Rafael Holdings, Inc.

Rafael Holdings, Inc. is a biotechnology company that develops pharmaceuticals and holds interests in clinical and early-stage companies that develop pharmaceuticals and medical devices, with its lead candidate Trappsol® Cyclo™ (remibetadex) as an investigational therapy for the potential treatment of Niemann-Pick Disease Type C (NPC), a rare, fatal and progressive genetic disorder. NPC is a devastating lysosomal storage disorder which can occur in both the pediatric and adult population, and many children diagnosed with NPC die before their fifth birthday. Despite two FDA-approved products treating various aspects of the disease, there still remains an unmet medical need and new therapies are urgently required. The global regulatory environment is increasingly stringent, unpredictable, and complex, with a global trend toward increased regulatory and enforcement activity related to all medical products. The rare pediatric disease priority review voucher program is intended to encourage development of therapies to prevent and treat rare pediatric diseases, and on February 3, 2026, Congress extended the rare pediatric disease PRV program until September 30, 2029.

The Company's primary focus is to obtain FDA approval of Trappsol® Cyclo™, for which it submitted a New Drug Application on October 28, 2026 following the recent completion of Cyclo's pivotal Phase 3 clinical trial, and, if approved, to bring that product to market. Trappsol® Cyclo™ has been granted Orphan Drug Designation (May 2010), Fast Track Designation (January 2017), and Rare Pediatric Disease Designation (December 2017) by FDA, and Orphan Drug Designation in Europe (April 2015). If Trappsol® Cyclo™ were to be approved under an orphan-designated indication, it would provide Cyclo with the exclusive right to sell Trappsol® Cyclo™ for the treatment of NPC for seven years in the United States following FDA drug approval, and would provide 10 years of market exclusivity in Europe following EMA regulatory approval, with an additional two years of exclusivity in Europe possible upon acceptance by the EMA's Pediatric Committee of Cyclo's pediatric investigation plan. The Company and the Portfolio Companies face substantial competition, and if competitors develop and market technologies or products more rapidly than those companies do or that are more effective, safer or less expensive than the product candidates that those companies develop, commercial opportunities will be negatively impacted.

The Company generates value through advancing the pipeline development of Trappsol® Cyclo™ as its primary focus and, as research and clinical results warrant, continued investment in its other Portfolio Companies, including Cyclo, LipoMedix, Barer, Rafael Medical Devices, Cornerstone and Day Three. Cyclo also continues to operate its legacy fine chemical business, consisting of the sale of cyclodextrins and related products to the pharmaceutical, nutritional, and other industries, primarily for use in diagnostics and specialty drugs. Historically, the Company owned real estate assets, and as of July 31, 2026, it holds a portion of a commercial building in Jerusalem, Israel as its sole remaining real estate asset. The Company also evaluates opportunities to expand its investment portfolio through strategic investments, including in therapeutics, that address high unmet medical needs, and continuously evaluates its other holdings to ensure the future focus of its resources is on core assets and specifically the Trappsol® Cyclo™ clinical development and commercialization efforts.

Cyclo Therapeutics, LLC is a clinical-stage wholly owned subsidiary that develops cyclodextrin-based products primarily for the potential treatment of NPC and other diseases. Cyclo filed a Type II Drug Master File with the FDA in 2014 for Trappsol® Cyclo™ (hydroxypropyl-β-cyclodextrin, IV) as a treatment for NPC, and in 2015 launched an International Clinical Program for Trappsol® Cyclo™ as a potential treatment for NPC. The Trappsol® Cyclo™ development program includes 5 studies: 1 completed Phase 1 study, 1 completed Phase 1/2 study, 1 ongoing Open Label Extension (OLE) study to the completed Phase 1 study, 1 completed Phase 3 study and a sub-study (outside the US) under the Phase 3 study in accordance with the current PIP agreed with the EMA. The TransportNPC™ Phase 3 multicenter, double-blind, randomized, placebo-controlled pivotal trial was authorized in more than 30 sites across 13 countries (Argentina, Australia, Brazil, Germany, Israel, Italy, Poland, Saudi Arabia, Spain, Taiwan, Turkey, UK and US), fully enrolled 94 patients for a total study duration period of four years, inclusive of a 2-year open-label extension, and in June 2026 achieved its Last Patient, Last Visit (LPLV) milestone after all 94 enrolled patients completed the 96-week evaluation period. The Phase 3 study did not meet the primary endpoint in the overall population; a prespecified analysis in patients receiving background miglustat and/or leucine therapy demonstrated a statistically significant treatment benefit. On October 28, 2026, Cyclo submitted an NDA to FDA seeking approval of Trappsol® Cyclo™ for the treatment of the neurovisceral manifestations of NPC in adult and pediatric patients from birth, and within 60 days of receipt, the FDA will determine whether the application is complete and acceptable for filing and, if accepted, whether Priority Review will be granted. The NDA includes a request for a rare pediatric disease priority review voucher.

LipoMedix is a clinical stage Israeli company based in Israel that is focused on the development of a product candidate, Promitil®, that holds the potential to be an innovative, safe, and effective cancer therapy based on liposome delivery. As of July 31, 2026, the Company's ownership interest in LipoMedix was approximately 95%. LipoMedix has completed 4 clinical studies with Promitil®, and in these four clinical studies, over 140 patients were treated with Promitil® as a single agent or in combination with other anticancer drugs or radiotherapy under a United States IND to assess the safety, PK profile, and preliminary efficacy, in addition to 40 patients who were treated under a compassionate use program. A new investigator-initiated study was launched in June 2026 at Assuta Ashdod Medical Center in Israel to evaluate Promitil in the cisplatin-ineligible population, designed to unfold over a 24-month duration with a focused cohort of 20 patients. Barer is a wholly-owned subsidiary holding equity interests in early stage cancer assets whose operations have been substantially curtailed, and its majority owned subsidiary Farber was formed around an agreement with Princeton University's Office of Technology Licensing for an exclusive worldwide license to its SHMT (serine hydroxymethyltransferase) inhibitor program. Cornerstone's development candidate is CPI-613® (devimistat), a stable analog of normally transient, acylated catalytic intermediates of lipoate, and overall, one thousand thirty-three (1033) patients have been exposed to CPI-613® (devimistat) throughout the various trials (25) in the proposed indications. Rafael Medical Devices is a medical device company whose current lead product is an orthopedic arthroscopy instrument for carpal and cubital tunnel syndrome, and on December 11, 2024, it received a substantial equivalence determination for the VECTR System from the FDA in response to its 510(k) premarket notification, with FDA's clearance 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. 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.

Significant operational developments during the period include the March 25, 2025 consummation of the Merger with Cyclo whereby Cyclo became a wholly-owned subsidiary, and the March 13, 2024 Cornerstone Restructuring as a result of which Rafael became a 67% owner of the issued and outstanding common stock of Cornerstone. In August 2023, Rafael Medical Devices sold an aggregate 31.6% equity interest to third parties for $925,000, and in February 2025, the Company 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. In July 2026, the Company converted the balance of an intercompany promissory note plus accrued interest, totaling $2,087,086, in exchange for Rafael Medical Devices' Class A Units, and as a result, the Company currently holds an 83% equity interest in Rafael Medical Devices. On March 14, 2025, Day Three Labs Manufacturing entered into an Asset Purchase Agreement and Licensing Agreement pursuant to which it sold certain assets and licensed certain applications of their Unlokt™ technology used in their cannabinoid ingredient manufacturing business to a third party in exchange for a $500,000 convertible note in the acquiring company and milestone payments. On April 16, 2026, Cyclo entered into an exclusive, worldwide, royalty-bearing Patent License Agreement with the Massachusetts Institute of Technology for certain patent rights relating to small molecules to improve myelination in Alzheimer's disease and APOE4 carriers.

The Company has limited resources and could find it difficult to raise additional capital, and its future success will likely depend on its ability to obtain regulatory approval and successfully commercialize Trappsol® Cyclo™ (remibetadex). The Company submitted a New Drug Application to FDA for Trappsol® Cyclo™ on October 28, 2026 based on a Phase 3 trial that did not meet its primary endpoint in the overall population, and FDA may refuse to file the NDA, issue a complete response letter, require additional clinical or nonclinical trials, or approve it only for a limited population or with labeling that limits market acceptance. Even if FDA approval were obtained for Trappsol® Cyclo™ for treatment of the designated Rare Pediatric Disease NPC, the Rare Pediatric Disease Priority Review Voucher Program may no longer be in effect or may have been revised at the time of any such approval, or the Company might not be able to capture the value of the program even if the program is still in effect. The Company is controlled by its principal stockholder, which limits the ability of other stockholders to affect the management of the Company.

The Company's primary focus is to obtain FDA approval of Trappsol® Cyclo™, for which it submitted a New Drug Application on October 28, 2026 following the recent completion of Cyclo's pivotal Phase 3 clinical trial, and, if approved, to bring that product to market. Within 60 days of receipt, the FDA will determine whether the application is complete and acceptable for filing and, if accepted, whether Priority Review will be granted, and if the application is accepted, the FDA will assign a Prescription Drug User Fee Act (PDUFA) target action date. The NDA includes a request for a rare pediatric disease priority review voucher. If Trappsol® Cyclo™ were to be approved under an orphan-designated indication, it would provide Cyclo with the exclusive right to sell Trappsol® Cyclo™ for the treatment of NPC for seven years in the United States following FDA drug approval, and would provide 10 years of market exclusivity in Europe following EMA regulatory approval, with an additional two years of exclusivity in Europe possible upon acceptance by the EMA's Pediatric Committee of Cyclo's pediatric investigation plan demonstrating that Trappsol® Cyclo™ addresses the pediatric population.

A second growth vector is the expansion of the pipeline through the Alzheimer's disease opportunity. On April 16, 2026, Cyclo entered into an exclusive, worldwide, royalty-bearing Patent License Agreement with the Massachusetts Institute of Technology for certain patent rights relating to small molecules to improve myelination in Alzheimer's disease and APOE4 carriers, under which Cyclo may develop and commercialize products containing hydroxypropyl-β-cyclodextrin for Alzheimer's disease. The Company also evaluates opportunities to expand its investment portfolio through strategic investments, including in therapeutics, that address high unmet medical needs, and may selectively invest in pre-clinical and clinical stage healthcare opportunities, including those in which it already owns interests, when determined to be consistent with its goals, and move toward clinical stage programs as research and development results warrant.

A third growth vector is the advancement of the other Portfolio Companies. LipoMedix is currently conducting an Investigator Initiated Study at Assuta Ashdod Medical Center in Israel while additionally exploring strategic options for the Promitil® program, including potential licensing opportunities, collaborations with industry partners, and investigator-initiated studies, and the new investigator-initiated study launched in June 2026 is designed to unfold over a 24-month duration with a focused cohort of 20 patients, with researchers currently exploring the opening of an additional clinical site in Israel to support the study. Rafael Medical Devices has initiated a sales effort in the United States and is establishing a network of distributors as it builds out its commercial presence for the VECTR System, is actively expanding its manufacturing volume and engaging with regional orthopedic distributors in the field of hand surgery, and has initiated design of its second product, a device candidate which is designed to be a follow on to the VECTR system that utilizes a retrograde release system. Rafael Medical Devices is seeking to assemble a portfolio of Class I, II and III devices to mitigate risk across a portfolio of devices with overlapping needs and markets, a strategy designed to minimize supply chain requirements while maximizing market potential. Cornerstone is currently exploring strategic alternatives to further its clinical development, and in February of 2025, Cornerstone sold the rights to telaglenastat to Synhale for a modest upfront payment and potential future milestones based on development achievements, with Synhale planning to develop the drug candidate for patients with pulmonary hypertension.

The Company continuously evaluates its other holdings to ensure the future focus of its resources is on core assets and specifically the Trappsol® Cyclo™ clinical development and commercialization efforts. The Company is currently reviewing Cornerstone's current efforts, prospects and available resources to determine the optimal operational direction. In November 2022, the Company resolved to curtail its early-stage development efforts, including pre-clinical research at Barer, and has since ceased almost all of such activity; going forward, the Company expects that Barer, through its Farber subsidiary, will primarily operate as an entity holding interest in these cancer-focused opportunities. The Company's internal and external investment decisions will be based on the progress and results of its clinical development and pre-clinical activities and other operational developments, and the availability of targets for investment, acquisition or licensing.

The Company has limited resources and could find it difficult to raise additional capital. As needed, the Company provides debt or equity funding to LipoMedix to support its development and clinical efforts, and the Company provides funding to LipoMedix through intercompany promissory notes which are used to support research and development activities. The Company's future success will likely depend on its ability to obtain regulatory approval and successfully commercialize Trappsol® Cyclo™ (remibetadex), and if it is unable to do so, or experiences significant delays in doing so, its business will be materially harmed. The Company and the Portfolio Companies may expend their limited resources to pursue a particular product candidate or an indication and fail to capitalize on product candidates or indications that may be more profitable or for which there is a greater likelihood of success.

The Company and the Pharmaceutical Companies are dependent upon third parties for a variety of functions, and these arrangements may not provide the benefits expected. Results of preclinical studies and early clinical trials may not be predictive of results of future preclinical studies or clinical trials. The Company's or the Pharmaceutical Companies' product candidates may cause significant adverse events, toxicities or other undesirable side effects when used alone or in combination with other approved products or investigational new drugs that may result in a safety profile that could preclude further development, prevent regulatory approval, prevent market acceptance or limit their commercial potential if regulatory approval were to be received or result in other significant negative consequences. Rafael Medical Devices' device candidates may cause significant adverse events, toxicities or other undesirable side effects when used alone or in combination with other approved or cleared devices or investigational or approved drugs that may result in a safety profile that could prevent regulatory approval, prevent market acceptance, limit their commercial potential, result in significant negative consequences, or potential product liability claims.

The Company relies significantly on information technology and any failure, inadequacy, interruption or security lapse of that technology, including any cyber security incidents, could harm its ability to operate its business and that of the Portfolio Companies effectively. The Company may not be able to consummate any investment, business combination, or other transaction. The Company is controlled by its principal stockholder, which limits the ability of other stockholders to affect the management of the Company. If the Company or the Portfolio Companies are unable to adequately maintain or protect their proprietary technology and product candidates and device candidates and services, if the scope of the patent protection obtained is not sufficiently broad, or if the terms of patents are insufficient to protect product candidates, device candidates, services or technologies for an adequate amount of time, competitors could develop and commercialize technology and products similar or identical to that technology or those product candidates, device candidates and services, and the ability to successfully commercialize technology or product candidates, device candidates or services may be materially impaired.

The most material risks to Rafael Holdings center on its dependence on a single lead asset with a failed primary endpoint and limited resources. The Company submitted a New Drug Application to FDA for Trappsol® Cyclo™ on October 28, 2026 based on a Phase 3 trial that did not meet its primary endpoint in the overall population, and FDA may refuse to file the NDA, issue a complete response letter, require additional clinical or nonclinical trials, or approve it only for a limited population or with labeling that limits market acceptance. Even if FDA approval were obtained for Trappsol® Cyclo™ for treatment of the designated Rare Pediatric Disease NPC, the Rare Pediatric Disease Priority Review Voucher Program may no longer be in effect or may have been revised at the time of any such approval, or the Company might not be able to capture the value of the program even if the program is still in effect. The Company has limited resources and could find it difficult to raise additional capital, and its future success will likely depend on its ability to obtain regulatory approval and successfully commercialize Trappsol® Cyclo™ (remibetadex). The Company and the Portfolio Companies face substantial competition, and if competitors develop and market technologies or products more rapidly than those companies do or that are more effective, safer or less expensive than the product candidates that those companies develop, commercial opportunities will be negatively impacted. The Company is controlled by its principal stockholder, which limits the ability of other stockholders to affect the management of the Company.

Management's message to shareholders centers on the Company's transformation into a biotechnology company whose primary focus is obtaining FDA approval of Trappsol® Cyclo™ and, if approved, bringing that product to market. The Company submitted a New Drug Application to FDA on October 28, 2026 following the recent completion of Cyclo's pivotal Phase 3 clinical trial, and within 60 days of receipt, the FDA will determine whether the application is complete and acceptable for filing and, if accepted, whether Priority Review will be granted. The Phase 3 study did not meet its primary endpoint in the overall population; a prespecified analysis in patients receiving background miglustat and/or leucine therapy demonstrated a statistically significant treatment benefit. The NDA includes a request for a rare pediatric disease priority review voucher. Management emphasizes that the Company also evaluates opportunities to expand its investment portfolio through strategic investments, including in therapeutics, that address high unmet medical needs, and continuously evaluates its other holdings to ensure the future focus of its resources is on core assets and specifically the Trappsol® Cyclo™ clinical development and commercialization efforts. The strategic priorities management has chosen to emphasize for the period ahead are, first, obtaining FDA approval of Trappsol® Cyclo™ and, if approved, commercializing the product; second, advancing the pipeline development of Trappsol® Cyclo™ as the primary focus and, as research and clinical results warrant, continued investment in the other Portfolio Companies, including Cyclo, LipoMedix, Barer, Rafael Medical Devices, Cornerstone and Day Three; and third, expanding the portfolio through opportunistic and strategic investments, including investments in therapeutics which address high unmet medical needs. Management notes that the focus of its efforts is subject to change with market conditions, results of its internal development efforts, the availability of investment opportunities on acceptable terms, the investment and acquisition opportunities it may pursue, and developments at those targets.