Rafael Holdings: Primary endpoint not statistically significant

The global, double-blind study enrolled patients ages 3 to 70 and compared intravenous treatment every two weeks with placebo over 96 weeks.

Rhea-AI Filing Summary

Rafael Holdings, Inc. (RFL) reported topline results from its subsidiary Cyclo Therapeutics’ pivotal Phase 3 TransportNPC study of Trappsol Cyclo in 94 patients with Niemann-Pick disease type C. At Week 96, the treatment showed a directionally favorable effect on the primary 4-domain NPC Clinical Severity Scale endpoint, but did not achieve statistical significance. A prespecified analysis of patients receiving background miglustat and/or leucine—approximately 83% of participants—showed a statistically significant effect.

Over 96 weeks, serious treatment-emergent adverse events were reported in 35.9% of Trappsol Cyclo participants versus 16.7% on placebo; treatment-related serious events were 3.1% versus 3.3%. No treatment-emergent adverse events resulted in death, and one treatment-related case of bilateral deafness was severe. A separate analysis comparing infantile-onset patients treated across the clinical program with matched external registry controls was described as supportive evidence of a treatment-associated survival benefit. Rafael said it remains on track to submit an NDA in the fourth quarter of 2026 following a previously announced pre-NDA meeting; the topline data, complete dataset and survival analysis remain subject to full analysis and FDA regulatory review.

1 point · 0 major

NegativeiHow this balance works

How this balance works

Rhea-AI gives every point it takes from this document a weight. Minor counts 1, Moderate 3 and Major 9, so one Major point outweighs several Minor ones. The bar adds up the weights on each side, and when neither side holds more than 65% of the total the balance reads Mixed.

It reads the document as published, with the same rules for every company, and it does not look at what the market expected or at how the stock traded, so a point can be objectively good on a day the stock falls.

Rhea-AI Sentiment measures something else, the tone of the wording.

How the balance worksHow Sentiment works

1 major · 2 points

How the balance works

Positive

• Minor pointPrespecified subgroup: statistically significant 4DNPCSS effect among approximately 83% of participants.

Negative

• Major pointPrimary endpoint: no statistical significance at Week 96 despite a directionally favorable effect.
• Moderate pointSerious TEAEs: 35.9% with Trappsol Cyclo versus 16.7% with placebo.

8-K Event Classification

4 items: 2.02, 7.01, 8.01, 9.01

4 items

Item 2.02 Results of Operations and Financial Condition Financial

Disclosure of earnings results, typically an earnings press release or preliminary financials.

Item 7.01 Regulation FD Disclosure Disclosure

Material non-public information disclosed under Regulation Fair Disclosure, often investor presentations or guidance.

Item 8.01 Other Events Other

Voluntary disclosure of events the company deems important to shareholders but not covered by other items.

Item 9.01 Financial Statements and Exhibits Exhibits

Financial statements, pro forma financial information, or exhibit attachments filed with this report.

Key Figures

TransportNPC enrollment: 94 patients Treatment period: 96 weeks Trappsol Cyclo dose: 2000 mg/kg every two weeks +5 more

8 metrics

TransportNPC enrollment 94 patients Pivotal Phase 3 study

Treatment period 96 weeks TransportNPC study

Trappsol Cyclo dose 2000 mg/kg every two weeks Intravenous treatment arm

Prespecified subgroup Approximately 83% of the study population Patients receiving background miglustat and/or leucine

Treatment-emergent adverse events Trappsol Cyclo: 93.8%; placebo: 100.0% Reported over the 96-week treatment period

Serious treatment-emergent adverse events Trappsol Cyclo: 35.9%; placebo: 16.7% Reported over the 96-week treatment period

Treatment-related serious adverse events Trappsol Cyclo: 3.1%; placebo: 3.3% Reported over the 96-week treatment period

Hearing-related treatment-emergent adverse events Trappsol Cyclo: 15.6%; placebo: 13.3% Most were mild or moderate

Key Terms

4-domain NPC Clinical Severity Scale, prespecified analysis, treatment-emergent adverse events, pre-NDA meeting

4 terms

4-domain NPC Clinical Severity Scale medical

"change in the 4-domain NPC Clinical Severity Scale (4DNPCSS) at Week 96"

prespecified analysis medical

"A prespecified analysis also evaluated change in 4DNPCSS"

treatment-emergent adverse events medical

"Treatment-emergent adverse events (TEAEs) were reported"

Events or symptoms that either appear for the first time or get worse after a patient starts a treatment; think of new or intensified side effects that show up once medicine or a medical device is used. Investors watch these closely because they affect whether a therapy can gain regulatory approval, be prescribed widely, or face legal and commercial setbacks—similar to how early customer complaints can sink a new product’s prospects.

pre-NDA meeting regulatory

"previously announced pre-NDA meeting with the FDA"

A pre-NDA meeting is a planned discussion between a drug developer and the medicines regulator held before submitting a New Drug Application, where the company presents its clinical, safety, and manufacturing data and asks specific questions about what the regulator expects for approval. It matters to investors because it can reveal whether a filing is on solid footing, identify potential gaps that could delay or derail approval, and reduce surprise regulatory setbacks—think of it as a dress rehearsal with the referee before the final match.

FAQ

AI-generated questions and answers. How Rhea-AI works. Not financial advice.

What were RFL’s Phase 3 TransportNPC results?

RFL said Trappsol Cyclo did not achieve statistical significance on the primary 4DNPCSS endpoint, although the effect was directionally favorable. A prespecified analysis among patients receiving background miglustat and/or leucine, approximately 83% of the study population, showed a statistically significant effect.

What safety findings did RFL report for Trappsol Cyclo?

Hearing-related treatment-emergent adverse events were reported in 15.6% of Trappsol Cyclo participants and 13.3% of placebo participants, and most were mild or moderate. One treatment-related bilateral deafness event in the Trappsol Cyclo group was severe; no treatment-emergent adverse events resulted in death.

How was RFL’s TransportNPC study designed?

TransportNPC was a global, double-blind, placebo-controlled study with 94 patients aged 3 to 70. Patients were randomized to intravenous Trappsol Cyclo at 2000 mg/kg every two weeks (63 patients) or placebo (31 patients) for 96 weeks.

AI-generated analysis. How Rhea-AI works. Not financial advice.

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UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

Washington, D.C. 20549

FORM 8-K

CURRENT REPORT

Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934

Date of Report (Date of earliest event reported): September 30, 2026

RAFAEL HOLDINGS, INC.

(Exact name of registrant as specified in its charter)

Delaware		1-38411		82-2296593
(State or other jurisdiction of Incorporation)		(Commission File Number)		(IRS Employer Identification No.)

520 Broad Street Newark, New Jersey		07102
(Address of principal executive offices)		(Zip Code)

Registrant’s telephone number, including area code: 212 658-1450

Not Applicable

(Former name or former address, if changed since last report.)

Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions (see General Instruction A.2. below):

¨ Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425)

¨ Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12)

¨ Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))

¨ Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c))

Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§240.12b-2 of this chapter).

Emerging growth company ☐

If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. ☐

Securities registered pursuant to Section 12(b)-2 of the Exchange Act:

Title of each class		Trading Symbol		Name of each exchange on which registered
Class B common stock, par value $0.01 per share		RFL		New York Stock Exchange

Item 7.01. Regulation FD  

On September 30, 2026, Rafael Holdings, Inc. (the “Company”) distributed over a wire service and posted the attached press release (the “Release”) to the investors page of the Company’s website (www.rafaelholdings.com) announcing topline efficacy and safety data from its Cyclo Therapeutics, LLC subsidiary’s pivotal Phase 3 TransportNPC™ study (CTD-TCNPC-301) evaluating Trappsol® Cyclo™ (intravenous hydroxypropyl-β-cyclodextrin) in 94 patients diagnosed with Niemann-Pick Disease Type C (NPC).  

A copy of the Release is furnished herewith as Exhibit 99.1 and is incorporated herein by reference.  

The Company is furnishing the information contained in this Report, including Exhibit 99.1, pursuant to Item 2.02 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 unless otherwise expressly stated in such filing. In addition, this Report  and the press release contain statements intended as “forward-looking statements” that are subject to the cautionary statements about forward-looking statements set forth in the press release.  

Item 8.01. Other Events.  

The information contained in Item 7.01 above is incorporated herein by reference into this Item 8.01.

Item 9.01 Financial Statements and Exhibits.

(d) Exhibits.

Exhibit No.		Document
99.1		Press Release, dated September 30, 2026.
104		Cover Page Interactive Data File, formatted in Inline XBRL document.

1

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: September 30, 2026

2

EXHIBIT INDEX

Exhibit Number		Document
99.1		Press Release, dated September 30, 2026.
104		Cover Page Interactive Data File, formatted in Inline XBRL document.

3

Exhibit 99.1

Rafael Holdings Announces Topline Results from the Pivotal Phase 3 TransportNPC^™ Study of Trappsol^® Cyclo^™ in Niemann-Pick Disease Type C (NPC)

Trappsol^® Cyclo™ did not achieve statistical significance but demonstrated a directionally favorable treatment effect versus placebo on the primary endpoint of change in the 4-domain NPC Clinical Severity Scale (4DNPCSS) at Week 96

A prespecified analysis in patients receiving background miglustat and/or leucine therapy, representing approximately 83% of the study population, showed a statistically significant effect on the 4DNPCSS

Trappsol® Cyclo™ demonstrated a well-tolerated safety and tolerability profile consistent with previous studies, with no new safety signals observed

Based upon its previously announced pre-NDA meeting, the Company remains on track to submit the NDA in the fourth quarter of 2026, consistent with prior guidance

Company to host investor conference call and webcast today, September 30, at 8:30 a.m. ET

NEWARK, NJ — September 30, 2026 — Rafael Holdings, Inc. (NYSE: RFL) today announced topline efficacy and safety data from its Cyclo Therapeutics, LLC subsidiary’s pivotal Phase 3 TransportNPC™ study (CTD-TCNPC-301) evaluating Trappsol^® Cyclo^™ (intravenous hydroxypropyl-β-cyclodextrin) in 94 patients diagnosed with Niemann-Pick Disease Type C (NPC). Trappsol^® Cyclo^™ was well tolerated and demonstrated a directionally favorable treatment effect on the primary endpoint, although the result did not achieve statistical significance. Notably, a prespecified analysis in patients receiving background miglustat and/or leucine therapy demonstrated a statistically significant and clinically meaningful treatment benefit. Based upon its previously announced pre-NDA meeting with the FDA, the Company remains on track to submit an NDA for Trappsol^® Cyclo^™ in the fourth quarter of 2026.

The Phase 3 TransportNPC^™ Study

The global, double-blind, placebo-controlled Phase 3 TransportNPC^™ study (CTD-TCNPC-301) enrolled 94 patients with NPC, ranging in age from 3 to 70 years. Patients were randomized to receive 2000 mg/kg of Trappsol^® Cyclo™ administered intravenously every two weeks (n=63) or placebo (n=31) for a 96-week period to assess change in 4DNPCSS.

A prespecified analysis also evaluated change in 4DNPCSS among patients receiving background miglustat therapy and/or leucine (a food supplement available in some European countries), representing approximately 83% of the study population.

· Primary endpoint: Trappsol® Cyclo™ demonstrated a directionally favorable treatment effect compared with placebo, indicating slowing of disease progression by 64% on change in 4DNPCSS at Week 96 (LS mean change from baseline of 0.46 vs 1.28 points; difference −0.81 points [95% CI −2.04, 0.41]; p=0.19), the result did not achieve statistical significance.

· Prespecified analysis: Among patients receiving background miglustat and/or leucine therapy (n=78), Trappsol® Cyclo™ indicating slowing of disease progression by 71% compared with placebo at Week 96 (LS mean change from baseline of 0.46 vs 1.57 points; difference −1.11 points [95% CI −2.19, −0.02]; p=0.046).

Safety and Tolerability

Over the 96-week treatment period, the safety profile of Trappsol® Cyclo™ was well tolerated. Adverse events were largely consistent with the underlying disease. Treatment-emergent adverse events (TEAEs) were reported as followed: Trappsol® Cyclo™, 93.8%; placebo, 100.0%. Serious TEAEs occurred more frequently with Trappsol® Cyclo™,35.9%, than with placebo 16.7%; however, serious TEAEs considered related to treatment were reported at similar rates 3.1% vs 3.3%. Hearing-related TEAEs were reported by 15.6% of participants receiving Trappsol® Cyclo™ and 13.3% receiving placebo, and most were mild or moderate in severity. One treatment-related event of bilateral deafness in the Trappsol® Cyclo™ group was severe. No TEAEs resulted in death, and one participant in the Trappsol® Cyclo™ group discontinued the study early because of a TEAE.

Separate Overall Survival Analysis

The Company also conducted a separate overall survival analysis comparing patients with infantile-onset NPC treated with Trappsol^® Cyclo^™ across its clinical development program with well-matched external controls from the International Niemann-Pick Disease Registry (INPDR). The external control cohort included patients with similar baseline characteristics and disease progression. Results from the analysis provide supportive evidence of a treatment-associated survival benefit with Trappsol^® Cyclo^™.

Specifically, these data indicated:

· INPDR comparison: Treatment with Trappsol^® Cyclo^™ (n=41) was associated with an 85% reduction in the risk of mortality compared with matched INPDR controls (n=93), HR=0.154; 95% CI: 0.025-0.950; p=0.044.

· Expanded historical control analysis: In a secondary analysis that expanded the control group to include additional matched historical cohorts from published natural history studies (n=133), treatment with Trappsol^® Cyclo^™ (n=41) was associated with a 94% reduction in the risk of mortality, HR=0.057; 95% CI: 0.011–0.306; p=0.0008.

The consistency and magnitude of the observed survival associations across both analyses provide additional supportive evidence for the potential clinical benefit of Trappsol^® Cyclo^™ in patients with infantile-onset NPC.

“The Phase 3 TransportNPC study is the most comprehensive trial in NPC conducted to date,” said Dr. Karen Mullen, Chief Medical Officer of Rafael Holdings. “We believe the totality of the data shared today provide a compelling rationale for the continued advancement of Trappsol Cyclo and its potential to offer clinically meaningful treatment benefit for those living with this devastating disease. We remain steadfast in our efforts to advance Trappsol Cyclo and are deeply grateful to the clinical investigators, patients, and caregivers whose courage and commitment were vital to completing this study.”

“NPC is a devastating, heterogeneous disease, and preserving function and stabilizing symptoms are critical,” said Dr. Caroline Hastings, Professor of Pediatric Hematology and Neurology at UCSF Benioff Children’s Hospital Oakland. “As a clinician who has cared for these patients for many years, I am encouraged by the clinically meaningful TransportNPC results. The study was rigorously conducted, and its findings align with the two prior trials for Trappsol Cyclo across a decade of development. I am hopeful that these data can move us closer to delivering a much-needed therapeutic option for families facing profound unmet need.”

2

NDA On Track for Fourth Quarter 2026

The Company remains on track to submit an NDA for Trappsol^® Cyclo^™ to the U.S. Food and Drug Administration in the fourth quarter of 2026 based upon its previously announced pre-NDA meeting. The topline data, complete dataset and overall survival analysis remain subject to full analysis and FDA regulatory review. The Company also plans to present the full results at an upcoming medical meeting.

Conference Call Information:

Date: Wednesday, September 30, 2026

Time: 8:30 a.m. ET

Domestic Dial-in Number: 1-877-425-9470

International Dial-in Number: 1-201-389-0878

Conference ID:13763049

Webcast Participant Link: https://viavid.webcasts.com/starthere.jsp?ei=1777956&tp_key=73c1065384

About 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. Our lead candidate is Trappsol^® Cyclo^™, and we have completed a pivotal Phase 3 study in NPC and are preparing for a planned NDA submission later this year. Niemann-Pick Disease Type C (“NPC”) is a rare, fatal and progressive genetic disorder. We also hold interests in other clinical-stage and early-stage pharmaceutical development companies and an orthopedic-focused medical device company.

Forward Looking Statements

This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements contained in this press release that do not relate to matters of historical fact should be considered forward-looking statements, including without limitation statements regarding our expectations surrounding the potential, safety, efficacy, and regulatory and clinical progress of our product candidates; plans regarding the further evaluation of clinical data; and the potential of our pipeline. These statements are neither promises nor guarantees, but involve known and unknown risks, uncertainties and other important factors that may cause our actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements, including, but not limited to, the risk that the FDA may not accept for filing or approve an NDA for Trappsol® Cyclo™ based on the available data, and those disclosed under the caption “Risk Factors” in our Annual Report on Form 10-K for the year ended July 31, 2025, our subsequent Quarterly Reports on Form 10-Q, and our other filings with the SEC. These factors could cause actual results to differ materially from those indicated by the forward-looking statements made in this press release. Any such forward-looking statements represent management’s estimates as of the date of this press release. While we may elect to update such forward-looking statements at some point in the future, we disclaim any obligation to do so, even if subsequent events cause our views to change.

Contact:

Barbara Ryan

Barbara.ryan@rafaelholdings.com

(203) 274-2825

3

Filing Exhibits & Attachments

4 documents

Press Releases

• EX-99.1 PRESS RELEASE, DATED SEPTEMBER 30, 2026 20.4 KB

Other Documents

• EX-101 XBRL SCHEMA FILE 3.0 KB
• EX-101 XBRL LABEL FILE 33.4 KB
• EX-101 XBRL PRESENTATION FILE 21.8 KB