Rafael Holdings (RFL) trial results, September 30, 2026 transcript

Thank you, Sherry, and good morning to all of you joining us today. Earlier this morning, Rafa Holdings announced top-line results from the pivotal Phase III transport NPC study of Trapsol Cyclo in Neiman-Pick disease, Type C. Joining me today are Joshua Fine, our Chief Operating Officer, and Dr. Karen Mullen, our Chief Medical Officer. Before we begin, please note that today's call will include forward-looking statements within the meeting of the Private Securities Litigation Reform Act of 1995.

These include statements about the potential safety, efficacy, and clinical benefit of TrapSol Cyclo, the interpretation of the study data, our regulatory plans, including the timing of an NDA submission, and the potential for FDA acceptance or approval. These statements are based on our current beliefs, expectations, and are subject to risks and uncertainties that could cause actual results to differ materially. These risks include those described under risk factors in our annual report on Form 10-K for the fiscal year ended July 31, 2026, and our other filings with the FCC. The top-line data and the survival analysis remain subject to full analysis and FDA review. Forward-looking statements speak only as of today, and we undertake no obligation to update them.

You can find today's press release containing today's data on the investor section of our website at rafaelholdings. com. I will now turn the call over to Joshua.

Thank you, Barbara. Hello, and good morning. Thank you for joining us as we announce this major milestone in our company and patients living with Neiman-Pig disease, type C, or NPC. We spent the last 15 years focused on the pursuit of developing Trapsocyclo for the treatment of this rare, fatal, progressive genetic disorder. NPC is characterized by a defect in the NPC protein affecting approximately 900 patients a year in the United States and 9,000 patients worldwide. The results presented this morning are a culmination of our rigorous dedication to the science and the patients who are in desperate need of effective therapeutic options.

Trapsal Cyclo has been developed to treat both the systemic and neurological manifestations of NPC. Across multiple clinical studies, we have shown encouraging results, bringing us to this morning's announcement reporting the top-line results from the Transport NPC study. A global double-blind placebo-controlled Phase III study in 94 patients with NEMAN-PIC type C. We are extremely encouraged by these results, and this data gives us confidence to continue advancing TrapSaw Cyclo. Based on our previously announced pre-NDA meeting with the FDA, we remain on track to submit our NDA for TrapSaw Cyclo in the fourth quarter of 2026 and remain eligible for a priority review voucher or PRV. I'd like to thank all the patients, caregivers, patient community members, and the Cyclotherapeutics and Rafael team members for their help and dedication throughout this process.

At this time, I'd like to introduce our Chief Medical Officer, Dr. Karen Mullins, who will walk you through the data in more detail.

Good morning This pivotal phase 3 double placebo study is the most comprehensive trial in MPC conducted to date spanning 13 countries and 27 sites comprising 94 patients randomized 2 to 1 to receive Trapsil Cyclo 2 mg per kg plus standard of care given intravenously every two patients to placebo with an age range of 3 to 70 years allowing the study to capture the broad spectrum of patients in this heterogeneic disease The primary endpoint was changed from baseline in the four-domain Newman-Pick-C clinical severity scale, known as 4D at week 96. The 4D is comprised of four domains, swallow, ambulation, sign motor, and speech. A lower number indicates improvement and a higher worsening. So improvement on the 4D scale is a negative value.

The primary endpoint was the modified intent to treat analysis on the MMRM. This showed a mean treatment difference of minus 0.811 in favor of Trapsil Cyclo with a p-value of 0.19. While this did not achieve statistical significance, it was directionally favorable towards Traxyl Cyclo and indicated a slowing of disease progression by 64% of the change of the 4D in 96 weeks. The study also included a pre-specified subgroup analysis of patients receiving background miglostat and or leucine. For clarity, leucine in this study is a food supplement available in some European countries. This subgroup represented 83% of the study population, 78 patients out of the 94. This subgroup, Trapsyl Cyclo, showed a mean treatment difference of minus 1.105, reaching a statistical significant p-value of 0.046, indicating a slowing of disease progression by 71% compared with placebo at 96 weeks.

Moving to safety. Trapsylcyclo was well tolerated over the 96-week period, consistent with previous studies. The adverse events are largely consistent with the underlying disease. Most were mild to moderate, with a comparable proportion of patients in each group reporting treatment-emergent adverse events. 93.8% in Trapsylcyclo versus 100% in the placebo group. Serious adverse events occurred more frequently with Trapsyl Cyclo, 35.9%, compared to placebo, 16.7%. However, those that were considered treatment-related adverse events were reported in a similar proportion of each group, 3.1% Trapsyl Cyclo versus 3.3% in placebo. For hearing, the majority of the hearing-related treatment emergent adverse events were mild to moderate. 15.6% in the trapsocyclo group versus 13.3% in the placebo group, and this included all ear-related adverse events.

Importantly, only one treatment-related event was severe with the patient requiring bilateral hearing aids in the Trapsil Cyclo group. No adverse events led to death. One participant in the Trapsil Cyclo group had an adverse event that led to early withdrawal from the study. As previously presented, an open-labeled pediatric sub-study of this phase 3 study was conducted. This enrolled 10 patients under the age of 3 in this highly progressive infantile form of MPC.

Of the patients who reached 96 weeks, 71% showed an improvement or stabilization on the clinical global impression change, and 29 of the patients showed deterioration The safety profile was considered well tolerated 27 reported serious adverse events non related study drug Separate from the phase three study an overall survival analysis comparing I going to turn the call over to management for the Rafael Holdings and I going to turn the call over to management for the Rafael Holdings This was a significant reduction in the risk of mortality, a hazard ratio of 0.154 and a p-value of 0.044. This comprised 41 patients treated with trapsocyclo and 93 matched controls from the registry. In a secondary analysis, to broaden the registry cohort with an additional matched external control from published natural history studies, Trapsil Cyclo was associated with a 94% reduction in the risk of mortality.

Hazard ratio 0.057, p-value 0.008. This analysis had a total of 133 matched external controls. The consistency and magnitude of these survival associations, we believe, provide additional supportive evidence of the potential clinical benefit of trapsocyclo in patients living with infantile onset MPC. The totality of these data provides a compelling rationale to continue advancing trapsocyclo for patients living with MPC. As a reminder, the top-line data, complete data set, and overall survival analysis remain subject to a full analysis and FDA regulatory review.

Finally, we are deeply grateful to the patients, caregivers, and clinical investigators whose participation was critical to completing the study. And I'll hand back to Josh.

Thank you, Karen. So, in summary, the company remains on track to submit our NDA for TrapSol Cyclo to the FDA in the fourth quarter of 2026. Over the coming weeks, our priorities are completing the full analysis of the Transport MPC dataset, preparing the NDA submission, then focusing on commercial readiness. Before we close, I would like to thank everyone who joined our call today and all of our stakeholders for your continued support on working with us to bring this much-needed therapy to the NPC community.

With that, operator, please open the line for questions.

Hey, Samant, it's good. Thank you for joining the call today. I'll take this first and then pass to Karen. And based on the outcomes of the pre-NDA meeting, I think what we got was an alignment on our submission strategy and a basic understanding of what the total data package was going to look like with the expectation that, you know, based on the interim, which we published, that our p-value wasn't achieved. Anything further than that I not able to provide unfortunately But we feel comfortable with the fact that we believe we are aligned with the FDA and have confidence that we can get this drug to these patients Great Thanks for that detail Now, given there are a couple of products already approved in the U. S. for NPC, and there is one pending for infantile onset, how do you think the data set here would be viewed in light of that, against that backdrop, I guess?

Good morning, Samalyn. Great to have you join us this morning. So yeah, you know, this is a devastating disease, and it's great to have options for these patients, and we know that they may well be used in combination. Obviously, there's no head-to-head studies where we are confident about our data, our totality of our data, and importantly, there's a real unmet need in the infantile form, the early infantile form, which is highly aggressive, and also not just treating the neurological symptoms, but also treating the visceral symptoms as well, where, as Josh has said, the development of trapped It's actually also for the visceral and neurological symptoms. So I think that if all our drugs are approved, it's great to have options for the community out there.

Great question. Of the four subdomains, there was a favorable direction to Trapsil-Cyclo, the main one being swallowing, which we know that that is probably one of the most important domains with regard to morbidity and mortality. So, we're seeing improvements across the board and the domains.

Sorry, Simant, you broke up a little. Can you ask – I heard the end of the question.

Yeah, I mean, you know, we've got a large totality of data across the 15 years of development, And, you know, as Josh said, we had good alignment in our pre-NDA meeting about the roadmap for our submission, which we're well on track for. If there is any additional analysis of data required by the FDA, we would absolutely be working with them to ensure that we would submit that in a timely manner for, you know, to be able to bring this to patients that matters.

I would like to thank everyone for their time today and joining this call and for their continued support of Rafael Holdings and Cyclotherapeutics. We look forward to speaking with you all in the future. Thank you.