with omaveloxolone and other new, future approved products and may need to demonstrate compelling advantages in efficacy, convenience, tolerability and safety to be commercially successful.
+Added: For example, omaveloxolone, was approved for the treatment of FA in adults and adolescents aged 16 and older by the FDA and the European Commission in February 2023 and February 2024, respectively.
+Added: We expect nomlabofusp, if approved, will compete with omaveloxolone and other new, future approved products and may need to demonstrate compelling advantages in efficacy, convenience, tolerability and safety to be commercially successful.
Other competitive factors, including biosimilar and gene therapy competition, could force us to lower prices or could result in reduced sales.
Many of our current or potential competitors, either alone or with strategic partners, have significantly greater financial resources and expertise in research and development, manufacturing, non-clinical testing, conducting clinical trials, obtaining regulatory approvals, and marketing approved products than we do.
−Removed: New products developed by others could emerge as competitors to CTI-1601 or any other potential product candidates, resulting in CTI-1601 or other product candidates being obsolete before we are able to recover expenses incurred in connection with their development or realize revenues from any commercialized product.
+Added: New products developed by others could emerge as competitors to nomlabofusp or any other potential product candidates, resulting in nomlabofusp or other product candidates being obsolete before we are able to recover expenses incurred in connection with their development or realize revenues from any commercialized product.
The pricing of our current product candidate, if and when approved for marketing, will depend, in part, on the pricing strategies adopted by our competitors.
1 unchanged sentence
Any new product could also affect our ability to recruit and retain clinical trial patients, to obtain and maintain designations or eligibility for expedited regulatory pathways, and to commercialize current and future product candidates.
−Removed: Given that we are still in a relatively early phase of development for CTI-1601, the recent approval and commercialization of omaveloxolone and the approval of any future competing technologies could provide competitors with a significant competitive advantage and may create an additional barrier to market acceptance of CTI-1601.
+Added: Given that we are still in a relatively early phase of development for nomlabofusp, the recent approval and commercialization of omaveloxolone and the approval of any future competing technologies could provide competitors with a significant competitive advantage and may create an additional barrier to market acceptance of nomlabofusp.
If we are not able to compete effectively against our current and future competitors, our business will not grow and our financial condition and results of operations will be adversely affected.
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Some countries in the European Union may impose automatic price reductions upon market entry of the second or third biosimilar competitor.
−Removed: In the United States, the Affordable Care Act authorized the FDA to approve biosimilars via a separate, abbreviated pathway.
+Added: In the United States, the ACA authorized the FDA to approve biosimilars via a separate, abbreviated pathway.
A growing number of companies have announced that they are in varying stages of development of biosimilar versions of existing biotechnology products.
2 unchanged sentences
Some companies developing biosimilars may seek to register their products as interchangeable biologics, which could make it easier for prescribers or pharmacists to substitute those biosimilars for our products.
−Removed: In addition, critics of the 12-year exclusivity period in the biosimilar pathway law will likely continue to seek to shorten the data exclusivity period and/or to encourage the FDA to interpret narrowly the law’s provisions regarding which new products receive data exclusivity.
+Added: In addition, critics of the 12-year exclusivity period in the biosimilar pathway law will likely continue to seek to shorten the data exclusivity period and/or to encourage the FDA to interpret narrowly the law’s provisions regarding which new products receive data exclusivity.
While we are unable to predict the precise impact of biosimilars, we expect in the future for there to be greater competition in the United States as a result of biosimilars and downward pressure on product prices and sales.
−Removed: These biosimilars or generics may affect the tier designation by third party payors and may require prior authorization for use of CTI-1601, thereby adding barriers to access.
+Added: These biosimilars or generics may affect the tier designation by third party payors and may require prior authorization for use of nomlabofusp, thereby adding barriers to access.
This additional competition could have a material adverse effect on our business, financial condition and results of operations.
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Competition for qualified personnel in the biopharmaceutical field is intense due to the limited number of individuals who possess the skills and experience required by our industry.
−Removed: We will need to hire additional personnel as we expand our clinical development and if we initiate commercial activities.
+Added: We will need to continue to hire additional personnel as we expand our clinical development and if we initiate commercial activities.
We may not be able to attract and retain quality personnel on acceptable terms, or at all.
−Removed: In addition, to the extent we hire personnel from competitors, we may be subject to
−Removed: allegations that they have been improperly solicited or that they have divulged proprietary or other confidential information, or that their former employers own their research output.
+Added: In addition, to the extent we hire personnel from competitors, we may be
+Added: subject to allegations that they have been improperly solicited or that they have divulged proprietary or other confidential information, or that their former employers own their research output.
We rely on consultants and advisors, including scientific, non-clinical, manufacturing and clinical advisors, to assist us in formulating our development and commercialization strategy.
These consultants and advisors may be employed by other employers and may have commitments under consulting or advisory contracts with other entities that may limit their availability to us.
−Removed: The loss of the services of our executive officers or other key employees could impede the achievement of our research, development and commercialization objectives and seriously harm our ability to successfully implement our business strategy.
−Removed: Furthermore, replacing executive officers and key employees may be difficult and may take an extended period of time because of the competition for talent, particularly with the limited number of individuals in our industry with the breadth of skills and experience required to successfully develop, gain regulatory approval of and commercialize products.
−Removed: In addition, a possible resurgence of vaccine resistant or more highly contagious or deadly variants of COVID-19 or other health epidemics may pose a risk to our ability to retain and rely on our executive officers and key employees, including the potential that one or more of such employees or members of their families may contract the virus, which could impact the ability of such employees to perform as expected, which in turn would adversely impact our current and planned operations.
+Added: In addition, a possible future pandemic, epidemic or outbreak of an infectious disease may pose a risk to our ability to retain and rely on our executive officers and key employees, including the potential that one or more of such employees or members of their families may contract the virus, which could impact the ability of such employees to perform as expected, which in turn would adversely impact our current and planned operations.
Recruiting and retaining qualified scientific, medical clinical, manufacturing, quality assurance, regulatory, legal, public company financial, business, sales, marketing and commercial personnel and implementing and improving our operational, financial and management systems will be critical to our ability to grow and succeed.
2 unchanged sentences
In addition, we may not be able to attract and retain these personnel on acceptable terms given the competition among numerous pharmaceutical companies for similar personnel.
−Removed: A possible resurgence of vaccine resistant, more contagious or more highly contagious variants of COVID-19 or other health epidemics may pose may also affect our ability to attract and successfully recruit these personnel, for one or more reasons.
We also experience competition for the hiring of scientific personnel from universities and research institutions.
1 unchanged sentence
If we are unable to continue to attract and retain high quality personnel, our ability to pursue our business strategy will be limited and our business, financial condition and results of operations would be adversely affected.
−Removed: Further, if we fail to expand and enhance our operational, financial and management systems in conjunction with potential future growth, such failure could have a material adverse effect on our business, financial condition and results of operations.
+Added: Further, if we fail to expand and enhance our operational, financial, management and compliance systems in conjunction with potential future growth, such failure could have a material adverse effect on our business, financial condition and results of operations.
We may be unable to successfully implement these tasks on a larger scale and, accordingly, may not achieve our research, development, business and growth goals.
−Removed: Our internal computer systems, or those of any vendors, contractors or consultants, may fail or suffer security breaches, which could result in a material disruption of our product development programs.
−Removed: Despite the implementation of security measures, our internal computer systems and those of third parties with which we contract are vulnerable to damage from cyber-attacks, computer viruses, unauthorized access, natural disasters, terrorism, war and telecommunication and electrical failures.
−Removed: The prevalent use of mobile devices that access confidential information also increases the risk of lost or stolen devices, security incidents and data security breaches, which could lead to the loss of confidential information or other intellectual property.
−Removed: Any system failure, accident or security breach that causes interruptions in our operations could result in a material disruption of our product development programs and business operations, in addition to possibly requiring substantial expenditures of resources to remedy.
−Removed: For example, the loss of clinical trial data from completed clinical trials could result in delays in our regulatory approval efforts and significantly increase our costs to recover or reproduce the data.
−Removed: To the extent that any disruption or security breach results in a loss or damage to our data or applications, or inappropriate disclosure of confidential or proprietary information, we may incur liabilities and the further development of our product candidates may be delayed.
−Removed: In addition, we may not have adequate insurance coverage to provide compensation for any losses associated with such events.
−Removed: We could be subject to risks caused by misappropriation, misuse, leakage, falsification or intentional or accidental release or loss of information maintained in the information systems and networks of our company, including personal information of our employees.
−Removed: In addition, outside parties may attempt to penetrate our systems or those of our vendors or fraudulently induce our employees or employees of our vendors to disclose sensitive information in order to gain access to our data.
−Removed: Like other companies, we may experience threats to our data and
−Removed: systems, including malicious codes and viruses, and other cyber-attacks.
−Removed: The number and complexity of these threats continue to increase over time.
−Removed: If a material breach of our security or that of one or more of our vendors, contractors or consultants occurs, the market perception of the effectiveness of our security measures could be harmed, we could lose business and our reputation and credibility could be damaged, all of which would materially adversely affect our business, financial condition and results of operations.
−Removed: We could be required to expend significant amounts of money and other resources to repair or replace information systems or networks.
−Removed: Although we develop and maintain systems and controls designed to prevent these events from occurring, the development and maintenance of these systems, controls and processes is costly and requires ongoing monitoring and updating as technologies change and efforts to overcome security measures become more sophisticated.
−Removed: Moreover, despite our efforts, the possibility of these events occurring cannot be eliminated entirely.
We may acquire businesses or products, or form strategic alliances, in the future, and we may not realize the benefits of such acquisitions or alliances.
5 unchanged sentences
Our development programs and the potential commercialization of our product candidates will require substantial additional cash to fund expenses.
−Removed: For CTI-1601, and any future product candidates, we may decide to collaborate with pharmaceutical and/or biotechnology companies for the development and potential commercialization of those product candidates in some or all markets.
+Added: For nomlabofusp, and any future product candidates, we may decide to collaborate with pharmaceutical and/or biotechnology companies for the development and potential commercialization of those product candidates in some or all markets.
We face significant competition in seeking appropriate collaborators.
−Removed: Whether we reach a definitive agreement for a collaboration for CTI-1601 or other potential product candidates 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.
−Removed: Those factors may include the design or results of clinical trials, the likelihood of approval by the FDA or similar regulatory authorities outside the United States, the potential market for the applicable product candidate, the costs and complexities of manufacturing and delivering such product candidate to patients, the potential of competing products, the existence of uncertainty with respect to our ownership of technology, which can exist if there is a challenge to such ownership without regard to the merits of the challenge and industry and market conditions generally.
+Added: Whether we reach a definitive agreement for a collaboration for nomlabofusp or other potential product candidates 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.
+Added: Those factors may include the design or results of clinical trials, the likelihood of approval by the FDA or similar regulatory authorities outside the United States, the potential market for the applicable product candidate, the costs and complexities of manufacturing and delivering such product candidate to patients, the potential of competing products, the existence of uncertainty
+Added: with respect to our ownership of technology, which can exist if there is a challenge to such ownership without regard to the merits of the challenge and industry and market conditions generally.
The collaborator may also consider alternative product candidates or technologies for similar indications that may be available to collaborate on and whether such collaboration could be more attractive than the one with us for our product candidate.
6 unchanged sentences
If we elect to increase our expenditures to fund development or commercialization activities on our own, we will need to obtain additional capital, which may not be available to us on acceptable terms if at all.
−Removed: If we do not have sufficient funds,
−Removed: we may not be able to further develop our product candidates or bring them to market and generate product revenue.
+Added: 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.
In addition, such efforts may require diversion of a disproportionate amount of our attention away from other day-to-day activities and require devotion of a substantial amount of our time to managing these activities.
7 unchanged sentences
We face risks related to health epidemics, and/or other outbreaks of communicable diseases, which could significantly disrupt our operations and may materially and adversely affect our business and financial conditions.
−Removed: Our business could be adversely impacted by the effects of a global health epidemics, such as, for example, a possible resurgence of vaccine resistant or more highly contagious or deadly variants of COVID-19 and the efforts to mitigate such outbreaks.
−Removed: Such global outbreaks of communicable diseases globally could materially and adversely impact our operations, including without limitation, our manufacturing and supply chain for CTI-1601 and our planned clinical trials, which have faced, and could continue to face, enrollment difficulties as hospitals or clinical trials sites experience closures.
+Added: Our business could be adversely impacted by the effects of a global pandemic, epidemic or outbreak of an infectious disease, such as, for example, a possible resurgence of vaccine resistant or more highly contagious or deadly variants of COVID-19 and the efforts to mitigate such outbreaks.
+Added: Such global outbreaks of communicable diseases globally could materially and adversely impact our operations, including without limitation, our manufacturing and supply chain for nomlabofusp and our planned clinical trials, which could continue to face, enrollment difficulties as hospitals or clinical trials sites experience closures.
Because FA is a rare disease, there are a limited number of patients in close proximity to clinical trial sites and clinical trial patients travel from throughout the United States to clinical trial sites to participate.
3 unchanged sentences
Future pandemics could adversely affect global economies and financial markets resulting in an economic downturn that could have a material adverse effect on our business and prospects.
−Removed: 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 expose us to criminal sanctions, civil penalties, contractual damages, reputational harm, administrative burdens and diminished profits and future earnings.
−Removed: The regulatory framework for the collection, use, safeguarding, sharing, transfer and other processing of information worldwide is rapidly evolving and is likely to remain uncertain for the foreseeable future.
−Removed: Globally, virtually every jurisdiction in which we may operate has established its own data security and privacy frameworks with which we must comply.
−Removed: For example, the European Union’s General Data Protection Regulation 2016/679 ("EU GDPR"), the UK General Data Protection Regulation (“UK GDPR”, together with the EU GDPR, the “GDPR”) and UK Data Protection Act 2018, which impose strict obligations on the processing of personal data, including personal health data, and the free movement of such data.
−Removed: The GDPR applies to any company established in the European Economic Area/ United Kingdom ("EEA/UK") as well as any company outside the EEA/UK Union that processes personal data in connection with the offering of goods or services to individuals in the EEA/UK or the monitoring of their behavior.
−Removed: The GDPR enhances data protection obligations for processors and controllers of personal data, including, for example, obligations relating to:
−Removed: processing health and other sensitive data;
−Removed: obtaining consent of individuals;
−Removed: providing notice to individuals regarding data processing activities;
−Removed: responding to data subject requests;
−Removed: taking certain measures when engaging third-party processors;
−Removed: notifying data subjects and regulators of data breaches;
−Removed: implementing safeguards to protect the security and confidentiality of personal data;
−Removed: and strict rules and restrictions on the international transfers of personal data.
−Removed: The GDPR prohibits the transfer of personal data to countries outside the EEA/UK, which are not considered by the European Commission and UK government as providing an “adequate”
−Removed: protection of personal data, including the United States, unless a valid GDPR transfer mechanism (for example, the European Commission approved Standard Contractual Clauses (“SCCs”) and the UK International Data Transfer Agreement/Addendum (“UK
−Removed: IDTA”)) has been put in place.
−Removed: Where relying on the SCCs /UK IDTA for data transfers, we may also be required to carry out transfer impact assessments to assess whether the recipient is subject to local laws which allow public authority access to personal data.
−Removed: The international transfer obligations under the EEA/UK data protection regimes will require significant effort and cost and may result in us needing to make strategic considerations around where EEA/UK personal data is transferred and which service providers we can utilize for the processing of EEA/UK personal data.
−Removed: Although the UK is regarded as a third country under the EU GDPR, the European Commission has issued a decision recognizing the UK as providing adequate protection under the EU GDPR (“Adequacy Decision”) and, therefore, transfers of personal data originating in the EEA to the UK remain unrestricted.
−Removed: The UK government has confirmed that personal data transfers from the UK to the EEA remain free flowing.
−Removed: The UK Government has also introduced a Data Protection and Digital Information Bill (“UK Bill”) into the UK legislative process.
−Removed: The aim of the UK Bill is to reform the UK’s data protection regime following Brexit.
−Removed: If passed, the final version of the UK Bill may have the effect of further altering the similarities between the UK and EEA data protection regime and threaten the UK Adequacy Decision from the EU Commission.
−Removed: This may lead to additional compliance costs and could increase our overall risk.
−Removed: The respective provisions and enforcement of the EU GDPR and UK GDPR may further diverge in the future and create additional regulatory challenges and uncertainties.
−Removed: The GDPR imposes additional obligations and risks upon our business and substantially increases the penalties to which we could be subject in the event of any non-compliance, including fines of up to €20 million or 4% of total worldwide annual revenue, whichever is higher.
−Removed: The GDPR also confers a private right of action on data subjects and consumer associations to lodge complaints with supervisory authorities, seek judicial remedies and obtain compensation for damages.
−Removed: Given the breadth and depth of changes in data protection obligations, if we are required to comply with the GDPR’s requirements, we will be required to spend significant time and resources to review our technologies, systems and practices, as well as those of any third-party service providers, contractors or consultants that process or transfer personal data collected in the EEA/UK.
−Removed: The GDPR and other changes in laws or regulations associated with the enhanced protection of certain types of sensitive data, such as healthcare data or other personal information from our clinical trials, could require us to change our business practices or lead to government enforcement actions, private litigation or significant fines and penalties against us, reputational harm and could have a material adverse effect on our business, financial condition or results of operations.
−Removed: Our computer systems, or those of any of our CROs, manufacturers, other contractors or consultants or potential future collaborators, may fail or suffer security or data privacy breaches or other unauthorized or improper access to, use of, or destruction of our proprietary or confidential data, employee data, or personal data, which could result in additional costs, loss of revenue, significant liabilities, harm to our brand and material disruption of our operations.
−Removed: Despite the implementation of security measures in an effort to protect systems that store our information, given their size and complexity and the increasing amounts of information maintained on our internal information technology systems, and those of our third-party CROs, other contractors (including sites performing our clinical trials) and consultants, these systems are potentially vulnerable to breakdown or other damage or interruption from service interruptions, system malfunction, natural disasters, terrorism, war and telecommunication and electrical failures, as well as security breaches from inadvertent or intentional actions by our employees, contractors, consultants, business partners, and/or other third parties, or from cyber-attacks by malicious third parties (including supply chain cyber-attacks or the deployment of harmful malware, ransomware, denial-of-service attacks, social engineering and other means to affect service reliability and threaten the confidentiality, integrity and availability of information), which may compromise our system infrastructure or lead to the loss, destruction, alteration, prevention of access to, disclosure, or dissemination of, or damage or unauthorized access to, our data (including trade secrets or other confidential information, intellectual property, proprietary business information, and personal information) or data that is processed or maintained on our behalf, or other assets, which could result in financial, legal, business and reputational harm to us.
−Removed: Companies have, in general, experienced an increase in phishing and social engineering attacks from third parties, and the increase in remote working further increases security threats.
−Removed: To the extent that any disruption or security incident were to result in any loss, destruction, unavailability, alteration, disclosure, or dissemination of, or damage or unauthorized access to, our applications, any other data processed or maintained on our behalf or other assets, or for it to be believed or reported that any of these occurred, we could incur liability, financial harm and reputational damage and the development and commercialization of our product candidates could be delayed.
−Removed: We cannot ensure that our data protection efforts and our investment in information technology, or the efforts or investments of CROs, consultants or other third parties, will prevent significant breakdowns or breaches in systems or other cyber incidents that cause loss, destruction, unavailability, alteration or dissemination of, or damage
−Removed: or unauthorized access to, our data and other data processed or maintained on our behalf or other assets that could have a material adverse effect upon our reputation, business, operations or financial condition.
−Removed: For example, if such an event were to occur and cause interruptions in our operations, it could result in a material disruption of our programs and the development of our product candidates could be delayed.
−Removed: In addition, the loss of clinical trial data for our product candidates could result in delays in our marketing approval efforts and significantly increase our costs to recover or reproduce the data.
−Removed: Further, any such event that leads to loss, damage, or unauthorized access to, or use, alteration, or disclosure or dissemination of, personal information, including personal information regarding our clinical trial subjects or employees, could harm our reputation directly, compel us to comply with federal and/or state breach notification laws and foreign law equivalents, subject us to mandatory corrective action, and otherwise subject us to liability under laws and regulations that protect the privacy and security of personal information, which could result in significant legal and financial exposure and reputational damages that could potentially have an adverse effect on our business.
−Removed: Notifications and follow-up actions related to a security incident could impact our reputation and cause us to incur significant costs, including legal expenses and remediation costs.
−Removed: For example, the loss of clinical trial data from completed or future clinical trials could result in delays in our regulatory approval efforts and significantly increase our costs to recover or reproduce the lost data.
−Removed: We expect to incur significant costs in an effort to detect and prevent security incidents, and we may face increased costs and requirements to expend substantial resources in the event of an actual or perceived security incident.
−Removed: We also rely on third parties to manufacture our product candidates, and similar events relating to their computer systems could also have a material adverse effect on our business.
−Removed: To the extent that any disruption or security incident were to result in any loss, destruction, or alteration of, or damage or unauthorized access to, our data or other information that is processed or maintained on our behalf, or inappropriate disclosure of or dissemination of any such information, we could be exposed to litigation and governmental investigations, the further development and commercialization of our product candidates could be delayed, and we could be subject to significant fines or penalties for any noncompliance with certain state, federal and/or international privacy and security laws.
−Removed: Our insurance policies may not be adequate to compensate us for the potential losses arising from any such disruption in or, failure or security breach of our systems or third-party systems where information important to our business operations or commercial development is stored.
−Removed: In addition, such insurance may not be available to us in the future on economically reasonable terms, or at all.
−Removed: Further, our insurance may not cover all claims made against us and could have high deductibles in any event, and defending a suit, regardless of its merit, could be costly and divert management attention.
+Added: We are subject to stringent and evolving U.S.
+Added: and foreign laws, regulations and rules, contractual obligations, industry standards, policies and other obligations related to data privacy and security.
+Added: Our actual or perceived failure to comply with such obligations could lead to regulatory investigations or actions;
+Added: fines and penalties;
+Added: disruptions of our business operations;
+Added: reputational harm;
+Added: loss of revenue or profits;
+Added: and other adverse business consequences.
+Added: In the ordinary course of business, we collect, receive, store, process, generate, use, transfer, disclose, make accessible, protect, secure, dispose of, transmit, and share (collectively, process) personal data and other sensitive information, including proprietary and confidential business data, trade secrets, intellectual property, data we collect about trial participants in connection with clinical trials, sensitive third-party data, business plans, transactions, financial information and medical information collected by our patient access management team (collectively, sensitive data).
+Added: Our data processing activities may subject us to numerous data privacy and security obligations, such as various laws, regulations, guidance, industry standards, external and internal privacy and security policies, contractual requirements, and other obligations relating to data privacy and security.
+Added: In the United States, federal, state, and local governments have enacted numerous data privacy and security laws, including data breach notification laws, personal data privacy laws, consumer protection laws (e.g., Section 5 of the Federal Trade Commission Act), and other similar laws (e.g., wiretapping laws).
+Added: For example, HIPAA, as amended by HITECH, imposes specific requirements relating to the privacy, security, and transmission of individually identifiable health information.
+Added: Additionally, in the past few years, numerous U.S.
+Added: states—including California, Virginia, Colorado, Connecticut, and Utah—have enacted comprehensive privacy laws that impose certain obligations on covered businesses, including providing specific disclosures in privacy notices and affording residents with certain rights concerning their personal data.
+Added: As applicable, such rights may include the right to access, correct, or delete certain personal data, and to opt-out of certain data processing activities, such as targeted advertising, profiling, and automated decision-making.
+Added: The exercise of these rights may impact our business and ability to provide our products and services.
+Added: Certain states also impose stricter requirements for processing certain personal data, including sensitive information, such as conducting data privacy impact assessments.
+Added: These state laws allow for statutory fines for noncompliance.
+Added: For example, the California Consumer Privacy Act of 2018, as amended by the California Privacy Rights Act of 2020 (CPRA) (collectively, CCPA) requires businesses to provide specific disclosures in privacy notices and honor requests of California residents to exercise certain privacy rights.
+Added: The CCPA provides for fines of up to $7,500 per intentional violation and allows private litigants affected by certain data breaches to recover significant statutory damages.
+Added: Although some U.S.
+Added: comprehensive privacy laws exempt some data processed in the context of clinical trials, these laws may increase compliance costs and potential liability with respect to other personal data we may maintain about California residents.
+Added: Similar laws are being considered in several other states, as well as at the federal and local levels, and we expect more jurisdictions to pass similar laws in the future.
+Added: Outside the United States, an increasing number of laws, regulations, and industry standards may govern data privacy and security.
+Added: For example, the European Union’s General Data Protection Regulation (EU GDPR), United Kingdom’s GDPR (UK GDPR) (collectively, the GDPR), Brazil’s General Data Protection Law (Lei Geral de Proteção de Dados Pessoais, or LGPD) (Law No.
+Added: 13,709/2018), and China’s Personal Information Protection Law (PIPL) impose strict requirements for processing personal data.
+Added: For example, under the GDPR, companies may face temporary or definitive bans on data processing and other corrective actions;
+Added: fines of up to 20 million Euros under the EU GDPR / 17.5 million pounds sterling under the UK GDPR or 4% of annual global revenue, whichever is greater;
+Added: or private litigation related to processing of personal data brought by classes of data subjects or consumer protection organizations authorized at law to represent their interests.
+Added: The Swiss Federal Act on Data Protection, or the FADP, also applies to the collection and processing of personal data, including health-related information, by companies located in Switzerland, or in certain circumstances, by companies located outside of Switzerland.
+Added: The FADP has been revised and adopted by the Swiss Parliament.
+Added: Companies must comply with the revised version of the FADP and its revised ordinances from September 1, 2023, which may result in an increase of costs of compliance, risks of noncompliance and penalties for noncompliance.
+Added: In addition, we may be unable to transfer personal data from Europe and other jurisdictions to the United States or other countries due to data localization requirements or limitations on cross-border data flows.
+Added: Europe and other jurisdictions have enacted laws requiring data to be localized or limiting the transfer of personal data to other countries.
+Added: In particular, the European Economic Area (EEA) and the UK have significantly restricted the transfer of personal data to the United States and other countries whose privacy laws it believes are inadequate.
+Added: Other jurisdictions may adopt similarly stringent interpretations of their data localization and cross-border data transfer laws.
+Added: Although there are currently various mechanisms that may be used to transfer personal data from the EEA and UK to the United States in compliance with law, such as the EEA standard contractual clauses, the UK’s International Data Transfer Agreement / Addendum, and the EU-U.S.
+Added: Data Privacy Framework and the UK extension thereto (which allows for transfers to relevant U.S.-based organizations who self-certify compliance and
+Added: participate in the Framework), these mechanisms are subject to legal challenges, and there is no assurance that we can satisfy or rely on these measures to lawfully transfer personal data to the United States.
+Added: If there is no lawful manner for us to transfer personal data from the EEA, the UK, or other jurisdictions to the United States, or if the requirements for a legally-compliant transfer are too onerous, we could face significant adverse consequences, including by limiting our ability to conduct clinical trial activities in Europe and elsewhere, the interruption or degradation of our operations, the need to relocate part of or all of our business or data processing activities to other jurisdictions (such as Europe) at significant expense, increased exposure to regulatory actions, substantial fines and penalties, the inability to transfer data and work with partners, vendors and other third parties, and injunctions against our processing or transferring of personal data necessary to operate our business.
+Added: Some European regulators have ordered certain companies to suspend or permanently cease certain transfers of personal data to recipients outside Europe for allegedly violating the GDPR’s cross-border data transfer limitations.
+Added: Additionally, companies that transfer personal data to recipients outside of the EEA and/or UK to other jurisdictions, particularly to the United States, are subject to increased scrutiny from regulators individual litigants and activist groups.
+Added: In addition to data privacy and security laws, we may be contractually subject to industry standards adopted by industry groups and may become subject to such obligations in the future.
+Added: We are also bound by other contractual obligations related to data privacy and security, and our efforts to comply with such obligations may not be successful.
+Added: We publish privacy policies, marketing materials, and other statements, such as compliance with certain certifications or self-regulatory principles, regarding data privacy and security.
+Added: If these policies, materials or statements are found to be deficient, lacking in transparency, deceptive, unfair, or misrepresentative of our practices, we may be subject to investigation, enforcement actions by regulators, or other adverse consequences.
+Added: Additionally, under various privacy laws and other obligations, we may be required to obtain certain consents to process personal data.
+Added: For example, some of our data processing practices may be challenged under wiretapping laws, if we obtain consumer information from third parties through various methods, including chatbot and session replay providers, or via third-party marketing pixels.
+Added: These practices may be subject to increased challenges by class action plaintiffs.
+Added: Our inability or failure to obtain consent for these practices could result in adverse consequences, including class action litigation and mass arbitration demands.
+Added: Obligations related to data privacy and security (and consumers’ data privacy expectations) are quickly changing, becoming increasingly stringent, and creating uncertainty.
+Added: Additionally, these obligations may be subject to differing applications and interpretations, which may be inconsistent or conflict among jurisdictions.
+Added: Preparing for and complying with these obligations requires us to devote significant resources and may necessitate changes to our services, information technologies, systems, and practices and to those of any third parties that process personal data on our behalf.
+Added: We may at times fail (or be perceived to have failed) in our efforts to comply with our data privacy and security obligations.
+Added: Moreover, despite our efforts, our personnel or third parties on whom we rely on may fail to comply with such obligations, which could negatively impact our business operations.
+Added: If we or the third parties on which we rely fail, or are perceived to have failed, to address or comply with applicable data privacy and security obligations, we could face significant consequences, including but not limited to:
+Added: government enforcement actions (e.g., investigations, fines, penalties, audits, inspections, and similar);
+Added: litigation (including class-action claims) and mass arbitration demands;
+Added: additional reporting requirements and/or oversight;
+Added: bans on processing personal data;
+Added: and orders to destroy or not use personal data.
+Added: In particular, plaintiffs have become increasingly more active in bringing privacy-related claims against companies, including class claims.
+Added: Some of these claims allow for the recovery of statutory damages on a per violation basis, and, if viable, carry the potential for monumental statutory damages, depending on the volume of data and the number of violations.
+Added: Any of these events could have a material adverse effect on our reputation, business, or financial condition, including but not limited to loss of customers;
+Added: inability to process personal data or to operate in certain jurisdictions;
+Added: limited ability to develop or commercialize our products;
+Added: expenditure of time and resources to defend any claim or inquiry;
+Added: adverse publicity;
+Added: or substantial changes to our business model or operations.
+Added: Our internal computer systems, as well as those of CROs, CMOs, vendors, contractors, and consultants, and potential collaborators may experience failures, unauthorized access, or security breaches, potentially causing a material disruption in our product development programs, operations, harm to our brand, significant liabilities, loss of revenue, and additional costs.
+Added: Despite implementing comprehensive security measures, both our internal computer systems and those of our contracted third party service providers are susceptible to various threats, including cyber-attacks, computer viruses,
+Added: unauthorized access, natural disasters, terrorism, war, and telecommunication and electrical failures.
+Added: The extensive use of mobile devices accessing confidential information further heightens the risks, leading to potential device loss, security incidents, and data breaches that could result in the loss of confidential information and intellectual property.
+Added: Any system failure, accident, or security breach causing interruptions in our operations may lead to a material disruption in our product development programs and business operations, potentially requiring substantial resources for recovery.
+Added: For instance, the loss of clinical trial data from completed trials could lead to delays in regulatory approval efforts and significantly increase costs for data recovery or reproduction.
+Added: We are exposed to risks stemming from misappropriation, misuse, leakage, falsification, or intentional or accidental release or loss of information maintained in our information systems and networks, including personal information of our employees.
+Added: External parties may attempt to penetrate our systems or induce our employees or those of our vendors to disclose sensitive information.
+Added: As with other companies, we face threats to our data and systems, including malicious codes, viruses, and cyber-attacks.
+Added: The increasing number and complexity of these threats over time pose a challenge.
+Added: A material breach in our security or that of our vendors, contractors, or consultants could harm the market perception of our security measures, resulting in business loss and damage to our reputation and credibility.
+Added: This could significantly adversely affect our business, financial condition, and results of operations, necessitating substantial amounts of money and resources to repair or replace information systems or networks.
+Added: Despite our continuous efforts, the possibility of such events occurring cannot be entirely eliminated.
+Added: In our endeavor to protect systems storing critical information, we have implemented security measures.
+Added: However, given their size and complexity and the increasing amounts of information maintained, these systems, including our internal information technology systems and those of third-party entities like Contract Research Organizations, Contract Manufacturing Organizations, contractors, and consultants, remain potentially vulnerable to breakdowns, interruptions, and security breaches.
+Added: Incidents such as service interruptions, system malfunctions, natural disasters, terrorism, war, telecommunication, and electrical failures, as well as security breaches from inadvertent or intentional actions by employees, contractors, consultants, and other third parties, including cyber-attacks by malicious entities, may compromise our system infrastructure.
+Added: This could lead to the loss, destruction, alteration, or unauthorized access to our data, including trade secrets, confidential information, intellectual property, proprietary business information, and personal information, or data processed or maintained on our behalf.
+Added: Such incidents could result in financial, legal, business, and reputational harm.
+Added: The rise in phishing and social engineering attacks and the increase in remote working further elevate security threats.
+Added: Any disruption or security incident could lead to loss, damage, or unauthorized access to data, potentially exposing us to litigation and governmental investigations, delaying the development and commercialization of our product candidates, and subjecting us to fines or penalties for noncompliance with privacy and security laws.
+Added: Notifications and actions following a security incident could impact our reputation and incur significant costs, including legal expenses and remediation.
+Added: Significant efforts and costs are expected for detection and prevention.
+Added: Our reliance on third parties for manufacturing introduces an additional layer of risk to our business.
+Added: Insurance policies, including a specific policy related to cybersecurity losses, may be insufficient, with potential availability issues in the future, high deductibles, and limitations in coverage, posing challenges in mitigating losses from disruptions, failures, or security breaches.
+Added: If our information technology systems or data, and/or those of third parties upon which we rely, are or were compromised, we could experience adverse consequences resulting from such compromise, including but not limited to regulatory investigations or actions, interruptions to operations or clinical trials, reputational harm, litigation, fines and penalties, disruptions of our business operations, and a loss of customers or sales.
+Added: In the ordinary course of our business, we, or the third parties upon which we rely, process proprietary, confidential, and sensitive data, including personal data (such as health-related data), intellectual property, and trade secrets.
+Added: Cyberattacks, malicious internet-based activity, online and offline fraud and other similar activities threaten the confidentiality, integrity, and availability of our sensitive data and information technology systems, and those of the third parties upon which we rely.
+Added: These threats are prevalent, continue to rise, and are becoming increasingly difficult to detect.
+Added: These threats come from a variety of sources, including traditional computer “hackers,” hacktivists, threat actors, personnel misconduct or error (such as through theft or misuse), organized criminal threat actors, sophisticated nation-states, and nation-state-supported actors.
+Added: Some actors now engage and are expected to continue to engage in cyber-attacks, including without limitation nation-state actors for geopolitical reasons and in
+Added: conjunction with military conflicts and defense activities.
+Added: During times of war and other major conflicts, we and the third parties upon which we rely may be vulnerable to a heightened risk of these attacks, including retaliatory cyber-attacks, that could materially disrupt our systems and operations, supply chain, and ability to produce, sell and distribute our goods and services.
+Added: We and the third parties upon which we rely are subject to a variety of evolving threats, including but not limited to, social engineering attacks (including through deep fakes, which may be increasingly more difficult to identify as fake, and phishing attacks), malicious code (such as viruses and worms), malware (including as a result of advanced persistent threat intrusions), denial-of-service attacks, credential stuffing, credential harvesting, personnel misconduct or error, ransomware attacks, supply-chain attacks, software bugs, server malfunction, software or hardware failures, loss of data or other information technology assets, adware, attacks enhanced or facilitated by AI, telecommunications failures, earthquakes, fire, flood, and other similar threats.
+Added: Ransomware attacks, including by organized criminal threat actors, nation-states, and nation-state-supported actors, are becoming increasingly prevalent and severe and can lead to significant interruptions, delays, or outages in our operations, disruption of clinical trials or otherwise affecting our ability to provide our products or product candidates, loss of sensitive data (including data related to clinical trials) and income, significant extra expenses to restore data or systems, reputational harm and the diversion of funds.
+Added: Extortion payments may alleviate the negative impact of a ransomware attack, but we may be unwilling or unable to make such payments (including, for example, if applicable laws or regulations prohibit such payments).
+Added: Remote work has become more common and has increased risks to our information technology systems and data, as more of our employees work from home, utilizing network connections, computers and devices outside our premises, including at home, while in transit or in public locations.
+Added: Future business transactions (such as acquisitions or integrations) could expose us to additional cybersecurity risks and vulnerabilities, as our systems could be negatively affected by vulnerabilities present in acquired or integrated entities’ systems and technologies.
+Added: Furthermore, we may discover security issues that were not found during due diligence of such acquired or integrated entities, and it may be difficult to integrate companies into our information technology environment and security program.
+Added: We rely on third-party service providers and technologies to operate critical business systems to process sensitive data in a variety of contexts, including, without limitation, cloud-based infrastructure, drug suppliers, data center facilities, encryption and authentication technology, employee email, content delivery to customers, and other functions.
+Added: Our ability to monitor these third parties’ information security practices and posture (including whether any unremediated vulnerabilities exist or have been exploited) is limited, and these third parties may not have adequate information security measures in place.
+Added: In addition, supply-chain attacks have increased in frequency and severity, and we cannot guarantee that third parties’ infrastructure in our supply chain or our third-party partners’ supply chains have not been compromised.
+Added: While we have implemented security measures designed to protect against security incidents, there can be no assurance that these measures will be effective.
+Added: We take steps designed to detect, mitigate, and remediate vulnerabilities in our information security systems (such as our hardware and/or software, including that of third parties upon which we rely).
+Added: We and the third parties upon which may rely may not, however, detect and remediate all such vulnerabilities including on a timely basis.
+Added: For example, we have identified certain vulnerabilities in our information systems, and we have taken steps to mitigate the risks associated with known vulnerabilities.
+Added: These steps include implementing compensating controls and other protective measures.
+Added: Further, we and the third parties upon which we rely may experience delays in developing and deploying remedial measures and patches designed to address identified vulnerabilities.
+Added: Vulnerabilities could be exploited and result in a security incident.
+Added: Any of the previously identified or similar threats could cause a security incident or other interruption that could result in unauthorized, unlawful, or accidental acquisition, modification, destruction, loss, alteration, encryption, disclosure of, or access to our sensitive information or our information technology systems, or those of the third parties upon whom we rely.
+Added: A security incident or other interruption could disrupt our ability (and that of third parties upon whom we rely) to provide our products.
+Added: We may expend significant resources or fundamentally change our business activities and practices (including our clinical trials) to try to protect against security incidents.
+Added: Certain data privacy and security obligations may require us to implement and maintain specific security measures or industry-standard or reasonable security measures to protect our information technology systems and sensitive data.
+Added: Applicable data privacy and security obligations may require us to notify relevant stakeholders, including affected individuals, customers, regulators, and investors, of security incidents.
+Added: Such disclosures are costly, and the disclosure or the failure to comply with such requirements could lead to adverse consequences.
+Added: If we (or a third party upon whom we rely) experience a security incident or are perceived to have experienced a security incident, we may experience adverse consequences.
+Added: These consequences may include:
+Added: government enforcement actions (for example, investigations, fines, penalties, audits, and inspections);
+Added: additional reporting requirements and/or oversight;
+Added: restrictions on processing sensitive data (including personal data);
+Added: litigation (including class claims);
+Added: indemnification obligations;
+Added: negative publicity;
+Added: reputational harm;
+Added: monetary fund diversions;
+Added: diversion of management attention;
+Added: interruptions in our operations (including availability of data);
+Added: financial loss;
+Added: and other similar harms.
+Added: Security incidents and attendant consequences may prevent or cause customers to stop using our products, deter new customers from using our products, and negatively impact our ability to grow and operate our business.
+Added: In addition to experiencing a security incident, third parties may gather, collect, or infer sensitive data about us from public sources, data brokers or other means that reveals competitively sensitive details about our organization and could be used to undermine our competitive advantage or market position.
+Added: Additionally, sensitive information of the Company could be leaked, disclosed, or revealed as a result of or in connection with the use of generative AI technologies.
+Added: Our contracts may not contain limitations of liability, and even where they do, there can be no assurance that limitations of liability in our contracts are sufficient to protect us from liabilities, damages, or claims related to our data privacy and security obligations.
+Added: In addition, our insurance coverage may not be adequate or sufficient in type or amount to protect us from or to mitigate liabilities arising out of our privacy and security practices.
+Added: The successful assertion of one or more large claims against us that exceeds our available insurance coverage, or results in changes to our insurance policies (including premium increases or the imposition of large deductible or co-insurance requirements), could have an adverse effect on our business.
We face potential product liability exposure, and, if claims are brought against us, we may incur substantial liability.
−Removed: The use of CTI-1601 and other potential product candidates in clinical trials, if any, and the sale of CTI-1601 and other potential product candidates, if developed and approved, exposes us to the risk of product liability claims.
−Removed: Product liability claims might be brought against us by patients, healthcare providers or others selling or otherwise coming into contact with CTI-1601 or other potential product candidates.
+Added: The use of nomlabofusp and other potential product candidates in clinical trials, if any, and the sale of nomlabofusp and other potential product candidates, if developed and approved, exposes us to the risk of product liability claims.
+Added: Product liability claims might be brought against us by patients, healthcare providers or others selling or otherwise coming into contact with nomlabofusp or other potential product candidates.
For example, we may be sued if any product we develop allegedly causes injury or death or is found to be otherwise unsuitable during product testing, manufacturing, marketing or sale.
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• substantial monetary awards to patients or other claimants;
−Removed: decreased demand for CTI-1601 or our other potential product candidates following marketing approval, if obtained;
+Added: • decreased demand for nomlabofusp or our other potential product candidates following marketing approval, if obtained;
• damage to our reputation and exposure to adverse publicity;
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• litigation costs;
−Removed: distraction of management’s attention from our primary business;
+Added: • distraction of management’s attention from our primary business;
• increased product liability costs;
• loss of revenue;
−Removed: the inability to successfully commercialize CTI-1601 or other potential product candidates, if approved.
+Added: • the inability to successfully commercialize nomlabofusp or other potential product candidates, if approved.
We maintain product liability insurance coverage for our clinical trials with a $5 million aggregate coverage limit.
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Moreover, in the future, we may not be able to maintain insurance coverage at a reasonable cost or in sufficient amounts to protect us against losses, including if insurance coverage becomes increasingly expensive.
−Removed: If we obtain marketing approval for CTI-1601 or other potential product candidates, we intend to expand our insurance coverage to include the sale of commercial products;
+Added: If we obtain marketing approval for nomlabofusp or other potential product candidates, we intend to expand our insurance coverage to include the sale of commercial products;
however, we may not be able to obtain this product liability insurance on commercially reasonable terms.
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We have limited experience in conducting or supervising clinical trials that must be performed to obtain data to submit in concert with applications for approval by the FDA, the EMA or other comparable foreign regulatory authorities.
−Removed: As a result, we expect to continue to rely on CROs, clinical data management organizations and consultants to design, conduct, supervise and monitor our non-clinical studies and clinical trials.
−Removed: We and our CROs are required to comply with various regulations, including the FDA’s regulations regarding current Good Clinical Practices ("cGCPs") which are enforced by regulatory agencies, including the FDA, and comparable foreign regulatory authorities to ensure the health, safety and rights of patients are protected in clinical development and clinical trials, and that trial data integrity is assured.
+Added: As a result, we expect to continue to rely on CROs, clinical trial sites, clinical data management organizations and consultants to design, conduct, supervise and monitor our non-clinical studies and clinical trials.
+Added: We, our CROs, and contractors are required to comply with various regulations, including the FDA’s regulations regarding current Good Clinical Practices ("cGCPs") which are enforced by regulatory agencies, including the FDA, and comparable foreign regulatory authorities to ensure the health, safety and rights of patients are protected in clinical development and clinical trials, and that trial data integrity is assured.
Regulatory authorities ensure compliance with these requirements through periodic inspections of trial sponsors, principal investigators and clinical trial sites.
Our expected reliance on third parties that we do not control does not relieve us of these responsibilities and requirements.
−Removed: If we or any of our CROs fail to comply with applicable requirements, the clinical data generated in our clinical trials may be deemed unreliable and the FDA, EMA or other comparable foreign regulatory authorities may require us to perform additional clinical trials before approving our marketing applications.
+Added: If we or any of our CROs, contractors, or clinical trial sites fail to comply with applicable requirements, the clinical data generated in our clinical trials may be deemed unreliable and the FDA, EMA or other comparable foreign regulatory authorities may require us to perform additional clinical trials before approving our marketing applications.
We cannot ensure that upon inspection by a given regulatory authority, such regulatory authority will determine that any of our clinical trials comply with such requirements.
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Failure to comply with these regulations may require us to repeat non-clinical studies and/or clinical trials, which would delay the regulatory approval process, and could also subject us to enforcement action, up to and including, civil and criminal penalties, which would materially adversely affect our business, financial condition and results of operations.
−Removed: Our CROs are not our employees, and except for remedies available to us under our agreements with such CROs, we cannot control whether or not they devote sufficient time and resources to our ongoing clinical and
−Removed: non-clinical programs.
−Removed: If CROs do not successfully carry out their contractual duties or obligations or meet expected deadlines or if the quality or accuracy of the clinical data they obtain is compromised due to the failure to adhere to our clinical protocols, regulatory requirements or for other reasons, our clinical trials may be extended, delayed or terminated and we may not be able to obtain regulatory approval for or successfully commercialize our product candidates.
+Added: Our CROs and contractors are not our employees, and except for remedies available to us under our agreements with such CROs and contractors, we cannot control whether or not they devote sufficient time and resources to our ongoing clinical and non-clinical programs.
+Added: If our CROs and contractors do not successfully carry out their contractual duties or obligations or meet expected deadlines or if the quality or accuracy of the clinical data they obtain is compromised due to the failure to adhere to our clinical protocols, regulatory requirements or for other
+Added: reasons, our clinical trials may be extended, delayed or terminated and we may not be able to obtain regulatory approval for or successfully commercialize our product candidates.
As a result, our operations and the commercial prospects for our product candidates would be harmed, our costs could increase and our ability to generate revenue could be delayed or reduced.
−Removed: In addition, operations of our CROs could be affected by earthquakes, power shortages, telecommunications failures, water shortages, floods, hurricanes, typhoons, fires, extreme weather conditions, medical epidemics and other natural or man-made disasters or business interruptions.
+Added: In addition, operations of our CROs and contractors could be affected by earthquakes, power shortages, telecommunications failures, water shortages, floods, hurricanes, typhoons, fires, extreme weather conditions, medical epidemics and other natural or man-made disasters or business interruptions.
If their facilities are unable to operate because of an accident or incident, even for a short period of time, some or all of our research and development programs may be harmed or delayed, and our operations and financial condition could suffer.
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These factors may materially adversely affect the willingness or ability of third parties to conduct our clinical trials and may subject us to unexpected cost increases that are beyond our control.
−Removed: Nevertheless, we are responsible for ensuring that each of our clinical trials is conducted in accordance with the applicable protocol, legal and regulatory requirements and scientific standards, and our reliance on CROs does not relieve us of our regulatory responsibilities.
+Added: Nevertheless, we are responsible for ensuring that each of our clinical trials is conducted in accordance with the applicable protocol, legal and regulatory requirements and scientific standards, and our reliance on CROs and contractors does not relieve us of our regulatory responsibilities.
In addition, we must, at times, share confidential information with third parties.
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Despite the contractual provisions employed when working with third parties, the need to share confidential information increases the risk that such confidential information become known by our competitors, are inadvertently incorporated into the technology of others, or are disclosed or used in violation of these agreements.
−Removed: Given that our proprietary position is based, in part, on our confidential information, a competitor’s discovery of our confidential information or other unauthorized use or disclosure would impair our competitive position and may have an adverse effect on our business.
+Added: Given that our proprietary position is based, in part, on our confidential information, a competitor’s discovery of our confidential information or other unauthorized use or disclosure would impair our competitive position and may have an adverse effect on our business.
Moreover, because we have relied on third parties, our internal capacity to perform these functions is limited.
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To the extent we are unable to engage new third-party providers, if necessary, and successfully manage the performance of third-party service providers in the future, our business may be adversely affected.
−Removed: Though we carefully manage our relationships with CROs, there can be no assurance that we will not encounter similar challenges or delays in the future or that these delays or challenges will not have a material adverse impact on our business, financial condition, results of operation and prospects.
+Added: Though we carefully manage our relationships with CROs, and contractors there can be no assurance that we will not encounter similar challenges or delays in the future or that these delays or challenges will not have a material adverse impact on our business, financial condition, results of operation and prospects.
We rely on third-party supply and manufacturing partners for drug supplies for our research and development, non-clinical activities, and clinical activities, and may do the same for any commercial supplies of our product candidates.
We rely on third-party supply and manufacturing partners to supply the materials and components for, and manufacture, our research and development, non-clinical and clinical study drug substance and drug product.
−Removed: We have not yet manufactured or formulated any product candidate on a commercial scale and may not be able to do so for any of our product candidates.
+Added: We have not yet manufactured or formulated nomlabofusp or any other product candidate on a commercial scale and may not be able to do so for any of our product candidates.
We will work to develop and optimize our manufacturing process;
however, we cannot be sure that the process will result in therapies that are safe, potent or effective.
+Added: Given our reliance on third parties and the risk of manufacturing commercial scale quantities, our ability to adequately commercially launch and/or supply nomlabofusp could be adversely affected.
We do not own manufacturing facilities or supply sources for such components, non-clinical and clinical study drug substance, product and materials, including devices that may be required for administration, but may develop these capabilities in the future.
There can be no assurance that our supply of research and development, non-clinical and clinical development of drugs and other materials will not be limited, interrupted, restricted in certain geographic regions or will be of satisfactory quality or continue to be available at acceptable prices.
−Removed: In particular,
−Removed: replacement of any product formulation manufacturer we may engage could require significant effort and expertise because there may be a limited number of qualified replacements.
−Removed: For example, we rely and expect to continue to rely on a small number of manufacturers to supply us with our requirements for drug substance and formulated drug product related to our CTI-1601 clinical program.
−Removed: The drug substance which is in frozen liquid form for CTI-1601 is currently manufactured for us by a third-party manufacturer, and the frozen liquid form of drug product is made at another manufacturer.
+Added: In particular, replacement of any product formulation manufacturer we may engage could require significant effort and expertise
+Added: because there may be a limited number of qualified replacements.
+Added: For example, we rely and expect to continue to rely on a small number of manufacturers to supply us with our requirements for drug substance and formulated drug product related to our nomlabofusp clinical program.
+Added: The drug substance which is in frozen liquid form for nomlabofusp is currently manufactured for us by a third-party manufacturer, and the frozen liquid form of drug product is made at another manufacturer.
We are undertaking a program with a third party manufacturer to begin to produce a lyophilized version of the drug product from the same drug substance, that, once available, we intend to use in certain of our future planned clinical trials.
Our research and development programs could be adversely affected by a significant interruption in these manufacturing services or in the supply of drug substance and formulated drugs.
−Removed: In addition, because we rely on multiple manufacturers for our CTI-1601 clinical program, termination of our agreements with any of these manufacturers could significantly adversely impact our current and planned operations.
+Added: In addition, because we rely on multiple manufacturers for our nomlabofusp clinical program, termination of our agreements with any of these manufacturers could significantly adversely impact our current and planned operations.
In the event that any of our suppliers or manufacturers fails to perform their obligations to us in relation to quality, timing or otherwise, or if our supply of components or other materials becomes limited or interrupted for other reasons, we may be forced to manufacture the materials ourselves, for which we currently do not have the capabilities or resources, or enter into an agreement with another third party, which we may not be able to do on reasonable terms, if at all.
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We also rely on third parties to store master and working cell banks.
−Removed: We currently have one master cell bank and one working cell bank for CTI-1601 and believe we would have adequate backup should any cell bank be lost in a catastrophic event.
+Added: We currently have one master cell bank and one working cell bank for nomlabofusp and believe we would have adequate backup should any cell bank be lost in a catastrophic event.
However, it is possible that we could lose multiple cell banks and have our manufacturing severely impacted by the need to replace the cell banks, which could materially and adversely affect our business, financial condition and results of operations.
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If we are unable to obtain or maintain third party manufacturing for product candidates, or to do so on commercially reasonable terms, we may not be able to develop and commercialize our product candidates successfully.
−Removed: Our or a third party’s failure to execute on our manufacturing requirements could adversely affect our business, financial condition and results of operations in a number of ways, including:
+Added: Our or a third party’s failure to execute on our manufacturing requirements could adversely affect our business, financial condition and results of operations in a number of ways, including:
• an inability to initiate or continue clinical trials of product candidates under development;
1 unchanged sentence
• loss of the cooperation of a collaborator, including termination or nonrenewal of the agreement at a time that is costly or inconvenient for us;
+Added: • delays in manufacturing associated with having to change manufacturers;
• subjecting our product candidates to additional inspections by regulatory authorities;
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The manufacturing facilities on which we rely may not continue to meet regulatory requirements and have limited capacity.
−Removed: All entities involved in the preparation of therapeutics for clinical trials or commercial sale, including our existing contract manufacturers for CTI-1601, are subject to extensive regulation.
+Added: All entities involved in the preparation of therapeutics for clinical trials or commercial sale, including our existing contract manufacturers for nomlabofusp, are subject to extensive regulation.
Some components of a finished therapeutic product approved for commercial sale or used in late-stage clinical trials must be manufactured in accordance with cGMP.
1 unchanged sentence
Poor control of production processes can lead to the introduction of adventitious agents or other contaminants, or to inadvertent changes in the properties or stability of our product candidates that may not be detectable in final product testing.
−Removed: We or our contract manufacturers must supply all necessary documentation in support of a BLA or NDA on a timely basis and where required, must adhere to the FDA’s or other regulator’s GLPs and cGMP regulations enforced by the FDA or other regulator through facilities inspection programs.
−Removed: The facilities and quality systems of some or all of our third party contractors must pass a pre-approval inspection for compliance with the applicable regulations as a condition of regulatory approval of CTI-1601 or any of our other potential products.
−Removed: In addition, the regulatory authorities may, at any time, audit or inspect a manufacturing facility involved with the preparation of CTI-1601 or our other potential products or the associated quality systems for compliance with the regulations applicable to the activities being conducted.
+Added: We or our contract manufacturers must supply all necessary documentation in support of a BLA or NDA on a timely basis and where required, must adhere to the FDA’s or other regulator’s GLPs and cGMP regulations enforced by the FDA or other regulators through facilities inspection programs.
+Added: The facilities and quality systems of some or all of our third party contractors must pass a pre-approval inspection for compliance with the applicable regulations as a condition of regulatory approval of nomlabofusp or any of our other potential products.
+Added: In addition, the regulatory authorities may, at any time, audit or inspect a manufacturing facility involved with the preparation of nomlabofusp or our other potential products or the associated quality systems for compliance with the regulations applicable to the activities being conducted.
If these facilities do not pass a pre-approval plant inspection, the FDA or other regulatory approval of the products will not be granted.
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The delays associated with the verification of a new manufacturer could negatively affect our ability to develop product candidates in a timely manner or within budget.
−Removed: These factors could also cause the delay of manufacturing development, clinical trials, regulatory submissions, required approvals or commercialization of CTI-1601 or any other product candidates, cause us to incur higher costs and prevent us from commercializing our products successfully.
+Added: These factors could also cause the delay of manufacturing development, clinical trials, regulatory submissions, required approvals or commercialization of nomlabofusp or any other product candidates, cause us to incur higher costs and prevent us from commercializing our products successfully.
Furthermore, if our suppliers fail to meet contractual requirements, and we are unable to secure one or more replacement suppliers capable of production at a substantially equivalent cost, our clinical trials may be delayed, or we could lose potential revenues.
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In the normal course of business, we periodically enter into academic, commercial, service, collaboration, licensing, consulting and other agreements that contain indemnification provisions.
−Removed: With respect to our academic and other research agreements, we typically indemnify the institution and related parties from losses arising from claims relating to the products, processes or services made, used, sold or performed pursuant to the agreements for which we have secured licenses, and from claims arising from our or our sublicensees’
−Removed: exercise of rights under the agreement.
−Removed: With respect to our collaboration and contract service agreements, we indemnify our collaborators from any third party product liability claims that could result from the production, use or consumption of the product, as well as for alleged infringements of any patent or other intellectual property right by a third party.
−Removed: With respect to consulting agreements, we indemnify consultants from claims arising from the good faith performance of their consulting services.
+Added: With respect to our academic and other research agreements, we typically indemnify the institution and related parties from losses arising from claims relating to the products, processes or services made, used, sold or performed pursuant to the agreements for which we have secured licenses, and from claims arising from our or our sublicensees’ exercise of rights under the agreement.
+Added: With respect to our collaboration and contract service agreements, we typically indemnify our collaborators from any third party product liability claims that could result from the production, use or consumption of the product, as well as for alleged infringements of any patent or other intellectual property right by a third party.
+Added: With respect to consulting agreements, we typically indemnify consultants from claims arising from the good faith performance of their consulting services.
Should our obligation under an indemnification provision exceed applicable insurance coverage or should we be denied insurance coverage, our business, financial condition and results of operations could be adversely affected.
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• we may be required to relinquish important rights, such as marketing and distribution rights;
−Removed: business combinations or significant changes in a collaborator’s business strategy may also adversely affect a collaborator’s willingness or ability to complete its obligations under any arrangement;
+Added: • business combinations or significant changes in a collaborator’s business strategy may also adversely affect a collaborator’s willingness or ability to complete its obligations under any arrangement;
• a collaborator could independently move forward with a competing drug candidate developed either independently or in collaboration with others, including our competitors;
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Risks Related to Our Intellectual Property Rights
−Removed: If, in the United States and other countries, we are unable to adequately protect our proprietary technology or maintain issued patents which are sufficient to protect CTI-1601 or potential product candidates, third parties could compete against us more directly, which would have a material adverse impact on our business, results of operations, financial condition and prospects.
+Added: If, in the United States and other countries, we are unable to adequately protect our proprietary technology or maintain issued patents which are sufficient to protect nomlabofusp or potential product candidates, third parties could compete against us more directly, which would have a material adverse impact on our business, results of operations, financial condition and prospects.
Our commercial success will depend in part on our success in obtaining and maintaining issued patents and other intellectual property rights in the United States and elsewhere and protecting our proprietary technology.
−Removed: do not adequately protect our intellectual property and proprietary technology, competitors may be able to use our technologies and erode or negate any competitive advantage we may have, which could harm our business and ability to achieve profitability.
+Added: If we do not adequately protect our intellectual property and proprietary technology, competitors may be able to use our
+Added: technologies and erode or negate any competitive advantage we may have, which could harm our business and ability to achieve profitability.
With respect to our patent portfolio, we in-license from WFUHS certain issued U.S.
−Removed: patents that relate to CTI-1601 and its use for treating FA.
−Removed: We also in-license from IU a United States patent and pending non-provisional applications in the United States and certain foreign countries that relate to the composition of CTI-1601 and methods of use, and certain U.S.
−Removed: patents relating to materials and methods of use relating to the development of CTI-1601.
−Removed: We also own or co-own pending international and United States non-provisional applications and United States provisional applications relating to methods of use of CTI-1601, biomarkers and to our platform technology.
+Added: patents that relate to nomlabofusp and its use for treating FA.
+Added: We also in-license from IU a United States patent and pending non-provisional applications in the United States and certain foreign countries that relate to the composition of nomlabofusp and methods of use, and certain U.S.
+Added: patents relating to materials and methods of use relating to the development of nomlabofusp.
+Added: We also own or co-own pending international PCT, foreign and United States non-provisional applications, a United States Patent, and United States provisional applications relating to the development of nomlabofusp, including methods of use of nomlabofusp, biomarkers and to our peptide delivery platform technology.
In some cases, we have only filed provisional patent applications on certain aspects of our technologies and each of these provisional patent applications is not eligible to become an issued patent until, among other things, we file a non-provisional patent application within 12 months of the filing date of the applicable provisional patent application.
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With respect to both in-licensed and owned intellectual property, we cannot predict whether the patent applications we and our licensors are currently pursuing will issue as patents in any particular jurisdiction or whether the claims of any issued patents will provide sufficient protection from competitors or other third parties.
−Removed: We cannot provide any assurances that any of our pending patent applications that mature into issued patents will include claims with a scope sufficient to protect CTI-1601, or other potential product candidates.
+Added: We cannot provide any assurances that any of our pending patent applications that mature into issued patents will include claims with a scope sufficient to protect nomlabofusp, or other potential product candidates.
Other parties have developed technologies that may be related or competitive to our approach and may have filed or may file patent applications and may have received or may receive patents that may overlap or conflict with our patent applications, either by claiming the same methods or formulations or by claiming subject matter that could dominate our patent position.
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Thus, any patents that we may own or exclusively license may not provide any protection against competitors.
−Removed: Furthermore, an adverse decision in an interference proceeding can result in a third party receiving the patent right sought by us, which in turn could affect our ability to develop, market or otherwise commercialize CTI-1601, and other potential product candidates.
+Added: Furthermore, an adverse decision in an interference proceeding can result in a third party receiving the patent right sought by us, which in turn could affect our ability to develop, market or otherwise commercialize nomlabofusp, and other potential product candidates.
Furthermore, though an issued patent is presumed valid and enforceable, its issuance is not conclusive as to its validity or its enforceability and it may not provide us with adequate proprietary protection or competitive advantages against competitors with similar products.
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It is difficult to detect infringers who do not advertise the components that are used in their products.
−Removed: Moreover, it may be difficult or impossible to obtain evidence of infringement in a competitor’s or potential competitor’s product.
+Added: Moreover, it may be difficult or impossible to obtain evidence of infringement in a competitor’s or potential competitor’s product.
Any litigation to enforce or defend our patent rights, even if we were to prevail, could be costly and time-consuming and would divert the attention of our management and key personnel from our business operations.
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Such proceedings could also provoke third parties to assert claims against us, including that some or all of the claims in one or more of our patents are invalid or otherwise unenforceable.
−Removed: If any of our patents covering CTI-1601 are invalidated or found unenforceable, our financial
+Added: If any of our patents covering nomlabofusp are invalidated or found unenforceable, our financial
position and results of operations would be materially and adversely impacted.
−Removed: In addition, if a court found that valid, enforceable patents held by third parties covered CTI-1601, our financial position and results of operations would also be materially and adversely impacted.
+Added: In addition, if a court found that valid, enforceable patents held by third parties covered nomlabofusp, our financial position and results of operations would also be materially and adversely impacted.
The degree of future protection for our proprietary rights is uncertain, and we cannot ensure that:
−Removed: any of our patents, or any of our pending patent applications, if issued, will include claims having a scope sufficient to protect CTI-1601 or any other products or product candidates;
+Added: • any of our patents, or any of our pending patent applications, if issued, will include claims having a scope sufficient to protect nomlabofusp or any other products or product candidates;
• any of our pending patent applications will issue as patents;
−Removed: we will be able to successfully develop and, if approved, commercialize CTI-1601 before our relevant patents expire;
+Added: • we will be able to successfully develop and, if approved, commercialize nomlabofusp before our relevant patents expire;
• we were the first to make the inventions covered by each of our patents and pending patent applications;
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Further, our trade secrets could otherwise become known or be independently discovered by our competitors.
−Removed: If we are unable to adequately protect our proprietary technology or maintain issued patents which are sufficient to protect CTI-1601 or potential future product candidates, third parties could compete against us more directly, which would have a material adverse impact on our business, results of operations, financial condition and prospects.
−Removed: Our key patent, which we license relates to CTI-1601 will expire in 2040 and we will lose our ability to rely upon this patent to prevent competing products from entering the market, which may impair our ability to generate revenue.
−Removed: We have in-licensed certain patents relating to CTI-1601 from WFUHS.
−Removed: patents relating to CTI-1601 and its use for the treatment of FA expire in 2024 and 2025, respectively.
−Removed: When these patents expire, we will be unable to use these patents to try to block others from marketing CTI-1601 in the United States We have also in-licensed an issued United State patent and pending non-provisional United States patent applications in the United States and certain foreign countries relating to the composition of CTI-1601 and methods of use from IU.
+Added: If we are unable to adequately protect our proprietary technology or maintain issued patents which are sufficient to protect nomlabofusp or potential future product candidates, third parties could compete against us more directly, which would have a material adverse impact on our business, results of operations, financial condition and prospects.
+Added: Our key patent, which we license relates to nomlabofusp will expire in 2040 and we will lose our ability to rely upon this patent to prevent competing products from entering the market, which may impair our ability to generate revenue.
+Added: We have in-licensed certain patents relating to nomlabofusp from WFUHS.
+Added: patents relating to nomlabofusp and its use for the treatment of FA expire in 2024 and 2025, respectively.
+Added: When these patents expire, we will be unable to use these patents to try to block others from marketing nomlabofusp in the United States We have also in-licensed an issued United States patent and pending non-provisional patent applications in the United States and certain foreign countries relating to the composition of nomlabofusp and methods of use from IU.
This United States patent will expire in 2040 at the earliest.
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We cannot predict whether these patent applications we and our licensors are currently pursuing will issue as patents in any particular jurisdiction or whether the claims of any issued patents will provide sufficient protection from competitors or other third parties.
−Removed: When these various patents, if issued, expire, we will be unable to use the patents to try to block others from marketing CTI-1601 in the United States.
−Removed: We own a certain United States provisional application and certain United States and foreign non-provisional applications relating to our platform technology which, if issued as patents, would be expected to expire in 2041-2043.
−Removed: The provisional application may not be timely converted into a non-provisional application, and we cannot predict whether these provisional applications and non-provisional patent applications will issue as patents in any particular jurisdiction, or whether the claims of any issued patents will provide sufficient protection from
−Removed: competitors or third parties for potential product candidates.
+Added: When these various patents, if issued, expire, we will be unable to use the patents to try to block others from marketing nomlabofusp in the United States.
+Added: We own a certain United States provisional application and certain United States and foreign non-provisional applications and a United States patent relating to our platform technology.
+Added: The United States Patent will expire in 2041 at the earliest, and the pending applications, if issued as patents, would be expected to expire in 2041-2044.
+Added: The provisional application may not be timely converted into a non-provisional application, and we cannot predict
+Added: whether these provisional applications and non-provisional patent applications will issue as patents in any particular jurisdiction, or whether the claims of any issued patents will provide sufficient protection from competitors or third parties for potential product candidates.
When these various patents expire, we will be unable to use the patents to try to block others from marketing products pertaining to our platform technology.
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Once our patents expire, we will be subject to competition from third parties who will be able to use the intellectual property covered by these patents, which could impair our ability to generate revenue and could adversely affect our business, financial condition and results of operations.
−Removed: We may infringe the intellectual property rights of others, which may prevent or delay our product development efforts and stop us from commercializing or may increase the costs of commercializing CTI-1601 or other potential product candidates, if approved.
+Added: We may infringe the intellectual property rights of others, which may prevent or delay our product development efforts and stop us from commercializing or may increase the costs of commercializing nomlabofusp or other potential product candidates, if approved.
Our success will depend in part on our ability to operate without infringing the intellectual property and proprietary rights of third parties.
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The pharmaceutical industry is characterized by extensive litigation regarding patents and other intellectual property rights.
−Removed: Third parties may allege that CTI-1601 or our other potential product candidates or the use of our technologies infringes patent claims or other intellectual property rights held by them or that we are employing their proprietary technology without authorization.
+Added: Third parties may allege that nomlabofusp or our other potential product candidates or the use of our technologies infringes patent claims or other intellectual property rights held by them or that we are employing their proprietary technology without authorization.
Patent and other types of intellectual property litigation can involve complex factual and legal questions, and their outcome is uncertain.
−Removed: Any claim relating to intellectual property infringement that is successfully asserted against us may require us to pay substantial damages, including treble damages and attorneys’
−Removed: fees if we are found to be willfully infringing another party’s patents, for past use of the asserted intellectual property and royalties and other consideration going forward if we are forced to take a license.
+Added: Any claim relating to intellectual property infringement that is successfully asserted against us may require us to pay substantial damages, including treble damages and attorneys’ fees if we are found to be willfully infringing another party’s patents, for past use of the asserted intellectual property and royalties and other consideration going forward if we are forced to take a license.
In addition, we may also be required to indemnify certain of our licensors, vendors or suppliers from any damages they incur related to any infringement of any third party intellectual property by our product candidates.
−Removed: In addition, if any such claim were successfully asserted against us and we could not obtain such a license, we may be forced to stop or delay developing, manufacturing, selling or otherwise commercializing CTI-1601.
+Added: In addition, if any such claim were successfully asserted against us and we could not obtain such a license, we may be forced to stop or delay developing, manufacturing, selling or otherwise commercializing nomlabofusp.
Even if we are successful in these proceedings, we may incur substantial costs and divert management time and attention in pursuing these proceedings, which could have a material adverse effect on us.
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In addition, intellectual property litigation or claims could force us to do one or more of the following:
−Removed: cease developing, selling or otherwise commercializing CTI-1601;
+Added: • cease developing, selling or otherwise commercializing nomlabofusp;
• cease preparations or development of our other potential product candidates;
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Litigation may be necessary to defend against these and other claims challenging inventorship or ownership.
−Removed: If we fail in defending any such claims, in addition to paying monetary
−Removed: damages, we may lose valuable intellectual property rights, such as exclusive ownership of, or right to use, valuable intellectual property.
+Added: If we fail in defending any such claims, in addition to paying monetary damages, we may lose valuable intellectual property rights, such as exclusive ownership of, or right to use, valuable intellectual property.
Such an outcome could have a material adverse effect on our business, financial condition and results of operations.
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PTO, or made a misleading statement, during prosecution.
−Removed: Third parties may also raise similar claims before administrative bodies in the United States or abroad, even outside the context of litigation.
+Added: Third parties may also raise similar claims before administrative bodies in the United States or abroad, even outside the context of
Such mechanisms include re-examination, post grant review and equivalent proceedings in foreign jurisdictions, e.g.
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Such proceedings could result in revocation or amendment of our patents in such a way that they no longer cover our product candidates or competitive products.
−Removed: The outcome following
−Removed: legal assertions of invalidity and unenforceability is unpredictable.
+Added: The outcome following legal assertions of invalidity and unenforceability is unpredictable.
With respect to validity, for example, we cannot ensure that there is no invalidating prior act, of which we and the patent examiner were unaware during prosecution.
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Accordingly, our efforts to enforce our intellectual property rights around the world may be inadequate to obtain a significant commercial advantage from the intellectual property that we develop or license, which would materially adversely affect our business, financial condition and results of operations.
−Removed: We are dependent on licensed intellectual property for CTI-1601.
−Removed: If we were to lose our rights to licensed intellectual property, we may not be able to continue developing or commercializing CTI-1601, if approved.
+Added: We are dependent on licensed intellectual property for nomlabofusp.
+Added: If we were to lose our rights to licensed intellectual property, we may not be able to continue developing or commercializing nomlabofusp, if approved.
We have an exclusive license with WFUHS, pursuant to which we exclusively license certain patent rights relating to the TAT-frataxin fusion protein and its use, on a worldwide basis.
−Removed: We have an exclusive license with IU, pursuant to which we exclusively license certain patent rights relating to CTI-1601 and its use for the treatment of mitochondrial diseases, on a worldwide basis.
+Added: We have an exclusive license with IU, pursuant to which we exclusively license certain patent rights relating to nomlabofusp and its use for the treatment of mitochondrial diseases, on a worldwide basis.
Our license agreements with WFUHS and IU impose, and we expect our future license agreements will impose, various development, diligence, commercialization, and other obligations on us in order to maintain the licenses.
In spite of our efforts, WFUHS, IU, or a future licensor might conclude that we have materially breached our obligations under such license agreements and seek to terminate the license agreements, thereby removing or limiting our ability to develop and commercialize products and technology covered by these license agreements.
−Removed: If these licenses are terminated, or if the underlying patent rights licensed thereunder fail to provide the intended exclusivity, competitors or other third parties would have the freedom to seek regulatory approval of, and to market, products identical to ours and we may be required to cease our development and commercialization of certain of our product candidates or of CTI-1601.
+Added: If these licenses are terminated, or if the underlying patent rights licensed thereunder fail to provide the intended exclusivity, competitors or other third parties would have the freedom to seek regulatory approval of, and to market, products identical to ours and we may be required to cease our development and commercialization of certain of our product candidates or of nomlabofusp.
Any of the foregoing could have a material adverse effect on our competitive position, business, financial conditions, results of operations, and prospects.
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The resolution of any contract interpretation disagreement that may arise could narrow what we believe to be the scope of our rights to the relevant intellectual property or technology or increase what we believe to be our financial or other obligations under the relevant agreement, either of which could have a material adverse effect on our business, financial condition, results of operations, and prospects.
−Removed: Moreover, if disputes over intellectual property that we have licensed prevent or impair our ability to maintain our current licensing arrangements on commercially acceptable terms, we may be unable to successfully develop and commercialize CTI-1601, which could have a material adverse effect on our business, financial conditions, results of operations, and prospects.
−Removed: Some intellectual property may have been discovered through government funded programs and thus may be subject to federal regulations such as “march-in”
−Removed: rights, certain reporting requirements and a preference for U.S.-based companies.
+Added: Moreover, if disputes over intellectual property that we have licensed prevent or impair our ability to maintain our current licensing arrangements on commercially acceptable terms, we may be unable to successfully develop and commercialize nomlabofusp, which could have a material adverse effect on our business, financial conditions, results of operations, and prospects.
+Added: Some intellectual property may have been discovered through government funded programs and thus may be subject to federal regulations such as “march-in” rights, certain reporting requirements and a preference for U.S.-based companies.
Compliance with such regulations may limit our exclusive rights and limit our ability to contract with non-U.S.
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government to use the invention or to have others use the invention on its behalf.
−Removed: government’s rights may also permit it to disclose the funded inventions and technology to third parties and to exercise march-in rights to use or allow third parties to use the technology we have licensed that was developed using U.S.
+Added: government’s rights may also permit it to disclose the funded inventions and technology to third parties and to exercise march-in rights to use or allow third parties to use the technology we have licensed that was developed using U.S.
government funding.
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government of such rights or by any third party of its reserved rights could have a material adverse effect on our competitive position, business, financial condition, results of operations, and prospects.
−Removed: We have not yet registered trademarks for a commercial trade name for CTI-1601 or other potential product candidates and failure to secure such registrations could adversely affect our business, financial condition and results of operations.
−Removed: We have not yet registered trademarks for a commercial trade name for CTI-1601 or other potential product candidates.
+Added: We have not yet registered trademarks for a commercial trade name for nomlabofusp or other potential product candidates and failure to secure such registrations could adversely affect our business, financial condition and results of operations.
+Added: We have not yet registered trademarks for a commercial trade name for nomlabofusp or other potential product candidates.
Any future trademark applications may be rejected during trademark registration proceedings.
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Opposition or cancellation proceedings may be filed against our trademarks, and our trademarks may not survive such proceedings.
−Removed: Moreover, any name we propose to use with our product candidates in the United States must be approved by the FDA, regardless of whether we have registered it, or applied to register it, as a trademark.
−Removed: The FDA typically conducts a review of proposed product names, including an evaluation of potential for confusion with other product names.
−Removed: the FDA objects to any of our proposed proprietary product names, we may be required to expend significant additional resources in an effort to identify a suitable substitute name that would qualify under applicable trademark laws, not infringe the existing rights of third parties and be acceptable to the FDA.
+Added: Moreover, any name we propose to use with our product candidates in the United States must be approved by the FDA, and similarly in many foreign jurisdictions regardless of whether we have registered it, or applied to register it, as a trademark.
+Added: The FDA typically conducts a review of proposed product names, including an
+Added: evaluation of potential for confusion with other product names.
+Added: If the FDA or a foreign regulatory authority objects to any of our proposed proprietary product names, we may be required to expend significant additional resources in an effort to identify a suitable substitute name that would qualify under applicable trademark laws, not infringe the existing rights of third parties and be acceptable to the FDA or other regulatory authorities.
Any trademarks we have obtained or may obtain may be infringed or successfully challenged, resulting in harm to our business.
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Our competitors may infringe our trademarks and we may not have adequate resources to enforce our trademarks.
−Removed: If we do not obtain additional protection under the Hatch-Waxman Amendments and similar foreign legislation by extending the patent terms and obtaining data exclusivity for CTI-1601, our business may be materially harmed.
−Removed: Depending upon the timing, duration and specifics of development and FDA marketing approval of CTI-1601 or our other potential product candidates, one or more of our U.S.
+Added: If we do not obtain additional protection under the Hatch-Waxman Amendments and similar foreign legislation by extending the patent terms and obtaining data exclusivity for nomlabofusp, our business may be materially harmed.
+Added: Depending upon the timing, duration and specifics of development and FDA marketing approval of nomlabofusp or our other potential product candidates, one or more of our U.S.
patents may be eligible for limited patent term restoration under the Drug Price Competition and Patent Term Restoration Act of 1984, (the "Hatch-Waxman Amendments").
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Patent reform legislation could increase the uncertainties and costs surrounding the prosecution of patent applications and the enforcement or defense of issued patents.
−Removed: The Leahy Smith America Invents Act ("the Leahy Smith Act") enacted in September 2011, brought significant changes to the U.S.
+Added: The Leahy Smith America Invents Act ("the Leahy Smith Act") enacted in
+Added: September 2011, brought significant changes to the U.S.
patent law system.
−Removed: These include provisions that affect the
−Removed: way patent applications are prosecuted and may affect patent litigation.
+Added: These include provisions that affect the way patent applications are prosecuted and may affect patent litigation.
The United States Patent Office continues to develop and implement new regulations and procedures to govern administration of the Leahy Smith Act, and many of the substantive changes to patent law associated with the Leahy Smith Act became effective on March 16, 2013.
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PTO and the relevant law-making bodies in other countries, the laws and regulations governing patents could change in unpredictable ways that would weaken our ability to obtain new patents or to enforce our existing patents and patents that we might obtain in the future.
−Removed: We may be subject to damages resulting from claims that we or our employees have wrongfully used or disclosed alleged trade secrets of our employees’
−Removed: former employers.
+Added: We may be subject to damages resulting from claims that we or our employees have wrongfully used or disclosed alleged trade secrets of our employees’ former employers.
Many of our employees have been previously employed at other biotechnology or pharmaceutical companies, including our competitors or potential competitors.
−Removed: Although we are not aware of any claims currently pending against us, we may be subject to claims that we or our employees inadvertently or otherwise used or disclosed the trade secrets or other proprietary information of our employees’
−Removed: former employers.
+Added: Although we are not aware of any claims currently pending against us, we may be subject to claims that we or our employees inadvertently or otherwise used or disclosed the trade secrets or other proprietary information of our employees’ former employers.
Litigation may be necessary to defend against these claims.
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If we fail in defending such claims, in addition to paying monetary claims, we may lose valuable intellectual property rights or personnel.
−Removed: A loss of key personnel or their work product could hamper or prevent our ability to develop and commercialize CTI-1601 or our other potential product candidates, which would materially adversely affect our business, financial condition and results of operations.
+Added: A loss of key personnel or their work product could hamper or prevent our ability to develop and commercialize nomlabofusp or our other potential product candidates, which would materially adversely affect our business, financial condition and results of operations.
Risks Related to Our Common Stock
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• our ability to obtain regulatory approvals for product candidates, and delays or failures to obtain such approvals;
−Removed: the results of, and delays in, current, and any future, non-clinical or clinical trials of CTI-1601 or any of our future product candidates, including any delays related to a resurgence of COVID-19 or other health crises;
−Removed: geopolitical unrest including the potential impact of the war in Ukraine and the possibility that the conflict could expand beyond eastern Europe,
+Added: • the results of, and delays in, current, and any future, non-clinical or clinical trials of nomlabofusp or any of our future product candidates, including any delays related to a future pandemic, epidemic or outbreak of an infectious disease;
+Added: • geopolitical tension, including the potential impact of ongoing conflict between Russia and Ukraine and the current conflict in Israel and Gaza (including any escalation or expansion);
• the entry into, or termination of, key agreements, including key licensing or collaboration agreements;
−Removed: the failure of CTI-1601 or any of our future product candidates, if approved for marketing and commercialization, to achieve commercial success;
+Added: • the failure of nomlabofusp or any of our future product candidates, if approved for marketing and commercialization, to achieve commercial success;
• issues in manufacturing our approved products, if any, or product candidates;
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These broad market fluctuations may also adversely affect the trading price of our common stock.
−Removed: In the past, following periods of volatility in the market price of a company’s securities, stockholders have often instituted class action securities litigation against those companies.
−Removed: Such litigation, if instituted, could result in substantial costs and diversion of management’s attention and resources, which could significantly impact our profitability and reputation.
+Added: In the past, following periods of volatility in the market price of a company’s securities, stockholders have often instituted class action securities litigation against those companies.
+Added: Such litigation, if instituted, could result in substantial costs and diversion of management’s attention and resources, which could significantly impact our profitability and reputation.
Any lawsuit to which we are a party, with or without merit, may result in an unfavorable judgment.
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The rules governing the standards that must be met for our management to assess our internal control over financial reporting pursuant to Section 404 of the Sarbanes-Oxley Act are complex and require significant documentation, testing and possible remediation.
−Removed: These stringent standards require that our audit committee be advised and regularly updated on management’s review of internal control over financial reporting.
+Added: These stringent standards require that our audit committee be advised and regularly updated on management’s review of internal control over financial reporting.
Our management may not be able to effectively and timely implement controls and procedures which respond to the increased regulatory compliance and reporting requirements that are applicable to us as a public company.
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Entities affiliated with Deerfield Management Company beneficially own or control approximately 38.6% of our outstanding common stock (assuming full exercise of our outstanding pre-funded warrants and no exercise of outstanding options) as of December 31, 2023, on a fully-diluted basis.
−Removed: Accordingly, such entities have substantial influence over the outcome of a corporate action by us requiring stockholder approval, including the election of directors, any merger, consolidation or sale of all or substantially all of our assets or any other significant corporate
+Added: Accordingly, such entities have substantial influence over the outcome of a corporate action by us requiring stockholder approval, including the election of directors, any merger, consolidation or sale of all or substantially all of our assets or any other significant corporate transaction.
These stockholders also may exert influence in delaying or preventing a change in control of the combined company, even if such change in control would benefit our other stockholders.
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We cannot be certain whether the reduced disclosure requirements applicable to smaller reporting companies will make our common shares less attractive to investors or otherwise limit our ability to raise additional funds.
−Removed: We are currently a “smaller reporting company”
−Removed: as defined in the Exchange Act of 1934 and have elected to take advantage of certain of the scaled disclosures available to smaller reporting companies, including simplified executive compensation disclosures in our filings, exemption from the provisions of Section 404(b) of the Sarbanes-Oxley Act requiring that an independent registered accounting firm provide an attestation report on the effectiveness of internal control over financial reporting and certain other decreased disclosure obligations in our SEC filings, including, among other things, only being required to provide two years of audited financial statements in annual reports.
+Added: We are currently a “smaller reporting company” as defined in the Exchange Act of 1934 and have elected to take advantage of certain of the scaled disclosures available to smaller reporting companies, including simplified executive compensation disclosures in our filings, exemption from the provisions of Section 404(b) of the Sarbanes-Oxley Act requiring that an independent registered accounting firm provide an attestation report on the effectiveness of internal control over financial reporting and certain other decreased disclosure obligations in our SEC filings, including, among other things, only being required to provide two years of audited financial statements in annual reports.
Reduced disclosure in our SEC filings due to our status as a smaller reporting company may make it harder for investors to analyze our results of operations and financial prospects.
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The current expectation is that we will retain our future earnings to fund the development and growth of our business.
−Removed: As a result, capital appreciation, if any, of our common stock will be stockholders’
−Removed: sole source of gain, if any, for the foreseeable future.
+Added: As a result, capital appreciation, if any, of our common stock will be stockholders’ sole source of gain, if any, for the foreseeable future.
Our failure to meet the continued listing requirements of The Nasdaq Stock Market LLC could result in a delisting of our Common Stock.
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Such a delisting would likely have a negative effect on the price of our common stock and would impair a stockholders ability to sell or purchase shares of common stock when they wish to do so.
−Removed: In the event of a delisting, we can provide no assurance that any action taken by us to restore compliance with listing requirements would allow the common stock to become listed again, stabilize the market price or improve the liquidity of the common stock, prevent the common stock from dropping below the Nasdaq minimum bid price requirement or prevent future noncompliance with Nasdaq’s listing requirements.
+Added: In the event of a delisting, we can provide no assurance that any action taken by us to restore compliance with listing requirements would allow the common stock to become listed again, stabilize the market price or improve the liquidity of the common stock, prevent the common stock from dropping below the Nasdaq minimum bid price requirement or prevent future noncompliance with Nasdaq’s listing requirements.
General Risk Factors
Financial reporting obligations of being a public company in the United States are expensive and time-consuming, and our management will be required to devote substantial time to new compliance matters.
−Removed: The obligations of being a public company in the United States require significant expenditures and place significant demands on our management and other personnel, including costs resulting from public company reporting obligations under the Securities Exchange Act of 1934, as amended, and the rules and regulations regarding corporate governance practices, including those under the Sarbanes-Oxley Act, the Dodd-Frank Wall
−Removed: Street Reform and Consumer Protection Act of 2010 (the "Dodd-Frank Act") and the listing requirements of Nasdaq on which our securities are listed.
+Added: The obligations of being a public company in the United States require significant expenditures and place significant demands on our management and other personnel, including costs resulting from public company reporting obligations under the Securities Exchange Act of 1934, as amended, and the rules and regulations regarding corporate governance practices, including those under the Sarbanes-Oxley Act, the Dodd-Frank Wall Street Reform and Consumer Protection Act of 2010 (the "Dodd-Frank Act") and the listing requirements of Nasdaq on which our securities are listed.
These rules require the maintenance of effective disclosure and financial controls and procedures, internal control over financial reporting and strong corporate governance practices, among many other complex rules that are often difficult to implement, monitor and maintain compliance with.
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Our results of operations could be adversely affected by general conditions in the global economy, geopolitical events and general conditions in the global financial markets.
−Removed: A severe or prolonged economic downturn due to geopolitical unrest resulting from the Russian invasion of Ukraine, the possibility that the conflict could expand beyond eastern Europe as well as the impact of the resurgence of more vaccine resistant or more highly contagious variants of COVID-19 or other health crises, or other factors could result in a variety of risks to our business, including, weakened demand for our product candidates and our ability to raise additional capital when needed on acceptable terms, if at all.
+Added: A severe or prolonged economic downturn due to geopolitical tension resulting from ongoing conflict between Russia and Ukraine and the current conflict in Israel and Gaza (including any escalation or expansion) or other factors could result in a variety of risks to our business, including, weakened demand for our product candidates and our ability to raise additional capital when needed on acceptable terms, if at all.
A weak or declining economy could also strain our suppliers, possibly resulting in supply disruption, or cause our customers to delay making payments for our products.
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Events involving limited liquidity, defaults, non-performance or other adverse developments that affect financial institutions, transactional counterparties or other companies in the financial services industry or the financial services industry generally, or concerns or rumors about any events of these kinds or other similar risks, have in the past and may in the future lead to market-wide liquidity problems.
−Removed: Most recently, on March 10, 2023, Silicon Valley Bank (“SVB”) was closed by the California Department of Financial Protection and Innovation, which appointed the Federal Deposit Insurance Corporation (“FDIC”) as receiver.
−Removed: Similarly, on March 12, 2023, Signature Bank and Silvergate Capital Corp.
−Removed: were each swept into receivership.
+Added: For example, in early 2023, several financial institutions closed and were taken into receivership by the Federal Deposit Insurance Corporation
Although we assess our banking and customer relationships as we believe necessary or appropriate, our access to funding sources and other credit arrangements in amounts adequate to finance or capitalize our current and projected future business operations could be significantly impaired by factors that affect us, the financial services industry or economy in general.
−Removed: These factors could include, among others, events such as liquidity constraints or failures, the ability to perform obligations
−Removed: under various types of financial, credit or liquidity agreements or arrangements, disruptions or instability in the financial services industry or financial markets, or concerns or negative expectations about the prospects for companies in the financial services industry.
+Added: These factors could include, among others, events such as liquidity constraints or failures, the ability to perform obligations under various types of financial, credit or liquidity agreements or arrangements, disruptions or instability in the financial services industry or financial markets, or concerns or negative expectations about the prospects for companies in the financial services industry.
In addition, investor concerns regarding the U.S.
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Any of these impacts, or any other impacts resulting from the factors described above or other related or similar factors not described above, could have material adverse impacts on our liquidity and our business, financial condition or results of operations.
−Removed: UNRESOLVED STAFF COMMENTS
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.