Greenwich LifeSciences, Inc. 10-Q

ITEM 1A. RISK FACTORS The Company is updating its risk factors disclosed in its Form 10-K for the year ended December 31, 2022 as follows: Risks associated with out-licensing GP2 or future product candidates in foreign countries could materially adversely affect the commercialization of our products. We may not be able to market products abroad if we cannot complete out-licensing transactions of GP2 or future product candidates by signing licensing agreements with regional companies in countries where we plan to commercialize our products but where we do not have any operations. Risks associated with out-licensing transactions of our products in foreign countries include: ● failure to obtain regulatory approval or intellectual property rights in any country which could lead to the termination of a licensing transaction in that country; ● the inability to obtain the issuance of patent claims or regulatory status in a foreign country that provide periods of market exclusivity or data exclusivity prior to the entry of generic or biosimilar forms of our products; ● the difficulty of pursuing legal remedies to disputes or to secure monetary damages in foreign countries; ● the inability to repatriate income from a licensing transaction in a foreign country to the U.S. or to other foreign countries where cash is needed; and ● the potential to not realize or to delay development or commercialization milestone payments due to unanticipated outcomes that prevent or delay the milestone. Risks associated with operating in foreign countries could materially adversely affect our product development. We may conduct future clinical trials in countries outside of the U.S. Consequently, we may be subject to risks related to operating in foreign countries. Risks associated with conducting operations in foreign countries include: ● differing regulatory requirements for drug approvals and regulation of approved drugs in foreign countries; more stringent privacy requirements for data to be supplied to our operations in the U.S., e.g. , General Data Protection Regulation in the European Union; ● difficulty in exporting patient samples or patient data back to the U.S. to conduct research and analyze clinical trial results due to exportation and data protection requirements; ● difficulty and costs associated with shipping drugs, clinical supplies, and patient samples in controlled temperature conditions over long distances; ● unexpected changes in tariffs, trade barriers and regulatory requirements; economic weakness, including inflation, or political instability in particular foreign economies and markets; compliance with tax, employment, immigration and labor laws for employees living or traveling abroad; foreign taxes, including withholding of payroll taxes; ● differing payor reimbursement regimes, governmental payors or patient self-pay systems and price controls; ● foreign currency fluctuations, which could result in increased operating expenses or reduced revenues, and other obligations incident to doing business or operating in another country; ● workforce uncertainty in countries where labor unrest is more common than in the U.S.; ● production shortages resulting from any events affecting raw material supply or manufacturing capabilities abroad; and ● business interruptions resulting from geopolitical actions, including war and terrorism. - 13 - Our future success is dependent on the regulatory approval of our product candidate. Our business is dependent on our ability to obtain regulatory approval for our product candidate in a timely manner. We cannot commercialize our product candidate in the U.S. without first obtaining regulatory approval for the product from the FDA. Similarly, we cannot commercialize our product candidate outside of the U.S. without obtaining regulatory approval from comparable foreign regulatory authorities. The FDA and foreign regulatory authorities may not allow patient data from all countries to be used to satisfy their specific country requirements for various reasons such as concerns of varying genetics and thus treatment responses by race or country of origin or differences in standard of care by country or regions within countries. The most recent U.S. approved breast cancer drugs may not be approved, available, affordable, or reimbursed in all countries in the world or in countries in which we may conduct clinical trials. Before obtaining regulatory approvals for the commercial sale of our product candidate for a target indication, we must demonstrate with substantial evidence gathered in preclinical studies and clinical trials, that the product candidate is safe and effective for use for that target indication and that the manufacturing facilities, processes and controls are adequate with respect to such product candidate. The time required to obtain approval by the FDA and comparable foreign regulatory authorities is unpredictable but typically takes many years following the commencement of preclinical studies and clinical trials and depends upon numerous factors, including the substantial discretion of the regulatory authorities. In addition, approval policies, regulations, or the type and amount of clinical data necessary to gain approval may change during the course of a product candidate’s clinical development and may vary among jurisdictions. Additional time may be required to do more manufacturing testing as well as to make multiple lots of commercial drug product, including the packaging of the drug product, based on the commercial requirements of each country. Even if a product candidate were to successfully obtain approval from the FDA and comparable foreign regulatory authorities, any approval might contain significant limitations related to use restrictions for specified age groups, warnings, precautions or contraindications, or may be subject to burdensome post-approval clinical trial or risk management requirements. Also, any regulatory approval of our current product candidate or any future product candidates we may pursue, once obtained, may be withdrawn. A new EU regulatory software system was implemented in 2023 to facilitate the submission of applications to conduct clinical trials in the EU. This new Clinical Trials Information System (CTIS) supports the flow of information between clinical trial sponsors, EU Member States, European Economic Area countries and the European Commission. This new unproven process for seeking approval to conduct clinical trials in EU member countries is based on new software, is conducted without direct interaction with EU regulators, and thus may create unexpected outcomes or delays, misunderstandings based on written interpretations and language differences, repeated submissions, protracted timelines based on staffing and EU holidays, and limited negotiations that can only take place in writing without any voice or video discussions. Failure to obtain regulatory approval in international jurisdictions would prevent our product candidate from being marketed and out-licensed abroad. In addition to regulations in the U.S., to market and sell our product candidate in the European Union, United Kingdom, many Asian countries or other jurisdictions, we must obtain separate regulatory approvals and comply with numerous and varying regulatory requirements. Approval by the FDA does not ensure approval by regulatory authorities in other countries or jurisdictions, and approval by one regulatory authority outside the U.S. does not ensure approval by regulatory authorities in other countries or jurisdictions or by the FDA. The regulatory approval process outside the U.S. generally includes all of the risks associated with obtaining FDA approval as well as risks attributable to the satisfaction of local regulations in foreign jurisdictions. The approval procedure varies among countries and can involve additional testing. The time required to obtain approval may differ substantially from that required to obtain FDA approval. We may not be able to obtain approvals from regulatory authorities outside the U.S. on a timely basis, if at all. Clinical trials accepted in one country may not be accepted by regulatory authorities in other countries. In addition, many countries outside the U.S. require that a product be approved for reimbursement before it can be approved for sale in that country. A product candidate that has been approved for sale in a particular country may not receive reimbursement approval in that country. We may not be able to file for regulatory approvals and may not receive necessary approvals to commercialize our product in any market. If we are unable to obtain approval of any of our current product candidate or any future product candidates we may pursue by regulatory authorities in the European Union, United Kingdom, Asia or elsewhere, the commercial prospects of that product candidate may be significantly diminished, our business prospects could decline, we may not be able to complete out-licensing transactions, and this could materially adversely affect our business, results of operations and financial condition. In the clinical trials using GP2, improper intradermal injections or poor HLA binding by GP2 may potentially jeopardize the outcome of the trials. GP2 is administered intradermally to patients with and without the HLA-A*02 allele. The effectiveness of GP2 is dependent upon attracting sufficient antigen presenting cells in the patient’s intradermal space and the association of GP2 with the HLA type of a patient to adequately train T cells to kill cancer cells, which may or may not be possible or consistent across all HLA types. It is possible that nurses may not successfully inject GP2 in the intradermal space or that certain HLA types may form weak or no association with GP2, potentially leading to weak or no immune response to GP2 and thus no benefit to patients with some or any HLA type. In the clinical trials using GP2, GM-CSF is also administered and its availability is dependent upon a third-party manufacturer, which may or may not reliably provide GM-CSF in the U.S. or in any other country, thus potentially jeopardizing the completion of the trials. GP2 is administered in combination with GM-CSF which is available in a lyophilized form exclusively from one manufacturer who only has marketing approval for sale of GM-CSF (Leukine) in the U.S, and not in any other country. We will need to export GM-CSF to any countries in which we conduct clinical trials relying on the U.S. registration, which may not always be successful. We will continue to be dependent on such manufacturer for our supply of GM-CSF in combination with GP2 in the ongoing GP2 trials and upon the potential commercialization of GP2. To successfully commercialize GP2 outside of the U.S., GM-CSF will need to be available in those countries, through a customized process that allows for individual patient use based on a doctor’s prescription or through registration of GM-CSF in those countries. We have not entered into a supply agreement with the manufacturer for GM-CSF, and instead rely on purchase orders to meet our supply needs. Any temporary interruptions or discontinuation of the availability of GM-CSF could have a material adverse effect on our operations. We are periodically involved in various litigation and/or regulatory proceedings that, if adversely decided or settled, could materially and adversely affect our business, financial condition, and results of operations. We are periodically party to or the subject of litigation, investigations, regulatory proceedings or other disputes. In general, claims made by or against us in disputes and other legal or regulatory proceedings can be expensive and time consuming to bring or defend against, requiring us to expend significant resources and divert the efforts and attention of our management and other personnel from our business operations. While we intend to pursue any claims made by us, or vigorously defend against any claims brought against us, we cannot predict the outcomes of such claims. Any failure to prevail in any claims made by us or any adverse determination against us in these legal and/or regulatory proceedings, or even the allegations contained in such proceedings, regardless of whether they are ultimately found to be without merit, may also result in settlements, injunctions, fines, penalties, or damages that could have a material adverse effect on our business, financial condition and results of operations. - 14 - We may hold cash and cash equivalents at various foreign subsidiaries and in countries outside of the US that may not be readily available to meet cash requirements. Currently a majority of our cash and cash equivalents is held by our U.S. parent company, however, our foreign subsidiary may in the future hold cash. Our U.S. parent company or our foreign subsidiary may hold cash balances outside the United States which may not be readily available, or may not be available without an additional tax burden, to meet our domestic or foreign cash requirements. U.S. tax laws may allow for reductions to the potential tax burden on repatriation of foreign cash; however, such actions would require us to record additional income tax expense and remit additional taxes, which could have a material adverse effect on our results of operations, cash flows and financial condition. In addition, foreign exchange rates may fluctuate leading to unexpected losses and inefficient utilization of cash in countries outside of the U.S. The COVID-19 coronavirus could adversely impact our business in the U.S. and in other countries, including several key activities, including clinical trial activities, manufacturing of drugs and clinical supplies, exportation of drug and supplies, and management of international payments and cash flow that are critical to our success. The global outbreak of COVID-19 continues to rapidly evolve, including the emergence of new strains that could have the potential to be as harmful as or more harmful than the original strains in 2020. As a result, businesses may close, staffing may be reduced, including clinical staffs, and limits may be placed on travel. The extent to which COVID-19 may impact our business will depend on future developments, which are highly uncertain and cannot be predicted with confidence, such as the ultimate impact of the disease on specific geographies, the duration of the outbreak, travel restrictions and social distancing in the United States and other countries, business closures or business disruptions and the effectiveness of actions taken in the United States and other countries to contain and treat the disease. The spread of COVID-19 throughout the world has also created global economic uncertainty, which may cause partners, suppliers and potential customers to closely monitor their costs and reduce their spending budget. Any of the foregoing could materially adversely affect our research and development activities, clinical trials, supply chain, financial condition and cash flows. If the COVID-19 outbreak continues to spread and evolve, we may need to limit operations or implement other limitations on our activities. There is a risk that countries or regions outside the United States may be less effective at vaccinations and containing COVID-19, in which case the risks described herein could be elevated significantly. We may be adversely affected by the effects of inflation and a potential recession. Inflation has the potential to adversely affect our liquidity, business, financial condition, and results of operations by increasing our overall cost structure. The existence of inflation in the economy has resulted in, and may continue to result in, higher interest rates and capital costs, shipping costs, supply shortages, increased costs of labor, weakening exchange rates, and other similar effects. As a result of inflation, we have experienced and may continue to experience, cost increases. In addition, poor economic and market conditions, including a potential recession, may negatively impact market sentiment, which would adversely affect our results of operations. If we are unable to take effective measures in a timely manner to mitigate the impact of the inflation as well as a potential recession, our business, financial condition, and results of operations could be adversely affected. - 15 - ITEM 2. UNREGISTERED SALES OF EQUITY SECURITIES AND USE OF PROCEEDS None . ITEM 3. DEFAULTS UPON SENIOR SECURITIES None. ITEM 4. MINE SAFETY DISCLOSURES Not applicable.