Rafael Holdings (RFL) details late-stage Trappsol Cyclo program and 2026 NDA plans
Rhea-AI Filing Summary
Rafael Holdings, Inc. furnished an investor presentation outlining progress of its lead drug candidate Trappsol® Cyclo for Niemann-Pick Disease Type C1 (NPC). The company is running a fully enrolled, global Phase 3 trial with 104 subjects in a 96-week study using 2000 mg/kg intravenous dosing every two weeks.
The Phase 3 interim analysis at 48 weeks in June 2025 led an independent data monitoring committee to recommend continuation to the 96-week final analysis. Last-patient-last-visit and a pre-NDA meeting were completed in June 2026, and the company expects New Drug Application submission and topline Phase 3 data in the second half of 2026.
The presentation highlights prior Phase 1/2 data showing stabilized or improved clinical scores in most completers, a safety profile characterized mainly by mild to moderate adverse events, and regulatory designations including Orphan Drug status in the US and EU, Fast Track in the US, and Rare Pediatric Disease designation that may qualify for a Priority Review Voucher. It also cites estimates that the global NPC market could exceed $920m by 2031.
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Insights
Rafael highlights a late-stage rare-disease program nearing NDA with supportive early data.
Rafael Holdings focuses its story on Trappsol® Cyclo, an intravenous therapy for Niemann-Pick Disease Type C1. The drug is in a pivotal 96-week Phase 3 study with 104 patients, building on earlier Phase 1/2 trials that showed stabilization or improvement on multiple NPC severity scales.
The presentation notes Orphan Drug, Fast Track and Rare Pediatric Disease designations, which together can streamline review and may support a Priority Review Voucher if approved. Safety data across trials show mostly mild to moderate adverse events, with hearing changes monitored but generally manageable while treatment continues.
Investors may view the completed last-patient-last-visit and pre-NDA meeting in June 2026, plus expected NDA submission and topline Phase 3 data in the second half of 2026, as key upcoming milestones. Actual value will depend on final efficacy, long-term safety, and how Trappsol® Cyclo competes or combines with other recently approved NPC therapies.
8-K Event Classification
Key Figures
Key Terms
Orphan Drug Designation regulatory
Rare Pediatric Disease regulatory
Priority Review Voucher regulatory
Phase 3 trial regulatory
New Drug Application regulatory
Niemann-Pick Disease Type C1 medical
FAQ
What is Rafael Holdings' lead drug program highlighted in the 8-K for RFL?
What stage is Trappsol Cyclo in for treating Niemann-Pick Disease Type C1?
When does Rafael Holdings expect NDA submission and topline Phase 3 data for Trappsol Cyclo?
What regulatory designations has Trappsol Cyclo received according to Rafael Holdings (RFL)?
How large is the Niemann-Pick Disease Type C1 market Rafael Holdings targets?
What safety profile has Trappsol Cyclo shown in Rafael Holdings’ clinical studies?
UNITED STATES
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| Title of each class | Trading Symbol | Name of each exchange on which registered | ||
Item 7.01. Regulation FD
From July 8, 2026, the slide presentation (the “Presentation”) attached hereto as Exhibit 99.1 will be available on the Registrant’s website at the following link: https://rafaelholdings.irpass.com/.
The Registrant is furnishing the information contained in this Report, including Exhibit 99.1, pursuant to Item 7.01 of Form 8-K promulgated by the Securities and Exchange Commission (the “SEC”). This information shall not be deemed to be “filed” with the SEC or incorporated by reference into any other filing with the SEC. In addition, the Presentation contains statements intended as “forward-looking statements” that are subject to the cautionary statements about forward-looking statements set forth in the Presentation.
Item 9.01 Financial Statements and Exhibits.
(d) Exhibits.
Exhibit No. |
Document | |
| 99.1 | Investor Presentation | |
| 104 | Cover Page Interactive Data File (embedded within the Inline XBRL document). |
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SIGNATURES
Pursuant to the requirements of the Securities Exchange Act of 1934, the Registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.
| RAFAEL HOLDINGS, INC. | |||
| By: | /s/ David Polinsky | ||
| Name: | David Polinsky | ||
| Title: | Chief Financial Officer | ||
| Dated: July 8, 2026 | |||
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EXHIBIT INDEX
Exhibit |
Document | |
99.1 |
Investor Presentation | |
| 104 | Cover Page Interactive Data File (embedded within the Inline XBRL document). |
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Exhibit 99.1
NYSE: RFL July 2026 | Investor Presentation
Forward-Looking Statements Some of the information in this presentation relates to future events or future business and financial performance. Such statements constitute forward-looking information within the meaning of the Private Securities Litigation Act of 1995. Such statements can be only predictions and the actual events or results may differ from those discussed due to, among other things, the risks described in the public filings and other publications of Rafael Holdings, Inc. Forward-looking statements are identified by words such as "anticipates", "projects", "expects", "plans", "intends", "believes", "estimates", "target", and other similar expressions that indicate trends and future events. The market data and certain other statistical information used throughout this presentation are based on independent industry publications, governmental publications, reports by market research firms or other independent sources. Some data are also based on the Company's good faith estimates. In addition, this presentation includes summaries of scientific activities and outcomes that have been condensed to aid the reader in gaining general understanding. The information about Rafael Holdings, Inc. and its subsidiaries is solely for information purposes and is not to be construed as an offer to sell or the solicitation of an offer to buy any security in any state. Factors that could cause the Company's results to differ materially from those expressed in forward looking statements include, without limitation, the Company's need for additional capital; the Company's reliance on its Trappsol® Cyclo product, which may never receive regulatory approval; the Company's ability to commercialize any of its proposed drug products if it receives regulatory approval; the outcome of the Company's clinical trials, which may not support the Company's product claims or may result in adverse side effects; the cost and timing of the Company's clinical trials; the Company's reliance on third parties to conduct clinical trials and to produce its products; other risks associated with being a clinical stage biotechnology company; a small number of the Company's customers account for a substantial portion of our revenue, and the loss of any of these customers would materially decrease our revenues; and the Company may be negatively affected by currency exchange rate fluctuations. This presentation is not to be copied, transmitted, displayed, distributed (for compensation or otherwise), or altered in any way without the prior written consent of Rafael Holdings, Inc. 2
Clinical Drug Development Trappsol® Cyclo 3 Focused on Bringing Trappsol® Cyclo to Market Real Estate Holding Medical Devices Rafael Holdings, Inc. NYSE: RFL / NYSE American: RFLW
Investment Highlights 4 Experienced team with strong track record of success Lead program Trappsol ® Cyclo in Phase 3 trial for the treatment of Niemann-Pick Disease Type C1 High unmet medical need in NPC; global market expected to reach >$920m by 2031 Independent unblinded Data Monitoring Committee (DMC) performed Interim analysis in June 2025 and recommended continuation of the study through final analysis at 96-weeks. Strong balance sheet with sufficient capital to fund through multiple potentially value creating milestones Late clinical-stage biotechnology company dedicated to developing life- changing medicines through science and innovation for patients and families living with challenging diseases Completed LPLV June 2026; Pre-NDA meeting completed; NDA submission and Topline data expected 2nd half 2026
5 Leadership Team Howard S. Jonas Chairman of the Board Karen Mullen, FFPM Chief Medical Officer David Polinsky Chief Financial Officer Joshua Fine Chief Operating Officer
6 Trappsol® Cyclo Is Being Evaluated in the Fully Enrolled TransportNPC Phase 3 Clinical Trial for Patients With Niemann-Pick Disease Type C1 48-week interim analysis (IA) from Phase 3 Trial completed June 13 Data monitoring committee recommended continuing study to the 96-week final analysis Potential to be a market leading treatment in newborn patients and above treating both systemic and neurological manifestations of NPC Orphan Drug Designation in US and EU, Fast Track in US, Rare Pediatric Disease Designated in US allowing for Priority Review Voucher eligibility Completed LPLV June 2026; Pre-NDA meeting completed; NDA submission and Topline data expected 2nd half 2026
Niemann-Pick Disease Type C1 Ongoing Pivotal Phase 3 Study 7
Niemann Pick Type C1 (NPC) Market Overview 8 Incidences 1/100,000 ~35/year in U.S. ~3% are age 3 and below Diagnosed Patients ~97% age 3 and up ~60% age 16 and up Median Survival Early infantile (2m-2): 4.6y Late infantile (3-6): 9.4y Juvenile (7-15): 15.4y Adult (16+): 12.2y Existing Cases >9,000 in 80 countries ~900 in U.S. • NPC can manifest at any age and is characterized by progressive organ failure and neurodegeneration • Recent studies estimate the prevalence of NPC in the US is approximately 2.9 cases per million, which translates to around 943 cases • Many of which are likely untreated due to challenges around diagnosis and rarity of the disease • Late onset of symptoms can lead to longer life spans, but it is extremely rare for any person with NPC to reach age 40 Sources: Battisti et al, 2003; Schicks et al, 2013; Sévin et al, 2007; Trendelenburg et al, 2006; Vanier et al, 2010), Burton BK, Ellis AG, Orr B, et al. Estimating the prevalence of Niemann-Pick disease (NPC) in the United States. Mol Genet Metab. 2021; (134) doi: 10.1016/j.ymgme.2021.06.011, Data commissioned by Tessellon Inc, for Cyclo Therapeutics, LLC.; Neimann Pick Foundation NPC is a rare, fatal, autosomal recessive lysosomal storage disease that disrupts lipid trafficking within cells, leading to the toxic buildup of unesterified cholesterol and glycosphingolipids in major organs. Overview
Trappsol® Cyclo Differentiated MOA 9 NPC1, a key regulator in late endosomal/lysosomal compartments, regulates cholesterol efflux Biallelic NPC1 mutations trap cholesterol in lysosomes, block autophagy and drive cell death Trappsol® Cyclo facilitates cholesterol release independent of NPC1/NPC2, bypassing transport blockades and offering significant potential benefits for NPC patients Uniquely Enables the Effective Transport of Cholesterol Out of Cells Baseline 14 Weeks Baseline 14 Weeks Baseline 14 Weeks Cholesterol as measured by Filipin staining at Baseline and after 7 doses over 14 weeks (3 Patients) 1500 Mg/kg (Mild) Reduction 2500 Mg/kg (Marked) Reduction 2500 Mg/kg (Marked) Reduction
10 Trappsol® Cyclo Summary of Completed Studies and Open-Label Extension Trappsol® Cyclo reaches the cerebrospinal fluid within hours of IV infusion, modulating cholesterol metabolism and clearing cellular cholesterol, mirroring preclinical NPC model effects Study 1011 Study 102 Demonstrated Trappsol® Cyclo was well-tolerated and may slow disease progression, with potential long- term stabilization compared to the natural course of NPC Study 2012 Phase 1 study in NPC patients ages 18 years and older showed Trappsol® Cyclo was well- tolerated with an acceptable safety and tolerability profile Consistent pharmacodynamic effects and safety profile observed in a 48-week Phase 1/2 study in NPC patients aged 2 years and older Potential to treat both the systemic and neurological manifestations of NPC and is well-tolerated with acceptable safety and tolerability profile 1. Molecular Genetics and Metabolism Report: Intravenous 2-hydroxypropyl-β-cyclodextrin (Trappsol® Cyclo ) demonstrates biological activity and impacts cholesterol metabolism in the central nervous system and peripheral tissues in adult subjects with Niemann-Pick Disease Type C1: Results of a phase 1 trial (2022) 2. Molecular Genetics and Metabolism Report: The Long-term administration of intravenous Trappsol® Cyclo (HPβCD) results in clinical benefits and stabilization or slowing of disease progression in patients with Niemann-Pick disease Type C1: Results of an international 48-week Phase I/II trial (2023) 9 of 9 (100%) completer patients exhibited stabilized or improved in CGI-I ratings, a clear indicator of efficacy in NPC-1 patients. 8 of 9 (89%) completer patients showed Improvements over disease progression (2.15 points per annum) in the 5D-NPC-SS.
11 Phase 1/2 Study (CTD-TCNPC-201) • Therapeutic benefit may be seen by 48 weeks vs. disease progression • Small cohort (9 patients) limits extensive analysis • Transient variations may mimic disease progression but should lessen in Phase 3 (CTD-TCNPC-301) • 9 completers: 2 at 1500 mg/kg | 4 at 2000 mg/kg | 3 at 2500 mg/kg • 3 excluded from analysis: • 1 with only baseline data • 2 discontinued before Week 48 (non-safety reasons) Data Included Key Outcomes 5D NPCSS primary endpoint for the Phase 3 study Potential benefit may be observed at or before 48 weeks
12 Phase 1/2 Study (CTD-TCNPC-201): Continued • 9 completers: 2 at 1500 mg/kg | 4 at 2000 mg/kg | 3 at 2500 mg/kg • 3 excluded from analysis: • 1 with only baseline data • 2 discontinued before Week 48 (non-safety reasons) Data Included Key Outcomes Individual data suggestive of potential benefit on 5D-NPC-SS & CGI-I • 67% (6/9) completers stabilized or improved on the 5D-NPC-SS • 89% (8/9) completers showed improvement over disease progression (2.15 points/year) on the 5D-NPC-SS • 100% (9/9) completers stabilized or improved in CGI-I ratings, indicating efficacy in NPC-1 patients
13 Phase 1/2 Study (CTD-TCNPC-201): Continued Dosage data suggestive of potential benefit on SARA, an exploratory measure • Multiple domains analyzed: gait, stance, sitting, speech, finger chase (L/R), nose-finger (L/R), fast alt hands (L/R), heel-shin (L/R) • 2500 mg/kg & 2000 mg/kg groups showed stabilized or improved gait, stance, sitting, speech vs. baseline • 2500 mg/kg suggestively improved gait, stance and speech at 48 weeks (Figure A-D) • 2000 mg/kg suggestively improved stance and stabilized sitting, speech at 48 weeks (Figure E-H) • Dose-ordered benefits observed; higher exposures may yield more consistent effects, though sample size is small • SARA domain scores analyzed at a group level for: • 2500 mg/kg | 2000 mg/kg | 1500 mg/kg doses • Patient-level data focused on: • Gait, stance, sitting and speech 1500 mg/kg group excluded from further analysis due to incomplete/missing 48-week data Data Included Key Outcomes
14 Ongoing Long-Term Extension (OLE) Study (CTD-TCNPC-102) Data Included is from an August 2023 Data Cut Key Outcomes from the OLE • To date, 3 patients remain on active treatment • All receive 1500 mg/kg biweekly via in-home infusions • All 5 patients showed slowed disease progression, with some stabilizing or improving • Suggestive evidence of Trappsol® Cyclo 's durability as a chronic medication • Safety and tolerability align with past and ongoing trials; well tolerated Efficacy Data From Ongoing Long-Term Extension (OLE) Study Suggestive evidence of durability of effect
15 Safety From Completed and Ongoing Long-Term Treatment Treatment-Emergent Adverse Events majority mild to moderate in severity, manageable and monitorable and most considered unrelated to Trappsol® Cyclo No evidence of any untoward effects of Trappsol® Cyclo on core organ systems (cardiovascular, respiratory, renal, hepatic, gastrointestinal systems or CNS) Safety and tolerability profile consistent across studies and treatment duration, irrespective of age spectrum and disease severity Hearing loss and infusion reactions (most localized) are adverse events of interest Events of hearing loss resolved in most patients, with hearing returning to baseline levels or improved and stabilized while patients continued on study drug A degree of hearing impairment remained at the last available auditory assessment in a limited number of patients The effect on hearing will continue to be monitored closely in the ongoing studies
16 Ongoing Pivotal Phase 3 Study in Niemann-Pick Disease Type C1 Number of Subjects 104 enrolled: 94 Core Study; 10 Sub Study Current Sites 30+ across 14 countries Duration 96-week trial Dose 2000 mg/kg via IV infusion Substudy (Patients 0-3)2 Requested as part of our adopted PIP to potentially treat as a prophylactic treatment option 96-week LPLV completed June 2026; Pre NDA Meeting completed; NDA submission and Topline data expected 2nd half calendar 2026 1. Substudy is only being conducted ex-US. Patients are not randomized and all patients in the 0-3 cohort receive Trappsol® Cyclo .
17 Trial Design: Core-Study (≥3 Years of Age) – Global Double-Blind, Randomized, Placebo-Controlled, Parallel-Group, Multicenter Study Number of Subjects 94 randomized (2:1 to Placebo) Primary Endpoint NPC Composite Severity Score Secondary Endpoints SCAFI, Swallow, Vineland-2 Exploratory Endpoints Inclusive of speech, liver and lung function Baseline Assessment Final Analysis (Week 96) Interim Analysis Completed (Week 48) Screening (2 Weeks) Hydroxypropyl-Beta-Cyclodextrin + SOC vs. Placebo + SOC Administered IV Every 2 Weeks Continuation of HPβCD + SOC until week 192 V1 Week-8 to -5 V2 Week-4 to -1 V3 Week 0 V4 Week 2 V5 Week 4 V9 Week 12 V15 Week 24 V21 Week 36 V27 Week 48 V33 Week 60 V39 Week 72 V45 Week 84 V51 Week 96 V52 Week 98 Study Drug Infusions Following Required Assessments every 2 weeks
18 Trial Design: Sub-Study (Newborn to <3 Years of Age) – Global Open Label Phase Baseline Assessment Final Analysis (Week 96) Screening (2 Weeks) Hydroxypropyl-Beta-Cyclodextrin + SOC Administered IV Every 2 Weeks Continuation of HPβCD + SOC until week 192 V1 Week-8 to -5 V2 Week-4 to -1 V3 Week 0 V4 Week 2 V5 Week 4 V9 Week 12 V15 Week 24 V21 Week 36 V27 Week 48 V33 Week 60 V39 Week 72 V45 Week 84 V51 Week 96 V52 Week 98 Study Drug Infusions Following Required Assessments every 2 weeks Number of Subjects 10 randomized Study Objectives • To evaluate the safety and tolerability • To evaluate the improvement using the CGI-S, CGI-C, CaGI-S, CaGI-C, and CaGI C24 scales • To evaluate the PK
19 Clinical Global Impression–Change (CGI-C) Bar Plot at data cutoff on 14-May-2025 • Graphs shows individual patients (N=10) • 2 patients have withdrawn from the study at week 48 for non-safety related reasons • Trappsol® Cyclo continues to demonstrate stabilization or improvement in the majority of patients and is well-tolerated consistent with previous studies
20 Safety from ongoing Substudy at data cutoff on 14-May-2025 • There were 146 AEs, the reported as mild (69%) moderate (29%), and Severe (2%) • No SAEs were considered by the principal investigators as related to or possibly related to study drug.
21 Trappsol® Cyclo Positioning in the Emerging NPC Treatment Paradigm • NPC landscape evolving from no therapy → multi-drug paradigm • Recent approvals (Zevra, IntraBio) enable combination approaches • Distinct upstream mechanism — removes cholesterol independent of NPC1/NPC2 • Complementary to approved therapies across disease layers • Competes for backbone disease-modifying role • IV only therapy to treat systemic aspects of disease as well as neurological • IV only therapy to that can be delivered at birth (full-term babies) • Positioned for combination standard of care • Opportunity to redefine NPC treatment paradigm
Attribute Trappsol® Cyclo Zevra (Miplyffa) IntraBio (Aqneursa) Mechanism of Action Direct Cholesterol clearance (root cause) lysosomal/ proteostasis enhancement, approved prescribing information states Unknown. neurological function modulation, approved prescribing information states Unknown. Therapeutic Target Systemic + CNS disease modification Primarily neurological progression Symptomatic neurological improvement Role in Treatment Paradigm Potential Backbone/ Foundational therapy Disease-modifying adjunct (with miglustat) Symptomatic monotherapy of add-on Clinical Impact Addresses underlying disease biology Slows progression via cellular pathways Improves function outcomes Patient Population Broad, including early/pediatric Adults and pediatrics patients 2 years of age and older Adults and pediatrics patients weighing ≥ 15 kg Administration IV (biweekly) Oral Oral Combination Potential High (mechanistically complementary) Moderate (already combo) High (symptom layer) 22 Target Product Profile Comparison
23 Investment Summary Phase 3 Clinical trial LPLV June 2026; NDA submission and Topline data expected 2nd half 2026 1. Intelligence, D. (n.d.). Niemann Pick Disease market size, sustainable insights and growth report 2025-2033. DataMIntelligence 2. As of April 30, 2026 Ability to Realize Potential Value Creation Significant Commercial Opportunity ~$30.5M Cash Balance2 ✓Global NPC market expected to reach >$920m by 20331 ✓Recent US approved NPC product pricing is consistent with pricing analogs ranging from $400K to $1.3M ✓Streamlined company focused on bringing Trappsol® Cyclo to market ✓ all-in-one Endoscopic Carpal Tunnel Release system, approved by FDA December 2024 ✓Sufficient capital to fund the company through multiple potentially value creating milestones
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