So one thing is the 25-foot walk test, which is pretty established, cognition testing, and the nine-hole peg test specifically. So those three are the established tests, which are also recorded during this study. So we will also expect data on those end points on top of just the EDSS clinical read-out.
Mayank Mamtani: Got it. And any comment on the brain volume changes schematics relative to NfL, given your interim at 24-week and then obviously, the final analysis at 72-week?
Daniel Vitt: Yes. I think brain volume change is believed to be a robust and sensitive measure of neurodegeneration in MS patients. Specifically, if it comes to the long time line, we have a 120-week full uptime in the CALLIPER study. So brain volume change should be a strong signal here. And we know that this is — they are traditionally is expected to correlate with disability and also then with NfL changes. There is to my knowledge, not too many publications on the direct correlation between brain volume change and NfL, but they all refer usually to disability change in the patients. And specifically, I think in the recent months, I think there were a couple of good publications where the office nicely separated inflammatory for non-inflammatory patients, which is, I think, very important to quantify any signal on NfL in progressive MS in contrast to relapsing, because as we all know, if there is an overlying relapse activities from the NfL side, usually has a high risk of overlay the signal of NfL.
Mayank Mamtani: Yes. Makes sense. Thank you. And then on the Phase 3 sample size reassessment or futility for ENSURE later in the year, could you just remind us of the different scenarios in terms of how high you have to increase the patient number or vice versa? Could you — given what you’re seeing versus placebo, because you don’t have an active competitor here, could you also — maybe a good — if you’re seeing the event rates that you expect or better than that? Is there a positive scenario where you could expedite the program? So maybe just loop in the scenarios there from the reassessment.
Daniel Vitt: Yes. Thank you for that question. It’s important that you asked that, I think. We need to repeat these things a couple of times. The FDA does not allow any acceleration of the program for the stopping for early response signals because that is — due to the statistical planning of such a study, they exclude this option, so we can’t do that. What we did is we — so it’s a futility analysis, so we can most likely or we hope to get a proceed as planned feedback from the committee. What could also be — we will have a couple of scenarios of sample size adjustment, but only if such ones which makes sense. I think it doesn’t make sense to make sample size adjustment if it’s getting a huge number of patients to that. So only these viable approaches could be an answer to that analysis. And else, we will maybe then have an answer that we should stop the study.
Mayank Mamtani: Okay. Thank you for taking my question.
Jessica Breu: Thank you, Mayank. We have one more on the queue Tom Smith with Leerink Partners. Tom, please un-mute yourself, and welcome to the call.
Tom Smith: Hey, guys. Good morning. Thanks for taking the question. Just a couple on our end, I guess, first, for the Phase II CALLIPER study, can you — and this extends I guess, across your entire MS program, but can you just remind us how you’re measuring neurofilament light chain, what assay you’re using and how much variability there is with measuring of marker? And then with respect to life cycle management, can you comment on whether you’re working on any additional IP for vidofludimus calcium or preclinical Nurr1 activator compounds that could help extend the franchise? Thanks very much.
Daniel Vitt: Yeah. Thank you, Tom, for the questions. First of all, I think, in the past, we commented a lot on the technologies here. I think what we are using is more or less state-of-the-art Simoa technology by Quanterix. We use also the newest dual-antibody test system there for this technology. So that is I think, really with the goal to reduce the signal noise ratio as much as possible. Another thing is that we do — we measure all the batches in parallel in one. So we really try to avoid any operational variability in testing that. So I think this — the data on NfL will be as precise as possible from a technology point of view right now. But to remind you, I think every technology has its own absolute level. So we just need to look always on relative changes on NfL at the read-out.
So that’s on the technology side. On more on the strategic side on IP and life cycle management, we don’t talk too much about, but of course, we’re doing that. And if you’ll read between the lines what we are telling you, I think what we — last year, when we identified that vidofludimus calcium is a potent activator of Nurr1, and this is importantly means also we see in the gene regulation, an up to 500% increase of gene regulation. This is really at the upper end of what you can get at all, and to my knowledge, really the only molecule in the clinics to test on something like that. This makes it an attractive platform. So it’s not only that vidofludimus has another trick, which is wonderful, because this opens up the avenue towards neuroprotection, it also gives us at Immunic — a platform of Nurr1 modulation.
And we are working here internally, but also in collaboration with researchers at different universities on one hand on the biology and on the other hand, also on the chemistry to broaden what we’re doing here. We have some IP filed on this. We have some interesting derivatives of vidofludimus calcium in research, yes, I think absolutely. So we think this is a great platform. And just think about the great biology, which was published and where a lot of work was done on Parkinson’s disease and other neurodegenerative diseases where Nurr1 is believed to play a major role. And this opens up a lot of potential for further preclinical and clinical work later.
Tom Smith: Got it. Super helpful. Appreciate you guys taking the questions.
Daniel Vitt: Thank you, Tom.
Jessica Breu: Thank you, Tom. This concludes our question-and-answer session. I would like to turn the conference back over to Daniel for any closing remarks.
Daniel Vitt: Yes. Thank you, Jessica, and thank you to today’s attendees for your insightful questions today. To summarize, we have a well-differentiated advanced clinical pipeline in various stages of development, with the top line data from our Phase 2 CALLIPER trial executed in April of next year and the ongoing enrollment of our Phase 3b and ENSURE trials, we continue to make meaningful progress on the clinical development of vidofludimus calcium. We also continue to strengthen our intellectual property position and remain committed to that effort. Further, the successful three-tranche PIPE financing earlier this year means that we are well capitalized to execute with 97.3 million on our balance sheet, which is expected to fund the company into the third quarter of 2024 – 2025 sorry.
As progress is made, we expect to also provide an update on our preparations for a Phase 2 clinical trial IMU-856 and its potential for the treatment of a broad array of serious gastrointestinal disorders. With that, I would like to close today’s call. Thank you very much for joining, and we’re very happy to answer any additional questions one on one.
Jessica Breu: Thank you for joining Immunic’s first quarter 2024 earnings call. The call has now concluded. You may now disconnect.
