Rafael Holdings 3rd Annual Guggenheim Healthcare Innovation Conference

Sure. Thank you. Take a breath first.

Yeah, no, it is a good run. Thank you for hosting us, Eddie, and thank you to Guggenheim for hosting us as well. We appreciate it. We are happy to be here. So, real quick on Rafael Holdings Cyclo Therapeutics. The two companies came together in March of 2025. At that point in time, Rafael had actually been the largest investor in Cyclo Therapeutics. Cyclo Therapeutics, which is where we are going to focus most of our time and most of the questions on, I believe, today, has actually been around since the 1990s. But in 2014 and 2015, they launched their study on Trappsol Cyclo for the treatment of Niemann-Pick type C. Over the last now 10-plus years, we have completed our phase I, phase I/II, and we just completed our pivotal phase III study for the treatment of the neurovisceral manifestations of Niemann-Pick type C from adult to birth.

That study completed in June of this year. In September, we reported out our top-line data on our pivotal study, and at the end of last month, we submitted our NDA to the FDA for what is now called remibetadex for the treatment of Niemann-Pick type C. We are predominantly an R&D company at this point in time, but our plan is to commercialize the asset and launch it here in the States. That is us in a nutshell.

Sure. I am going to start this one off and then pass it over to you.

Yeah, absolutely. The study kicked off in 2021.

It was a two-year, 94-patient double-blind study with a 48-week interim look. That study design was actually done collectively and fairly collaboratively with the FDA, who wanted us to extend out our study for two years as a result of what we think were some of the things that they were seeing in the industry at the time.

The endpoints Yeah. The endpoints are the composite score of the 4D, which is swallow, ambulation, fine motor, and speech.

These endpoints were developed with the FDA based on their feedback of previous other molecules that they were looking at. During the kickoff of our phase III trial, not only did we add that as a primary endpoint, but we also looked at Trappsol Cyclo against standard of care and placebo against standard of care, which is important. Part of what we did in the development of that is, in order to participate in the study, miglustat was also being used at this time as a standard of care for both placebo and Trappsol. Those patients that came in had to be on background miglustat for three months as part of coming into entry of the study.

When you think collectively as our program worked out in our specification, our pre-specified covariate with the FDA, it was done with purpose at the beginning of the study.

Yeah, sure. As Mike said, and as you stated, we missed on our primary.

The pre-specified covariate that we saw was actually an incredibly exciting moment for us. It represented a very large portion of our patient population, and as Mike said, the clarity was that it was all patients were either on remibetadex miglustat or placebo and miglustat. The patient population itself was large enough to get us excited. Additionally, as we looked at some of the underlying data, we saw some pretty compelling trends in the individual domains, and then as we've also published, the sub-study data from the 0 to three patient population was incredibly influential and incredibly exciting. As we've noted, at 48 weeks, we saw eight of 10 patients either stabilize or improvement, and this is a patient population that is the most severely affected.