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What changed in Rafael Holdings, Inc.'s 10-K — 2024 vs 2025

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Paragraph-level year-over-year comparison of Rafael Holdings, Inc.'s 2024 and 2025 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 2025 report.

+815 added−780 removedSource: 10-K (2025-10-29) vs 10-K (2024-11-07)

Top changes in Rafael Holdings, Inc.'s 2025 10-K

815 paragraphs added · 780 removed · 538 edited across 8 sections

Item 1. Business

Business — how the company describes what it does

130 edited+129 added−72 removed166 unchanged
Biggest changeFDARA requires that any original NDA or BLA submitted on or after August 18, 2020, for a new active ingredient, must contain studies of molecularly targeted pediatric cancers, unless a deferral or a waiver is granted, if the drug that is the subject of the application is intended for the treatment of an adult cancer and directed at a molecular target that the FDA determines to be substantially relevant to the growth or progression of a pediatric cancer. 14 Orphan drug designation and exclusivity Under the Orphan Drug Act, the FDA may designate a drug product as an “orphan drug” if it is intended to treat a rare disease or condition, generally meaning that it affects fewer than 200,000 individuals in the United States, or more in cases in which there is no reasonable expectation that the cost of developing and making a drug product available in the United States for treatment of the disease or condition will be recovered from sales of the product.
Biggest changeOrphan drug designation and exclusivity Under the Orphan Drug Act, the FDA may designate a drug product as an “orphan drug” if it is intended to treat a rare disease or condition, generally meaning that it affects fewer than 200,000 individuals in the United States, or more in cases in which there is no reasonable expectation that the cost of developing and making a drug product available in the United States for treatment of the disease or condition will be recovered from sales of the product.
Our internal and external investment decisions will be based on the progress and results of our development and pre-clinical activities and other operational developments, and the availability of targets for investment, acquisition or licensing.
Our internal and external investment decisions will be based on the progress and results of our clinical development and pre-clinical activities and other operational developments, and the availability of targets for investment, acquisition or licensing.
Additionally, appropriate packaging must be selected and tested, and stability studies must be conducted to demonstrate that the drug candidate does not undergo unacceptable deterioration in that packaging over its shelf life.
Additionally, appropriate packaging must be selected and tested, and stability studies must be conducted in the selected packaging to demonstrate that the drug candidate does not undergo unacceptable deterioration in that packaging over its shelf life.
These include, among other things: ● establishment registration and device listing with the FDA; ● continued adherence to the QSR requirements; ● marketing, labeling, advertising, and promotion regulations, which require that promotion is truthful, not misleading, fairly balanced and provides adequate directions for use, and that all claims are substantiated and in accordance with the provisions of the approved label, and which also prohibit the promotion of products for unapproved or “off-label” uses and impose other restrictions on labeling, in accordance with FDA guidance on off-label dissemination of information and responding to unsolicited requests for information; ● clearance or approval of product modifications to 510(k)-cleared, De Novo classified or PMA-approved devices that could significantly affect safety or effectiveness or that would constitute a major change in intended use of a cleared device; 17 ● medical device reporting regulations, which require that a manufacturer report to the FDA if a device it markets may have caused or contributed to a death or serious injury, or has malfunctioned and the device or a similar device that it markets would be likely to cause or contribute to a death or serious injury if the malfunction were to occur; ● correction, removal, and recall reporting regulations, which require that manufacturers report to the FDA field corrections and product recalls or removals if undertaken to reduce a risk to health posed by the device or to remedy a violation of the FFDCA that may present a risk to health; ● complying with requirements governing Unique Device Identifiers on devices and also requiring the submission of certain information about each device to the FDA’s Global Unique Device Identification Database; ● the FDA’s recall authority, whereby the agency can order device manufacturers to recall from the market a product that is in violation of governing laws and/or regulations; and ● post-market surveillance activities and regulations, which apply when deemed by the FDA to be necessary to protect the public health or to provide additional safety and effectiveness data for the device.
These include, among other things: ● establishment registration and device listing with the FDA; ● continued adherence to the QSR requirements; ● marketing, labeling, advertising, and promotion regulations, which require that promotion is truthful, not misleading, fairly balanced and provides adequate directions for use, and that all claims are substantiated and in accordance with the provisions of the approved label, and which also prohibit the promotion of products for unapproved or “off-label” uses and impose other restrictions on labeling, in accordance with FDA guidance on off-label dissemination of information and responding to unsolicited requests for information; ● clearance or approval of product modifications to 510(k)-cleared, De Novo classified or PMA-approved devices that could significantly affect safety or effectiveness or that would constitute a major change in intended use of a cleared device; ● medical device reporting regulations, which require that a manufacturer report to the FDA if a device it markets may have caused or contributed to a death or serious injury, or has malfunctioned and the device or a similar device that it markets would be likely to cause or contribute to a death or serious injury if the malfunction were to occur; ● correction, removal, and recall reporting regulations, which require that manufacturers report to the FDA field corrections and product recalls or removals if undertaken to reduce a risk to health posed by the device or to remedy a violation of the FFDCA that may present a risk to health; ● complying with requirements governing Unique Device Identifiers on devices and also requiring the submission of certain information about each device to the FDA’s Global Unique Device Identification Database; ● the FDA’s recall authority, whereby the agency can order device manufacturers to recall from the market a product that is in violation of governing laws and/or regulations; and ● post-market surveillance activities and regulations, which apply when deemed by the FDA to be necessary to protect the public health or to provide additional safety and effectiveness data for the device.
Restrictions under applicable federal and state and analogous foreign healthcare laws and regulations include the following: ● the federal Anti-Kickback Statute, which prohibits, among other things, knowingly and willfully offering, paying, soliciting or receiving remuneration to induce or in return for purchasing, leasing, ordering, or arranging for or recommending the purchase, lease, or order of any item or service reimbursable under Medicare, Medicaid or other federal healthcare programs; ● the federal False Claims Act, which prohibits any person from knowingly presenting, or causing to be presented, a false claim for payment to the federal government or knowingly making, using, or causing to be made or used a false record or statement material to a false or fraudulent claim to the federal government; ● the federal Health Insurance Portability and Accountability Act of 1996, or HIPAA, which created additional federal criminal laws that prohibit, among other things, knowingly and willfully executing, or attempting to execute, a scheme to defraud any healthcare benefit program or making false statements relating to healthcare matters; ● HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act, and their respective implementing regulations, including the Final Omnibus Rule published in January 2013, which impose obligations, including mandatory contractual terms, with respect to safeguarding the privacy, security, and transmission of individually identifiable protected health information, including breach notification regulations; ● new regulations adopted by the Securities and Exchange Commission, or SEC, effective December 18, 2023, that require greater disclosure regarding cybersecurity risk management, strategy and governance, as well as disclosure of material cybersecurity incidents, which may require reporting of a cybersecurity incident before its impact has been fully assessed or the underlying issue has been remediated, which could divert management’s attention from incident response and could potentially reveal system vulnerabilities to threat actors, and for which failure to timely report such incidents under these or other similar rules could also result in monetary fines, sanctions or other forms of liability. ● analogous state data privacy and security laws and regulations that govern the collection, use, disclosure, transfer, storage, disposal, and protection of personal information, such as social security numbers, medical and financial information, and other information, including data breach laws that require timely notification to individuals, and at times regulators, the media or credit reporting agencies, if a company has experienced the unauthorized access or acquisition of personal information, as well as the California Consumer Privacy Act or CCPA, which, among other things, contains new disclosure obligations for businesses that collect personal information about California residents and affords those individuals numerous rights relating to their personal information that may affect companies’ ability to use personal information or share it with business partners, and the California Privacy Rights Act, or CPRA, which expands the scope of the CCPA, imposes new restrictions on behavioral advertising, and establishes a new California Privacy Protection Agency that will enforce the law and issue regulations, and became “operative” on January 1, 2023, with a 12-month “lookback provision” applicable to personal data collected on or after January 1, 2022, and the various state laws and regulations may be more restrictive and not preempted by United States federal laws; ● analogous foreign data protection laws, including among others the EU General Data Protection Regulation, or the GDPR, and EU member states’ implementing legislation, which imposes data protection requirements that include strict obligations and restrictions on the ability to collect, analyze, and transfer EU personal data, a requirement for prompt notice of data breaches to data subjects and supervisory authorities in certain circumstances, and possible substantial fines for any violations (including possible fines for certain violations of up to the greater of 20 million Euros or 4% of total worldwide annual turnover of the preceding financial year), with legal requirements in foreign countries relating to the collection, storage, processing, and transfer of personal data continuing to evolve and varying widely across jurisdictions; ● the United States civil monetary penalties statute, which imposes penalties against any person who is determined to have presented or caused to be presented a claim to a federal health program that the person knows or should know is for an item or service that was not provided as claimed or is false or fraudulent; ● the federal Physician Payments Sunshine Act, which requires certain manufacturers of drugs, devices, biologics, and medical supplies to report annually to the Centers for Medicare & Medicaid Services information related to payments and other transfers of value made by that entity to physicians and teaching hospitals, as well as ownership and investment interests held by physicians and their immediate family members; 21 ● analogous state and foreign laws and regulations, such as state anti-kickback and false claims laws, which may apply to healthcare items or services that are reimbursed by non-governmental third-party payors, including private insurers; and ● state laws requiring pharmaceutical companies to comply with the pharmaceutical industry’s voluntary compliance guidelines and the relevant compliance guidance promulgated by the federal government.
Restrictions under applicable federal and state and analogous foreign healthcare laws and regulations include the following: ● the federal Anti-Kickback Statute, which prohibits, among other things, knowingly and willfully offering, paying, soliciting or receiving remuneration to induce or in return for purchasing, leasing, ordering, or arranging for or recommending the purchase, lease, or order of any item or service reimbursable under Medicare, Medicaid or other federal healthcare programs; ● the federal False Claims Act, which prohibits any person from knowingly presenting, or causing to be presented, a false claim for payment to the federal government or knowingly making, using, or causing to be made or used a false record or statement material to a false or fraudulent claim to the federal government; 24 ● the federal Health Insurance Portability and Accountability Act of 1996, or HIPAA, which created additional federal criminal laws that prohibit, among other things, knowingly and willfully executing, or attempting to execute, a scheme to defraud any healthcare benefit program or making false statements relating to healthcare matters; ● HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act, and their respective implementing regulations, including the Final Omnibus Rule published in January 2013, which impose obligations, including mandatory contractual terms, with respect to safeguarding the privacy, security, and transmission of individually identifiable protected health information, including breach notification regulations; ● new regulations adopted by the Securities and Exchange Commission, or SEC, effective December 18, 2023, that require greater disclosure regarding cybersecurity risk management, strategy and governance, as well as disclosure of material cybersecurity incidents, which may require reporting of a cybersecurity incident before its impact has been fully assessed or the underlying issue has been remediated, which could divert management's attention from incident response and could potentially reveal system vulnerabilities to threat actors, and for which failure to timely report such incidents under these or other similar rules could also result in monetary fines, sanctions or other forms of liability; ● analogous state data privacy and security laws and regulations that govern the collection, use, disclosure, transfer, storage, disposal, and protection of personal information, such as social security numbers, medical and financial information, and other information, including data breach laws that require timely notification to individuals, and at times regulators, the media or credit reporting agencies, if a company has experienced the unauthorized access or acquisition of personal information, as well as the California Consumer Privacy Act or CCPA, which, among other things, contains new disclosure obligations for businesses that collect personal information about California residents and affords those individuals numerous rights relating to their personal information that may affect companies’ ability to use personal information or share it with business partners, and the California Privacy Rights Act, or CPRA, which expands the scope of the CCPA, imposes new restrictions on behavioral advertising, and establishes a new California Privacy Protection Agency that will enforce the law and issue regulations, and became “operative” on January 1, 2023, with a 12-month “lookback provision” applicable to personal data collected on or after January 1, 2022, and the various state laws and regulations may be more restrictive than and not preempted by United States federal laws; ● analogous foreign data protection laws, including among others the EU General Data Protection Regulation, or the GDPR, and EU member states’ implementing legislation, which imposes data protection requirements that include strict obligations and restrictions on the ability to collect, analyze, and transfer EU personal data, a requirement for prompt notice of data breaches to data subjects and supervisory authorities in certain circumstances, and possible substantial fines for any violations (including possible fines for certain violations of up to the greater of 20 million Euros or 4% of total worldwide annual turnover of the preceding financial year), with legal requirements in foreign countries relating to the collection, storage, processing, and transfer of personal data continuing to evolve and varying widely across jurisdictions; ● the United States civil monetary penalties statute, which imposes penalties against any person who is determined to have presented or caused to be presented a claim to a federal health program that the person knows or should know is for an item or service that was not provided as claimed or is false or fraudulent; ● the federal Physician Payments Sunshine Act, which requires certain manufacturers of drugs, devices, biologics, and medical supplies to report annually to the Centers for Medicare & Medicaid Services information related to payments and other transfers of value made by that entity to physicians and teaching hospitals, as well as ownership and investment interests held by physicians and their immediate family members; ● analogous state and foreign laws and regulations, such as state anti-kickback and false claims laws, which may apply to healthcare items or services that are reimbursed by non-governmental third-party payors, including private insurers; and ● state laws requiring pharmaceutical companies and medical device companies to comply with the pharmaceutical industry's or the medical device industry’s voluntary compliance guidelines and the relevant compliance guidance promulgated by the federal government.
The drug candidate is initially introduced into a small number of healthy human subjects or, in certain indications such as cancer, patients with the target disease or condition (e.g., cancer) and tested for safety, dosage tolerance, absorption, metabolism, distribution, excretion and, if possible, to gain an early indication of its effectiveness and to determine optimal dosage. Phase 2.
The drug candidate is initially introduced into a small number of healthy human subjects or, in certain indications such as cancer, patients with the target disease or condition (e.g., cancer) and tested for safety, dosage tolerance, absorption, metabolism, distribution, excretion and, if possible, to gain an early indication of its potential effectiveness and to determine optimal dosage. Phase 2.
Certain countries also mandate implementation of commercial compliance programs. The aforementioned EU requirements are generally applicable in the European Economic Area, or EEA, which consists of the 27 EU member states plus Norway, Liechtenstein, and Iceland. Many other countries have specific requirements for classification, registration, and post-marketing surveillance that are independent of the countries discussed above.
Certain countries also mandate implementation of commercial compliance programs. The aforementioned EU requirements are generally applicable in the European Economic Area, or EEA, which consists of the 27 EU member states plus Norway, Liechtenstein, and Iceland. 23 Many other countries have specific requirements for classification, registration, and post-marketing surveillance that are independent of the countries discussed above.
The time required to obtain approval or certification by a foreign country may be longer or shorter than that required for FDA approval or clearance, and the requirements may differ significantly. The EU has adopted specific directives and regulations regulating the design, manufacture, clinical investigation, conformity assessment, labeling, and adverse event reporting for medical devices.
The time required to obtain approval or certification by a foreign country may be longer or shorter than that required for FDA approval or clearance, and the requirements may differ significantly. 21 The EU has adopted specific directives and regulations regulating the design, manufacture, clinical investigation, conformity assessment, labeling, and adverse event reporting for medical devices.
The European Commission recently extended the implementation period to the end of 2027 for high-risk devices and to the end of 2028 for medium- and low-risk devices. 18 The MDR establishes a uniform, transparent, predictable, and sustainable regulatory framework across the EU for medical devices and ensures a high level of safety and health while supporting innovation.
The European Commission recently extended the implementation period to the end of 2027 for high-risk devices and to the end of 2028 for medium- and low-risk devices. The MDR establishes a uniform, transparent, predictable, and sustainable regulatory framework across the EU for medical devices and ensures a high level of safety and health while supporting innovation.
Our global operations are also subject to foreign anti-corruption laws, such as the United Kingdom Bribery Act, among others. As part of our global compliance program, we seek to address anti-corruption risks proactively. COMPETITION We and the Portfolio Companies operate in highly competitive segments.
Our global operations are also subject to foreign anti-corruption laws, such as the United Kingdom Bribery Act, among others. As part of our global compliance program, we seek to address anti-corruption risks proactively. 25 COMPETITION We and the Portfolio Companies operate in highly competitive segments.
The drug candidate is administered to a limited number of patients in the target patient population to identify possible adverse effects and safety risks, to preliminarily evaluate the efficacy of the product for a specific targeted disease, and to determine dosage tolerance and optimal dosage. Phase 3 .
The drug candidate is administered to a limited number of patients in the target patient population to identify possible adverse effects and safety risks, to preliminarily evaluate the potential efficacy of the product for a specific targeted disease, and to determine dosage tolerance and optimal dosage. Phase 3 .
Such studies must be conducted in accordance with GCP, including review and approval by an independent ethics committee, or IEC, and informed consent from subjects. The GCP requirements encompass both ethical and data integrity standards for clinical studies.
Such studies must be conducted in accordance with GCP, including review and approval by an independent ethics committee, or IEC, and include informed consent from subjects. The GCP requirements encompass both ethical and data integrity standards for clinical studies.
Real Estate Our current commercial real estate holdings consist of a portion of a building in Israel. Prior to its sale in August 2022, we also owned the 520 Property. On August 22, 2022, the Company completed the sale of the 520 Property for a purchase price of $49.4 million.
Real Estate Our current commercial real estate holdings consist of a portion of a building in Israel. Prior to its sale in August 2022, we also owned the 520 Property. On August 22, 2022, we completed the sale of the 520 Property for a purchase price of $49.4 million.
As of September 16, 2023, Rafael Medical Devices had filed the following patent application related to its devices with the USPTO and PCT: Patent application entitled, Compression Anchor Systems, Devices, Instruments, Implants and Methods of Assembly and Use; and patent application entitled Videoscopic Arthroscopic Instruments, Devices, and Systems and Methods of Use and Assembly.
As of September 16, 2023, Rafael Medical Devices had filed the following patent applications related to its devices with the USPTO and PCT: patent application entitled, Compression Anchor Systems, Devices, Instruments, Implants and Methods of Assembly and Use; and patent application entitled Videoscopic Arthroscopic Instruments, Devices, and Systems and Methods of Use and Assembly.
A predicate device is a legally marketed device that is not subject to premarket approval, i.e. , a device that was legally marketed prior to May 28, 1976 (pre-amendments device) and for which a PMA is not required, a device that has been reclassified from Class III to Class II or I, or a device that was found substantially equivalent through the 510(k) process.
A predicate device is a legally marketed device that is not subject to premarket approval, i.e. , a device that was legally marketed prior to May 28, 1976 (pre-amendment device) and for which a PMA is not required, a device that has been reclassified from Class III to Class II or I, or a device that was found substantially equivalent through the 510(k) process.
We plan to continue to selectively invest in pre-clinical and clinical stage healthcare opportunities, including those in which we already own interests, when determined to be consistent with our goals, and move toward clinical stage programs as research and development results warrant, while being ready to exploit other opportunities that may arise.
We may selectively invest in pre-clinical and clinical stage healthcare opportunities, including those in which we already own interests, when determined to be consistent with our goals, and move toward clinical stage programs as research and development results warrant, while being ready to exploit other opportunities that may arise.
We make available free of charge our Annual Report on Form 10-K, quarterly reports on Form 10-Q, current reports on Form 8-K and all amendments to these reports, and all beneficial ownership reports on Forms 3, 4 and 5 filed by directors, officers and beneficial owners of more than 10% of our equity through the investor relations page of our web site (https://rafaeholdings.irpass.com) as soon as reasonably practicable after such material is electronically filed with the Securities and Exchange Commission.
We make available free of charge our Annual Report on Form 10-K, quarterly reports on Form 10-Q, current reports on Form 8-K and all amendments to these reports, and all beneficial ownership reports on Forms 3, 4 and 5 filed by directors, officers and beneficial owners of more than 10% of our equity through the investor relations page of our website (https://rafaeholdings.irpass.com) as soon as reasonably practicable after such material is electronically filed with the Securities and Exchange Commission.
Toxicokinetic (TK) exposures of Cmax (peak concentration) and area under the curve (AUC) of CPI-613® (devimistat) from GLP Tox studies in rats and minipigs have shown safety margins expected to cover PK exposures of Cmax and AUC of CPI-613® (devimistat) in pancreatic cancer patients at doses studied.
Toxicokinetic (TK) exposures of Cmax (peak concentration) and area under the curve (AUC) of CPI-613® (devimistat) from GLP Tox studies in rats and minipigs have suggested safety margins expected to cover PK exposures of Cmax and AUC of CPI-613® (devimistat) in pancreatic cancer patients at doses studied.
An applicant seeking approval to market and distribute a new drug product in the United States must typically undertake the following: ● completion of preclinical laboratory tests, animal studies and formulation studies in compliance with the FDA’s good laboratory practice, or GLP, regulations; ● submission to the FDA of an Investigational New Drug, or IND, application, which must take effect before human clinical trials may begin; ● approval by an independent institutional review board, or IRB, representing each clinical site before each clinical trial may be initiated at each site; ● performance of adequate and well-controlled human clinical trials in accordance with good clinical practices, or GCP, to establish the safety and efficacy of the proposed drug product for each indication; ● submission of pediatric study plans and generation of data, unless inapplicable or otherwise deferred or waived, that are adequate to assess the safety and effectiveness of the drug candidate for the proposed indication(s) in all relevant pediatric subpopulations, and to support dosing and administration for each pediatric subpopulation for which the product is determined to be safe and effective; ● preparation and submission to the FDA of an NDA requesting marketing for one or more proposed indications; ● review by an FDA advisory committee, where appropriate if applicable; ● satisfactory completion of one or more FDA inspections of the manufacturing facility or facilities at which the product, or components thereof, are produced and packaged to assess compliance with current Good Manufacturing Practices, or cGMP, requirements and to assure that the facilities, methods and controls are adequate to preserve the product’s identity, strength, quality and purity; ● satisfactory completion of FDA audits of clinical trial sites to assure compliance with GCP and the integrity of the clinical data; ● payment of user fees and securing FDA approval of the NDA; and ● compliance with any post-approval requirements, including the potential requirement to implement a Risk Evaluation and Mitigation Strategy, or REMS, and the potential requirement to conduct post-approval studies.
An applicant seeking approval to market and distribute a new drug product in the United States must typically undertake the following: ● completion of preclinical laboratory tests, animal studies and formulation studies in compliance with the FDA’s good laboratory practice, or GLP, regulations; ● submission to the FDA of an Investigational New Drug, or IND, application, which must take effect before human clinical trials may begin; ● approval by an independent institutional review board, or IRB, representing each clinical site before each clinical trial may be initiated at each site; ● performance of adequate and well-controlled human clinical trials in accordance with good clinical practices, or GCP, requirements to establish the safety and efficacy of the proposed drug product for each proposed indication; ● submission of pediatric study plans and generation of data, unless inapplicable or otherwise deferred or waived, that are adequate to assess the safety and effectiveness of the drug candidate for the proposed indication(s) in all relevant pediatric subpopulations, and to support dosing and administration for each pediatric subpopulation for which the product is determined to be safe and effective; ● preparation and submission to the FDA of an NDA requesting marketing for one or more proposed indications; ● review by an FDA advisory committee, where appropriate if applicable; ● satisfactory completion of one or more FDA inspections of the manufacturing facility or facilities at which the product, or components thereof, are produced and packaged to assess compliance with current Good Manufacturing Practices, or cGMP, requirements and to assure that the facilities, methods and controls are adequate to preserve the product’s identity, strength, quality and purity; ● satisfactory completion of FDA audits of clinical trial sites to assure compliance with GCP and the integrity of the clinical data; ● payment of user fees and securing FDA approval of the NDA; and ● compliance with any post-approval requirements, including the potential requirement to implement a Risk Evaluation and Mitigation Strategy, or REMS, and the potential requirement to conduct post-approval studies. 12 Before an applicant begins testing a compound with potential therapeutic value in humans, the drug candidate enters the preclinical testing stage.
The investigational drug is administered to an expanded number of patients in the target patient population, generally at geographically dispersed clinical trial sites, in well-controlled clinical trials to generate enough data to statistically evaluate the efficacy and safety of the product for approval, to establish the overall risk-benefit profile of the product, and to provide adequate information for the labeling of the product.
The investigational drug is administered to an expanded number of patients in the target patient population, generally at geographically dispersed clinical trial sites, in well-controlled clinical trials to generate enough data to statistically evaluate the efficacy and safety of the product for approval, to establish the overall risk-benefit profile of the product, and to provide adequate information for the labeling of the product. 13 Phase 4 .
QSR compliance is necessary to receive and maintain FDA clearance or approval to market new and existing medical devices, and it is also necessary for distributing in the United States certain devices exempt from FDA clearance and approval requirements.
QSR compliance is necessary to receive and maintain FDA clearance, approval, or marketing authorization to market new and existing medical devices, and it is also necessary for distributing in the United States certain devices exempt from FDA clearance and approval requirements.
Patients harboring germline mutations in the BRCA1 and/or BRCA2 genes have significantly increased life-time risk of developing breast, ovarian cancer, pancreatic, and prostate cancer. Tumors with BRCA mutations are susceptible to platinum-based chemotherapy and hypersensitive to agents that inhibit poly(ADP-ribose) polymerase (PARP).
Patients harboring germline mutations in the BRCA1 and/or BRCA2 genes have significantly increased lifetime risk of developing breast, ovarian, pancreatic, and prostate cancer. Tumors with BRCA mutations are susceptible to platinum-based chemotherapy and hypersensitive to agents that inhibit poly(ADP-ribose) polymerase (PARP).
The 520 Property serves as the headquarters of the Company and affiliated entities, IDT Corporation (“IDT”), and Genie Energy, Ltd. (“Genie”), who occupy the second through fourth floors. Our holding in Israel is a condominium portion of an office building built in 2004 located in the Har Hotzvim section of Jerusalem, Israel.
The 520 Property serves as the headquarters of the Company and affiliated entities, IDT Corporation ("IDT"), and Genie Energy, Ltd. (“Genie”), who occupy the third through fourth floors. Our holding in Israel is a condominium portion of an office building built in 2004 located in the Har Hotzvim section of Jerusalem, Israel.
Cornerstone received negative results of its Avenger 500 Phase 3 study for Devimistat in pancreatic cancer as well as a recommendation to stop its ARMADA 2000 Phase 3 study due to a determination that the trial would unlikely achieve its primary endpoint (the “Data Events”).
In October 2021, Cornerstone received negative results of its Avenger 500 Phase 3 study for Devimistat in pancreatic cancer as well as a recommendation to stop its ARMADA 2000 Phase 3 study due to a determination that the trial would be unlikely to achieve its primary endpoint (the “Data Events”).
Our goal within biopharma is to expand our portfolio and develop and bring to market therapeutics which address high unmet medical needs, opportunistic investments, acquisitions and in-licensing of assets.
Our goal within biopharma is to develop and bring to market therapeutics which address high unmet medical needs, opportunistic investments, acquisitions and in-licensing of assets.
Phase 4 . Post-approval studies may be required to be conducted, or a sponsor may decide on its own to conduct them, in order to collect additional data after initial regulatory approval. These studies are used to gain additional experience and additional safety and/or efficacy data from the treatment of patients in the intended therapeutic indication.
Post-approval studies may be required to be conducted, or a sponsor may decide on its own to conduct them, in order to collect additional data after initial regulatory approval. These studies are used to gain additional experience and additional safety and/or efficacy data from the treatment of patients in the approved therapeutic indication.
Depreciation expense for the year ended July 31, 2024 includes depreciation of acquired assets from the Day Three Acquisition and Cornerstone Acquisition. COMPETITION With respect to our real estate business, we compete for commercial (office and retail) tenants in Jerusalem, Israel. The commercial real estate market is highly competitive.
Depreciation expense for the year ended July 31, 2025 includes depreciation of acquired assets from the Day Three Acquisition, Cornerstone Acquisition and Cyclo Merger. COMPETITION With respect to our real estate business, we compete for commercial (office and retail) tenants in Jerusalem, Israel. The commercial real estate market is highly competitive.
Promitil® was stable in plasma with a half-life of approximately 20 hours (vs 40-50 minutes for naked MMC). Next Steps for Clinical Development: Homologous recombination (HR) is an evolutionarily conserved process for repairing DNA double-strand breaks with high fidelity, and the BRCA1 and BRCA2 proteins play essential roles in this process.
Promitil® was stable in plasma with a half-life of approximately 20 hours (vs 40-50 minutes for naked MMC). Next Steps: Homologous recombination (HR) is an evolutionarily conserved process for repairing DNA double-strand breaks with high fidelity, and the BRCA1 and BRCA2 proteins are considered to play essential roles in this process.
Promitil® was given by intravenous infusion once every 3 or 4 weeks and appears to be well-tolerated at a dose up to 2 mg/kg. Except for mild myelosuppression, no other toxicities such as skin irritation, mouth ulcers, neuropathic pain, diarrhea, or hair loss were reported.
Promitil® was given by intravenous infusion once every 3 or 4 weeks and appeared to be well-tolerated at a dose up to 2 mg/kg. Except for mild myelosuppression, no other toxicities such as skin irritation, mouth ulcers, neuropathic pain, diarrhea, or hair loss were reported in these studies.
The obligations for registration in EUDAMED and other mandatory uses of the system will start six months after the entire EUDAMED system (including all six modules) has been declared fully functional following an independent audit and an EU Commission notice to be published in the Official Journal and in accordance with the transitional provisions set out in the MDR.
The obligations for registration in EUDAMED and other mandatory uses of the system had originally been planned to start six months after the entire EUDAMED system (including all six modules) had been declared fully functional following an independent audit and an EU Commission notice to be published in the Official Journal and in accordance with the transitional provisions set out in the MDR.
This proprietary molecule, known as Promitil – Pegylated Liposomal Mitomycin-C Lipidic Prodrug (PL-MLP) – is designed to overcome the toxicity associated with the clinical use of mitomycin-C and turns it into a targeted, anticancer therapeutic that could potentially become the treatment of choice in a variety of cancers with high unmet need.
This proprietary molecule, known as Promitil – pegylated liposomal mitomycin-C lipidic prodrug (PL-MLP) – is designed with the goal of overcoming the toxicity associated with the clinical use of mitomycin-C and turns it into a targeted, anticancer therapeutic that could potentially become a treatment in a variety of cancers with high unmet need.
Our web site also contains information not incorporated into this Annual Report on Form 10-K or our other filings with the Securities and Exchange Commission.
Our website also contains information not incorporated into this Annual Report on Form 10-K or our other filings with the Securities and Exchange Commission.
LipoMedix LipoMedix is a clinical stage Israeli company focused on the development of a product candidate that holds the potential to be an innovative, safe, and effective cancer therapy based on liposome delivery. As of July 31, 2024, the Company’s ownership interest in LipoMedix was approximately 95%.
LipoMedix is a clinical stage company based in Israel that is focused on the development of a product candidate that holds the potential to be an innovative, safe, and effective cancer therapy based on liposome delivery. As of July 31, 2025, our ownership interest in LipoMedix was approximately 95%.
The company owns all manufacturing and commercial rights to the product and manufactures using a validated, commercial-scale process using a team of contract manufacturing service providers. LipoMedix’s Promitil ® and other pipeline candidates are based on an active pharmaceutical ingredient (API) referred to as MLP (abbreviation of mitomycin-C lipid-based prodrug) that is formulated into customized nanoparticles.
We own all manufacturing and commercial rights to the product and have manufactured using a validated, commercial-scale process using a team of contract manufacturing service providers. 27 LipoMedix’s Promitil ® and other pipeline candidates are based on an active pharmaceutical ingredient (API) referred to as MLP (abbreviation of mitomycin-C lipid-based prodrug) that is formulated into customized nanoparticles.
In 2019, the Company established Barer, a preclinical cancer metabolism research operation, to focus on developing a pipeline of novel therapeutic compounds, including compounds designed to regulate cancer metabolism with potentially broader application in other indications beyond cancer. Barer has been comprised of scientists and academic advisors that are experts in cancer metabolism, chemistry, and drug development.
In 2019, we established Barer, originally as a preclinical cancer metabolism research operation, to focus on developing a pipeline of novel therapeutic compounds, including compounds designed to regulate cancer metabolism with potentially broader application in other indications beyond cancer. Barer was comprised of scientists and academic advisors that are experts in cancer metabolism, chemistry, and drug development.
Cornerstone also has obtained U.S. orphan drug designation for CPI-613® (devimistat) in the treatment of pancreatic cancer, AML, MDS, Burkitt’s Lymphoma, Peripheral T-cell Lymphoma (PTCL), soft tissue sarcoma, and biliary cancer. Cornerstone maintains U.S. and international trademarks covering its lead development compounds (CPI-613® (devimistat) and Telaglenastat (CB-839)).
Cornerstone also has obtained U.S. orphan drug designation (ODD) for CPI-613® (devimistat) in the treatment of Pancreatic cancer, AML, MDS, Burkitt’s Lymphoma, Peripheral T-cell Lymphoma (PTCL), Soft tissue sarcoma, and Biliary cancer, and EMA ODD for Pancreatic cancer, AML, Burkitt’s Lymphoma, and Biliary cancer. Cornerstone maintains US. and international trademarks covering its lead development compound (CPI-613® (devimistat)).
Cornerstone maintains an exclusive license agreement with the Research Foundation of the State University of New York at Stony Brook, or RF, granting Cornerstone the exclusive right to make, use and sell products covered under specified technology relating to lipoic acid derivatives with the right to grant sublicenses. This license agreement was amended in 2004, 2007 and 2017.
Cornerstone maintains (i) an exclusive license agreement with the Research Foundation of the State University of New York at Stony Brook, or RF, granting Cornerstone the exclusive right to make, use and sell products covered under specified technology relating to lipoic acid derivatives with the right to grant sublicenses.
These suggest that CPI-613® holds the potential to have anti-cancer activity. Combining CPI-613® with generalized metabolic stressors like chemotherapy holds the potential to result in the effective killing of even the most intractable tumors like pancreatic cancer. These effects were observed in Cornerstone’s Phase 1/2 trials to date (Alistar, et al., 2017; Pardee et al., 2018).
These data suggest that CPI-613® may hold the potential to have anti-cancer activity. Combining CPI-613® with generalized metabolic stressors like chemotherapy could hold the potential to result in the effective killing of even the most intractable tumors like pancreatic cancer. These effects were observed in Cornerstone's Phase I/II trials to date (Alistar, et al., 2017; Pardee et al., 2018).
Additional patent applications may be filed as studies continue. Patents that LipoMedix has obtained and patents that may issue in the future based on LipoMedix’s currently pending patent applications for its platform technologies are scheduled to expire in years 2032 through 2040. These dates do not include potential patent term extensions.
Additional patent applications may be filed as studies continue. Patents that LipoMedix has obtained and patents that may issue in the future based on LipoMedix’s currently pending patent applications for its platform technologies are scheduled to expire in years 2032 through 2040.
RP Finance is an entity associated with members of the family of Howard Jonas (Executive Chairman, Chairman of the Board, and controlling stockholder of the Company) which holds 37.5% equity interest of RP Finance. RP Finance holds debt and equity investments in Cornerstone.
RP Finance is an entity in which vehicles associated with members of the family of Howard S. Jonas (Executive Chairman, Chief Executive Officer, President, Chairman of the Board, and controlling stockholder of the Company), hold an aggregate 37.5% equity interest. RP Finance holds debt and equity investments in Cornerstone.
The Pharmaceutical Companies currently rely, and expect to continue to rely, on third parties for the manufacture of their product candidates for preclinical and clinical testing, as well as for commercial manufacture of any products that they may commercialize.
The Pharmaceutical Companies currently rely, and we expect us and them to continue to rely, on third parties for the manufacture of their product candidates for preclinical and clinical testing, as well as for commercial manufacture of any products that they may commercialize should they receive regulatory approval.
Rafael Medical Devices has assembled an in-house team with expertise in engineering, device development quality control, and design discovery who have been part of teams that have created successful commercial medical devices in the past. It has begun to expand its expert network of experienced device creators, key opinion leaders, and is working to begin generating a commercial presence.
Rafael Medical Devices has assembled an in-house team with expertise in engineering, device development quality control, and design who have been part of teams that have created successful commercial medical devices in the past. It has begun to expand its expert network of experienced device creators, key opinion leaders. Orthopedics comprise a large addressable market.
Manufacturers are required to take FSCAs, which are defined as any corrective action for technical or medical reasons to prevent or reduce a risk of a serious incident associated with the use of a medical device that is made available on the market.
Manufacturers are required to take FSCAs, which are defined as any corrective action for technical or medical reasons to prevent or reduce a risk of a serious incident associated with the use of a medical device that is made available on the market. An FSCA may include the recall, modification, exchange, destruction or retrofitting of the device.
Four patent applications covering the use of Promitil®, in combination with other chemotherapies and with radiotherapy, targeting of Promitil ® with a folate ligand, and a reformulation of Promitil ® with co-encapsulated mitomycin prodrug and doxorubicin have been approved by the USPTO or EPO in 2018-2020.
These dates do not include potential patent term extensions. 26 Four patent applications covering the use of Promitil®, in combination with other chemotherapies and with radiotherapy, targeting of Promitil ® with a folate ligand, and a reformulation of Promitil ® with co-encapsulated mitomycin prodrug and doxorubicin have been approved by the USPTO or EPO in 2018-2020.
Initial patient enrollment in the U.S. Phase I study commenced in September 2017, and in May 2020 Cyclo announced Top Line data demonstrating Trappsol® Cyclo™ was well tolerated in this study. Cyclo is currently conducting a Phase III Clinical Trial Evaluating Trappsol ® Cyclo™ in Pediatric and Adult Patients with Niemann-Pick Disease, Type C1.
Phase I study commenced in September 2017 and in May 2020, Cyclo announced Top Line data indicating Trappsol® Cyclo™ was well tolerated in this study. Cyclo is currently conducting a Phase 3 Clinical Trial evaluating Trappsol ® Cyclo™ in Pediatric and Adult Patients with Niemann-Pick Disease, Type C1.
In April 2023, the Company first invested in Day Three, a company which empowers third-party manufacturers to reimagine their existing cannabis offerings enabling them to bring to market better, cleaner, more precise and predictable versions by utilizing Day Three’s pharmaceutical-grade technology and innovation like Unlokt™.
In April 2023, we first invested in Day Three, a company which empowers third-party manufacturers to reimagine their existing product offerings enabling those third-party manufacturers to bring to market better, cleaner, more precise and predictable versions of their products by utilizing Day Three’s technology and innovation like Unlokt™.
Rafael possesses a 2/3 ownership interest in Altira. 22 Patents The designation of Trappsol ® Cyclo™ as an orphan drug for the treatment of NPC1 by the FDA and European regulators would provide Cyclo with seven years, and 10 to 12 years, of market exclusivity, respectively, if it were to receive regulatory approval for its designated orphan indication.
Patents The designation of Trappsol ® Cyclo™ as an orphan drug for the treatment of NPC1 by the FDA and European regulators would provide Cyclo with seven years in the US, and 10 to 12 years in the EU, of market exclusivity, respectively, if it were to receive regulatory approval for its designated orphan indication.
As of July 31, 2024, the space is fully leased to two tenants; one of which is an IDT subsidiary. 24 Depreciation expense of property, plant and equipment was $ 137 thousand and $78 thousand as of July 31, 2024 and 2023 , respectively.
As of July 31, 2025, the space is fully leased to two tenants; one of which is an IDT subsidiary. Depreciation expense of property, plant and equipment was $146 thousand and $137 thousand for the years ended July 31, 2025 and 2024, respectively.
The failure to comply with requirements under the FFDCA and other applicable laws at any time during the product development process, approval process or after approval may subject an applicant and/or sponsor to a variety of administrative or judicial sanctions, including refusal by the FDA to approve pending applications, withdrawal of an approval, imposition of a clinical hold, issuance of warning letters and other types of compliance letters, product recalls, product seizures, total or partial suspension of production or distribution, injunctions, fines, refusals of government contracts, restitution, disgorgement of profits, or civil or criminal investigations and penalties brought by the FDA and the Department of Justice or other governmental entities. 9 Each of Cyclo Therapeutics’, LipoMedix’s, Barer’s, and Cornerstone’s (collectively referred to as the “Pharmaceutical Companies”) current product candidates must be approved by the FDA through a New Drug Application, or NDA.
The failure to comply with requirements under the FFDCA and other applicable laws at any time during the product development process, approval process or after approval may subject an applicant and/or sponsor to a variety of administrative or judicial sanctions, including refusal by the FDA to approve pending applications, withdrawal of an approval, imposition of a clinical hold, issuance of warning letters and other types of compliance letters, product recalls, product seizures, total or partial suspension of production or distribution, injunctions, fines, refusals of government contracts, restitution, disgorgement of profits, or civil or criminal investigations and penalties brought by the FDA and the Department of Justice or other governmental entities.
If the FDA disagrees with a manufacturer’s determination not to seek a new 510(k) or other form of marketing authorization for a modification to a 510(k)-cleared product, the FDA can require the manufacturer to cease marketing and/or request the recall of the modified device until 510(k) clearance or PMA approval is obtained or a De Novo classification is granted.
If the FDA disagrees with a manufacturer’s determination not to seek a new 510(k) or other form of marketing authorization for a modification to a 510(k)-cleared product, the FDA can require the manufacturer to cease marketing and/or request the recall of the modified device until 510(k) clearance or PMA approval is obtained or a De Novo classification is granted. 19 The PMA process is more demanding than either the 510(k) premarket notification process or the De Novo classification process and includes stringent clinical investigation and other requirements.
Post-Approval Requirements Any drug that receives FDA approval is subject to continuing regulation by the FDA, including, among other things, requirements relating to recordkeeping, continued adherence to cGMP, periodic reporting, product sampling and distribution, advertising and promotion, and reporting of adverse experiences with the product.
If post-marketing clinical studies fail to verify the anticipated clinical benefit, FDA may withdraw approval. 15 Post-Approval Requirements Any drug that receives FDA approval is subject to continuing regulation by the FDA, including, among other things, requirements relating to recordkeeping, continued adherence to cGMP, periodic reporting, product sampling and distribution, advertising and promotion, and reporting of adverse experiences with the product.
It is believed to be selectively taken up by cancer cells. As a result, CPI-613® (devimistat) holds the potential to be minimally toxic to healthy cells (i.e., safe, and well tolerated), potentially allowing extended treatment courses. Moreover, its toxicity profile may allow CPI-613® (devimistat) to be used in combination with other drugs and in older patients.
As a result, CPI-613® (devimistat) could hold the potential to be minimally toxic to healthy cells (i.e., potentially safe and well tolerated), potentially allowing extended treatment courses. Moreover, its emerging toxicity profile may allow CPI-613® (devimistat) to be used in combination with other drugs and in older patients.
For example, products with orphan drug designation are not subject to user fees. 11 The FDA initially reviews all NDAs and BLAs submitted to identify if there are any deficiencies before it can officially accept the applications for in-depth review, also known as “filing” of the NDA or BLA.
The FDA initially reviews all NDAs and BLAs submitted to identify if there are any deficiencies before it can officially accept the applications for in-depth review, also known as “filing” of the NDA or BLA.
An FSCA may include the recall, modification, exchange, destruction or retrofitting of the device. 19 The advertising and promotion of medical devices in the EU is subject to some general principles set forth in EU legislation. Under the MDR, only devices that are CE marked may be marketed and advertised in the EU in accordance with their intended purpose.
The advertising and promotion of medical devices in the EU is subject to some general principles set forth in EU legislation. Under the MDR, only devices that are CE marked may be marketed and advertised in the EU in accordance with their intended purpose.
Receipt of such a designation does not necessarily mean that a product candidate will receive an expedited approval. 12 Accelerated approval pathway The FDA may grant accelerated approval to a product for a serious or life-threatening condition that provides meaningful therapeutic advantage to patients over existing treatments based upon a determination that the product has an effect on a surrogate endpoint that is reasonably likely to predict clinical benefit.
Accelerated approval pathway The FDA may grant accelerated approval to a product for a serious or life-threatening condition that provides meaningful therapeutic advantage to patients over existing treatments based upon a determination that the product has an effect on a surrogate endpoint that is reasonably likely to predict clinical benefit.
The FDA’s regulations are intended to help ensure the protection of human subjects enrolled in non-IND foreign clinical studies, as well as the quality and integrity of the resulting data.
The FDA’s regulations are intended to help ensure the protection of human subjects enrolled in non-IND foreign clinical studies, as well as the quality and integrity of the resulting data. They further help ensure that non-IND foreign studies are conducted in a manner comparable to that required for IND studies.
In the U.S., our product candidates and device candidates are regulated as either drugs or biological products under the Federal Food, Drug and Cosmetic Act, or FFDCA, and the Public Health Service Act, or PHSA, and their implementing regulations, or as medical devices under the FFDCA and its implementing regulations, each as amended and enforced by the FDA.
There is a global trend toward increased regulatory and enforcement activity related to all medical products. 11 In the U.S., our product candidates and device candidates are regulated as either drugs or biological products under the Federal Food, Drug and Cosmetic Act, or FFDCA, and the Public Health Service Act, or PHSA, and their implementing regulations, or as medical devices under the FFDCA and its implementing regulations, each as amended and enforced by the FDA.
Rafael Medical Devices Rafael Medical Devices is a medical device company currently concentrating on developing surgical and procedural devices designed to provide meaningful advantages to patients and healthcare providers in the orthopedic market. One of its current lead products is an orthopedic arthroscopy instrument for carpal tunnel syndrome.
Synhale plans to develop the drug candidate for patients with pulmonary hypertension. Rafael Medical Devices Rafael Medical Devices is a medical device company currently concentrating on developing surgical and procedural devices designed to provide meaningful advantages to patients and healthcare providers in the orthopedic market. Its current lead product is an orthopedic arthroscopy instrument for carpal and cubital tunnel syndrome.
The submission of an NDA or BLA is subject to the payment of substantial user fees; a waiver of such fees may be obtained under certain limited circumstances.
The submission of an NDA or BLA is subject to the payment of substantial user fees; a waiver of such fees may be obtained under certain limited circumstances. For example, products with orphan drug designation are not subject to user fees.
Day Three Labs’ majority-owned subsidiary, Day Three Labs Manufacturing, is dedicated to the commercialization of technology for the cannabis and hemp industries and has developed technological solutions specifically engineered for increased bioavailability of cannabinoids, and Day Three Labs delivers those technologies as a processing service to other third-party manufacturers.
Day Three Labs’ majority-owned subsidiary, Day Three Labs Manufacturing, is dedicated to the commercialization of technology for the cannabis and hemp industries and has developed technological solutions specifically engineered for increased bioavailability of cannabinoids.
Day Three Labs Manufacturing, a majority-owned subsidiary of Day Three Labs, owns several families of US and international patents and patent applications related the service it provides to other third-party manufacturers to increase the bioavailability of cannabinoids.
Day Three Labs Manufacturing, a majority-owned subsidiary of Day Three Labs, owns several families of US and international patents and patent applications related to increasing the bioavailability of cannabinoids.
For all of the product candidates, the Pharmaceutical Companies intend to identify and qualify additional manufacturers to provide the active pharmaceutical ingredient and the formulation and fill-and-finish. Cyclo is developing its lead product candidate, Trappsol ® Cyclo™, for the proposed treatment of Niemann-Pick Disease, Type C1.
For all of the product candidates, the Pharmaceutical Companies intend to identify and qualify additional manufacturers to provide the active pharmaceutical ingredient and the formulation and fill-and-finish. We are developing our lead product candidate, Trappsol ® Cyclo™, for the proposed treatment of NPC1.
Day Three Labs Day Three Labs is a technology company focused on creating solutions for increased bioavailability of other third-party manufacturers’ hydrophobic compounds, with a specific focus on compounds used as active ingredients in pharmaceutical and food supplement products. Day Three Labs maintains its manufacturing, sales and marketing activities in the United States, and research and development activities in Israel.
Day Three Labs Day Three Labs is a technology company focused on creating solutions for increased bioavailability of other third-party manufacturers’ products, with a specific focus on compounds used as active ingredients in pharmaceutical and food supplement products.
Review And Approval Or Clearance Of Medical Devices In The United States Unless an exemption applies, each medical device commercially distributed in the United States requires either FDA clearance of a Premarket Notification, or 510(k), FDA approval of a Premarket Approval, or PMA, application, or FDA marketing authorization in response to a De Novo request.
Consequently, the future of the program and its potential applicability to our product candidates remain unknown at this time. 18 Review And Approval, Clearance Or Marketing Authorization Of Medical Devices In The United States Unless an exemption applies, each medical device commercially distributed in the United States requires either FDA clearance of a Premarket Notification, or 510(k), FDA approval of a Premarket Approval, or PMA, application, or FDA marketing authorization in response to a De Novo request.
(Sapir E, Pffefer R, Wygoda M, Purim O, Levy A, Corn B, Amitay Y, Ohana P, Gabizon A. Pegylated Liposomal Mitomycin C Lipidic Prodrug in Combination with External Beam Radiation Therapy in Patients with Advanced Cancer: A Phase 1 Study.
Invest New Drugs. 2020;38(5):1411-1420.) ● Phase 1B of Promitil-based chemo-radiotherapy in patients with advanced cancers. (Sapir E, Pffefer R, Wygoda M, Purim O, Levy A, Corn B, Amitay Y, Ohana P, Gabizon A. Pegylated Liposomal Mitomycin C Lipidic Prodrug in Combination with External Beam Radiation Therapy in Patients with Advanced Cancer: A Phase 1 Study.
They further help ensure that non-IND foreign studies are conducted in a manner comparable to that required for IND studies. 10 Clinical trials involve the administration of the investigational product to human subjects under the supervision of qualified investigators in accordance with GCP requirements, which include, among other things, the requirement that all research subjects provide their informed consent in writing before their participation in any clinical trial.
Clinical trials involve the administration of the investigational product to human subjects under the supervision of qualified investigators in accordance with GCP requirements, which include, among other things, the requirement that all research subjects provide their informed consent in writing before their participation in any clinical trial.
The FDA will not approve an application unless it determines that the manufacturing processes and all facilities are in compliance with cGMP requirements and adequate to assure consistent production of the product within required specifications. Additionally, before approving an NDA or BLA, the FDA will typically inspect one or more clinical trial sites to assure compliance with GCP.
The FDA will not approve an application unless it determines that the manufacturing processes and all facilities are in compliance with cGMP requirements and adequate to assure consistent production of the product within required specifications.
We also further seek to expand our portfolio through opportunistic and strategic investments including therapeutics which address high unmet medical needs. Historically, the Company owned real estate assets. In 2020, the Company sold an office building located in Piscataway, New Jersey and in August 2022, the Company sold the 520 Property.
We also further seek to expand our portfolio through opportunistic and strategic investments, including investments in therapeutics which address high unmet medical needs. Historically, the Company owned real estate assets.
(Nasdaq: CYTH), (“Cyclo Therapeutics” or “Cyclo”), a clinical stage biotechnology company dedicated to developing Trappsol® Cyclo™, which is being evaluated in clinical trials for the potential treatment of Niemann-Pick Disease Type C1 (“NPC1”), a rare, fatal and progressive genetic disorder, a majority equity interest in LipoMedix Pharmaceuticals Ltd. (“LipoMedix”), a clinical stage pharmaceutical company, Barer Institute Inc.
Our lead candidate is Trappsol® Cyclo™, which is being evaluated in clinical trials for the potential treatment of Niemann-Pick Disease Type C1 (“NPC1”), a rare, fatal and progressive genetic disorder. We also hold: (i) a majority equity interest in LipoMedix Pharmaceuticals Ltd. (“LipoMedix”), a clinical stage pharmaceutical company; (ii) Barer Institute Inc.
The FDA is required to refer an application for a novel drug to an advisory committee or explain why such referral was not made. Typically, an advisory committee is a panel of independent experts, including clinicians and other scientific experts, that reviews, evaluates and provides a recommendation as to whether the application should be approved and under what conditions.
Typically, an advisory committee is a panel of independent experts, including clinicians and other scientific experts, that reviews, evaluates and provides a recommendation as to whether the application should be approved and under what conditions.
The Pharmaceutical Companies obtain supplies from these established contract manufacturers on a purchase-order basis and do not have long-term supply arrangements in place. The Pharmaceutical Companies do not currently have arrangements in place for a redundant supply of bulk drug substance or drug product, however, they may seek to add that capability if they move toward commercialization of specific candidates.
The Pharmaceutical Companies do not currently have arrangements in place for a redundant supply of bulk drug substance or drug product, however, they may seek to add that capability if they move toward regulatory approval and potential commercialization of specific candidates.
As of July 31, 2024 , the Company holds a portion of a commercial building in Jerusalem, Israel as its sole remaining owned real estate asset. In May 2023, the Company first invested in Cyclo Therapeutics. Cyclo is a clinical-stage biotechnology company that develops cyclodextrin-based products for the potential treatment of neurodegenerative diseases.
As of July 31, 2025, we hold a portion of a commercial building in Jerusalem, Israel as our sole remaining real estate asset. In May 2023, we first invested in Cyclo, a clinical-stage biotechnology company that develops cyclodextrin-based products for the potential treatment of neurodegenerative diseases. Cyclo’s lead drug candidate is Trappsol® Cyclo™ (hydroxypropyl beta cyclodextrin), a treatment for NPC1.
Cyclo’s lead drug candidate is Trappsol® Cyclo™ (hydroxypropyl beta cyclodextrin), a treatment for Niemann-Pick Disease, type C1 (“NPC1”). NPC1 is a rare and fatal autosomal recessive genetic disease resulting in disrupted cholesterol metabolism that impacts the brain, lungs, liver, spleen, and other organs. In January 2017 the FDA granted Fast Track designation to Trappsol® Cyclo™ for the treatment of NPC1.
NPC1 is a rare and fatal autosomal recessive genetic disease resulting in disrupted cholesterol metabolism that impacts the brain, lungs, liver, spleen, and other organs. In January 2017, the FDA granted Fast Track designation to Trappsol® Cyclo™ for the treatment of NPC1. Initial patient enrollment in the U.S.
A company that is found to have improperly promoted off-label uses or engaged in any other false or misleading promotion may be subject to significant liability and enforcement actions. 13 In addition, the distribution of prescription pharmaceutical products is subject to the Prescription Drug Marketing Act, or PDMA, and its implementing regulations, as well as the Drug Supply Chain Security Act, or DSCA, and its implementing regulations, which together regulate, among other things, the distribution and tracking and tracing of prescription drugs and prescription drug samples at the federal level, and set minimum standards for the regulation of drug distributors by the states.
In addition, the distribution of prescription pharmaceutical products is subject to the Prescription Drug Marketing Act, or PDMA, and its implementing regulations, as well as the Drug Supply Chain Security Act, or DSCA, and its implementing regulations, which together regulate, among other things, the distribution and tracking and tracing of prescription drugs and prescription drug samples at the federal level, and set minimum standards for the regulation of drug distributors by the states.
Prolonged survival was observed when compared to untreated controls in these animal models. GLP toxicology studies showed that any adverse events related to CPI-613® (devimistat) were considered transient and mostly observed during acute dosing; animals returned to normal post-dose (i.e., toxicities were reversible or recoverable).
GLP toxicology studies indicated that any adverse events related to CPI-613® (devimistat) were considered transient and mostly observed during acute dosing; animals returned to normal post-dose (i.e., toxicities appeared to be reversible or recoverable).
Cornerstone maintains a low single-digit royalty agreement with Altira Capital and Consulting, LLC (“Altira”), pursuant to which Cornerstone is granted sole ownership of certain patents directed to lipoic acid derivatives and other technology.
This license agreement was amended in 2004, 2007 and 2017 and (ii) Cornerstone maintains a low single-digit royalty agreement with Altira Capital and Consulting, LLC ("Altira"), pursuant to which Cornerstone is granted sole ownership of certain patents directed to lipoic acid derivatives and other technology. Rafael possesses a two-thirds ownership interest in Altira.
The MDR requires that before placing a device, other than a custom-made device, on the market, manufacturers (as well as other economic operators such as authorized representatives and importers) must register by submitting identification information to the electronic system (EUDAMED), unless they have already registered.
However, even in these cases, manufacturers must comply with a number of new or reinforced requirements set forth in the MDR, in particular the obligations described below. 22 The MDR requires that before placing a device, other than a custom-made device, on the market, manufacturers (as well as other economic operators such as authorized representatives and importers) must register by submitting identification information to the electronic system (EUDAMED), unless they have already registered.
Day Three Labs Manufacturing has also filed for trademark protection over the use of the term UNLOKT, which it uses as the brand name for the other third-party manufacturers’ cannabinoids processed using its technology.
Day Three Labs Manufacturing has also filed for trademark protection over the use of the term UNLOKT, which it uses as the brand name for the other third-party manufacturers’ cannabinoids processed using its technology. Additional patent and trademark applications may be filed as development progresses across the Portfolio Companies as deemed to be in its best interest.
The first applicant to obtain approval of an orphan drug is eligible for seven years of exclusivity for a drug, or twelve years of exclusivity for a biologic, during which FDA may not approve the same drug for the same approved orphan indication unless the subsequent product is shown to be clinically superior or if the FDA withdraws exclusive approval or revokes orphan drug designation, or if the marketing application (NDA or BLA) for the orphan drug is withdrawn for any reason, or if the holder of the orphan exclusive approval fails to assure a sufficient quantity of the orphan drug.
The first applicant to obtain approval of an orphan drug is eligible for seven years of exclusivity for a drug, or twelve years of exclusivity for a biologic, during which FDA may not approve the same drug for the same approved orphan indication unless the subsequent product is shown to be clinically superior or if the FDA withdraws exclusive approval or revokes orphan drug designation, or if the marketing application (NDA or BLA) for the orphan drug is withdrawn for any reason, or if the holder of the orphan exclusive approval fails to assure a sufficient quantity of the orphan drug. 17 Patent term restoration and extension A patent claiming a new drug product or its method of use or its method of manufacturing may be eligible for a limited patent term extension, also known as patent term restoration, under the Hatch-Waxman Act, which permits a patent restoration of up to five years for patent term lost during product development and the FDA regulatory review process.
In the area of SHMT inhibitors, a US provisional application was filed on May 21, 2024. Pursuant to a Collaboration and Assignment Agreement between Farber and Ludwig Institute for Cancer Research Ltd. (“Ludwig”), Farber assigned its rights to these patents to Ludwig. Cornerstone patents its technology, inventions, and improvements that it considers important to the development of its business.
In the area of SHMT inhibitors, a US provisional application was filed on May 22, 2025. Pursuant to a Collaboration and Assignment Agreement between Farber and Ludwig Institute for Cancer Research Ltd. (“Ludwig”), Farber assigned its rights to these patents relating to T-cel nutrients to Ludwig.

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Item 1A. Risk Factors

Risk Factors — what could go wrong, per management

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Biggest changeIn addition, some of the Pharmaceutical Companies’ competitors may have ongoing clinical trials for product candidates that are in development to treat the same indications as the Pharmaceutical Companies’ product candidates, and patients who would otherwise be eligible for the Pharmaceutical Companies’ clinical trials may instead enroll in clinical trials of the Pharmaceutical Companies’ competitors’ product candidates and therefore be ineligible or otherwise unwilling to enroll in the Pharmaceutical Companies’ clinical trials. 32 Patient enrollment is also affected by other factors including: ● size and nature of the patient population; ● severity of the disease under investigation; ● availability and efficacy of approved drugs for the disease under investigation; ● patient eligibility (inclusion and exclusion) criteria for the trial in question as defined in the protocol; ● perceived risks and benefits of the product candidate under study; ● clinicians’ and patients’ perceptions as to the potential advantages of the product candidate being studied in relation to other available therapies, including any new products that may be approved or future product candidates being investigated for the indications the Pharmaceutical Companies are investigating; ● delays in or temporary suspension of the enrollment of patients in planned clinical trials due to the COVID-19 pandemic or other public health emergencies; ● ability to obtain and maintain patient consents; ● patient referral practices of physicians; ● the ability to monitor patients adequately during and after treatment; ● proximity and availability of clinical trial sites for prospective patients; and ● the risk that patients enrolled in clinical trials will drop out of the trials before completion, including as a result of contracting COVID-19 or other health conditions or being forced to quarantine, or, because they may be late-stage cancer patients or have other conditions and will not survive the full durations of the clinical trials. 33 These factors may make it difficult for the Pharmaceutical Companies to enroll enough patients to complete their clinical trials in a timely and cost-effective manner.
Biggest changePatient enrollment is also affected by other factors including: ● size and nature of the patient population; ● severity of the disease under investigation; ● availability and efficacy of approved drugs for the disease under investigation; ● patient eligibility (inclusion and exclusion) criteria for the trial in question as defined in the protocol; ● perceived risks and benefits of the product candidate under study; ● clinicians’ and patients’ perceptions as to the potential advantages of the product candidate being studied in relation to other available therapies, including any new products that may be approved or future product candidates being investigated for the indications the Pharmaceutical Companies are investigating; 35 ● delays in or temporary suspension of the enrollment of patients in planned clinical trials due to the COVID-19 pandemic or other public health emergencies; ● ability to obtain and maintain patient consents and clinical trial enrollment; ● patient referral practices of physicians; ● the ability to monitor patients adequately during and after treatment; ● proximity and availability of clinical trial sites for prospective patients; and ● the risk that patients enrolled in clinical trials will drop out of the trials before completion, including as a result of contracting COVID-19 or other health conditions or being forced to quarantine, or, because they may be late-stage cancer patients or have other conditions and will not survive the full durations of the clinical trials.
These payors may not view the Pharmaceutical Companies’ products, if any, as cost-effective, and coverage and reimbursement may not be available to our or the Pharmaceutical Companies’ customers, or those of any future collaborators, or may not be sufficient to allow the Pharmaceutical Companies’ products, if any, to be marketed on a competitive basis.
These payors may not view our or the Pharmaceutical Companies’ products, if any, as cost-effective, and coverage and reimbursement may not be available to our or the Pharmaceutical Companies’ customers, or those of any future collaborators, or may not be sufficient to allow our or the Pharmaceutical Companies’ products, if any, to be marketed on a competitive basis.
An inability to promptly obtain coverage and adequate reimbursement rates from both government-funded and private payors for any of the Pharmaceutical Companies’ product candidates for which they, or any future collaborator, obtain regulatory approval could significantly harm our and the Pharmaceutical Companies’ operating results, our and the Pharmaceutical Companies’ ability to raise capital needed to commercialize products, and our and the Pharmaceutical Companies’ overall financial condition.
An inability to promptly obtain coverage and adequate reimbursement rates from both government-funded and private payors for our or any of the Pharmaceutical Companies’ product candidates for which they, or any future collaborator, obtain regulatory approval could significantly harm our and the Pharmaceutical Companies’ operating results, our and the Pharmaceutical Companies’ ability to raise capital needed to commercialize products, and our and the Pharmaceutical Companies’ overall financial condition.
In addition, the information we or they choose to publicly disclose regarding a particular study or clinical trial is based on what is typically extensive information, and you or others may not agree with what we determine is material or otherwise appropriate information to include in our disclosure.
In addition, the information we or they choose to publicly disclose regarding a particular study or clinical trial is based on what is typically extensive information, and you or others may not agree with what we determine is material or otherwise appropriate information to include in our disclosure.
If these third parties do not properly and successfully carry out their contractual duties or meet expected deadlines, the Portfolio Companies and may not be able to obtain regulatory approval of or commercialize their product candidates.
If these third parties do not properly and successfully carry out their contractual duties or meet expected deadlines, the Portfolio Companies may not be able to obtain regulatory approval of or commercialize their product candidates.
The Portfolio Companies’ business could be materially adversely affected by business disruptions caused by third-party providers that could materially adversely affect their and our potential future revenue and financial condition and increase their and our costs and expenses.
Our and the Portfolio Companies’ business could be materially adversely affected by business disruptions caused by third-party providers that could materially adversely affect their and our potential future revenue and financial condition and increase their and our costs and expenses.
As a result, if we or the Portfolio Companies enter into future collaboration agreements and strategic partnerships or out-license the Pharmaceutical Companies’ product candidates or Rafael Medical Devices’ device candidates, we may not be able to realize the benefit of such transactions if we are unable to successfully integrate them with our or their existing operations and company culture, which could delay our or their timelines or otherwise adversely affect our or their business.
As a result, if we or the Portfolio Companies enter into future collaboration agreements and strategic partnerships or out-license our, the Pharmaceutical Companies’ product candidates or Rafael Medical Devices’ device candidates, we may not be able to realize the benefit of such transactions if we are unable to successfully integrate them with our or their existing operations and company culture, which could delay our or their timelines or otherwise adversely affect our or their business.
For example, they may be subject to the following: state anti-kickback and false claims laws that may apply to sales or marketing arrangements and claims involving healthcare items or services reimbursed by non-governmental third party payors, including private insurers, or that apply regardless of payor; state laws that require pharmaceutical companies to comply with the pharmaceutical industry’s voluntary compliance guidelines and the relevant compliance guidance promulgated by the federal government; state laws that require drug and device manufacturers to report information related to payments and other transfers of value to physicians and other healthcare providers, marketing expenditures, or drug pricing; state and local laws requiring the registration of pharmaceutical and device sales and medical representatives; and state and foreign laws, such as the GDPR governing 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.
For example, they may be subject to the following: state anti-kickback and false claims laws that may apply to sales or marketing arrangements and claims involving healthcare items or services reimbursed by non-governmental third party payors, including private insurers, or that apply regardless of payor; state laws that require pharmaceutical companies to comply with the pharmaceutical industry’s and medical device industry's voluntary compliance guidelines and the relevant compliance guidance promulgated by the federal government; state laws that require drug and device manufacturers to report information related to payments and other transfers of value to physicians and other healthcare providers, marketing expenditures, or drug pricing; state and local laws requiring the registration of pharmaceutical and device sales and medical representatives; and state and foreign laws, such as the GDPR governing 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.
If the Pharmaceutical Companies or Rafael Medical Devices or their respective employees, independent contractors, consultants, commercial partners, and vendors violate these laws, they and we may be subject to investigations, enforcement actions and/or significant penalties, including the imposition of significant civil, criminal, and administrative penalties, damages, disgorgement, monetary fines, imprisonment, possible exclusion from participation in Medicare, Medicaid and other federal healthcare programs, contractual damages, reputational harm, diminished profits and future earnings, additional reporting requirements and/or oversight if they or we become subject to a corporate integrity agreement or similar agreement to resolve allegations of non-compliance with these laws, and curtailment of the Pharmaceutical Companies’ and Rafael Medical Devices’ operations, any of which could adversely affect their ability to operate their business and their and our results of operations.
If we, the Pharmaceutical Companies or Rafael Medical Devices or their respective employees, independent contractors, consultants, commercial partners, and vendors violate these laws, they and we may be subject to investigations, enforcement actions and/or significant penalties, including the imposition of significant civil, criminal, and administrative penalties, damages, disgorgement, monetary fines, imprisonment, possible exclusion from participation in Medicare, Medicaid and other federal healthcare programs, contractual damages, reputational harm, diminished profits and future earnings, additional reporting requirements and/or oversight if they or we become subject to a corporate integrity agreement or similar agreement to resolve allegations of non-compliance with these laws, and curtailment of our, the Pharmaceutical Companies’ and Rafael Medical Devices’ operations, any of which could adversely affect their ability to operate their business and their and our results of operations.
The entities in which we hold interests or in which we may invest may not make necessary payments or take other actions to protect intellectual property or other rights that they own, license or have acquired from third parties, which could result in the loss or impairment of those rights and the reduction of the value of our interests.
The entities in which we hold interests or in which we may invest may not make necessary payments or take other actions to protect intellectual property or other rights that we or they own, license or have acquired from third parties, which could result in the loss or impairment of those rights and the reduction of the value of our interests.
To the extent that we fail to obtain such assignments, such assignments do not contain a self-executing assignment of intellectual property rights or such assignment agreements are breached, we may be forced to bring claims against third parties, or defend claims they may bring against us, to determine the ownership of what we regard as our intellectual property, and this may interfere with our ability to capture the commercial value of such intellectual property.
To the extent that we or they fail to obtain such assignments, such assignments do not contain a self-executing assignment of intellectual property rights or such assignment agreements are breached, we may be forced to bring claims against third parties, or defend claims they may bring against us, to determine the ownership of what we regard as our intellectual property, and this may interfere with our ability to capture the commercial value of such intellectual property.
Any potential acquisition or strategic partnership may entail numerous risks, including: ● increased operating expenses and cash requirements; ● the assumption of additional indebtedness or contingent liabilities; ● the issuance of our equity securities; ● assimilation of operations, intellectual property and products of an acquired company, including difficulties associated with integrating new personnel; ● the diversion of our management’s attention from our existing programs and initiatives in pursuing such a strategic merger or acquisition; ● retention of key employees, the loss of key personnel and uncertainties in our ability to maintain key business relationships; ● risks and uncertainties associated with the other party to such a transaction, including the prospects of that party and their existing products or product candidates, devices or device candidates, and any regulatory approvals or clearances; and ● assumption of the regulatory risks, costs, and responsibilities associated with the other party’s existing products or product candidates, devices or device candidates, and any regulatory approvals or clearances; ● our inability to generate revenue from acquired technology and/or products sufficient to meet our objectives in undertaking the acquisition or even to offset the associated acquisition and maintenance costs.
Any potential acquisition or strategic partnership may entail numerous risks, including: ● increased operating expenses and cash requirements; ● the assumption of additional indebtedness or contingent liabilities; ● the issuance of our equity securities; ● assimilation of operations, intellectual property and products of an acquired company, including difficulties associated with integrating new personnel; ● the diversion of our management’s attention from our existing programs and initiatives in pursuing such a strategic merger or acquisition; ● retention of key employees, the loss of key personnel and uncertainties in our ability to maintain key business relationships; ● risks and uncertainties associated with the other party to such a transaction, including the prospects of that party and their existing products or product candidates, devices or device candidates, and any regulatory approvals or clearances; ● assumption of the regulatory risks, costs, and responsibilities associated with the other party’s existing products or product candidates, devices or device candidates, and any regulatory approvals or clearances; and ● our inability to generate revenue from acquired technology and/or products sufficient to meet our objectives in undertaking the acquisition or even to offset the associated acquisition and maintenance costs.
Similar to the federal Anti-Kickback Statute, a person or entity does not need to have actual knowledge of the statute or specific intent to violate it in order to have committed a violation; 69 ● HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act, and their respective implementing regulations, which impose requirements on certain healthcare providers, health plans, and healthcare clearinghouses, known as covered entities, and their respective business associates that perform services for them that involve the use or disclosure of individually identifiable protected health information, as well as their covered subcontractors, including breach notification regulations; ● new regulations adopted by the Securities and Exchange Commission, or SEC, effective December 18, 2023, that require greater disclosure regarding cybersecurity risk management, strategy and governance, as well as disclosure of material cybersecurity incidents, which may require reporting of a cybersecurity incident before its impact has been fully assessed or the underlying issue has been remediated, which could divert management’s attention from incident response and could potentially reveal system vulnerabilities to threat actors, and for which failure to timely report such incidents under these or other similar rules could also result in monetary fines, sanctions or other forms of liability. ● analogous state data privacy and security laws and regulations that govern the collection, use, disclosure, transfer, storage, disposal, and protection of personal information, such as social security numbers, medical and financial information, and other information, including data breach laws that require timely notification to individuals, and at times regulators, the media or credit reporting agencies, if a company has experienced the unauthorized access or acquisition of personal information, as well as the California Consumer Privacy Act or CCPA, which, among other things, contains new disclosure obligations for businesses that collect personal information about California residents and affords those individuals numerous rights relating to their personal information that may affect companies’ ability to use personal information or share it with business partners, and the California Privacy Rights Act, or CPRA, which expands the scope of the CCPA, imposes new restrictions on behavioral advertising, and establishes a new California Privacy Protection Agency that will enforce the law and issue regulations, and became “operative” on January 1, 2023, with a 12-month “lookback provision” applicable to personal data collected on or after January 1, 2022, and the various state laws and regulations may be more restrictive and not preempted by United States federal laws; ● analogous foreign data protection laws, including among others the EU General Data Protection Regulation, or the GDPR, EU member states’ implementing legislation, and the UK GDPR, which imposes data protection requirements that include strict obligations and restrictions on the ability to collect, analyze, and transfer EEA or UK personal data, a requirement for prompt notice of data breaches to data subjects and supervisory authorities in certain circumstances, and possible substantial fines for any violations (including possible fines for certain violations of up to the greater of 20 million Euros or 4% of total worldwide annual turnover of the preceding financial year), with legal requirements in foreign countries relating to the collection, storage, processing, and transfer of personal data continuing to evolve and varying widely across jurisdictions; and ● the federal Physician Payments Sunshine Act, which requires certain manufacturers of drugs, devices, biologicals and medical supplies for which payment is available under Medicare, Medicaid or the Children’s Health Insurance Program (with certain exceptions) to report annually to CMS information related to payments or other transfers of value made to physicians (defined to include doctors, dentists, optometrists, podiatrists, and chiropractors) and teaching hospitals, as well as ownership and investment interests held by physicians and their immediate family members.
Similar to the federal Anti-Kickback Statute, a person or entity does not need to have actual knowledge of the statute or specific intent to violate it in order to have committed a violation; ● HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act, and their respective implementing regulations, which impose requirements on certain healthcare providers, health plans, and healthcare clearinghouses, known as covered entities, and their respective business associates that perform services for them that involve the use or disclosure of individually identifiable protected health information, as well as their covered subcontractors, including breach notification regulations; ● new regulations adopted by the Securities and Exchange Commission, or SEC, effective December 18, 2023, that require greater disclosure regarding cybersecurity risk management, strategy and governance, as well as disclosure of material cybersecurity incidents, which may require reporting of a cybersecurity incident before its impact has been fully assessed or the underlying issue has been remediated, which could divert management's attention from incident response and could potentially reveal system vulnerabilities to threat actors, and for which failure to timely report such incidents under these or other similar rules could also result in monetary fines, sanctions or other forms of liability; ● analogous state data privacy and security laws and regulations that govern the collection, use, disclosure, transfer, storage, disposal, and protection of personal information, such as social security numbers, medical and financial information, and other information, including data breach laws that require timely notification to individuals, and at times regulators, the media or credit reporting agencies, if a company has experienced the unauthorized access or acquisition of personal information, as well as state laws such as the California Consumer Privacy Act or CCPA, which, among other things, contains new disclosure obligations for businesses that collect personal information about California residents and affords those individuals numerous rights relating to their personal information that may affect companies’ ability to use personal information or share it with business partners, and the California Privacy Rights Act, or CPRA, which expands the scope of the CCPA, imposes new restrictions on behavioral advertising, and establishes a new California Privacy Protection Agency that will enforce the law and issue regulations, and became “operative” on January 1, 2023, with a 12-month “lookback provision” applicable to personal data collected on or after January 1, 2022, and the various state laws and regulations may be more restrictive than and not preempted by United States federal laws; ● analogous foreign data protection laws, including among others the EU General Data Protection Regulation, or the GDPR, EU member states’ implementing legislation, and the UK GDPR, which imposes data protection requirements that include strict obligations and restrictions on the ability to collect, analyze, and transfer EEA or UK personal data, a requirement for prompt notice of data breaches to data subjects and supervisory authorities in certain circumstances, and possible substantial fines for any violations (including possible fines for certain violations of up to the greater of 20 million Euros or 4% of total worldwide annual turnover of the preceding financial year), with legal requirements in foreign countries relating to the collection, storage, processing, and transfer of personal data continuing to evolve and varying widely across jurisdictions; and ● the federal Physician Payments Sunshine Act, which requires certain manufacturers of drugs, devices, biologicals and medical supplies for which payment is available under Medicare, Medicaid or the Children’s Health Insurance Program (with certain exceptions) to report annually to CMS information related to payments or other transfers of value made to physicians (defined to include doctors, dentists, optometrists, podiatrists, and chiropractors) and teaching hospitals, as well as ownership and investment interests held by physicians and their immediate family members.
Among the provisions of the ACA of potential importance to the Pharmaceutical Companies’ business and the Pharmaceutical Companies’ product candidates are the following: ● an annual, non-deductible fee on any entity that manufactures or imports specified branded prescription drugs and biologic agents; ● an increase in the statutory minimum rebates a manufacturer must pay under the Medicaid Drug Rebate Program, or MDRP; ● a new methodology by which rebates owed by manufacturers under the MDRP are calculated for drugs that are inhaled, infused, instilled, implanted or injected; ● expansion of healthcare fraud and abuse laws, including the civil False Claims Act and the federal Anti-Kickback Statute, new government investigative powers and enhanced penalties for noncompliance; 51 ● a new Medicare Part D coverage gap discount program, in which manufacturers must agree to now offer 70% point-of-sale discounts off negotiated prices of applicable brand drugs to eligible beneficiaries during their coverage gap period, as a condition for the manufacturer’s outpatient drugs to be covered under Medicare Part D; ● extension of manufacturers’ Medicaid rebate liability to individuals enrolled in Medicaid managed care organizations; ● expansion of eligibility criteria for Medicaid programs; ● expansion of the entities eligible for discounts under the Public Health Service pharmaceutical pricing program; ● new requirements to report certain financial arrangements with physicians and teaching hospitals for eventual publication; ● a new requirement to annually report drug samples that manufacturers and distributors provide to physicians for eventual publication; ● a new Patient-Centered Outcomes Research Institute to oversee, identify priorities in, and conduct comparative clinical effectiveness research, along with funding for such research; and ● a Center for Medicare and Medicaid Innovation within CMS to test innovative payment and service delivery models.
Among the provisions of the ACA of potential importance to the Pharmaceutical Companies’ business and the Pharmaceutical Companies’ product candidates are the following: ● an annual, non-deductible fee on any entity that manufactures or imports specified branded prescription drugs and biologic agents; ● an increase in the statutory minimum rebates a manufacturer must pay under the Medicaid Drug Rebate Program, or MDRP; ● a new methodology by which rebates owed by manufacturers under the MDRP are calculated for drugs that are inhaled, infused, instilled, implanted or injected; ● expansion of healthcare fraud and abuse laws, including the civil False Claims Act and the federal Anti-Kickback Statute, new government investigative powers and enhanced penalties for noncompliance; ● a new Medicare Part D coverage gap discount program, in which manufacturers must agree to now offer 70% point-of-sale discounts off negotiated prices of applicable brand drugs to eligible beneficiaries during their coverage gap period, as a condition for the manufacturer’s outpatient drugs to be covered under Medicare Part D; 47 ● extension of manufacturers’ Medicaid rebate liability to individuals enrolled in Medicaid managed care organizations; ● expansion of eligibility criteria for Medicaid programs; ● expansion of the entities eligible for discounts under the Public Health Service pharmaceutical pricing program; ● new requirements to report certain financial arrangements with physicians and teaching hospitals for eventual publication; ● a new requirement to annually report drug samples that manufacturers and distributors provide to physicians for eventual publication; ● a new Patient-Centered Outcomes Research Institute to oversee, identify priorities in, and conduct comparative clinical effectiveness research, along with funding for such research; and ● a Center for Medicare and Medicaid Innovation within CMS to test innovative payment and service delivery models.
Further, collaborations involving the Portfolio Companies’ product candidates and device candidates are subject to numerous risks, which may include the following: ● collaborators have significant discretion in determining the efforts and resources that they will apply to a collaboration; ● collaborators may not pursue development and commercialization of the Portfolio Companies’ product candidates or device candidates or may elect not to continue or renew development or commercialization of their product candidates or device candidates based on clinical trial results, changes in their strategic focus due to the acquisition of competitive products, availability of funding or other external factors, such as a business combination that diverts resources or creates competing priorities; ● collaborators may delay clinical trials, provide insufficient funding for a clinical trial, stop a clinical trial, abandon a product candidate or device candidate, repeat or conduct new clinical trials or require a new formulation of a product candidate or device candidate for clinical testing; ● collaborators could independently develop, or develop with third parties, products that compete directly or indirectly with the Pharmaceutical Companies’ product candidates and Rafael Medical Devices’ device candidates; 67 ● a collaborator with marketing and distribution rights to one or more product candidates or device candidates may not commit sufficient resources to their marketing and distribution in the event that they were to receive regulatory approval or clearance; ● collaborators may not properly maintain or defend our or the Portfolio Companies’ intellectual property rights or may use our or their intellectual property or proprietary information in a way that gives rise to actual or threatened litigation that could jeopardize or invalidate our or their intellectual property or proprietary information or expose us or them to potential liability; ● disputes may arise between us and/or the Portfolio Companies and a collaborator that cause the delay or termination of the research, development or commercialization of a product candidate or device candidate, or that result in costly litigation or arbitration that diverts management attention and resources; ● collaborations may be terminated and, if terminated, may result in a need for additional capital to pursue further development or commercialization of the applicable product candidates or device candidates; and ● collaborators may own or co-own intellectual property covering our or the Portfolio Companies’ products that results from our or their collaborating with them, and in such cases, we and they would not have the exclusive right to commercialize such intellectual property.
Further, collaborations involving our and the Portfolio Companies’ product candidates and device candidates are subject to numerous risks, which may include the following: ● collaborators have significant discretion in determining the efforts and resources that they will apply to a collaboration; ● collaborators may not pursue development and commercialization of our and the Portfolio Companies’ product candidates or device candidates or may elect not to continue or renew development or commercialization of their product candidates or device candidates based on clinical trial results, changes in their strategic focus due to the acquisition of competitive products, availability of funding or other external factors, such as a business combination that diverts resources or creates competing priorities; ● collaborators may delay clinical trials, provide insufficient funding for a clinical trial, stop a clinical trial, abandon a product candidate or device candidate, repeat or conduct new clinical trials or require a new formulation of a product candidate or device candidate for clinical testing; ● collaborators could independently develop, or develop with third parties, products that compete directly or indirectly with our, the Pharmaceutical Companies’ product candidates and Rafael Medical Devices’ device candidates; 58 ● a collaborator with marketing and distribution rights to one or more product candidates or device candidates may not commit sufficient resources to their marketing and distribution in the event that they were to receive regulatory approval or clearance; ● collaborators may not properly maintain or defend our or the Portfolio Companies’ intellectual property rights or may use our or their intellectual property or proprietary information in a way that gives rise to actual or threatened litigation that could jeopardize or invalidate our or their intellectual property or proprietary information or expose us or them to potential liability; ● disputes may arise between us and/or the Portfolio Companies and a collaborator that cause the delay or termination of the research, development or commercialization of a product candidate or device candidate, or that result in costly litigation or arbitration that diverts management attention and resources; ● collaborations may be terminated and, if terminated, may result in a need for additional capital to pursue further development or commercialization of the applicable product candidates or device candidates; and ● collaborators may own or co-own intellectual property covering our or the Portfolio Companies’ products that results from our or their collaborating with them, and in such cases, we and they would not have the exclusive right to commercialize such intellectual property.
The Pharmaceutical Companies, the FDA, other comparable regulatory authorities or an IRB may suspend or halt clinical trials of a product candidate at any time for various reasons, including a belief that subjects in such trials are being exposed to inadequate clinical benefit and/or unacceptable health risks or adverse side effects. 34 Further, if any of the Pharmaceutical Companies’ product candidates obtains regulatory approval, toxicities associated with such product candidates previously not seen during clinical testing may also develop after such approval and lead to a number of potentially significant negative consequences, including, but not limited to: ● regulatory authorities may suspend, limit or withdraw approvals of such product, or seek an injunction against its manufacture or distribution; ● regulatory authorities may require additional warnings on the label, including “boxed” warnings, or issue safety alerts, Dear Healthcare Provider letters, press releases or other communications containing warnings or other safety information about the product; ● the Pharmaceutical Companies may be required to change the way the product is administered or conduct additional clinical trials or post-approval studies; ● the Pharmaceutical Companies may be required to develop and implement a risk evaluation and mitigation strategy, or REMS, which could include, among other things, a medication guide outlining the risks of such side effects for distribution to patients, and potentially limitations or even restrictions on prescribing, dispensing, and/or distribution; ● the Pharmaceutical Companies may be subject to fines, injunctions or the imposition of criminal penalties; ● we and/or the Pharmaceutical Companies could be sued and held liable for harm caused to patients; and ● our reputation may suffer.
We, the Pharmaceutical Companies, the FDA, other comparable regulatory authorities or an IRB may suspend or halt clinical trials of a product candidate at any time for various reasons, including a belief that subjects in such trials are being exposed to inadequate clinical benefit and/or unacceptable health risks or adverse side effects. 36 Further, if any of our or the Pharmaceutical Companies’ product candidates obtains regulatory approval, toxicities associated with such product candidates previously not seen during clinical testing may also develop after any such approval and lead to a number of potentially significant negative consequences, including, but not limited to: ● regulatory authorities may suspend, limit or withdraw approvals of such product, or seek an injunction against its manufacture or distribution; ● regulatory authorities may require additional warnings on the label, including “boxed” warnings, or issue safety alerts, Dear Healthcare Provider letters, press releases or other communications containing warnings or other safety information about the product; ● we or the Pharmaceutical Companies may be required to change the way the product is administered or conduct additional clinical trials or post-approval studies; ● we or the Pharmaceutical Companies may be required to develop and implement a risk evaluation and mitigation strategy, or REMS, which could include, among other things, a medication guide outlining the risks of such side effects for distribution to patients, and potentially limitations or even restrictions on prescribing, dispensing, and/or distribution; ● we and/or the Pharmaceutical Companies may be subject to fines, injunctions or the imposition of criminal penalties; ● we and/or the Pharmaceutical Companies could be sued and held liable for harm caused to patients; and ● our reputation may suffer.
In addition, a person or entity does not need to have actual knowledge of this statute or specific intent to violate it in order to have committed a violation; ● federal civil and criminal false claims laws, including the federal civil False Claims Act, and civil monetary penalty laws, which prohibit, among other things, individuals or entities from knowingly presenting, or causing to be presented, claims for payment or approval from Medicare, Medicaid, or other federal government programs that are false or fraudulent or knowingly making a false statement to improperly avoid, decrease or conceal an obligation to pay money to the federal government, including federal healthcare programs.
In addition, a person or entity does not need to have actual knowledge of this statute or specific intent to violate it in order to have committed a violation; 59 ● federal civil and criminal false claims laws, including the federal civil False Claims Act, and civil monetary penalty laws, which prohibit, among other things, individuals or entities from knowingly presenting, or causing to be presented, claims for payment or approval from Medicare, Medicaid, or other federal government programs that are false or fraudulent or knowingly making a false statement to improperly avoid, decrease or conceal an obligation to pay money to the federal government, including federal healthcare programs.
Regardless of merit or eventual outcome, liability claims may result in: ● decreased demand for any product candidates or medicines that the Pharmaceutical Companies may develop; ● injury to the Pharmaceutical Companies’ reputation and significant negative media attention; 49 ● withdrawal of clinical trial participants; ● significant costs to defend the related litigation; ● substantial monetary awards to trial participants or patients; ● loss of revenue; ● reduced resources of the Pharmaceutical Companies’ management to pursue the Pharmaceutical Companies’ business strategy, and diverted time and attention from executing on that strategy; and ● the inability to commercialize any medicines that the Pharmaceutical Companies may develop.
Regardless of merit or eventual outcome, liability claims may result in: ● decreased demand for any product candidates or medicines that the Pharmaceutical Companies may develop; ● injury to the Pharmaceutical Companies’ reputation and significant negative media attention; ● withdrawal of clinical trial participants; ● significant costs to defend the related litigation; ● substantial monetary awards to trial participants or patients; ● loss of revenue; ● reduced resources of the Pharmaceutical Companies’ management to pursue the Pharmaceutical Companies’ business strategy, and diverted time and attention from executing on that strategy; and ● the inability to commercialize any medicines that the Pharmaceutical Companies may develop.
If any third-party patents were held by a court of competent jurisdiction to cover the manufacturing process of our product candidates, constructs or molecules used in or formed during the manufacturing process, any final product itself if it received regulatory approval, or our device candidates, the holders of any such patents may be able to block our ability to commercialize the product candidate or device candidate unless we obtain a license under the applicable patents, or until such patents expire or they are determined to be held invalid or unenforceable.
If any third-party patents were held by a court of competent jurisdiction to cover the manufacturing process of our or their product candidates, constructs or molecules used in or formed during the manufacturing process, any final product itself if it received regulatory approval, or our device candidates, the holders of any such patents may be able to block our ability to commercialize the product candidate or device candidate unless we obtain a license under the applicable patents, or until such patents expire or they are determined to be held invalid or unenforceable.
Further, if any of Rafael Medical Devices’ device candidates obtains regulatory approval, marketing authorization or clearance, toxicities or other serious adverse events associated with such device candidates previously not seen during clinical testing may also develop after such approval, marketing authorization, or clearance and lead to a number of potentially significant negative consequences, including, but not limited to: ● Regulatory authorities may suspend, limit or withdraw approvals, marketing authorizations or clearances of such device, if any, or seek an injunction against its manufacture or distribution; ● regulatory authorities may require additional warnings on the label, including “boxed” warnings, or issue safety alerts, Dear Healthcare Provider letters, press releases or other communications containing warnings or other safety information about the product; ● Rafael Medical Devices may be required to change the way the device is implanted or conduct additional clinical trials or post-approval studies; ● Rafael Medical Devices may be subject to fines, injunctions or the imposition of criminal penalties; ● we or Rafael Medical Devices could be sued and held liable for harm caused to patients; and ● Rafael Medical Devices and our reputation may suffer.
Further, for any of Rafael Medical Devices’ device candidates that obtains regulatory approval, marketing authorization or clearance, toxicities or other serious adverse events associated with such device candidates previously not seen during clinical testing may also develop after such approval, marketing authorization, or clearance and lead to a number of potentially significant negative consequences, including, but not limited to: ● Regulatory authorities may suspend, limit or withdraw approvals, marketing authorizations or clearances of such device, if any, or seek an injunction against its manufacture or distribution; ● regulatory authorities may require additional warnings on the label, including “boxed” warnings, or issue safety alerts, Dear Healthcare Provider letters, press releases or other communications containing warnings or other safety information about the product; ● Rafael Medical Devices may be required to change the way the device is implanted or other used or conduct additional clinical trials or post-approval studies; ● Rafael Medical Devices may be subject to fines, injunctions or the imposition of criminal penalties; ● we or Rafael Medical Devices could be sued and held liable for harm caused to patients; and ● Rafael Medical Devices and our reputation may suffer.
If one or more third-party sponsor is the first to receive approval for an alternative product(s) for the same orphan-designated indication as the Pharmaceutical Companies’ product candidate, even if FDA were to conclude that the Pharmaceutical Companies’ product candidate is not the “same drug” as the alternative product(s), the prior approval(s) of such alternative product(s) could result in a delay in the regulatory review of the Pharmaceutical Companies’ product candidate and/or requests for the conduct of additional clinical trials that may further delay the prospects for any approval of the Pharmaceutical Companies’ product candidate.
If one or more third-party sponsor is the first to receive approval for an alternative product(s) for the same orphan-designated indication as our or the Pharmaceutical Companies’ product candidate, even if FDA were to conclude that the Pharmaceutical Companies’ product candidate is not the “same drug” as the alternative product(s), the prior approval(s) of such alternative product(s) could result in a delay in the regulatory review of our or the Pharmaceutical Companies’ product candidate and/or requests for the conduct of additional clinical trials that may further delay the prospects for any approval of our or the Pharmaceutical Companies’ product candidate.
If the FDA or a comparable foreign regulatory authority does not approve these facilities for the manufacture of any approved or cleared products or if they withdraw any approval in the future, the Portfolio Companies may need to find alternative manufacturing facilities, which would require the incurrence of significant additional time and costs and materially adversely affect the ability to develop, obtain regulatory approval or clearance for or market any product candidates or device candidates, if approved or cleared.
If the FDA or a comparable foreign regulatory authority does not approve these facilities for the manufacture of any approved or cleared products or if they withdraw any approval in the future, we or the Portfolio Companies may need to find alternative manufacturing facilities, which would require the incurrence of significant additional time and costs and materially adversely affect the ability to develop, obtain regulatory approval or clearance for or market any product candidates or device candidates, if approved or cleared.
If the FDA does not conclude that certain of the Pharmaceutical Companies’ product candidates satisfy the requirements for the Section 505(b)(2) regulatory approval pathway, or if the requirements for such product candidates under Section 505(b)(2) are not as they expect, the approval pathway for those product candidates will likely take significantly longer, cost significantly more and entail significantly greater complications and risks than anticipated, and in either case may not be successful.
If the FDA does not conclude that certain of the Pharmaceutical Companies’ product candidates, if any, satisfy the requirements for the Section 505(b)(2) regulatory approval pathway, or if the requirements for such product candidates under Section 505(b)(2) are not as they expect, the approval pathway for those product candidates will likely take significantly longer, cost significantly more and entail significantly greater complications and risks than anticipated, and in either case may not be successful.
Any regulatory approvals that the Pharmaceutical Companies may receive for their product candidates will require the regular submission of reports to regulatory authorities and surveillance to monitor the safety and efficacy of the product, may contain significant limitations related to use restrictions for specified age groups or patient populations, warnings, precautions or contraindications, and may include burdensome post-approval study or risk management requirements.
Any regulatory approvals that we or the Pharmaceutical Companies may receive for their product candidates will require the regular submission of reports to regulatory authorities and surveillance to monitor the safety and efficacy of the product, may contain significant limitations related to use restrictions for specified age groups or patient populations, warnings, precautions or contraindications, and may include burdensome post-approval study or risk management requirements.
If we are unable to extend the expiration date of our existing patents or obtain new patents with longer expiry dates, our competitors may be able to take advantage of our investment in development and clinical trials by referencing our clinical and preclinical data to obtain approval of competing products following our patent expiration and launch their product earlier than might otherwise be the case.
If we or they are unable to extend the expiration date of our existing patents or obtain new patents with longer expiry dates, our competitors may be able to take advantage of our investment in development and clinical trials by referencing our clinical and preclinical data to obtain approval of competing products following our patent expiration and launch their product earlier than might otherwise be the case.
Because patent applications can take many years to issue and may be confidential for 18 months or more after filing, there may be applications now pending of which we are unaware and which may later result in issued patents that we may infringe by commercializing our product candidates or device candidates if they receive approval or clearance or our services or technologies.
Because patent applications can take many years to issue and may be confidential for 18 months or more after filing, there may be applications now pending of which we and they are unaware and which may later result in issued patents that we or they may infringe by commercializing our or their product candidates or device candidates if they receive approval or clearance or our or their services or technologies.
If any of our patents are challenged, invalidated, or circumvented by third parties or otherwise limited or expire prior to the commercialization of our products, services or technologies, and if we do not own or have exclusive rights to other enforceable patents protecting our products, services or other technologies, competitors and other third parties could market products and use processes that are substantially similar, or superior, to ours and theirs, and our business would suffer.
If any of our or their patents are challenged, invalidated, or circumvented by third parties or otherwise limited or expire prior to the commercialization of our products, services or technologies, and if we do not own or have exclusive rights to other enforceable patents protecting our products, services or other technologies, competitors and other third parties could market products and use processes that are substantially similar, or superior, to ours and theirs, and our business would suffer.
Disruptions at the FDA and other government agencies caused by funding shortages or global health concerns could hinder their ability to hire, retain or deploy key leadership and other personnel, or otherwise prevent new or modified products from being developed, approved or commercialized in a timely manner or at all, which could negatively impact our business.
Disruptions at the FDA and other government agencies caused by funding shortages, government shutdowns or global health concerns could hinder their ability to hire, retain or deploy key leadership and other personnel, or otherwise prevent new or modified products from being developed, approved or commercialized in a timely manner or at all, which could negatively impact our business.
The following examples are illustrative: ● others may be able to develop and/or practice processes or technologies that are similar to our processes or technologies or aspects of our processes or technologies, but that are not covered by the claims of the patents that we own or control, assuming such patents have issued or do issue; ● we or our licensors or any future strategic partners might not have been the first to conceive or reduce to practice the inventions covered by the issued patents or pending patent applications that we own or have exclusively licensed; ● we or our licensors or any future strategic partners might not have been the first to file patent applications covering certain of our inventions; ● others may independently develop similar or alternative processes or technologies or duplicate any of our processes or technologies without infringing our intellectual property rights; ● it is possible that our pending patent applications will not lead to issued patents; ● issued patents that we own or have exclusively licensed may not provide us with any competitive advantage, or may be held invalid or unenforceable, as a result of legal challenges by our competitors; ● our competitors might conduct research and development activities in countries where we do not have patent rights and then use the information learned from such activities to develop competitive products for sale in our major commercial markets; ● third parties performing manufacturing or testing for us using our product candidates or device candidates, including our processes and technologies, could use the intellectual property of others without obtaining a proper license; ● parties may assert an ownership interest in our intellectual property and, if successful, such disputes may preclude us from exercising exclusive rights over that intellectual property; ● we may not develop or in-license additional proprietary technologies that are patentable; ● we may not be able to obtain and maintain necessary licenses on commercially reasonable terms, or at all; and ● the patents of others may have an adverse effect on our business.
The following examples are illustrative: ● others may be able to develop and/or practice processes or technologies that are similar to our or their processes or technologies or aspects of our processes or technologies, but that are not covered by the claims of the patents that we or they own or control, assuming such patents have issued or do issue; ● we or our licensors or any future strategic partners might not have been the first to conceive or reduce to practice the inventions covered by the issued patents or pending patent applications that we own or have exclusively licensed; ● we or our licensors or any future strategic partners might not have been the first to file patent applications covering certain of our inventions; ● others may independently develop similar or alternative processes or technologies or duplicate any of our processes or technologies without infringing our intellectual property rights; ● it is possible that our or their pending patent applications will not lead to issued patents; ● issued patents that we own or have exclusively licensed may not provide us with any competitive advantage, or may be held invalid or unenforceable, as a result of legal challenges by our competitors or other third parties; ● our competitors might conduct research and development activities in countries where we do not have patent rights and then use the information learned from such activities to develop competitive products for sale in our major commercial markets; ● third parties performing manufacturing or testing for us using our product candidates or device candidates, including our processes and technologies, could use the intellectual property of others without obtaining a proper license; ● parties may assert an ownership interest in our intellectual property and, if successful, such disputes may preclude us from exercising exclusive rights over that intellectual property; ● we may not develop or in-license additional proprietary technologies that are patentable; ● we may not be able to obtain and maintain necessary licenses on commercially reasonable terms, or at all; and ● the patents of others may have an adverse effect on our business.
Nor is it clear whether other legislative changes will be adopted, if any, or how such changes would affect the demand for the Pharmaceutical Companies’ products if they were to receive regulatory approval. 52 In addition, other legislative changes have been proposed and adopted since the ACA was enacted. On August 2, 2011, the U.S.
Nor is it clear whether other legislative changes will be adopted, if any, or how such changes would affect the demand for the Pharmaceutical Companies’ products if they were to receive regulatory approval. In addition, other legislative changes have been proposed and adopted since the ACA was enacted. On August 2, 2011, the U.S.
The Portfolio Companies may, in the future, form or seek strategic alliances, create joint ventures or collaborations, or enter into licensing arrangements with third parties that they believe will complement or augment their development and commercialization efforts with respect to the Pharmaceutical Companies’ product candidates, any future product candidates that we or they may develop, Rafael Medical Devices’ device candidates, and any future device candidates that we or they may develop.
We and the Portfolio Companies may, in the future, form or seek strategic alliances, create joint ventures or collaborations, or enter into licensing arrangements with third parties that they believe will complement or augment their development and commercialization efforts with respect to our and the Pharmaceutical Companies’ product candidates, any future product candidates that we or they may develop, Rafael Medical Devices’ device candidates, and any future device candidates that we or they may develop.
The FDA’s and other regulatory authorities’ policies may change, and additional government regulations may be enacted that could prevent, limit or delay regulatory approval of the Pharmaceutical Companies’ product candidates. We also cannot predict the likelihood, nature or extent of government regulation that may arise from future legislation or administrative action, either in the United States or abroad.
The FDA’s and other regulatory authorities’ policies may change, and additional government regulations may be enacted that could prevent, limit or delay regulatory approval of our or the Pharmaceutical Companies’ product candidates. We also cannot predict the likelihood, nature or extent of government regulation that may arise from future legislation or administrative action, either in the United States or abroad.
Top-line data also remain subject to audit and verification procedures that may result in the final data being materially different from the preliminary data we and/or Rafael Medical Devices previously published. Even complete data from an individual study or clinical trial may be evaluated different and result in different conclusions based upon subsequent data from a subsequently completed study.
Top-line data also remain subject to audit and verification procedures that may result in the final data being materially different from the preliminary data we and/or Rafael Medical Devices previously published. Even complete data from an individual study or clinical trial may be evaluated differently and result in different conclusions based upon subsequent data from a subsequently completed study.
In addition, if the FDA or a comparable foreign regulatory authority approves a product candidate, the manufacturing processes, labeling, packaging, distribution, adverse event reporting, storage, advertising, promotion, import, export, and recordkeeping for the Pharmaceutical Companies’ products will be subject to extensive and ongoing regulatory requirements and associated personnel and financial commitments.
In addition, if the FDA or a comparable foreign regulatory authority approves a product candidate, the manufacturing processes, labeling, packaging, distribution, adverse event reporting, storage, advertising, promotion, import, export, and recordkeeping for us or the Pharmaceutical Companies’ products will be subject to extensive and ongoing regulatory requirements and associated personnel and financial commitments.
In addition, patent reform legislation may pass in the future that could lead to additional uncertainties and increased costs surrounding the prosecution, enforcement and defense of our patents and pending patent applications. Recent U.S. Supreme Court rulings have narrowed the scope of patent protection available in certain circumstances and weakened the rights of patent owners in certain situations.
In addition, patent reform legislation may pass in the future that could lead to additional uncertainties and increased costs surrounding the prosecution, enforcement and defense of our and their patents and pending patent applications. Recent U.S. Supreme Court rulings have narrowed the scope of patent protection available in certain circumstances and weakened the rights of patent owners in certain situations.
Patent applications in the United States and elsewhere are published approximately 18 months after the earliest filing for which priority is claimed, with such earliest filing date being commonly referred to as the priority date. Therefore, patent applications covering our product candidates or device candidates could have been filed by others without our knowledge.
Patent applications in the United States and elsewhere are published approximately 18 months after the earliest filing for which priority is claimed, with such earliest filing date being commonly referred to as the priority date. Therefore, patent applications covering our and their product candidates or device candidates could have been filed by others without our knowledge.
Additionally, pending patent applications that have been published can, subject to certain limitations, be later amended in a manner that could cover our product candidates, device candidates, or the use of our products. The scope of a patent claim is determined by an interpretation of the law, the written disclosure in a patent, and the patent’s prosecution history.
Additionally, pending patent applications that have been published can, subject to certain limitations, be later amended in a manner that could cover our or their product candidates, device candidates, or the use of our products. The scope of a patent claim is determined by an interpretation of the law, the written disclosure in a patent, and the patent’s prosecution history.
If one or more equity research analysts ceases coverage of our company or fails to publish reports on us regularly, demand for our stock could decrease, which in turn could cause our stock price or trading volume to decline. We may be subject to securities litigation, which is expensive and could divert management attention.
If one or more equity research analysts ceases coverage of our company or fails to publish reports on us regularly, demand for our stock could decrease, which in turn could cause our stock price or trading volume to decline. 79 We may be subject to securities litigation, which is expensive and could divert management attention.
We expect that healthcare reform measures that may be adopted in the future could have a material adverse effect on our and the Pharmaceutical Companies’ industry generally and on our or their ability to maintain or increase sales of any of the Pharmaceutical Companies’ product candidates that are successfully developed, receive regulatory approval for, and are commercialized.
We expect that healthcare reform measures that may be adopted in the future could have a material adverse effect on our and the Pharmaceutical Companies’ industry generally and on our or their ability to maintain or increase sales of any of the Pharmaceutical Companies’ product candidates that are successfully developed, receive regulatory approval, and are commercialized.
As a result, top-line data should be viewed with caution until the final data are available, and then, until the full study results have been completely evaluated by the FDA. From time to time, we and/or Rafael Medical Devices may also disclose interim data from preclinical studies or clinical trials.
As a result, top-line data should be viewed with caution until the final data are available, and then, until the full study results have been completely evaluated by the FDA. 50 From time to time, we and/or Rafael Medical Devices may also disclose interim data from preclinical studies or clinical trials.
Rafael Medical Devices may not maintain adequate insurance for environmental liability or toxic tort claims that may be asserted against them in connection with their storage or disposal of hazardous materials. 63 In addition, Rafael Medical Devices may incur substantial costs in order to comply with current or future environmental, health and safety laws and regulations.
Rafael Medical Devices may not maintain adequate insurance for environmental liability or toxic tort claims that may be asserted against them in connection with their storage or disposal of hazardous materials. In addition, Rafael Medical Devices may incur substantial costs in order to comply with current or future environmental, health and safety laws and regulations.
We also have registered all shares of common stock that we may issue under our equity compensation plans or that are issuable upon exercise of outstanding options. These shares can be freely sold in the public market upon issuance, and once vested, subject to volume limitations applicable to affiliates.
We also have registered all shares of common stock that we may issue under our equity compensation plans or that are issuable upon exercise of outstanding options. These shares can be freely sold in the public market upon issuance, and once vested, are not subject to volume limitations applicable to affiliates.
As a result, top-line data should be viewed with caution until the final data are available, and then, until the full study results have been completely evaluated by the FDA. 35 From time to time, we and/or the Pharmaceutical Companies may also disclose interim data from preclinical studies and clinical trials.
As a result, top-line data should be viewed with caution until the final data are available, and then, until the full study results have been completely evaluated by the FDA. From time to time, we and/or the Pharmaceutical Companies may also disclose interim data from preclinical studies and clinical trials.
If the commercial launch of a product candidate that has received regulatory approval for which the Pharmaceutical Companies recruit a sales force and establish marketing capabilities is delayed or does not occur for any reason, they would have prematurely or unnecessarily incurred these commercialization expenses.
If the commercial launch of a product candidate that has received regulatory approval for which we or the Pharmaceutical Companies recruit a sales force and establish marketing capabilities is delayed or does not occur for any reason, they would have prematurely or unnecessarily incurred these commercialization expenses.
We can give no assurance that all of the potentially relevant art relating to our patents and patent applications has been found; overlooked prior art could be used by a third party to challenge the validity, enforceability, and scope of our patents or prevent a patent from issuing from a pending patent application.
We and they can give no assurance that all of the potentially relevant art relating to our patents and patent applications has been found; overlooked prior art could be used by a third party to challenge the validity, enforceability, and scope of our patents or prevent a patent from issuing from a pending patent application.
Outside of the United States, patents we own or license may become subject to patent opposition or similar proceedings, which may result in loss of scope of some claims or the entire patent. In addition, such proceedings are very complex and expensive and may divert our management’s attention from our core business.
Outside of the United States, patents we or they own or license may become subject to patent opposition or similar proceedings, which may result in loss of scope of some claims or the entire patent. In addition, such proceedings are very complex and expensive and may divert our management’s attention from our core business.
Any claims we assert against perceived infringers could provoke these parties to assert counterclaims against us or them alleging that we infringe their patents. In patent litigation in the United States, defendant counterclaims alleging invalidity or unenforceability are commonplace. The outcome following legal assertions of invalidity and unenforceability is unpredictable.
Any claims we and they assert against perceived infringers could provoke these parties to assert counterclaims against us or them alleging that we infringe their patents. In patent litigation in the United States, defendant counterclaims alleging invalidity or unenforceability are commonplace. The outcome following legal assertions of invalidity and unenforceability is unpredictable.
The resolution of any contract interpretation disagreement that may arise could affect the scope of our rights to the relevant intellectual property or technology, or affect financial or other obligations under the relevant agreement, either of which could have a material adverse effect on our business, financial condition, results of operations and prospects.
The resolution of any contract interpretation disagreement that may arise could affect the scope of our and their rights to the relevant intellectual property or technology, or affect financial or other obligations under the relevant agreement, either of which could have a material adverse effect on our business, financial condition, results of operations and prospects.
It is difficult to predict whether or how these orders will be rescinded and replaced under the current or future Administrations. The policies and priorities of any Administration and the U.S. Congress are unknown and could materially impact the regulations governing the Pharmaceutical Companies’ product candidates.
It is difficult to predict whether or how these orders will be rescinded and replaced under the current or future Administrations. The policies and priorities of any Administration and the U.S. Congress are unknown and could materially impact the regulations governing our or the Pharmaceutical Companies’ product candidates.
The Pharmaceutical Companies’ or Rafael Medical Devices’ failure or any failure by these third parties to comply with these regulations or to recruit a sufficient number of patients may require them to repeat clinical trials and/or to perform additional clinical studies, which would delay the regulatory approval process.
We, the Pharmaceutical Companies’ or Rafael Medical Devices’ failure or any failure by these third parties to comply with these regulations or to recruit a sufficient number of patients may require them to repeat clinical trials and/or to perform additional clinical studies, which would delay the regulatory approval process.
Patients treated with oncology product candidates may also be undergoing surgical, radiation and/or chemotherapy treatments, which can cause side effects or adverse events that are unrelated to the product candidate but may still impact the risk-benefit profile of the product candidate and the success of clinical trials.
Patients treated with product candidates may also be undergoing surgical, radiation and/or chemotherapy treatments, which can cause side effects or adverse events that are unrelated to the product candidate but may still impact the risk-benefit profile of the product candidate and the success of clinical trials.
If that occurs, Rafael Medical Devices or its collaborators will not be able, or may be delayed in their efforts, to commercialize Rafael Medical Devices’ device candidates. 61 Product liability lawsuits against Rafael Medical Devices or their collaborators or us could cause substantial liabilities and could limit commercialization of any medical devices that Rafael Medical Devices or their collaborators may develop.
If that occurs, Rafael Medical Devices or its collaborators will not be able, or may be delayed in their efforts, to commercialize Rafael Medical Devices’ device candidates. Product liability lawsuits against Rafael Medical Devices or their collaborators or us could cause substantial liabilities and could limit commercialization of any medical devices that Rafael Medical Devices or their collaborators may develop.
In addition, in a patent infringement proceeding, there is a risk that a court will decide that a patent of ours is invalid or unenforceable, in whole or in part, and that we do not have the right to stop the other party from exploiting the claimed subject matter at issue.
In addition, in a patent infringement proceeding, there is a risk that a court will decide that a patent of ours or theirs is invalid or unenforceable, in whole or in part, and that we do not have the right to stop the other party from exploiting the claimed subject matter at issue.
It is not uncommon for a manufacturer of a previously approved product to file a citizen petition with the FDA seeking to delay approval of, or impose additional approval requirements for, pending competing products. If successful, such petitions can significantly delay, or even prevent, the approval of a new product.
It also is not uncommon for a manufacturer of a previously approved product to file a citizen petition with the FDA seeking to delay approval of, or impose additional approval requirements for, pending competing products. If successful, such petitions can significantly delay, or even prevent, the approval of a new product.
The Pharmaceutical Companies may not be able to obtain orphan drug designation or obtain or maintain the benefits associated with orphan drug designation, such as orphan drug exclusivity and, even if they do, that exclusivity may not prevent the FDA or other comparable foreign regulatory authorities from approving competing products.
We and the Pharmaceutical Companies may not be able to obtain orphan drug designation or obtain or maintain the benefits associated with orphan drug designation, such as orphan drug exclusivity and, even if they do, that exclusivity may not prevent the FDA or other comparable foreign regulatory authorities from approving competing products.
The Portfolio Companies may not directly control the manufacturing process of, and may be completely dependent on, contract manufacturing partners for compliance with cGMP requirements and any other regulatory requirements of the FDA or other regulatory authorities for the manufacture of product candidates and device candidates and of any products that receive regulatory approval or clearance.
We or the Portfolio Companies may not directly control the manufacturing process of, and may be completely dependent on, contract manufacturing partners for compliance with cGMP requirements and any other regulatory requirements of the FDA or other regulatory authorities for the manufacture of product candidates and device candidates and of any products that receive regulatory approval or clearance.
Our success depends on our ability to develop, manufacture, market, and sell our product candidates and device candidates, if approved, and our delivery of services and use of proprietary technologies without alleged or actual infringement, misappropriation or other violation of the patents and other intellectual property rights of third parties.
Our and their success depends on our and their ability to develop, manufacture, market, and sell our and their product candidates and device candidates, if approved, and our and their delivery of services and use of proprietary technologies without alleged or actual infringement, misappropriation or other violation of the patents and other intellectual property rights of third parties.
An adverse outcome in a litigation or proceeding involving our patents could limit our ability to assert our patents against those parties or other competitors, and may curtail or preclude our ability to exclude third parties from making, using, importing, and selling similar or competitive products, services, or technologies.
An adverse outcome in a litigation or proceeding involving our or their patents could limit our ability to assert our patents against those parties or other competitors, and may curtail or preclude our ability to exclude third parties from making, using, importing, and selling similar or competitive products, services, or technologies.
If we fail in prosecuting or defending any such claims, in addition to paying monetary damages, we may lose valuable intellectual property rights or personnel. Such intellectual property rights could be awarded to a third party, and we could be required to obtain a license from such third party to commercialize our technology or products.
If we or they fail in prosecuting or defending any such claims, in addition to paying monetary damages, we may lose valuable intellectual property rights or personnel. Such intellectual property rights could be awarded to a third party, and we or they could be required to obtain a license from such third party to commercialize our technology or products.
Even after approval, marketing authorization, or clearance for Rafael Medical Devices’ products is obtained, they and the products are subject to extensive postmarket regulation by the FDA, including with respect to advertising, marketing, labeling, manufacturing, distribution, import, export, and clinical evaluation.
Even after approval, marketing authorization, or clearance for Rafael Medical Devices’ products is obtained, they and their products are subject to extensive postmarket regulation by the FDA, including with respect to advertising, marketing, labeling, manufacturing, distribution, import, export, and clinical evaluation.
Nevertheless, the Portfolio Companies are responsible for ensuring that each of their studies is conducted in accordance with the applicable protocol, legal and regulatory requirements, and scientific standards, and our reliance on third parties does not relieve us of our regulatory responsibilities.
Nevertheless, we and the Portfolio Companies are responsible for ensuring that each of their studies is conducted in accordance with the applicable protocol, legal and regulatory requirements, and scientific standards, and our reliance on third parties does not relieve us of our regulatory responsibilities.
We seek to protect our respective trade secrets, in part, by entering into non-disclosure and confidentiality agreements with parties who have access to them prior to disclosing our proprietary information, such as our consultants and vendors, or our former or current employees.
We and they seek to protect our respective trade secrets, in part, by entering into non-disclosure and confidentiality agreements with parties who have access to them prior to disclosing our proprietary information, such as our consultants and vendors, or our former or current employees.
Such a license may not be available on commercially reasonable terms or at all. Even if we are successful in prosecuting or defending against such claims, litigation could result in substantial costs and be a distraction to our management and scientific personnel.
Such a license may not be available on commercially reasonable terms or at all. Even if we and they are successful in prosecuting or defending against such claims, litigation could result in substantial costs and be a distraction to our management and scientific personnel.
Disputes regarding ownership or inventorship of intellectual property can also arise in other contexts, such as collaborations and sponsored research. We may be subject to claims that former collaborators or other third parties have an ownership interest in our patents or other intellectual property.
Disputes regarding ownership or inventorship of intellectual property can also arise in other contexts, such as collaborations and sponsored research. We and they may be subject to claims that former collaborators or other third parties have an ownership interest in our patents or other intellectual property.
The Pharmaceutical Companies’ and Rafael Medical Devices’ relationships with customers, physicians, and third-party payors may be subject, directly or indirectly, to federal and state healthcare fraud and abuse laws, false claims laws, health information privacy and security laws, and other healthcare laws and regulations.
Our, the Pharmaceutical Companies’ and Rafael Medical Devices’ relationships with customers, physicians and third-party payors may be subject, directly or indirectly, to federal and state healthcare fraud and abuse laws, false claims laws, health information privacy and security laws, and other healthcare laws and regulations.
The patent positions of biopharmaceutical companies can be highly uncertain and involve complex legal, scientific, and factual questions for which important legal principles remain unresolved. As a result, the issuance, scope, validity, enforceability, and commercial value of our patent rights may be uncertain.
The patent positions of biopharmaceutical companies can be highly uncertain and involve complex legal, scientific, and factual questions for which important legal principles remain unresolved. As a result, the issuance, scope, validity, enforceability, and commercial value of our and their patent rights may be uncertain.
Competitors may use our technologies in jurisdictions where we have not obtained patent protection to develop such competitors’ own products and may also export infringing products to territories where we have patent protection, but where enforcement is not as strong as that in the United States.
Competitors may use our and their technologies in jurisdictions where we have not obtained patent protection to develop such competitors’ own products and may also export infringing products to territories where we have patent protection, but where enforcement is not as strong as that in the United States.
Any of these events could prevent the Pharmaceutical Companies from achieving or maintaining market acceptance of the particular product candidate, if approved, and could significantly harm the standing and reputation of the Pharmaceutical Companies among health-care providers and patients, and could seriously harm our business.
Any of these events could prevent us or the Pharmaceutical Companies from achieving or maintaining market acceptance of the particular product candidate, if approved, could significantly harm the standing and reputation of the Pharmaceutical Companies among health-care providers and patients, and could seriously harm our business.
The regulatory approval processes of the FDA and comparable foreign regulatory authorities are lengthy, time consuming and inherently unpredictable, and if the Pharmaceutical Companies are ultimately unable to obtain regulatory approval for their product candidates, our or their business will be substantially harmed.
The regulatory approval processes of the FDA and comparable foreign regulatory authorities are lengthy, time consuming and inherently unpredictable, and if the Pharmaceutical Companies are ultimately unable to obtain regulatory approval for their product candidates, our and their business will be substantially harmed.
We may choose not to seek patent protection for certain innovations or products and may choose not to pursue patent protection in certain jurisdictions, and, under the laws of certain jurisdictions, patents or other intellectual property rights may be unavailable or limited in scope and, in any event, any patent protection we obtain may be limited.
We and they may choose not to seek patent protection for certain innovations or products and may choose not to pursue patent protection in certain jurisdictions, and, under the laws of certain jurisdictions, patents or other intellectual property rights may be unavailable or limited in scope and, in any event, any patent protection we or they obtain may be limited.
For example, we cannot be certain that such activities by these licensors have been or will be conducted diligently or in compliance with applicable laws and regulations or will result in valid and enforceable patents and other intellectual property rights.
For example, we and they cannot be certain that such activities by these licensors have been or will be conducted diligently or in compliance with applicable laws and regulations or will result in valid and enforceable patents and other intellectual property rights.
The Leahy-Smith Act and its implementation could increase the uncertainties and costs surrounding the prosecution of our patent applications and the enforcement or defense of our issued patents, all of which could have a material adverse effect on our business and financial condition.
The Leahy-Smith Act and its implementation could increase the uncertainties and costs surrounding the prosecution of our and their patent applications and the enforcement or defense of our issued patents, all of which could have a material adverse effect on our business and financial condition.
However, we may be unable to acquire or in-license intellectual property rights relating to, or necessary for, any such products or technology from third parties on commercially reasonable terms or at all. In that event, we may be unable to develop or commercialize such products or technology.
However, we or they may be unable to acquire or in-license intellectual property rights relating to, or necessary for, any such products or technology from third parties on commercially reasonable terms or at all. In that event, we or they may be unable to develop or commercialize such products or technology.
Numerous third-party patents exist in the fields relating to our products and services, and it is difficult for industry participants, including us and them, to identify all third-party patent rights relevant to our product candidates, device candidates, services, and technologies.
Numerous third-party patents exist in the fields relating to our and their products and services, and it is difficult for industry participants, including us and them, to identify all third-party patent rights relevant to our product candidates, device candidates, services, and technologies.
These products may compete with our product candidates or device candidates, and our patents or other intellectual property rights may not be effective or sufficient to prevent such competitors from competing. Accordingly, our efforts to protect our intellectual property rights in such countries may be inadequate.
These products may compete with our and their product candidates or device candidates, and our patents or other intellectual property rights may not be effective or sufficient to prevent such competitors from competing. Accordingly, our and their efforts to protect our intellectual property rights in such countries may be inadequate.
The degree of future protection for our proprietary rights is uncertain because legal means afford only limited protection and may not adequately protect our rights or permit us to gain or keep a competitive advantage.
The degree of future protection for our and their proprietary rights is uncertain because legal means afford only limited protection and may not adequately protect our rights or permit us to gain or keep a competitive advantage.
Despite these efforts, however, any of these parties may breach the agreements and disclose our trade secrets and other unpatented or unregistered proprietary information, and once disclosed, we are likely to lose trade secret protection.
Despite these efforts, however, any of these parties may breach the agreements and disclose our or their trade secrets and other unpatented or unregistered proprietary information, and once disclosed, we are likely to lose trade secret protection.
If such third parties succeed in registering or developing common law rights in such trademarks, and if we are not successful in challenging such third-party rights, we may not be able to use these trademarks to market our products in those countries.
If such third parties succeed in registering or developing common law rights in such trademarks, and if we and they are not successful in challenging such third-party rights, we may not be able to use these trademarks to market our products in those countries.
If these third parties do not successfully carry out their contractual duties or obligations or meet expected deadlines, if they need to be replaced, or if the quality or accuracy of the preclinical and/or clinical data they obtain is compromised due to the failure to adhere to preclinical or clinical protocols or regulatory requirements or for other reasons, the Pharmaceutical Companies’ and Rafael Medical Devices’ preclinical studies and clinical trials may be extended, delayed or terminated, and they may not be able to complete development of, obtain regulatory approval of, or successfully commercialize their product candidates or device candidates.
If these third parties do not successfully carry out their contractual duties or obligations or meet expected deadlines, if they need to be replaced, or if the quality or accuracy of the nonclinical and preclinical and/or clinical data they obtain is compromised due to the failure to adhere to nonclinical and preclinical or clinical protocols or regulatory requirements or for other reasons, our, the Pharmaceutical Companies’ and Rafael Medical Devices’ nonclinical and preclinical studies and clinical trials may be extended, delayed or terminated, and they may not be able to complete development of, obtain regulatory approval of, or successfully commercialize their product candidates or device candidates.
To achieve commercial success for any approved medicine for which the Pharmaceutical Companies retain sales and marketing responsibilities, they must either develop a sales and marketing organization or outsource these functions to other third parties.
To achieve commercial success for any approved medicine for which we or the Pharmaceutical Companies retain sales and marketing responsibilities, they must either develop a sales and marketing organization or outsource these functions to other third parties.

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Item 1C. Cybersecurity

Cybersecurity — threats and controls disclosure

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Biggest changeThroughout the year, we also regularly train our employees on cybersecurity awareness, confidential information protection and simulated phishing attacks. 97 Our cybersecurity risk management extends to risks associated with our use of third-party service providers. For instance, we conduct risk and compliance assessments of third-party service providers that request access to our information assets.
Biggest changeThroughout the year, we also regularly train our employees on cybersecurity awareness, confidential information protection and simulated phishing attacks. Our cybersecurity risk management extends to risks associated with our use of third-party service providers. For instance, we conduct risk and compliance assessments of third-party service providers that request access to our information assets.

Item 3. Legal Proceedings

Legal Proceedings — active lawsuits and investigations

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Biggest changeItem 3. Legal Proceedings Legal proceedings disclosure is presented in Note 21 to our Consolidated Financial Statements included in Item 8 to Part II of this Annual Report. The Company may from time to time be subject to legal proceedings that may arise in the ordinary course of business.
Biggest changeItem 3. Legal Proceedings Legal proceedings disclosure is presented in Note 23 to our Consolidated Financial Statements included in included in Item 8 to Part II of this Annual Report. The Company may from time to time be subject to legal proceedings that may arise in the ordinary course of business.
Although there can be no assurance in this regard, other than noted above, the Company does not expect any of those legal proceedings to have a material adverse effect on the Company’s results of operations, cash flows or financial condition. Item 4. Mine Safety Disclosures Not applicable. 98 Part II
Although there can be no assurance in this regard, other than noted above, the Company does not expect any of those legal proceedings to have a material adverse effect on the Company’s results of operations, cash flows or financial condition. Item 4. Mine Safety Disclosures Not applicable. 80 Part II

Item 4. Mine Safety Disclosures

Mine Safety Disclosures — required of mining issuers

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Biggest changeItem 4. Mine Safety Disclosures. 98 Part II Item 5. Market for Registrant’s Common Equity, Related Stockholder Matters and Issuer Purchases of Equity Securities. 99 Item 6. [Reserved]. 99 Item 7A. Quantitative and Qualitative Disclosures about Market Risk. 100 Item 7. Management’s Discussion and Analysis of Financial Condition and Results of Operations. 100 Item 8.
Biggest changeItem 4. Mine Safety Disclosures 80 Part II Item 5. Market for Registrant’s Common Equity, Related Stockholder Matters and Issuer Purchases of Equity Securities 81 Item 6. [Reserved] 81 Item 7A. Quantitative and Qualitative Disclosures about Market Risks 90 Item 7. Management's Discussion and Analysis of Financial Condition and Results of Operations 82 Item 8.

Item 5. Market for Registrant's Common Equity

Market for Common Equity — stock, dividends, buybacks

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Biggest changeWe do not anticipate paying dividends on our common stock unless and until we achieve sustainable profitability (after satisfying all of our operational needs) and retain certain minimum cash reserves. Distributions will be subject to the need to retain earnings for investment in growth opportunities or the acquisition of complementary assets.
Biggest changeOn October 27, 2025, the last sales price reported on the NYSE for the Class B common stock was $1.35 per share. We do not anticipate paying dividends on our common stock unless and until we achieve sustainable profitability (after satisfying all of our operational needs) and retain certain minimum cash reserves.
The information required by Item 201(d) of Regulation S-K will be contained in our Proxy Statement for our Annual Stockholders Meeting, which we will file with the Securities and Exchange Commission within 120 days after July 31, 2024, and which is incorporated by reference herein.
The information required by Item 201(d) of Regulation S-K will be contained in our Proxy Statement for our Annual Stockholders Meeting, which we will file with the Securities and Exchange Commission within 120 days after July 31, 2025, and which is incorporated by reference herein.
The payment of dividends in any specific period will be at the sole discretion of our Board of Directors.
Distributions will be subject to the need to retain earnings for investment in growth opportunities or the acquisition of complementary assets. The payment of dividends in any specific period will be at the sole discretion of our Board of Directors.
The number of holders of record of our Class B common stock does not include the number of persons whose shares are in nominee or in “street name” accounts through brokers. On November 5, 2024, the last sales price reported on the NYSE for the Class B common stock was $1.81 per share.
Jonas has voting and dispositive power over all shares of Class A common stock. The number of holders of record of our Class B common stock does not include the number of persons whose shares are in nominee or in “street name” accounts through brokers.
Removed
On November 5, 2024, there were 249 holders of record of our Class B common stock and one holder of record of our Class A common stock. Howard Jonas has voting and dispositive power over all shares of Class A common stock.
Added
Warrants to purchase our Class B common stock trades on the NYSE American under the symbol “RFL-WT.” Trading commenced on April 1, 2025. On October 23, 2025, there were 289 holders of record of our Class B common stock and one holder of record of our Class A common stock. Howard S.
Added
As of October 23, 2025, we had outstanding publicly-traded Warrants to purchase an aggregate of 380,253 shares of our common stock (the “Public Warrants”) at an exercise price of $14.19 per share held by [to update] holders of record.
Added
The Warrants were initially issued by Cyclo on December 11, 2020 in connection with its underwritten public offering and, in connection with the merger with Cyclo, were automatically converted to warrants to purchase shares of Rafael’s Class B common stock with the exercise price and number of shares issuable on exercise adjusted as per the exchange ratio used in the merger.
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The Public Warrants are exercisable at any time during the five years following the date of the original issuance of the warrants to purchase Cyclo common stock, expiring at 5:00 pm EST on December 11, 2025. On October 27, 2025, the last sales price reported on the NYSE American for the Public Warrants was $.08 per share.

Item 7. Management's Discussion & Analysis

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

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Biggest changeConsolidated income (loss) and expenses for our Real Estate segment were as follows: Year Ended July 31, Change 2024 2023 $ % (in thousands) Rental – Third Party $ 174 $ 171 $ 3 2 % Rental – Related Party 108 108 — — % General and administrative (142 ) (138 ) (4 ) (3 )% Depreciation and amortization (60 ) (63 ) 3 5 % Income from operations $ 80 $ 78 $ 2 3 % 103 Consolidated Operations Our consolidated income and expense line items below loss from operations were as follows: Year Ended July 31, Change 2024 2023 $ % (in thousands) Loss from operations $ (102,627 ) $ (15,043 ) $ (87,584 ) (582 )% Interest income 2,383 3,253 (870 ) (27 )% Impairment of investments - Other Pharmaceuticals — (334 ) 334 100 % Loss on initial investment in Day Three upon acquisition (1,633 ) — (1,633 ) (100 )% Realized gain on available-for-sale securities 1,772 154 1,618 1051 % Realized gain (loss) on investment in equity securities (46 ) 309 (355 ) (115 )% Realized gain on investment - Cyclo 424 — 424 (100 )% Unrealized gain on equity securities — 33 (33 ) (100 )% Unrealized gain on investment - Cyclo 37 2,663 (2,626 ) 100 % Unrealized gain on convertible notes receivable, due from Cyclo 1,191 — 1,191 100 % Unrealized gain on investment - Hedge Funds 63 220 (157 ) (71 )% Recovery of receivables from Cornerstone 31,305 — 31,305 100 % Interest expense (248 ) — (248 ) (100 )% Other income 118 — 118 100 % Loss from continuing operations before income taxes (67,261 ) (8,745 ) (58,516 ) (669 )% Benefit from income taxes 2,680 255 2,425 951 % Equity in loss of Day Three (422 ) (203 ) (219 ) 108 % Consolidated net loss from continuing operations (65,003 ) (8,693 ) (56,310 ) (648 )% Income from discontinued operations related to 520 Property — 6,478 (6,478 ) 100 % Net loss attributable to noncontrolling interests (30,593 ) (339 ) (30,254 ) (8924 )% Net loss attributable to Rafael Holdings, Inc. $ (34,410 ) $ (1,876 ) $ (32,534 ) (1734 )% Interest income and realized gains on available-for-sale securities.
Biggest changeThe increase in general and administrative expenses during the year ended July 31, 2025 compared to the year ended July 31, 2024 is primarily the result of an increase in accounting and legal fees as well as building operating expenses and office rent. 85 Consolidated Operations Our consolidated income and expense line items below loss from operations were as follows: Year Ended July 31, Change 2025 2024 $ % (in thousands) Loss from operations $ (29,159 ) $ (102,627 ) $ 73,468 72 % Interest income 1,996 2,383 (387 ) (16 )% Loss on initial investment in Day Three upon acquisition — (1,633 ) 1,633 (100 )% Realized gain on available-for-sale securities 178 1,772 (1,594 ) (90 )% Realized loss on investment in equity securities — (46 ) 46 (100 )% Realized gain on investment - Cyclo — 424 (424 ) (100 )% Unrealized (loss) gain on investment - Cyclo (5,144 ) 37 (5,181 ) 14,003 % Unrealized (loss) gain on convertible notes receivable, due from Cyclo (719 ) 1,191 (1,910 ) (160 )% Unrealized gain on investment - Hedge Funds — 63 (63 ) (100 )% Recovery of receivables from Cornerstone — 31,305 (31,305 ) (100 )% Interest expense (658 ) (248 ) (410 ) (165 )% Other income, net 310 118 192 163 % Loss before income taxes (33,196 ) (67,261 ) 34,065 51 % Benefit from income taxes 2,553 2,680 (127 ) (5 )% Equity in loss of Day Three — (422 ) 422 (100 )% Consolidated net loss (30,643 ) (65,003 ) 34,360 53 % Net loss attributable to noncontrolling interests (123 ) (30,593 ) 30,470 100 % Net loss attributable to Rafael Holdings, Inc. $ (30,520 ) $ (34,410 ) $ 3,890 11 % Interest income.
Investing Activities Cash used in investing activities for the year ended July 31, 2024 was primarily due to purchases of available-for-sale securities of approximately $155.7 million, purchase of $4.0 million in convertible notes receivable from Cyclo, and the investment in Cyclo common stock and warrants of $6.8 million, partially offset by proceeds of $153.4 million from sales and maturities of available-for-sale securities and $2.5 million in proceeds from hedge funds.
Cash used in investing activities for the year ended July 31, 2024 was primarily due to purchases of available-for-sale securities of approximately $155.7 million, purchases of $4.0 million in convertible notes receivable, due from Cyclo, and the investment in Cyclo common stock and warrants of $6.8 million, partially offset by proceeds of $153.4 million from sales and maturities of available-for-sale securities and $2.5 million in proceeds from hedge funds.
In October 2021, Cornerstone received negative results of its Avenger 500 Phase 3 study for Devimistat in pancreatic cancer as well as a recommendation to stop its ARMADA 2000 Phase 3 study due to a determination that the trial would unlikely achieve its primary endpoint (the “Data Events”).
In October 2021, Cornerstone received negative results of its Avenger 500 Phase 3 study for Devimistat in pancreatic cancer as well as a recommendation to stop its ARMADA 2000 Phase 3 study due to a determination that the trial would be unlikely to achieve its primary endpoint (the “Data Events”).
Due to the Data Events, RP Finance fully impaired its then debt and equity investments in Cornerstone. 101 On March 13, 2024, Cornerstone consummated a restructuring of its outstanding debt and equity interests (the “Cornerstone Restructuring”).
Due to the Data Events, RP Finance fully impaired its then debt and equity investments in Cornerstone. On March 13, 2024, Cornerstone consummated a restructuring of its outstanding debt and equity interests (the “Cornerstone Restructuring”).
Barer’s majority owned subsidiary, Farber Partners, LLC (“Farber”), was formed around one such agreement with Princeton University’s Office of Technology Licensing (“Princeton”) for technology from the laboratory of Professor Joshua Rabinowitz, in the Department of Chemistry, Princeton University, for an exclusive worldwide license to its SHMT (serine hydroxymethyltransferase) inhibitor program.
Barer’s majority owned subsidiary, Farber Partners, LLC (“Farber”), was formed around one such agreement with Princeton University’s Office of Technology Licensing (“Princeton”) for technology from the laboratory of Dr. Joshua Rabinowitz, in the Department of Chemistry, Princeton University, for an exclusive worldwide license to its SHMT (serine hydroxymethyltransferase) inhibitor program.
Critical Accounting Estimates We have chosen accounting policies that we believe are appropriate to accurately and fairly report our operating results and financial condition in conformity with U.S. GAAP. We apply these accounting policies in a consistent manner. Our significant accounting policies are discussed in Note 2, “Summary of Significant Accounting Policies,” in our accompanying consolidated financial statements.
Critical Accounting Estimates We have chosen accounting policies that we believe are appropriate to accurately and fairly report our operating results and financial condition in conformity with U.S. GAAP. We apply these accounting policies in a consistent manner. Our significant accounting policies are discussed in Note 2, “Summary of Significant Accounting Policies”, in our accompanying consolidated financial statements.
In performing the qualitative assessment, the Company considers certain events and circumstances specific to the reporting unit and the entity as a whole, such as macroeconomic conditions, industry and market considerations, overall financial performance and cost factors when evaluating whether it is more likely than not that the fair value of the reporting unit is less than its carrying amount.
In performing the qualitative assessment, management considers certain events and circumstances specific to the reporting unit and the entity as a whole, such as macroeconomic conditions, industry and market considerations, overall financial performance and cost factors when evaluating whether it is more likely than not that the fair value of any of the reporting units is less than its carrying amount.
Initial patient enrollment in the U.S. Phase I study commenced in September 2017, and in May 2020 Cyclo announced Top Line data demonstrating Trappsol® Cyclo™ was well tolerated in this study. Cyclo is currently conducting a Phase III Clinical Trial Evaluating Trappsol ® Cyclo™ in Pediatric and Adult Patients with Niemann-Pick Disease, Type C1.
Initial patient enrollment in the U.S. Phase I study commenced in September 2017 and in May 2020, Cyclo announced Top Line data indicating Trappsol ® Cyclo™ was well tolerated in this study. Cyclo is currently conducting a Phase 3 Clinical Trial evaluating Trappsol ® Cyclo™ in Pediatric and Adult Patients with Niemann-Pick Disease, Type C1.
Cyclo’s lead drug candidate is Trappsol® Cyclo™ (hydroxypropyl beta cyclodextrin), a treatment for Niemann-Pick Disease, type C1 (“NPC1”). NPC1 is a rare and fatal autosomal recessive genetic disease resulting in disrupted cholesterol metabolism that impacts the brain, lungs, liver, spleen, and other organs. In January 2017 the FDA granted Fast Track designation to Trappsol® Cyclo™ for the treatment of NPC1.
Cyclo’s lead drug candidate is Trappsol ® Cyclo™ (hydroxypropyl beta cyclodextrin), a treatment for NPC1. NPC1 is a rare and fatal autosomal recessive genetic disease resulting in disrupted cholesterol metabolism that impacts the brain, lungs, liver, spleen, and other organs. In January 2017, the FDA granted Fast Track designation to Trappsol ® Cyclo™ for the treatment of NPC1.
We evaluate the performance of our Healthcare segment based primarily on research and development efforts and results of clinical trials, and our Infusion Technology and Real Estate segments based primarily on results of operations. Accordingly, the income and expense line items below loss from operations are only included in the discussion of consolidated results of operations.
We evaluate the performance of our Healthcare segment based primarily on results of clinical trials and loss from operations, and the Infusion Technology and Real Estate segments based primarily on revenues and income (loss) from operations. Accordingly, the income and expense line items below loss from operations are only included in the discussion of consolidated results of operations.
In the quantitative assessment, the Company compares the fair value of the reporting unit to its carrying amount, which includes goodwill. If the fair value exceeds the carrying value, no impairment loss exists. If the fair value is less than the carrying amount, a goodwill impairment loss is measured and recorded.
In the quantitative assessment, we compare the fair value of the reporting unit to its carrying amount, which includes goodwill. If the fair value exceeds the carrying value, no impairment loss exists. If the fair value is less than the carrying amount, a goodwill impairment loss is measured and recorded.
Financing Activities Cash used in financing activities for the year ended July 31, 2024 was primarily related to a principal payment of $0.8 million on the installment note acquired during the Day Three Acquisition, partially offset by the proceeds from sale of RMD membership units of $0.9 million.
Cash provided by financing activities for the year ended July 31, 2024 was primarily related to the proceeds from sale of Rafael Medical Devices membership units of $0.9 million, and partially offset by a principal payment of $0.8 million on the installment note acquired during the Day Three Acquisition.
The Company is also permitted to bypass the qualitative assessment and proceed directly to the quantitative test. If the Company chooses to undertake the qualitative assessment and concludes that it is more likely than not that the fair value of the reporting unit is less than its carrying amount, the Company would then proceed to the quantitative impairment test.
We are also permitted to bypass the qualitative assessment and proceed directly to the quantitative test. If we choose to undertake the qualitative assessment and conclude that it is more likely than not that the fair value of a reporting unit is less than its carrying amount, we would then proceed to the quantitative impairment test.
Item 7. Management’s Discussion and Analysis of Financial Condition and Results of Operations This Annual Report contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934, including statements that contain the words “believes,” “anticipates,” “expects,” “plans,” “intends” and similar words and phrases.
Item 7. Management’s Discussion and Analysis of Financial Condition and Results of Operations This Annual Report contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934, including statements that contain the words “believes”, “anticipates”, “expects”, “plans”, “intends” and similar words and phrases.
In April 2023, the Company first invested in Day Three, a company which empowers third-party manufacturers to reimagine their existing cannabis offerings enabling them to bring to market better, cleaner, more precise and predictable versions by utilizing Day Three’s pharmaceutical-grade technology and innovation like Unlokt™.
In April 2023, we first invested in Day Three, a company which empowers third-party manufacturers to reimagine their existing product offerings enabling those third-party manufacturers to bring to market better, cleaner, more precise and predictable versions of their products by utilizing Day Three’s technology and innovation like Unlokt™.
The Company expects its balance of cash and cash equivalents, and available-for-sale securities, to be sufficient to meet our obligations for at least the next 12 months from the filing of this Annual Report on Form 10-K.
We expect the balance of cash and cash equivalents to be sufficient to meet our obligations for at least the next 12 months from the filing of this Annual Report on Form 10-K.
As of July 31, 2024, the Company holds a portion of a commercial building in Jerusalem, Israel as its remaining owned real estate asset. In May 2023, the Company first invested in Cyclo Therapeutics. Cyclo is a clinical-stage biotechnology company that develops cyclodextrin-based products for the potential treatment of neurodegenerative diseases.
As of July 31, 2025, we hold a portion of a commercial building in Jerusalem, Israel as our sole remaining real estate asset. In May 2023, we first invested in Cyclo, a clinical-stage biotechnology company that develops cyclodextrin-based products for the potential treatment of neurodegenerative diseases.
The fair value of identifiable intangible assets is based on detailed valuations that use information and assumptions provided by management, including expected future cash flows. We allocate any excess purchase price over the fair value of the identifiable net assets and liabilities acquired to goodwill. Identifiable intangible assets with finite lives are amortized over their useful lives.
The fair value of identifiable intangible assets, in-process research and development ("IPR&D") and customer relationships, is based on detailed valuations that use information and assumptions provided by management, including expected future cash flows. We allocate any excess purchase price over the fair value of the identifiable net assets and liabilities acquired to goodwill.
(Nasdaq: CYTH), (“Cyclo Therapeutics” or “Cyclo”), a clinical stage biotechnology company dedicated to developing Trappsol® Cyclo™, which is being evaluated in clinical trials for the potential treatment of Niemann-Pick Disease Type C1 (“NPC1”), a rare, fatal and progressive genetic disorder, a majority equity interest in LipoMedix Pharmaceuticals Ltd. (“LipoMedix”), a clinical stage pharmaceutical company, Barer Institute Inc.
Our lead candidate is Trappsol ® Cyclo™, which is being evaluated in clinical trials for the potential treatment of Niemann-Pick Disease Type C1 (“NPC1”), a rare, fatal and progressive genetic disorder. We also hold: (i) a majority equity interest in LipoMedix Pharmaceuticals Ltd. (“LipoMedix”), a clinical stage pharmaceutical company; (ii) Barer Institute Inc.
Recovery of receivables from Cornerstone. We recorded an increase in recovery of receivables from Cornerstone of approximately $31.3 million for the year ended July 31, 2024. See Note 3 to our accompanying consolidated financial statements for more information related to this matter. Benefit from income taxes .
We recorded an increase in recovery of receivables from Cornerstone Pharmaceuticals of approximately $31.3 million for the year ended July 31, 2024. See Note 6 to our accompanying consolidated financial statements for more information related to this matter. 86 Interest expense. Interest expense was $0.7 million and $0.2 million for the years ended July 31, 2025 and 2024, respectively.
The Company owns a 37.5% equity interest in RP Finance LLC (“RP Finance”), which was, until March 13, 2024 (the date of the RP Finance Consolidation, as described in Note 3 to the Consolidated Financial Statements), accounted for under the equity method.
We own a 37.5% equity interest in RP Finance LLC (“RP Finance”), which was, until March 13, 2024 (the date of the RP Finance Consolidation (as described in Note 6 to the Consolidated Financial Statements)), accounted for under the equity method. RP Finance is an entity in which vehicles associated with members of the family of Howard S.
In performing the Company’s annual goodwill impairment test, the Company is permitted to first assess qualitative factors to determine whether it is more likely than not the fair value of the Company’s reporting unit is less than its carrying amount, including goodwill.
The process of evaluating the potential impairment of goodwill requires significant judgment. In performing our annual goodwill impairment test, we are permitted to first assess qualitative factors to determine whether it is more likely than not that the fair value of any of our reporting units is less than its carrying amount, including goodwill.
In addition to its own internal discovery efforts, Barer pursued collaborative research agreements and in-licensing opportunities with leading scientists from top academic institutions.
Barer was comprised of scientists and academic advisors that are experts in cancer metabolism, chemistry, and drug development. In addition to its own internal discovery efforts, Barer pursued collaborative research agreements and in-licensing opportunities with leading scientists from top academic institutions.
In January 2024, the Company entered into a series of transactions with Day Three and certain shareholders, acquiring a controlling interest of Day Three and subsequently consolidating Day Three’s results (the “Day Three Acquisition”). Results of Operations Our business consists of three reportable segments - Healthcare, Infusion Technology, and Real Estate.
In January 2024, we entered into a series of transactions with Day Three and certain of its shareholders, acquiring a controlling interest in Day Three and subsequently consolidating Day Three's results (the “Day Three Acquisition”).
(“Rafael Medical Devices”), an orthopedic-focused medical device company developing instruments to advance minimally invasive surgeries, and a majority interest in Day Three Labs, Inc.
(“Cornerstone”), formerly known as Rafael Pharmaceuticals Inc., a cancer metabolism-based therapeutics company; (iv) a majority interest in Rafael Medical Devices, LLC (“Rafael Medical Devices”), an orthopedic-focused medical device company developing instruments to advance minimally invasive surgeries; and (v) a majority interest in Day Three Labs, Inc.
RP Finance is an entity associated with members of the family of Howard Jonas (Executive Chairman, Chairman of the Board, and controlling stockholder of the Company) which holds 37.5% equity interest of RP Finance. RP Finance holds debt and equity investments in Cornerstone.
Jonas (Executive Chairman, Chief Executive Officer, President, Chairman of the Board, and controlling stockholder of the Company), hold an aggregate 37.5% equity interest. RP Finance holds debt and equity investments in Cornerstone.
The entirety of the expenses in the Healthcare segment relate to the activities of Barer, LipoMedix, Farber, Cornerstone, and Rafael Medical Devices. As of July 31, 2024, we held a 100% interest in Barer, a 95% interest in LipoMedix, a 93% interest in Farber, a 67% interest in Cornerstone, and a 68% interest in Rafael Medical Devices.
As of July 31, 2025, we held a 100% interest in Barer and Cyclo, a 95% interest in LipoMedix, a 93% interest in Farber, a 67% interest in Cornerstone, and a 73% interest in Rafael Medical Devices. Product revenue.
The following discussion should be read in conjunction with the Consolidated Financial Statements and Notes thereto included in Item 8 of this Annual Report. Overview Rafael Holdings, Inc.
The following discussion should be read in conjunction with the Consolidated Financial Statements and Notes thereto included in Item 8 of this Annual Report. Overview Rafael Holdings, Inc. (“Rafael Holdings”, “Rafael”, “we” or the “Company”) is a biotechnology company that develops pharmaceuticals and holds interests in clinical and early-stage companies that develop pharmaceuticals and medical devices.
At that point, the Company will make a determination as to whether or not to file an NDA for Trappsol® Cyclo™. LipoMedix is a clinical stage Israeli company focused on the development of a product candidate that holds the potential to be an innovative, safe, and effective cancer therapy based on liposome delivery.
LipoMedix is a clinical stage company based in Israel that is focused on the development of a product candidate that holds the potential to be an innovative, safe, and effective cancer therapy based on liposome delivery. As of July 31, 2025, our ownership interest in LipoMedix was approximately 95%.
We recognized a loss of approximately $422 and $203 thousand from our ownership interest in Day Three due to operating results for the years ended July 31, 2024 and 2023, respectively. As of January 2, 2024, Day Three is a majority-owned subsidiary which is consolidated. See Note 10 to our accompanying consolidated financial statements for further information regarding the acquisition.
Equity in loss of Day Three. We recognized a loss of $0.4 million from our ownership interest in Day Three due to operating results for the year ended July 31, 2024. As of January 2, 2024, Day Three is a majority-owned subsidiary which is consolidated. Net loss attributable to noncontrolling interests.
The Company regularly monitors current business conditions and other factors including, but not limited to, adverse industry or economic trends and lower projections of profitability that may impact future operating results. The process of evaluating the potential impairment of goodwill requires significant judgement.
Goodwill We assess goodwill for impairment on an annual basis as of May 31, or more frequently when events and circumstances occur indicating that the recorded goodwill may be impaired. Management regularly monitors current business conditions and other factors including, but not limited to, adverse industry or economic trends and lower projections of profitability that may impact future operating results.
The IPR&D acquired as part of the Cornerstone Acquisition, accounted for as an asset acquisition, was expensed immediately as a component of in-process research and development expense in the consolidated statement of operations and comprehensive loss as it had no alternative future use. 108 Off-Balance Sheet Arrangements We do not have any “off-balance sheet arrangements,” as defined in relevant SEC regulations, that are reasonably likely to have a current or future effect on our financial condition, results of operations, liquidity, capital expenditures or capital resources.
Off-Balance Sheet Arrangements We do not have any “off-balance sheet arrangements”, as defined in relevant SEC regulations, that are reasonably likely to have a current or future effect on our financial condition, results of operations, liquidity, capital expenditures or capital resources. 89
We recorded an unrealized gain of $37 thousand and $2.7 million related to the change in fair value in our investment in Cyclo for the years ended July 31, 2024 and 2023, respectively. Unrealized gain on convertible notes receivable, due from Cyclo.
We recorded an unrealized loss of $5.1 million during the year ended July 31, 2025, prior to the Cyclo Merger. We recorded an unrealized gain of $37 thousand for the year ended July 31, 2024. Unrealized (loss) gain on convertible notes receivable, due from Cyclo.
Research and development expenses decreased for the year ended July 31, 2024 as compared to the year ended July 31, 2023. Research and development expenses are derived from activity at Barer, LipoMedix, Farber, Cornerstone, Day Three, and Rafael Medical Devices.
Research and development expenses are derived from activity at Cyclo, Barer, LipoMedix, Farber, Cornerstone, and Rafael Medical Devices.
Net loss attributable to noncontrolling interests. The change in the net loss attributable to noncontrolling interests is primarily attributed to the net loss of Cornerstone which includes $89.9 million in IPR&D expenses.
The change in the net loss attributable to noncontrolling interests is primarily attributed to acquisition of Cornerstone and Day Three and the consolidation of their activity.
In November 2022, the Company resolved to curtail its early-stage development efforts, including pre-clinical research at Barer Institute. Since then, the Company has sought partners for Farber programs and has entered into a license agreement for one of its technologies.
Since then, we have sought partners for Farber programs and has entered into a license agreement for one of its technologies that is in the pre-clinical research stage with the Ludwig Institute of Cancer Research and has transferred majority ownership of another one of its technologies, SHMT, to a new company, Forme Therapeutics, that is being managed by Dr.
Liquidity and Capital Resources As of July 31, Change 2024 2023 $ % (in thousands) Balance Sheet Data: Cash and cash equivalents $ 2,675 $ 21,498 $ (18,823 ) (88 )% Convertible note receivable, related party — 1,921 (1,921 ) (100 )% Convertible note receivable 1,146 — 1,146 100 % Installment note payable 1,700 — 1,700 100 % Working capital 64,988 80,796 (15,808 ) (20 )% Total assets 96,832 98,829 (1,997 ) (2 )% Total equity attributable to Rafael Holdings, Inc. 82,185 100,293 (18,108 ) (18 )% Noncontrolling interests 4,073 (3,664 ) 7,737 211 % Total equity 86,258 96,629 (10,371 ) (11 )% Year Ended July 31, Change 2024 2023 $ % (in thousands) Cash flows used in Operating activities of continuing operations $ (7,802 ) $ (10,247 ) $ 2,445 24 % Investing activities of continuing operations (10,820 ) (26,960 ) 16,140 60 % Financing activities of continuing operations (179 ) (218 ) 39 18 % Effect of exchange rates on cash and cash equivalents (22 ) (146 ) 124 85 % Operating, investing, and financing activities of discontinued operations — 32,532 (32,532 ) (100 )% Decrease in cash and cash equivalents $ (18,823 ) $ (5,039 ) (13,784 ) 274 % 105 Capital Resources As of July 31, 2024, we held cash and cash equivalents of approximately $2.7 million and available-for-sale securities valued at approximately $63.3 million.
Liquidity and Capital Resources As of July 31, Change 2025 2024 $ % Balance Sheet Data: (in thousands) Cash and cash equivalents $ 52,769 $ 2,675 $ 50,094 1873 % Convertible notes receivable classified as available-for-sale 1,858 1,146 712 62 % Installment note payable — 1,700 (1,700 ) (100 )% Working capital 45,114 64,988 (19,874 ) (31 )% Total assets 114,109 96,832 17,277 18 % Total equity attributable to Rafael Holdings, Inc. 94,391 82,185 12,206 15 % Noncontrolling interests 3,980 4,073 (93 ) 2 % Total equity $ 98,371 $ 86,258 $ 12,113 14 % Year Ended July 31, Change 2025 2024 $ % Cash flows (used in) provided by: (in thousands) Operating activities $ (18,924 ) $ (7,802 ) $ (11,122 ) (143 )% Investing activities 44,035 (10,820 ) 54,855 507 % Financing activities 24,830 (179 ) 25,009 13972 % Effect of exchange rates on cash and cash equivalents 153 (22 ) 175 795 % Increase (decrease) in cash and cash equivalents $ 50,094 $ (18,823 ) $ 68,917 (366 )% Capital Resources As of July 31, 2025, we held cash and cash equivalents of approximately $52.8 million.
We recorded an unrealized gain of $1.2 million related to the convertible note receivable due from Cyclo for the year ended July 31, 2024. Unrealized gain on investment - Hedge Fund s. We recorded an unrealized gain of approximately $63 thousand and an unrealized gain of approximately $220 thousand for the years ended July 31, 2024 and 2023, respectively.
We recorded an unrealized loss of $0.7 million for the year ended July 31, 2025, on our convertible notes receivable, due from Cyclo. The outstanding principal and accrued interest on the Cyclo Convertible Notes were forgiven in the Cyclo Merger. Unrealized gain on investment - Hedge Fund s.
The critical accounting policies that involve the most significant management judgments and estimates used in preparation of our consolidated financial statements, or are the most sensitive to change from outside factors, are discussed below. 106 Investments Measured at Fair Value We have elected the fair value option to account for our investment in and convertible notes due from Cyclo. over which we have significant influence.
The critical accounting policies that involve the most significant management judgments and estimates used in preparation of our consolidated financial statements, or are the most sensitive to change from outside factors are: Business Combinations The purchase price for acquisitions are allocated to the assets acquired and liabilities assumed based on their estimated fair values at the date of acquisition.
As a result of the Cornerstone Restructuring, Rafael became a 67% owner of the issued and outstanding common stock of Cornerstone (the “Cornerstone Acquisition”), and Cornerstone became a consolidated subsidiary of Rafael. The Cornerstone Acquisition is accounted for as an acquisition of a variable interest entity that is not a business in accordance with U.S. GAAP.
As a result of the Cornerstone Restructuring, Rafael became a 67% owner of the issued and outstanding common stock of Cornerstone (the “Cornerstone Acquisition”), and Cornerstone became a consolidated subsidiary of Rafael. See Note 6 to the Consolidated Financial Statements for additional information on the Cornerstone Restructuring, Cornerstone Acquisition, and RP Finance Consolidation.
In 2019, the Company established Barer, a preclinical cancer metabolism research operation, to focus on developing a pipeline of novel therapeutic compounds, including compounds designed to regulate cancer metabolism with potentially broader application in other indications beyond cancer. Barer has been comprised of scientists and academic advisors that are experts in cancer metabolism, chemistry, and drug development.
LipoMedix is currently exploring strategic options for its lead candidate, including potential licensing opportunities, collaborations with industry partners, and investigator-initiated studies. 82 In 2019, we established Barer, originally as a preclinical cancer metabolism research operation, to focus on developing a pipeline of novel therapeutic compounds, including compounds designed to regulate cancer metabolism with potentially broader application in other indications beyond cancer.
The Company’s primary focus is to expand our investment portfolio through opportunistic and strategic investments including therapeutics, which address high unmet medical needs. Upon closing of the planned merger with Cyclo, the Company intends to focus its efforts on making Trappsol ® Cyclo™ its lead clinical program. 100 Historically, the Company owned real estate assets.
We also look to expand our investment portfolio through opportunistic and strategic investments including that address high unmet medical needs. We continuously evaluate our other holdings to ensure the focus of our resources are on core assets and specifically the continued development of Trappsol ® Cyclo™. Historically, we owned real estate assets.
Cash used in financing activities for the year ended July 31, 2023 was primarily related to repayment of the $15.0 million note payable in connection with the sale of 520 Property and for payment of taxes related to shares withheld for employee taxes on vesting of shares granted to employees.
Financing Activities Cash used in financing activities for the year ended July 31, 2025 was primarily related to net proceeds from the issuance of common stock in the Rights Offering of $25 million offset by a payment related to shares withheld for employee taxes of $0.2 million.
As of July 31, 2023, the Company recorded $825,000 of the funds received related to the sale within prepaid expenses and other current assets and other liabilities within the consolidated balance sheets. General and administrative expenses . General and administrative expenses consist mainly of payroll, stock-based compensation expense, benefits, facilities, consulting and professional fees.
General and administrative expenses consist mainly of payroll, stock-based compensation expense, benefits, facilities, consulting and professional fees.
Cash used in investing activities for the year ended July 31, 2023 was primarily due to purchases of available-for-sale securities of approximately $204.8 million, the investment in Day Three of $3.0 million, the purchase of investment in Cyclo common stock and warrants of $2.1 million, the loan of $2.0 million to Cornerstone and the purchase of equity securities of $1.6 million.
Investing Activities Cash provided by investing activities for the year ended July 31, 2025 was primarily due to proceeds of $80.7 million from sales and maturities of available-for-sale securities and $2.5 million in proceeds from hedge funds, offset by purchases of available-for-sale securities of approximately $17.0 million, purchases of $19.5 million in convertible notes receivable, due from Cyclo, and net cash used in the Cyclo Merger of 2.7 million.
Research and development expenses increased by $502 thousand during the year ended July 31, 2024 compared to the year ended July 31, 2023 due to the acquisition of Day Three in January 2024.
In addition, legal and other professional fees increased by $0.6 million compared to the year ended July 31, 2024, primarily due to services related to the Cyclo Merger. Research and development expenses. Research and development expenses increased for the year ended July 31, 2025 compared to the year ended July 31, 2024.
Operating Activities Cash used in operating activities decreased by $2.4 million from cash used of $10.2 million for the year ended July 31, 2023 to cash used of $7.8 million for the year ended July 31, 2024, as the increase in the loss from continuing operations was more than offset by the impact from non-cash items, such as $89.9 million in in-process research and development expense, $31.3 million from the recovery of receivables from Cornerstone, and changes in assets and liabilities.
Cash generated from operating assets and liabilities included the collection of interest receivables of $0.5 million and a decrease in prepaid expenses and prepaid clinical costs of $0.9 million. 87 For the year ended July 31, 2024, cash used in operating activities was $7.8 million, impacted by a net loss of $65.0 adjusted for non-cash items totaling $57.8 million.
Interest income was $2.4 million and $3.3 million for the years ended July 31, 2024 and 2023, respectively. The decrease is primarily due to maturity and sales activity which resulted in an increase of realized gains on available-for-sale securities of $1.6 million for the year ended July 31, 2024. Impairment of investments - Other Pharmaceuticals .
We recognized a realized gain of $0.2 million for the year ended July 31, 2025 related to the maturity of certain available-for-sale securities and the sale of our available-for-sale securities in November 2024. We recognized a realized gain on available-for-sale securities of $1.8 million for the year ended July 31, 2024, related to the sale and maturity activity.
The decrease in the net income attributable to discontinued operations for the year ended July 31, 2024 as compared to the year ended July 31, 2023 was due to a gain on the sale of the 520 Property of $6.8 million. See Note 14 to our accompanying consolidated financial statements for further information regarding discontinued operations.
Loss on initial investment in Day Three upon acquisition. We recognized a loss of $0 and $1.6 million on initial investment in Day Three upon acquisition for the years ended July 31, 2025 and 2024. In January 2024, we acquired Day Three. See Note 13 to our accompanying consolidated financial statements for more information. Realized gain on available-for-sale securities.
Healthcare Segment Our consolidated expenses for our Healthcare segment were as follows: Year Ended July 31, Change 2024 2023 $ % (in thousands) General and administrative $ (8,338 ) $ (8,794 ) $ 456 5 % Research and development (3,668 ) (6,312 ) 2,644 42 % IPR&D expense (89,861 ) — (89,861 ) 100 % Depreciation and amortization (165 ) (15 ) (150 ) (1000 )% Loss from operations $ (102,032 ) $ (15,121 ) $ (86,911 ) (575 )% To date, the Healthcare segment has not generated any revenues.
Healthcare segment Results of operations for our Healthcare segment were as follows: Year Ended July 31, Change 2025 2024 $ % (in thousands) Product revenue $ 515 $ — $ 515 100 % Cost of product revenue (28 ) — (28 ) (100 )% General and administrative (13,165 ) (8,338 ) (4,827 ) (58 )% Research and development (12,568 ) (3,668 ) (8,900 ) (243 )% In-process research and development — (89,861 ) 89,861 100 % Depreciation and amortization (48 ) (165 ) 117 71 % Loss from operations $ (25,294 ) $ (102,032 ) $ 76,738 75 % The Healthcare segment is comprised of the activities of Barer, LipoMedix, Farber, Cornerstone, Cyclo, and Rafael Medical Devices.
Removed
(“Rafael Holdings”, “Rafael”, “we” or the “Company”) is a holding company with interests in clinical and early-stage pharmaceutical companies (the “Pharmaceutical Companies”), including an investment in (and planned merger with) Cyclo Therapeutics Inc.
Added
(“Barer”), a wholly-owned cancer research focused entity whose operations have been substantially curtailed; (iii) a majority interest in Cornerstone Pharmaceuticals, Inc.
Removed
(“Barer”), a wholly-owned preclinical cancer metabolism research operation, and a majority interest in Cornerstone Pharmaceuticals, Inc. (“Cornerstone”), formerly known as Rafael Pharmaceuticals Inc., a cancer metabolism-based therapeutics company. We also hold a majority interest in Rafael Medical Devices, LLC.
Added
(“Day Three”), a company which empowers third-party manufacturers to reimagine their existing product offerings by utilizing Day Three’s technology and innovation like Unlokt™. Our primary focus has been the continued development of Trappsol ® Cyclo™ through the completion of its ongoing pivotal Phase 3 clinical trial, the potential filing for regulatory approval and ultimately, if approved, commercialization of the product.
Removed
(“Day Three”), a company which empowers third-party manufacturers to reimagine their existing cannabis offerings enabling them to bring to market better, cleaner, more precise and predictable versions by utilizing Day Three’s pharmaceutical-grade technology and innovation like Unlokt™. Day Three and Rafael Medical Devices, together with the Pharmaceutical Companies, represent our “Portfolio Companies”).
Added
On March 25, 2025, we consummated the Merger with Cyclo whereby Cyclo became a wholly-owned subsidiary of the Company. See Note 3 to our Consolidated Financial Statements for more information on the Merger with Cyclo.
Removed
In November 2022, the Company resolved to curtail its early-stage development efforts, including pre-clinical research at Barer. The decision was taken to reduce spending as the Company focuses on exploring strategic opportunities. Since then, the Company has sought partners for programs at Farber and has entered into a license agreement for one of its technologies.
Added
As needed, we provide debt or equity funding to Lipomedix to support its development and clinical efforts.
Removed
In 2020, the Company sold an office building located in Piscataway, New Jersey and, on August 22, 2022, the Company sold the building at 520 Broad Street in Newark, New Jersey that serves as headquarters for the Company and several tenants and an associated public garage (the “520 Property”).
Added
In November 2022, we resolved to curtail our early-stage development efforts, including pre-clinical research at Barer.
Removed
See Notes 11 and 12 to the Consolidated Financial Statements for more information on the Company’s investments in Cyclo. As discussed in more detail below, on August 21, 2024, the Company entered into a merger agreement with Cyclo.
Added
Joshua Rabinowitz with the goal of developing SHMT. Going forward, we expect that Barer will primarily operate as an entity holding interest in these two cancer-focused opportunities.
Removed
In the event the merger is consummated, the Company intends to fund the TransportNPC phase III clinical trial, evaluating Trappsol® Cyclo™ in Niemann Pick C, to its interim analysis in the middle of 2025 and focus its efforts on Trappsol ® Cyclo™ as its lead clinical program.
Added
The Company is currently reviewing Cornerstone’s current efforts, prospects and available resources to determine its optimal operational direction. In May 2021, we formed Rafael Medical Devices, an orthopedic-focused medical device company developing instruments to advance minimally invasive surgeries. In August 2023, Rafael Medical Devices sold an aggregate 31.6% equity interest to third parties for $925,000.
Removed
As of July 31, 2024, the Company’s ownership interest in LipoMedix was approximately 95%. LipoMedix has completed various clinical stages of Promitil® including Phase 1A (solid tumors) and 1B (as single agent and in combination with capecitabine and/or bevacizumab in colorectal cancer). Another phase 1B testing Promitil® as radiosensitizer is ongoing and near completion.
Added
In February 2025, we invested approximately $582,000 in cash, and Rafael Medical Devices raised approximately $44,000 from third parties in exchange for Rafael Medical Devices' Class A Units. We currently hold a 73% equity interest in Rafael Medical Devices.
Removed
A total of 149 patients have been treated with Promitil® as a single agent, or in combination with other anticancer drugs or radiotherapy, under the framework of a phase 1A and two 1B clinical studies and under named patient approval for compassionate use.
Added
On December 11, 2024, Rafael Medical Devices received a substantial equivalence determination for the VECTR System from the Food and Drug Administration (“FDA”) in response to Rafael Medical Devices’ 510(k) premarket notification.
Removed
The Company was determined to be the accounting acquirer for financial reporting purposes. See Note 3 to the Consolidated Financial Statements for additional information regarding the transaction.
Added
The FDA’s clearance of the VECTR System is for use in minimally invasive ligament or fascia release surgeries, such as carpal tunnel release in the wrist and cubital tunnel release in the elbow. The VECTR System has been classified into Class II and is subject to special controls (performance standards).
Removed
In conjunction with the Cornerstone Restructuring and Cornerstone Acquisition, the Company reassessed its relationship with RP Finance, and as a result determined that RP Finance is still a variable interest entity and that the Company became the primary beneficiary of RP Finance as the Company now holds the ability to control repayment of the RP Finance Line of Credit which directly impacts RP Finance’s economic performance.
Added
Rafael Medical Devices' development of future products will depend upon the success of the VECTR System and our Company's ability to identify attractive opportunities in the marketplace.
Removed
Therefore, following the Cornerstone Restructuring and Cornerstone Acquisition, the Company consolidated RP Finance (the “RP Finance Consolidation”). See Note 3 to the Consolidated Financial Statements for additional information on the Consolidation. In May 2021, the Company formed Rafael Medical Devices, an orthopedic-focused medical device company developing instruments to advance minimally invasive surgeries.
Added
On March 14, 2025, Day Three Labs Manufacturing, a majority owned subsidiary of Day Three, entered into an Asset Purchase Agreement and Licensing Agreement (the “DTLM Sale Agreement”), pursuant to which they sold assets and licensed certain applications of their Unlokt™ technology used in their cannabinoid ingredient manufacturing business.
Removed
In August 2023, the Company raised $925,000 from third parties in exchange for 31.6% ownership of Rafael Medical Devices.
Added
See Note 13 in the Notes to our Consolidated Financial Statements for additional information. 83 Results of Operations Our business consists of three reportable segments - Healthcare, Infusion Technology, and Real Estate.
Removed
On August 1, 2023, Rafael Medical Devices closed on the sale of membership units in exchange for $925,000, and following that sale, the Company holds a 68% voting interest based on the outstanding equity interests in Rafael Medical Devices.
Added
Total revenue for the Healthcare segment for the year ended July 31, 2025, increased to approximately $515 thousand compared to $0 for the year ended July 30, 2024. This increase is primarily due to the inclusion of product revenue generated by Cyclo following the Cyclo Merger in March 2025. General and administrative expenses .
Removed
The Company operations have been scaled to meet the current needs which has led to reduced overall general and administrative expenses.
Added
The increase in general and administrative expenses during the year ended July 31, 2025 compared to the year ended July 31, 2024 is primarily due to the consolidation of Cyclo's general and administrative expenses, amounting to $3.6 million, following the Cyclo Merger in March 2025.

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Item 7A. Quantitative and Qualitative Disclosures About Market Risk

Market Risk — interest-rate, FX, commodity exposure

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Biggest changeItem 7A. Quantitative and Qualitative Disclosures about Market Risks FOREIGN CURRENCY RISK Revenue from tenants located in Israel represented 44% and 53% of our consolidated revenues, inclusive of revenue from discontinued operations, for the years ended July 31, 2024 and 2023, respectively. The entirety of these revenues is in currencies other than the U.S. Dollar.
Biggest changeItem 7A. Quantitative and Qualitative Disclosures about Market Risks FOREIGN CURRENCY RISK Revenue from tenants located in Israel represented 34% and 44% of our consolidated revenues for the years ended July 31, 2025 and 2024, respectively. The entirety of these revenues is in currencies other than the U.S. Dollar.
Removed
INVESTMENT RISK In addition to, but separate from our primary business, we will hold a portion of our assets in hedge funds. Investments in hedge funds carry a degree of risk and depend to a great extent on correct assessments of the future course of price movements of securities and other instruments.
Removed
There can be no assurance that our investment managers will be able to accurately predict these price movements. The securities markets have in recent years been characterized by great volatility and unpredictability. Our passive interests in other entities are not currently liquid and we cannot assure that we will be able to liquidate them when we desire, or ever.
Removed
Accordingly, the value of our investments may go down as well as up and we may not receive the amounts originally invested upon redemption.

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