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Biopharmaceutical product development is a highly speculative undertaking and involves a substantial degree of risk.
−Removed: To date, we have focused primarily on developing our lead product candidates, CPI-006, CPI-818 and ciforadenant, and researching additional product candidates.
+Added: To date, we have focused primarily on developing our lead product candidates, mupadolimab, CPI-818 and ciforadenant, and researching additional product candidates.
We have incurred significant operating losses since we were founded in January 2014 and have not yet generated any revenue from sales.
If our product candidates are not approved, we may never generate any revenue.
−Removed: We incurred a net loss of $6.0 million, $46.7 million and $46.9 million for the years ended December 31, 2020, 2019 and 2018, respectively, and $11.6 million and $12.9 million for the three months ended March 31, 2021 and 2020, respectively.
−Removed: We had an accumulated deficit of $234.7 million as of March 31, 2021.
−Removed: We expect to continue to incur losses for the foreseeable future, and we anticipate these losses will increase as we continue our development of, seek regulatory approval for and, if approved, begin to commercialize CPI-006, CPI-818 and ciforadenant, and as we develop other product candidates.
+Added: We incurred a net loss of $6.0 million, $46.7 million and $46.9 million for the years ended December 31, 2020, 2019 and 2018, respectively, and $23.3 million and $23.5 million for the six months ended June 30, 2021 and 2020, respectively.
+Added: We had an accumulated deficit of $246.5 million as of June 30, 2021.
+Added: We expect to continue to incur losses for the foreseeable future, and we anticipate these losses will increase as we continue our development of, seek regulatory approval for and, if approved, begin to commercialize mupadolimab, CPI-818 and ciforadenant, and as we develop other product candidates.
Even if we achieve profitability in the future, we may not be able to sustain it in subsequent periods.
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We will require substantial additional financing to achieve our goals, and a failure to obtain this necessary capital when needed on acceptable terms, or at all, could force us to delay, limit, reduce or terminate our product development, other operations or commercialization efforts.
−Removed: Since commencing our operations in 2014, the majority of our efforts have been focused on the research and development of CPI-006, CPI-818 and ciforadenant.
−Removed: We believe that we will continue to expend substantial resources for the foreseeable future as we continue clinical development of, seek regulatory approval for and, if approved, prepare for the commercialization of CPI-006, CPI-818 and ciforadenant, as well as product candidates under our other development programs.
+Added: Since commencing our operations in 2014, the majority of our efforts have been focused on the research and development of mupadolimab, CPI-818 and ciforadenant.
+Added: We believe that we will continue to expend substantial resources for the foreseeable future as we continue clinical development of, seek regulatory approval for and, if approved, prepare for the commercialization of mupadolimab, CPI-818 and ciforadenant, as well as product candidates under our other development programs.
These expenditures will include costs associated with research and development, conducting preclinical studies and clinical trials, obtaining regulatory approvals, manufacturing and supply, sales and marketing and general operations.
In addition, other unanticipated costs may arise.
−Removed: Because the outcome of any clinical trial and/or regulatory approval process is highly uncertain, we may not be able to accurately estimate the actual amounts necessary to successfully complete the development, regulatory approval process and commercialization of CPI-006, CPI-818 and ciforadenant or any other product candidates.
−Removed: As of March 31, 2021, we had capital resources consisting of cash, cash equivalents and marketable securities of $68.0 million.
−Removed: We do not expect our existing capital resources to be sufficient to enable us to fund the completion of all of our ongoing and planned clinical trials and remaining development program of any of CPI-006, CPI-818 or ciforadenant through commercialization.
+Added: Because the outcome of any clinical trial and/or regulatory approval process is highly uncertain, we may not be able to accurately estimate the actual amounts necessary to successfully complete the development, regulatory approval process and commercialization of mupadolimab, CPI-818 and ciforadenant or any other product candidates.
+Added: As of June 30, 2021, we had capital resources consisting of cash, cash equivalents and marketable securities of $66.5 million.
+Added: We do not expect our existing capital resources to be sufficient to enable us to fund the completion of all of our ongoing and planned clinical trials and remaining development program of any of mupadolimab, CPI-818 or ciforadenant through commercialization.
In addition, while Angel Pharmaceuticals has received outside investment of approximately $41.0 million in connection with its formation and licensing of certain of our intellectual property, such cash is not available for our use.
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For example, in October 2020 we formed Angel Pharmaceuticals with a group of investors in China to create a new China-based biopharmaceutical company with a mission to bring innovative quality medicines to Chinese patients for treatment of serious diseases including cancer, autoimmune diseases and infectious diseases.
−Removed: We granted Angel Pharmaceuticals a license to rights to develop and commercialize our three clinical-stage candidates – CPI-006, CPI-818 and ciforadenant – in greater China and Angel obtained global rights to our BTK inhibitor preclinical programs.
+Added: We granted Angel Pharmaceuticals a license to rights to develop and commercialize our three clinical-stage candidates – mupadolimab, CPI-818 and ciforadenant – in greater China and Angel obtained global rights to our BTK inhibitor preclinical programs.
In addition, additional funding may not be available to us on acceptable terms, or at all, and any additional fundraising efforts may divert our management from their day-to-day activities, which may adversely affect our ability to develop and commercialize our product candidates.
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The amount and timing of any expenditures needed to implement our development and commercialization programs will depend on numerous factors, including, but not limited to:
−Removed: ● the type, number, scope, progress, expansions, results of and timing of our ongoing and planned clinical trials of CPI-006, CPI-818 and ciforadenant and any of our planned preclinical studies and clinical trials of other product candidates which we are pursuing or may choose to pursue in the future;
−Removed: ● whether our current Phase 3 clinical trial of CPI-006 is successful;
+Added: ● the type, number, scope, progress, expansions, results of and timing of our ongoing and planned clinical trials of mupadolimab, CPI-818 and ciforadenant and any of our planned preclinical studies and clinical trials of other product candidates which we are pursuing or may choose to pursue in the future;
● the impact of changes in the COVID-19 pandemic, including the impact of vaccines and therapeutic treatments;
−Removed: ● the need for, and the progress, costs and results of, any additional clinical trials of CPI-006, CPI-818 and ciforadenant or any of our other product candidates we may initiate based on the results of our planned clinical trials or discussions with the FDA, including any additional trials the FDA or other regulatory agencies may require;
+Added: ● the need for, and the progress, costs and results of, any additional clinical trials of mupadolimab, CPI-818 and ciforadenant or any of our other product candidates we may initiate based on the results of our planned clinical trials or discussions with the FDA, including any additional trials the FDA or other regulatory agencies may require;
● the costs of obtaining, maintaining and enforcing our patents and other intellectual property rights;
−Removed: ● the costs and timing of obtaining or maintaining manufacturing for CPI-006, CPI-818 and ciforadenant and our other product candidates, including commercial manufacturing if any product candidate is approved;
+Added: ● the costs and timing of obtaining or maintaining manufacturing for mupadolimab, CPI-818 and ciforadenant and our other product candidates, including commercial manufacturing if any product candidate is approved;
● the costs and timing of establishing sales and marketing capabilities;
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● the costs associated with being a public company.
−Removed: Several of these factors are outside of our control and if we are unable to obtain funding on a timely basis, we will be unable to complete the clinical trials for CPI-006, CPI-818 and ciforadenant and our other product candidates, and we may be required to significantly curtail some or all of our activities.
+Added: Several of these factors are outside of our control and if we are unable to obtain funding on a timely basis, we will be unable to complete the clinical trials for mupadolimab, CPI-818 and ciforadenant and our other product candidates, and we may be required to significantly curtail some or all of our activities.
The COVID-19 pandemic could adversely impact our business, including our clinical trials, and financial condition.
−Removed: In December 2019, a novel strain of coronavirus, COVID-19, was reported to have surfaced in Wuhan, China.
−Removed: Since then, the COVID-19 pandemic has spread to most countries, including the United States and European and Asia-Pacific countries, including countries in which we have planned or active clinical trial sites.
−Removed: As the COVID-19 pandemic continues to spread around the globe, we will likely experience disruptions that could severely impact our business and clinical trials, including:
+Added: The COVID-19 pandemic has spread to most countries, including the United States and European and Asia-Pacific countries, including countries in which we have planned or active clinical trial sites.
+Added: As the COVID-19 pandemic continues to spread around the globe, including the spread of more contagious and virulent variants, we will likely experience disruptions that could severely impact our business and clinical trials, including:
● delays or difficulties in enrolling patients in our clinical trials;
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If we are unable to advance our product candidates through clinical development, obtain regulatory approval and ultimately commercialize such product candidates, or experience significant delays in doing so, our business will be materially harmed.
−Removed: We have invested a significant portion of our efforts and financial resources in the development of our most advanced product candidates, CPI-006, ciforadenant and CPI-818, which are being evaluated in Phase 3, Phase 1b/2 and Phase 1/1b clinical trials, respectively.
−Removed: Although we believe our Phase 3 trial of CPI-006 for the treatment of hospitalized patients with COVID-19, if it meets its primary endpoint, may be sufficient to support submission of a Biologics License Application (”BLA”) by the FDA, the FDA may disagree and we may be required to conduct additional trials to support the submission of a BLA CPI-006.
+Added: We have invested a significant portion of our efforts and financial resources in the development of our most advanced product candidates, mupadolimab, CPI-818 and ciforadenant, which are being evaluated in Phase 1/1b, Phase 1/1b and Phase 1b/2 clinical trials, respectively.
We have no products on the market and our ability to achieve and sustain profitability depends on obtaining regulatory approvals for and successfully commercializing our product candidates, either alone or with third parties.
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● varying interpretations of data by the FDA and similar foreign regulatory agencies.
−Removed: In addition, disruptions at the FDA and other regulatory agencies that are unrelated to our company or our products could also cause delays to the regulatory approval process for our products.
−Removed: For example, over the last several years, including from December 2018 into January 2019, the U.S.
−Removed: government has shut down several times and certain regulatory agencies, including the FDA, have had to furlough critical employees and stop critical activities.
−Removed: If a prolonged government shutdown occurs, it could significantly impact the ability of the FDA to timely review and process our regulatory submissions.
We could find that the product candidates we or our collaborators pursue are not safe or effective.
−Removed: Furthermore, if one or more of our product candidates, particularly in relation to the adenosine pathway, generally prove to be ineffective, unsafe or commercially unviable, the development of our entire platform and pipeline could be delayed, potentially permanently.
+Added: Furthermore, if one or more of our product candidates generally prove to be ineffective, unsafe or commercially unviable, the development of our entire platform and pipeline could be delayed, potentially permanently.
Any of these occurrences may materially and adversely affect our business, financial condition, results of operations and prospects.
Of the large number of drugs in development in the pharmaceutical industry, only a small percentage result in the submission of a New Drug Application (“NDA”) or BLA to the FDA or comparable marketing applications to foreign regulatory authorities, and even fewer are approved for commercialization.
−Removed: Furthermore, even if we do receive regulatory approval to market CPI-006, CPI-818 or ciforadenant, any such approval may be subject to limitations on the indicated uses for which we may market the product.
−Removed: Accordingly, even if we are able to obtain the requisite financing to continue to fund our development programs, we cannot assure our stockholders that CPI-006, CPI-818 or ciforadenant
−Removed: will be successfully developed or commercialized.
−Removed: If we or any of our existing or potential future collaborators are unable to develop, or obtain regulatory approval for, or, if approved, successfully commercialize CPI-006, CPI-818 or ciforadenant, we may not be able to generate sufficient revenue to continue our business.
+Added: Furthermore, even if we do receive regulatory approval to market mupadolimab, CPI-818 or ciforadenant, any such approval may be subject to limitations on the indicated uses for which we may market the product.
+Added: Accordingly, even if we are able to obtain the requisite financing to continue to fund our development programs, we cannot assure our stockholders that mupadolimab, CPI-818 or ciforadenant will be successfully developed or commercialized.
+Added: If we or any of our existing or potential future collaborators are unable to develop, or obtain regulatory approval for, or, if approved, successfully commercialize mupadolimab, CPI-818 or ciforadenant, we may not be able to generate sufficient revenue to continue our business.
Clinical drug development involves a lengthy and expensive process with an uncertain outcome, and the results of preclinical studies and early clinical trials are not necessarily predictive of future results.
−Removed: Any product candidate we or any of our existing or potential future collaborators advance into clinical trials, including CPI-006, CPI-818 and ciforadenant , may not have favorable results in later clinical trials, if any, or receive regulatory approval.
+Added: Any product candidate we or any of our existing or potential future collaborators advance into clinical trials, including mupadolimab, CPI-818 and ciforadenant , may not have favorable results in later clinical trials, if any, or receive regulatory approval.
Clinical testing is expensive and can take many years to complete, and its outcome is inherently uncertain.
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The results of preclinical studies and early clinical trials of our product candidates may not be predictive of the results of later-stage clinical trials.
−Removed: Product candidates in later stages of clinical trials may fail to show the desired safety and efficacy traits despite having progressed through preclinical studies and initial clinical trials.
+Added: Product candidates in later stages of clinical trials may fail to show the desired safety and efficacy traits despite having progressed through preclinical
+Added: studies and initial clinical trials.
A number of companies in the biopharmaceutical industry have suffered significant setbacks in advanced clinical trials due to lack of efficacy or adverse safety profiles, notwithstanding promising results in earlier trials.
Furthermore, our ongoing and planned clinical trials will need to demonstrate sufficient safety and efficacy for approval by regulatory authorities in larger patient populations.
+Added: In March 2018, we began enrolling patients in our Phase 1/1b trial evaluating mupadolimab in cancer patients.
+Added: The protocol is designed to enroll successive cohorts of patients with advanced cancers who will receive increasing doses of mupadolimab both alone, or in combination with ciforadenant or an anti-PD-1.
+Added: Mupadolimab has been well tolerated in the clinical trial at doses up to 24 mg/kg, although a limited number of patients have been enrolled and the follow-up period has necessarily been short, and we have observed one patient with Grade 3 anemia.
+Added: We have seen 1 patient develop Grade 3 hyponatremia at a dose of 24 mg/kg.
+Added: However, CD73 is involved in several physiological systems and the administration of anti-CD73 antibodies such as mupadolimab could result in unforeseen safety issues.
+Added: Similar to our Phase 1/1b clinical trial of ciforadenant, it is possible that patients enrolled in our Phase 1/1b clinical trial for mupadolimab could respond in unexpected ways and that the administration of mupadolimab in combination with ciforadenant and pembrolizumab could exacerbate immune system related adverse events.
+Added: As a result, there can be no assurance that we will be able to establish the safety and efficacy of mupadolimab or that we will be able to successfully complete our Phase 1/1b clinical trial.
Since the initiation of our Phase 1/1b clinical trial in January 2016, ciforadenant has been administered to more than 300 cancer patients and, while it has generally been well tolerated, there have been possibly drug-related or drug-related serious adverse events observed during the trial, and limited information is available concerning long-term safety and efficacy.
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As a result, there can be no assurance that the results of historical clinical studies of ciforadenant conducted by third parties or the results of our clinical studies to-date will be indicative of the ongoing results of our Phase 1/1b clinical trial or amended Phase 1b/2 clinical trial, Genentech’s Phase 1b/2 clinical trial or any future clinical trial of ciforadenant.
−Removed: In March 2018, we began enrolling patients in our Phase 1/1b trial evaluating CPI-006 in cancer patients.
−Removed: The protocol is designed to enroll successive cohorts of patients with advanced cancers who will receive increasing doses of CPI-006 both alone, or in combination with ciforadenant or an anti-PD-1.
−Removed: CPI-006 has been well tolerated in the clinical trial at doses up to 24 mg/kg, although a limited number of patients have been enrolled and the follow-up period has necessarily been short, and we have observed one patient with Grade 3 anemia.
−Removed: We have seen 1 patient develop Grade 3 hyponatremia at a dose of 24 mg/kg.
−Removed: However, CD73 is involved in several physiological systems and the administration of anti-CD73 antibodies such as CPI-006 could result in unforeseen safety issues.
−Removed: Similar to our Phase 1/1b clinical trial of ciforadenant, it is possible that patients enrolled in our Phase 1/1b clinical trial for CPI-006 could respond in unexpected ways and that the administration of CPI-006 in combination with ciforadenant and pembrolizumab could exacerbate immune system related adverse events.
−Removed: As a result, there can be no assurance that we will be able to establish the safety and efficacy of CPI-006 or that we will be able to successfully complete our Phase 1/1b clinical trial.
−Removed: In July 2020, we initiated a Phase 1 clinical trial with CPI-006 in hospitalized COVID-19 patients.
−Removed: As of March 4, 2021, we have enrolled 29 patients in our Phase 1 trial and have not observed any safety issues.
−Removed: In February 2021, we initiated a Phase 3 trial with CPI-006 in hospitalized COVID-19 patients.
−Removed: The Phase 3 trial is planned to enroll approximately 1,000 patients and in such a larger patient population there may be unforeseen safety issues and there can be no assurance that we will be able to successfully complete our Phase 3 clinical trial.
In March 2019, we initiated a multi-center Phase 1/1b clinical trial evaluating CPI-818 in patients with various malignant T-cell lymphomas.
−Removed: Similar to our clinical trials of ciforadenant and CPI-006, it is possible that patients enrolled in our Phase 1/1b clinical trial for CPI-818 could respond in unexpected ways.
+Added: Similar to our clinical trials of ciforadenant and mupadolimab, it is possible that patients enrolled in our Phase 1/1b clinical trial for CPI-818 could respond in unexpected ways.
Under our collaboration with Angel Pharmaceuticals, it will be responsible for the clinical development and commercialization, including all related expenses, of the licensed pipeline programs in greater China, and for the pre-clinical BTK program globally.
−Removed: It plans to initiate clinical trials in greater China for CPI-006, CPI-818 and ciforadenant in the next 12 to 18 months and such trials will be subject to many of the same risks as our ongoing clinical programs.
+Added: It plans to initiate clinical trials in greater China for mupadolimab, CPI-818 and ciforadenant in the next 12 to 18 months and such trials will be subject to many of the same risks as our ongoing clinical programs.
For the foregoing reasons, we cannot be certain that our ongoing or planned clinical trials or any other future clinical trials will be successful.
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Delays in the completion of our planned clinical trials for product candidates could significantly affect our product development costs.
−Removed: While we initiated our Phase 1/1b clinical trial for ciforadenant in January 2016, our Phase 1/1b clinical trial for CPI-006 in cancer in March 2018, our Phase 1/1b clinical trial for CPI-818 in March 2019 and our Phase 3 clinical trial for CPI-006 for COVID-19 patients in February 2021, we do not know whether any of our other planned trials, including a planned front-line Phase 2 trial of ciforadenant in RCC patients, will begin on time in the future or whether any of our trials will be completed on schedule, if at all.
+Added: While we initiated our Phase 1/1b clinical trial for ciforadenant in January 2016, our Phase 1/1b clinical trial for mupadolimab in cancer in March 2018, our Phase 1/1b clinical trial for CPI-818 in March 2019, we do not know whether any of our other planned trials, including a planned front-line Phase 2 trial of ciforadenant in RCC patients, will begin on time in the future or whether any of our trials will be completed on schedule, if at all.
The commencement and completion of clinical trials can be delayed for a number of reasons, including delays related to:
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● subjects failing to enroll or remain in our trial at the rate we expect;
−Removed: ● subjects choosing an alternative treatment or vaccine for the indication for which we are developing CPI-006, CPI-818 and ciforadenant or other product candidates, or participating in competing clinical trials;
+Added: ● subjects choosing an alternative treatment or vaccine for the indication for which we are developing mupadolimab, CPI-818 and ciforadenant or other product candidates, or participating in competing clinical trials;
● lack of adequate funding to continue the clinical trial;
● subjects experiencing severe or unexpected drug-related adverse effects;
−Removed: ● a facility manufacturing CPI-006, CPI-818 and ciforadenant, any of our other product candidates or any of their components being ordered by the FDA or other regulatory authorities to temporarily or permanently shut down due to violations of good manufacturing practice (“cGMP”) regulations or other applicable requirements, or infections or cross-contaminations of product candidates in the manufacturing process;
+Added: ● a facility manufacturing mupadolimab, CPI-818 and ciforadenant, any of our other product candidates or any of their components being ordered by the FDA or other regulatory authorities to temporarily or permanently shut down due to violations of good manufacturing practice (“cGMP”) regulations or other applicable requirements, or infections or cross-contaminations of product candidates in the manufacturing process;
● any changes to our manufacturing process that may be necessary or desired;
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For example, if we make manufacturing or formulation changes to our product candidates, we may need to conduct additional studies to bridge our modified product candidates to earlier versions.
−Removed: Further, if one or more clinical trials are delayed, our competitors may be able to bring products to market before we do, and the commercial viability of CPI-006, CPI-818 and ciforadenant or other product candidates could be significantly reduced.
+Added: Further, if one or more clinical trials are delayed, our competitors may be able to bring products to market before we do, and the commercial viability of mupadolimab, CPI-818 and ciforadenant or other product candidates could be significantly reduced.
Any of these occurrences may harm our business, financial condition and prospects significantly.
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We also make assumptions, estimations, calculations and conclusions as part of our analyses of data, and we may not have received or had the opportunity to fully and carefully evaluate all data.
−Removed: As a result, the top-line or preliminary results that we report may differ from future results of the same studies, or different conclusions or considerations may qualify such results,
−Removed: once additional data have been received and fully evaluated.
+Added: As a result, the top-line or preliminary results that we report may differ from future results of the same studies, or different conclusions or considerations may qualify such results, once additional data have been received and fully evaluated.
Top-line or preliminary data also remain subject to audit and verification procedures that may result in the final data being materially different from the top-line or preliminary data we previously published.
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From time to time, we may also disclose interim data from our preclinical studies and clinical trials.
−Removed: For instance, in September and October 2020, we reported interim data from our Phase 1 clinical trial of CPI-006 for the treatment of COVID-19 and in December 2020 we reported interim data from our Phase 1/1b clinical trial of CPI-818 for the treatment of T-cell lymphoma.
−Removed: Interim data from clinical trials that we may complete are subject to the risk that one or more of the clinical outcomes may materially change as patient enrollment continues and more patient data become available.
+Added: For instance, in September and October 2020, we reported interim data from our Phase 1 clinical trial of mupadolimab for the treatment of COVID-19 and in December 2020 we reported interim data from our Phase 1/1b clinical trial of CPI-818 for the treatment of T-cell lymphoma.
+Added: Interim data from clinical trials that we may complete are subject to the risk that one or more of the clinical outcomes may materially change as patient enrollment continues and more patient data
+Added: become available.
Adverse differences between interim data and final data could significantly harm our business prospects.
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Any delay in obtaining, or inability to obtain, applicable regulatory approvals would prevent us or any of our existing or potential future collaborators from commercializing our product candidates.
−Removed: We are conducting clinical trials for CPI-006, CPI-818 and ciforadenant, and we and Angel Pharmaceuticals may in the future, conduct additional clinical trials of product candidates, at sites outside the United States, and the FDA may not accept data from trials conducted in foreign locations.
−Removed: We are currently conducting our Phase 3 trial with CPI-006 in hospitalized patients with COVID-19 at sites in North America, Europe, South Africa and Latin America.
−Removed: We are also conducting oncology clinical trials with CPI-818, ciforadenant and CPI-006 in North America, Australia and South Korea.
−Removed: In addition, Angel Pharmaceuticals currently intends to initiate clinical trials in China for CPI-006, CPI-818 and ciforadenant in the next 12 to 18 months, and we expect its clinical trial activity in China to be part of our planned global pivotal study for ciforadenant.
+Added: We are conducting clinical trials for mupadolimab, CPI-818 and ciforadenant, and we and Angel Pharmaceuticals may in the future, conduct additional clinical trials of product candidates, at sites outside the United States, and the FDA may not accept data from trials conducted in foreign locations.
+Added: We are currently conducting oncology clinical trials with mupadolimab, CPI-818 and ciforadenant in North America, Australia and South Korea.
+Added: In addition, Angel Pharmaceuticals currently intends to initiate clinical trials in China for mupadolimab and CPI-818 in the next 12 to 18 months.
While the FDA may accept data from clinical trials conducted outside the United States, acceptance of this data is subject to certain conditions imposed by the FDA.
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There can be no assurance the FDA will accept data from trials conducted outside of the United States, including any trials conducted by us or Angel Pharmaceuticals.
−Removed: If the FDA does not accept the data from our or Angel Pharmaceuticals’ clinical trials for CPI-006, CPI-818 or ciforadenant, or any other product candidates, it would likely result in the need for additional trials, which would be costly and time-consuming and delay or permanently halt our development of CPI-006, CPI-818 and ciforadenant or any other product candidates.
+Added: If the FDA does not accept the data from our or Angel Pharmaceuticals’ clinical trials for mupadolimab, CPI-818 or ciforadenant, or any other product candidates, it would likely result in the need for additional trials, which would be costly and time-consuming and delay or permanently halt our development of mupadolimab, CPI-818 and ciforadenant or any other product candidates.
If we are required by the FDA or similar regulatory authorities to obtain approval, clearance or certification of a companion diagnostic device in connection with approval of one of our product candidates, and we do not obtain or face delays in obtaining approval, clearance or certification of a companion diagnostic device, we will not be able to commercialize the product candidate and our ability to generate revenue will be materially impaired.
According to FDA guidance, if the FDA determines that a companion diagnostic device is essential to the safe and effective use of a novel therapeutic product or indication, the FDA generally will not approve the therapeutic product or new therapeutic product indication if the companion diagnostic is not also approved or cleared for that indication.
−Removed: We plan to collaborate with patient diagnostic companies during our clinical trial enrollment process to help identify patients with tumor gene alterations that we believe are most likely to respond to our product candidates.
+Added: We may collaborate with patient diagnostic companies during our clinical trial enrollment process to help identify patients with tumor gene alterations that we believe are most likely to respond to our product candidates.
If a satisfactory companion diagnostic is not commercially available, we may be required to create or obtain one that would be subject to regulatory approval requirements.
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In addition, the process of finding and diagnosing subjects may prove costly.
−Removed: In February 2021, we initiated a Phase 3 trial with CPI-006 in hospitalized patients with COVID-19.
−Removed: This trial is planned to enroll 1,000 patients at multiple sites in North America, Europe, South Africa and Latin America.
−Removed: The completion of enrollment of this trial will be affected by many factors including whether vaccines reduce the population of hospitalized COVID-19 patients, the impact of a number of clinical trials that are recruiting from the same patient population as our trial the potential unwillingness of clinical trial sites to put patients on our trial due to a lack of hospital resources.
−Removed: We are also enrolling patients with T-cell lymphomas in our Phase 1/1b clinical trial of CPI-818.
+Added: In February 2021, we initiated a Phase 3 trial with mupadolimab in hospitalized patients with COVID-19.
+Added: This trial was planned to enroll 1,000 patients at multiple sites in North America, Europe, South Africa and South America.
+Added: On July 15, 2021, we announced the discontinuation of the Phase 3 clinical trial due to positive trends exhibited by
+Added: COVID-19 vaccines in lowering serious infection and hospitalization.
+Added: We are also enrolling patients with head and neck cancer in our Phase 1/1b clinical trial with mupadolimab and with T-cell lymphomas in our Phase 1/1b clinical trial of CPI-818.
If patients are unwilling to participate in our studies for any reason, including the existence of competitive clinical trials for similar patient populations, the availability of approved therapies or negative perceptions of the safety or efficacy of our product candidates, the timeline for recruiting subjects, conducting studies and obtaining regulatory approval of our product candidates may be delayed.
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For example, possibly drug-related or drug-related serious adverse events have been observed during our Phase 1/1b clinical trial and our amended Phase 1b/2 clinical trial in patients receiving combination therapy with ciforadenant and Tecentriq include hemolytic anemia, encephalitis, hepatitis, pneumonitis, mucositis, myocarditis and dermatitis.
−Removed: Other toxicities observed during our Phase 1/1b clinical trial and our amended
−Removed: Phase 1b/2 clinical trial were mild and are commonly seen in patients with advanced cancers, such as nausea, vomiting, fatigue, rash, diarrhea, fever, abdominal pain, cough, constipation and decreased appetite.
+Added: Other toxicities observed during our Phase 1/1b clinical trial and our amended Phase 1b/2 clinical trial were mild and are commonly seen in patients with advanced cancers, such as nausea, vomiting, fatigue, rash, diarrhea, fever, abdominal pain, cough, constipation and decreased appetite.
Other immune-oncology drugs also have been found occasionally to induce immune related toxicities such as colitis, hepatitis, pneumonitis, meningitis, myocarditis and various endocrine diseases.
Such side effects could also be exacerbated when ciforadenant is administered in combination with Tecentriq which is provided for in a portion of our Phase 1/1b clinical trial and amended Phase 1b/2 clinical trial as well as in Genentech’s Phase 1b/2 clinical trial under our collaboration agreement, or when ciforadenant is administered in higher doses, which we added as part of a protocol amendment.
−Removed: In March 2018, we began enrolling patients in our Phase 1/1b clinical trial evaluating CPI-006.
−Removed: We have completed the dose escalation stage where patients receive CPI-006 alone and in combination with ciforadenant and we selected the recommended dose of 18 mg/kg and initiated the disease expansion phase in both the monotherapy and the combination arm with ciforadenant of our CPI-006 clinical trial.
−Removed: We are also enrolled patients in the dose escalation phase in the pembrolizumab combination arm of the trial.
−Removed: To date, only a limited number of patients have been enrolled and the follow-up period has been short.
−Removed: No dose-limiting toxicities have been observed at doses up to and including 18 mg/kg.
−Removed: In July 2020, we began enrolling COVID-19 patients in a Phase 1 clinical trial, and in February 2021, a Phase 3 clinical trial of CPI-006.
−Removed: As of March 4, 2021,no serious adverse events have been observed, however, the follow-up period has necessarily been short.
−Removed: COVID-19 is a poorly understood disease with multiple organ dysfunction and potential adverse effects of CPI-006 in these patients may be difficult to predict.
+Added: In March 2018, we began enrolling patients in our Phase 1/1b clinical trial evaluating mupadolimab.
+Added: We have completed the dose escalation stage where patients receive mupadolimab alone and in combination with ciforadenant and we selected the recommended dose of 18 mg/kg and initiated the disease expansion phase in both the monotherapy and the combination arm with ciforadenant of our mupadolimab clinical trial.
+Added: We are also enrolling patients in the dose escalation phase in the pembrolizumab combination arm of the trial.
+Added: To date, approximately 100 patients have been enrolled.
+Added: No dose-limiting toxicities had been observed at doses up to and including 18 mg/kg.
+Added: In July 2020, we began enrolling COVID-19 patients in a Phase 1 clinical trial, and in February 2021, a Phase 3 clinical trial of mupadolimab.
+Added: As of July 15, 2021, no serious adverse events have been observed, however, the follow-up period has necessarily been short.
+Added: COVID-19 is a poorly understood disease with multiple organ dysfunction and potential adverse effects of mupadolimab in these patients may be difficult to predict.
In March 2019, we initiated a multi-center Phase 1/1b clinical trial evaluating CPI-818 in patients with various malignant T-cell lymphomas and have completed enrollment in the dose escalation portion of the trial.
−Removed: As of March 4, 2021, a limited number of patients have been enrolled and, although no serious adverse events have been observed, the follow-up period has necessarily been short.
+Added: As of July 15, 2021, a limited number of patients have been enrolled and, although no serious adverse events have been observed, the follow-up period has necessarily been short.
Many times side effects are only detectable after investigational products are tested in large-scale, Phase 3 clinical trials or, in some cases, after they are made available to patients on a commercial scale after approval.
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We may not be successful in our efforts to identify or discover additional product candidates.
−Removed: The success of our business depends primarily upon our ability to develop and commercialize CPI-006, CPI-818 and ciforadenant.
−Removed: Although CPI-006, CPI-818 and ciforadenant are currently in clinical development, our research programs may fail to identify other potential product candidates, or advance them into and through clinical development for a number of reasons.
+Added: The success of our business depends primarily upon our ability to develop and commercialize mupadolimab, CPI-818 and ciforadenant.
+Added: Although mupadolimab, CPI-818 and ciforadenant are currently in clinical development, our research programs may fail to identify other potential product candidates, or advance them into and through clinical development for a number of reasons.
Our research methodology may be unsuccessful in identifying other potential product candidates or our other potential product candidates may be shown to have harmful side effects or may have other characteristics that may make the products unmarketable or unlikely to receive marketing approval.
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We do not have the ability to conduct all aspects of our preclinical testing or clinical trials ourselves.
−Removed: As a result, we are dependent on third parties to conduct our Phase 3 clinical trial for CPI-006, our Phase 1/1b clinical trial and our amended Phase 1b/2 clinical trial for ciforadenant, our Phase 1/1b and Phase 1 clinical trials for CPI-006, and our Phase 1/1b clinical trial for CPI-818, and expect to continue to be dependent on third parties to conduct any future clinical studies of CPI-006, CPI-818 and ciforadenant and preclinical and clinical trials for our other product candidates.
+Added: As a result, we are dependent on third parties to conduct our Phase 1/1b clinical trial for mupadolimab, our Phase 1/1b clinical trial for CPI-818 and our Phase 1/1b clinical trial and our amended Phase 1b/2 clinical trial for ciforadenant, and expect to continue to be dependent on third parties to conduct any future clinical studies of mupadolimab, CPI-818 and ciforadenant and preclinical and clinical trials for our other product candidates.
The timing of the initiation and completion of these trials will therefore be controlled by such third parties and may occur at times substantially different from our estimates.
−Removed: Specifically, we use and rely on medical institutions, clinical investigators, CROs and consultants to conduct our trials in accordance with our clinical protocols and regulatory requirements.
+Added: Specifically, we use and rely on medical institutions, clinical investigators, CROs and consultants to
+Added: conduct our trials in accordance with our clinical protocols and regulatory requirements.
Such CROs, investigators and other third parties play a significant role in the conduct of these trials and subsequent collection and analysis of data, and we will control only certain aspects of their activities.
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If these relationships and any related compensation result in perceived or actual conflicts of interest, or the FDA concludes that the financial relationship may have affected the interpretation of the study, the integrity of the data generated at the applicable clinical trial site may be questioned and the utility of the clinical trial itself may be jeopardized, which could result in the delay or rejection of any NDA or BLA we submit by the FDA.
−Removed: Any such delay or rejection could prevent us from commercializing CPI-006, CPI-818 and ciforadenant or our other product candidates.
+Added: Any such delay or rejection could prevent us from commercializing mupadolimab, CPI-818 and ciforadenant or our other product candidates.
We rely on third parties to conduct some or all aspects of our manufacturing, research and preclinical and clinical testing, and these third parties may not perform satisfactorily.
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We do not currently have nor do we plan to acquire the infrastructure or internal capability to manufacture our clinical drug supplies for use in the conduct of our trials, and we lack the resources and the capability to manufacture any of our product candidates on a clinical or commercial scale.
−Removed: We currently rely on several different manufacturers who supply different parts of the ciforadenant and CPI-818 molecules, on one manufacturer for CPI-006 drug substance and on other third-party manufacturers to produce our other product candidates.
+Added: We currently rely on several different manufacturers who
+Added: supply different parts of the ciforadenant and CPI-818 molecules, on one manufacturer for mupadolimab drug substance and on other third-party manufacturers to produce our other product candidates.
All entities involved in the preparation of therapeutics for clinical studies or commercial sale, including our existing contract manufacturers for our product candidates, are subject to extensive regulation.
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If any such inspection or audit identifies a failure to comply with applicable regulations or if a violation of our product specifications or applicable regulations occurs independent of such an inspection or audit, we or the relevant regulatory authority may require remedial measures that may be costly and/or time-consuming for us or a third party to implement and that may include the temporary or permanent suspension of a clinical study or commercial sales or the temporary or permanent closure of a facility.
−Removed: Such violations could also result
−Removed: in civil and/or criminal penalties, and the FDA may impose regulatory sanctions including, among other things, refusal to approve a pending application for a new drug product or biologic product, revocation of a pre-existing approval or closing one or more manufacturing facilities.
+Added: Such violations could also result in civil and/or criminal penalties, and the FDA may impose regulatory sanctions including, among other things, refusal to approve a pending application for a new drug product or biologic product, revocation of a pre-existing approval or closing one or more manufacturing facilities.
In addition, if supply from an approved manufacturer is interrupted, there could be a significant disruption in commercial supply.
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If we were to experience any supply chain issues, including as a result of the COVID-19 pandemic, our product supply could be seriously disrupted.
−Removed: We expect that the logistical challenges associated with our supply chain will grow more complex as we expand enrollment in our clinical trials for CPI-006 and CPI-818 and as we commence any clinical trials for additional product candidates.
+Added: We expect that the logistical challenges associated with our supply chain will grow more complex as we expand enrollment in our clinical trials for mupadolimab, CPI-818 and ciforadenant and as we commence any clinical trials for additional product candidates.
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.
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Following potential approval of any of our product candidates, the FDA may impose significant restrictions on a product’s indicated uses or marketing or impose ongoing requirements for potentially costly and time consuming post-approval studies, post-market surveillance or clinical trials.
−Removed: Following approval, if any, of CPI-006, CPI-818 and ciforadenant or any other product candidate, such candidate will also be subject to ongoing FDA requirements governing the labeling, packaging, storage, distribution, safety surveillance, advertising, promotion, recordkeeping and reporting of safety and other post-market information.
+Added: Following approval, if any, of mupadolimab, CPI-818 and ciforadenant or any other product candidate, such candidate will also be subject to ongoing FDA requirements governing the labeling, packaging, storage, distribution, safety surveillance, advertising, promotion, recordkeeping and reporting of safety and other post-market information.
If we or a regulatory agency discovers previously unknown problems with a product, such as adverse events of unanticipated severity or frequency, or problems with the facility where the product is manufactured, a regulatory agency may impose restrictions on that product, the manufacturing facility or us, including requesting recall or withdrawal of the product from the market or suspension of manufacturing.
−Removed: If we or the manufacturing facilities for CPI-006, CPI-818 and ciforadenant or any other product candidate that may receive regulatory approval, if any, fail to comply with applicable regulatory requirements, a regulatory agency may:
+Added: If we or the manufacturing facilities for mupadolimab, CPI-818 and ciforadenant or any other product candidate that may receive regulatory approval, if any, fail to comply with applicable regulatory requirements, a regulatory agency may:
● issue warning letters or untitled letters;
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The FDA has the authority to require a risk evaluation and mitigation strategy (“REMS”) as part of an NDA or BLA or after approval, which may impose further requirements or restrictions on the distribution or use of an approved drug, such as limiting prescribing to certain physicians or medical centers that have undergone specialized training, limiting treatment to patients who meet certain safe-use criteria and requiring treated patients to enroll in a registry.
−Removed: In addition, if CPI-006, CPI-818 and ciforadenant or any of our other product candidates is approved, our product labeling, advertising and promotion will be subject to regulatory requirements and continuing regulatory review.
+Added: In addition, if mupadolimab, CPI-818 and ciforadenant or any of our other product candidates is approved, our product labeling, advertising and promotion will be subject to regulatory requirements and continuing regulatory review.
The FDA strictly regulates the promotional claims that may be made about prescription products.
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Further, the FDA’s and other regulatory authorities’ policies may change and additional government regulations may be enacted that could prevent, limit or delay regulatory approval of our product candidates.
−Removed: For instance, the EU has adopted the Clinical Trials Regulation (“CTR”) in April 2014, which is expected to come into application in 2022.
+Added: For instance, the EU has adopted the Clinical Trials Regulation (“CTR”) in April 2014, which is expected to become applicable by early 2022.
The CTR will be directly applicable in all EU member states, repealing the current Clinical Trials Directive.
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If we are slow or unable to adapt to changes in existing requirements or the adoption of new requirements or policies, or if we are not able to maintain regulatory compliance, we may be subject to enforcement action and we may not achieve or sustain profitability.
−Removed: 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.
+Added: 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
+Added: products from being developed, approved or commercialized in a timely manner or at all, which could negatively impact our business.
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.
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The FDA intends to use this risk-based assessment system to identify the categories of regulatory activity that can occur within a given geographic area, ranging from mission critical inspections to resumption of all regulatory activities.
+Added: Additionally, on April 15, 2021, the FDA issued a guidance document in which the FDA described its plans to conduct voluntary remote interactive evaluations of certain drug manufacturing facilities and clinical research sites.
+Added: According to the guidance, the FDA intends to request such remote interactive evaluations in situations where an in-person inspection would not be prioritized, deemed mission-critical, or where direct inspection is otherwise limited by travel restrictions, but where the FDA determines that remote evaluation would be appropriate.
Regulatory authorities outside the United States may adopt similar restrictions or other policy measures in response to the COVID-19 pandemic.
−Removed: If a prolonged
−Removed: government shutdown occurs, or if global health concerns continue to prevent the FDA or other regulatory authorities from conducting their regular inspections, reviews, or other regulatory activities, it could significantly impact the ability of the FDA or other regulatory authorities to timely review and process our regulatory submissions, which could have a material adverse effect on our business.
−Removed: Even if we receive regulatory approval we still may not be able to successfully commercialize CPI-006, CPI-818 and ciforadenant or any other product candidate, and the revenue that we generate from sales, if any, could be limited.
−Removed: Even if CPI-006, CPI-818 and ciforadenant or any of our other product candidates receive regulatory approval, they may not gain market acceptance among physicians, patients, healthcare payors or the medical community.
+Added: If a prolonged government shutdown occurs, or if global health concerns continue to prevent the FDA or other regulatory authorities from conducting their regular inspections, reviews, or other regulatory activities, it could significantly impact the ability of the FDA or other regulatory authorities to timely review and process our regulatory submissions, which could have a material adverse effect on our business.
+Added: Even if we receive regulatory approval we still may not be able to successfully commercialize mupadolimab, CPI-818 and ciforadenant or any other product candidate, and the revenue that we generate from sales, if any, could be limited.
+Added: Even if mupadolimab, CPI-818 and ciforadenant or any of our other product candidates receive regulatory approval, they may not gain market acceptance among physicians, patients, healthcare payors or the medical community.
The degree of market acceptance of our product candidates will depend on a number of factors, including:
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If any product candidate is approved but does not achieve an adequate level of acceptance by physicians, hospitals, healthcare payors or patients, we may not generate sufficient revenue from that product candidate and may not become or remain profitable.
−Removed: Our efforts to educate the medical community and third-party payors regarding the benefits of CPI-006, CPI-818 and ciforadenant or any of our other product candidates may require significant resources and may never be successful.
+Added: Our efforts to educate the medical community and third-party payors regarding the benefits of mupadolimab, CPI-818 and ciforadenant or any of our other product candidates may require significant resources and may never be successful.
Failure to obtain or maintain adequate coverage and reimbursement for our product candidates, if approved, could limit our ability to market those products and decrease our ability to generate revenue.
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Each third-party payor separately decides which products it will cover and establishes the reimbursement level, and there is no guarantee that any of our product candidates that may be approved for marketing by regulatory authorities will receive adequate coverage or reimbursement levels.
−Removed: Obtaining and maintaining coverage approval for a product
−Removed: candidate is time-consuming, costly and may be difficult.
+Added: Obtaining and maintaining coverage approval for a product candidate is time-consuming, costly and may be difficult.
We may be required to conduct expensive pharmacoeconomic studies to justify coverage and reimbursement or the level of coverage and reimbursement relative to other therapies.
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For example, in March 2010, the Patient Protection and Affordable Care Act, as amended by the Health Care and Education Reconciliation Act, collectively referred to as the ACA, was enacted with a goal of reducing the cost of healthcare and substantially changing the way healthcare is financed by both governmental and private insurers.
−Removed: The ACA, among other things, subjected biological products to potential competition by lower-cost biosimilars;
+Added: ACA, among other things, subjected biological products to potential competition by lower-cost biosimilars;
addressed a new methodology by which rebates owed by manufacturers under the Medicaid Drug Rebate Program are calculated for drugs that are inhaled, infused, instilled, implanted or injected;
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Since its enactment, there have been judicial, executive and Congressional challenges to certain aspects of the ACA.
−Removed: For example, the Tax Cuts and Jobs Act was enacted, which, among other things, removes penalties for not complying with the ACA’s individual mandate to carry health insurance.
−Removed: On December 14, 2018, a U.S.
−Removed: District Court Judge in the Northern District of Texas, ruled that the individual mandate is a critical and inseverable feature of the ACA, and therefore, because it was repealed as part of the Tax Act, the remaining provisions of the ACA are invalid as well.
−Removed: On December 18, 2019, the U.S.
−Removed: Court of Appeals for the 5th Circuit upheld the District Court's decision that the individual mandate was unconstitutional but remanded the case back to the District Court to determine whether the remaining provisions of the ACA are invalid as well.
−Removed: Supreme Court is currently reviewing the case, although it is unclear when a decision will be made or how the Supreme Court will rule.
−Removed: In addition, there may be other efforts to challenge, replace, modify, repeal, or otherwise invalidate the ACA.
−Removed: We are continuing to monitor any changes to the ACA that, in turn, may potentially impact our business in the future.
+Added: On June 17, 2021, the U.S.
+Added: Supreme Court dismissed the most recent judicial challenge to the ACA brought by several states without specifically ruling on the constitutionality of the ACA.
+Added: Prior to the Supreme Court’s decision, President Biden issued an executive order to initiate a special enrollment period from February 15, 2021 through August 15, 2021 for purposes of obtaining health insurance coverage through the ACA marketplace.
+Added: The executive order also instructed certain governmental agencies to review and reconsider their existing policies and rules that limit access to healthcare, including among others, reexamining Medicaid demonstration projects and waiver programs that include work requirements, and policies that create unnecessary barriers to obtaining access to health insurance coverage through Medicaid or the ACA.
+Added: It is unclear how other healthcare reform measures of the Biden administration or other efforts, if any, to challenge, repeal or replace the ACA will impact our business.
In addition, other legislative changes have been proposed and adopted in the United States since the Affordable Care Act was enacted.
−Removed: These new laws, among other things, included aggregate reductions of Medicare payments to providers of 2% per fiscal year that will remain in effect through 2030, with the exception of a temporary suspension from May 1, 2020 through March 31, 2021, unless additional Congressional action is taken.
+Added: These new laws, among other things, included aggregate reductions of Medicare payments to providers of 2% per fiscal year that will remain in effect through 2030, with the exception of a temporary suspension from May 1, 2020 through December 31, 2021, unless additional Congressional action is taken.
In addition, in January 2013, the American Taxpayer Relief Act of 2012 was signed into law, which, among other things, further reduced Medicare payments to several types of providers, including hospitals, imaging centers and cancer treatment centers.
Recently there has been heightened governmental scrutiny over the manner in which manufacturers set prices for their marketed products, which has resulted in several Congressional inquiries and proposed bills designed to, among other things, reform government program reimbursement methodologies.
−Removed: Additionally, individual states in the United States have also
−Removed: become increasingly active in passing legislation and implementing regulations designed to control pharmaceutical product pricing, including price or patient reimbursement constraints, discounts, restrictions on certain product access and marketing cost disclosure and transparency measures, and, in some cases, designed to encourage importation from other countries and bulk purchasing.
+Added: Additionally, individual states in the United States have also become increasingly active in passing legislation and implementing 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.
We expect that the ACA, these new laws and other healthcare reform measures that may be adopted in the future may result in additional reductions in Medicare and other healthcare funding, more rigorous coverage criteria, new payment methodologies and additional downward pressure on the price that we receive for any approved product.
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In general, however, the healthcare budgetary constraints in most European Union member states have resulted in restrictions on the pricing and reimbursement of medicines by relevant health service providers.
−Removed: Coupled with ever-increasing European Union and national regulatory burdens on those wishing to develop and market products, this could prevent or delay marketing approval of our product candidates, restrict or regulate post-approval activities and affect our ability to commercialize our product candidates, if approved.
+Added: Coupled with ever-increasing European Union and national regulatory burdens on those wishing to develop and market products, this could prevent or delay marketing approval of our product candidates, restrict or
+Added: regulate post-approval activities and affect our ability to commercialize our product candidates, if approved.
In markets outside of the United States and European Union, reimbursement and healthcare payment systems vary significantly by country, and many countries have instituted price ceilings on specific products and therapies.
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Any processes adopted by the FDA to implement the BPCIA could have a material adverse effect on the future commercial prospects for our biological products.
−Removed: Though ciforadenant and CPI-818 are small molecules and will not be regulated as biological products, CPI-006, which we are evaluating in a Phase 1/1b oncology clinical trial and a Phase 1 COVID-19 clinical trial, is a biological product.
+Added: Though ciforadenant and CPI-818 are small molecules and will not be regulated as biological products, mupadolimab, which we are evaluating in a Phase 1/1b oncology clinical trial, is a biological product.
We believe that any of our future product candidates approved as a biological product under a BLA should qualify for the twelve-year period of exclusivity.
−Removed: However, there is a risk that this exclusivity could be shortened due to Congressional action or otherwise, or that the FDA will not consider our product candidates to be reference
−Removed: products for competing products, potentially creating the opportunity for generic competition sooner than anticipated.
+Added: However, there is a risk that this exclusivity could be shortened due to Congressional action or otherwise, or that the FDA will not consider our product candidates to be reference products for competing products, potentially creating the opportunity for generic competition sooner than anticipated.
Other aspects of the BPCIA, some of which may impact the BPCIA exclusivity provisions, have also been the subject of recent litigation.
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While we have not obtained nor have we sought to obtain orphan designation for any product candidate, we believe many of the potential indications of our product candidates, if approved, could qualify for orphan drug designation.
−Removed: For instance, if CPI-006, CPI-818 or ciforadenant is approved for the treatment of certain solid tumors with small patient populations, such as melanoma, renal or triple-negative breast cancer, it is possible that it could qualify for orphan drug designation with respect to such indications.
+Added: For instance, if mupadolimab, CPI-818 or ciforadenant is approved for the treatment of certain solid tumors with small patient populations, such as melanoma, renal or triple-negative breast cancer, it is possible that it could qualify for orphan drug designation with respect to such indications.
As a result, we may seek to obtain orphan drug designation for our product candidates for any qualifying indications they may be approved for in the future.
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We may expend our limited resources to pursue a particular product candidate and fail to capitalize on product candidates that may be more profitable or for which there is a greater likelihood of success.
−Removed: Because we have limited financial and managerial resources, we focus on specific product candidates, including CPI-006, CPI-818 and ciforadenant.
+Added: Because we have limited financial and managerial resources, we focus on specific product candidates, including mupadolimab, CPI-818 and ciforadenant.
As a result, we may forgo or delay pursuit of opportunities with other product candidates that later prove to have greater commercial potential.
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In October 2020, we formed Angel Pharmaceuticals with a group of investors in China to create a new China-based biopharmaceutical company with a mission to bring innovative quality medicines to Chinese patients for treatment of serious diseases including cancer, autoimmune diseases and infectious diseases.
−Removed: We granted Angel Pharmaceuticals a license to rights to develop and commercialize our three clinical-stage candidates – CPI-006, CPI-818 and ciforadenant – in greater China and obtained global rights to our BTK inhibitor preclinical programs.
−Removed: While certain of our executive
−Removed: officers and directors will initially be on the board of directors of Angel Pharmaceuticals, we have limited control over it and so we will be subject to many of the same risks set forth above with respect to all collaborations.
+Added: We granted Angel Pharmaceuticals a license to rights to develop and commercialize our three clinical-stage candidates – mupadolimab, CPI-818 and ciforadenant – in greater China and obtained global rights to our BTK inhibitor preclinical programs.
+Added: While certain of our executive officers and directors will initially be on the board of directors of Angel Pharmaceuticals, we have limited control over it and so we will be subject to many of the same risks set forth above with respect to all collaborations.
Angel Pharmaceuticals will also be subject to many of the same risks that are set forth in this “Risk Factors” section pertaining to operations, government regulation, and intellectual property, which may adversely affect Angel Pharmaceuticals’ ability to develop and commercialize products.
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We also compete with these organizations to recruit management, scientists and clinical development personnel, which could negatively affect our level of expertise and our ability to execute our business plan.
−Removed: We will also face competition in establishing clinical trial sites, registering subjects for clinical trials and in identifying and in-licensing new product candidates.
+Added: We will also face
+Added: competition in establishing clinical trial sites, registering subjects for clinical trials and in identifying and in-licensing new product candidates.
Smaller or early-stage companies may also prove to be significant competitors, particularly through collaborative arrangements with large and established companies.
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These companies include Bristol-Myers Squibb (nivolumab, ipilimumab), Merck (pembrolizumab), Genentech (atezolizumab) and AstraZeneca (durvalumab, tremelimumab).
−Removed: There is also intense competition to develop COVID-19 therapeutic drugs and vaccines, many of which are further along in clinical development than CPI-006.
−Removed: If any such therapeutic drugs or vaccines were to gain approval, the utility of CPI-006 as a therapeutic for the treatment of COVID-19 could be negated.
+Added: There is also intense competition to develop COVID-19 therapeutic drugs and vaccines, many of which are further along in clinical development than mupadolimab.
+Added: If any such therapeutic drugs or vaccines were to gain approval, the utility of mupadolimab as a therapeutic for the treatment of COVID-19 could be negated.
Many of our competitors have significantly greater financial, technical, manufacturing, marketing, sales and supply resources or experience than we do.
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We have no internal sales, marketing or distribution capabilities.
−Removed: If CPI-006, CPI-818 and ciforadenant or any of our other product candidates ultimately receives regulatory approval, we may not be able to effectively market and distribute the product candidate.
−Removed: We may have to seek collaborators or invest significant amounts of financial and management resources to develop internal sales, distribution and marketing capabilities, some of which will be committed prior to any confirmation that CPI-006, CPI-818 and ciforadenant or any of our other product candidates will be approved, if at all.
+Added: If mupadolimab, CPI-818 and ciforadenant or any of our other product candidates ultimately receives regulatory approval, we may not be able to effectively market and distribute the product candidate.
+Added: We may have to seek collaborators or invest significant amounts of financial and management resources to develop internal sales, distribution and marketing capabilities, some of which will be committed prior to any confirmation that mupadolimab, CPI-818 and ciforadenant or any of our other product candidates will be approved, if at all.
We may not be able to enter into collaborations or hire consultants or external service providers to assist us in sales, marketing and distribution functions on acceptable financial terms or at all.
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● we may not be able to attract and build an effective marketing department or sales force;
−Removed: ● the cost of establishing a marketing department or sales force may exceed our available financial resources and the revenue generated by CPI-006, CPI-818 and ciforadenant or any other product candidates that we may develop, in-license or acquire;
+Added: ● the cost of establishing a marketing department or sales force may exceed our available financial resources and the revenue generated by mupadolimab, CPI-818 and ciforadenant or any other product candidates that we may develop, in-license or acquire;
● our direct sales and marketing efforts may not be successful.
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In these countries, pricing negotiations with governmental authorities can take considerable time after the receipt of marketing approval for a product candidate.
−Removed: To obtain reimbursement or pricing
−Removed: approval in some countries, we may be required to conduct clinical trials to compare the cost-effectiveness of our product candidates to other available therapies, which is time-consuming and costly.
+Added: To obtain reimbursement or pricing approval in some countries, we may be required to conduct clinical trials to compare the cost-effectiveness of our product candidates to other available therapies, which is time-consuming and costly.
If reimbursement of our future products is unavailable or limited in scope or amount, or if pricing is set at unsatisfactory levels, we may be unable to achieve or sustain profitability.
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If we are not able to retain our management, particularly our President and Chief Executive Officer, Dr.
−Removed: Miller, and to attract, on acceptable terms, additional
−Removed: qualified personnel necessary for the continued development of our business, we may not be able to sustain our operations or grow.
+Added: Miller, and to attract, on acceptable terms, additional qualified personnel necessary for the continued development of our business, we may not be able to sustain our operations or grow.
Although we have executed employment agreements with each member of our current executive management team, including Dr.
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We may encounter difficulties in managing our growth and expanding our operations successfully.
−Removed: We will need to grow our organization substantially to continue development and pursue the potential commercialization of CPI-006, CPI-818 and ciforadenant and our other product candidates.
−Removed: As we seek to advance CPI-006, CPI-818 and ciforadenant and other product candidates, we will need to expand our financial, development, regulatory, manufacturing, marketing and sales capabilities or contract with third parties to provide these capabilities for us.
+Added: We will need to grow our organization substantially to continue development and pursue the potential commercialization of mupadolimab, CPI-818 and ciforadenant and our other product candidates.
+Added: As we seek to advance mupadolimab, CPI-818 and ciforadenant and other product candidates, we will need to expand our financial, development, regulatory, manufacturing, marketing and sales capabilities or contract with third parties to provide these capabilities for us.
As our operations expand, we expect that we will need to manage additional relationships with various strategic partners, suppliers and other third parties.
−Removed: Our future financial performance and our ability to commercialize our product candidates and to compete effectively will depend, in part, on our ability to manage any future growth effectively.
+Added: Our future financial performance and our ability to
+Added: commercialize our product candidates and to compete effectively will depend, in part, on our ability to manage any future growth effectively.
We are subject to various federal and state healthcare laws and regulations, and our failure to comply with these laws and regulations could harm our results of operations and financial condition.
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in addition, the government may assert that a claim including items or services resulting from a violation of the federal Anti-Kickback Statute constitutes a false or fraudulent claim for purposes of the federal False Claims Act;
−Removed: ● the federal Health Insurance Portability and Accountability Act of 1996 (“HIPAA”), which imposes criminal and civil liability for executing a scheme to defraud any healthcare benefit program or making
−Removed: false statements relating to healthcare matters.
+Added: ● the federal Health Insurance Portability and Accountability Act of 1996 (“HIPAA”), which imposes criminal and civil liability for executing a scheme to defraud any healthcare benefit program or making false statements relating to healthcare matters.
Similar to the federal Anti-Kickback Statute, a person or entity does not need to have actual knowledge of the statute or specific intent to violate it to have committed a violation;
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In the event of contamination or injury, we could be held liable for damages or be penalized with fines in an amount exceeding our resources, and our clinical trials or regulatory approvals could be suspended.
−Removed: If product liability lawsuits are brought against us, we may incur substantial liabilities and may be required to limit commercialization of CPI-006, CPI-818 and ciforadenant or our other product candidates.
−Removed: We face an inherent risk of product liability as a result of the clinical testing of CPI-006, CPI-818 and ciforadenant, and the planned clinical testing of our other product candidates and will face an even greater risk if we commercialize our product candidates.
−Removed: For example, we may be sued if CPI-006, CPI-818 and ciforadenant or our other product candidates allegedly cause injury or are found to be otherwise unsuitable during product testing, manufacturing, marketing or sale.
+Added: If product liability lawsuits are brought against us, we may incur substantial liabilities and may be required to limit commercialization of mupadolimab, CPI-818 and ciforadenant or our other product candidates.
+Added: We face an inherent risk of product liability as a result of the clinical testing of mupadolimab, CPI-818 and ciforadenant, and the planned clinical testing of our other product candidates and will face an even greater risk if we commercialize our product candidates.
+Added: For example, we may be sued if mupadolimab, CPI-818 and ciforadenant or our other product candidates allegedly cause injury or are found to be otherwise unsuitable during product testing, manufacturing, marketing or sale.
Any such product liability claims may include allegations of defects in manufacturing, defects in design, a failure to warn of dangers inherent in the product candidate, negligence, strict liability and a breach of warranties.
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Regardless of the merits or eventual outcome, liability claims may result in:
−Removed: ● decreased demand for CPI-006, CPI-818 and ciforadenant or our other product candidates;
+Added: ● decreased demand for mupadolimab, CPI-818 and ciforadenant or our other product candidates;
● injury to our reputation;
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● loss of revenue;
−Removed: ● the inability to commercialize CPI-006, CPI-818 and ciforadenant or our other product candidates;
+Added: ● the inability to commercialize mupadolimab, CPI-818 and ciforadenant or our other product candidates;
● a decline in our stock price.
We have product liability insurance coverage in an amount and on terms and conditions that are customary for similarly situated companies and that are satisfactory to our board of directors.
−Removed: Our inability to retain sufficient product liability insurance at an acceptable cost to protect against potential product liability claims could prevent or inhibit the commercialization of CPI-006, CPI-818 and ciforadenant or our other product candidates.
+Added: Our inability to retain sufficient product liability insurance at an acceptable cost to protect against potential product liability claims could prevent or inhibit the commercialization of mupadolimab, CPI-818 and ciforadenant or our other product candidates.
Although we plan to maintain such insurance, any claim that may be brought against us could result in a court judgment or settlement in an amount that is not covered, in whole or in part, by our insurance or that is in excess of the limits of our insurance coverage.
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We and any of our existing or potential future collaborators will be required to report to regulatory authorities if any products that may be approved in the future cause or contribute to adverse medical events, and any failure to do so would result in sanctions that would materially harm our business.
−Removed: If we and any of our existing or potential future collaborators are successful in commercializing our products, the FDA and foreign regulatory authorities would require that we and any of our existing or potential future
−Removed: collaborators report certain information about adverse medical events if those products may have caused or contributed to those adverse events.
+Added: If we and any of our existing or potential future collaborators are successful in commercializing our products, the FDA and foreign regulatory authorities would require that we and any of our existing or potential future collaborators report certain information about adverse medical events if those products may have caused or contributed to those adverse events.
The timing of our obligation to report would be triggered by the date we become aware of the adverse event as well as the nature of the event.
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For example, we rely on our license agreement with Vernalis for rights with respect to the intellectual property covering ciforadenant and certain development candidates under our A2B receptor antagonist program.
−Removed: Further, we rely on our license agreement with The Scripps Research Institute for rights related to our lead development candidate for our anti-CD73 program, CPI-006.
+Added: Further, we rely on our license agreement with The Scripps Research Institute for rights related to our lead development candidate for our anti-CD73 program, mupadolimab.
These and other licenses we may enter into in the future may not provide adequate rights to use such intellectual property and technology in all relevant fields of use or in all territories in which we may wish to develop or commercialize our technology and products in the future.
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Therefore, we cannot be certain that our licensors or collaborators will prosecute, maintain, enforce and defend such intellectual property rights in a manner consistent with the best interests of our business, including by taking reasonable measures to protect the confidentiality of know-how and trade secrets, or by paying all applicable prosecution and maintenance fees related to intellectual property registrations for any of our product candidates.
−Removed: We also cannot be certain that our licensors have
−Removed: drafted or prosecuted the patents and patent applications licensed to us in compliance with applicable laws and regulations, which may affect the validity and enforceability of such patents or any patents that may issue from such applications.
+Added: We also cannot be certain that our licensors have drafted or prosecuted the patents and patent applications licensed to us in compliance with applicable laws and regulations, which may affect the validity and enforceability of such patents or any patents that may issue from such applications.
If they fail to do so, this could cause us to lose rights in any applicable intellectual property that we in-license, and as a result our ability to develop and commercialize products or product candidates may be adversely affected and we may be unable to prevent competitors from making, using and selling competing products.
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This failure to properly protect the intellectual property rights relating to our product candidates could have a material adverse effect on our financial condition and results of operations.
−Removed: While we have rights to an issued composition-of-matter patent in the United States and corresponding issued patents in certain foreign territories covering ciforadenant, we cannot be certain that the claims in any of our patent applications covering composition-of-matter of our other product candidates will be considered patentable by the United States Patent and Trademark Office (“USPTO”), courts in the United States or by the patent offices and courts in foreign countries, nor can we be certain that the claims in our issued composition-of-matter patents will not be found invalid or unenforceable if challenged.
+Added: While we have rights to an issued composition-of-matter patent in the United States and corresponding issued patents in certain foreign territories covering ciforadenant, we cannot be certain that the claims in any of our patent
+Added: applications covering composition-of-matter of our other product candidates will be considered patentable by the United States Patent and Trademark Office (“USPTO”), courts in the United States or by the patent offices and courts in foreign countries, nor can we be certain that the claims in our issued composition-of-matter patents will not be found invalid or unenforceable if challenged.
The patent application process is subject to numerous risks and uncertainties, and there can be no assurance that we or any of our existing or potential future collaborators will be successful in protecting our product candidates by obtaining and defending patents.
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Numerous third-party U.S.
−Removed: and foreign issued patents and
−Removed: pending patent applications exist in the fields in which we are developing product candidates.
+Added: and foreign issued patents and pending patent applications exist in the fields in which we are developing product candidates.
There may be third-party patents or patent applications with claims to materials, formulations, methods of manufacture or methods for treatment related to the use or manufacture of our product candidates.
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As the biotechnology industry expands and more patents are issued, the risk increases that our product candidates may be subject to claims of infringement of the patent rights of third parties.
−Removed: Because patent applications are maintained as confidential for a certain period of time, until the relevant application is published we may be unaware of third-party patent applications that, if issued as patents, may be infringed by commercialization of CPI-006, CPI-818 and ciforadenant or our other product candidates, and cannot be certain that we were the first to file a patent application related to a product candidate or technology.
+Added: Because patent applications are maintained as confidential for a certain period of time, until the relevant application is published we may be unaware of third-party patent applications that, if issued as patents, may be infringed by commercialization of mupadolimab, CPI-818 and ciforadenant or our other product candidates, and cannot be certain that we were the first to file a patent application related to a product candidate or technology.
Moreover, because patent applications can take many years to issue, there may be currently-pending patent applications that may later result in issued patents that our product candidates may infringe.
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● cause development delays;
−Removed: ● prevent us from commercializing CPI-006, CPI-818 and ciforadenant or our other product candidates until the asserted patent expires or is held finally invalid or not infringed in a court of law;
+Added: ● prevent us from commercializing mupadolimab, CPI-818 and ciforadenant or our other product candidates until the asserted patent expires or is held finally invalid or not infringed in a court of law;
● require us to develop non-infringing technology, which may not be possible on a cost-effective basis;
● require us to enter into royalty or licensing agreements, which may not be available on commercially reasonable terms, or at all.
−Removed: Although no third party has asserted a claim of patent infringement against us as of the date of this report, others may hold proprietary rights that could prevent CPI-006, CPI-818 and ciforadenant or our other product candidates from being marketed.
−Removed: Any patent-related legal action against us claiming damages and seeking to enjoin commercial activities relating to our product candidates or processes could subject us to potential liability for damages, including treble damages if we were determined to willfully infringe, and require us to obtain a license to manufacture or market CPI-006, CPI-818 and ciforadenant or our other product candidates.
+Added: Although no third party has asserted a claim of patent infringement against us as of the date of this report, others may hold proprietary rights that could prevent mupadolimab, CPI-818 and ciforadenant or our other product candidates from being marketed.
+Added: Any patent-related legal action against us claiming damages and seeking to enjoin commercial activities relating to our product candidates or processes could subject us to potential liability for damages, including treble damages if we were determined to willfully infringe, and require us to obtain a license to manufacture or market mupadolimab, CPI-818 and ciforadenant or our other product candidates.
Defense of these claims, regardless of their merit, would involve substantial litigation expense and would be a substantial diversion of employee resources from our business.
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In addition, we cannot be certain that we could redesign our product candidates or processes to avoid infringement, if necessary.
−Removed: Accordingly, an adverse determination in a judicial or administrative proceeding, or the failure to obtain necessary licenses, could prevent us from developing and commercializing CPI-006, CPI-818 and ciforadenant or our other product candidates, which could harm our business, financial condition and operating results.
+Added: Accordingly, an adverse determination in a judicial or administrative proceeding, or the failure to obtain necessary licenses, could prevent us from developing and commercializing mupadolimab, CPI-818 and ciforadenant or our other product candidates, which could harm our business, financial condition and operating results.
In addition, intellectual property litigation, regardless of its outcome, may cause negative publicity and could prohibit us from marketing or otherwise commercializing our product candidates and technology.
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Such a loss of patent protection would have a material adverse impact on our business.
−Removed: Interference proceedings provoked by third parties or brought by us or declared by the USPTO may be necessary to determine the priority of inventions with respect to our patents or patent applications or those of our licensors.
+Added: Interference proceedings provoked by third parties or brought by us or declared by the USPTO may be necessary to determine the priority of inventions with respect to our patents or patent applications or those of our
An unfavorable outcome could require us to cease using the related technology or to attempt to license rights to it from the prevailing party.
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These include provisions that affect the way patent applications will be prosecuted and may also affect patent litigation.
−Removed: In particular, under the Leahy-Smith Act, the United States transitioned in March 2013 to a “first to file” system in which the first inventor to file a patent
−Removed: application will be entitled to the patent.
+Added: In particular, under the Leahy-Smith Act, the United States transitioned in March 2013 to a “first to file” system in which the first inventor to file a patent application will be entitled to the patent.
Third parties are allowed to submit prior art before the issuance of a patent by the USPTO, and may become involved in post-grant proceedings including opposition, derivation, reexamination, inter-partes review or interference proceedings challenging our patent rights or the patent rights of others.
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As is common in the pharmaceutical industry, in addition to our employees, we engage the services of consultants to assist us in the development of our product candidates.
−Removed: Many of these consultants, and many of our employees, were previously employed at, or may have previously provided or may be currently providing consulting services to, other pharmaceutical companies including our competitors or potential competitors.
+Added: Many of these consultants, and many of our
+Added: employees, were previously employed at, or may have previously provided or may be currently providing consulting services to, other pharmaceutical companies including our competitors or potential competitors.
We may become subject to claims that we, our employees or a consultant inadvertently or otherwise used or disclosed trade secrets or other information proprietary to their former employers or their former or current clients.
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If we do not obtain patent term extension for our product candidates, our business may be materially harmed.
−Removed: Depending upon the timing, duration and specifics of potential FDA marketing approval of CPI-006, CPI-818, ciforadenant or other product candidates, one or more of our U.S.
+Added: Depending upon the timing, duration and specifics of potential FDA marketing approval of mupadolimab, CPI-818, ciforadenant or other product candidates, one or more of our U.S.
patents may be eligible for limited patent term restoration under the Drug Price Competition and Patent Term Restoration Act of 1984 (“Hatch-Waxman Amendments”).
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In addition, Congress may pass patent reform legislation that is unfavorable to us.
−Removed: The Supreme Court has ruled on several patent cases in recent years, either narrowing the scope of patent protection available in certain circumstances or weakening the rights of patent owners in certain situations.
+Added: The Supreme Court has ruled on several patent cases in recent years, either narrowing the scope of patent protection
+Added: available in certain circumstances or weakening the rights of patent owners in certain situations.
In addition to increasing uncertainty with regard to our ability to obtain patents in the future, this combination of events has created uncertainty with respect to the value of patents, once obtained.
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We may not be able to protect our intellectual property rights throughout the world.
−Removed: While we have issued patents directed at ciforadenant in the United States and certain foreign territories, and pending patent applications directed at CPI-006, CPI-818, ciforadenant and other product candidates in the United States and other countries, filing, prosecuting and defending patents on CPI-006, CPI-818, ciforadenant and our other product candidates in all countries throughout the world would be prohibitively expensive, and our intellectual property rights in some countries outside the United States can be less extensive than those in the United States.
+Added: While we have issued patents directed at ciforadenant in the United States and certain foreign territories, and pending patent applications directed at mupadolimab, CPI-818, ciforadenant and other product candidates in the United States and other countries, filing, prosecuting and defending patents on mupadolimab, CPI-818, ciforadenant and our other product candidates in all countries throughout the world would be prohibitively expensive, and our intellectual property rights in some countries outside the United States can be less extensive than those in the United States.
In addition, the laws of some foreign countries do not protect intellectual property rights to the same extent as federal and state laws in the United States.
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Our stock price has been volatile.
−Removed: The stock market in general and the market for stock of pharmaceutical companies in particular have experienced extreme volatility that has often been unrelated to the operating performance
−Removed: of particular companies.
+Added: The stock market in general and the market for stock of pharmaceutical companies in particular have experienced extreme volatility that has often been unrelated to the operating performance of particular companies.
The market price for our common stock may be influenced by those factors discussed in this “Risk Factors” section and many others, including:
1 unchanged sentence
● results of the clinical trials, and the results of trials of our competitors or those of other companies in our market sector;
−Removed: ● results for our Phase 3 clinical trial of CPI-006 for COVID-19;
−Removed: ● regulatory approval of CPI-006, CPI-818, ciforadenant and our other 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 approval of mupadolimab, CPI-818, ciforadenant and our other product candidates, or limitations to specific label indications or patient populations for its use, or changes or delays in the regulatory review process;
● Angel Pharmaceuticals’ ability to develop and commercialize product candidates in China;
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Because a small number of our existing stockholders own a majority of our voting stock, a stockholder’s ability to influence corporate matters will be limited.
−Removed: As of March 31, 2021, our executive officers, directors and greater than 5% stockholders, in the aggregate, owned approximately 41% of our outstanding common stock, including 1,458,000 shares of our common stock subject to prefunded warrants as described in Note 1 of our financial statements included in Part I, Item 1 of this quarterly report on Form 10-Q for the three months ended March 31, 2021.
+Added: As of June 30, 2021, our executive officers, directors and greater than 5% stockholders, in the aggregate, owned approximately 48% of our outstanding common stock, including 1,458,000 shares of our common stock subject to prefunded warrants as described in Note 1 of our financial statements included in Part I, Item 1 of this quarterly report on Form 10-Q for the three and six months ended June 30, 2021.
As a result, such persons, acting together, have the ability to control our management and affairs and substantially all matters submitted to our stockholders for approval, including the election and removal of directors and approval of any significant transaction.
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333-237040), covering the offering of up to $200 million of shares of common stock, preferred stock, warrants and units and entered into the Sales Agreement with Jefferies to sell shares of our common stock, from time to time, with aggregate gross sales proceeds of up to $50,000,000, through an at-the-market equity offering program under which Jefferies will act as our sales agent.
−Removed: As of March 31, 2021, we had sold 463,991 shares of common stock pursuant to the Sales Agreement.
+Added: As of June 30, 2021, we had sold 4,264,865 shares of common stock pursuant to the Sales Agreement.
In February 2021, we sold 9,783,660 shares of our common stock for net proceeds of $32.0 million in an underwritten public offering pursuant to our Registration Statement on Form S-3 (File No.
−Removed: As of March 31, 2021, $48.1 million remained for sale under the Sales Agreement.
+Added: As of June 30, 2021, $36.6 million remained for sale under the Sales Agreement.
Sales of a substantial number of shares of our common stock by our existing stockholders in the public market could cause our stock price to fall.
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We are an “emerging growth company,” as defined in the JOBS Act.
−Removed: For as long as we continue to be an emerging growth company, we may take advantage of exemptions from various reporting requirements that are applicable to other 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 of Sarbanes-Oxley, reduced disclosure obligations regarding executive compensation in our Annual Report on Form 10-K and our periodic reports and proxy statements and exemptions from the requirements of holding nonbinding advisory votes on executive compensation and stockholder approval of any golden parachute payments not previously approved.
+Added: For as long as we continue to be an emerging growth company, we may take advantage of exemptions from various reporting requirements that are applicable to other public companies that are not emerging growth companies, including, but not limited to, not being
+Added: required to comply with the auditor attestation requirements of Section 404 of Sarbanes-Oxley, reduced disclosure obligations regarding executive compensation in our Annual Report on Form 10-K and our periodic reports and proxy statements and exemptions from the requirements of holding nonbinding advisory votes on executive compensation and stockholder approval of any golden parachute payments not previously approved.
We will remain an emerging growth company until the earlier of (1) December 31, 2021, (2) the last day of the fiscal year in which we have total annual gross revenue of at least $1.07 billion, (3) the last day of the fiscal year in which we are deemed to be a “large accelerated filer” as defined in Rule 12b-2 under the Exchange Act, which would occur if the market value of our common stock held by non-affiliates exceeded $700.0 million as of the last business day of the second fiscal quarter of such fiscal year, or (4) the date on which we have issued more than $1.0 billion in non-convertible debt securities during the prior three-year period.
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Any failure to maintain internal control over financial reporting could severely inhibit our ability to accurately report our financial condition, results of operations or cash flows.
−Removed: If we are unable to conclude that our internal control over financial reporting is effective, or if our independent registered public accounting firm determines we have a material weakness or significant deficiency in our internal control over financial reporting once that firm begin its Section 404 reviews, investors may lose confidence in the accuracy and
−Removed: completeness of our financial reports, the market price of our common stock could decline, and we could be subject to sanctions or investigations by Nasdaq, the SEC or other regulatory authorities.
+Added: If we are unable to conclude that our internal control over financial reporting is effective, or if our independent registered public accounting firm determines we have a material weakness or significant deficiency in our internal control over financial reporting once that firm begin its Section 404 reviews, investors may lose confidence in the accuracy and completeness of our financial reports, the market price of our common stock could decline, and we could be subject to sanctions or investigations by Nasdaq, the SEC or other regulatory authorities.
Failure to remedy any material weakness in our internal control over financial reporting, or to implement or maintain other effective control systems required of public companies, could also restrict our future access to the capital markets.
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This provision may limit a stockholder’s ability to bring a claim in a judicial forum that it finds favorable for disputes with us or our directors, officers or other employees, which may discourage such lawsuits against us and our directors, officers and other employees.
−Removed: Alternatively, if a court were to find this provision in our 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: Alternatively, if a court were to find this provision in our 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.
This provision would not apply to suits brought to enforce a duty or liability created by the Exchange Act or any other claim for which the U.S.
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We may also experience security breaches that may remain undetected for an extended period.
−Removed: Any such security breach may compromise information stored on our networks, or those of our vendors, and may result in significant data losses or theft of our intellectual property or proprietary business information.
+Added: Any such security breach may compromise information stored on our
+Added: networks, or those of our vendors, and may result in significant data losses or theft of our intellectual property or proprietary business information.
Further, if such an event were to occur and cause interruptions in our operations, it could result in a material disruption of our development programs and our business operations, whether due to a loss of our trade secrets or other similar disruptions.
For example, the loss of clinical trial data from completed or future clinical trials could result in delays in our regulatory approval efforts and significantly increase our costs to recover or reproduce the data.
−Removed: In addition, such a breach may require notification to governmental agencies, the media or individuals pursuant to various federal and state privacy and security laws, if applicable, including HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act, and regulations implemented thereunder, as well as regulations promulgated by the Federal Trade Commission and state breach notification laws.
+Added: In addition, such a breach may require notification under applicable data privacy and security laws.
We would also be exposed to a risk of loss, including financial assets or litigation and potential liability, which could materially adversely affect our business, reputation, financial condition, results of operations and prospects.
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The GDPR has and will continue to increase compliance burdens on us, including by mandating potentially burdensome documentation requirements and granting certain rights to individuals to control how we collect, use, disclose, retain and process information about them.
−Removed: The processing of sensitive personal data, such as physical health condition, may impose heightened compliance burdens under the GDPR and is a topic of active interest among foreign regulators.
−Removed: Further, recent legal developments in Europe have created complexity and uncertainty regarding transfers of personal data from the EEA to the United States, e.g.
−Removed: on July 16, 2020, the Court of Justice of the European Union, or the CJEU invalidated the EU-US Privacy Shield Framework, or the Privacy Shield under which personal data could be transferred from the EEA to US entities who had self-certified under the Privacy Shield scheme.
+Added: The processing of
+Added: sensitive personal data, such as physical health condition, may impose heightened compliance burdens under the GDPR and is a topic of active interest among foreign regulators.
+Added: In addition, the GDPR prohbits the transfer of personal data from the EEA to the United States and other jurisdictions that the European Commission does not recognize as having “adequate” data protection laws unless a data transfer mechanism has been put in place.
+Added: On July 16, 2020, the Court of Justice of the European Union, (the “CJEU”) limited how organizations could lawfully transfer personal data from the EEA to the United States by invalidating invalidated the EU-US Privacy Shield Framework, (“Privacy Shield”) under which personal data could be transferred from the EEA to United States entities who had self-certified under the Privacy Shield scheme.
While the CJEU upheld the adequacy of the standard contractual clauses (a standard form of contract approved by the European Commission as an adequate personal data transfer mechanism, and potential alternative to the Privacy Shield), it made clear that reliance on them alone may not necessarily be sufficient in all circumstances.
Use of the standard contractual clauses must now be assessed on a case-by-case basis taking into account the legal regime applicable in the destination country, in particular applicable surveillance laws and rights of individuals and additional measures and/or contractual provisions may need to be put in place, however, the nature of these additional measures is currently uncertain.
+Added: The CJEU went on to state that if a competent supervisory authority believes that the standard contractual clauses cannot be complied with in the destination country and the required level of protection cannot be secured by other means, such supervisory authority is under an obligation to suspend or prohibit that transfer.
+Added: The European Commission has published revised standard contractual clauses for data transfers from the EEA:
+Added: the revised clauses must be used for relevant new data transfers from September 27, 2021;
+Added: existing standard contractual clauses arrangements must be migrated to the revised clauses by December 27, 2022.
+Added: We will be required to implement the revised standard contractual clauses, in relation to relevant existing contracts and certain additional contracts and arrangements, within the relevant time frames.
+Added: There is some uncertainty around whether the revised clauses can be used for all types of data transfers, particularly whether they can be relied on for data transfers to non-EEA entities subject to the GDPR.
+Added: These recent developments are likely to require us to review and amend the legal mechanisms by which we make and/or receive personal data transfers to/in the United States.
As supervisory authorities issue further guidance on personal data export mechanisms, including circumstances where the standard contractual clauses cannot be used, and/or start taking enforcement action, we could suffer additional costs, complaints and/or regulatory investigations or fines, and/or if we are otherwise unable to transfer personal data between and among countries and regions in which we operate, it could affect the manner in which we provide our services, the geographical location or segregation of our relevant systems and operations, and could adversely affect our financial results.
In addition, the GDPR provides for robust regulatory enforcement and fines of up to €20 million or 4% of the annual global revenue of the noncompliant company, whichever is greater.
−Removed: Further, from January 1, 2021, we will have to comply with the GDPR and the UK GDPR, which, together with the amended UK Data Protection Act 2018, retains the GDPR in United Kingdom national law, the latter regime having the ability to separately fine up to the greater of £17.5 million or 4% of global turnover.
−Removed: The relationship between the United Kingdom and the EU in relation to certain aspects of data protection law remains unclear, and it is unclear how United Kingdom data protection laws and regulations will develop in the medium to longer term, and how data transfers to and from the United Kingdom will be regulated in the long term.
−Removed: Currently there is a four to six-month grace period agreed in the EU and United Kingdom Trade and Cooperation Agreement, ending June 30, 2021 at the latest, whilst the parties discuss an adequacy decision.
−Removed: However, it is not clear whether (and when) an adequacy decision may be granted by the European Commission enabling data transfers from EU member states to the United Kingdom long term without additional measures.
+Added: Further, from January 1, 2021, we have to comply with the GDPR and the UK GDPR, which, together with the amended UK Data Protection Act 2018, retains the GDPR in United Kingdom national law, the latter regime having the ability to separately fine up to the greater of £17.5 million or 4% of global turnover.
+Added: The relationship between the United Kingdom and the EU in relation to certain aspects of data protection law remains unclear, and it is unclear how United Kingdom data protection laws and regulations will develop in the medium to longer term.
These changes may lead to additional costs and increase our overall risk exposure.
+Added: On June 28, 2021, the European Commission adopted an adequacy decision in favor of the United Kingdom, enabling data transfers from EU member states to the United Kingdom without additional safeguards.
+Added: However, the United Kingdom adequacy decision will automatically expire in June 2025 unless the European Commission renews or extends that decision and remains under review by the Commission during this period.
As we expand into other foreign countries and jurisdictions, we may be subject to additional laws and regulations that may affect how we conduct business.
3 unchanged sentences
Our operations could be subject to earthquakes, power shortages, telecommunications failures, water shortages, floods, hurricanes, typhoons, fires, extreme weather conditions, medical epidemics and pandemics, such as the COVID-19 pandemic, and other natural or manmade disasters or business interruptions, for which we are predominantly self-insured.
−Removed: We currently rely on several different manufacturers who supply different parts of the ciforadenant molecule and CPI-818 molecule, on one manufacturer for CPI-006 drug substance and on other third-party manufacturers to produce our other product candidates.
−Removed: Our ability to obtain clinical supplies of CPI-006, CPI-818 and ciforadenant or our other product candidates could be disrupted if the operations of these suppliers were affected by a man-made or natural disaster or other business interruption.
+Added: We currently rely on several different manufacturers who supply different parts of the ciforadenant molecule and CPI-818 molecule, on one manufacturer for mupadolimab drug substance and on other third-party manufacturers to
+Added: produce our other product candidates.
+Added: Our ability to obtain clinical supplies of mupadolimab, CPI-818 and ciforadenant or our other product candidates could be disrupted if the operations of these suppliers were affected by a man-made or natural disaster or other business interruption.
The occurrence of any of these business disruptions could seriously harm our operations and financial condition and increase our costs and expenses.
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Under the CARES Act, federal NOL carryforwards arising in tax years beginning after December 31, 2017 and before January 1, 2021 may be carried back to each of the five tax years preceding the tax year of such loss.
−Removed: The changes in the carryforward and carryback periods as well as the limitation on use of NOL carryforwards may significantly impact our ability to use NOL carryforwards, particularly for tax years
−Removed: beginning after December 31, 2020, as well as the timing of any such use, and could adversely affect our results of operations.
+Added: The changes in the carryforward and carryback periods as well as the limitation on use of NOL carryforwards may significantly impact our ability to use NOL carryforwards, particularly for tax years beginning after December 31, 2020, as well as the timing of any such use, and could adversely affect our results of operations.
If securities or industry analysts do not publish research or reports or publish unfavorable research or reports about our business, our stock price and trading volume could decline.
11 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.