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What changed in Bio Green Med Solution, Inc.'s 10-K — 2022 vs 2023

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Paragraph-level year-over-year comparison of Bio Green Med Solution, Inc.'s 2022 and 2023 10-K annual filings, covering the Business, Risk Factors, Legal Proceedings, Cybersecurity, MD&A and Market Risk sections. Every new, removed and edited paragraph is highlighted side-by-side so you can see exactly what management changed in the 2023 report.

+362 added−332 removedSource: 10-K (2024-03-21) vs 10-K (2023-03-08)

Top changes in Bio Green Med Solution, Inc.'s 2023 10-K

362 paragraphs added · 332 removed · 245 edited across 5 sections

Item 1. Business

Business — how the company describes what it does

76 edited+20 added−25 removed216 unchanged
Biggest changeThe following table summarizes our current development programs: ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ PROGRAM INDICATION ​ PHASE Transcriptional Regulation ​ ​ ​ ​ ​ ​ ​ ​ Fadraciclib CDK inhibitor (oral) ​ ​ ​ ​ Solid tumors – multiple cohorts defined by tumor histology and a basket cohort ​ ​ ​ Phase 1/2 to achieve proof of concept (in progress) ​ Fadraciclib CDK inhibitor (oral) ​ ​ Leukemias – multiple cohorts defined by leukemia type and a ​ ​ ​ Phase 1/2 to achieve proof of concept (in progress) ​ ​ ​ ​ basket cohort ​ ​ ​ Mitosis Regulation ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Plogosertib PLK inhibitor (oral) ​ Solid tumors – multiple cohorts defined by tumor histology and a basket cohort ​ ​ Phase 1/2 to achieve proof of concept (in progress) ​ ​ ​ ​ ​ ​ ​ ​ ​ NB: AML: acute myeloid leukemia; CDK: cyclin-dependent kinase; CLL: chronic lymphocytic leukemia; MDS: myelodysplastic syndrome; PLK: polo-like kinase.
Biggest changeThe aim of the current streamlined studies is to assess safety and identify signals of clinical activity which may lead to registration-enabling outcomes. 5 Table of Contents The following table summarizes our current development programs: PROGRAM INDICATION PHASE Transcriptional Regulation Fadraciclib CDK inhibitor (oral) Solid tumors – multiple cohorts defined by tumor histology and a basket cohort Phase 1/2 to achieve proof of concept Mitosis Regulation Plogosertib PLK inhibitor (oral) Solid tumors – multiple cohorts defined by tumor histology and a basket cohort Phase 1/2 to achieve proof of concept # CDK: cyclin-dependent kinase; PLK: polo-like kinase. # Study to resume recruitment following introduction of new oral formulation.
The process required by the FDA before our drug candidates may be marketed in the United States generally involves the following: ● completion of extensive nonclinical laboratory tests, which may include animal studies and formulation studies, all performed in accordance with the FDA’s good laboratory practice, or GLP, regulations; ● submission to the FDA of an investigational new drug application, or IND, which must become effective before clinical trials may begin and must be updated annually or when significant changes are made; ● approval by an IRB or ethics committee at each clinical site before the trial is initiated at such sites; 14 Table of Contents ● performance of adequate and well-controlled clinical trials in accordance with good clinical practice, or GCP, and other clinical-trial related regulations to establish the safety and efficacy of the drug candidate for each proposed indication; ● preparation and submission of a new drug application, or NDA, to the FDA; ● a determination by the FDA within 60 days of its receipt of an NDA to file the application for review; ● satisfactory completion of an FDA Advisory Committee review, if applicable; ● satisfactory completion of an FDA pre-approval inspection of the manufacturing facilities at which the product is produced to assess compliance with current good manufacturing practice requirements, or cGMP, regulations; ● potential audit of selected clinical trial sites to assess compliance with GCP and the integrity of the clinical data submitted in support of the NDA ; and ● FDA review and approval of the NDA to permit commercial marketing of the drug product for particular approved indications for use in the United States.
The process required by the FDA before our drug candidates may be marketed in the United States generally involves the following: ● completion of extensive nonclinical laboratory tests, which may include animal studies and formulation studies, all performed in accordance with the FDA’s good laboratory practice, or GLP, regulations; ● submission to the FDA of an investigational new drug application, or IND, which must become effective before clinical trials may begin and must be updated annually or when significant changes are made; ● approval by an IRB or ethics committee at each clinical site before the trial is initiated at such sites; ● performance of adequate and well-controlled clinical trials in accordance with good clinical practice, or GCP, and other clinical-trial related regulations to establish the safety and efficacy of the drug candidate for each proposed indication; ● preparation and submission of a new drug application, or NDA, to the FDA; ● a determination by the FDA within 60 days of its receipt of an NDA to file the application for review; ● satisfactory completion of an FDA Advisory Committee review, if applicable; ● satisfactory completion of an FDA pre-approval inspection of the manufacturing facilities at which the product is produced to assess compliance with current good manufacturing practice requirements, or cGMP, regulations; ● potential audit of selected clinical trial sites to assess compliance with GCP and the integrity of the clinical data submitted in support of the NDA; and ● FDA review and approval of the NDA to permit commercial marketing of the drug product for particular approved indications for use in the United States.
Recent clinical data show that treatment failure after CDK4/6 inhibitors is associated with amplification of cyclin E (Turner NC et al, JCO, 2019). Treatment of patients failing CDK4/6 inhibitors with CDK2/9 inhibitors, such as fadraciclib, may provide extended benefit to these patients.
Clinical data show that treatment failure after CDK4/6 inhibitors is associated with amplification of cyclin E (Turner NC et al, JCO, 2019). Treatment of patients failing CDK4/6 inhibitors with CDK2/9 inhibitors, such as fadraciclib, may provide extended benefit to these patients.
Fadraciclib synergizes with venetoclax in preclinical models at clinically achievable concentrations, supporting the clinical investigation of combination regimens of fadraciclib and venetoclax. In a Phase 1 study, i.v. fadraciclib was evaluated in combination with venetoclax in patients with relapsed or refractory (R/R) CLL.
Fadraciclib synergizes with venetoclax in preclinical models at clinically achievable concentrations, supporting the clinical investigation of combination regimens of fadraciclib and venetoclax. In a Phase 1 study, i.v. fadraciclib was evaluated in combination with venetoclax in patients with relapsed or refractory CLL.
Item 1. Business The following Business Section contains forward-looking statements. Our actual results could differ materially from those anticipated in these forward-looking statements as a result of certain risks, uncertainties and other factors including the risk factors set forth in Part I, Item 1A of this Annual Report on Form 10-K.
Item 1. Busin ess The following Business Section contains forward-looking statements. Our actual results could differ materially from those anticipated in these forward-looking statements as a result of certain risks, uncertainties and other factors including the risk factors set forth in Part I, Item 1A of this Annual Report on Form 10-K.
Published preclinical data Preclinical data suggest that fadraciclib may benefit adults and children with hematological malignancies, including AML, acute lymphocytic leukemias, or ALL, and in particular leukemias with MLL-r, CLL, B-cell lymphomas, multiple myelomas, and patients with certain solid tumors, including breast and uterine cancers, and neuroblastomas. ● Prolonged survival and reduced tumor burden in MYCN-addicted neuroblastoma The MYCN oncogene is over-expressed in several types of cancer, most notably neuroblastoma, and also rhabdomyosarcoma, medulloblastoma, astrocytoma, Wilms’ tumor and small cell lung cancer.
Published preclinical data Preclinical data suggest that fadraciclib may benefit adults and children with hematological malignancies, including AML, acute lymphocytic leukemias, or ALL, and in particular leukemias with MLL-r, CLL, B-cell lymphomas, multiple myelomas, and patients with certain solid tumors, including breast and uterine cancers, and neuroblastomas. 9 Table of Contents ● Prolonged survival and reduced tumor burden in MYCN-addicted neuroblastoma The MYCN oncogene is over-expressed in several types of cancer, most notably neuroblastoma, and also rhabdomyosarcoma, medulloblastoma, astrocytoma, Wilms’ tumor and small cell lung cancer.
Additionally, marketing authorization may be granted to a similar product for the same indication at any time if: ● the second applicant can establish that its product, although similar, is safer, more effective or otherwise clinically superior; 24 Table of Contents ● the applicant consents to a second orphan medicinal product application; or ● the applicant cannot supply enough orphan medicinal product.
Additionally, marketing authorization may be granted to a similar product for the same indication at any time if: ● the second applicant can establish that its product, although similar, is safer, more effective or otherwise clinically superior; 23 Table of Contents ● the applicant consents to a second orphan medicinal product application; or ● the applicant cannot supply enough orphan medicinal product.
In addition to the IRA’s drug price negotiation provisions, President Biden’s Executive Order 14087, issued in October 2022, called for the CMS innovation center to prepare and submit a report to the White House on potential payment and delivery modes that would complement to IRA, lower drug costs, and promote access to innovative drugs.
In addition to the IRA’s drug price negotiation provisions, Executive Order 14087, issued in October 2022, called for the CMS innovation center to prepare and submit a report to the White House on potential payment and delivery modes that would complement to IRA, lower drug costs, and promote access to innovative drugs.
There are no approved drugs that directly target MYCN, prompting investigation of indirect approaches such as suppression of MYCN gene expression via CDK9 inhibition, or exploitation of a synthetic lethal relationship between MYCN amplification/overexpression and inhibition of CDK2. ● May reverse drug resistance associated with addiction of cancer cells to cyclin E, the partner protein of CDK2 Fadraciclib as a single agent can induce tumor growth delay in HER2-positive breast cancer cells addicted to cyclin E and resistant to trastuzumab, while administration of fadraciclib in combination with trastuzumab resulted in regression or sustained tumor growth inhibition. ● May have activity in KRAS-mutated cancers Researchers led by Frank McCormick , PhD of University of California San Francisco and NCI’s Frederick National Lab for Cancer Research reported that overactive KRAS mutants are impeded by CDK9 inhibition ( Pui Lai L , et al, SLAS Discovery I-II 2021) .
There are no approved drugs that directly target MYCN, prompting investigation of indirect approaches such as suppression of MYCN gene expression via CDK9 inhibition, or exploitation of a synthetic lethal relationship between MYCN amplification/overexpression and inhibition of CDK2. ● May reverse drug resistance associated with addiction of cancer cells to cyclin E, the partner protein of CDK2 Fadraciclib as a single agent can induce tumor growth delay in HER2-positive breast cancer cells addicted to cyclin E and resistant to trastuzumab, while administration of fadraciclib in combination with trastuzumab resulted in regression or sustained tumor growth inhibition. ● May have activity in KRAS-mutated cancers Researchers led by Frank McCormick, PhD of University of California San Francisco and NCI’s Frederick National Lab for Cancer Research reported that overactive KRAS mutants are impeded by CDK9 inhibition (Lai LP, et al, SLAS Discovery 2021).
In this report, “Cyclacel,” the “Company,” “we,” “us,” and “our” refer to Cyclacel Pharmaceuticals, Inc. General We are a clinical-stage biopharmaceutical company working to develop innovative cancer medicines based on cell cycle, transcriptional regulation and mitosis control biology.
In this report, “Cyclacel,” the “Company,” “we,” “us,” and “our” refer to Cyclacel Pharmaceuticals, Inc. General We are a clinical-stage biopharmaceutical company working to develop innovative cancer medicines based on cell cycle, transcriptional regulation, epigenetics and mitosis biology.
We have 3 patent applications pending in the United States, 4 before the EPO and 30 pending patent applications in other countries. No assurances can be given that any patents will be issued with respect to the pending applications, nor that the claims will provide equivalent coverage in all jurisdictions.
We have 3 patent applications pending in the United States, 4 before the EPO and 25 pending patent applications in other countries. No assurances can be given that any patents will be issued with respect to the pending applications, nor that the claims will provide equivalent coverage in all jurisdictions.
The PREA requires a sponsor that is planning to submit a marketing application for a product that includes a new active ingredient, new indication, new dosage form, new dosing regimen or new route of administration to submit an initial Pediatric Study Plan, or PSP, within sixty days of an end-of-Phase 2 meeting or, if there is no such meeting, as early as practicable before the initiation of the Phase 3 or Phase 2/3 clinical trial.
The PREA requires a sponsor that is planning to submit a marketing application for a product that includes a new active ingredient, new indication, new dosage form, new dosing regimen or new route of administration to submit an initial Pediatric Study Plan, or PSP, within sixty days of an end-of-Phase 2 meeting or, if there is no such meeting, as early as 16 Table of Contents practicable before the initiation of the Phase 3 or Phase 2/3 clinical trial.
Even if a product qualifies for one or more of these programs, the FDA may later decide that the product no longer meets the conditions for qualification or decide that the time period for FDA review or approval will not be shortened. 18 Table of Contents fast track, priority review and breakthrough therapy designations do not change the scientific or medical standards for approval or the quality of evidence necessary to support approval but may expedite the development or approval process.
Even if a product qualifies for one or more of these programs, the FDA may later decide that the product no longer meets the conditions for qualification or decide that the time period for FDA review or approval will not be shortened. fast track, priority review and breakthrough therapy designations do not change the scientific or medical standards for approval or the quality of evidence necessary to support approval but may expedite the development or approval process.
Generally we plan to develop compounds through the Phase 2 proof-of-efficacy stage before seeking a partner. We may enter into partnering arrangements earlier than Phase 2 proof-of-concept trials where appropriate, or in connection with drug programs outside our core competency in oncology. 12 Table of Contents Licenses Some of our programs are based on technology licensed from others.
Generally we plan to develop compounds through the Phase 2 proof-of-efficacy stage before seeking a partner. We may enter into partnering arrangements earlier than Phase 2 proof-of-concept trials where appropriate, or in connection with drug programs outside our core competency in oncology. Licenses Some of our programs are based on technology licensed from others.
Once RP2D has been established, the trial will immediately enter proof-of-concept, cohort stage, using a Simon 2-stage design, where single agent fadraciclib will be administered to patients in up to eight cohorts defined by histology thought to be sensitive to the drug’s mechanism of action and informed by the clinical activity of fadraciclib in previous studies.
Once RP2D has been established, the trial will immediately enter proof-of-concept, cohort stage, using a Simon 2-stage design, where single agent fadraciclib will be administered to patients in up to eight cohorts defined by histology or molecular subtype thought to be sensitive to the drug’s mechanism of action and informed by the clinical activity of fadraciclib in previous studies.
Breakthrough therapy designation provides all the features of fast track designation in addition to intensive guidance on an efficient development program beginning as early as Phase 1, and FDA organizational commitment to expedited development, including involvement of senior managers and experienced review and regulatory staff in a proactive, collaborative, cross-disciplinary review, where appropriate.
Breakthrough therapy designation provides all the features of fast track 17 Table of Contents designation in addition to intensive guidance on an efficient development program beginning as early as Phase 1, and FDA organizational commitment to expedited development, including involvement of senior managers and experienced review and regulatory staff in a proactive, collaborative, cross-disciplinary review, where appropriate.
Data presented at the 2018 Annual Meeting of the American Association of Cancer Research demonstrated strong synergy between, 10 Table of Contents fadraciclib, and venetoclax in primary CLL, cells obtained from patients, including those with 17p deletions. In addition, the combination was active in two CLL samples which were resistant to either agent alone.
Data presented at the 2018 Annual Meeting of the American Association of Cancer Research demonstrated strong synergy between, fadraciclib, and venetoclax in primary CLL, cells obtained from patients, including those with 17p deletions. In addition, the combination was active in two CLL samples which were resistant to either agent alone.
Any reduction in reimbursement from Medicare or other government programs may result in a similar reduction in payments from private payors. There have been, and likely will continue to be, legislative and regulatory proposals at the foreign, federal and state levels directed at broadening the availability of healthcare and containing or lowering the cost of healthcare.
Any reduction in reimbursement from Medicare or other government programs may result in a similar reduction in payments from private payors. 25 Table of Contents There have been, and likely will continue to be, legislative and regulatory proposals at the foreign, federal and state levels directed at broadening the availability of healthcare and containing or lowering the cost of healthcare.
Positive preliminary data from the study was presented during a poster presentation at the 34 th EORTC-NCI-AACR (ENA) Symposium on Molecular Targets and Cancer Therapeutics and at our R&D Day on October 31, 2022 a principal investigator from Seoul National University Hospital showed preclinical data demonstrating sensitivity to fadra in biliary tract and pancreatic cancer cells obtained from patient specimens.
Encouraging preliminary data from the study were presented during a poster presentation at the 34 th EORTC-NCI-AACR (ENA) Symposium on Molecular Targets and Cancer Therapeutics. At our R&D Day on October 31, 2022, a principal investigator from Seoul National University Hospital showed preclinical data demonstrating sensitivity to fadra in biliary tract and pancreatic cancer cells obtained from patient specimens.
Some state laws require pharmaceutical companies to comply with the pharmaceutical industry’s voluntary compliance guidelines, or the relevant compliance guidance promulgated by the federal government, in addition to requiring drug manufacturers to report information related to payments to physicians and other health care providers or marketing expenditures to the extent that those laws impose requirements that are more stringent than the Physician Payments Sunshine Act.
Some state laws require pharmaceutical companies to comply with the pharmaceutical industry’s voluntary compliance guidelines, or the relevant compliance guidance promulgated by the 20 Table of Contents federal government, in addition to requiring drug manufacturers to report information related to payments to physicians and other health care providers or marketing expenditures to the extent that those laws impose requirements that are more stringent than the Physician Payments Sunshine Act.
Notably, on December 20, 2019, President Trump signed the Further Consolidated Appropriations Act for 2020 into law (P.L. 116-94) that includes a piece of bipartisan legislation called the Creating and Restoring Equal Access to Equivalent Samples Act of 2019 (the CREATES Act).
Notably, on December 20, 2019, the Further Consolidated Appropriations Act for 2020 was signed into law (P.L. 116-94) that includes a piece of bipartisan legislation called the Creating and Restoring Equal Access to Equivalent Samples Act of 2019 (the CREATES Act).
Manufacturers and other entities involved in the manufacture and distribution of approved drugs are required to register their establishments with the FDA and certain state agencies and are subject to periodic prescheduled or unannounced inspections by the FDA and 20 Table of Contents certain state agencies for compliance with cGMP and other laws.
Manufacturers and other entities involved in the manufacture and distribution of approved drugs are required to register their establishments with the FDA and certain state agencies and are subject to periodic prescheduled or unannounced inspections by the FDA and certain state agencies for compliance with cGMP and other laws.
In addition, regional healthcare authorities and individual hospitals are increasingly using bidding procedures to determine what pharmaceutical products and which suppliers will be included in their prescription drug and other 26 Table of Contents healthcare programs. These measures could reduce the ultimate demand for our products, once approved, or put pressure on our product pricing.
In addition, regional healthcare authorities and individual hospitals are increasingly using bidding procedures to determine what pharmaceutical products and which suppliers will be included in their prescription drug and other healthcare programs. These measures could reduce the ultimate demand for our products, once approved, or put pressure on our product pricing.
State and foreign laws also govern the privacy and security of 21 Table of Contents health information in some circumstances, many of which differ from each other in significant ways and often are not preempted by HIPAA, thus complicating compliance efforts.
State and foreign laws also govern the privacy and security of health information in some circumstances, many of which differ from each other in significant ways and often are not preempted by HIPAA, thus complicating compliance efforts.
Phase 1 explores both schedule and escalating doses of oral fadraciclib as a single-agent in a 28-day cycle with a primary 7 Table of Contents objective of identifying maximum tolerated dose or MTD and/or the recommended Phase 2 dose or RP2D.
Phase 1 explores both schedule and escalating doses of oral fadraciclib as a single-agent in a 28-day cycle with a primary objective of identifying maximum tolerated dose or MTD and/or the recommended Phase 2 dose or RP2D.
In addition to composition of matter claims, we seek coverage for solid state forms, polymorphic and crystalline forms, medical uses, combination therapies, specific regimens, pharmaceutical forms of our compounds and synthetic routes where available and appropriate.
In addition to composition of matter claims, we seek 12 Table of Contents coverage for solid state forms, polymorphic and crystalline forms, medical uses, combination therapies, specific regimens, pharmaceutical forms of our compounds and synthetic routes where available and appropriate.
According to the amended language, a sponsor may fulfill nonclinical testing requirements by completing various in vitro assays (e.g., cell-based assays, organ chips, or microphysiological systems), in silico studies (i.e., computer modeling), other human or nonhuman biology-based tests (e.g., bioprinting), or in vivo animal tests.
According to the amended language, a sponsor may fulfill nonclinical testing requirements by completing various in 14 Table of Contents vitro assays (e.g., cell-based assays, organ chips, or microphysiological systems), in silico studies (i.e., computer modeling), other human or nonhuman biology-based tests (e.g., bioprinting), or in vivo animal tests.
The anti-mitotic program is evaluating plogosertib, a PLK1 inhibitor, in solid tumors and hematological malignancies. Our strategy is to build a diversified biopharmaceutical business based on a pipeline of novel drug candidates addressing oncology and hematology indications.
The epigenetic/anti-mitotic program is evaluating plogosertib, a PLK1 inhibitor, in solid 4 Table of Contents tumors and hematological malignancies. Our strategy is to build a diversified biopharmaceutical business based on a pipeline of novel drug candidates addressing oncology and hematology indications.
We expect that changes or additions to the ACA, the Medicare and Medicaid programs and changes stemming from other healthcare reform measures, 25 Table of Contents especially with regard to healthcare access, financing or other legislation in individual states, could have a material adverse effect on the health care industry in the United States.
We expect that future changes or additions to the ACA, the Medicare and Medicaid programs and changes stemming from other healthcare reform measures, especially with regard to healthcare access, financing or other legislation in individual states, could have a material adverse effect on the health care industry in the United States.
Labile proteins rapidly depleted by short CDK9 inhibitor exposure include MCL1, MYCN, MYC, MYB, BCL2A1 and MDM2. o MCL1 is overexpressed in many types of cancer acting as a survival and drug resistance mechanism. o MYC proto-oncogenes encode MYC family proteins which are overexpressed in over 50% of human cancers often via gene amplification.
Labile proteins rapidly depleted by short exposure to a CDK2/9 inhibitor, such as fadraciclib, include MCL1, MYCN, MYC, MYB, BCL2A1 and MDM2. o MCL1 is overexpressed in many types of cancer acting as a survival and drug resistance mechanism. o MYC proto-oncogenes encode MYC family proteins which are overexpressed in over 50% of human cancers often via gene amplification.
More recently, in August 2022, President Biden signed into the law the Inflation Reduction Act of 2022, or the IRA. Among other things, the IRA has multiple provisions that may impact the prices of drug products that are both sold into the Medicare program and throughout the United States.
In August 2022, the Inflation Reduction Act of 2022, or the IRA, was signed into law. Among other things, the IRA has multiple provisions that may impact the prices of drug products that are both sold into the Medicare program and throughout the United States.
Several biopharmaceutical companies have CDK or MCL1 inhibitors in clinical trials including Amgen, AstraZeneca, Blueprint, Carrick, Dainippon Sumitomo, Eli Lilly, G1 Therapeutics, Kronos Bio, MEI Pharma, Merck, Novartis, Otsuka, Pfizer, Prelude, Servier, Syros, Tiziana and Vincerx.
Several biopharmaceutical companies have CDK inhibitors in clinical trials including Allorion Therapeutics , Amgen, AstraZeneca, Blueprint, Carrick, Dainippon Sumitomo, Eli Lilly, G1 Therapeutics, Incyclix Bio, Incyte, Kronos Bio, MEI Pharma, Merck, Novartis, Otsuka, Pfizer, Prelude, Servier, Syros, Tiziana and Vincerx.
We have retained worldwide rights to commercialize plogosertib. Business Strategy We plan to continue to build a diversified biopharmaceutical business focused on hematology and oncology based on a pipeline of novel drug candidates and utilizing our area of historical expertise in cancer cell cycle and mitosis biological mechanisms.
Business Strategy We plan to continue to build a diversified biopharmaceutical business focused on hematology and oncology based on a pipeline of novel drug candidates and utilizing our area of historical expertise in cancer cell cycle and mitosis biological mechanisms.
No dose-limiting toxicities have been observed. ​ Published preclinical data Preclinical data presented at the 2016 28th EORTC-NCI-AACR Molecular Targets and Cancer Therapeutics Symposium and at the 2017 Annual Meeting of the American Association of Cancer Research demonstrated the therapeutic potential of plogosertib as a targeted anti-cancer agent.
Published preclinical data Preclinical data presented at the 2016 28th EORTC-NCI-AACR Molecular Targets and Cancer Therapeutics Symposium and at the 2017 Annual Meeting of the American Association of Cancer Research demonstrated the therapeutic potential of plogosertib as a targeted anti-cancer agent.
Chronic lymphocytic leukemia (CYC065-02, i.v., NCT03739554) CLL cell survival depends on the expression of anti-apoptotic proteins, including MCL1 and BCL2. In this context, targeting MCL1 or BCL2 releases pro-death signals and commits CLL cells to apoptosis.
The study is not currently recruiting. 8 Table of Contents Chronic lymphocytic leukemia (CYC065-02, i.v., NCT03739554) CLL cell survival depends on the expression of anti-apoptotic proteins, including MCL1 and BCL2. In this context, targeting MCL1 or BCL2 releases pro-death signals and commits CLL cells to apoptosis.
Clinical development Phase 1/2 Study in advanced solid tumors and lymphomas (CYC140-101, orally dosed) ​ Similar to fadraciclib, this ongoing open-label Phase 1/2 registration-directed trial uses a streamlined design and seeks to first determine in a dose escalation stage the RP2D for single-agent plogosertib.
Our translational biology program supports the development of plogosertib in solid tumor and hematological malignancy indications. Clinical development Phase 1/2 Study in advanced solid tumors and lymphomas (CYC140-101, orally dosed) Similar to fadraciclib, this ongoing open-label Phase 1/2 registration-directed trial uses a streamlined design and seeks to first determine in a dose escalation stage the RP2D for single-agent plogosertib.
Patents and Proprietary Technology Patents and Proprietary Rights We own 16 patents granted in the United States, 8 granted by the European Patent Office, or EPO, and 46 granted in other countries worldwide. In addition, we have a license to 15 patents granted in the US, by the EPO or worldwide.
Patents and Proprietary Technology Patents and Proprietary Rights We own 14 patents granted in the United States, 5 granted by the European Patent Office, or EPO, and 30 granted in other countries worldwide. In addition, we have a license to 11 patents granted in the US, by the EPO or worldwide.
We are aware of several published patent applications, and understand that others may exist, that could support claims that, if granted and held valid, would cover various aspects of our developmental programs, including in some cases particular uses of our drug candidates fadraciclib and plogosertib, or other therapeutic candidates, or substances, processes and techniques that we use in the course of our research and development and manufacturing operations. 13 Table of Contents In addition, we understand that other applications and patents exist relating to potential uses of fadraciclib and plogosertib which are not part of our current clinical programs for those compounds.
We are aware of several published patent applications, and understand that others may exist, that could support claims that, if granted and held valid, would cover various aspects of our developmental programs, including in some cases particular uses of our drug candidates fadraciclib and plogosertib, or other therapeutic candidates, or substances, processes and techniques that we use in the course of our research and development and manufacturing operations.
Oral fadraciclib, both as a single agent and in combinations, will be administered to patients in up to seven cohorts relevant to the drug’s mechanism of action and informed by the clinical activity of fadraciclib in previous studies.
Oral fadraciclib, both as a single agent and in combinations, will be administered to patients in up to seven cohorts relevant to the drug’s mechanism of action and informed by the clinical activity of fadraciclib in previous studies. 14 patients have been enrolled in this study through five dose levels.
Our clinical development strategy is focused on two ongoing programs in transcriptional regulation and mitosis control biology. Focus on the cell cycle and cancer Our core area of expertise is in cell cycle biology and our scientists include recognized leaders in this field.
Our clinical development strategy is focused on two ongoing programs in transcriptional 11 Table of Contents regulation and epigenetics/mitosis control biology. We have retained worldwide rights to commercialize fadraciclib and plogosertib. Focus on the cell cycle and cancer Our core area of expertise is in cell cycle biology and our scientists include recognized leaders in this field.
Under the EU’s new Clinical Trials Regulation, which took effect in January 2022, there will be a centralized application procedure where one EU Member State’s competent authority takes the lead in reviewing part I of the application, which contains scientific and medicinal product documentation, and the other national authorities only have 22 Table of Contents limited involvement.
All suspected unexpected serious adverse reactions to the investigated drug that occur during the clinical trial have to be reported to the competent national authority and the Ethics Committee of the Member State where they occurred. 21 Table of Contents Under the EU’s new Clinical Trials Regulation, which took effect in January 2022, there will be a centralized application procedure where one EU Member State’s competent authority takes the lead in reviewing part I of the application, which contains scientific and medicinal product documentation, and the other national authorities only have limited involvement.
Clinical testing also must satisfy extensive good clinical practice, or GCP, requirements, including those relating to informed consent. 15 Table of Contents Clinical Trials For purposes of an NDA submission, clinical trials are typically conducted in the following three sequential phases, which may overlap: ● Phase 1 : The clinical trials are initially conducted in a limited population to test the drug candidate for safety, dose tolerance, absorption, metabolism, distribution and excretion in healthy humans.
Clinical Trials For purposes of an NDA submission, clinical trials are typically conducted in the following three sequential phases, which may overlap: ● Phase 1 : The clinical trials are initially conducted in a limited population to test the drug candidate for safety, dose tolerance, absorption, metabolism, distribution and excretion in healthy humans.
The FDA or the clinical trial sponsor may suspend a clinical trial at any time on various grounds, including a finding that the subjects or patients are being exposed to an unacceptable health risk.
The FDA or the clinical trial sponsor may suspend a clinical trial at any time on various grounds, including a finding that the subjects or patients are being exposed to an unacceptable health risk. Clinical testing also must satisfy extensive good clinical practice, or GCP, requirements, including those relating to informed consent.
Cancer cells are much more sensitive to PLK1 depletion than normal cells with intact cell cycle checkpoints. Inhibiting PLK1 blocks proliferation by prolonged mitotic arrest followed by onset of cancer cell death.
Cancer cells are much more sensitive to PLK1 depletion than normal cells with intact cell cycle checkpoints. Inhibiting PLK1 blocks proliferation by prolonged mitotic arrest followed by onset of cancer cell death. The lead drug in our anti-mitotic program is plogosertib (formerly known as CYC140).
The manufacturing facilities for our product candidates must meet applicable cGMP requirements to the FDA's or comparable foreign regulatory authorities' satisfaction before any product is approved and our commercial products can be manufactured. We rely, and expect to continue to rely, on third parties for the production of clinical and commercial quantities of our products in accordance with cGMP regulations.
The manufacturing facilities for our product candidates must meet applicable cGMP requirements to the FDA's or comparable foreign regulatory authorities' satisfaction before any product is approved and our commercial products can be manufactured.
Copies of our reports, proxy statements and other information may be inspected and copied at the public reference facilities maintained by the SEC at SEC Headquarters, Public Reference Room, 100 F Street, N.E., Washington D.C. 20549. The public may obtain information on the operation of the SEC’s Public Reference Room by calling the SEC at 1-800-SEC-0330.
Available information We file reports, proxy statements and other information with the Securities and Exchange Commission, or the SEC. Copies of our reports, proxy statements and other information may be inspected and copied at the public reference facilities maintained by the SEC at SEC Headquarters, Public Reference Room, 100 F Street, N.E., Washington D.C. 20549.
Our codes of conduct clearly outline our commitment to diversity and inclusion, where all employees are welcomed in an environment designed to make them feel comfortable, respected, and accepted regardless of their age, race, national origin, gender, religion, disability or sexual orientation. We have a set of policies explicitly setting forth our expectations for nondiscrimination and a harassment-free work environment.
We offer competitive compensation for our employees and strongly embrace a pay for performance philosophy in setting and adjusting compensation. 26 Table of Contents Our codes of conduct clearly outline our commitment to diversity and inclusion, where all employees are welcomed in an environment designed to make them feel comfortable, respected, and accepted regardless of their age, race, national origin, gender, religion, disability or sexual orientation.
The cohorts will include patients with breast cancer (selected for metastatic, hormone receptor positive, HER-2 negative, post-CDK4/6 inhibitor; HER-2 refractory; or triple negative), colorectal (including KRAS mutant), endometrial, hepatobiliary and ovarian cancers, and certain lymphomas. An additional basket cohort will enroll patients with mechanistically relevant biomarkers, including MCL1, MYC and cyclin E, regardless of histology.
The cohorts are expected to include patients with breast cancer (selected for metastatic, hormone receptor positive, HER-2 negative, post-CDK4/6 inhibitor; HER-2 refractory; or triple negative), colorectal (including KRAS mutant), endometrial, hepatobiliary, ovarian cancers, and certain lymphomas.
Orphan Drugs Under the Orphan Drug Act, the FDA may grant orphan drug designation to a drug intended to treat a rare disease or condition, defined as a disease or condition with a patient population of fewer than 200,000 individuals in the United States, or a patient population greater than 200,000 individuals in the United States and when there is no reasonable expectation that the cost of developing and making available the drug in the United States will be recovered from sales 19 Table of Contents in the United States for that drug.
Even if an SPA is agreed to, approval of the NDA is not guaranteed because a final determination that an agreed-upon protocol satisfies a specific objective, such as the demonstration of efficacy, or supports an approval decision, will be based on a complete review of all the data in the NDA. 18 Table of Contents Orphan Drugs Under the Orphan Drug Act, the FDA may grant orphan drug designation to a drug intended to treat a rare disease or condition, defined as a disease or condition with a patient population of fewer than 200,000 individuals in the United States, or a patient population greater than 200,000 individuals in the United States and when there is no reasonable expectation that the cost of developing and making available the drug in the United States will be recovered from sales in the United States for that drug.
The study design and preliminary data were presented at a poster during the 2019 Annual Meeting of the American Society of Hematology . Fadraciclib is administered intravenously via four-hour infusion on days 1 and 15 in combination with daily venetoclax on days 1 to 15. Initial dose escalation is 33% and 25% upon occurrence of DLT.
Fadraciclib is administered intravenously via four-hour infusion on days 1 and 15 in combination with daily venetoclax on days 1 to 15. Initial dose escalation is 33% and 25% upon occurrence of DLT.
Conditional approval 23 Table of Contents In specific circumstances, E.U. legislation (Article 14(7) Regulation (EC) No 726/2004 and Regulation (EC) No 507/2006 on Conditional Marketing Authorizations for Medicinal Products for Human Use) enables applicants to obtain a conditional marketing authorization prior to obtaining the comprehensive clinical data required for an application for a full marketing authorization.
Under the above described procedures, before granting the marketing authorization, the EMA or the competent authorities of the Member States of the EEA make an assessment of the risk-benefit balance of the product on the basis of scientific criteria concerning its quality, safety and efficacy. 22 Table of Contents Conditional approval In specific circumstances, E.U. legislation (Article 14(7) Regulation (EC) No 726/2004 and Regulation (EC) No 507/2006 on Conditional Marketing Authorizations for Medicinal Products for Human Use) enables applicants to obtain a conditional marketing authorization prior to obtaining the comprehensive clinical data required for an application for a full marketing authorization.
Twenty four patients have been dosed to date in the first seven dose escalation levels. ​ Advanced cancers (CYC065-01, i.v., NCT02552953) Fadraciclib, using i.v. administration, has been evaluated in a first-in-human, single agent, ascending dose, Phase 1 trial to assess its safety, tolerability, pharmacokinetics and pharmacodynamics in patients with advanced solid tumors.
We believe that fadraciclib’s inhibition of CDK2 and CDK9 may be superior to inhibiting either CDK2 or CDK9 alone. Advanced cancers (CYC065-01, i.v., NCT02552953) Fadraciclib, using i.v. administration, has been evaluated in a first-in-human, single agent, ascending dose, Phase 1 trial to assess its safety, tolerability, pharmacokinetics and pharmacodynamics in patients with advanced solid tumors.
The SEC maintains a website that contains reports, proxy statements and other information regarding Cyclacel. The address of the SEC website is http://www.sec.gov.
The public may obtain information on the operation of the SEC’s Public Reference Room by calling the SEC at 1-800-SEC-0330. The SEC maintains a website that contains reports, proxy statements and other information regarding Cyclacel. The address of the SEC website is http://www.sec.gov.
Similarly, an IRB can suspend or terminate approval of a clinical trial at its institution if the clinical trial is not being conducted in accordance with the clinical protocol, GCP, or other IRB requirements or if the drug has been associated with unexpected serious harm to patients. 16 Table of Contents NDA Submission and Review by the FDA Assuming successful completion of all required testing in accordance with all applicable regulatory requirements, the results of product development, preclinical studies and clinical trials are submitted to the FDA as part of an NDA requesting approval to market the product for one or more indications.
NDA Submission and Review by the FDA Assuming successful completion of all required testing in accordance with all applicable regulatory requirements, the results of product development, preclinical studies and clinical trials are submitted to the FDA as part of an NDA requesting approval to market the product for one or more indications.
The principal purposes of our equity incentive plans are to attract, retain and reward personnel through the granting of equity-based compensation awards in order to increase shareholder value and our success by motivating such individuals to perform to the best of their abilities to achieve our objectives. 27 Table of Contents We recognize that our industry is specialized and dynamic and a significant aspect of our success is our continued ability to execute our human capital strategy of attracting, engaging, developing and retaining highly skilled talent.
The principal purposes of our equity incentive plans are to attract, retain and reward personnel through the granting of equity-based compensation awards in order to increase shareholder value and our success by motivating such individuals to perform to the best of their abilities to achieve our objectives.
These findings support the hypothesis that dual targeting of the MCL1- and BCL2-dependent mechanisms could induce synergistic cell death by apoptosis and highlight an opportunity to rationally disrupt the pathways promoting survival of leukemia cells.
These findings support the hypothesis that dual targeting of the MCL1- and BCL2-dependent mechanisms could induce synergistic cell death by apoptosis and highlight an opportunity to rationally disrupt the pathways promoting survival of leukemia cells. 10 Table of Contents Mitosis Regulation Program Polo-Like-Kinase inhibitor — Plogosertib In our Polo-like Kinase, or PLK, inhibitor program, we have discovered potent and selective small molecule inhibitors of PLK1.
The protocol allows for expansion of a cohort based on response which may allow acceleration of the clinical development and registration plan for fadraciclib. The primary objective of Phase 2 is to achieve proof of concept and determine preliminary efficacy by overall response rate. Safety, pharmacokinetics or PK and efficacy will be investigated for all subjects.
The primary objective of Phase 2 is to achieve proof of concept and determine preliminary efficacy by overall response rate. Safety, pharmacokinetics and efficacy will be investigated for all subjects. Exploratory objectives are to investigate clinical pharmacodynamics and pharmacogenomics of fadraciclib.
The protocol allows for expansion of individual cohorts based on response which may allow acceleration of the clinical development and registration plan for plogosertib.
The protocol allows for expansion of individual cohorts based on response which may allow acceleration of the clinical development and registration plan for plogosertib. Fifteen patients have been treated at the first five dose escalation levels with no dose limiting toxicities observed.
Moreover, 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 and enacted federal and state legislation designed to, among other things, bring more transparency to product pricing, review the relationship between pricing and manufacturer patient programs, and reform government program reimbursement methodologies for drug products.
These changes include aggregate reductions to Medicare payments to providers of up to 2% per fiscal year pursuant to the Budget Control Act of 2011, which began in 2013 and was extended by the Consolidated Appropriations Act for 2023, and will remain in effect through 2032 unless additional Congressional action is taken. 24 Table of Contents Moreover, 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 and enacted federal and state legislation designed to, among other things, bring more transparency to product pricing, review the relationship between pricing and manufacturer patient programs, and reform government program reimbursement methodologies for drug products.
In some cases, the FDA may condition approval of an NDA for a drug candidate on the sponsor’s agreement to conduct a Phase 4, which includes additional clinical trials to further assess the drug’s safety and effectiveness after NDA approval.
In some cases, the FDA may condition approval of an NDA for a drug candidate on the sponsor’s agreement to conduct a Phase 4, which includes additional clinical trials to further assess the drug’s safety and effectiveness after NDA approval. 15 Table of Contents In the Consolidated Appropriations Act for 2023, Congress amended the FDCA to require sponsors of a Phase 3 clinical trial, or other “pivotal study” of a new drug to support marketing authorization, to submit a diversity action plan for such clinical trial.
As a result, we are dependent on corporate partners, licensees or other third parties for the manufacturing of clinical and commercial scale quantities of all of our products. We believe that this strategy will enable us to direct operational and financial resources to the development of our product candidates rather than diverting resources to establishing a manufacturing infrastructure.
As a result, we are dependent on corporate partners, licensees or other third parties for the manufacturing of clinical (and eventually commercial) scale quantities of all of our products.
Recent data with another PLK1 inhibitor in clinical development, suggest that PLK1 inhibition may be effective in KRAS-mutated metastatic colorectal cancer. Plogosertib is a novel, small molecule, selective, PLK1 inhibitor which has demonstrated potent and selective target inhibition (PLK1 IC50 approximately 3 nM) and impressive efficacy in human tumor xenografts at non-toxic doses.
Plogosertib is a novel, small molecule, selective, PLK1 inhibitor which has demonstrated an epigenetic mechanism, potent and selective target inhibition (PLK1 IC50 approximately 3 nM) and impressive efficacy in human tumor xenografts at non-toxic doses. Plogosertib has improved pharmaceutical properties over earlier, clinical stage, PLK inhibitors.
Our breach of an existing license or failure to obtain a license to technology required to develop, test and commercialize our products may seriously harm our business.
Our breach of an existing license or failure to obtain a license to technology required to develop, test and commercialize our products may seriously harm our business. In March 2023 we terminated our license agreement with Daiichi Sankyo Co., Ltd. for patents and patent applications covering sapacitabine for commercial reasons.
A sponsor can submit amendments to an agreed upon initial PSP at any time if changes to the pediatric plan need to be considered based on data collected from pre-clinical studies, early-phase clinical trials or other clinical development programs. 17 Table of Contents If regulatory approval of a product is granted, such approval is limited to the conditions of use (e.g., patient population, indication) described in the application and may entail further limitations on the indicated uses for which such product may be marketed.
The FDA and the sponsor must reach an agreement on the PSP. A sponsor can submit amendments to an agreed upon initial PSP at any time if changes to the pediatric plan need to be considered based on data collected from pre-clinical studies, early-phase clinical trials or other clinical development programs.
We are also a proud equal opportunity employer and cultivate a highly collaborative and entrepreneurial culture. Legal Proceedings From time to time, we may be involved in routine litigation incidental to the conduct of our business. As of December 31, 2022, we were not party to any material legal proceedings. Corporate information We were incorporated in Delaware in August 1997.
We have a set of policies explicitly setting forth our expectations for nondiscrimination and a harassment-free work environment. We are also a proud equal opportunity employer and cultivate a highly collaborative and entrepreneurial culture. Legal Proceedings From time to time, we may be involved in routine litigation incidental to the conduct of our business.
Our active and planned Phase 1/2 clinical studies use of oral administration as empirical data from our clinical studies suggests that daily dosing by the oral route is a preferred strategy for both our drugs. We also conducted certain early clinical studies using i.v. administration.
Clinical Development Pipeline Our pipeline of innovative medicines aims to provide safe and effective anticancer treatment options to patients combined with the convenience of oral administration. Our preclinical and clinical studies suggests that daily dosing by the oral route is a preferred strategy for both our drugs. We also conducted certain early clinical studies using i.v. administration.
Our corporate headquarters are located at 200 Connell Drive, Suite 1500, Berkeley Heights, New Jersey 07922, and our telephone number is 908-517-7330. Our employees are located in the United States and the United Kingdom. Available information We file reports, proxy statements and other information with the Securities and Exchange Commission, or the SEC.
As of December 31, 2023, we were not party to any material legal proceedings. Corporate information We were incorporated in Delaware in August 1997. Our corporate headquarters are located at 200 Connell Drive, Suite 1500, Berkeley Heights, New Jersey 07922, and our telephone number is 908-517-7330. Our employees are located in the United States and the United Kingdom.
In part 3 of the study high bioequivalence of an oral formulation of fadraciclib was reported at the 32 nd EORTC-NCI-AACR (ENA) Symposium in October 2020 .
In part 3 of the study high bioequivalence of an oral formulation of fadraciclib was reported at the 32 nd EORTC-NCI-AACR (ENA) Symposium in October 2020. Dose limiting toxicities were reversible neutropenia, thrombocytopenia, febrile neutropenia, diarrhea, hypomagnesemia, white blood cell lysis syndrome and its associated electrolyte abnormalities and liver enzyme elevations.
Government Regulation The FDA and comparable regulatory agencies in state and local jurisdictions, as well as in foreign countries, impose substantial regulatory requirements upon the clinical development, manufacture, marketing and distribution of drugs.
We believe that this strategy will enable us to direct operational and financial resources to the development of our product candidates rather than diverting resources to establishing a manufacturing infrastructure. 13 Table of Contents Government Regulation The FDA and comparable regulatory agencies in state and local jurisdictions, as well as in foreign countries, impose substantial regulatory requirements upon the clinical development, manufacture, marketing and distribution of drugs.
Phase 1 explores both schedule and escalating doses of oral fadraciclib as a single-agent in a 28-day cycle with a primary objective of identifying MTD and/or the RP2D . Once RP2D has been established, the trial will immediately enter proof-of-concept, cohort stage, using a Simon 2-stage design.
Leukemias Phase 1/2 study in hematological malignancies (CYC065-102, dosed orally, NCT05168904) This is an open-label, multicenter, Phase 1/2 registration-directed trial using a streamlined design. Phase 1 explores both schedule and escalating doses of oral fadraciclib as a single-agent in a 28-day cycle with a primary objective of identifying MTD and/or the RP2D .
Fadraciclib has single agent efficacy in AML xenografts and the potential to be combined with approved AML therapies.
Fadraciclib has single agent efficacy in AML xenografts and the potential to be combined with approved AML therapies. In leukemia cells harboring the rearranged MLL-r, fadraciclib reduced both MCL1 expression and CDK9 dependent transcription of MLL-regulated leukemogenic genes.
CDK2 and CDK9 inhibitors have been shown to induce apoptosis of cancer cells. CDK2/9 inhibition may also overcome aberrant cell cycle control in certain non-malignant diseases of proliferation.
CDK2 and CDK9 inhibitors have been shown to induce apoptosis of cancer cells.
PLK1 is a serine/threonine kinase with a central role in cell division, or the mitotic phase of the cell cycle, and is an important regulator of the DNA damage checkpoint. PLK1 over-expressing tumors include colorectal, esophageal, gastric, leukemia, lung, lymphoma, ovarian and squamous cell cancers, as well as MYC amplified cancers including breast.
Polo Kinase was discovered by Professor David Glover, our former Chief Scientist. PLK1 is a serine/threonine kinase with a central role in cell division, or the mitotic phase of the cell cycle, and is an important regulator of the DNA damage checkpoint.
In leukemia cells harboring the rearranged MLL-r, fadraciclib reduced both MCL1 expression and CDK9 dependent transcription of MLL-regulated leukemogenic genes. 9 Table of Contents We completed enrollment in a Phase 1 study evaluating i.v. fadraciclib in combination with venetoclax in patients with relapsed or refractory AML or MDS.
We completed enrollment in a Phase 1 study evaluating i.v. fadraciclib in combination with venetoclax in patients with relapsed or refractory AML or MDS. The study design and preliminary data were presented at a poster during the 2019 Annual Meeting of the American Society of Hematology .
Centers for Medicare and Medicaid Services, or CMS, to test innovative payment and service delivery models to lower Medicare and Medicaid spending. Following several years of litigation in the federal courts, in June 2021, the U.S. Supreme Court upheld the ACA when it dismissed a legal challenge to the ACA’s constitutionality.
Centers for Medicare and Medicaid Services, or CMS, to test innovative payment and service delivery models to lower Medicare and Medicaid spending.
Fadraciclib targets: ● CDK2, which drives cell cycle transition and is activated by cyclin E. ● CDK9 regulates transcription of certain genes through phosphorylation of RNA polymerase II c-terminal domain Ser2, blocking new mRNA. MCL1 mRNA and protein are labile (rapidly turned over). Blocking CDK9-dependent transcription quickly leads to loss of MCL1 protein, resulting in apoptosis in MCL1-dependent cancer cells.
We intend to test this hypothesis in patient cohorts during the proof of concept stage of our Phase 1/2 CYC065-101 study. ● CDK9/cyclin T regulates transcription of certain genes through phosphorylation of RNA polymerase II C-terminal domain Ser2. MCL1 mRNA and protein are labile (turn over rapidly).
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The lead drug in our anti-mitotic program is plogosertib (formerly known as CYC140). 5 Table of Contents Clinical Development Pipeline Our pipeline of innovative medicines aims to provide safe and effective anticancer treatment options to patients combined with the convenience of oral administration.
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Fadraciclib inhibits CDK2, which is activated by Cyclin E, an oncogene to which cancer cells become addicted and CDK9 which regulates transcription of certain genes through phosphorylation of RNA polymerase II . We believe that CDK2 and CDK9 inhibition together may be superior to CDK2 or CDK9 inhibition alone.
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The aim of the current streamlined studies is to assess safety and identify signals of clinical activity which may lead to registration-enabling outcomes.
Added
CDK2/9 inhibition may also overcome aberrant cell cycle control in certain non-malignant diseases of proliferation. 6 Table of Contents Fadraciclib mechanism and potential biomarkers: ● CDK2/cyclin E drives cell cycle transition: o The cyclin dependent kinase inhibitor 2A (CDKN2A) gene encodes two tumor suppressor proteins p16INK4A and p14ARF. p16INK4A inhbits the activity of CDK4/6 and p14ARF inhibits MDM2-mediated degradation of p53.

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Item 1A. Risk Factors

Risk Factors — what could go wrong, per management

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Biggest changeIf we do not pay a proper claim for indemnification in full within 60 days after we receive a written claim for such indemnification, except in the case of a claim for an advancement of expenses, in which case such period is 20 days, our restated certificate of incorporation and our restated bylaws authorize the claimant to bring an action against us and prescribe what constitutes a defense to such action. 61 Table of Contents Section 145 of the Delaware General Corporation Law permits a corporation to indemnify any director or officer of the corporation against expenses (including attorney’s fees), judgments, fines and amounts paid in settlement actually and reasonably incurred in connection with any action, suit or proceeding brought by reason of the fact that such person is or was a director or officer of the corporation, if such person acted in good faith and in a manner that he reasonably believed to be in, or not opposed to, the best interests of the corporation, and, with respect to any criminal action or proceeding, if he or she had no reason to believe his or her conduct was unlawful.
Biggest changeSection 145 of the Delaware General Corporation Law permits a corporation to indemnify any director or officer of the corporation against expenses (including attorney’s fees), judgments, fines and amounts paid in settlement actually and reasonably incurred in connection with any action, suit or proceeding brought by reason of the fact that such person is or was a director or officer of the corporation, if such person acted in good faith and in a manner that he reasonably believed to be in, or not opposed to, the best interests of the corporation, and, with respect to any criminal action or proceeding, if he or she had no reason to believe his or her conduct was unlawful.
Most recently, in August 2022, President Biden signed into the law the Inflation Reduction Act of 2022, or the IRA. Among other things, the IRA has multiple provisions that may impact the prices of drug products that are both sold into the Medicare program and throughout the United States.
Most recently, in August 2022, President Biden signed into law the Inflation Reduction Act of 2022, or the IRA. Among other things, the IRA has multiple provisions that may impact the prices of drug products that are both sold into the Medicare program and throughout the United States.
Failure can occur at any stage of the testing and we may experience numerous unforeseen events during, or as a result of, the clinical trial process that could delay or prevent commercialization of our current or future drug candidates, including, but not limited to: ● delays in securing clinical investigators or trial sites for our clinical trials; ● delays in obtaining institutional review board, or IRB, and regulatory approvals to commence a clinical trial; ● failure to obtain regulatory authority permission to conduct a clinical trial, after review of an investigational new drug or equivalent foreign application or amendment; ● slower than anticipated rates of subject recruitment and enrollment, or not reaching the targeted number of subjects because of competition for patients from other trials; ● negative or inconclusive results from clinical trials, as demonstrated by our announcement on February 24, 2017 that our SEAMLESS Phase 3 study failed to reach its primary endpoint; ● inability to generate satisfactory preclinical or other nonclinical data, including, toxicology, or other in vivo or in vitro data or diagnostics to support the initiation or continuation of clinical trials; ● unforeseen safety issues; ● failure by clinical sites or contract research organizations, or CROs, or other third parties to adhere to clinical trial requirements, GCP, or other applicable regulatory requirements; ● subjects discontinuing participating in our clinical trials at a greater than expected rate; ● imposition by the FDA of a clinical hold or the requirement by other similar regulatory agencies that one or more clinical trials be delayed or halted; ● uncertain dosing issues that may or may not be related to incompletely explored pharmacokinetic and pharmacodynamics behaviors; ● approval and introduction of new therapies or changes in standards of practice or regulatory guidance that render our clinical trial endpoints or the targeting of our proposed indications less attractive; ● inability to monitor patients adequately during or after treatment or problems with investigator or patient compliance with the trial protocols; ● inability to replicate in large, controlled studies safety and efficacy data obtained from a limited number of patients in uncontrolled trials; ● the ultimate affordability of the cost of clinical trials of our product candidates; ● changes in regulatory requirements and guidance that require amending or submitting new clinical protocols or performing additional nonclinical studies; and ● unavailability of clinical trial supplies.
Failure can occur at any stage of the testing and we may experience numerous unforeseen events during, or as a result of, the 27 Table of Contents clinical trial process that could delay or prevent commercialization of our current or future drug candidates, including, but not limited to: ● delays in securing clinical investigators or trial sites for our clinical trials; ● delays in obtaining institutional review board, or IRB, and regulatory approvals to commence a clinical trial; ● failure to obtain regulatory authority permission to conduct a clinical trial, after review of an investigational new drug or equivalent foreign application or amendment; ● slower than anticipated rates of subject recruitment and enrollment, or not reaching the targeted number of subjects because of competition for patients from other trials; ● negative or inconclusive results from clinical trials, as demonstrated by our announcement on February 24, 2017 that our SEAMLESS Phase 3 study failed to reach its primary endpoint; ● inability to generate satisfactory preclinical or other nonclinical data, including, toxicology, or other in vivo or in vitro data or diagnostics to support the initiation or continuation of clinical trials; ● unforeseen safety issues; ● failure by clinical sites or contract research organizations, or CROs, or other third parties to adhere to clinical trial requirements, GCP, or other applicable regulatory requirements; ● subjects discontinuing participating in our clinical trials at a greater than expected rate; ● imposition by the FDA of a clinical hold or the requirement by other similar regulatory agencies that one or more clinical trials be delayed or halted; ● uncertain dosing issues that may or may not be related to incompletely explored pharmacokinetic and pharmacodynamics behaviors; ● approval and introduction of new therapies or changes in standards of practice or regulatory guidance that render our clinical trial endpoints or the targeting of our proposed indications less attractive; ● inability to monitor patients adequately during or after treatment or problems with investigator or patient compliance with the trial protocols; ● inability to replicate in large, controlled studies safety and efficacy data obtained from a limited number of patients in uncontrolled trials; ● the ultimate affordability of the cost of clinical trials of our product candidates; ● changes in regulatory requirements and guidance that require amending or submitting new clinical protocols or performing additional nonclinical studies; and ● unavailability of clinical trial supplies.
If we obtain FDA approval for any of our product candidates and begin commercializing those products in the United States, our operations may be subject to various federal and state fraud and abuse laws, including, without limitation, the federal Anti-Kickback Statute, the federal False Claims Act, and physician sunshine laws and regulations.
If we obtain FDA approval for any of our product candidates and begin commercializing those products in the United States, our operations may be subject to various federal and state fraud and abuse laws, including, without limitation, the federal Anti-Kickback Statute, the federal False Claims Act, and physician payments sunshine laws and regulations.
Depending upon the timing, duration and specifics of FDA marketing approval of our product candidates, if any, one or more of our United States patents may be eligible for limited patent term restoration under the Drug Price Competition and Patent Term Restoration Act of 1984, referred to as the Hatch-Waxman Act.
Depending upon the timing, duration and specifics of FDA marketing approval of our product candidates, if any, one or more of our United States patents may be eligible for limited patent term extension under the Drug Price Competition and Patent Term Restoration Act of 1984, referred to as the Hatch-Waxman Act.
If we continue to fail to comply with the continued listing requirements of the Nasdaq Capital Market, our common stock may be delisted and the price of our common stock and our ability to access the capital markets could be negatively impacted. Our common stock is currently listed for trading on the Nasdaq Capital Market (“Nasdaq”).
If we fail to comply with the continued listing requirements of the Nasdaq Capital Market, our common stock may be delisted and the price of our common stock and our ability to access the capital markets could be negatively impacted. Our common stock is currently listed for trading on the Nasdaq Capital Market (“Nasdaq”).
The market price of our common and preferred stock may fluctuate substantially due to a variety of factors, including: ● announcements of technological innovations or new products or services by us or our competitors; announcements concerning our competitors or the biotechnology industry in general; ● new regulatory pronouncements and changes in regulatory guidelines; ● general and industry-specific economic conditions; ● additions to or departures of our key personnel; ● changes in financial estimates or recommendations by securities analysts; ● variations in our quarterly results; and ● announcements about our collaborators or licensors; and ● changes in accounting principles 59 Table of Contents The stock markets have from time-to-time experienced significant price and volume fluctuations that have affected the market prices for publicly traded securities.
The market price of our common and preferred stock may fluctuate substantially due to a variety of factors, including: ● announcements of technological innovations or new products or services by us or our competitors; announcements concerning our competitors or the biotechnology industry in general; ● new regulatory pronouncements and changes in regulatory guidelines; ● general and industry-specific economic conditions; ● additions to or departures of our key personnel; ● changes in financial estimates or recommendations by securities analysts; ● variations in our quarterly results; and ● announcements about our collaborators or licensors; and ● changes in accounting principles The stock markets have from time-to-time experienced significant price and volume fluctuations that have affected the market prices for publicly traded securities.
Even if we successfully complete the clinical trials for one or more of our product candidates, the product candidates may fail for other reasons, including, without limitation, the possibilities that the product candidates will: ● fail to receive the regulatory approvals required to market them as drugs; ● be subject to proprietary rights held by others requiring the negotiation of a license agreement prior to marketing; ● be difficult or expensive to manufacture on a commercial scale; ● have adverse side effects that make their use less desirable; or ● fail to compete effectively with product candidates or other treatments commercialized by our competitors.
Even if we successfully complete the clinical trials for one or more of our product candidates, the product candidates may fail for other reasons, including, without limitation, the possibilities that the product candidates will: ● fail to receive the regulatory approvals required to market them as drugs; ● be subject to proprietary rights held by others requiring the negotiation of a license agreement prior to marketing; 34 Table of Contents ● be difficult or expensive to manufacture on a commercial scale; ● have adverse side effects that make their use less desirable; or ● fail to compete effectively with product candidates or other treatments commercialized by our competitors.
Our future funding requirements will depend on many factors, including: ● the scope, rate of progress and cost of our clinical trials and other research and development activities; ● the costs and timing of seeking and obtaining regulatory approvals; ● the costs of filing, prosecuting, defending and enforcing any patent claims and other intellectual property rights; ● the costs associated with establishing sales and marketing capabilities; ● the costs of acquiring or investing in businesses, products and technologies; ● the effect of competing technological and market developments; and ● the payment, other terms and timing of any strategic alliance, licensing or other arrangements that we may establish.
Our future funding requirements will depend on many factors, including: ● the scope, rate of progress and cost of our clinical trials and other research and development activities; ● the costs and timing of seeking and obtaining regulatory approvals; ● the costs of filing, prosecuting, defending and enforcing any patent claims and other intellectual property rights; ● the costs associated with establishing sales and marketing capabilities; ● the costs of acquiring or investing in businesses, products and technologies; ● the effect of competing technological and market developments; and 48 Table of Contents ● the payment, other terms and timing of any strategic alliance, licensing or other arrangements that we may establish.
To the extent we elect to fund the full 47 Table of Contents development of a drug candidate or the commercialization of a drug at our expense, we will need to raise substantial additional funding to: ● fund research and development and clinical trials connected with our research; ● fund clinical trials and seek regulatory approvals; ● build or access manufacturing and commercialization capabilities; ● implement additional internal control systems and infrastructure; ● commercialize and secure coverage, payment and reimbursement of our drug candidates, if any such candidates receive regulatory approval; ● maintain, defend and expand the scope of our intellectual property; and ● hire additional management, sales and scientific personnel.
To the extent we elect to fund the full development of a drug candidate or the commercialization of a drug at our expense, we will need to raise substantial additional funding to: ● fund research and development and clinical trials connected with our research; ● fund clinical trials and seek regulatory approvals; ● build or access manufacturing and commercialization capabilities; ● implement additional internal control systems and infrastructure; ● commercialize and secure coverage, payment and reimbursement of our drug candidates, if any such candidates receive regulatory approval; ● maintain, defend and expand the scope of our intellectual property; and ● hire additional management, sales and scientific personnel.
Consequently, changes in exchange rates, and in particular a weakening of the United States dollar, may adversely affect our results of operations. Security breaches, loss of data and other disruptions could compromise sensitive information related to our business or prevent us from accessing critical information and expose us to liability, which could adversely affect our business and our reputation.
Consequently, changes in exchange rates, and in particular a weakening of the United States dollar, may adversely affect our results of operations. Security incidents, loss of data and other disruptions could compromise sensitive information related to our business or prevent us from accessing critical information and expose us to liability, which could adversely affect our business and our reputation.
In addition, even if we were to obtain regulatory approval in one or more jurisdictions, regulatory authorities may approve any of our drug candidates for fewer or more limited indications than we request, may not approve prices we may propose to charge for our products, may grant approval contingent on the performance of costly post-marketing clinical trials (referred to as “conditional” or “accelerated” approval depending on the jurisdiction), or may approve a drug candidate with a label that does not include the labeling claims necessary or desirable for the successful commercialization of that drug candidate.
In addition, even if we were to obtain regulatory approval in one or more jurisdictions, regulatory authorities may approve any of our drug candidates for fewer or more limited indications than we request, may not approve prices we may propose to charge for our products, may grant approval contingent on the performance of costly post-marketing 31 Table of Contents clinical trials (referred to as “conditional” or “accelerated” approval depending on the jurisdiction), or may approve a drug candidate with a label that does not include the labeling claims necessary or desirable for the successful commercialization of that drug candidate.
We may be subject to, or may in the future become subject to, U.S. federal and state, and foreign laws and regulations imposing obligations on how we collect, use, disclose, store and process personal information. Our actual or perceived failure to comply with such obligations could result in liability or reputational harm and could harm our business.
We may be subject to, or may in the future become subject to, U.S. federal and state, and international laws and regulations imposing obligations on how we collect, use, disclose, store and process personal information. Our actual or perceived failure to comply with such obligations could result in liability or reputational harm and could harm our business.
We face four primary risks relative to protecting this critical information: loss of access; inappropriate disclosure; inappropriate modification; and inadequate monitoring of our controls over the first three risks. We utilize information technology, or IT, systems and networks to process, transmit and store electronic information in connection with our business activities.
We face four primary risks relative to protecting this critical information: loss of access; unauthorized disclosure; unauthorized modification; and inadequate monitoring of our controls over the first three risks. We utilize information technology, or IT, systems and networks to process, transmit and store electronic information in connection with our business activities.
As a public company, we are subject to Section 404 of the Sarbanes Oxley Act relating to internal control over financial reporting. We have completed a formal process to evaluate our internal controls for purposes of Section 404, and we concluded that as of December 31, 2022, our internal control over financial reporting was effective.
As a public company, we are subject to Section 404 of the Sarbanes Oxley Act relating to internal control over financial reporting. We have completed a formal process to evaluate our internal controls for purposes of Section 404, and we concluded that as of December 31, 2023, our internal control over financial reporting was effective.
The withdrawal of the United Kingdom from the European Union and the subsequent separation of the data protection regimes of these territories mean we are required to comply with separate data protection laws in the European Union and the United Kingdom, which may lead to additional compliance costs and could increase our overall risk.
The withdrawal of the United Kingdom from the European Union and the subsequent separation of the data protection regimes of these territories means we are required to comply with separate data protection laws in the European Union and the United Kingdom, which may lead to additional compliance costs and could increase our overall risk.
For example, the ACA, among other things, amends the intent requirement of the federal anti-kickback and criminal healthcare fraud statutes. A person or entity no longer needs to have actual knowledge of this statute or specific intent to violate it.
For example, the ACA, among other things, amended the intent requirement of the federal anti-kickback and criminal healthcare fraud statutes. A person or entity no longer needs to have actual knowledge of this statute or specific intent to violate it.
In addition, our independent certified public accounting firm has not provided an opinion on the effectiveness of our internal controls over financial reporting for the year ended December 31, 2022 because we are a smaller reporting company.
In addition, our independent certified public accounting firm has not provided an opinion on the effectiveness of our internal controls over financial reporting for the year ended December 31, 2023 because we are a smaller reporting company.
In addition to continuing pressure on prices and cost containment measures, legislative developments at the European Union or EU member state level may result in significant additional requirements or obstacles that may increase our operating costs. 40 Table of Contents We cannot predict the likelihood, nature or extent of government regulation that may arise from future legislation or administrative or executive action.
In addition to continuing pressure on prices and cost containment measures, legislative developments at the European Union or EU member state level may result in significant additional requirements or obstacles that may increase our operating costs. We cannot predict the likelihood, nature or extent of government regulation that may arise from future legislation or administrative or executive action.
Notwithstanding the reverse stock split and our compliance with the Nasdaq Capital market requirements, we cannot be sure that our share price will comply with the requirements for continued listing of our common stock on the Nasdaq Capital Market in the future, or that we will comply with the other continued listing requirements.
Notwithstanding the Reverse Stock Split and our compliance with the Nasdaq Capital market requirements, we cannot be sure that our share price will continue to comply with the requirements for continued listing of our common stock on the Nasdaq Capital Market in the future, or that we will continue to comply with the other continued listing requirements.
Market acceptance and sales of our product candidates that we develop, if approved, will depend on reimbursement policies, and may be affected by future healthcare reform measures. Government authorities and third-party payors, such as private health insurers and health maintenance organizations, decide which drugs they will cover and establish payment levels.
Market acceptance 36 Table of Contents and sales of our product candidates that we develop, if approved, will depend on reimbursement policies, and may be affected by future healthcare reform measures. Government authorities and third-party payors, such as private health insurers and health maintenance organizations, decide which drugs they will cover and establish payment levels.
Other potential consequences include, among other things: ● restrictions on the marketing or manufacturing of the product, complete withdrawal of the product from the market or product recalls; ● fines, warning letters or other enforcement-related letters or clinical holds on post-approval clinical trials; ● refusal of the FDA to approve pending BLAs or supplements to approved BLAs, or suspension or revocation of product approvals; ● product seizure or detention, or refusal to permit the import or export of products; ● injunctions or the imposition of civil or criminal penalties; and ● consent decrees, corporate integrity agreements, debarment, or exclusion from federal health care programs; or mandated modification of promotional materials and labeling and the issuance of corrective information.
Other potential consequences include, among other things: 33 Table of Contents ● restrictions on the marketing or manufacturing of the product, complete withdrawal of the product from the market or product recalls; ● fines, warning letters or other enforcement-related letters or clinical holds on post-approval clinical trials; ● refusal of the FDA to approve pending NDAs or supplements to approved NDAs, or suspension or revocation of product approvals; ● product seizure or detention, or refusal to permit the import or export of products; ● injunctions or the imposition of civil or criminal penalties; and ● consent decrees, corporate integrity agreements, debarment, or exclusion from federal health care programs; or mandated modification of promotional materials and labeling and the issuance of corrective information.
In addition, sales, marketing and business arrangements in the health care industry are subject to extensive laws and regulations intended to prevent fraud, kickbacks, self-dealing and other abusive practices. These laws and regulations may restrict or prohibit a wide range of pricing, discounting, marketing and promotion, sales commission, customer incentive programs and other business arrangements.
In addition, sales, marketing and business arrangements 46 Table of Contents in the health care industry are subject to extensive laws and regulations intended to prevent fraud, kickbacks, self-dealing and other abusive practices. These laws and regulations may restrict or prohibit a wide range of pricing, discounting, marketing and promotion, sales commission, customer incentive programs and other business arrangements.
Additional funding may not be available to us on 44 Table of Contents favorable terms, or at all, particularly in light of the current economic conditions. Changes to United Kingdom tax legislation related to research and development tax credits may reduce or eliminate the cash flow benefit we receive from these tax credits.
Additional funding may not be available to us on favorable terms, or at all, particularly in light of the current economic conditions. Changes to United Kingdom tax legislation related to research and development tax credits may reduce or eliminate the cash flow benefit we receive from these tax credits.
We cannot be certain that the clinical development of our drug candidates in preclinical testing or clinical development will be successful, that we will receive regulatory approvals required to commercialize them or that any of our other research and drug discovery programs will yield a drug candidate suitable for investigation 46 Table of Contents through clinical trials.
We cannot be certain that the clinical development of our drug candidates in preclinical testing or clinical development will be successful, that we will receive regulatory approvals required to commercialize them or that any of our other research and drug discovery programs will yield a drug candidate suitable for investigation through clinical trials.
However, trade secrets are difficult to protect. Our employees, consultants, contractors, outside scientific collaborators and other advisors may unintentionally or willfully disclose our confidential information to competitors, and confidentiality agreements may not provide an adequate remedy in the event of unauthorized disclosure of confidential information.
However, trade secrets are difficult to protect. Our employees, consultants, contractors, outside scientific collaborators and other advisors may unintentionally or willfully disclose our confidential information to competitors, and confidentiality agreements may not provide an adequate remedy in the event of unauthorized disclosure of confidential 53 Table of Contents information.
Thus, the terms of our preferred stock might hamper a third party’s acquisition of our company. 58 Table of Contents Our certificate of incorporation and bylaws and certain provisions of Delaware law may delay or prevent a change in our management and make it more difficult for a third-party to acquire us.
Thus, the terms of our preferred stock might hamper a third party’s acquisition of our company. Our certificate of incorporation and bylaws and certain provisions of Delaware law may delay or prevent a change in our management and make it more difficult for a third-party to acquire us.
The Hatch-Waxman Act permits a patent restoration term of up to five years as compensation for patent term lost during product development and the FDA regulatory review process.
The Hatch-Waxman Act permits a patent term extension of up to five years as compensation for patent term lost during product development and the FDA regulatory review process.
Failure to achieve and maintain a diverse workforce and leadership team, compensate our employees competitively and fairly, maintain a safe and inclusive environment or promote the well-being of our employees could affect our reputation and also result in lower performance and an inability to retain valuable employees.
Failure to achieve and maintain a diverse workforce and leadership team, 37 Table of Contents compensate our employees competitively and fairly, maintain a safe and inclusive environment or promote the well-being of our employees could affect our reputation and also result in lower performance and an inability to retain valuable employees.
If any of our relationships with these third-party laboratories, CROs or clinical investigators terminate, we may not be able to enter into arrangements with alternative laboratories, CROs or investigators or to do so in a timely manner or on commercially reasonable terms.
If any of our relationships with these third-party laboratories, CROs or clinical investigators 50 Table of Contents terminate, we may not be able to enter into arrangements with alternative laboratories, CROs or investigators or to do so in a timely manner or on commercially reasonable terms.
We must comply with laws and regulations associated with the international transfer of personal data based on the location in which the personal data originates and the location in which it is processed.
We must comply with laws and regulations associated with the international transfer of personal data based on the location in which the personal data originates and the location in which it is processed and/or controlled.
If the security holder determines to sell a substantial number of shares into the market at any given time, there may not be sufficient demand in the market to purchase the shares without a decline in the market price for our 60 Table of Contents common stock.
If the security holder determines to sell a substantial number of shares into the market at any given time, there may not be sufficient demand in the market to purchase the shares without a decline in the market price for our common stock.
Further, upon completion of this offering and 45 Table of Contents in our operations as a public company, future government shutdowns could impact our ability to access the public markets and obtain necessary capital in order to properly capitalize and continue our operations.
Further, upon completion of this offering and in our operations as a public company, future government shutdowns could impact our ability to access the public markets and obtain necessary capital in order to properly capitalize and continue our operations.
Effective internal controls are necessary for us to produce reliable financial reports and are important in the prevention of financial fraud. If we cannot produce reliable financial reports or prevent fraud, our business and operating results could be harmed.
Effective internal controls are necessary for us to produce reliable financial reports and are important in the prevention of financial 56 Table of Contents fraud. If we cannot produce reliable financial reports or prevent fraud, our business and operating results could be harmed.
In addition, because we are incorporated in Delaware, we are governed by the provisions of Section 203 of the Delaware General Corporation Law, which limits the ability of large stockholders to complete a business combination with, or acquisition of, us.
In addition, because we are incorporated in Delaware, we are governed by the provisions of Section 203 of the Delaware General Corporation Law, which limits the ability of large stockholders to complete a business combination 59 Table of Contents with, or acquisition of, us.
Clinical failure can occur at any stage of clinical development. Clinical trials may produce negative or inconclusive results, and we or any future collaborators may decide, or regulatory authorities may require us, to conduct additional clinical trials or nonclinical studies.
Clinical failure can occur at any stage of clinical development. Clinical trials may produce negative or 29 Table of Contents inconclusive results, and we or any future collaborators may decide, or regulatory authorities may require us, to conduct additional clinical trials or nonclinical studies.
As of December 31, 2022, our cash and cash equivalents were $18.3 million. Based on our current operating plan, there is substantial doubt regarding our ability to continue as a going concern for a period of one year after the date that our financial statements for the year ended December 31, 2022 are issued.
As of December 31, 2023, our cash and cash equivalents were $3.4 million. Based on our current operating plan, there is substantial doubt regarding our ability to continue as a going concern for a period of one year after the date that our financial statements for the year ended December 31, 2023 are issued.
The laws that may affect our ability to operate include: ● The federal Anti-Kickback Statute, which prohibits, among other things, persons from knowingly and willfully soliciting, receiving, offering or paying remuneration, directly or indirectly, to induce, or in return for, the purchase or recommendation of an item or service reimbursable under a federal healthcare program, such as the Medicare and Medicaid programs; ● Federal civil and criminal false claims laws and civil monetary penalty laws, which prohibit, among other things, individuals or entities from knowingly presenting, or causing to be presented, claims for payment from Medicare, Medicaid, or other third-party payors that are false or fraudulent; ● The federal Health Insurance Portability and Accountability Act of 1996 (HIPAA), which created new federal criminal statutes that prohibit executing a scheme to defraud any healthcare benefit program and making false statements relating to healthcare matters; ● HIPAA, as amended by the Health Information Technology and Clinical Health Act, and its implementing regulations, which imposes specified requirements relating to the privacy, security, and transmission of individually identifiable health information; ● The federal physician payments sunshine requirements under the ACA require manufacturers of drugs, devices, biologics, and medical supplies to report annually to the HHS information related to payments and other transfers of value to physicians, other healthcare providers, and teaching hospitals, and ownership and investment interests held by physicians and other healthcare providers and their immediate family members and applicable group purchasing organizations; and ● State law equivalents of each of the above federal laws, such as anti-kickback and false claims laws that may apply to items or services reimbursed by any third-party payor, including governmental and private payors, to comply with the pharmaceutical industry’s voluntary compliance guidelines and the relevant compliance guidance promulgated by the federal government, or otherwise restrict payments that may be made to healthcare providers and other potential referral sources; state laws that require drug manufacturers to report information related to payments and other transfers of value to physicians and other healthcare providers or marketing expenditures, and state laws governing the privacy and security of health information in specified circumstances, many of which differ from each other in significant ways and may not have the same effect, thus complicating compliance efforts.
The laws that may affect our ability to operate include: ● The federal Anti-Kickback Statute, which prohibits, among other things, persons from knowingly and willfully soliciting, receiving, offering or paying remuneration, directly or indirectly, to induce, or in return for, the purchase or recommendation of an item or service reimbursable under a federal healthcare program, such as the Medicare and Medicaid programs; ● Federal civil and criminal false claims laws and civil monetary penalty laws, which prohibit, among other things, individuals or entities from knowingly presenting, or causing to be presented, claims for payment from Medicare, Medicaid, or other government payors that are false or fraudulent or making a false statement to avoid, decrease or conceal an obligation to pay money to the federal government; ● The federal Health Insurance Portability and Accountability Act of 1996 (HIPAA), which created new federal criminal statutes that prohibit executing a scheme to defraud any healthcare benefit program and making false statements relating to healthcare matters; 41 Table of Contents ● HIPAA, as amended by the Health Information Technology and Clinical Health Act, and its implementing regulations, which imposes specified requirements relating to the privacy, security, and transmission of individually identifiable health information; ● The federal physician payments sunshine requirements under the ACA require manufacturers of drugs, devices, biologics, and medical supplies to report annually to the CMS information related to payments and other transfers of value to physicians, certain advanced non-physician healthcare providers, and teaching hospitals, and ownership and investment interests held by physicians and other healthcare providers and their immediate family members; and ● State law equivalents of each of the above federal laws, such as anti-kickback and false claims laws that may apply to items or services reimbursed by any third-party payor, including governmental and private payors, to comply with the pharmaceutical industry’s voluntary compliance guidelines and the relevant compliance guidance promulgated by the federal government, or otherwise restrict payments that may be made to healthcare providers and other potential referral sources; state laws that require drug manufacturers to report information related to payments and other transfers of value to physicians and other healthcare providers or marketing expenditures, and state laws governing the privacy and security of health information in specified circumstances, many of which differ from each other in significant ways and may not have the same effect, thus complicating compliance efforts.
In order to receive regulatory approval of a drug candidate, we must present all relevant data and information obtained during our research and 33 Table of Contents development, including research conducted prior to our licensure of the drug candidate.
In order to receive regulatory approval of a drug candidate, we must present all relevant data and information obtained during our research and development, including research conducted prior to our licensure of the drug candidate.
Compliance with environmental laws and regulations may be expensive, and current or future environmental regulations may impair our research, development and production efforts. ​ 43 Table of Contents Our business and operations would suffer in the event of system failures.
Compliance with environmental laws and regulations may be expensive, and current or future environmental regulations may impair our research, development and production efforts. Our business and operations would suffer in the event of system failures.
In one case we have opposed a European patent relating to human aurora kinase and the patent was finally revoked (with no appeal filed). 54 Table of Contents There has been substantial litigation and other proceedings regarding patent and other intellectual property rights in the pharmaceutical and biotechnology industries.
In one case we have opposed a European patent relating to human aurora kinase and the patent was finally revoked (with no appeal filed). There has been substantial litigation and other proceedings regarding patent and other intellectual property rights in the pharmaceutical and biotechnology industries.
We may automatically convert the convertible preferred stock into common stock if the closing price of our common stock exceeds $59,220 per share. There is a risk of fluctuation in the price of our common stock between the time when we may first elect to automatically convert the preferred and the automatic conversion date.
We may automatically convert the convertible preferred stock into common stock if the closing price of our common stock exceeds $888,300 per share. There is a risk of fluctuation in the price of our common stock between the time when we may first elect to automatically convert the preferred and the automatic conversion date.
These arrangements may place the development of our drug candidates outside our control, may require us to relinquish important rights, or may otherwise be on terms unfavorable to us.
These arrangements may place the 52 Table of Contents development of our drug candidates outside our control, may require us to relinquish important rights, or may otherwise be on terms unfavorable to us.
For example, in 2013, we issued an aggregate of 140,373 shares of our common stock in exchange for an aggregate of 877,869 shares of our preferred stock in arms-length negotiations between us and the other parties who had approached us to propose the exchanges.
For example, in 2013, we issued an aggregate of 9,358 shares of our common stock in exchange for an aggregate of 877,869 shares of our preferred stock in arms-length negotiations between us and the other parties who had approached us to propose the exchanges.
Regulatory authorities have substantial discretion in the approval process and may refuse to accept any application or may decide that our data are insufficient for approval and require additional nonclinical studies or clinical trials.
Regulatory authorities have substantial discretion in the approval process and may refuse to accept any 30 Table of Contents application or may decide that our data are insufficient for approval and require additional nonclinical studies or clinical trials.
Our competitors may also have more experience: 35 Table of Contents ● developing drug candidates; ● conducting preclinical and clinical trials; ● obtaining regulatory approvals; and ● commercializing product candidates. Our competitors may succeed in obtaining patent protection and regulatory approval and may market drugs before we do.
Our competitors may also have more experience: ● developing drug candidates; ● conducting preclinical and clinical trials; ● obtaining regulatory approvals; and ● commercializing product candidates. Our competitors may succeed in obtaining patent protection and regulatory approval and may market drugs before we do.
A delisting of our common stock from the Nasdaq Capital Market could materially reduce the liquidity of our common stock and result in a corresponding material reduction in the price of our common stock.
A delisting of our common stock from the Nasdaq Capital Market could materially 47 Table of Contents reduce the liquidity of our common stock and result in a corresponding material reduction in the price of our common stock.
Numerous foreign, federal and state laws and regulations govern collection, dissemination, use and confidentiality of personally identifiable health information, including state privacy and confidentiality laws (including state laws requiring disclosure of breaches); federal and state consumer protection and employment laws; HIPAA; and European and other foreign data protection laws.
Numerous foreign, federal and state laws and regulations govern collection, dissemination, use and confidentiality of personally identifiable health information, including state privacy and confidentiality laws (including state laws 43 Table of Contents requiring disclosure of breaches); federal and state consumer protection and employment laws; HIPAA; and European and other international data protection laws.
If we are required to change manufacturers for any reason, we will be required to verify that the new manufacturer maintains facilities and procedures that comply with quality standards and with all applicable regulations and guidelines.
If we are required to change manufacturers for any reason, we will be required to 51 Table of Contents verify that the new manufacturer maintains facilities and procedures that comply with quality standards and with all applicable regulations and guidelines.
If we are unable to obtain or maintain third-party manufacturing for 51 Table of Contents product candidates, or to do so on commercially reasonable terms, we may not be able to develop and commercialize our product candidates successfully.
If we are unable to obtain or maintain third-party manufacturing for product candidates, or to do so on commercially reasonable terms, we may not be able to develop and commercialize our product candidates successfully.
Dependence on collaborative arrangements or strategic alliances will subject us to a number of risks, including the risks that: ● we may not be able to control the amount and timing of resources that our collaborators may devote to the drug candidates; ● our collaborators may experience financial difficulties; ● we may be required to relinquish important rights such as marketing and distribution rights; ● business combinations or significant changes in a collaborator’s business strategy may also adversely affect a collaborator’s willingness or ability to complete its obligations under any arrangement; ● a collaborator could independently move forward with a competing drug candidate developed either independently or in collaboration with others, including our competitors; and ● collaborative arrangements are often terminated or allowed to expire, which would delay development and may increase the cost of developing our drug candidates. ​ 52 Table of Contents Risks Related to our Intellectual Property If we fail to enforce adequately or defend our intellectual property rights, our business may be harmed.
Dependence on collaborative arrangements or strategic alliances will subject us to a number of risks, including the risks that: ● we may not be able to control the amount and timing of resources that our collaborators may devote to the drug candidates; ● our collaborators may experience financial difficulties; ● we may be required to relinquish important rights such as marketing and distribution rights; ● business combinations or significant changes in a collaborator’s business strategy may also adversely affect a collaborator’s willingness or ability to complete its obligations under any arrangement; ● a collaborator could independently move forward with a competing drug candidate developed either independently or in collaboration with others, including our competitors; and ● collaborative arrangements are often terminated or allowed to expire, which would delay development and may increase the cost of developing our drug candidates.
Although there are legal mechanisms to facilitate the transfer of personal data from the European Economic Area (EEA), and Switzerland to the United States, the decision of the European Court of Justice that invalidated the safe harbor framework has increased uncertainty around compliance with EU privacy law requirements.
Although there are legal mechanisms to facilitate the transfer of personal data from the UK, EEA, and Switzerland to the United States, the decision of the Court of Justice of the EU (CJEU) that invalidated the safe harbor framework has increased uncertainty around compliance with EU privacy law requirements.
In addition, our directors may only be removed for cause and amended and restated bylaws limit the ability of our stockholders to call special meetings of stockholders. As at December 31, 2022, we had 335,273 shares of 6% Convertible Exchangeable Preferred Stock, 237,745 shares of Series B Preferred Stock and 264 shares of Series A Preferred Stock issued and outstanding.
In addition, our directors may only be removed for cause and amended and restated bylaws limit the ability of our stockholders to call special meetings of stockholders. As at December 31, 2023, we had 335,273 shares of 6% Convertible Exchangeable Preferred Stock, 119,000 shares of Series B Preferred Stock and 264 shares of Series A Preferred Stock issued and outstanding.
When the United States dollar weakens against the British pound or the Euro, the United States dollar 48 Table of Contents value of the foreign currency denominated expense increases, and when the United States dollar strengthens against the British pound or the Euro, the United States dollar value of the foreign currency denominated expense decreases.
When the United States dollar weakens against the British pound or the Euro, the United States dollar value of the foreign currency denominated expense increases, and when the United States dollar strengthens against the British pound or the Euro, the United States dollar value of the foreign currency denominated expense decreases.
For example, the collection, use, disclosure, transfer, or other processing of personal data regarding individuals in the European Union, including personal health data, is subject to the General Data Protection Regulation, or GDPR, which took effect across all Member States of the European Economic Area, or EEA, on May 25, 2018.
For example, the collection, use, disclosure, transfer, or other processing of personal data regarding individuals in the European Union, including personal health data, is subject to the General Data Protection Regulation, or GDPR, which took effect across all Member States of the European Economic Area, or EEA, on May 25, 2018, and as still in effect in the United Kingdom as the UK GDPR.
Litigation may be necessary to defend against these claims. If we fail in defending such claims, in addition to paying monetary damages, we may lose valuable intellectual property rights or personnel. A loss of key research personnel or their work product could hamper or prevent our ability to commercialize certain potential drugs, which could severely harm our business.
If we fail in defending such claims, in addition to paying monetary damages, we may lose valuable intellectual property rights or personnel. A loss of key research personnel or their work product could hamper or prevent our ability to commercialize certain potential drugs, which could severely harm our business.
Despite the implementation of security measures, our internal and cloud-based computer systems and those of our contractors and consultants are vulnerable to damage from such cyber-attacks, including computer viruses, unauthorized access, natural disasters, terrorism, war and telecommunication and electrical failures. Such an event could cause interruption of our operations.
Despite the implementation of security measures, our internal and cloud-based computer systems and those of our contractors and consultants are vulnerable to damage from such cybersecurity incidents, including computer viruses, social engineering, unauthorized access, natural disasters, terrorism, war and telecommunication and electrical failures. Such an event could cause interruption of our operations.
Patents, if issued, may be challenged, invalidated or circumvented. 55 Table of Contents U.S. patents and patent applications may also be subject to interference proceedings, and U.S. patents may be subject to Inter Partes Review (IPR), Post Grant Review (PGR) or reexamination proceedings in the USPTO (and foreign patents may be subject to opposition or comparable proceedings in the corresponding foreign patent office), which proceedings could result in either loss of the patent or denial of the patent application or loss or reduction in the scope of one or more of the claims of the patent or patent application.
U.S. patents and patent applications may also be subject to interference proceedings, and U.S. patents may be subject to Inter Partes Review (IPR), Post Grant Review (PGR) or reexamination proceedings in the USPTO (and foreign patents may be subject to opposition or comparable proceedings in the corresponding foreign patent office), which proceedings could result in either loss of the patent or denial of the patent application or loss or reduction in the scope of one or more of the claims of the patent or patent application.
Our stock can trade in small volumes which may make the price of our stock highly volatile. The last reported price of our stock may not represent the price at which you would be able to buy or sell the stock. The market prices for securities of companies comparable to us have been highly volatile.
The last reported price of our stock may not represent the price at which you would be able to buy or sell the stock. The market prices for securities of companies comparable to us have been highly volatile.
Factors giving rise to this volatility may include: ● disclosure of actual or potential clinical results with respect to product candidates we are developing; ● regulatory developments in both the United States and abroad; ● developments concerning proprietary rights, including patents and litigation matters; ● public concern about the safety or efficacy of our product candidates or technology, or related technology, or new technologies generally; ● concern about the safety or efficacy of our product candidates or technology, or related technology, or new technologies generally; ● public announcements by our competitors or others; and ● general market conditions and comments by securities analysts and investors.
Factors giving rise to this volatility may include: ● disclosure of actual or potential clinical results with respect to product candidates we are developing; ● regulatory developments in both the United States and abroad; ● developments concerning proprietary rights, including patents and litigation matters; ● public concern about the safety or efficacy of our product candidates or technology, or related technology, or new technologies generally; ● concern about the safety or efficacy of our product candidates or technology, or related technology, or new technologies generally; ● public announcements by our competitors or others; and ● general market conditions and comments by securities analysts and investors. 57 Table of Contents Fluctuations in our operating losses could adversely affect the price of our common stock.
These threats pose a risk to the security of our systems and networks and the confidentiality, availability and integrity of our data. There can be no assurance that we will be successful in preventing cyber-attacks or successfully mitigating their effects.
These threats pose a risk to the security of our systems and networks and the confidentiality, availability and integrity of our 49 Table of Contents data. There can be no assurance that we will be successful in preventing cybersecurity incidents or successfully mitigating their effects.
Our or a third-party’s failure to execute on our manufacturing requirements could adversely affect our business in a number of ways, including: ● an inability to initiate or continue clinical trials of product candidates under development, which may impact our potential economic benefits; ● delay in submitting regulatory applications, or receiving regulatory approvals, for product candidates; ● loss of the cooperation of a collaborator; ● subjecting our product candidates to additional inspections by regulatory authorities; ● requirements to cease distribution or to recall batches of our product candidates; and ● in the event of approval to market and commercialize a product candidate, an inability to meet commercial demands for our products. ​ If we fail to enter into and maintain successful strategic alliances for our drug candidates, we may have to reduce or delay our drug candidate development or increase our expenditures.
Our or a third-party’s failure to execute on our manufacturing requirements could adversely affect our business in a number of ways, including: ● an inability to initiate or continue clinical trials of product candidates under development, which may impact our potential economic benefits; ● delay in submitting regulatory applications, or receiving regulatory approvals, for product candidates; ● loss of the cooperation of a collaborator; ● subjecting our product candidates to additional inspections by regulatory authorities; ● requirements to cease distribution or to recall batches of our product candidates; and ● in the event of approval to market and commercialize a product candidate, an inability to meet commercial demands for our products.
The above limitations on liability and our indemnification obligations limit the personal liability of our directors and officers for monetary damages for breach of their fiduciary duty as directors by shifting the burden of such losses and expenses to us.
We have entered into indemnification agreements with each of our officers and directors. The above limitations on liability and our indemnification obligations limit the personal liability of our directors and officers for monetary damages for breach of their fiduciary duty as directors by shifting the burden of such losses and expenses to us.
We anticipate that we will face increased competition in the future as new companies enter the markets and as scientific developments progress. If our drug candidates obtain regulatory approvals, but do not compete effectively in the marketplace, our business will suffer.
We anticipate that we will face increased competition in the future as new companies enter the markets and as scientific developments progress. If our drug candidates obtain regulatory approvals, but do not compete effectively in the marketplace, our business will suffer. Our future product candidates for which we obtain approval may face competition sooner than anticipated.
HIPAA establishes a set of national privacy and security standards for the protection of individually identifiable health information, including protected health information, or PHI, by health plans, certain healthcare clearinghouses and healthcare providers that submit certain covered transactions electronically, or covered entities, and their “business associates,” which are persons or entities that perform certain services for, or on behalf of, a covered entity that involve 42 Table of Contents creating, receiving, maintaining or transmitting PHI.
HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act (HITECH), establishes a set of U.S. national privacy and security standards for the protection of individually identifiable health information, including protected health information, or PHI, by health plans, certain healthcare clearinghouses and healthcare providers that submit certain covered transactions electronically, or covered entities, and their “business associates,” which are persons or entities that perform certain services for, or on behalf of, a covered entity that involve creating, receiving, maintaining or transmitting PHI.
Patent and Trademark Office’s, or USPTO’s, standards are uncertain and could change in the future. Consequently, the issuance and scope of patents cannot be predicted with certainty.
Patent and Trademark Office’s, or USPTO’s, standards are uncertain and could change in the future. Consequently, the issuance and scope of patents cannot be predicted with certainty. Patents, if issued, may be challenged, invalidated or circumvented.
Anti-takeover provisions of Delaware law and our amended and restated certificate of incorporation and amended and restated bylaws may make a change in control or efforts to remove management more difficult.
Anti-takeover provisions of Delaware law and our amended and restated certificate of incorporation and amended and restated bylaws may make a change in control or efforts to remove management more difficult. Also, under Delaware law, our Board of Directors may adopt additional anti-takeover measures.
Moreover, market prices for stocks of biotechnology-related and technology companies frequently reach levels that bear no relationship to the performance of these companies. These market prices generally are not sustainable and are highly volatile.
Moreover, market prices for stocks of biotechnology-related and technology companies frequently reach levels that bear no relationship to the performance of these companies.
A sustained labor shortage or increased turnover rates within our employee base caused by COVID-19 or related issues such as vaccine mandates, or as a result of general macroeconomic factors, have led and in the future could lead to increased costs, such as increased 37 Table of Contents overtime to meet demand and increased wages to attract and retain employees.
A sustained labor shortage or increased turnover rates within our employee base as a result of general macroeconomic factors have led and in the future could lead to increased costs, such as increased overtime to meet demand and increased wages to attract and retain employees.
To the extent equity valuations, including the trading price of our common stock, are depressed as a result of economic disruptions or other uncertainties, for example due to the COVID-19 pandemic, rising inflationary pressures, the ongoing Russian invasion of Ukraine or other factors, the potential magnitude of this dilution will increase.
To the extent equity valuations, including the trading price of our common stock, are depressed as a result 45 Table of Contents of economic disruptions or other uncertainties, for example due to rising inflationary pressures, ongoing military conflicts or other factors, the potential magnitude of this dilution will increase.
Various laws and regulations govern the use, manufacture, storage, handling and disposal of hazardous materials. We may be sued for any injury or contamination that results from our use or the use by third parties of these materials.
We cannot eliminate the risk of accidental contamination or discharge and any resultant injury from those materials. Various laws and regulations govern the use, manufacture, storage, handling and disposal of hazardous 44 Table of Contents materials. We may be sued for any injury or contamination that results from our use or the use by third parties of these materials.
As of December 31, 2022, there were 335,273 shares of our preferred stock issued and outstanding.
As of December 31, 2023, there were 335,273 shares of our 6% Convertible Exchangeable Preferred Stock issued and outstanding.
If we fail to comply with the regulatory requirements in international markets and/or receive applicable marketing approvals, our target market will be reduced and our ability to realize the full market potential of our product candidates will be harmed. ​ Even if we successfully complete the clinical trials for one or more of our product candidates, the product candidates may fail for other reasons.
If we fail to comply with the regulatory requirements in international markets and/or receive applicable marketing approvals, our target market will be reduced and our ability to realize the full market potential of our product candidates will be harmed.
Enforcing a claim that a party illegally obtained and is using our trade secrets is difficult, expensive and time consuming, and the outcome is unpredictable. In addition, courts outside the United States may be less willing to protect trade secrets. The failure to obtain or maintain trade secret protection could adversely affect our competitive position.
Enforcing a claim that a party illegally obtained and is using our trade secrets is difficult, expensive and time consuming, and the outcome is unpredictable. In addition, courts outside the United States may be less willing to protect trade secrets.
In a derivative action, (i.e., one brought by or on behalf of the corporation), indemnification may be provided only for expenses actually and reasonably incurred by any director or officer in connection with the defense or settlement of such an action or suit if such person acted in good faith and in a manner that he or she reasonably believed to be in, or not opposed to, the best interests of the corporation, except that no indemnification shall be provided if such person shall have been adjudged to be liable to the corporation, unless and only to the extent that the court in which the action or suit was brought shall determine that the defendant is fairly and reasonably entitled to indemnity for such expenses despite such adjudication of liability.
In a derivative action, (i.e., one brought by or on behalf of the corporation), indemnification may be provided only for expenses actually and reasonably incurred by any director or officer in connection with the defense or settlement of such an action or suit if such person acted in good faith and in a manner that he or she reasonably believed to be in, or not opposed to, the best interests of the corporation, except that no indemnification shall be provided if such person shall have been adjudged to be liable to the corporation, unless and only to the extent that the court in which the action or suit was brought shall determine that the defendant is fairly and reasonably entitled to indemnity for such expenses despite such adjudication of liability. 62 Table of Contents The rights conferred in the restated certificate of incorporation and the restated bylaws are not exclusive, and we are authorized to enter into indemnification agreements with our directors, officers, employees and agents and to obtain insurance to indemnify such persons.
We may not be able to initiate or continue clinical trials for our drug candidates if we are unable to locate and enroll a sufficient number of research subjects to participate in these trials, including as a result challenges posed by the ongoing COVID-19 pandemic.
We may not be able to initiate or continue clinical trials for our drug candidates if we are unable to locate and enroll a sufficient number of research subjects to participate in these trials.
To the extent that any disruption or security breach were to result in a loss of or damage to our data or applications, or inappropriate disclosure of confidential or proprietary information, we could incur liability and the further development of our product candidates could be delayed. ​ Risks Related to Our Business and Financial Condition We have a history of operating losses and we may never become profitable.
To the extent that any disruption or security breach were to result in a loss of or damage to our data or applications, or inappropriate disclosure of confidential or proprietary information, we could incur liability and the further development of our product candidates could be delayed.
The ACA, among other things, increased the minimum Medicaid rebates owed by manufacturers under the Medicaid Drug Rebate Program and extended the rebate program to individuals enrolled in Medicaid managed care organizations, established annual fees and taxes on manufacturers of certain branded prescription drugs and biologics, and created a new Medicare Part D coverage gap discount program, in which manufacturers must agree to offer 70% (increased from 50% pursuant to the Bipartisan Budget Act of 2018, effective as of 2019) point-of-sale discounts off negotiated prices of applicable brand drugs and biologics to eligible beneficiaries during their coverage gap period, as a condition for the manufacturer’s outpatient drugs or biologics to be covered under Medicare Part D.
The ACA, among other things, increased the minimum Medicaid rebates owed by manufacturers under the Medicaid Drug Rebate Program and extended the rebate program to individuals enrolled in Medicaid managed care organizations, established annual fees and taxes on manufacturers of certain branded prescription drugs and biologics, and created a new Medicare Part D coverage gap discount program, in which manufacturers must agree to offer 70% (increased from 50% pursuant to the Bipartisan Budget Act of 2018, effective as of 2019) point-of-sale discounts off negotiated prices of applicable brand drugs and biologics to eligible beneficiaries during their coverage gap period, as a condition for the manufacturer’s outpatient drugs or biologics to be covered under Medicare Part D. 39 Table of Contents We expect that future changes or additions to the ACA, the Medicare and Medicaid programs and changes stemming from other healthcare reform measures, especially with regard to healthcare access, financing or other legislation in individual states, could have a material adverse effect on the health care industry in the United States.
In order to execute our business strategy, we will need to expand our development, control and regulatory capabilities and develop financial, manufacturing, marketing and sales capabilities or contract with third parties to provide these capabilities for us. If our operations expand, we expect that we will need to manage additional relationships with various collaborative partners, suppliers and other third parties.
In order to execute our business strategy, we will need to expand our development, control and regulatory capabilities and develop financial, manufacturing, marketing and sales capabilities or contract with third parties to provide these capabilities for us.
Similarly, Vermont requires pharmaceutical manufacturers to disclose price information on certain prescription drugs, and to provide notification to the state if introducing a new drug with a WAC in excess of the Medicare Part D specialty drug threshold. In December 2020, the U.S.
Similarly, Vermont requires pharmaceutical manufacturers to disclose price information on certain prescription drugs, and to provide notification to the state if introducing a new drug with a WAC in excess of the Medicare Part D specialty drug threshold. In addition, in recent years, several states have formed prescription drug affordability boards (PDABs).

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Item 3. Legal Proceedings

Legal Proceedings — active lawsuits and investigations

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Biggest changeItem 3. Legal Proceedings From time to time, we may be involved in routine litigation incidental to the conduct of our business. As of December 31, 2022, we were not a party to any material legal proceedings. Item 4. Mine Safety Disclosures Not applicable. PART II
Biggest changeItem 3. Legal Proceedings From time to time, we may be involved in routine litigation incidental to the conduct of our business. As of December 31, 2023, we were not a party to any material legal proceedings. Item 4. Mine Safety Disclosures Not applicable. PART II

Item 5. Market for Registrant's Common Equity

Market for Common Equity — stock, dividends, buybacks

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Biggest changeAny future determination relating to our dividend policy will be made at the discretion of our Board of Directors and will depend on a number of factors, including future earnings, capital requirements, financial conditions, future prospects, contractual restrictions and other factors that our Board of Directors may deem relevant. Item 6. [Reserved]
Biggest changeAny future determination relating to our dividend policy will be made at the discretion of our Board of Directors and will depend on a number of factors, including future earnings, capital requirements, financial conditions, future prospects, contractual restrictions and other factors that our Board of Directors may deem relevant. Unregistered Sales of Securities None. Issuer Purchases of Equity Securities None.
Holders of Common Stock On March 6, 2023, we had approximately 19 registered holders of record of our 12,539,189 shares of common stock outstanding. On March 6, 2023, the closing sale price of our common stock as reported by NASDAQ was $0.7485 per share.
On March 15, 2024, we had approximately 11 registered holders of record of our 1,318,257 shares of common stock outstanding. On March 15, 2024, the closing sale price of our common stock as reported by Nasdaq was $2.43 per share.
Added
Holders of Common Stock We effected a 15:1 reverse stock split of the our common stock on December 18, 2023 (the “Reverse Stock Split”). All share and per share information has been retroactively adjusted to give effect to the Reverse Stock Split for all periods presented, unless otherwise indicated.

Item 7. Management's Discussion & Analysis

Management's Discussion & Analysis (MD&A) — revenue / margin commentary

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Biggest changeWhile we have plans in place to mitigate this risk, which primarily consist of raising additional capital through a combination of public or private equity or debt financings or by entering into partnership agreements for further development of our drug candidates, there is no guarantee that we will be successful in these mitigation efforts. ​ Contractual Obligations The following table summarizes our long-term contractual obligations as of December 31, 2022 (in thousands): ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Payments Due by Period ​ ​ ​ Less than ​ ​ ​ ​ More than ​ ​ Total ​ 1 year ​ 1 – 3 years ​ 3 – 5 years ​ 5 years Operating Lease Obligations (1) ​ $ 170 ​ $ 67 ​ $ 104 ​ $ — ​ $ — (1) Operating lease obligations relate primarily to leasing office space at our Berkeley Heights, New Jersey location.
Biggest changeWhile we have plans in place to 68 Table of Contents mitigate this risk, which primarily consist of raising additional capital through a combination of public or private equity or debt financings or by entering into partnership agreements for further development of our drug candidates, there is no guarantee that we will be successful in these mitigation efforts.
The increase in other income primarily relates to royalties receivable under a December 2005 Asset Purchase Agreement, or APA, whereby Xcyte Therapies, Inc., or Xcyte (a business acquired by us in March 2006) sold through the APA and other related agreements certain assets and intellectual property which are not related to our product development plans to ThermoFisher Scientific Company, or TSC.
The decrease in other income primarily relates to royalties receivable under a December 2005 Asset Purchase Agreement, or APA, whereby Xcyte Therapies, Inc., or Xcyte (a business acquired by us in March 2006) sold through the APA and other related agreements certain assets and intellectual property which are not related to our product development plans to ThermoFisher Scientific Company, or TSC.
Certain factors that could cause results to differ materially from those projected or implied in the forward-looking statements are set forth in this Annual Report on Form 10-K for the year ended December 31, 2022 under the caption “Item 1A — Risk factors”. We encourage you to read those descriptions carefully.
Certain factors that could cause results to differ materially from those projected or implied in the forward-looking statements are set forth in this Annual Report on Form 10-K for the year ended December 31, 2023 under the caption “Item 1A — Risk factors”. We encourage you to read those descriptions carefully.
As discussed in Note 1 of the Notes to the Consolidated Financial Statements accompanying this Annual Report on Form 10-K, under ASC Topic 205-40, Presentation of Financial Statements - Going Concern , management is 69 Table of Contents required at each reporting period to evaluate whether there are conditions and events, considered in the aggregate, that raise substantial doubt about an entity’s ability to continue as a going concern within one year after the date that the financial statements are issued.
As discussed in Note 1 of the Notes to the Consolidated Financial Statements accompanying this Annual Report on Form 10-K, under ASC Topic 205-40, Presentation of Financial Statements - Going Concern , management is required at each reporting period to evaluate whether there are conditions and events, considered in the aggregate, that raise substantial doubt about an entity’s ability to continue as a going concern within one year after the date that the financial statements are issued.
Current business and capital market risks could have a detrimental effect on the availability of sources of funding and our ability to access them in the future, which may delay or impede our progress of advancing our drugs currently in the clinical pipeline to approval by the FDA or EMA for commercialization.
Current business and capital market risks could have a detrimental effect on the availability of sources of 67 Table of Contents funding and our ability to access them in the future, which may delay or impede our progress of advancing our drugs currently in the clinical pipeline to approval by the FDA or EMA for commercialization.
All statements, other than statements of historical fact, that address activities, events or developments that we intend, expect, project, believe or anticipate will or may occur in the future are forward-looking 63 Table of Contents statements.
All statements, other than statements of historical fact, that address activities, events or developments that we intend, expect, project, believe or anticipate will or may occur in the future are forward-looking statements.
Financing activities Net cash provided by financing activities was $3.0 million for the year ended December 31, 2022 as a direct result of receiving approximately: - $3.2 million in net proceeds from the issuance of common stock under a Controlled Equity Offering Sales Agreement with Cantor Fitzgerald & Co., - offset by dividend payments of approximately $0.2 million to the holders of our 6% Convertible Exchangeable Preferred Stock. ​ Net cash provided by financing activities was $21.7 million for the year ended December 31, 2021 as a direct result of receiving approximately: - $13.5 million in net proceeds from the issuance of common stock under an underwriting agreement with Oppenheimer & Co.
Net cash provided by financing activities was $3.0 million for the year ended December 31, 2022 as a direct result of receiving approximately: - $3.2 million in net proceeds from the issuance of common stock under a Controlled Equity Offering Sales Agreement with Cantor Fitzgerald & Co., - offset by dividend payments of approximately $0.2 million to the holders of our 6% Convertible Exchangeable Preferred Stock.
We reported no revenues for the years ended December 31, 2021 and 2022, and do not expect to report revenue for the foreseeable future. During 2022, our primary focus has been on our transcriptional regulation program, which is evaluating fadraciclib, a CDK2/9 inhibitor, in solid tumors and hematological malignancies .
We reported revenue of $0.4 million for the year ended December 31, 2023 and no revenues for the year ended December 31, 2022. We do not expect to report revenue for the foreseeable future. During 2023, our primary focus has been on our transcriptional regulation program, which is evaluating fadraciclib, a CDK2/9 inhibitor, in solid tumors and hematological malignancies .
As the funding advanced through intercompany loans is that of a long-term investment in nature, unrealized foreign exchange gains and losses on such funding will be recognized in other comprehensive income (loss) until repayment of the intercompany loan becomes foreseeable.
As the funding advanced through intercompany loans is that of a long-term investment in nature, unrealized foreign exchange gains and losses on such funding will be recognized in other comprehensive income (loss) until repayment of the intercompany loan becomes foreseeable. Income tax benefit We record research and development tax credits within income taxes.
Typically, CROs and CRAs bill monthly for services performed, or based upon milestones achieved. We accrue unbilled clinical trial expenses based on estimates of the level of services performed each period. Moreover, clinical trial costs related to patient enrollment are accrued as patients are entered into and progress through the trial. We also perform outsourced laboratory and manufacturing activities.
We accrue unbilled clinical trial expenses based on estimates of the level of services performed each period. Moreover, clinical trial costs related to patient enrollment are accrued as patients are entered into and progress through the trial. We also perform outsourced laboratory and manufacturing activities.
We accrue for unbilled laboratory and manufacturing activities performed by third parties based on estimates of their progress towards completing the requested tasks. As of December 31, 2022, we accrued $3.3 million of clinical trial, laboratory, and manufacturing costs that we believe had been incurred as of year-end but had not been invoiced.
We accrue for unbilled laboratory and manufacturing activities performed by third parties based on estimates of their progress towards completing the requested tasks. As of December 31, 2023, we accrued $3.7 million research and development costs, that we have estimated to have been incurred as of year-end but had not been invoiced.
Changes in any of these variables could result in significant adjustments to the expense recognized for share-based payments.
Changes in any of these variables could result in significant adjustments to the costs recognized for share-based payments. 75 Table of Contents
Research and development expenses relating to plogosertib increased by $2.0 million for the year ending December 31, 2022 relative to the respective comparative period.
Research and development expenses relating to plogosertib decreased by $0.6 million for the year ending December 31, 2023 relative to the respective comparative period.
Unfavorable unrealized foreign exchange movements related to intercompany loans resulted in a loss of $21.2 million for the year ended December 31, 2022 compared to a loss of $2.1 million for the year ended December 31, 2021.
Favorable unrealized foreign exchange movements related to intercompany loans resulted in a gain of $12.9 million for the year ended December 31, 2023 compared to a loss of $21.2 million for the year ended December 31, 2022.
The following table summarizes the total general and administrative expenses for the years ended December 31, 2021 and 2022 (in thousands except percentages): ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Year Ended ​ December 31, ​ Difference ​ 2022 2021 $ % Total general and administrative expenses $ 7,382 ​ $ 7,461 ​ $ (79) ​ (1) ​ Total general and administrative expenses represented 33% and 27% of our operating expenses for the years ended December 31, 2021 and 2022, respectively.
The following table summarizes the total general and administrative expenses for the years ended December 31, 2023 and 2022 (in thousands except percentages): ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Year Ended ​ ​ December 31, ​ Difference ​ 2023 2022 $ % Total general and administrative expenses ​ $ 6,718 ​ $ 7,382 ​ $ (664) ​ (9) ​ Total general and administrative expenses represented 26% and 27% of our operating expenses for the years ended December 31, 2023 and 2022, respectively.
Research and development expenses primarily include: ● Clinical trial and regulatory-related costs; ● Payroll and personnel-related expenses, including consultants and contract research organizations; ● Preclinical studies and materials; ● Technology license costs; ● Stock-based compensation; and ● Rent and facility expenses for our office. ​ The following table provides information with respect to our research and development expenditures for the years ended December 31, 2021 and 2022 (in thousands except percentages): ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Year Ended ​ December 31, ​ Difference ​ 2022 2021 $ % Transcriptional Regulation (fadraciclib) $ 14,043 ​ $ 11,105 ​ $ 2,938 ​ 26 Anti-mitotic (plogosertib) ​ 5,546 ​ ​ 3,579 ​ ​ 1,967 ​ 55 Other research and development expenses ​ 685 ​ ​ 793 ​ ​ (108) ​ (14) Total research and development expenses $ 20,274 ​ $ 15,477 ​ $ 4,797 ​ 31 ​ Research and development expenses represented 67% and 73% of our operating expenses for the years ended December 31, 2021 and 2022, respectively.
Research and development expenses primarily include: ● Clinical trial and regulatory-related costs; ● Payroll and personnel-related expenses, including consultants and contract research organizations; ● Preclinical studies and materials; ● Technology license costs; ● Stock-based compensation; and ● Rent and facility expenses for our office. ​ 70 Table of Contents The following table provides information with respect to our research and development expenditures for the years ended December 31, 2023 and 2022 (in thousands except percentages): ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Year Ended ​ ​ December 31, ​ Difference ​ ​ 2023 2022 $ % Transcriptional Regulation (fadraciclib) ​ $ 13,358 ​ $ 14,043 ​ $ (685) ​ (5) Epigenetic/anti-mitotic (plogosertib) ​ ​ 4,987 ​ ​ 5,546 ​ ​ (559) ​ (10) Other research and development expenses ​ ​ 810 ​ ​ 685 ​ ​ 125 ​ 18 Total research and development expenses ​ $ 19,155 ​ $ 20,274 ​ $ (1,119) ​ (6) ​ Research and development expenses represented 74% and 73% of our operating expenses for the years ended December 31, 2023 and 2022, respectively.
These shares have been treated as issued and outstanding for purposes of earnings per share and general financial reporting. ​ On August 15, 2022, due to expiry of the Registration Statement, the Sales Agreement was mutually terminated.
In all periods presented, the shares subject to the rescission rights were treated as issued and outstanding for purposes of earnings per share and general financial reporting. 69 Table of Contents On August 15, 2022, due to expiry of the Registration Statement, the Sales Agreement was mutually terminated.
Research and development expenses increased by $4.8 million from $15.5 million for the year ended December 31, 2021 to $20.3 million for the year ended December 31, 2022. Expenditure for the transcriptional regulation program increased by $2.9 million for the year ending December 31, 2022 relative to the respective comparative period.
Research and development expenses decreased by $1.1 million from $20.3 million for the year ended December 31, 2022 to $19.2 million for the year ended December 31, 2023. Expenditure for the transcriptional regulation program decreased by $0.7 million for the year ending December 31, 2023 relative to the respective comparative period.
This was due to an increase in clinical trial costs of $2.7 million associated with the 65 Table of Contents progression of clinical trials for the evaluation of plogosertib in Phase 1/2 studies, offset by a decrease in non-clinical expenditure of $0.7 million.
This decrease was primarily due to a decrease in clinical trial costs of $0.2 million associated with the progression of clinical trials for the evaluation of plogosertib in Phase 1/2 studies, and a decrease in manufacturing and other non-clinical expenditure of $0.4 million.
When recording these accruals, we must make judgments about the progress of our various clinical activities. We (as well as our CROs and CRAs) are reliant on information being provided timely and accurately by the multitude of clinics and hospitals where the studies are being conducted, some of which are located internationally.
We (as well as our CROs and CRAs) are reliant on information being provided timely and accurately by the multitude of clinics and hospitals where the studies are being conducted, some of which are located internationally. We must also make estimates about the progress our third-party vendors are making towards completing laboratory and manufacturing activities.
The level of tax credits recoverable is linked directly to qualifying research and development expenditure incurred in any one year. The future We expect to continue to be eligible to receive United Kingdom research and development tax credits for the year ending December 2023 and will continue to elect to receive payment of the tax credit.
The future We expect to continue to be eligible to receive United Kingdom research and development tax credits for the year ending December 31, 2024 and will continue to elect to receive payment of the tax credit.
Based on our current operating plan, we anticipate that our cash and cash equivalents of $18.3 million as of December 31, 2022 will allow us to meet our liquidity requirements to the fourth quarter of 2023.
Based on our current operating plan, we anticipate that our cash and cash equivalents of $3.4 million as of December 31, 2023 will allow us to meet our liquidity requirements into April of 2024. As of March 21, 2024 our cash balance on hand was approximately $3.4 million.
We measure compensation cost for all stock-based awards at fair value on date of grant and recognize compensation over the requisite service period. The fair value of restricted stock and restricted stock units is determined based on the number of shares granted and the quoted price of our common stock on the date of grant.
The fair value of restricted stock and restricted stock units is determined based on the number of shares granted and the quoted price of our common stock on the date of grant.
Accrued Research and Development Costs Accrued research and development costs comprise our best estimates related to the cost of clinical trials, laboratory, and manufacturing activities that were incurred, but not paid or invoiced, as of the end of a reporting period. 70 Table of Contents Data management and monitoring of our clinical trials are performed with the assistance of contract research organizations, or CROs, or clinical research associates, or CRAs, in accordance with our standard operating procedures.
Accrued Research and Development Costs Accrued research and development costs comprise our best estimates related to the cost of clinical trials, laboratory, and manufacturing activities that were incurred, but not paid or invoiced, as of the end of a reporting period.
Therefore, all unrealized foreign exchange gains or losses arising on the intercompany loans are recognized in other comprehensive income until repayment of the intercompany loan becomes foreseeable.
The intercompany loans outstanding are not expected to be repaid in the foreseeable future and the nature of the funding advanced is of a long-term investment nature. Therefore, all unrealized foreign exchange gains or losses arising on the intercompany loans are recognized in other comprehensive income until repayment of the intercompany loan becomes foreseeable.
A total of 3,281,067 shares, for gross proceeds of approximately $7.6 million, had been sold pursuant to the Sales Agreement, including 2,528,642 shares during the year ended December 31, 2022 for gross proceeds of approximately $3.4 million. ​ On March 12, 2021, we entered into an Underwriting Agreement (the “Underwriting Agreement”) with Oppenheimer & Co.
A total of 218,738 shares, for gross proceeds of approximately $7.6 million, had been sold pursuant to the Sales Agreement, including 168,576 shares during the year ended December 31, 2022 for gross proceeds of approximately $3.4 million.
The lease for our Berkeley Heights location, which was entered into in April 2022, expires in July 2025.
The lease for our Berkeley Heights location, which was entered into in April 2022, expires in July 2025. The table does not include any amouns relating to a short term lease for offices in Dundee, Scotland.
Dividend on Preferred Stock On December 6, 2022, the Board of Directors declared a quarterly cash dividend in the amount of $0.15 per share on our Preferred Stock. The cash dividend was paid on February 1, 2023 to the holders of record of the Preferred Stock as of the close of business on January 13, 2023.
Dividend on Preferred Stock On January 12, 2024, the Board of Directors declared a quarterly cash dividend in the amount of $0.15 per share on our 6% Convertible Exchangeable Preferred Stock.
Accordingly, we presented $1.3 million and $144,000 as other income received from TSC during the years ended December 31, 2022 and 2021 respectively.
Accordingly, we presented $50,000 and $1.3 million as other income received from TSC during the years ended December 31, 2023 and 2022 respectively. We have no knowledge of TSC’s activities and cannot predict when we may receive income under the APA, if any.
Critical Accounting Policies and Estimates Our discussion and analysis of our financial condition and results of operations is based on our financial statements, which have been prepared in accordance with accounting principles generally accepted in the United States.
Recently Issued Accounting Pronouncements Please see Note 2 to the consolidated financial statements for a discussion of the potential effects that recently issued, but not yet effective, accounting standards will have on our financial statements when adopted in a future period. 74 Table of Contents Critical Accounting Policies and Estimates Our discussion and analysis of our financial condition and results of operations is based on our financial statements, which have been prepared in accordance with accounting principles generally accepted in the United States.
The future We anticipate that overall research and development expenses for the year ended December 31, 2023 will be broadly similar compared to the year ended December 31, 2022 as we continue our Phase 1/2 programs. General and administrative General and administrative expenses include costs for administrative personnel, legal and other professional expenses and general corporate expenses.
The future We anticipate that overall research and development expenses for the year ended December 31, 2024 will decrease compared to the year ended December 31, 2023 as we focus on our Phase 1/2 programs in advanced solid tumors and lymphomas.
Beyond 2023, we cannot be certain to be eligible to receive this tax credit or if eligible, the amount that may be receivable due to proposed changes by HMRC to the elibility criteria. 67 Table of Contents Liquidity and Capital Resources The following is a summary of our key liquidity measures as of December 31, 2021 and 2022 (in thousands): ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ December 31, ​ 2022 2021 Cash and cash equivalents ​ $ 18,345 ​ $ 36,559 Working capital: ​ ​ ​ ​ ​ ​ Current assets ​ $ 24,411 ​ $ 40,942 Current liabilities ​ (7,392) ​ (5,294) Total working capital ​ $ 17,019 ​ $ 35,648 ​ Cash Flows Cash provided by (used in) operating, investing and financing activities for the years ended December 31, 2021 and 2022 is summarized as follows (in thousands): ​ ​ ​ ​ ​ ​ ​ ​ ​ Year Ended December 31, ​ 2022 2021 Net cash used in operating activities ​ $ (20,827) ​ $ (18,540) Net cash used in investing activities ​ (7) ​ (27) Net cash provided by financing activities ​ 2,998 ​ 21,737 ​ Operating activities Net cash used in operating activities increased by $2.3 million, from $18.5 million for the year ended December 31, 2021 to $20.8 million for the year ended December 31, 2022.
Liquidity and Capital Resources The following is a summary of our key liquidity measures as of December 31, 2023 and 2022 (in thousands): ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ December 31, ​ 2023 2022 Cash and cash equivalents ​ $ 3,378 ​ $ 18,345 Working capital: ​ ​ ​ ​ ​ ​ Current assets ​ $ 7,444 ​ $ 24,411 Current liabilities ​ (8,161) ​ (7,511) Total working capital ​ $ (717) ​ $ 16,900 ​ Cash Flows Cash provided by (used in) operating, investing and financing activities for the years ended December 31, 2023 and 2022 is summarized as follows (in thousands): ​ ​ ​ ​ ​ ​ ​ ​ ​ Year Ended December 31, ​ 2023 2022 Net cash used in operating activities ​ $ (16,112) ​ $ (20,827) Net cash used in investing activities ​ (6) ​ (7) Net cash provided by financing activities ​ 848 ​ 2,998 ​ 73 Table of Contents Operating activities Net cash used in operating activities decreased by $4.7 million, from $20.8 million for the year ended December 31, 2022 to $16.1 million for the year ended December 31, 2023.
Cantor could sell the our common stock by any method permitted by law deemed to be an “at the market offering” as defined in Rule 415(a)(4) of the Securities Act. ​ On August 12, 2022, we became aware that the shelf registration statement on Form S-3 (file number 333-231923) (the “Registration Statement”) associated with this Sales Agreement had expired on June 21, 2022.
On August 12, 2022, we became aware that the shelf registration statement on Form S-3 (file number 333-231923) (the “Registration Statement”) associated with this Sales Agreement had expired on June 21, 2022.
The increase in cash used by operating activities was primarily the result of an increase in our year-over-year net loss of $2.3 million, an increase in working capital of $0.2 million and a decrease in change in lease liability of $0.1 million, offset by an increase in stock compensation costs of $0.3 million.
The decrease in cash used by operating activities was primarily the result of a change in working capital of $6.3 million, offset by an increase in net loss of $1.3 million. The $6.3 million change in working capital was primarily due to decreased balances in clinical trial deposits and receivables for research and development tax credits.
This represents approximately 17% of our total research and development expense for the year ended December 31, 2022. The comparable accrual for unbilled research and development costs as of December 31, 2021 was approximately $2.3 million. This accrual represented approximately 15% of our total research and development expense for the year ended December 31, 2021.
This represents approximately 19% of our total research and development expense for the year ended December 31, 2023. As of December 31, 2022, we accrued $3.6 million research and development costs, that we have estimated to have been incurred as of year-end but had not been invoiced.
Investing activities Net cash used in investing activities decreased by $20,000 for the year ended December 31, 2022 due to a decrease in capital expenditures on IT equipment.
A cash receipt of approximately $4.8 million in research and development tax credit was received during the year ended December 31, 2023. Investing activities Net cash used in investing activities decreased by $1,000 for the year ended December 31, 2023 due to a slight decrease in capital expenditures on information technology (“IT”) during the respective comparative period.
The following table summarizes total income tax benefit from such credits for the years ended December 31, 2021 and 2022 (in thousands except percentages): ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Year Ended ​ December 31, ​ Difference ​ 2022 2021 $ % Income tax benefit $ 4,717 ​ $ 3,847 ​ $ 870 ​ 23 Total income tax benefit $ 4,717 ​ $ 3,847 ​ $ 870 ​ 23 ​ The income tax benefit increased significantly by approximately $0.9 million, from $3.8 million for the year ended December 31, 2021 to $4.7 million for the year ended December 31, 2022.
Credit is taken for research and development tax credits, which are claimed from the United Kingdom’s taxation and customs authority (HMRC), in respect of qualifying research and development costs incurred. 72 Table of Contents The following table summarizes total income tax benefit from such credits for the years ended December 31, 2023 and 2022 (in thousands except percentages): ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Year Ended ​ ​ December 31, ​ Difference ​ ​ 2023 2022 $ % Total income tax benefit ​ $ 2,996 ​ $ 4,717 ​ $ (1,721) ​ (36) ​ The income tax benefit decreased significantly by approximately $1.7 million, from $4.7 million for the year ended December 31, 2022 to $3.0 million for the year ended December 31, 2023, due to legislative changes that took effect in April 2023.
Other income (expense), net The following table summarizes the other income (expense) for years ended December 31, 2021 and 2022 (in thousands except percentages): ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Year Ended ​ December 31, ​ Difference ​ 2022 2021 $ % Foreign exchange gains $ 233 ​ $ 44 ​ $ 189 ​ 430 Interest income 210 ​ 16 ​ 194 ​ 1,213 Other income, net 1,298 ​ 144 ​ 1,154 ​ 801 Total other income $ 1,741 ​ ​ 204 ​ $ 1,537 ​ 753 ​ Total other income, net, increased by approximately $1.5 million from approximately $0.2 million for the year ended December 31, 2021 to approximately $1.7 million for the year ended December 31, 2022.
The future We expect general and administrative expenditures for the year ended December 31, 2024 to remain relatively flat compared to the year ended December 31, 2023. 71 Table of Contents Other income (expense), net The following table summarizes the other income (expense) for years ended December 31, 2023 and 2022 (in thousands except percentages): ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Year Ended ​ ​ December 31, ​ Difference ​ ​ 2023 2022 $ % Foreign exchange gains (losses) ​ $ (414) ​ $ 233 ​ $ (647) ​ (278) Interest income ​ 266 ​ 210 ​ 56 ​ 27 Other income (expense), net ​ 50 ​ 1,298 ​ (1,248) ​ (96) Total other income (expense), net ​ $ (98) ​ ​ 1,741 ​ $ (1,839) ​ (106) ​ Total other income, net, decreased by approximately $1.8 million from an income of approximately $1.7 million for the year ended December 31, 2022 to an expense of approximately $0.1 million for the year ended December 31, 2023.
Such forward-looking statements are not guarantees of future performance and actual results will likely differ, perhaps materially, from those suggested by such forward-looking statements. Overview We are a clinical-stage biopharmaceutical company developing innovative cancer medicines based on cell cycle, transcriptional regulation and mitosis control biology.
Such forward-looking statements are not guarantees of future performance and actual results will likely differ, perhaps materially, from those suggested by such forward-looking statements. We effected a 15:1 reverse stock split of our common stock on December 18, 2023 (the “Reverse Stock Split”).
Inc., and Brookline Capital Markets, a division of Arcadia Securities, LLC, and - $4.0 million from the issuance of common stock under a controlled equity offering sales agreement with Cantor Fitzgerald & Co., and 68 Table of Contents - offset by dividend payments of approximately $0.2 million to the holders of our 6% Convertible Exchangeable Preferred Stock. - ​ Funding Requirements and Going Concern As of December 31, 2022, we had cash and cash equivalents of $18.3 million We have incurred losses since our inception and as of December 31, 2022, we had an accumulated deficit of $406.2 million.We expect to continue to incur substantial operating losses in the future.
Funding Requirements and Going Concern As of December 31, 2023, we had cash and cash equivalents of $3.4 million We have incurred losses since our inception and as of December 31, 2023, we had an accumulated deficit of $428.3 million.We expect to continue to incur substantial operating losses in the future.
The future We expect general and administrative expenditures for the year ended December 31, 2023 to remain relatively flat compared to the year ended December 31, 2022.
We did not have any revenue for the year ended December 31, 2022 and do not expect to report revenue for the foreseeable future.
Prior to becoming aware of the expiration, we sold an aggregate of 3,117,100 shares of our common stock at market prices, following the expiration of the Registration Statement and through August 12, 2022, for aggregate proceeds of approximately $4,494,496. There was no sale of shares post August 12, 2022.
Prior to becoming aware of the expiration, but following the expiration, we sold an aggregate of 132,473 shares of our common stock at market prices for aggregate proceeds of approximately $2,721,187. The sale of these shares were subject to potential rescission rights by certain stockholders.
We must also make estimates about the progress our third-party vendors are making towards completing laboratory and manufacturing activities. Stock-based Compensation We grant stock options, restricted stock units and restricted stock to officers, employees, directors and consultants under our 2018 Equity Incentive Plan (the 2018 Plan) and the 2020 Inducement Equity Incentive Plan.
Stock-based Compensation We grant stock options, restricted stock units and restricted stock to officers, employees, directors and consultants under our 2018 Equity Incentive Plan (the 2018 Plan) and the 2020 Inducement Equity Incentive Plan. We measure compensation cost for all stock-based awards at fair value on date of grant and recognize compensation over the requisite service period.
This was due to an increase in clinical trial costs of $2.2 million associated with the progression of clinical trials for the evaluation of fadraciclib in Phase 1/2 studies, along with an increase in non-clinical expenditure of $0.7 million.
This decrease was primarily due to a decrease in clinical trial costs of $2.2 million associated with the temporary halt in the Phase 1/2 study in hematological malignancies and the completion of a bioequivalence study during the prior year, offset by an increase in manufacturing and other non-clinical expenditure of $1.6 million.
The anti-mitotic program is evaluating plogosertib, a PLK1 inhibitor, in advanced cancers. We currently retain all marketing rights worldwide to the compounds associated with our drug programs. Agreements to Sell Securities On August 12, 2021, we entered into a Controlled Equity Offering Sales Agreement (the “Sales Agreement”) with Cantor Fitzgerald & Co.
The epigenetic/anti-mitotic program is evaluating plogosertib, a PLK1 inhibitor, in advanced cancers. We currently retain all marketing rights worldwide to the compounds associated with our drug programs. Revenue We have not generated any revenues from product sales to date. Our product candidates will require significant additional research and development efforts, including extensive preclinical and clinical testing.
The closing of the offering occurred on March 16, 2021, and the net proceeds to us (including exercise of the over- 64 Table of Contents allotment option) were approximately $13.5 million, after deducting placement agent fees and other offering expenses payable by us.
Each Common Warrant has an exercise price of $3.19 per share, is exercisable immediately following their original issuance and will expire seven years from the original issuance date. The closing of the offering occurred on December 26, 2023, and the net proceeds to us were approximately $1.0 million, after deducting placement agent fees and other offering expenses payable by us.
As a result of these potential rescission rights, we reclassified 3,117,100 shares, with an aggregate purchase price of $4,494,496 of our common stock as temporary equity, presented outside of stockholders’ equity. The reclassification of these shares shall remain for a period of one year from the transaction date.
As a result of these rescission rights, we classified 207,807 shares (including 75,333 previously issued and outstanding shares sold for which the Company did not receive proceeds and which were reclassified to temporary equity as of September 30, 2022), with an aggregate redemption value of $4,494,496 of our common stock as stock outside stockholders equity.
We have intercompany loans in place between our parent company based in New Jersey and our subsidiary based in Scotland. The intercompany loans outstanding are not expected to be repaid in the foreseeable future and the nature of the funding advanced is of a long-term investment nature.
Foreign exchange gains (losses) Foreign exchange gains decreased by $0.6 million to a loss of $0.4 million for the year ended December 31, 2023 compared to a gain of approximately $0.2 million for the year ended December 31, 2022. We have intercompany loans in place between our parent company based in New Jersey and our subsidiary based in Scotland.
Removed
The sale of these shares may be subject to potential rescission rights by certain shareholders. As of December 31, 2022, there have been no claims or demands to exercise such rights.
Added
All share and per share information has been retroactively adjusted to give effect to the Reverse Stock Split for all periods presented, unless otherwise indicated. Overview We are a clinical-stage biopharmaceutical company developing innovative cancer medicines based on cell cycle, transcriptional regulation, epigenetics and mitosis control biology.
Removed
Inc., as representative of the underwriters identified therein (collectively, the “Underwriters”), pursuant to which we agreed to issue and sell 1,807,143 shares of common stock, $0.001 par value per share, at a public offering price of $7.00 per share (the “Offering”) along with a 30-day overallotment option to purchase up to an additional 271,071 shares of common stock at the public offering price, less underwriting discounts and commissions.
Added
All product candidates that we advance to clinical testing will require regulatory approval prior to commercial use and will require significant costs for commercialization. We have recognized revenue of $0.4 million for the year ended December 31, 2023 related to the recovery of clinical manufacturing costs associated with an investigator sponsored study managed by Cedars Sinai Medical Center.
Removed
Results of Operations Years Ended December 31, 2021 and 2022 Results of Continuing Operations Research and development We expense all research and development costs as they are incurred.
Added
We continue to work to raise additional capital however as of the date of the Consolidated Financial Statements accompanying this Annual Report on Form 10-K, there is no guarantee that we will be able to raise additional funds to extend operations past April 2024.
Removed
Our general and administrative expenditures remained relatively flat at approximately $7.4 million for each of the years ended December 31, 2021 and 2022.
Added
Agreements to Sell Securities On December 21, 2023, we entered into a securities purchase agreement (the “Securities Purchase Agreement”) with certain institutional investors (the “Purchasers”).
Removed
During the year ended December 31, 2022 as compared to the year ended December 31, 2021, there were increases in employment costs of $0.3 million, stock compensation costs of $0.2 million and professional costs of $0.2 million, offset by reductions in facility costs of $0.6 million.
Added
Pursuant to the Securities Purchase Agreement, we agreed to sell in a registered direct offering (“Registered Direct Offering”) 168,500 shares (“Shares”) of our common stock, $0.001 par value per share ( “Common Stock”), and pre-funded warrants (“Pre-Funded Warrants”) to purchase up to 219,700 shares of Common Stock.
Removed
We have no knowledge of TSC’s activities and cannot predict when we may receive income under the APA, if any. 66 Table of Contents Foreign exchange gains (losses) Foreign exchange gains increased by approximately $189,000 to a gain of $233,000 for the year ended December 31, 2022 compared to a gain of approximately $44,000 for the year ended December 31, 2021.
Added
The Pre-Funded Warrants have an exercise price of $0.001 per share and are immediately exercisable and can be exercised at any time after their original issuance until such Pre-Funded Warrants are exercised in full.
Removed
Income tax benefit Credit is taken for research and development tax credits, which are claimed from the United Kingdom’s taxation and customs authority (HMRC), in respect of qualifying research and development costs incurred.
Added
Each Share was sold at a price of $3.315 and each Pre-Funded Warrant was sold at a price of $3.314 (equal to the purchase price per Share minus the exercise price of the Pre-Funded Warrant).
Removed
Inc., - $4.5 million from warrant exercises associated with a co-placement agency agreement with Roth Capital Partners, LLC, Ladenburg Thalmann & Co.
Added
Pursuant to the Securities Purchase Agreement, in a concurrent private placement (together with the Registered Direct Offering, the “Offerings”), we also agreed to issue to the Purchasers unregistered warrants (“Common Warrants”) to purchase up to 388,200 shares of Common Stock.
Added
Ladenburg Thalmann & Co. Inc. (the “Placement Agent”) acted as the exclusive placement agent for the Offerings, pursuant to a placement agency agreement dated December 21, 2023, by and between us and the Placement Agent.
Added
On December 21, 2023, in a separate concurrent insider private placement (the “Insider Private Placement”), we also entered into a Securities Purchase Agreement with certain of our executive officers (the “Insider Securities Purchase Agreement”) pursuant to which we agreed to sell in a private placement (i) 6,070 shares of Common Stock and warrants to purchase 6,070 shares of Common Stock on the same terms as the Common Warrants issued to the Purchasers in the Offerings to Spiro Rombotis, our Chief Executive Officer, and (ii) 1,886 shares of Common Stock and warrants to purchase 1,886 shares of Common Stock on the same terms as the Common Warrants issued to the Purchasers in the Offerings to Paul McBarron, our Executive Vice President-Finance, Chief Financial Officer and Chief Operating Officer.
Added
Each such share of Common Stock and accompanying warrant was sold at a purchase price of $3.315, which was the same purchase price for the Shares sold in the Registered Direct Offering. On August 12, 2021, we entered into a Controlled Equity Offering Sales Agreement (the “Sales Agreement”) with Cantor Fitzgerald & Co.
Added
Cantor could sell our common stock by any method permitted by law deemed to be an “at the market offering” as defined in Rule 415(a)(4) of the Securities Act.
Added
We also restated our loss per share as a result of $135,000 of associated fees not initially accounted for as accretion to the maximum redemption amount of the shares subject to potential rescission.
Added
During the third quarter of 2023, upon expiration of the rescission rights and with no claims or demands to exercise such rights, we reclassified all 207,807 shares back to permanent equity.
Added
The cash dividend of approximately $50,000 was paid on February 1, 2024 to the holders of record of the 6% Convertible Exchangeable Preferred Stock as of the close of business on January 22, 2024.
Added
Results of Operations Years Ended December 31, 2023 and 2022 Results of Continuing Operations Revenues The following table summarizes the revenues for years ended December 31, 2023 and 2022 (in thousands except percentages): ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Year ended December 31, ​ Difference ​ 2023 2022 ​ $ % Clinical trial supply ​ 420 ​ — ​ 420 ​ 100 Total Revenue ​ $ 420 ​ $ — ​ $ 420 ​ 100 ​ We recognize recognized $420,000 of revenue for the year ended December 31, 2023.
Added
This revenue relates to recovery of clinical manufacturing costs associated with an investigator sponsored study managed by Cedars-Sinai Medical Center. There were no revenues recognized for the comparative periods in 2022. We do not expect to report revenue for the foreseeable future. Research and development We expense all research and development costs as they are incurred.
Added
General and administrative General and administrative expenses include costs for administrative personnel, legal and other professional expenses and general corporate expenses.
Added
Our general and administrative expenditures decreased by $0.7 million from $7.4 million for the year ended December 31, 2022 to $6.7 million for the year ended December 31, 2023. This decrease was primarily due to a non-recurring $0.4 million cost associated with the Controlled Equity Offering Sales Agreement with Cantor Fitzgerald & Co.
Added
(the “Sales Agreement”) in the comparative prior period.
Added
The level of tax credits recoverable is linked directly to qualifying research and development expenditure incurred in any one year and the availability of trading losses.
Added
The legislative changes which took effect in April 2023 have been partially reversed in early 2024 resulting in additional income tax benefit of $0.8 million in relation to expenditure incurred during the year ended December 31, 2023 and receivable during the second quarter of 2024.
Added
Beyond 2024, there is no guarantee that we will be eligible to receive this tax credit or if eligible, any amount that may be receivable due to proposed changes by HMRC to the eligibility criteria would be correctly estimated.
Added
We expect research and development tax credits for the year ending December 31, 2024 to be lower compared to the year ended December 31, 2023.

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