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Our clinical trials have been funded by approximately $171.0 million in cumulative nondilutive grants, awarded primarily by the National Institute of Aging, or NIA, a division of the National Institutes of Health.
−Removed: On October 13, 2021, we closed our initial public offering, or IPO, whereby we received net proceeds of $37.9 million, excluding net proceeds from the overallotment exercise.
−Removed: On November 12, 2021, the Company received $6.3 million of net proceeds resulting from the exercise of the overallotment option.
+Added: On October 13, 2021, we completed our initial public offering, or IPO, whereby we received net proceeds of $37.9 million.
+Added: On November 12, 2021, we received an additional $6.3 million in net proceeds resulting from the exercise of the overallotment option held by the underwriters in our IPO.
+Added: On November 15, 2022, we completed a follow-on public offering whereby we received net proceeds of $5.2 million.
We have no products approved for commercialization and have never generated any revenue from product sales.
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● conduct our ongoing and planned clinical trials of CT1812, as well as initiate and complete additional clinical trials;
−Removed: ● pursue regulatory approval of CT1812 for the treatment of mild-to-moderate Alzheimer’s disease, or AD, dry age-related macular degeneration, or dry AMD, and Parkinson’s disease, or PD, and dementia with Lewy bodies, or DLB, and other age-related degenerative diseases and disorders of the central nervous system, or CNS, and retina;
−Removed: ● seek to discover and develop additional clinical and preclinical product candidates using Novel Improved Conditioned Extraction, or NICE, screening platform;
+Added: ● pursue regulatory approval of CT1812 for the treatment of mild-to-moderate Alzheimer’s disease, or AD, dry age-related macular degeneration, or GA secondary to dry AMD, and Parkinson’s disease, or PD, and dementia with Lewy bodies, or DLB, and other age-related degenerative diseases and disorders of the central nervous system, or CNS, and retina;
+Added: ● seek to discover and develop additional clinical and preclinical product candidates from libraries generated using Novel Improved Conditioned Extraction, or NICE, screening platform, as well as other molecule generating and screening strategies;
● adapt our regulatory compliance efforts to incorporate requirements applicable to marketed products;
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Even if we achieve profitability, we may not be able to sustain or increase profitability on a quarterly or annual basis.
+Added: Because of the numerous risks and uncertainties associated with therapeutic development, we are unable to accurately predict the timing or amount of increased expenses or when, or if, we will be able to achieve profitability.
+Added: If we are required by the FDA to perform studies in addition to those we currently anticipate, or if there are any delays in completing our clinical trials or the development of our candidates or any future therapeutic candidates, our expenses could increase beyond our current expectations and revenue could be further delayed.
+Added: Even if we or any future collaborators do generate sales, we may never achieve, sustain or increase profitability on a quarterly or annual basis.
+Added: Our failure to sustain profitability would depress the market price of our stock and could impair our ability to raise capital, expand our business, diversify our therapeutic offerings or continue our operations.
+Added: If we continue to suffer losses, investors may not receive any return on their investment and may lose their entire investment.
Our failure to become and remain profitable would depress the value of our company and could impair our ability to raise capital, expand our business, maintain our development efforts, obtain product approvals, diversify our offerings or continue our operations.
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We have not yet completed Phase 2 clinical trials and have no history of commercializing products, which may make it difficult for an investor to evaluate the success of our business to date and to assess our future viability.
−Removed: We commenced operations in 2007, and our operations to date have been largely focused on developing our clinical and preclinical product candidates and our Novel, Improved Conditioned Extraction, or NICE, screening platform, or NICE screening platform.
+Added: We commenced operations in 2007, and our operations to date have been largely focused on developing our clinical and preclinical product candidates and our NICE screening platform.
To date, we have not yet demonstrated our ability to successfully complete pivotal clinical trials, obtain regulatory approvals, manufacture a product on a commercial scale, or arrange for a third party to do so on our behalf, or conduct sales and marketing activities necessary for successful commercialization.
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Our operations have required substantial amounts of capital since inception, and we expect our expenses to increase significantly in the foreseeable future.
−Removed: Identifying potential product candidates and conducting preclinical testing and clinical trials is a time-consuming, expensive and uncertain process that takes years to complete, and we may never generate the necessary data or results required to obtain regulatory approval and achieve product sales.
−Removed: We expect to continue to incur significant expenses and operating losses over the next several years as we complete our ongoing clinical trials of our product candidates, initiate future clinical trials of our product candidates, seek marketing approval for CT1812 for the treatment of age-related degenerative diseases and disorders of the CNS and retina, such as AD, dry AMD, PD and DLB, and advance any of our other product candidates we may develop or otherwise acquire.
+Added: Identifying potential product candidates and conducting preclinical testing and clinical trials is a time-consuming, expensive and uncertain process that takes years to complete, and we may never
+Added: generate the necessary data or results required to obtain regulatory approval and achieve product sales.
+Added: We expect to continue to incur significant expenses and operating losses over the next several years as we complete our ongoing clinical trials of our product candidates, initiate future clinical trials of our product candidates, seek marketing approval for CT1812 for the treatment of age-related degenerative diseases and disorders of the CNS and retina, such as AD, GA secondary to dry AMD, PD and DLB, and advance any of our other product candidates we may develop or otherwise acquire.
In addition, our product candidates, if approved, may not achieve commercial success.
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As of December 31, 2022, we had $41.6 million in cash and cash equivalents and have not generated positive cash flows from operations.
−Removed: Based on our current business plans, we believe that the net proceeds from our IPO, together with our existing cash and cash equivalents and income from our non-dilutive grants, will be sufficient for us to fund our operating expenses and capital expenditures requirements into the second half of 2023.
+Added: Based on our current business plans, we believe that our existing cash and cash equivalents and income from our non-dilutive grants will be sufficient for us to fund our operating expenses and capital expenditures requirements into the second half of 2024.
We have based these estimates on assumptions that may prove to be incorrect or require adjustment as a result of business decisions, and we could utilize our available capital resources sooner than we currently expect.
Our future capital requirements will depend on many factors, including, but not limited to :
−Removed: ● the scope, progress, costs and results of our ongoing and planned clinical trials of CT1812, as well as the associated costs, including any unforeseen costs we may incur as a result of preclinical study or clinical trial delays due to the COVID-19 pandemic or other delays;
+Added: ● the scope, progress, costs and results of our ongoing and planned clinical trials of CT1812, as well as the associated costs, including any unforeseen costs we may incur as a result of preclinical study or clinical trial delays due to supply chain disruptions or other delays ;
● the scope, progress, costs and results of preclinical development, laboratory testing and clinical trials for any future product candidates we may decide to pursue;
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● the costs and timing of process development and manufacturing scale-up activities associated with our product candidates and other programs we advance them through preclinical and clinical development;
−Removed: ● the availability, timing and receipt of any future NIA Grants;
+Added: ● the availability, timing and receipt of any future non-dilutive grants from the NIA, or NIA Grants;
● the number and development requirements of other product candidates that we may pursue;
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● our ability to establish collaborations to commercialize CT1812 or any of our other product candidates outside the United States;
+Added: ● macroeconomic factors such as inflationary pressures, rising interest rates, liquidity constraints, failures and instability in U.S.
+Added: and international financial banking systems, supply disruptions due to political unrest, conflict and war or other factors, and pandemics such as the COVID-19 pandemic;
● the costs and timing of preparing, filing and prosecuting patent applications, maintaining and enforcing our intellectual property rights and defending any intellectual property-related claims;
● the additional costs we may incur as a result of operating as a public company, including our efforts to enhance operational systems and hire additional personnel, including enhanced internal controls over financial reporting.
−Removed: We believe the net proceeds from our IPO will not be sufficient to fund any of our product candidates through regulatory approval, and we will need to raise substantial additional capital to complete the development and commercialization of C1812 and our product candidates.
+Added: We believe our existing cash and cash equivalents and income from our non-dilutive grants will not be sufficient to fund any of our product candidates through regulatory approval, and we will need to raise substantial additional capital to complete the development and commercialization of C1812 and our product candidates.
If we receive regulatory approval for any of these product candidates, we expect to incur significant commercialization expenses related to product manufacturing, sales, marketing and distribution, depending on where we choose to commercialize.
Additional funds may not be available on a timely basis, on favorable terms, or at all, and such funds, if raised, may not be sufficient to enable us to continue to implement our long-term business strategy.
−Removed: Further, our ability to raise additional capital may be adversely impacted by recent volatility in the equity markets in the United States and worldwide resulting from the ongoing COVID-19 pandemic.
+Added: Further, our ability to raise additional capital may be adversely impacted by recent volatility in the equity markets
+Added: in the United States and worldwide resulting from the ongoing COVID-19 pandemic.
If we are unable to raise sufficient additional capital, we could be forced to curtail our planned operations and the pursuit of our growth strategy .
+Added: The economic environment may make it difficult to raise capital on acceptable terms or at all.
+Added: Our ability to raise additional funds when needed and on acceptable terms or at all will depend on financial, economic and market conditions and other factors, over which we may have no or limited control.
+Added: For example, the continued challenging capital markets environment, lower prices for many securities and concerns about potential recessionary factors may affect our ability to raise additional funding through sales of our securities or issuance of indebtedness, which may harm our liquidity, force us to delay, limit or terminate certain or all of our product discovery, therapeutic development, research operations or commercialization planning efforts or cause us to grant rights to develop and market products or therapeutic candidates that we would otherwise prefer to develop and market ourselves.
+Added: If adequate funds are not available on commercially acceptable terms when needed, we may be forced to delay, reduce or terminate the development or commercialization of all or part of our research programs or our product candidates or any future therapeutic candidate, or we may be unable to take advantage of future business opportunities.
+Added: Market volatility, liquidity constraints, failures and instability in U.S and international financial banking systems, geopolitical tensions resulting from the ongoing war between Ukraine and Russia, heightened or fluctuating inflation and interest rates and the related impact on U.S.
+Added: and global economies or other economic or other factors could also adversely impact our ability to access capital as and when needed or increase our costs in order to raise capital.
+Added: We cannot guarantee that future financing will be available in sufficient amounts, or on commercially reasonable terms, or at all.
+Added: Current capital market conditions, including the impact of inflation, have increased borrowing rates and can be expected to significantly increase our cost of capital as compared to prior periods.
+Added: Moreover, the terms of any financing may adversely affect the holdings or the rights of our stockholders, the issuance of additional securities, whether equity or debt, by us, or the possibility of such issuance, may cause the market price of our stock to decline.
+Added: The incurrence of indebtedness could 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.
+Added: We could also be required to seek funds through arrangements with collaborators or others at an earlier stage than otherwise would be desirable and we may be required to relinquish rights to our product candidates or any future therapeutics candidates or otherwise agree to terms unfavorable to us, any of which may have a material adverse effect on our business, operating results and prospects.
To date, we have partially relied on non-dilutive grants to cover certain of our capital requirements for our clinical trials, and we may fail to continue to receive non-dilutive funding.
−Removed: To date, we have partially relied on the availability of non-dilutive grants from the NIA, or NIA Grants.
−Removed: Although we currently anticipate applying for and potentially receiving additional NIA Grants, we cannot be certain that our grant applications will be successful, that additional NIA Grants will be made available to support our clinical trials or that we will continue to satisfy the award criteria of prior NIA Grants that have already been awarded to us.
+Added: To date, we have partially relied on the availability of NIA Grants.
+Added: Although we have applied for and currently anticipate receiving additional NIA Grants, we cannot be certain that our grant applications will be successful, that additional NIA Grants will be made available to support our clinical trials or that we will continue to satisfy the award criteria of prior NIA Grants that have already been awarded to us.
If we fail to continue to receive NIA Grants, our ability to continue our clinical programs for CT1812 may be impaired and delayed, and we may otherwise need to seek additional financing through dilutive methods, such as through equity or debt financings.
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Additionally, negative results in any of our ongoing and planned clinical trials of CT1812 that are funded with NIA Grants may result in our failure to receive additional NIA Grants to fund future clinical trials.
−Removed: The NIA recently issued guidance providing extensions and flexibility for certain NIA Grant recipients conducting NIA-funded clinical trials and human subject studies that are impacted by the declared public health emergency for the COVID-19 pandemic.
−Removed: The ultimate impact of the COVID-19 pandemic on our clinical trials is highly uncertain and subject to change.
−Removed: We have not made a formal assessment with respect to the NIA’s current and expanded flexibilities in light of the COVID-19 pandemic, but we continue to monitor the situation closely and are prepared to take all necessary steps to ensure the safety of all human participants and research staff involved in our clinical trials.
Due to the significant resources required for the development of our product candidates, we must prioritize development of certain product candidates and/or certain disease indications.
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We seek to maintain a process of prioritization and resource allocation among our programs to maintain a balance between aggressively advancing our lead product candidate, CT1812, in identified indications and exploring additional indications or mechanisms as well as developing future product candidates.
−Removed: However, due to the significant resources required for the development of our product candidates, we must focus on specific diseases and disease pathways and decide which product candidates to pursue and the amount of resources to allocate to each such product candidate.
+Added: However, due to the significant resources required for the development of our product candidates, we must focus on specific diseases and disease pathways and decide which product candidates to pursue from time to time and the amount of time and resources to allocate to each such product candidate.
Our decisions concerning the allocation of research, development, collaboration, management and financial resources toward particular product candidates or therapeutic areas may not lead to the development of any viable commercial product and may divert resources away from better opportunities.
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Such a stock price decline could occur even when we have met any previously publicly stated revenue or earnings guidance we may provide .
−Removed: Our business has been, and could continue to be adversely affected by, the ongoing COVID-19 global pandemic and the efforts to mitigate it in regions where we or third parties on which we rely have significant manufacturing facilities, concentrations of clinical trial sites or other business operations.
−Removed: The COVID-19 pandemic could adversely affect our business and our financial results and could cause a disruption to the development of our product candidates, as well as the business or operations of our manufacturers or other third parties with whom we conduct business.
−Removed: Our business has been and could continue to be adversely affected by the effects of the evolving and ongoing COVID-19 pandemic, which was declared by the World Health Organization as a global pandemic.
−Removed: As COVID-19, including any new strains or variants of COVID-19, continue to spread, we may experience ongoing disruptions that could severely impact our business and clinical trials, including:
−Removed: ● delays or difficulties in enrolling and retaining patients in our clinical trials;
−Removed: ● delays or difficulties in clinical site initiation, including difficulties in recruiting clinical site investigators and clinical site staff;
−Removed: ● delays in clinical sites receiving the supplies and materials needed to conduct our clinical trials, interruption of, or delays in receiving, supplies of our product candidates from our contract manufacturing organizations due to staffing shortages, production slowdowns, or stoppages and disruptions in materials and reagents or interruptions in global shipping that may affect the transport of clinical trial materials;
−Removed: ● changes in federal and local regulations as part of a response to the COVID-19 outbreak which may require us to change the ways in which our clinical trials are conducted, which may result in unexpected costs, or to discontinue the clinical trials altogether;
−Removed: ● the diversion of healthcare resources away from the conduct of clinical trials, including the diversion of healthcare professionals and other staff involved in our clinical trials and healthcare facilities serving as clinical trial sites;
−Removed: ● the interruption of key clinical trial activities, such as clinical trial site monitoring, due to limitations on travel imposed or recommended by federal or state governments, employers and others, or interruption of clinical trial subject visits and study procedures, the occurrence of which could affect the integrity of clinical trial data;
−Removed: ● limitations on employee resources that would otherwise be focused on the conduct of our preclinical studies and clinical trials, including because of sickness of employees or their families or the desire of employees to avoid contact with large groups of people, an increased reliance on working from home, school closures, or mass transit disruptions;
−Removed: ● limitations on maintaining our corporate culture that facilitates the transfer of institutional knowledge within our organization and fosters innovation, teamwork, and a focus on execution;
−Removed: ● interruption of or delays in the operations of the FDA or other regulatory authorities, which may impact review and approval timelines;
−Removed: ● delays in necessary interactions with regulators, ethics committees, and other important agencies and contractors due to limitations in employee resources or forced furlough of government or contractor personnel;
−Removed: ● additional delays, difficulties or interruptions as a result of current or future shutdowns due to the COVID-19 pandemic in countries where we or our third-party service providers operate;
−Removed: ● the risk that participants enrolled in our clinical trials or study staff conducting the clinical trial visits will acquire COVID-19 while the clinical trial is ongoing, which could impact the results of the clinical trial, including by increasing the number of observed adverse events, or the ability to complete study visits and collect data.
−Removed: These and other disruptions in our operations and the global economy could negatively impact our business, operating results and financial condition.
−Removed: Our clinical trials have been, and may in the future be, affected by the COVID-19 pandemic.
−Removed: For example, the COVID-19 pandemic may impact patient enrollment in our ongoing and future clinical trials of CT1812.
−Removed: In particular, some sites have in the past or may in the future pause enrollment to focus on, and direct resources to, COVID-19, while at other sites, patients may choose not to enroll or continue participating in the clinical trial as a result of the pandemic.
−Removed: In addition, patient visits to medical providers in the United States have slowed as a result of the COVID-19 pandemic.
−Removed: Further, according to the Centers for Disease Control and Prevention, people who have serious chronic medical conditions are at higher risk of getting very sick from COVID-19.
−Removed: As a result, potential patients in our ongoing and future clinical trials of CT1812 may choose to not enroll, not participate in follow-up clinical visits or drop out of the trial as a precaution against contracting COVID-19.
−Removed: Further, some patients may not be able or willing to comply with clinical trial protocols if quarantines impede patient movement or interrupts healthcare services.
−Removed: We are unable to predict with confidence the duration of such patient enrollment delays and difficulties.
−Removed: If patient enrollment is delayed for an extended period of time, our ongoing or future clinical trials could be delayed or otherwise adversely affected.
−Removed: Similarly, our ability to recruit and retain principal investigators and site staff who, as healthcare providers, may have heightened exposure to COVID-19, including any new strains or variants of COVID-19, may be adversely impacted.
−Removed: Ongoing or planned clinical trials may also be impacted by interruptions or delays in the operations of the FDA and comparable foreign regulatory authorities.
−Removed: For example, we have made certain adjustments to the
−Removed: operation of our trials in an effort to ensure the monitoring and safety of patients and minimize risks to trial integrity during the pandemic in accordance with the guidance issued by the FDA, and may need to make further adjustments in the future.
−Removed: We have also initiated our clinical trial protocols to enable remote visits to mitigate any potential impacts as a result of the COVID-19 pandemic.
−Removed: Many of these adjustments are new, may not be effective, may affect the integrity of data collected, and may have unforeseen effects on the progress and completion of our clinical trials and the findings from such clinical trials.
−Removed: In addition, we may encounter a shortage in supplies of, or in delays in shipping, our study drug or other components of the clinical trial vital for successful conduct of the trial.
−Removed: Further, the successful conduct of our ongoing and future clinical trials depends on retrieving laboratory, imaging and other data from patients.
−Removed: Any failure by the vendors with which we work with to send us such data could impair the progress of such clinical trials.
−Removed: These events could delay our clinical trials, increase the cost of completing our clinical trials and negatively impact the integrity, reliability or robustness of the data from our clinical trials.
−Removed: Furthermore, quarantines, shelter-in-place and similar government orders, or the perception that such orders, shutdowns or other restrictions on the conduct of business operations could occur, related to COVID-19, including any new strains or variants of COVID-19, or other infectious diseases, could impact personnel at our study sites or third-party manufacturing facilities upon which we rely, or the availability or cost of materials, which could disrupt the supply chain for our drug and combination therapy candidates.
−Removed: To the extent our suppliers and service providers are unable to comply with their obligations under our agreements with them or they are otherwise unable to deliver or are delayed in delivering goods and services to us due to the COVID-19 pandemic, our ability to continue meeting clinical supply demand for our product candidates or otherwise advancing development of our product candidates may become impaired.
−Removed: The spread of COVID-19, including any new strains or variants of COVID-19, and actions taken to reduce such spread may also materially affect us economically.
−Removed: While the potential economic impact brought by, and the duration of, the COVID-19 pandemic may be difficult to assess or predict, there could be a significant disruption of global financial markets, reducing our ability to access capital, which could in the future negatively affect our liquidity and financial position.
−Removed: In addition, the trading prices for other pharmaceutical companies have been highly volatile as a result of the COVID-19 pandemic.
−Removed: As a result, we may face difficulties raising capital through sales of our common stock or such sales may be on unfavorable terms.
−Removed: COVID-19, including any new strains or variants of COVID-19, and actions taken to reduce its spread continue to rapidly evolve.
−Removed: The extent to which COVID-19 may impede the development of our product candidates, reduce the productivity of our employees, disrupt our supply chains, delay our clinical trials, reduce our access to capital or limit our business development activities, will depend on future developments, which are highly uncertain and cannot be predicted with confidence.
−Removed: To the extent the ongoing COVID-19 pandemic adversely affects our business and results of operations, it may also have the effect of heightening many of the other risks and uncertainties described in this “Risk Factors” section .
Risks Related to Discovery, Development and Regulatory Approval of Our Product Candidates
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● whether we are required by the U.S.
−Removed: Food and Drug Administration, or FDA, or similar foreign regulatory agencies to conduct additional clinical trials or other studies beyond those planned to support the approval and commercialization of our product candidates or any future product candidates;
+Added: Food and Drug Administration, or FDA, or similar foreign regulatory agencies to conduct additional clinical trials or other studies beyond those planned to support the approval and commercialization of our product candidates or any future product candidates, if approved;
● acceptance of our proposed indications and primary endpoint assessments relating to the proposed indications of our product candidates by the FDA and similar foreign regulatory authorities;
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● our ability to achieve sufficient market acceptance, coverage and adequate reimbursement from third-party payors and adequate market share and revenue for any approved products;
−Removed: ● the COVID-19 pandemic, which may result in clinical site closures, delays to patient enrollment, patients discontinuing their treatment or follow up visits or changes to trial protocols;
+Added: ● supply chain disruptions, which may result in clinical site closures, delays to patient enrollment or changes to trial protocols;
● our ability to successfully develop a commercial strategy and thereafter commercialize our product candidates or any future product candidates in the United States and internationally, if approved for marketing, reimbursement, sale and distribution in such countries and territories, whether alone or in collaboration with others;
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We may not successfully expand our pipeline of product candidates, including by pursuing additional indications for CT1812 or by in-licensing or acquiring additional product candidates for other diseases.
−Removed: A key element of our strategy is to build and expand our pipeline of product candidates, including by developing CT1812 for the treatment of dry AMD and age-related degenerative diseases and disorders of the CNS beyond indications in AD, and by identifying other product candidates using our NICE platform.
+Added: A key element of our strategy is to build and expand our pipeline of product candidates, including by developing CT1812 for the treatment of GA secondary to dry AMD and age-related degenerative diseases and disorders of the CNS beyond indications in AD, and by identifying other product candidates from libraries created using our NICE platform as
+Added: well as new molecule and screening strategies.
In addition, we may in-license or acquire additional product candidates for other diseases.
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Clinical trials can be delayed or terminated for a variety of reasons, including delays or failures related to:
−Removed: ● the COVID-19 pandemic, which may result in clinical site closures, delays to patient enrollment, patients discontinuing their treatment or follow up visits or changes to trial protocols;
+Added: ● supply chain disruptions, which may result in clinical site closures, delays to patient enrollment or changes to trial protocols;
● the FDA or comparable foreign regulatory authorities disagreeing as to the design or implementation of our clinical trials;
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● patient referral practices of physicians;
−Removed: ● risk that enrolled subjects will drop out before completion of the trial, including as a result of contracting COVID-19 or other health conditions or being forced to quarantine;
+Added: ● risk that enrolled subjects will drop out before completion of the trial, including as a result of contracting health conditions;
● ability to monitor patients adequately during and after treatment;
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If unacceptable side effects arise in the development of our product candidates, we, the FDA, the IRBs at the institutions in which our studies are conducted or the data safety monitoring board, or DSMB could suspend or terminate our clinical trials or the FDA or comparable foreign regulatory authorities could order us to cease clinical trials or deny approval of our product candidates for any or all targeted indications.
−Removed: Treatment-related side effects may not be appropriately
−Removed: recognized or managed by the treating medical staff.
+Added: Treatment-related side effects may not be appropriately recognized or managed by the treating medical staff.
We expect to have to train medical personnel using our product candidates to understand the side effect profiles for our clinical trials and upon any commercialization of any of our product candidates.
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The historical failure rate for product candidates in our industry is high.
−Removed: The results from preclinical studies or clinical trials of a product candidate may not predict the results of later clinical trials of the product candidate, and interim, topline, or preliminary results of a clinical trial are not
−Removed: necessarily indicative of final results.
+Added: The results from preclinical studies or clinical trials of a product candidate may not predict the results of later clinical trials of the product candidate, and interim, topline, or preliminary results of a clinical trial are not necessarily 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 preclinical studies and initial clinical trials.
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A number of companies in the biopharmaceutical, pharmaceutical and biotechnology industries have suffered significant setbacks in clinical development even after achieving promising results in earlier studies.
−Removed: For the foregoing reasons, we cannot be certain that any of our ongoing and planned preclinical studies or clinical trials will be successful or acceptable to the FDA or other regulatory authorities .
+Added: Additionally, some of our past clinical trials have utilized an “open-label” trial design.
+Added: An “open-label” clinical trial is one where both the patient and investigator know whether the patient is receiving the investigational product candidate or either an existing approved drug or placebo.
+Added: Most typically, open-label clinical trials test only the investigational product candidate and sometimes may do so at different dose levels.
+Added: Open-label clinical trials are subject to various limitations that may exaggerate any therapeutic effect as patients in open-label clinical trials are aware when they are receiving treatment.
+Added: Open-label clinical trials may be subject to a “patient bias” where patients perceive their symptoms to have improved merely due to their awareness of receiving an experimental treatment.
+Added: In addition, open-label clinical trials may be subject to an “investigator bias” where those assessing and reviewing the physiological outcomes of the clinical trials are aware of which patients have received treatment and may interpret the information of the treated group more favorably given this knowledge.
+Added: The results from an open-label trial may not be predictive of future clinical trial results with any of our product candidates when studied in a controlled environment with a placebo or active control.
+Added: For all of the foregoing reasons, we cannot be certain that any of our ongoing and planned preclinical studies or clinical trials will be successful or acceptable to the FDA or other regulatory authorities .
Interim “top-line” and preliminary data from studies or trials that we announce or publish from time to time may change as more data become available and are subject to audit and verification procedures that could result in material changes in the final data.
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Efforts by biopharmaceutical and pharmaceutical companies in treating AD have seen limited success in drug development.
−Removed: Only one disease-modifying therapeutic option has been approved by the FDA.
−Removed: Biogen’s Aduhelm, a monoclonal antibody administered via infusion, received accelerated approval from the FDA on June 7, 2021.
−Removed: We cannot be certain that our oral, small-molecule approach will lead to the development of approvable or marketable
−Removed: With the exception of Aduhelm, the only drugs approved by the FDA to treat patients with AD address the symptoms of the disease.
−Removed: Since 2003, over 500 clinical studies have been completed and only Aduhelm has been approved by the FDA, compared to a success rate of 50% to 80% for all other drug candidates.
+Added: Only two disease-modifying therapeutic option has been approved by the FDA.
+Added: Specifically, Biogen’s Aduhelm received accelerated approval on June 7, 2021 and the FDA granted accelerated approval to Eisai’s Leqembi on January 6, 2023.
+Added: Aduhelm and Leqembi are monoclonal antibodies administered via infusion reported to reduce Aβ plaques and protofibrils.
+Added: We cannot be certain that our oral, small-molecule approach will lead to the development of approvable or marketable products.
+Added: With the exception of Aduhelm and Leqembi, the only drugs approved by the FDA to treat patients with AD address the symptoms of the disease.
As a result, the FDA has a limited set of products to rely on in evaluating CT1812.
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We have never conducted pivotal clinical trials, and we may be unable to do so for any product candidates we may develop.
−Removed: We will need to successfully complete pivotal clinical trials in order to obtain the approval of the FDA, EMA or other regulatory agencies to market CT1812 or any future product candidate.
+Added: We will need to successfully complete pivotal clinical trials in order to obtain the approval of the FDA, the European Medicines Agency, or EMA, or other regulatory agencies to market CT1812 or any future product candidate.
Carrying out pivotal clinical trials is a complicated process that requires significant financial resources.
−Removed: As an organization, we have not previously conducted any later stage or pivotal clinical trials.
+Added: organization, we have not previously conducted any later stage or pivotal clinical trials.
In order to do so, we will need to expand our clinical development and regulatory capabilities, and we may be unable to recruit and train qualified personnel.
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We may require more time and incur greater costs than our competitors and may not succeed in obtaining regulatory approvals of product candidates that we develop.
−Removed: Failure to commence or complete, or delays in, our planned clinical trials, could prevent us from or delay us in commercializing our product candidates.
+Added: Failure to commence or complete, or delays in, our planned clinical trials, could prevent us from or delay us in commercializing our product candidates, if approved.
A Breakthrough Therapy designation by the FDA, even if granted for any of our product candidates, may not lead to a faster development or regulatory review or approval process, and it does not increase the likelihood that our product candidates will receive marketing approval.
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Even if we believe a particular product candidate is eligible for this designation, we cannot assure you that the FDA would decide to grant it.
−Removed: Fast Track designation may not result in a faster development
−Removed: process, review or approval compared to conventional FDA procedures.
+Added: Fast Track designation may not result in a faster development process, review or approval compared to conventional FDA procedures.
The FDA may withdraw Fast Track designation if it believes that the designation is no longer supported by data from our clinical development program.
1 unchanged sentence
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
+Added: 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.
Average review times at the FDA have fluctuated in recent years as a result.
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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: On March 18, 2020, the FDA announced its intention to temporarily postpone routine surveillance inspections of domestic manufacturing facilities.
+Added: Since March 2020, when foreign and domestic inspections of facilities were largely placed on hold, the FDA has been working to resume pre-pandemic levels of inspection activities, including routine surveillance, bioresearch monitoring and pre-approval inspections.
Regulatory authorities outside the United States may adopt similar restrictions or other policy measures in response to the COVID-19 pandemic.
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In addition, the Phase 1 single and multiple ascending dose studies of CT1812 in healthy volunteers (COG0101) as well as the first-in-patient study (COG0102) were conducted in Australia.
+Added: We have opened additional clinical trial site in the Netherlands and are opening sites in the Czech Republic and Spain for our SHINE study.
The acceptance of study data from clinical trials conducted outside the United States or another jurisdiction by the FDA, any comparable foreign regulatory authority may be subject to certain conditions or may not be accepted at all.
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medical practice;
−Removed: ● the trials were performed pursuant to good clinical practice, or GCP, requirements;
−Removed: ● if necessary, the FDA is able to validate the data through an on-site inspection.
+Added: ● the trials were performed by clinical investigators of recognized competence, or GCP, requirements;
+Added: ● the data may be considered valid without the need for an on-site inspection by the FDA or, if the FDA considers such as inspection to be necessary, the FDA is able to validate the data through an on-site inspection or other appropriate means.
Many foreign regulatory authorities have similar requirements.
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There can be no assurance that the FDA or any comparable foreign regulatory authority will accept data from trials conducted outside of the United States or the applicable jurisdiction.
−Removed: If the FDA or any comparable foreign regulatory authority does not accept such data, it would result in the need for additional trials, which would be costly and time-consuming and delay
−Removed: aspects of our business plan, and which may result in product candidates that we may develop not receiving approval or clearance for commercialization in the applicable jurisdiction .
+Added: If the FDA or any comparable foreign regulatory authority does not accept such data, it would result in the need for additional trials, which would be costly and time-consuming and delay aspects of our business plan, and which may result in product candidates that we may develop not receiving approval or clearance for commercialization in the applicable jurisdiction .
If we are not successful in identifying, developing and commercializing additional product candidates, our ability to expand our business and achieve our strategic objectives would be impaired.
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A component of our strategy is to evaluate our product candidates in multiple indications based, in part, on our evaluation of certain biomarkers in a disease area.
−Removed: For example, we intend to evaluate CT1812 and other product candidates discovered through our NICE platform in other diseases beyond indications in AD, such as dry AMD, geographic atrophy, or GA, and synucleinopathies, including PD and DLB.
+Added: For example, we intend to evaluate CT1812 and other product candidates discovered through our NICE platform in other diseases beyond indications
+Added: in AD, such as GA secondary to dry AMD, and synucleinopathies, including PD and DLB.
However, we may find that while we have seen promising results in one neurodegenerative disease, that effect is not replicated across other indications with promising similarities.
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● the research methodology used may not be successful in identifying potential product candidates;
−Removed: ● we may be unable to identify viable product candidates through our NICE platform;
+Added: ● we may be unable to identify viable product candidates through our NICE platform and other molecule generating and screening strategies;
● competitors may develop alternatives that render our additional product candidates obsolete;
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In some cases, the intended price for such product is also subject to approval.
−Removed: Further, while regulatory approval of a product candidate in one country does not ensure approval in any other country, a failure or delay in obtaining regulatory approval in one
−Removed: country may have a negative effect on the regulatory approval process in others.
+Added: Further, while regulatory approval of a product candidate in one country does not ensure approval in any other country, a failure or delay in obtaining regulatory approval in one country may have a negative effect on the regulatory approval process in others.
If we or any future collaborators fail to comply with the regulatory requirements in international markets or to obtain all required marketing approvals, the target market for a particular potential product will be reduced, which would limit our ability to realize the full market potential for the product and adversely affect our business.
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We have not submitted an NDA to the FDA or comparable applications to other regulatory authorities for CT1812 and may not be in a position to do so for several years, if ever.
−Removed: If we are unable to obtain the necessary regulatory approvals for CT1812, we will not be able to commercialize CT1812 in AD, dry AMD, PD and DLB or other age-related degenerative diseases and disorders of the CNS and retina, and our financial position will be materially adversely affected and we may not be able to generate sufficient revenue to continue our business .
+Added: If we are unable to obtain the necessary regulatory approvals for CT1812, we will not be able to commercialize CT1812 in AD, GA secondary to dry AMD, PD and DLB or other age-related degenerative diseases and disorders of the CNS and retina, and our financial position will be materially adversely affected and we may not be able to generate sufficient revenue to continue our business .
We will need to increase the size of our organization, and we may experience difficulties in managing growth.
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We will need to continue to expand our managerial, operational, finance and other resources in order to manage our operations and clinical trials, continue our development activities and commercialize CT1812, our lead product candidate, or any future product candidates.
−Removed: Our management and personnel, systems and facilities currently in place may not be adequate to support this future growth.
+Added: Our management and personnel, systems and facilities currently in place may not be adequate to support this future growth and we expect will lead to increasing costs.
Our need to effectively execute our growth strategy requires that we:
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We may not be able to attract and retain quality personnel on acceptable terms, or at all.
+Added: The expansion of our operations may lead to significant costs and may divert our management and business development resources.
+Added: Any inability to manage growth or raise funds to support our growth could delay the execution of our business plans or disrupt our operations.
In addition, to the extent we hire personnel from competitors, we may be 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 .
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We collect and maintain information in digital and other forms that is necessary to conduct our business, and we are increasingly dependent on information technology systems and infrastructure to operate our business.
−Removed: ordinary course of our business, we collect, store and transmit large amounts of confidential information, including intellectual property, proprietary business information and personal information.
+Added: In the ordinary course of our business, we collect, store and transmit large amounts of confidential information, including
+Added: intellectual property, proprietary business information and personal information.
It is critical that we do so in a secure manner to maintain the privacy, security, confidentiality and integrity of such confidential information.
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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: As a result of the COVID-19 pandemic, we may face increased risks of a security breach or disruption due to our reliance on internet technology and the number of our employees who are working remotely, which may create additional opportunities for cybercriminals to exploit vulnerabilities.
+Added: We may face increased risks of a security breach or disruption due to our reliance on internet technology and the number of our employees who work on a hybrid basis, at home and in the office.
+Added: This may create additional opportunities for cybercriminals to exploit vulnerabilities.
The costs to us to investigate, mitigate and remediate security incidents, breaches, disruptions, network security problems, bugs, viruses, worms, malicious software programs and security vulnerabilities could be significant.
In November 2021 we were the subject of a phishing scheme involving a fraudulent email and wire instructions, resulting in the loss of approximately $0.5 million in corporate funds.
−Removed: We took immediate action to contain and eradicate the security breach, including the implementation of control enhancements to prevent a similar situation from occurring again.
+Added: We took immediate action to contain and eradicate the security breach, including the implementation of control enhancements in an effort to prevent a similar situation from occurring again.
We also subsequently submitted a claim for the loss under our cyber-security insurance policy whereby we received net proceeds of $0.5 million.
We believe this was an isolated event and do not believe our technology systems have been compromised.
−Removed: While we have not experienced any other losses relating to cyber-attacks or other information security breaches such as the one that occurred in November 2021, there can be no assurance (i) that we will ever recover the funds lost, (ii) that our insurance carriers will honor our claim and make a payment to us under our cyber-security policy, or (iii) that we will not suffer additional losses in the future.
+Added: While we have not experienced any other losses relating to cyber-attacks or other information security breaches such as the one that occurred in November 2021, there can be no assurance that we will ever recover the funds lost or that we will not suffer additional losses in the future.
Additionally, while we have implemented security measures to protect our data security and information technology systems, our efforts to address these problems may not be successful, and these problems could result in unexpected interruptions, delays, cessation of service, negative publicity and other harm to our business and our competitive position.
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Failure to comply with health and data protection laws and regulations could lead to government enforcement actions and civil or criminal penalties, private litigation or adverse publicity and could negatively affect our operating results and business.
−Removed: We are subject to or affected by federal, state and foreign data protection laws and regulations which address privacy and data security.
+Added: We are subject to or affected by federal, state and foreign data protection laws and regulations that address privacy and data security.
In the United States, numerous federal and state laws and regulations, including the U.S.
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Many similar privacy laws have been proposed at the federal level and in other states.
−Removed: Foreign data protection laws, including Regulation 2016/679, known as the General Data Protection Regulation, or GDPR, may also apply to health-related and other personal information data subjects in the EU or the United Kingdom, or UK.
+Added: Foreign data protection laws, including Regulation 2016/679, known as the General Data Protection Regulation, or GDPR, may also apply to health-related and other personal information data subjects in the European Union or the United Kingdom.
The GDPR went into effect on May 25, 2018.
Companies that must comply with the GDPR face increased compliance obligations and risk, including robust regulatory enforcement of data protection requirements as well as potential fines for noncompliance of up to €20 million or 4% of annual global revenue of the noncompliance company, whichever is greater.
−Removed: The GDPR imposes numerous requirements for the collection, use, storage and disclosure of personal information of EU or UK data subjects, including requirements relating to providing notice to and obtaining consent from data subjects, personal data breach notification, cross-border transfers of personal information, and honoring and providing for the rights of EU or UK individuals in relation to their personal information, including the right to access, correct and delete their data.
+Added: The GDPR imposes numerous requirements for the collection, use, storage and disclosure of personal information of European Union or United Kingdom data subjects, including requirements relating to providing notice to and obtaining consent from data subjects, personal data breach notification, cross-border transfers of personal information, and honoring and providing for the rights of European Union or United Kingdom individuals in relation to their personal information, including the right to access, correct and delete their data.
Compliance with U.S.
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The patent position of biotechnology and pharmaceutical companies generally is highly uncertain, involves complex legal and factual questions, and has in recent years been the subject of much litigation.
−Removed: The standards that the USPTO and its foreign counterparts use to grant patents are not always applied predictably or uniformly.
+Added: The standards that the U.S.
+Added: Patent and Trademark Office, or USPTO, and its foreign counterparts use to grant patents are not always applied predictably or uniformly.
In addition, the laws of foreign countries may not protect our rights to the same extent as the laws of the United States, and many companies have encountered significant problems in protecting and defending such rights in foreign jurisdictions.
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Patent reform legislation in the United States, including the Leahy-Smith America Invents Act, or the Leahy-Smith Act, could increase those uncertainties and costs surrounding the prosecution of our patent applications and the enforcement or defense of our issued patents.
−Removed: The Leahy-Smith Act was signed into law on September 16, 2011
−Removed: and includes a number of significant changes to U.S.
−Removed: These include provisions that affect the way patent applications are prosecuted, redefine prior art and provide more efficient and cost-effective avenues for competitors to challenge the validity of patents.
+Added: The Leahy-Smith Act was signed into law on September 16, 2011 and includes a number of significant changes to U.S.
+Added: These include provisions that affect the way
+Added: patent applications are prosecuted, redefine prior art and provide more efficient and cost-effective avenues for competitors to challenge the validity of patents.
These include allowing third-party submission of prior art to the USPTO during patent prosecution and additional procedures to attack the validity of a patent by USPTO administered post-grant proceedings, including post-grant review, inter partes review, and derivation proceedings.
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Moreover, in foreign jurisdictions where we do have patent rights, proceedings to enforce such rights could result in substantial costs and divert our efforts and attention from other aspects of our business, could put our patents at risk of being invalidated or interpreted narrowly, and our patent applications at risk of not issuing.
−Removed: Additionally, such
−Removed: proceedings could provoke third parties to assert claims against us.
−Removed: We may not prevail in any lawsuits that we initiate and the damages or other remedies awarded, if any, may not be commercially meaningful.
+Added: Additionally, such proceedings could provoke third parties to assert claims against us.
+Added: We may not prevail in any lawsuits that we
+Added: initiate and the damages or other remedies awarded, if any, may not be commercially meaningful.
Thus, we may not be able to stop a competitor from marketing and selling in foreign countries products and services that are the same as or similar to our products and services, and our competitive position in the international market would be harmed.
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Various extensions may be available, but the life of a patent, and the protection it affords, is limited.
−Removed: In the United States, a patent’s term may be lengthened by patent term adjustment, which compensates a patentee for administrative delays by the U.S.
−Removed: Patent and Trademark Office, or USPTO, in examining and granting a patent, or may be shortened if a patent is terminally disclaimed over an earlier filed patent.
+Added: In the United States, a patent’s term may be lengthened by patent term adjustment, which compensates a patentee for administrative delays by the USPTO in examining and granting a patent, or may be shortened if a patent is terminally disclaimed over an earlier filed patent.
Even if patents covering our product candidates are obtained, once the patent life has expired, we may be open to competition from competitive products, including generics or biosimilars.
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Depending upon the timing, duration and specifics of FDA marketing approval of our drug candidates, one or more of our U.S.
−Removed: patents may be eligible for limited patent term extension, or PTE, under the Drug Price Competition and Patent Term Restoration Act of 1984, referred to as the Hatch-Waxman Amendments.
+Added: patents may be eligible for limited patent term extension, or PTE, under the Drug Price Competition and Patent Term Restoration Act of 1984, or the Hatch-Waxman Amendments.
The Hatch-Waxman Amendments permit a patent restoration term of up to five years beyond the normal expiration of the patent as compensation for patent term lost during development and the FDA regulatory review process, which is limited to the approved indication (and potentially additional indications approved during the period of extension) covered by the patent.
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Depending upon the timing, duration and specifics of FDA marketing approval of our drug candidates, certain of our product candidates may be eligible for marketing exclusivity.
−Removed: The FDCA provides a five-year period of non-patent marketing exclusivity within the United States to the first applicant to obtain approval of an NDA for a new chemical entity, or NCE.
+Added: The Food, Drug and Cosmetic Act, or FDCA, provides a five-year period of non-patent marketing exclusivity within the United States to the first applicant to obtain approval of an NDA for an NCE.
A drug is an NCE if the FDA has not previously approved any other new drug containing the same active moiety, which is the molecule or ion responsible for the action of the drug substance.
If market exclusivity is granted for an NCE, during the exclusivity period, the FDA may not accept for review or approve an abbreviated new drug application, or ANDA, or a 505(b)(2) NDA submitted by another company for another version of such drug where the applicant does not own or have a legal right of reference to all the data required for approval.
−Removed: However, an application may be submitted after four years if it contains a certification of patent invalidity or non-infringement to one of the patents listed in the FDA’s publication Approved Drug Products with Therapeutic Equivalence Evaluations , which we refer to as the Orange Book, with the FDA by the innovator NDA holder.
+Added: However, an application may be submitted after four years if it contains a certification of patent invalidity or non-infringement to one of the patents listed in the Orange Book, with the FDA by the innovator NDA holder.
The FDCA also provides three years of marketing exclusivity for an NDA, or supplement to an existing NDA if new clinical investigations, other than bioavailability studies, that were conducted or sponsored by the applicant are deemed by the FDA to be essential to the approval of the application, for example new indications, dosages, dosage forms or strengths of an existing drug.
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A certification that the new drug will not infringe the Orange Book-listed patents for the applicable approved drug candidate, or that such patents are invalid, is called a paragraph IV certification.
−Removed: If the third party submits a paragraph IV certification to the FDA, a notice of the paragraph IV certification must also be sent to us
−Removed: once the third party’s ANDA is accepted for filing by the FDA.
−Removed: We may then initiate a lawsuit to defend the patents identified in the notice.
+Added: If the third party submits a paragraph IV certification to the FDA, a notice of the paragraph IV certification must also be sent to us once the third party’s ANDA is accepted for filing by the FDA.
+Added: We may then initiate a lawsuit to defend the
+Added: patents identified in the notice.
The filing of a patent infringement lawsuit within 45 days of receipt of the notice automatically prevents the FDA from approving the third party’s ANDA until the earliest of 30 months or the date on which the patent expires, the lawsuit is settled, or the court reaches a decision in the infringement lawsuit in favor of the third party.
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The risks described elsewhere pertaining to our intellectual property rights also apply to any intellectual property rights that we may in-license, and any failure by us or our potential licensors to obtain, maintain, defend and enforce these rights could harm our business.
−Removed: In some cases we may not have control over the prosecution, maintenance or enforcement of the patents that we may license, and may not have sufficient ability to provide input into the patent prosecution, maintenance and defense process with respect to such patents, and our potential
−Removed: licensors may fail to take the steps that we believe are necessary or desirable in order to obtain, maintain, defend and enforce the licensed patents .
+Added: In some cases we may not have control over the prosecution, maintenance or enforcement of the patents that we may license, and may not have sufficient ability to provide input into the patent prosecution, maintenance and defense process with respect to such patents, and our potential licensors may fail to take the steps that we believe are necessary or desirable in order to obtain, maintain, defend and enforce the licensed patents .
Third-party claims or litigation alleging infringement of patents or other proprietary rights, or seeking to invalidate patents or other proprietary rights, may delay or prevent the development and commercialization of any of our product candidates including our lead product candidate, CT1812.
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Our reliance on third parties requires us to share our trade secrets, which increases the possibility that a competitor will discover them or that our trade secrets will be misappropriated or disclosed.
−Removed: Because we expect to rely on third parties to manufacture our product candidates, and we expect to continue to collaborate with third parties on the development of our product candidates, we must, at times, share trade secrets with them.
+Added: Because we expect to rely on third parties to manufacture our product candidates and expect to continue to collaborate with third parties on the development of our product candidates, we must, at times, share trade secrets with them.
We seek to protect our proprietary technology in part by entering into confidentiality agreements and, if applicable, material transfer agreements, consulting agreements or other similar agreements with our advisors, employees, third-party contractors and consultants prior to beginning research or disclosing proprietary information.
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The market opportunities for CT1812, if approved, may be smaller than we anticipate.
−Removed: We expect to initially seek approval for CT1812 for AD, dry AMD, PD and DLB and other age-related degenerative diseases and disorders of the CNS and retina.
+Added: We expect to initially seek approval for CT1812 for AD, GA secondary to dry AMD, PD and DLB and other age-related degenerative diseases and disorders of the CNS and retina.
Our estimates of market potential have been derived from a variety of sources, including scientific literature, patient foundations and market research and may prove to be incorrect.
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In addition, we have limited control over the ability of our contract manufacturers to maintain adequate quality control, quality assurance and qualified personnel.
−Removed: If the FDA or a comparable foreign regulatory authority finds these facilities inadequate for the manufacture of our product candidates or if such facilities are subject to enforcement action in the future or are otherwise inadequate, we may need to find alternative manufacturing facilities, which would significantly impact our ability to develop, obtain regulatory approval for or market our product candidates.
+Added: If the FDA or a comparable foreign regulatory authority finds these facilities inadequate for the manufacture of our product candidates or if such facilities are subject to enforcement action in the future or are otherwise inadequate, we may need to find alternative manufacturing facilities, which we may not be able to do on reasonable terms, if at all,, which would significantly impact our ability to develop, obtain regulatory approval for or market our product candidates.
+Added: In some cases, the technical skills required to manufacture our product candidates may be unique or proprietary to the original manufacturer and we may have difficulty, or there may be contractual restrictions prohibiting us from, transferring such skills to a back-up or alternate supplier, or we may be unable to transfer such skills at all.
+Added: In addition, if we are required to change CMOs for any reason, we will be required to verify that the new manufacturer maintains facilities and procedures that comply with quality standards and with all applicable regulations.
+Added: 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.
+Added: In addition, changes in manufacturers often involve changes in manufacturing procedures and processes, which could require that we conduct bridging studies between our prior clinical supply used in our clinical trials and that of any new manufacturer.
+Added: We may be unsuccessful in demonstrating the comparability of clinical supplies which could require the conduct of additional clinical trials.
We currently rely on third parties at key stages in our supply chain.
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We have not yet engaged any manufacturers for the commercial supply of our product candidates.
−Removed: Although we intend to enter into such agreements prior to commercial launch of any of our product candidates, we may be unable to enter into any such agreement or do so on commercially reasonable terms, which could have a material adverse impact upon our business.
−Removed: Moreover, if there is a disruption to one or more of our third-party manufacturers’ or suppliers’ relevant operations, or if we are unable to enter into arrangements for the commercial supply of our product candidates, we will have no other means of producing our product candidates until they restore the affected facilities or we or they procure alternative manufacturing facilities or sources of supply.
+Added: Although we intend to enter into such agreements prior to commercial launch of any of our product candidates, if approved, we may be unable to enter into any such agreement or do so on commercially reasonable terms, which could have a material adverse impact upon our business.
+Added: Moreover, if there is a disruption to one or more of our third-party manufacturers’ or suppliers’ relevant operations, or if we are unable to enter into arrangements for the commercial supply of our product candidates, if approved, we will have no other means of producing our product candidates until they restore the affected facilities or we or they procure alternative manufacturing facilities or sources of supply.
Our ability to progress our preclinical and clinical programs could be materially and adversely impacted if any of the third-party suppliers upon which we rely were to experience a significant business challenge, disruption or failure due to issues such as financial difficulties or bankruptcy, issues relating to other customers such as regulatory or quality compliance issues, or other financial, legal, regulatory or reputational issues.
Additionally, any damage to or destruction of our third-party manufacturers’ or suppliers’ facilities or equipment may significantly impair our ability to manufacture our product candidates on a timely basis.
−Removed: In addition, to manufacture our product candidates in the quantities which we believe would be required to meet anticipated market demand, our third-party manufacturers would likely need to increase manufacturing capacity and we may need to secure alternative sources of commercial supply, which could involve significant challenges and may require additional regulatory approvals.
−Removed: In addition, the development of commercial-scale manufacturing capabilities may require us and our third-party manufacturers to invest substantial additional funds and hire and retain the technical personnel who have the necessary manufacturing experience.
+Added: In addition, to manufacture our product candidates in the quantities we believe would be required to meet anticipated market demand, our third-party manufacturers would likely need to increase manufacturing capacity and we may need to secure alternative sources of commercial supply, which could involve significant challenges and may require additional regulatory approvals.
+Added: In addition, the development of commercial- scale manufacturing capabilities may require us and our third-party manufacturers to invest substantial additional funds and hire and
+Added: retain the technical personnel who have the necessary manufacturing experience.
Neither we nor our third-party manufacturers may successfully complete any required increase to existing manufacturing capacity in a timely manner, or at all.
−Removed: If our manufacturers or we are unable to purchase the raw materials necessary for the manufacture of our product candidates on acceptable terms, at sufficient quality levels or in adequate quantities, if at all, the commercial launch of our product candidates would be delayed or there would be a shortage in supply, which would impair our ability to generate revenues from the sale of such product candidates, if approved .
+Added: If our manufacturers or we are unable to purchase the raw materials necessary for the manufacture of our product candidates on acceptable terms, at sufficient quality levels or in adequate quantities, if at all, the commercial launch of our product candidates, if approved, would be delayed or there would be a shortage in supply, which would impair our ability to generate revenues from the sale of such product candidates, if approved .
Our product candidates have never been manufactured on a commercial scale, and there are risks associated with scaling up manufacturing to commercial scale.
In particular, we will need to develop a larger scale manufacturing process that is more efficient and cost-effective to commercialize our potential products, which may not be successful.
−Removed: Our product candidates have never been manufactured on a commercial scale, and there are risks associated with scaling up manufacturing to commercial scale including, among others, cost overruns, potential problems with
−Removed: process scale-up, process reproducibility, stability issues, lot consistency and timely availability of raw materials.
+Added: Our product candidates have never been manufactured on a commercial scale, and there are risks associated with scaling up manufacturing to commercial scale including, among others, cost overruns, potential problems with process scale-up, process reproducibility, stability issues, lot consistency and timely availability of raw materials.
There is no assurance that our third-party manufacturers will be successful in establishing a larger-scale commercial manufacturing process for our product candidates which achieves our objectives for manufacturing capacity and cost of goods.
In addition, there is no assurance that our third-party manufacturers will be able to manufacture our product candidates to specifications acceptable to the FDA or other regulatory authorities, to produce it in sufficient quantities to meet the requirements for the potential launch of such products or to meet potential future demand.
−Removed: Our failure to properly or adequately scale scaling up manufacturing for commercial scale would adversely affect our business, results of operations and financial condition .
+Added: Our failure to properly or adequately scale up manufacturing for commercial scale would adversely affect our business, results of operations and financial condition .
We rely on third parties in the conduct of all of our clinical trials.
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This could be difficult, costly or impossible, and our preclinical studies or clinical trials may need to be extended, delayed, terminated or repeated.
−Removed: As a result we may not be able to obtain regulatory approval in a timely fashion, or at all, for the applicable product candidate, our business, financial results and the commercial prospects for our product candidates would be harmed, our costs could increase, and our ability to generate revenues could be delayed .
+Added: As a result we may not be able to obtain
+Added: regulatory approval in a timely fashion, or at all, for the applicable product candidate, our business, financial results and the commercial prospects for our product candidates would be harmed, our costs could increase, and our ability to generate revenues could be delayed .
We face significant competition in an environment of rapid technological and scientific change, and there is a possibility that our competitors may achieve regulatory approval before us or develop therapies that are safer, more advanced or more effective than ours, which may negatively impact our ability to successfully market or commercialize any product candidates we may develop and ultimately harm our financial condition.
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We may face competition with respect to any of our product candidates that we seek to develop or commercialize in the future from major pharmaceutical companies, specialty pharmaceutical companies, and biotechnology companies worldwide.
−Removed: Potential competitors also include academic institutions,
−Removed: government agencies, and other public and private research organizations that conduct research, seek patent protection, and establish collaborative arrangements for research, development, manufacturing, and commercialization.
+Added: Potential competitors also include academic institutions, government agencies, and other public and private research organizations that conduct research, seek patent protection, and establish collaborative arrangements for research, development, manufacturing, and commercialization.
There are a number of large pharmaceutical and biotechnology companies that are currently pursuing the development of product candidates for the treatment of the diseases and disorders for which we have research programs, including AD, dry AMD, PD and DLB.
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The availability of our competitors’ products could limit the demand, and the price we are able to charge, for any products that we may develop and commercialize.
−Removed: See “Risks Related to Our Intellectual Property.” The successful commercialization of our product candidates will depend in part on the extent to which governmental authorities and health insurers establish adequate coverage, reimbursement levels and pricing policies.
+Added: See “Risks Related to Our Intellectual Property.” The successful commercialization of our product candidates will depend in part on the extent to which governmental authorities and health insurers establish
+Added: adequate coverage, reimbursement levels and pricing policies.
Failure to obtain or maintain coverage and adequate reimbursement for our product candidates, if approved, could limit our ability to market those products and decrease our ability to generate revenue .
−Removed: The successful commercialization of our product candidates will depend in part on the extent to which governmental authorities and health insurers establish adequate coverage, reimbursement levels and pricing policies.
+Added: The successful commercialization of our product candidates, if approved, will depend in part on the extent to which governmental authorities and health insurers establish adequate coverage, reimbursement levels and pricing policies.
Failure to obtain or maintain coverage and adequate reimbursement for our product candidates, if approved, could limit our ability to market those drugs and decrease our ability to generate revenue.
The availability and adequacy of coverage and reimbursement by governmental healthcare programs such as Medicare and Medicaid, private health insurers and other third-party payors are essential for most patients to be able to afford prescription medications such as our product candidates, if approved.
−Removed: Our ability to achieve acceptable levels of coverage and reimbursement for products by governmental authorities, private health insurers and other organizations will have an effect on our ability to successfully commercialize our product candidates.
−Removed: Even if we obtain coverage for our product candidates by a third-party payor, the resulting reimbursement payment
−Removed: rates may not be adequate or may require co-payments that patients find unacceptably high.
−Removed: We cannot be sure that coverage and reimbursement in the United States, the European Union or elsewhere will be available for our product candidates or any product that we may develop, and any reimbursement that may become available may be decreased or eliminated in the future.
+Added: Our ability to achieve acceptable levels of coverage and reimbursement for products by governmental authorities, private health insurers and other organizations will have an effect on our ability to successfully commercialize our product candidates, if approved.
+Added: Even if we obtain coverage for our product candidates, if approved, by a third-party payor, the resulting reimbursement payment rates may not be adequate or may require co-payments that patients find unacceptably high.
+Added: We cannot be sure that coverage and reimbursement in the United States, the European Union or elsewhere will be available for our product candidates, if approved, or any product that we may develop, and any reimbursement that may become available may be decreased or eliminated in the future.
Third-party payors increasingly are challenging prices charged for biopharmaceutical products and services, and many third-party payors may refuse to provide coverage and reimbursement for particular drugs or biologics when an equivalent generic drug, biosimilar or a less expensive therapy is available.
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These payors may deny or revoke the reimbursement status of a given product or establish prices for new or existing marketed products at levels that are too low to enable us to realize an appropriate return on our investment in our product candidates.
−Removed: If reimbursement is not available or is available only at limited levels, we may not be able to successfully commercialize our product candidates and may not be able to obtain a satisfactory financial return on our investment in the development of product candidates.
+Added: If reimbursement is not available or is available only at limited levels, we may not be able to successfully commercialize our product candidates, if approved, and may not be able to obtain a satisfactory financial return on our investment in the development of product candidates.
There is significant uncertainty related to the insurance coverage and reimbursement of newly- approved products.
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In many countries, the prices of medical products are subject to varying price control mechanisms as part of national health systems.
−Removed: Other countries allow companies to fix their own prices for medical products, but monitor and control company profits.
+Added: Other countries allow companies to fix their own prices for medical
+Added: products, but monitor and control company profits.
Additional foreign price controls or other changes in pricing regulation could restrict the amounts that we are able to charge for our product candidates.
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We currently do not have a marketing or sales organization.
−Removed: In order to commercialize our product candidates in the United States and foreign jurisdictions, we must build our marketing, sales, distribution, managerial and other non-technical capabilities or make arrangements with third parties to perform these services, and we may not be successful in doing so.
+Added: In order to commercialize our product candidates, if approved, in the United States and foreign jurisdictions, we must build our marketing, sales, distribution, managerial and other non-technical capabilities or make arrangements with third parties to perform these services, and we may not be successful in doing so.
If any of our product candidates receive regulatory approval, we expect to establish a sales organization with technical expertise and supporting distribution capabilities to commercialize each such product candidate, which will be expensive and time consuming.
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Healthcare legislation, including potentially unfavorable pricing regulations or other healthcare reform initiatives, may increase the difficulty and cost for us to obtain marketing approval of and commercialize our product candidates.
−Removed: The United States and many foreign jurisdictions have enacted or proposed legislative and regulatory changes affecting the healthcare system.
−Removed: 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 products.
+Added: The United States and many foreign jurisdictions have enacted or proposed legislative and regulatory changes affecting the healthcare system, including 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 products.
In recent years, Congress has considered reductions in Medicare reimbursement levels for products administered by physicians.
−Removed: CMS, the agency that administers the Medicare and Medicaid programs, also has authority to revise reimbursement rates and to implement coverage restrictions for some products.
+Added: The Centers for Medicare & Medicaid Services, or CMS, the agency that administers the Medicare and Medicaid programs, also has authority to revise reimbursement rates and to implement coverage restrictions for some products.
Cost reduction initiatives and changes in coverage implemented through legislation or regulation could decrease utilization of and reimbursement for any approved products.
2 unchanged sentences
The Patient Protection and Affordable Care Act, as amended by the Health Care and Education Affordability Reconciliation Act, or collectively the Affordable Care Act substantially changed the way healthcare is financed by both governmental and private insurers, and significantly impacts the pharmaceutical industry.
−Removed: The Affordable Care Act is intended to broaden access to health insurance, reduce or constrain the growth of healthcare spending, enhance remedies against healthcare fraud and abuse, add new transparency requirements for healthcare and health insurance industries, impose new taxes and fees on pharmaceutical and medical device manufacturers, and impose additional health policy reforms.
+Added: The Affordable Care Act is intended to broaden access to health insurance, reduce or constrain the growth of healthcare spending, enhance remedies against healthcare fraud and abuse, add new transparency requirements for healthcare and health insurance industries, impose new taxes and fees on pharmaceutical and medical device manufacturers, and impose additional health policy
Among other things, the Affordable Care Act expanded manufacturers’ rebate liability under the Medicaid Drug Rebate Program by increasing the minimum Medicaid rebate for both branded and generic products, expanded the 340B program, and revised the definition of average manufacturer price, or AMP, which could increase the amount of Medicaid rebates manufacturers are required to pay to states.
3 unchanged sentences
Since that time, there have been significant ongoing efforts to modify or eliminate the Affordable Care Act.
−Removed: 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 of 1986, as amended, or the Code, commonly referred to as the individual mandate.
+Added: 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 of 1986, as amended, or the Code or the individual mandate.
Other legislative changes have been proposed and adopted since the passage of the Affordable Care Act.
−Removed: The Budget Control Act of 2011, among other things, created the Joint Select Committee on Deficit Reduction to recommend proposals in spending reductions to Congress.
+Added: The Budget Control Act of 2011, among other things, created the Joint Select Committee on Deficit Reduction, or the Joint Select Committee, to recommend proposals in spending reductions to Congress.
The Joint Select Committee did not achieve its targeted deficit reduction of an amount greater than $1.2 trillion for the fiscal years 2012 through 2021, triggering the legislation’s automatic reductions to several government programs.
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Subsequent legislation extended the 2% reduction, on average, to 2030 unless additional Congressional action is taken.
−Removed: However, pursuant to the Coronavirus Aid, Relief and Economic Security Act, or CARES Act, the 2% Medicare sequester reductions were suspended from May 1, 2020 through December 31, 2021 due to the COVID-19 pandemic.
+Added: However, pursuant to the Coronavirus Aid, Relief and Economic Security Act, or CARES Act, the 2% Medicare sequester reductions were suspended from May 1, 2020 through March 31, 2022 due to the COVID-19 pandemic.
+Added: As of July 2, 2022, the 2% sequester reduction resumed.
The sequester will remain in place through 2030.
On January 2, 2013, the American Taxpayer Relief Act was signed into law, 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: The Affordable Care Act has also been subject to challenges in the courts.
+Added: The Inflation Reduction Act of 2022 contains substantial drug pricing reforms, including the establishment of a drug price negotiation program within the U.S.
+Added: Department of Health and Human Services that would require manufacturers to charge a negotiated “maximum fair price” for certain selected drugs or pay an excise tax for noncompliance, the establishment of rebate payment requirements on manufacturers of certain drugs payable under Medicare Parts B and D to penalize price increases that outpace inflation, and requires manufacturers to provide discounts on Part D drugs.
+Added: Substantial penalties can be assessed for noncompliance with the drug pricing provisions in the Inflation Reduction Act of 2022.
+Added: The Inflation Reduction Act of 2022 could have the effect of reducing the prices we can charge and reimbursement we receive for our products, if approved, thereby reducing our profitability, and could have a material adverse effect on our financial condition, results of operations and growth prospects.
+Added: The effect of Inflation Reduction Act of 2022 on our business and the pharmaceutical industry in general is not yet known.
+Added: The Affordable Care Act, or ACA, has also been subject to challenges in the courts.
On December 14, 2018, a Texas U.S.
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Further changes to and under the Affordable Care Act remain possible but it is unknown what form any such changes or any law proposed to replace or revise the Affordable Care Act would take, and how or whether it may affect our business in the future.
−Removed: We expect that changes to the Affordable Care Act, the Medicare and Medicaid programs, changes allowing the federal government to directly negotiate 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.
+Added: We expect that changes to the Affordable Care Act, the Medicare and Medicaid programs 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.
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.
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If we develop a small molecule product candidate that obtains regulatory approval, additional competitors could enter the market with generic versions of such drugs, which may result in a material decline in sales of affected products.
−Removed: Under the Drug Price Competition and Patent Term Restoration Act of 1984, or the Hatch-Waxman Act, a pharmaceutical manufacturer may file an abbreviated new drug application, or ANDA, seeking approval of a generic version of an approved, small molecule innovator product.
+Added: Under the Hatch-Waxman Act, a pharmaceutical manufacturer may file an ANDA seeking approval of a generic version of an approved, small molecule innovator product.
Under the Hatch-Waxman Act, a manufacturer may also submit an NDA, under section 505(b)(2) of the Federal Food, Drug, and Cosmetic Act that references the FDA’s prior approval of the small molecule innovator product.
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The Hatch-Waxman Act also provides for certain periods of regulatory exclusivity, which preclude FDA approval (or in some circumstances, FDA filing and review) of an ANDA or 505(b)(2) NDA.
−Removed: In addition to the benefits of regulatory exclusivity, an innovator NDA holder may have patents claiming the active ingredient, product formulation or an approved use of the drug, which would be listed with the product in the FDA publication, “Approved Drug Products with Therapeutic Equivalence Evaluations,”
−Removed: known as the Orange Book.
−Removed: If there are patents listed in the Orange Book for a product, a generic or 505(b)(2) applicant that seeks to market its product before expiration of the patents must include in their applications what is known as a “Paragraph IV” certification, challenging the validity or enforceability of, or claiming non-infringement of, the listed patent or patents.
+Added: In addition to the benefits of regulatory exclusivity, an innovator NDA holder may have patents claiming the active ingredient, product formulation or an approved use of the drug, which would be listed with the product in the Orange Book.
+Added: If there are patents listed in the Orange Book for a product, a generic or 505(b)(2) applicant that seeks to market its product before expiration of the patents must include in their applications a paragraph IV certification, challenging the validity or enforceability of, or claiming non-infringement of, the listed patent or patents.
Notice of the certification must be given to the patent owner and NDA holder and if, within 45 days of receiving notice, either the patent owner or NDA holder sues for patent infringement, approval of the ANDA or 505(b)(2) NDA is stayed for up to 30 months.
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A person or entity does not need to have actual knowledge of the statute or specific intent to violate it in order to have committed a violation;
−Removed: civil False Claims Act (which can be enforced through “qui tam,” or whistleblower actions, by private citizens on behalf of the federal government), prohibits any person from, among other things, knowingly presenting, or causing to be presented false or fraudulent claims for payment of government funds or knowingly making, using or causing to be made or used, a false record or statement material to an obligation to pay money to the government or knowingly and improperly avoiding, decreasing or concealing an obligation to pay money to the U.S.
+Added: False Claims Act (which can be enforced through “qui tam,” or whistleblower actions, by private citizens on behalf of the federal government), prohibits any person from, among other things, knowingly presenting, or causing to be presented false or fraudulent claims for payment of government funds or knowingly making, using or causing to be made or used, a false record or statement material to an obligation to pay money to the government or knowingly and improperly avoiding, decreasing or concealing an obligation to pay money to the U.S.
federal government ;
−Removed: federal Health Insurance Portability and Accountability Act of 1996, or HIPAA, which imposes criminal liability and amends provisions on the reporting, investigation, enforcement, and penalizing of civil liability for, among other things, knowingly and willfully executing, or attempting to execute, a scheme to defraud any healthcare benefit program, or knowingly and willfully falsifying, concealing or covering up a material fact or making any materially false statement, in connection with the delivery of, or payment for healthcare benefits, items or services by a healthcare benefit program, which includes both government and privately funded benefits programs;
+Added: ● HIPAA , which imposes criminal liability and amends provisions on the reporting, investigation, enforcement, and penalizing of civil liability for, among other things, knowingly and willfully executing, or attempting to execute, a scheme to defraud any healthcare benefit program, or knowingly and willfully falsifying, concealing or covering up a material fact or making any materially false statement, in connection with the delivery of, or payment for healthcare benefits, items or services by a healthcare benefit program, which includes both government and privately funded benefits programs;
similar to the U.S.
−Removed: federal Anti-Kickback Statute, a
−Removed: person or entity does not need to have actual knowledge of the statute or specific intent to violate it in order to have committed a violation;
+Added: federal Anti-Kickback Statute, a person or entity does not need to have actual knowledge of the statute or specific intent to violate it in order to have committed a violation ;
● state laws and regulations, including state anti-kickback and false claims laws, that may apply to our business practices, including but not limited to, research, distribution, sales and marketing arrangements and claims involving healthcare items or services reimbursed by any third-party payer, including private insurers;
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Further, existing tax laws, statutes, rules, regulations or ordinances could be interpreted, changed, modified or applied adversely to us.
−Removed: For example, the U.S.
−Removed: government enacted significant tax reforms in the past, and certain provisions of any new laws may adversely affect us.
−Removed: Changes in recent years include, but are not limited to, a federal corporate tax rate decrease to 21% for tax years beginning after December 31, 2017, a reduction to the maximum deduction allowed for net operating losses generated in tax years after December 31, 2017, eliminating carrybacks of net operating losses, and providing for indefinite carryforwards for losses generated in tax years after
−Removed: December 31, 2017.
−Removed: The legislation is unclear in many respects and could be subject to potential amendments and technical corrections, and will be subject to interpretations and implementing regulations by the Treasury and Internal Revenue Service, any of which could mitigate or increase certain adverse effects of the legislation.
In addition, it is unclear how these U.S.
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tax laws and regulations, or their interpretation and application could have an adverse effect on our business, financial conditions and results of operations.
+Added: We are unable to predict whether such changes will occur and, if so, the ultimate impact on our business .
We are subject to U.S.
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The trading price of our common stock could be highly volatile and could be subject to wide fluctuations in response to various factors, some of which are beyond our control.
−Removed: In particular, the trading prices for biopharmaceutical companies have been highly volatile as a result of the COVID-19 pandemic.
+Added: In particular, the trading prices for biopharmaceutical companies have been highly volatile as a result of supply chain disruptions and the COVID-19 pandemic.
These factors include those discussed in this “Risk Factors” section and others such as:
−Removed: ● results from, and any delays in, our current and future clinical trials with CT1812 or any other future clinical development programs, including any delays related to the COVID-19 pandemic;
−Removed: ● announcements of regulatory approval or disapproval of CT1812 or any future product candidates;
−Removed: ● failure or discontinuation of any of our research and development programs;
−Removed: ● the termination of any future collaborations or license agreements;
−Removed: ● delays in the commercialization of CT1812 or any future product candidates;
−Removed: ● public misperception regarding the use of our product candidates;
−Removed: ● acquisitions and sales of new products or product candidates, technologies or businesses;
−Removed: ● manufacturing and supply issues related to our product candidates for clinical trials or future product candidates for commercialization;
−Removed: ● quarterly variations in our results of operations or those of our competitors;
−Removed: ● changes in coverage and recommendations by securities analysts;
−Removed: ● announcements by us or our competitors of new products or product candidates, significant contracts, commercial relationships, acquisitions or capital commitments;
−Removed: ● developments with respect to intellectual property rights;
−Removed: ● our commencement of, or involvement in, litigation;
−Removed: ● changes in financial estimates or guidance;
−Removed: ● any major changes in our board of directors or management;
−Removed: ● new legislation or regulation in the United States relating to the sale or pricing of pharmaceuticals;
−Removed: ● FDA or other U.S.
−Removed: or foreign regulatory actions affecting us or our industry;
−Removed: ● product liability claims or other litigation or public concern about the safety of our product candidates;
−Removed: ● market conditions in the biopharmaceutical sectors;
−Removed: ● general economic conditions in the United States and abroad.
+Added: ● the commencement, enrollment, or results of our current and future preclinical studies and clinical trials, and the results of trials of our competitors or those of other companies in our market sector;
+Added: ● regulatory approval of our product candidates, or limitations to specific label indications or patient populations for its use, or changes or delays in the regulatory review process;
+Added: ● regulatory developments in the United States and foreign countries;
+Added: ● changes in the structure of healthcare payment systems, especially in light of current reforms to the United States healthcare system;
+Added: ● the success or failure of our efforts to acquire, license, or develop additional product candidates;
+Added: ● innovations or new products developed by us or our competitors;
+Added: ● announcements by us or our competitors of significant acquisitions, strategic partnerships, joint ventures, or capital commitments;
+Added: ● manufacturing, supply or distribution delays or shortages;
+Added: ● any changes to our relationship with manufacturers, suppliers, licensors, future collaborators, or other strategic partners;
+Added: ● achievement of expected product sales and profitability;
+Added: ● variations in our financial results or those of companies that are perceived to be similar to us;
+Added: ● market conditions in the biopharmaceutical sector and issuance of securities analysts’ reports or recommendations;
+Added: ● trading volume of our common stock;
+Added: ● an inability to obtain additional funding;
+Added: ● sales of our stock by insiders and stockholders;
+Added: ● additions or departures of key personnel;
+Added: ● intellectual property, product liability, or other litigation against us;
+Added: ● general economic, industry and market conditions, including with respect to the financial markets in the United States and worldwide resulting from inflation, the ongoing COVID-19 pandemic and the conflict between Russia and Ukraine.
In addition, the stock markets in general, and the markets for biopharmaceutical stocks in particular, have experienced extreme volatility that may have been unrelated to the operating performance of the issuer.
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If we sell shares of our common stock in future financings, stockholders may experience dilution and, as a result, our stock price may decline.
−Removed: Because we expect our expenses to increase significantly in the foreseeable future and because, based on our current business plans, we believe that the net proceeds from our IPO, together with our cash, cash equivalents, and marketable securities prior to the IPO, will be sufficient for us to fund our operating and capital expenditures into the second half of 2023.
−Removed: We may from time to time issue additional shares of common stock or other securities.
+Added: Because we expect our expenses to increase significantly in the foreseeable future and because, based on our current business plans, we believe that our cash, cash equivalents and non-dilutive grant funding, will be sufficient for us to fund our operating and capital expenditures into the second half of 2024.
+Added: As a result, we may from time to time issue additional shares of common stock or other securities to raise capital.
These issuances may be at a discount from the current trading price of our common stock.
−Removed: As a result, our stockholders would experience dilution upon the purchase of any shares of our common stock sold at such discount.
+Added: Our stockholders would experience dilution upon the purchase of any shares of our common stock sold at such discount.
In addition, as opportunities present themselves, we may enter into financing or similar arrangements in the future, including the issuance of debt securities, preferred stock or common stock.
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Sales of a substantial number of shares of our common stock in the public market could cause our stock price to fall.
−Removed: If our stockholders sell, or indicate an intention to sell, substantial amounts of our common stock in the public market after the lock-up and other legal restrictions on resale in connection with our IPO terminate, the trading price of our common stock could decline.
−Removed: The lock-up agreements pertaining to our IPO will expire April 5, 2022 (the 180 th day after the effectiveness of the registration statement on Form S-1 relating to our IPO).
−Removed: Based upon the number of shares outstanding as of December 31, 2021, after the lock-up agreements expire, up to approximately 10,931,039 additional shares of common stock will be eligible for sale in the public market, all of which shares are held by directors, executive officers, affiliates, and certain significant stockholders and will be subject to Rule 144 under the Securities Act.
−Removed: The underwriters may, however, in their sole discretion, permit our officers, directors and other stockholders who are subject to these lock-up agreements to sell shares prior to the expiration of the lock-up agreements.
−Removed: In addition, following the closing of our IPO, we filed a registration statement on Form S-8 (File No.
−Removed: 333-260686) under the Securities Act, registering the issuance of 7,334,485 shares of our common stock subject to options or other equity awards issued or reserved for future issuance under our equity incentive plans.
−Removed: Shares registered under the registration statement on Form S-8 will be available for sale in the public market subject to vesting arrangements and exercise of options, the lock-up agreements described above and the restrictions of Rule 144 in the case of our affiliates.
−Removed: Subsequent to the IPO, holders of approximately 3,377,925 shares of our common stock, or approximately 15.8% of our total outstanding shares of common stock, were entitled to rights with respect to the registration of their shares under the Securities Act, subject to the lock-up agreements described above (as applicable) and certain exceptions.
−Removed: Registration of these shares under the Securities Act would result in the shares becoming freely
−Removed: tradable without restriction under the Securities Act, except for shares purchased by affiliates.
−Removed: Any sales of securities by these stockholders could have a material adverse effect on the trading price of our common stock .
+Added: Sales of a substantial number of shares of our common stock in the public market or the perception that these sales might occur, could depress the market price of our common stock and could impair our ability to raise capital through the sale of additional equity securities.
+Added: We are unable to predict the effect that sales may have on the prevailing market price of our common stock.
+Added: Sales of significant number of shares of our common stock may make it more difficult for us to sell equity or equity-related securities in the future at a time and price that we deem reasonable or appropriate, and make it more difficult for you to sell shares of our common stock .
+Added: We have also registered or intend to register all shares of our common stock subject to options or other equity awards issued or reserved for future issuance under our equity incentive plans.
+Added: As a result, these shares will be available for sale in the public market subject to vesting arrangements and exercise of options, and restrictions under applicable securities laws.
+Added: In addition, our directors, executive officers and certain affiliates may in the future establish programmed selling plans under Rule 10b5-1 of the Exchange Act for the purpose of effecting sales of our common stock.
+Added: If any of these events cause a large number of our shares to be sold in the public market, the sales could reduce the trading price of our common stock and impede our ability to raise future capital.
+Added: In December 2022, we filed a registration statement on Form S-3 relating to the registration of our common stock, preferred stock, debt securities, warrants, units and subscription rights or any combination thereof.
+Added: Concurrently with the filing of such registration statement, we entered into an "at-the-market"
+Added: offering program, or ATM, which provides for the offering, issuance and sale by us of up shares of our common stock from time to time for aggregate gross proceeds of up to $40 million in sales deemed to be “at-the-market offerings” as defined by the Securities Act of 1933, as amended.
+Added: For the period ended December 31, 2022, we have sold and issued no shares of common stock pursuant to the ATM.
+Added: In addition, in March 2023, we entered into a Purchase Agreement with Lincoln Park Capital Fund, LLC, or Lincoln Park, providing for the sale of up to $35.0 million worth of shares of our common stock.
+Added: Any additional sale or issuance of securities pursuant to this registration statement or otherwise may result in dilution to our stockholders and may cause the market price of our stock to decline.
+Added: Furthermore, new investors purchasing securities that we may issue and sell in the future could obtain rights superior to the rights of our existing stockholders.
+Added: We are also authorized to grant stock options and other equity-based awards to our employees, directors and consultants pursuant to our 2021 Equity Incentive Plan.
+Added: The number of shares available for future grant under the 2021 will automatically increase each year by up to 5% of all shares of our capital stock outstanding as of December 31 of the prior calendar year, subject to the ability of our board of directors or compensation committee to take action to reduce the size of the increase in any given year.
+Added: Currently, we plan to register any increase in the number of shares available for issuance under the 2021 Plan promptly following the effectiveness of any such increase.
+Added: If our board of directors elects to increase the number of shares available for future grant under the 2021 Plan, our stockholders may experience additional dilution, and our stock price may fall.
Our ability to use net operating loss carryforwards and other tax attributes may be limited.
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The federal research and development tax credits will begin to expire in 2027, if not utilized.
−Removed: Utilization of NOL carryforwards and credits may be subject to an annual limitation due to the “ownership change” provisions under Sections 382 and 383 of the Internal Revenue Code of 1986, as amended, or the Code.
+Added: Utilization of NOL carryforwards and credits may be subject to an annual limitation due to the “ownership change” provisions under Sections 382 and 383 of the Code.
An “ownership change” is generally defined as a cumulative change in the ownership interest of significant stockholders over a rolling three-year period in excess of 50 percentage points.
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Our third amended and restated certificate of incorporation and amended and restated bylaws each contain provisions that could delay or prevent changes in control or changes in our management without the consent of our board of directors.
−Removed: These provisions will include the following:
+Added: These provisions include the following:
● a classified board of directors with three-year staggered terms, which may delay the ability of stockholders to change the membership of a majority of our board of directors;
7 unchanged sentences
● advance notice procedures that stockholders must comply with in order to nominate candidates to our board of directors or to propose matters to be acted upon at a stockholders’ meeting, which may discourage or deter a potential acquiror from conducting a solicitation of proxies to elect the acquiror’s own slate of directors or otherwise attempting to obtain control of us.
−Removed: We are also subject to the anti-takeover provisions contained in Section 203 of the Delaware General Corporation Law.
+Added: We are also subject to the anti-takeover provisions contained in Section 203 of the Delaware General Corporation Law, or the DGCL.
Under Section 203, a corporation may not, in general, engage in a business combination with any holder of 15% or more of its capital stock unless the holder has held the stock for three years or, among other exceptions, the board of directors has approved the transaction .
Our third amended and restated certificate of incorporation and amended and restated bylaws provide that the Court of Chancery of the State of Delaware will be the exclusive forum for certain disputes between us and our stockholders, which could limit our stockholders’ ability to obtain a favorable judicial forum for disputes with us or our directors, officers or employees.
−Removed: Our third amended and restated certificate of incorporation and amended and restated bylaws provide that the Court of Chancery of the State of Delaware (or, in the event that the Court of Chancery does not have jurisdiction, the United States District Court for the District of Delaware or other state courts of the State of Delaware) is the exclusive forum for any derivative action or proceeding brought on our behalf, any action asserting a claim of breach of fiduciary duty, any action asserting a claim against us arising pursuant to the Delaware General Corporation Law, our third amended and restated certificate of incorporation or our amended and restated bylaws, or any action asserting a claim against us that is governed by the internal affairs doctrine;
−Removed: provided that, the exclusive forum provision will not apply to suits brought to enforce any liability or duty created by the Exchange Act of 1934, as amended, or the Exchange Act, or any other claim for which the federal courts have exclusive jurisdiction;
+Added: Our third amended and restated certificate of incorporation and amended and restated bylaws provide that the Court of Chancery of the State of Delaware (or, in the event that the Court of Chancery does not have jurisdiction, the United States District Court for the District of Delaware or other state courts of the State of Delaware) is the exclusive forum for any derivative action or proceeding brought on our behalf, any action asserting a claim of breach of fiduciary duty, any action asserting a claim against us arising pursuant to the DGCL, our third amended and restated certificate of incorporation or our amended and restated bylaws, or any action asserting a claim against us that is governed by the internal affairs doctrine;
+Added: provided that, the exclusive forum provision will not apply to suits brought to enforce any liability or duty created by the Exchange Act, or any other claim for which the federal courts have exclusive jurisdiction;
and provided further that, if and only if the Court of Chancery of the State of Delaware dismisses any such action for lack of subject matter jurisdiction, such action may be brought in another state or federal court sitting in the State of Delaware.
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Furthermore, the enforceability of similar choice of forum provisions in other companies’ certificates of incorporation has been challenged in legal proceedings, and it is possible that a court could find these types of provisions to be inapplicable or unenforceable.
−Removed: While the Delaware courts have determined that such choice of forum provisions are facially valid, a stockholder may nevertheless seek to bring a claim in a venue other than those designated in the exclusive forum provisions,
−Removed: and there can be no assurance that such provisions will be enforced by a court in those other jurisdictions.
−Removed: If a court were to find the choice of forum provision contained in our third amended and restated certificate of incorporation and amended and restated bylaws to be inapplicable or unenforceable in an action, we may incur additional costs associated with resolving such action in other jurisdictions, which could adversely affect our business and financial condition .
+Added: While the Delaware courts have determined that such choice of forum provisions are facially valid, a stockholder may nevertheless seek to bring a claim in a venue other than those designated in the exclusive forum provisions, and there can be no assurance that such provisions will be enforced by a court in those other jurisdictions.
+Added: If a court were to find the choice of forum provision contained in our third amended and restated certificate of incorporation and amended and restated bylaws to be inapplicable or unenforceable in an action, we may incur
+Added: additional costs associated with resolving such action in other jurisdictions, which could adversely affect our business and financial condition .
We do not currently intend to pay dividends on our common stock, and, consequently, your ability to achieve a return on your investment will depend on appreciation in the price of our common stock.
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General Risk Factors
−Removed: Unfavorable global economic or political conditions could adversely affect our business, financial condition or results of operations.
+Added: Unfavorable global economic or political conditions has in the past and could in the future adversely affect our business, financial condition or results of operations.
Our business is susceptible to general conditions in the global economy and in the global financial markets.
Further, the impacts of political unrest, including as a result geopolitical tension, such as a deterioration in the relationship between the U.S.
−Removed: and China or escalation in conflict between Russia and Ukraine, including any additional sanctions, export controls or other restrictive actions that may be imposed by the U.S.
−Removed: and/or other countries against governmental or other entities in, for example, Russia, also could lead to disruption, instability and volatility in the global markets, which may have an adverse impact on our business or ability to access the capital markets.
−Removed: A severe or prolonged economic downturn, including a recession or depression resulting from the ongoing COVID-19 pandemic, or political disruption could result in a variety of risks to our business, including weakened demand for our product candidates or any future product candidates, if approved, and our ability to raise additional capital when needed on acceptable terms, if at all.
+Added: and China or the conflict between Russia and Ukraine, including any additional sanctions, export controls or other restrictive actions that may be imposed by the U.S.
+Added: and/or other countries against governmental or other entities in, for example, Russia, also has in the past and could in the future lead to disruption, instability and volatility in the global markets, which may have an adverse impact on our business or ability to access the capital markets.
+Added: A severe or prolonged economic downturn, including rises in interest rates, liquidity constraints, failures and instability in U.S.
+Added: and international financial banking systems, inflation, recession or depression, or political disruption has and could result in a variety of risks to our business, including weakened demand for our product candidates or any future product candidates, if approved, and our ability to raise additional capital when needed on acceptable terms, if at all.
A weak or declining economy or political disruption could also strain our manufacturers or suppliers, possibly resulting in supply disruption, or cause our customers to delay making payments for our potential products.
+Added: Key national economies, including the United States, have been affected from time to time by economic downturns or recessions, supply chain constraints, heightened and fluctuating inflation and interest rates, restricted credit, poor liquidity, reduced corporate profitability, volatility in credit, equity and foreign exchange markets, bankruptcies and overall uncertainty with respect to the economy.
+Added: In particular, in relation to uncertainty around inflation and the U.S.
+Added: Federal Reserve’s measures to slow inflation, the stock market has been exceptionally volatile.
+Added: In addition, U.S.
+Added: debt ceiling and budget deficit concerns have increased the possibility of additional credit-rating downgrades and economic slowdowns, or a recession in the United States.
+Added: The impact of this or any further downgrades to the U.S.
+Added: government’s sovereign credit rating or its perceived creditworthiness could adversely affect the U.S.
+Added: and global financial markets and economic conditions.
Any of the foregoing could materially and adversely affect our business, financial condition, results of operations and prospects, and we cannot anticipate all of the ways in which the political or economic climate and financial market conditions could adversely impact our business .
+Added: Adverse developments affecting the financial services industry, including events or concerns involving liquidity, defaults or non-performance by financial institutions or transactional counterparties, could adversely affect our business, financial condition or results of operations.
+Added: 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.
+Added: 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.
+Added: Similarly, on March 12, 2023, Signature Bank and Silvergate Capital Corp.
+Added: were each swept into receivership.
+Added: 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
+Added: our current and projected future business operations could be significantly impaired by factors that affect us, the financial services industry or economy in general.
+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.
+Added: In addition, investor concerns regarding the U.S.
+Added: or international financial systems could result in less favorable commercial financing terms, including higher interest rates or costs and tighter financial and operating covenants, or systemic limitations on access to credit and liquidity sources, thereby making it more difficult for us to acquire financing on acceptable terms or at all.
+Added: Any decline in available funding or access to our cash and liquidity resources could, among other risks, adversely impact our ability to meet our operating expenses, financial obligations or fulfill our other obligations, result in breaches of our contractual obligations or result in violations of federal or state wage and hour laws.
+Added: 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.
If securities or industry analysts do not publish research or reports about our business, or if they issue an adverse or misleading opinion regarding our stock, our stock price and trading volume could decline.
The trading market for our common stock may be influenced by the research and reports that industry or securities analysts publish about us or our business.
−Removed: We do not currently have, and may never obtain, research coverage by securities and industry analysts.
−Removed: If no or few securities or industry analysts commence coverage of us, the trading price for our stock could be negatively impacted.
−Removed: In the event we obtain securities or industry analyst coverage, if any of the analysts who cover us issue an adverse or misleading opinion regarding us, our business model, our intellectual property or our stock performance, or if our clinical trials and operating results fail to meet the expectations of analysts, our stock price would likely decline.
+Added: If any of the analysts who cover us issue an adverse or misleading opinion regarding us, our business model, our intellectual property or our stock performance, or if our clinical trials and operating results fail to meet the expectations of analysts, our stock price would likely decline.
If one or more of these analysts cease coverage of us or fail to publish reports on us regularly, we could lose visibility in the financial markets, which in turn could cause our stock price or trading volume to decline .
2 unchanged sentences
We may be the target of this type of litigation in the future.
−Removed: Regardless of the
−Removed: merits or the ultimate results of such litigation, securities litigation brought against us could result in substantial costs and divert our management’s attention from other business concerns .
+Added: Regardless of the merits or the ultimate results of such litigation, securities litigation brought against us could result in substantial costs and divert our management’s attention from other business concerns.
We have incurred, and will continue to incur, significant costs as a result of operating as a public company, and our management will devote substantial time to new compliance initiatives.
7 unchanged sentences
We are subject to Section 404 and the related rules of the SEC, which generally require our management and independent registered public accounting firm to report on the effectiveness of our internal control over financial reporting.
−Removed: Beginning with the second annual report that we will be required to file with the SEC, Section 404 requires an annual management assessment of the effectiveness of our internal control over financial reporting.
+Added: Section 404 requires an annual management assessment of the effectiveness of our internal control over financial reporting.
However, for so long as we remain an emerging growth company as defined in the JOBS Act, we intend to take advantage of certain exemptions from various reporting requirements that are applicable to public companies that are not emerging growth companies, including, but not limited to, not being required to comply with the auditor attestation requirements of Section 404.
−Removed: Once we are no longer an emerging growth company or, if prior to such date, we opt to no longer take advantage of the applicable exemption, we will be required to include an opinion from our independent registered public accounting firm on the effectiveness of our internal control over financial reporting.
+Added: Once we are deemed to be a large accelerated filer or an accelerated filer, we will be required to include an attestation report on internal control over financial reporting.
During the course of our review and testing, we may identify deficiencies and be unable to remediate them before we must provide the required reports.
15 unchanged sentences
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.