Hello and welcome to the Immunic Therapeutics Conference Call. All participants will be in listen-only mode. [Operator Instructions] Please note, today’s event is being recorded. I would now like to turn the conference over to Jessica Breu. Ms. Breu, please go ahead.

Yes. Thank you, Keith. Good morning and welcome to Immunic conference call and webcast to discuss yesterday's press release regarding the positive top line data from our Phase 2 EMPhASIS trial, of IMU-838 and relapsing-remitting multiple sclerosis, which we are very excited about and which we want to share with you on today's call. My name is Jessica Breu, Head of Investor Relations and Communications at Immunic. Speaking on today's call are with me, Dr. Daniel Vitt, our Chief Executive Officer and President; and Dr. Andreas Muehler, our Chief Medical Officer. Before we begin, I would like to remind you that this webcast may contain forward-looking statements. Such statements can be identified by words, such as may, will, expect, anticipate, estimate or words with similar meaning and such statements involves a number of risks and uncertainties that could cause 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 results of any revision to these forward-looking statements in light of new information or future events. Please refer to Immunic's SEC filing 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 Dr. Daniel Vitt. Please go ahead.

Yes. Thank you, Jessica, and a warm welcome for today's call also from my end. It's a great moment for the Immunic team today, especially considering the short, but intense history of the company. Immunic has three products in development: IMU-838, an oral drug candidate targeting intracellular immune metabolism via the interesting target DHODH, which is currently tested in four clinical Phase 2 trials is the front runner of the program. On top of the EMPhASIS trial in multiple sclerosis patients, IMU-838 is currently actively tested in ulcerative colitis, primarily sclerosing cholangitis and since June also in COVID-19 patients leveraging the broad spectrum antiviral activity of IMU-838 through DHODH inhibition. But let us focus on today’s topic, the unblinded top line data from the Phase 2 clinical trial in relapsing-remitting MS. Multiple sclerosis is a lifelong disease. And unfortunately the majority of MS diagnosis are emerging in the second and third decade of life. Therefore, persistence and compliance are very important factors for helping patients with MS. Commonly used treatments have shown substantially rates of treatment discontinuation. At Immunic, we have focused our development efforts to address those needs of patients, which are kind of easy, convenient, and safe therapies that allow them to avoid treatment interruptions. There are a couple of therapies approved for treating different forms of stages of multiple sclerosis. In 2016, the overall global market size was around $22 billion. Currently there's no specific guidance on which therapies or medications are used in which sequence, typically treatments are escalated over time considering assistant high MS disease activity on the treatment of base medications, risk of long-term immunosuppression, patients preferences or risk perceptions, and overall safety, and of course, tolerability aspects. We believe that currently under medical need to be an oral base medication for MS patients with balance of good safety/tolerability/convenience profile combined with a robust clinical activity. Based on the mentioned currently limitations of available treatments, IMU-838, is intended to be a selective once-daily oral medication for relapsing-remitting MS patients with a well-balanced combination of favorable safety and convenience profile with robust clinical activity, which has a convenient safety profile of an oral drug without to adverse events disturbing social activities, and in particular having no or low PML risk, as well as offering long-term treatment duration through less risk for discontinuation, and high patient compliance. For doctors, we're targeting robust clinical activity combined with easy on and off dosing, few monitoring requirements and no black box warning for hepatotoxicity. And with this, I would like to hand over to Andreas for the more interesting part of this presentation. So Andreas, please show us the data.

Thank you. Yes, I'm very happy to present the top line data from our Phase 2 trial that in relapsing-remitting MS that we received late last week. So this slide introduces the patient population used in this Phase 2 trial of IMU-838, as well as points out the study had a 24-week blinded treatment period. This is the period for which we're reporting the top line data today, as well as an extended treatment period of up to 9.5 years, which is currently ongoing, and which is intended to observe long-term safety of IMU-838. This slide here, graphically summarizes the study design for this study. The study randomizes relapsing-remitting MS patients into two active treatment arms with 30 and 45 milligrams once-daily of IMU-838, as well as placebo. After completing the 24-week blinded treatment period, patients have the option to enroll the extended treatment period in which patients were randomized to either 30 or 45 milligrams IMU-838. In this trial a total of 209 patients received at least one dose of study drug and 96 patients were treated with placebo as well as with 45 milligrams of IMU-838 and 71 patients were treated with 30 milligrams IMU-838. As very few patients discontinued drug treatment during the 24-week blinded treatment period. We will come back to a more detailed analysis for the reason of discontinuations later on. A total of 197 patients completed the 24-week blinded treatment period. This slide also contains a summary of the baseline characteristics for the randomized patients. This slide is intended to introduce the primary and key secondary endpoints of the study. This study used the MRI base end points were four MRI examinations at week 6, 12, 18, and 24 were compared to baseline MRI. The primary key secondary study end points were based on…

Yes. Thank you, Andreas, and I really love this results. Really great, great outcome. And so it's maybe time for another summary. So I think the key message here is IMU-838 showed compelling clinical activity in this Phase 2 trial with unique safety properties compared with current treatment options. And we believe that this would allow for a safe and easy to use treatment option with robust therapeutic effects for early relapsing-remitting MS in patients with mild to moderate disease activity. Given these exciting results, we are also accelerating our preparations for the fuller potential clinical Phase 3 testing of IMU-838 in patients suffering from MS. Yes, with this, I would like to open the line for questions. I hand over to Jessica taking care of on that.

Yes. Thank you, Daniel. I think Keith will be in charge of coordinating the question. So Keith, please go ahead.

Yes. Thank you. [Operator Instructions] And the first question comes from Liana Moussatos from Wedbush.

Thank you for taking my questions and congratulations on the outstanding data. What would you expect the relapse data to be with two years of treatment based on the 24-week results that you presented today?

So thank you for this question. I think that taking the meta-analysis that I have presented that is available from [indiscernible] and that showed a very good correlation factor. We should see a more than 30% relapse reduction rate. However, this is to be confirmed in a large Phase 3 program that that we hope to kick off soon.

Thank you.

Thank you. And the next question comes from Matt Kaplan with Ladenburg Thalmann.

Hi. Good morning guys, and congrats on the very clean results and positive results and thanks for the detailed presentation. Maybe I'm jumping the gun a little bit. Can you give us kind of your initial thoughts on what a Phase 3 program could look like, given what you're seeing here and understanding that obviously you have to have some discussions with FDA and, and your advisors as well?

Yes. I think the -- overall, we believe that we will follow the guidelines and the recommendations that'd be able to see from our regulatory advice meetings that we've already done. We had done several of those. And we believe that we have to provide some of the studies that will follow the regulatory guidance as pivotal trials, but we also think that a head-to-head trial definitely is also needed here with an active comparator as a supportive option here in this trial. But I think I would reframe it a little bit from making any more comments at this point so that we can give you a guidance once we have more clarification on -- we have seen the analysis of the full data and also we have our final discussions with clinical and statistical advisors as well as regulatory advisors based on these data.

Great. Great. Thank you. And then in terms of the presentation in September at the ACTRIMS-ECTRIMS joint meeting, what should we expect to see additional data or more detailed data at that time?

Absolutely, because I think some of the safety data, I think we want to dive deeper to give you a lot more detail. I think on the basic adverse events of VFC [ph], but also I think as you probably know this, we don't have EDSS or disability data or brain atrophy data here, which are actually done during the trial, but we have not yet available from these top line data, which I think is one of the differentiating factors of DHODH drug versus other MS drugs is -- there effect on disability relapsed independent disability and on EDSS progression. Hopefully we can present at least first data. It is the same I think with relapse data. The study would have been -- would have to be much larger and longer in terms of follow-up to have meaningful data. But I think we very much look forward to at least get a signal on EDSS disability progression, and also on brain atrophy data.

Great. Thanks. Thank you very much and congrats on the results, and look forward to the presentation in September.

Yes. Thank you, Matt.

Thanks, Matt.

Thank you. And the next question comes from George Farmer with BMO Capital.

Hi, good morning and my congratulations as well. Very clean data set. I was wondering if you could comment on incidence of diarrhea and alopecia rates in the trial. I know you said it was early in your analysis, but do you have any feel for that yet?

So I can only answer what I've already said here is that, of course, we had a very close medical monitoring, blinded medical monitoring during the conduct of the trial. And I know that these incidence rates for alopecia, neutropenia and diarrhea are extremely low here in this trial. So whatever the full data sets will show me in terms of how these are distributed between the treatment arms. I don't think that will change the outcome of the safety analysis, but in general, we don't have the data yet. But I know that the incidence rates were extremely low in this trial.

Okay. That's good to hear. And what do we know about PML risk with Aubagio? And do you think that that could be a concern with IMU-838?

So you said PML.

Aubagio.

Okay. So I think at the moment most urologists think that Aubagio being a DHODH inhibitor, and DHODH inhibitor displaying broad antiviral properties. And for teriflunomide, Aubagio, this has already been shown and in different viruses and their publications around us, and we have also presented the data, especially when we started the COVID-19 trial and our R&D data provided lots of broad antiviral data. So it's believed that teriflunomide carries either no or very low risk of PML. So sometimes it's very difficult to assess. I think in the -- some of these PMLs that are happening in these MS patients, they often have taken several drugs and it's very hard to pin them on a specific drug. But in general, I think everybody believes that teriflunomide has either no or very low risk, but usually I think there's even publication that basically point out that teriflunomide because being [indiscernible] has no PML risk. And given the broad anti-viral activities that we have seen for IMU-838, I think we hope that we can replicate this from the data -- from the clinical data. However, I think given that PML fortunately is a very rare event, I think this is something that needs maybe hundreds, thousands of patients being treated before you can make a conclusive statement on PML risk.

Okay. And one more, if I may. I noticed that about three quarters of the patients had no prior therapy for their disease, yet over half of them had been diagnosed over 4 years. Is this a Typical MS patient population in clinical trials?

So I think as you probably know that a lot of these placebo controlled clinical trials in MS have shifted towards resource -- countries where there's no sufficient medical resources where you can do these trials and have a high participation rate. So, this I think what you point out is absolutely correct. I think it is -- it just demonstrates that these placebo controlled clinical trials have been basically used a patient population that is specific for the countries that we are -- where you can do these trials. When you look at the previous Phase 2 trial, for example, it was done and that, I think also I looked when we looked at the illustration with the other Phase 2 trials have used a very similar population, or -- because there was already the shifts to maybe Central Eastern European countries for these Phase 2 trials. And I think this is surely a reflection of the countries that we were in.

Okay, great. Thanks, Andreas.

Yes. Thank you for the question.

Thank you. And the next question comes from Yasmeen Rahimi with Piper Sandler.

Hi, team. Congrats on the great data. I have a number of questions for you. So maybe let's start off with efficacy. Can you kindly comment on what would the effects on total lesion or MRI activity be, if we would have assessed the endpoint at 36 weeks? So you shared with us that teriflunomide showed an improvement of 60% reduction in MRI activity at week 36. Your analysis was at 70% at 24 weeks. So is there any insight that you have that you could have gone longer, you could have seen a better efficacy or stronger efficacy than you saw, even though 70% is phenomenal. And then I have two follow-up questions for you.

Okay. Thank you, Yas. So I think I probably have to disappoint you a little bit because for all the other Phase 2 trials, if you look at the data and for example, look at teriflunomide data when they report the cumulative number of these MRI lesions over time, and for example, in teriflunomide, they've also done every 6 weeks an MRI up to 36 weeks, they’ve shown that the -- basically a differentiation between the treatment groups and the placebo groups was quite proportional at each time point. So you could see the separation already at 6 and 12 weeks. And if you would just analyze the data, for example, at different time points, even in a teriflunomide trial, it would be very similar to the final outcome of the 61% lesion reduction at week 36. So I believe the longer duration maybe helping you in terms of the variability of the data and basically having more or having less confidence in [indiscernible] and so forth that helps with the statistics. However, I think it doesn't change the proportion of lesion suppression to my mind. Every other Phase 2 trial is similar designed to our trial has shown that in longer treatment duration or -- so it doesn't lead to a different proportion of patients that have lesion suppression, or have no lesions, or I think that these end points look very similar when you look at different time points. But in this slide, I really wanted to point out, and I took the main statistical analysis for the Phase 2 trial in the slide that I presented just to make sure that you really compare the main statistical analysis for which the p-values and for which the main statistical analysis was published rather than the data in between, for example, at week 24, which are available from graphs and so forth. But I don't think they often provide the detail for then for the primary analysis. So, yes, I think you have follow-up questions.

Thank you, Andreas. The second one is -- thank you for the careful analysis of the liver enzymes in Hy’s Law. So do you think what type of additional data do you need to generate to really prevent a potential black box warning that has been seen with teriflunomide? Is there any other studies that would be required by the agency?

I think to my mind, it's a question of additional patients. These -- the black box warning are often based on -- showing catastrophic events, for example, acute liver failure with these drugs and not solely only the liver enzyme elevations. They take liver enzyme elevations as a signal, but most of these from what I've seen is black box warning come after you have cases of acute liver failure. However, I think the agency has been very adamant about that, for example, these high loss cases, and also a biomarker called miR-122 are indicative of the risk of these acute liver failure cases. Although this biomarker is not yet fully validated, the FDA looks at these data from this biomarker. We have done this biomarker in Phase 1 trials, and really could show that we have no increase of the miR-122 biomarker. We have shown that we have no elevated risk of liver enzyme elevations. We have no [indiscernible] cases. But at the end of the day, I think you need just more patients to show the same again and have no acute liver failure cases and I think that's what required. I think, given that we have a much larger Phase 3 program than the Phase 2 program that I just presented, I think -- the role I have to continue collecting these data that we’ve collected here in the Phase 2 trial and continue collecting these data and more patients and I think this would probably give the regulators a little bit more confidence to avoid the black box warning.

Maybe I can, Yas, maybe -- this Daniel. Maybe I can add something here. There's [indiscernible] and that’s why we put in the chemicals structures of teriflunomide [indiscernible] of 838 in this presentation. I don’t see a very close structure similarity and therefore -- that’s also [indiscernible] you cannot expect a class effect here. And I think class is really refers to the chemical class of molecules. And I think Andreas showed his wonderful data on safety, and we really want to be very transparent on deliver effect here. And I think so far, it looks really very good and personally I think there's a high chance that we don’t have that problem.

Thank you, team. And then one last question. I know we're waiting granular data for diarrhea, alopecia, and neutropenia, but if you look at the totality of the event and you compared it to the component study, are they inline? Is there any reason why maybe those side effects would maybe differentiate or show up in the MS trial versus the COMPONENT study? So if you could just kind of give us a little bit more granular data to the extent you can would be very helpful.

Yes. So the quick answer is no. I'm absolutely confident that there's nothing to be shown. And I feel unfortunate is that you’re asking about this and I can't give you a more detailed answer. But I know we had a very high EMPhASIS on basically in a blinded fashion, looking at cases of alopecia, neutropenia and diarrhea. And in some of these categories basically were zero and some of them were one or two that showed up in this trial. So even in the worst case, if you would assume that all in one treatment arm, it's absolutely no signals expected on these adverse events.

Thank you team and congratulations again.

Thanks, Yas.

Thank you, Yas.

Thank you. And the next question comes from Raghuram Selvaraju with H.C. Wainwright.

Hi. Thanks so much for taking my questions. And again, congratulations on this excellent data. I wanted to ask about curve separation in the study. If you look at earlier time points before the 36 weeks -- sorry, the 24 weeks, can you give us a sense of when you first started to see separation of the treatment arms versus placebo with respect to the lesion endpoint?

So I, I think I can only say that the data that I've seen so far show a proportional effect for all the time points, so starting at week 6. However, there's more variability at week 6, just because I think with timeline [ph], you get more of a -- of less variability between these patients, because some of these patients of course have more lesions at one time point, but not at another one. So that average is over time, but the separation of the placebo and [indiscernible] treatment curves comes basically already at the first time, but that's actually consistent with other drugs. You have seen it from teriflunomide, like I pointed out, but we have also seen it from other drugs that have a very early separation right away in terms of MRI activity. I hope that all I -- I mean, with the data that we -- that our Coordinating Investigator will present, probably the time force of these effects, we will have more data on that as well. But I think the data are really proportional for of the time points.

Okay. That's very helpful. And then also with respect to the 30 milligram versus the 45, can you say definitively at this juncture whether one really looks meaningfully better versus the other, and if it is indeed the 30 milligram dose that might potentially be the most appropriate to carry forward into Phase 3, or if you haven't made a decision yet regarding that, or if indeed you intend to take forward both doses into Phase 3.

So I think that one question is easy. We haven't made a final decision yet because we would have to wait until we have the full data. I think from all the data that I've seen so far, the clear statement is 30 and 45 milligram have equal efficacy and equal safety actually. So I do not see any reason to favor one or the other. Regulators usually favor the lowest effective dose to be taken forward into a Phase 3 program. But as I said, I think I want to hold judgment until I've seen all the data.

Okay. And then with respect to the Phase 3 design, and I understand that this is potentially a premature inquiry. But can you give us a sense of what kind of potential comparators might you envision using? I believe that in your previous prepared remarks regarding the Phase 3 design, you had indicated that it would indeed be on a comparator controlled basis. But what comparators, hypothetically, would you consider most appropriate to utilize in the Phase 3 context?

Okay. So theoretically you could take any comparator, yes. But I think in a lot of ways you will probably take comparators that establish superiority in some of the trials and you will also -- I think to a certain extent, look at an oral option as a comparator in these Phase 3 trials. But I think I’m sorry, I can't say more at this point because I think it would be premature to release more information. And I apologize for that. I feel awful, but I would love to say more, but let's wait a little bit longer. And we -- as we said, I think we'll update you shortly about our Phase 3 development program.

And do you continue to expect that the Phase 3 would potentially be done with a partner on board, or are you considering all options at this point, including conducting the Phase 3 right now?

Yes. That’s a good point, Ram. I think, first of all, this is great data, and I think that gives us much more options than we had two days ago. So that's a good thing. And of course, we will speak to different companies and there are multiple ways forward. You can imagine you can have a territorial partner or a global partner or we just can continue on our own. We keep the options open, of course, and I think we are starting a dialogue with everybody who is interested in join forces. Yes, I think it's a low risk way forward for everybody who is interested in that space. It could be interesting option for a lot of companies, though. It's too early to say what is our priority here, but we are open for any kind of discussion.

Thank you very much and congrats again on the data.

Thank you.

Thank you, Ram.

Thank you. And the next question comes from Zegbeh Jallah with ROTH Capital.

Good morning. I will echo congrats on the data. Explains how quickly this study enrolled, and it does sound like you are having some conversations with partners. So that's really good. I think I just kind of wanted to follow-up on Yas's question. On the efficacy, which kind of looks comparable to Aubagio base on the MRI analysis. But any thoughts about, perhaps, seeing greater efficacy relative to Aubagio when you look at EDSS or any of the analyze rate later on?

So I think I -- unfortunately, I think I have to say we have to go to be at least as effective as teriflunomide and what we have shown is that we succeeded in that. Numerically, we have a higher rate of lesion suppression with the 30 milligram dose than Aubagio. But I think what it really means and we have to look at more of the data that come out from this trial. Like I said, I think EDSS data, brain atrophy data that gives us a little bit more confidence going forward, what do you compare? This should be in Phase 3. And I think it would be hard to make any prediction of a comparison to teriflunomide at this point, given the data that we have. And I think the -- what I can say is that I think on the safety tolerability side, I think we are very confident that on the [indiscernible] size, we are very confident that IMU-838 is considerably more convenient and offers a much better profile for patients in [indiscernible] teriflunomide. Whether we can establish an efficacy, I think depends a little bit more on the data that we get over the next weeks.

Thank you. And just a quick follow-up here. You mentioned perhaps accelerating Phase 3 development, can you provide any details on what options might be available to you and when you plan to meet with the FDA?

So, of course, with these Phase 2 data, once we have all the data, the next step would be end of Phase 2 meeting with both FDA and EMA, and that's definitely something that we accelerate right now based on these data, because we have good data to show them. There's also a lot of other things that you have to prepare for going into Phase 3. We have really, I think, been very good and we presented this on the R&D data in terms of manufacturing. I think we have done great steps forward towards Phase 3. And there's additional data there that we'll expect over the next weeks to come from other area so that we complete the Phase 2 -- end of Phase 2 package. I would assume that an end of Phase 2 meeting may be something that's happening in early 2021, but I think I can't give you more detailed guidance on that.

That was helpful and thanks for the very detailed presentation. That was very informative.

All right. No, thank you.

Thank you, Zegbeh.

Thank you. And the next question comes from John Newman with Canaccord.

Hi, guys. Thanks for taking the question and add my congrats and very clean data set. Just two quick ones. The first one is, I believe you also looked at efficacy at 12 weeks. Just wondering if you'll be presenting that in the upcoming data presentation, or if you could comment on whether you started to see any efficacy at 12 weeks rather than 24. Second question is, I just wondered if you could talk a little bit about whether the PK profile that you saw earlier was consistent with what you saw here? And the reason I'm asking is because I believe you previously explained that Aubagio has about a 6-month washout period, whereas this [indiscernible] does not. Thank you.

So I think the last question first. We had very few discontinuations in this trial, so I cannot tell you much about the washout period. But I think the trough levels that we see in these, our MS patients are very consistent to our previous data. So we don't see any difference there. And then the first question was the -- sorry, remind me again, I'm too old to remember two questions. Don’t do this to me.

No, I'm sorry. So, I believe the study design also involves measuring …

12 weeks.

… patients at 12-week, yes. Thank you.

Yes. So it comes back to me now. I just need a minute sometimes. So 12 weeks, there is no formal statistical analysis. I think, as I pointed out, we have done a former statistical analysis on week 24. Of course, I've seen how, for example, CUA lesions or [indiscernible] develop over time. And as I said before, it's a linear event. The proportion of events we see separation of the curves at 6 weeks and at 12 weeks already. And if you look at the 12-week, I think you see a very clear treatment difference and also before that, but we ask for 12 weeks. In 12 weeks a numerical difference between placebo -- and very consistent numerical difference between placebo and the [indiscernible] treatment arms, but these were not tested statistically.

Great. Thank you.

And I think we need to be careful that -- yes, that we are not running further into trading hours here.

Sure. Thank you very much.

Thank you. And as it does conclude the question session, I would like to return the floor to Daniel Vitt for any closing comments.

Yes, sure. So I think all is said already, but I want to thank you all for listening on the great day for Immunic today, and also thank you for asking those good questions today. And to repeat once again, the company is also open for questions anyhow in the future. And we try to keep our very open communication policy here. So thank you once again and goodbye and speak soon to everybody.

Yes, thank you. The conference has now concluded. Thank you for attending today's presentation. You may now disconnect your lines.