Good morning, and welcome to Immunic’s Third Quarter 2024 Earnings Call. My name is Jessica Breu, Vice President, Investor Relations and Communications at Immunic. I will also be the moderator today. Speaking on the call are Dr. Daniel Vitt, our Chief Executive Officer, Glenn Whaley, our Chief Financial Officer; as well as Jason Tardio, our President and Chief Operating Officer. Please note that all participants will be in listen-only mode, and this event is being recorded. After today’s presentation, there will be an opportunity to ask questions. [Operator Instructions] Before we begin, I would like to remind you that this presentation may contain forward-looking statements. Such statements can be identified by words such as may, will, expect, anticipate, estimate, or words with a similar meaning. And, such statements involve a number of risks and uncertainties that could cause in Immunic’s actual results to differ materially from those discussed here. Please note that these forward-looking statements reflect Immunic’s opinions only as of the date of this presentation, and it undertakes no obligation to revise or publicly release the result of any revision to these forward-looking statements in light of new information or future events. Please refer to Immunic’s SEC filings for a more detailed description of the risk factors that may affect Immunic’s results and these forward-looking statements. I would now like to turn the call over to our CEO, Dr. Daniel Vitt, to begin the presentation. Daniel?

Thank you, Jessica. I would also like to welcome everybody to today’s Q3 2024 earnings call. Earlier this morning, we announced our financial results for the third quarter and nine months ended September 30, 2024. During the call today, we will walk through our third quarter 2024 achievements and subsequent highlights, financial and operating results as well as our clinical development programs, including anticipated upcoming milestones. As Jessica noted, after the presentation, you will have the opportunity to ask questions. Let’s start with the review of our third quarter 2024 and subsequent highlights. In July, our management team was strengthened with the addition of Jason Tardio, as President and Chief Operating Officer, bringing with him a wealth of experience launching and commercializing multiple sclerosis drugs for major biotechnology and pharmaceutical companies. Jason has already proven to be invaluable, leading internal efforts to prepare for the potential commercialization of vidofludimus calcium. Jason also has been collaborating closely with Patrick Walsh, our Chief Business Officer, to prepare the company for a range of potential partnership outcomes for vidofludimus calcium as well as our other drug candidates, where we are leveraging his extensive partnering experience. Additionally, Werner Gladdines was promoted to Chief Development Officer. Werner joined Immunic in January of 2021 as Head of IMU-838 Program, and he has held positions of increasing responsibility since then. In his new role, he takes over additional strategic and operational responsibilities for Immunic’s overall clinical operations functions. In July, we also strengthened our Board of Directors with the appointment of Simona Skerjanec, a thought-leader in brain health with decades of experience in drug development and commercialization. Over a 30-year career in the United States and internationally, Simona has led research and development efforts, culminating in numerous regulatory drug approvals and successful commercial launches, working at companies…

Sure. And thank you, Daniel. The ECTRIMS Congress is the premier meeting of the year in the field of multiple sclerosis and brings together over 9,000 of the world’s top clinicians, researchers, and healthcare professionals. We are particularly excited to have had the opportunity to present data at this meeting to further support the differentiation of vidofludimus calcium as a potential treatment for both relapsing and progressive multiple sclerosis. More specifically, we shared additional data from the interim analysis of our ongoing Phase 2 CALLIPER trial in progressive multiple sclerosis that showed that vidofludimus calcium not only had a significant impact on reducing serum neurofilament light chain across the total study population, but also consistently reduces neurofilament light chain levels compared to baseline across different patient subgroups based on age and disability scores. These observations are important as neurofilament proteins are a marker of neuronal degeneration and serve as an important biomarker of disease activity in multiple sclerosis. With recent data showing that lower neurofilament light levels indicate a lower risk of future disability progression in progressive MS patients. We also prevented compelling data on fatigue from post-hoc analysis of the CALVID-1 trial, which evaluated the safety and efficacy of vidofludimus calcium 45 milligrams in patients hospitalized for COVID-19. As mentioned earlier, fatigue is the most frequent symptom reported by patients with multiple sclerosis. And for many patients, it is the most disabling and chronic symptom. Given the broad spectrum antiviral effects of vidofludimus calcium and its potential to prevent reactivation of the Epstein-Barr virus or EBV, which has been linked to fatigue in multiple sclerosis, we sought to understand the impact of vidofludimus on fatigue in Post COVID syndrome patients. Results of this analysis show that 80% of patients who received placebo reported fatigue compared to only 50% of patients who received vidofludimus calcium. Fatigue was further decreased from weeks 9 to 17 to 33% for patients on placebo and only 17% for patients on vidofludimus calcium, thus supporting the antiviral effects of vidofludimus and how it may contribute to lower fatigue levels. This hypothesis we further assess by determining effects on fatigue using patient questionnaires as well as analysis of the anti-EBV effect in our ongoing CALLIPER and ENSURE trials. Lastly, we presented additional preclinical evidence supporting that vidofludimus calcium enhanced the expression of Nurr1 target genes, important for neuronal survival, further suggesting the neuroprotective benefit of this assay. And, also reduce infiltrating T helper cells in the spinal cord and the number of pro-inflammatory T helper cells in the peripheral in marine EAE models. In addition to these data presentations, Immunic also filled an exhibitor booth for the first time at this important meeting. This served as a great opportunity to engage the MS community and further increase awareness of vidofludimus calcium as a potential treatment for MS. Back to you, Daniel.

Yes. Thank you, Jason. In October, we announced a positive outcome of the interim analysis of our Phase 3 ENSURE program of vidofludimus calcium in relapsing multiple sclerosis or RMS. An Independent Data Monitoring Committee, IDMC, reviewed unblinded data and based on this, recommended that the trials are not futile and should continue as planned without any changes, marking the successful achievement of a critical milestone for the program. While Immunic remain blinded to our data, the IDMC favorable recommendations corroborate our initial assumptions of the design, powering and relapse rate of the twin Phase III trials and to suggest that they are in-line with the data observed so far. In particular, the plan sample size seems appropriate to address the statistical assumptions for the primary endpoint of time to first relapse. We are confident in vidofludimus calcium’s potential to transform the RMS market and continue to believe that the Phase III program provides a clear and straightforward path towards seeking potential regulatory approval in RMS. That concludes our summary of the third quarter 2024 and most recent highlights. I am very pleased with the scientific and clinical achievements we have made across our programs. As it relates to vidofludimus calcium, we continue to advance both our twin Phase 3 ENSURE trials in patients with relapsing MS and our Phase 2 CALLIPER trial in progressive MS. We are very excited to read out the topline data of the CALLIPER trial in just a couple of months from now expected in April 2025. Based on the strong clinical evidence today, we continue to pursue partnering discussions with global and regional pharmaceutical companies. Our team has also been busy advancing our IMU-856 Program, which has the potential to become a game changer for the treatment of a broad range of gastrointestinal disorders. I would now like to turn the call over to Glenn, to provide a financial overview. Glenn?

Thank you, Daniel. I will now review the financial and operating results for the third quarter and nine months ended September 30, 2024. Let me start with a review of our cash position. We ended the third quarter of 2024 with $59.1 million in cash and cash equivalents, which we expect to be able to fund our operations into the third quarter of 2025. Regarding the operating results, R&D expenses were $21.4 million for the three months ended September 30, 2024, as compared to $19.8 million for the three months ended September 30, 2023. The increase was mainly driven by increases in external development costs related to our clinical trials, which was partly offset by a decrease from the deprioritization of the izumerogant program in psoriasis and castration-resistant prostate cancer last year. For the nine months ended September 30, 2024, R&D expenses were $58.4 million as compared to $63.9 million for the nine months ended September 30, 2023. The decrease was mainly driven by the deprioritization of the izumerogant program in psoriasis and castration-resistant prostate cancer and the completion of the Phase 1 clinical trial of IMU-856 in celiac disease last year. This was partially offset by an increase in external development costs related to the vidofludimus calcium program as well as an increase in personnel expenses. G&A expenses were $4.4 million for the three months ended September 30, 2024 as compared to $3.8 million for the same period ended September 30, 2023. The increase was primarily related to personnel expenses. For the nine months ended September 30, 2024, G&A expenses were $14 million as compared to $11.9 million for the same period ended September 30, 2023. The increase was primarily related to personnel expenses, legal and consultancy expenses and other across numerous categories. Interest income remained unchanged at $0.8…

Thank you, Glenn. I would now like to provide an update on our clinical development programs and anticipated upcoming milestones. Our next important clinical readout, which we are eagerly anticipating, will be the topline data from our Phase 2 CALLIPER trial of vidofludimus calcium in progressive MS in April of next year. In addition to the overall PMS population, the data would also deliver insights on its sub-forms, including non-relapsing secondary progressive MS, a subtype with the highest unmet medical need. Should the topline data continue to show a neuroprotective effect and the Phase 2 trial meets its primary and key secondary endpoints, we may also be able to position the drug as the first oral treatment option for non-relapsing secondary progressive MS. Additionally, we are progressing as planned with our Phase 3 ENSURE program of vidofludimus calcium in relapsing MS and expect to complete the first of our identical twin Phase 3 ENSURE trials in the second quarter of 2026. The completion of the second ENSURE trial is expected in the second half of 2026. As it relates to our second clinical program, IMU-856, we remain very enthusiastic and believe that its innovative mode of action is uniquely suited to treat a broad range of serious gastrointestinal disorders by targeting physiological intestinal epithelium regeneration, resulting in gut wall healing with the absence of broad immunosuppression seen in many currently available gastrointestinal drugs in use today. It bears repeating that data from our Phase 1b clinical proof-of-concept trial of IMU-856 in patients with celiac disease during periods of gluten-free diet and gluten challenge demonstrated significant improvements over placebo in four key dimensions of clinical outcomes in celiac disease: protection of the gut architecture, improvement of patients’ symptoms, enhancement of nutrient absorption and a strong biomarker response. As previously reported, we have begun preparing for Phase 2 clinical testing of IMU-856. And, in addition to celiac disease, we are also exploring a number of other clinical applications for other gastrointestinal disorders, where the renewal of the gut wall is important. We are currently exploring options to separately fund this unique asset and are openly considering different avenues. Let me hand over to Jason, at this point again to emphasize vidofludimus calcium’s unique profile.

Thank you, Daniel. Now, part of the reason I joined Immunic, just a few months ago was because of what I see as a tremendous opportunity and a tremendous potential for vidofludimus to transform the MS market and to potentially become the leading therapeutic within the oral disease modifying therapy segment. The profile of this drug candidate is unique given its first-in-class dual mode of action approach designed to address the full spectrum of multiple sclerosis from stages of relapses and focal inflammation through the progressive stages where neurodegeneration takes hold. As a first-in-class Nurr1 activator, vidofludimus calcium goes beyond inflammation, providing direct neuroprotective effects and thereby offering potential benefits for both relapsing, progressive MS patients. In addition, vidofludimus is also a highly selective DHODH inhibitor associated with potent anti-inflammatory effects, which we know plays a key part in the relapsing forms of multiple sclerosis. We believe this mode of action combine with an exceptional safety and tolerability profile and the convenience of once-daily oral administration gives vidofludimus calcium a potentially best-in-class benefit risk profile within the oral class of medicines. Initially, it’s worth highlight that we do not believe there is going to be any first dose or on-treatment monitoring necessary, which means this will be an easy medicine to start newly diagnosed patients on and also a very easy medicine to switch patients to, remembering that about 65% of the market today is a switch category. We also do not anticipate any safety concerns or black box warnings specific to the vidofludimus calcium. Given this profile and if approved across the vast indications of multiple sclerosis, we believe vidofludimus calcium has the potential to transform the oral disease modifying therapy market with expected peak sales of this product ranging from US$2 billion to US$6 billion. This brings us to the end of our formal presentation. Jessica, please open the call for the Q&A session.

Yes. Thank you, Jason and Daniel and Glenn, for walking us through the third quarter and subsequent highlights, as well as our clinical development pipeline and upcoming value inflection points. We will now begin the question-and-answer session. As a reminder, if you joined the webcast via the Zoom platform, there are two ways to submit questions. You can either submit your questions in writing via the Q&A tool of the Zoom portal, or if you would like to speak with us directly, please use the raise hand function of the Zoom portal to queue your question. Our first guest today is William Wood from B. Riley. William, welcome, and please unmute yourself.

Thank you so much. We really appreciate you, taking our questions, and congrats on another successful quarter. We have a couple of questions, on our end. So the first is, just thinking about your CALLIPER study, coming up readout in April. This is in PMS, so SPMS including active and non-active as well as PBMS. What level of detail should we expect a topline readout across these populations for both your primary as well as your secondary endpoints presented, possibly CDW, NfL, and or GFAB? Essentially, I’m trying to, are we going to just get an overall population data, or should we expect some of these subpopulation data also? And then, I have a follow-up. Thank you.

Yes. Thank you, William, for that wonderful question. And, I have good news. So, we plan to really, come out with detailed data on the general and the subforms, tested during the study, as we did for the interim analysis a year ago. And also, we really tried to have everything possible available at the readout, including the very important clinical endpoint, so confirmed disability worsening, the biomarker, NfL, but also GFAB, given that the duration of the study allows to also evaluate that exploratory biomarker, and also the brain atrophy data, of course. So, it will be quite comprehensive data we’re expecting in April next year.

Excellent. It’s great to hear. And then, just a quick second one. You also have as you noted, you have your ongoing Post COVID investigator-led trial, going on in Germany. You’re looking to enroll, looks like, about 376 patients. It’s got a 56 day timeline, and it’s obviously evaluating fatigue, a key issue in multiple sclerosis. Maybe you could remind me when we might expect the data here possibly before ENSURE’s readout in 2026? And if so, how should we think about the results in this Post COVID trial, how it might highlight your dual-MOA and success in ENSURE? And then, remind me if there’s any type of subtype analysis or earmarking of patients in either ENSURE or CALLIPER that are diagnosed with Post COVID syndrome? Thank you. I’ll hop back into queue.

Okay. I hope I remember everything from the questions. So, starting with the Post COVID study, this is an investigator-sponsored trial. And therefore, we really can’t give any guidance on the speed of recruitment. I know that the study kicked off and they have patients in, but we are not a sponsor. We provide here the drug. But, we’re excited about the specific analysis here. The role of fatigue is super important in multiple sclerosis. And, it’s interesting to see the overlap and the role of EBV, expected in both in MS, but also in Post COVID syndrome. Therefore, it could be scientifically and medically very meaningful thing, even if it’s an investigator-sponsored trial. So, we want to learn, and we want to use that knowledge for the patients, to have a better treatment option, also to understand why and to what extent vidofludimus calcium can really make a difference here on preventing fatigue. And then, there was a second part of the question. I forgot what that was.

Yes. Just if you’re earmarking, or making note of or any type of sub-analysis going on in ENSURE or CALLIPER for these Post COVID syndrome patients, just to sort of understand how that might translate, their data might translate to these larger trials?

Yes. That’s a good point. It’s not predefined, in the study, as far as I know. But, we will see if that shows up in the general safety monitoring of the study.

Yes.

And, if we have data, we will likely also extract that, maybe not at a topline data readout, but maybe at a later time point then.

Great. Makes sense. Thank you again, and I’ll hop back in the queue. Congrats again on a very nice quarter.

Thank you, William.

Thank you, William. The next one I have in the queue here is Yasmeen Rahimi with Piper Sandler. Yas, please unmute yourself and go ahead.

Hey. Good morning, team. This is [Jungkook] (ph) on for Yas.

Hi, Jungkook.

Thanks for taking our questions. First, to the extent, can you comment on what do you see on a blinded basis for CALLIPER, in regards to safety and efficacy? And secondly, given that CALLIPER has different PMS subpopulations for disability worsening, can you detail which subgroup is most likely experienced the biggest treatment effect?

Thank you. Let me start with the first thing. We see blinded data. We can’t conclude anything from that. So and, therefore, we should not speculate on anything on the blinded data for CALLIPER. So far, what I hear from the clinical team, the study is progressing as expected. So, that’s all I can say. On the sub-indications, that’s a good point. I think there is clearly, there are three sub-indications predefined in CALLIPER, the Active Secondary Progressive, Non-Active Secondary Progressive and Primary Progressive MS. And, I think the Non-Active Secondary Progressive and Primary Progressive populations are kind of similar, on the issue that they don’t have relapses, that we you don’t measure lesions in the brain, no inflammatory lesions, but they still progress on disability. And, given that we have certain inclusion criteria for baseline EDSS score, so we think those should be in the same ballpark of placebo disease activity in those patients. It’s a little bit different, I think, for the active SPMS patients, given that there are still some inflammatory activity. And therefore, we expect that to be a little bit, generally, I think, a little bit higher. But also, the number of those patients, it’s a smaller subgroup in the study. It’s 9% of the patients in the study.

I got it. Thank you.

Thank you, Jungkook. Next one in the queue here is Faisal Khurshid from Leerink Partners. Faisal, please unmute yourself, and good morning.

Hey, guys. Good morning. This is, Matt Cowper on for Faisal Khurshid. Thanks for taking my question. A couple from me. What hazard ratio for disability worsening will you be looking for in CALLIPER to feel good about vidofludimus’ potential in PMS? And then, pending positive data, in CALLIPER, is there any opportunity for an accelerated registrational path in PMS, or would you have to run a trial similar to what we see with the BTKs in PMS? Thank you.

Yes. Thank you, Matt. Hazard ratio assumptions. I think there is no predefined bar right now, of what you need to show, of course, but there is a little of a perception of KOLs, what they perceive as medically meaningful. And, we asked the questions of the medical team. There was, we had a meeting with some of our KOLs not too long ago, and my colleague Andreas asked the team, what do you expect? And, the discussion more or less came around, okay, if it’s a 15% benefit on disability protection that is something. At 20%, I think everybody agreed that, that’s a real signal. So, we think that there’s no hard line, but a 20% benefit would be a big win for the molecule. And, then the better, the higher the difference, the better for the drug, of course. And, on accelerated approval, that’s definitely an opportunity. But, again, it depends on the data, on the one hand and the distribution of the data. And there, for example, how similar are things between the subgroups and so forth. And then, and the signal strength, for example, in the biggest population in the study, and in non-active secondary progressive patients. And, that may qualify for having at least a discussion with the FDA on any kind of expedited way forward. However, we can’t guarantee that this is an opportunity, but definitely worth a try.

Great. Thanks for the insight and taking my questions.

Thank you.

Thank you, Matt. Just for full transparency here, we also had the question on accelerated or expedited approval two times in the chat. So, I guess this is answered now. Next one in the queue here is Matt Kaplan from Ladenburg. Matt, please unmute yourself and go ahead.

Hey. Good morning, guys. Just wanted to stay on the CALLIPER study a little bit in progressive MS. Can you talk a little bit about the unmet need, in PMS and specifically also the subgroups of PMS as well?

Oh, yes. Good that you asked. I think this is so super important, and I think we can’t say often enough that this is really one of the areas where there is the highest need. And specifically, for non-active secondary progressive MS, there’s currently not a single treatment approved. So, that clearly is a huge unmet need. Maybe, Jason, you have a little bit of comments also on the number of patients affected there, answering that question. And, just to complete it for the same, it’s not the same, but similar in primary progressive where you currently, we only have approved as an infusion. There’s no oral drug approved. And also, I think on the effect size, it’s good to have another option as well for PPMS patients. But maybe, Jason, you can add a little bit more color on that.

Sure. Happy to do so, Daniel and Matt. Thank you for the question. So clearly, look, there’s a huge unmet need in the progressive side of this disease, specifically, and the non-relapsing secondary progressive MS, phenotype or subtype. As Daniel mentioned, there’s no currently approved medicines. We know that in across the seven major markets, there’s approximately a 175,000 patients diagnosed with non-relapsing secondary progressive MS. So, it’s a big opportunity, represents about 15% of the total, MS population. Also, on the primary progressive side, we know that there’s approximately a 120,000 or so patients diagnosed across the major markets, representing about 10% of the total population. There is only one treatment approved to-date, in primary progressive MS and that is Ocrelizumab or Ocrevus. But, I also think it’s important to note that, as patients progress, as they, get into these more neurodegenerative forms of the disease, they’re normally a little bit older in age. They normally have more, accumulation of disability, both physical and cognitive disability. And just as patients age, you have a normal breakdown or wear down of the body’s natural immune system. And so, in these primary progressive patients, though Ocrevus is currently approved, there is some reluctance about putting these type of patients on immunosuppressant, right, broad B cell depleting, therapies. And so, again, the uniqueness of vidofludimus calcium given its dual mechanism of both the neuron activation and highly selective inhibition of DHODH, is that we think it’s going to have a very, very strong neuroprotective play. It’s not immunosuppressant. So, if approved and we show a good signal here, we believe it could become a gold standard-of-care in the progressive forms of the disease.

Thank you.

Thank you, Matt. And maybe a follow-up, question for Jason here in the chat. Can you share more details on the calculation of the peak sales mentioned, regarding market share?

Yes. I mean, I’m not going to get into the intricacies of total market capture. What I can tell you is that we’ve done a lot of work to understand both the bottoms up and the top down of forecast and opportunity for this respective medicine. It’s quite clear even with 20 approved, 20 plus approved therapies in the relapsing forms of the disease, there continues to be a huge unmet need. A couple of data points that I think are worth mentioning. Of the roughly 900,000 patients that are currently diagnosed with relapsing forms of multiple sclerosis across the major markets today, only about 525,000 of them are currently on a disease modifying therapy. So, there’s a huge delta between the number of patients diagnosed and those currently on therapy. And, there’s a lot of reasons as to why patients are not on therapy. But many of the most common reasons are patients had a poor experience with an initial therapy, meaning that the tolerability associated with the medicine, was worse than the disease itself. There are many patients, especially early in their diagnosis, that have concerns about some of the safety signals of the available therapies and it’s not surprising. These are young, people in the prime of their life. They have a long life ahead of them. And of course, if you have a medicine that potentially causes severe and serious opportunistic infections or potentially increases the risk of malignancies, that could certainly be a concern to many of these young patients. Again, there’s also an unmet need for medicines that have a unique mechanism to stop this continued disability progression even in the relapsing forms of the disease. Vidofludimus calcium is going to address all these concerns. And so, we believe that it is a wonderful option and will fill a need in the relapsing forms of the market. And therefore, all of the research that we’ve done to-date supports significant uptake of this potential medicine, right? And, I’ve discussed without, NOSIUM here a little bit about the progressive side, but it goes without saying again. Clearly, if this medicine shows signals in the progressive side, it ultimately becomes approved. We think that the efficacy, the uniqueness of this mechanism, the Nurr1 activation that clearly provides neuroprotective benefits and the balance of all of this with a great safety and tolerability profile really will differentiate this medicine. And again, we think it has the potential to disrupt the oral disease modifying therapy category, and that’s why we’re so hopeful.

Thank you, Jason. Again, if you have a question, please use the raise hand function of the Zoom portal or the Q&A tool. And, we actually have one more on the Q&A tool. Is Immunic in any negotiations to partner with big pharmaceutical at this moment, or are you still looking for a partner for non-dilutive cash raises?

So, Daniel, why don’t I take that? So, as you would imagine, there is significant interest in vidofludimus calcium. There are very few late-stage, there’s little to no late-stage therapies in development for multiple sclerosis and even in neuroscience in general. So certainly, companies that have an existing interest in MS and companies that have an existing interest in neurology or neuroscience, we are talking to just about every single one of them. I will not get into specifics around where we are at in those negotiations, but I can tell you that, again, there’s significant interest. I think the interest has even increased over the course of the last couple of months, given some of the market dynamics specific to the recent failures of the BTK inhibitors and the relapsing forms of the disease. Again, I think that you have many companies taking a fresh and different look at the potential for vidofludimus calcium. So, we’re in ongoing discussions, but nothing more specific to provide at this point.

Thank you, Jason, and thank you for all the questions. This concludes our question-and-answer session today. I would like to turn the conference back over to Daniel, for any closing remarks.

Yes. Thank you, Jessica. And, thanks to everyone on the call today for your always insightful questions and good discussion here. I would like to end the call by reiterating how excited we are about the potential for our advanced clinical pipeline programs, especially lead asset vidofludimus calcium, which is targeted to elevate the standard-of-care for the full spectrum of MS patients. We are pleased with the milestones we have achieved with this program and look forward to reporting topline data from our Phase 2 CALLIPER trial as expected in April of next year, while continuing the enrollment in our Phase 3 ENSURE trials. Additionally, as progress is made, we expect to also provide an update in our preparations for Phase 2 clinical trial of IMU-856 and its unique potential for the treatment of a broad array of serious gastrointestinal disorders and beyond. With that, I would like to close today’s call. Thank you again for joining, and we are very happy to answer any additional questions one-on-one. So, please do not hesitate to reach out.

Thank you for joining Immunic’s third quarter 2024 earnings call. The call has now concluded. You may now disconnect.