Immunic Inc (IMUX) 2020 Q2 法說會逐字稿

Hello, and welcome to Immunic Therapeutics conference call. (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's conference call and webcast to discuss yesterday's press release regarding the positive top line data from our Phase II EMPhASIS trial of IMU-838 in 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, estimates or words with similar meaning and such statements involve 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 result of any revisions 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 Dr. Daniel Vitt. Please go ahead.

Yes. Thank you, Jessica, and a warm welcome. Warm welcome for -- to 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 3 products in development, IMU-838, an oral drug candidate targeting intracellular immune metabolism via the interesting target DHODH, which is currently tested in 4 clinical Phase II 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, primary 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 II clinical trial in relapsing-remitting MS. Multiple sclerosis is a lifelong disease and unfortunately, the majority of the medical diagnosis are emerging in the second and third decade of life. Therefore, persistence and compliance are very important factors for helping patients with MS. Currently used treatments have shown substantial rates of treatment discontinuation. At Immunic, we have focused our development efforts to address the need of patients which require an easy, convenient and safe therapies that allow them to avoid treatment interruptions.

There are a couple of therapies approved for treating different forms or stages of multiple sclerosis. In 2016, the overall global market size was around $22 billion. Currently, there is no specific guidance on which therapies or medications are used in which sequence. Typically, treatments are escalated over time, considering persistent high MS disease activity, undertreatment with base medications, risk of long-term immunosuppression, patients' preferences or risk perceptions, and overall safety and, of course, tolerability aspects. We believe that currently unaddressed medical need to be an oral base medication for MS patients with balance of good safety, tolerability, convenience profile, combined with the robust clinical activity.

Based on the mentioned currently limitations of available treatment, 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 a robust clinical activity, which has a convenient safety profile of an oral drug without 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 who are targeting robust clinical activity, combined with easy on and off dosing, few monitoring requirements and no black box warning for hepatotoxicity.

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 II trial that -- in relapsing-remitting MS that we received late last week. So this slide introduces the patient population used in this Phase II trial of IMU-838 as well as point 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 2 active treatment arms with 30- and 45-milligram once-daily of IMU-838 well as placebo. After completing the 24-week blinded treatment period, patients had the option to enroll in 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 1 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 the 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 summer -- for the randomized patients.

This slide is intended to introduce the primary and key secondary endpoints of the study. This study used MRI-based endpoints where 4 MRI examinations at week 6, 12, 18 and 24 were compared to baseline MRI. The primary and key secondary study endpoints were based on the cumulative number of combined unique active lesions in MRI, referred to as CUA MRI lesions. Basically, the endpoint counts all of the new MRI detectable lesions, whether being gadolinium-enhanced lesions or lesions on T1 or T2 weighted images, using all of the treatment MRI examinations as compared to the baseline MRI and avoiding double counting. This analysis of the MRI was performed by an independent central and blinded MRI reader. The primary endpoint analyzed these data for the 45-milligram IMU-838 dose, whereas the key secondary endpoints was -- used the 30-milligram IMU-838 data.

So let's start with the efficacy data on this trial. So we are happy to report and I'm excited to be the one bringing this news, that both primary and key secondary endpoints were met with high statistical significance. But let's dive deeper into the top line data that are currently available to us.

The primary endpoint analysis has shown that treatment of -- with 45 milligrams IMU-838 over 24 weeks, suppressed an average 62% of CUA MRI lesions as compared to placebo. You can picture the endpoint as showing, for example a -- while placebo patients show an average of 10 new MRI lesions. These are not the actual numbers, just illustration. Patients treated with 45 milligrams IMU-838 show an average 83.8 new MRI lesions at the same -- in the same time period. The analysis showed a statistically significant superiority of 45 milligrams IMU-838 over placebo with a p-value of 0.0002. The 30-milligram dose of IMU-838 showed a 70% suppression of CUA MRI lesions over 24-week as compared to placebo. Taking my example again for placebo patients having 10 new MRI lesions, again, this is for illustrative purposes, that means 30-milligram patients only shows 3 new MRI lesions over the 24-week period. The NOI, the analysis showed us that this statistically significant superiority of 30 milligrams IMU-838 over placebo with a p-value of less than 0.0001.

The analysis of the primary and key secondary endpoints represent the main statistical analysis for this trial as described in a preplanned statistical analysis plan. All other endpoints of this trial are all analyzed descriptively in agreement with general regulatory guidance and established scientific practices. So just to point out for the upcoming slides.

This slide provides some illustration on the general relevance of the MRI lesion suppression data from this trial in light of other Phase II trials for other first-line oral medications currently commercially available for patients with relapsing-remitting multiple sclerosis. Although comparison between trials are often difficult and we point out some of the differences on this slide, Immunic believes that the MRI lesion suppression of IMU-838 compares favorably to other established first-line and oral medications in relapsing-remitting MS.

The next slide is intended to show that MRI lesion reduction data are predictive of relapse reduction, an endpoint that is usually used in Phase III clinical trials in relapsing-remitting MS. A very large meta-analysis, including 54 published trials has shown that there is a robust association between the effect of MRI lesions and the effect of the same treatment on relapses with a high correlation factor.

Let's now continue with displaying some of the additional secondary endpoints that we already have available to Immunic as part of the top line data. This slide looks at gadolinium-enhancing MRI lesions. Both cumulative numbers of new gadolinium-enhancing lesions over 24 weeks and the number of patients without any gadolinium-enhancing lesions over 24 weeks show recognizable numerical advantage of the IMU-838 treatment arms over placebo.

This slide summarizes the data on the relapse related endpoint of this Phase II trial. As relapse events are much less frequent than for some of the occurrence of new MRI lesions, which was the assessment with -- being the primary objective here in this trial, we would need to say that any assessment of relapse-related endpoints usually requires a much larger patient population to be studied, with much longer follow-up period than 24 weeks of this trial. Therefore, the study was not powered to make any more thorough relapse-based assessment. However, and despite those limitations of the study, a positive signal was already detected that would indicate less relapse rate in more relapse-free patients in the IMU-838 treatment arms.

Given the limitations of such small and short duration trial, we're extremely pleased with what we have already observed such as signal related regarding relapse-related endpoints.

I would like to take the opportunity now to summarize the efficacy related results from the top line data of this Phase II trial of IMU-838 in relapsing-remitting MS patients. Primary and secondary key endpoints were met with high statistical significance. We also believe that there is equal efficacy of both dosages used in this trial, 30- and 45-milligram IMU-838. All other secondary endpoints, including those based on other MRI parameters and also endpoints based on relapse events provided a noticeable signal and numerical benefit for the IMU-838 treatment arms in a consistent fashion as compared to placebo. Data on IMU-838 inhibitional MRI lesions are very encouraging and compare favorably to other first-line oral medications.

So let's now continue on safety, which I think you also would be interested to see. The first slide shows the rate of treatment-emergent adverse events for the IMU-838 treatment arms and placebo. There is no noticeable trend for higher rates of adverse events with higher doses of IMU-838. There were only 3 serious treatment-emergent adverse events in this trial, and those are listed here. The highest dose of 45 milligrams IMU-838 did not show any serious adverse events in this trial, as digitally no on-study deaths were observed in this trial.

This slide in more detail summarizes an important safety endpoint or the important safety endpoint of treatment discontinuation due to adverse events. We had already shown earlier the low overall discontinuation rate in this trial, basically 4.2% for the 30-milligram dose; 5.8% for the 45-milligram dose; and 7.2% for the placebo group. More importantly, 3 patients in the placebo group and only 2 patients in the combined IMU-838 treatment arms discontinued treatment due to adverse events, either by investigator decision or due to protocol-described criteria. The adverse events leading to treatment discontinuation are also summarized here. We believe that this represents a good indicator for the favorable safety and tolerability profile of IMU-838 in this relapsing-remitting multiple sclerosis patient population.

As we have done for efficacy, this slide provides some illustration on the treatment discontinue rates from this trial, with the sum of these data from, again, the same first-line and oral medications that are currently commercially available for patients with relapsing-remitting MS. While often treatment discontinuation rates between trials may be difficult to compare, some of these drugs show much higher discontinuation rates on active treatment than for placebo. Immunic believes that the discontinuation rates for IMU-838 and placebo in this trial compare favorably to other established first-line and oral medications in relapsing-remitting MS.

I would like to start a section of this presentation now that deals particularly with liver events and the potential for drug-induced liver injury. Based on the black box warning for hepatotoxicity of teriflunomide and also other commercially available relapse-remitting MS medications, Immunic has always considered this a potential areas for differentiation of IMU-838 and has very closely monitored liver events and liver enzyme elevations. And to date, no signal for hepatotoxicity anywhere in the IMU-838 development program had been observed.

We first need to point out that vidofludimus, the active component in IMU-838, and teriflunomide are structurally unrelated. Teriflunomide has also shown, as those numbers from its label show, increased rates of enzyme elevations in the 2 approved doses of teriflunomide as compared to placebo. The label also has very specific requirements for laboratory-based monitoring, particularly during the initial treatment periods.

Immunic has previously reported the detailed safety results of the component trial in rheumatoid arthritis patients unblinded a few years ago. The careful analysis of liver events in this trial had not shown any signal for hepatotoxicity, in particular when comparing against the baseline rates of liver events in a placebo group. Immunic, again, has done a very thorough analysis of liver and also renal events in this Phase II trial of IMU-838 in relapsing-remitting MS patients. In general, there was no increased rate of liver events or renal events following IMU-838 treatment over 24 weeks as compared to placebo.

But let's dive in a little bit deeper. We also looked -- next slide. We also look at the rate of liver enzyme elevations using different thresholds of 5x, 10x and 15x upper limit of normal range for these liver enzymes. As you can see from this slide, the rate of elevations of liver enzymes included both ALT, AST, both the major liver enzymes, were very low. Additionally, there was no increase of rate of liver enzyme elevations in either IMU-838 treatment arm as compared to placebo.

But let's go to another important analysis that is an important assessment for drug-induced liver injury. This slide summarizes the so-called Hy's Law assessment of liver events. The Hy's Law assessment looks for concurrent increases of liver enzyme above 3x upper limit novel and of total bilirubin of more than 2x upper limit normal. There were no Hy's Law cases in the entire IMU-838 development program, with approximately 650 human volunteers and patients exposed to vidofludimus today. This analysis also confirms that there were no Hy's Law cases in this trial as well. The scatter plot also shows that in graphical representation, that there are very few elevations of ALT, one of the liver enzymes or bilirubin, and those are comparable between IMU-838 treatment arms and placebo. Immunic believes that the EMPhASIS trial in relapsing-remitting MS patients, again, does not demonstrate a signal for hepatotoxicity for IMU-838.

So here, I would like to take the opportunity to summarize the safety-related results of the top line data of this Phase II trial. Consistent with prior data sets in other patient population, administration of IMU-838 in this trial was observed to be well tolerated. They were also providing further evidence of the favorable safety profile of IMU-838 in this relapsing-remitting patient population. A general safety profile is comparable to the placebo group. We have seen a very low rate of treatment discontinuations and IMU-838 discontinuation rates compare favorably to many other oral and first-line medications already available in relapse-remitting MS.

In summary, we believe that the favorable safety profile of IMU-838 was observed. There was no increase in liver or renal events as compared to placebo, and there is no signal for any hepatotoxicity elevation of liver enzymes that could be observed.

I think you would also be interested that I give you an outlook for the overall relapsing-remitting MS development program of IMU-838. So the analysis of the full Phase II trial data is ongoing beyond these top line data that are currently available, that presented to you. Some of the more detailed data are not yet available. From the thorough blinded safety monitoring of the trial conduct, we already know that the incidence of important adverse events was low and we do not expect any change in conclusions after analysis of the full data set. However, once we obtain and analyze the full data set of this trial, the coordinating investigator of this trial is expected to present more detailed data at an upcoming scientific meeting in early September.

Immunic has already started preparations for a potential Phase III program some time ago, and given the availability of the Phase II data, we are continuing preparations for such Phase III program. We will provide more guidance on the intended Phase III program once full data is available, discussions with experts, clinical and statistical experts as well as regulatory authorities, have been completed.

I was very excited that I was able to present these data to you, and I'm handing over back to Daniel.

Yes. Thank you, Andreas. And so I really love these results, really, a 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 II 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 tumoral disease activity. Given these exciting results, we're also accelerating our preparation for the further potential clinical Phase III testing of IMU-838 in patients suffering from MS.

Yes. With this, I would like to open the line for questions and hand it over to Jessica, taking care of that.

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

(Operator Instructions) And the first question comes from Liana Moussatos from Wedbush.

Congratulations on the outstanding data. What would you expect the relapse data to be with 2 years of treatment based on the 24-week result that you presented today?

So thank you for this question. I think taking the meta-analysis that I presented, that is available from Maria Pia Sormani 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 III program that we hope to kick off soon.

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

Congrats on the very clean results and positive results and thanks for the detailed presentation. Maybe I'm jumping the gun a little bit, but can you give us kind of your initial thoughts on what a Phase III program could look like? Given what you're seeing here and understanding that, obviously, you have to have some discussions with FDA and your advisers as well.

Yes. I think the -- overall, we believe that we will follow the guidelines and the recommendations that we have received 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 has 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 refrain a little bit from making any more comments at this point than -- so that we can give you 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 advisers as well as regulatory advisers based on these data.

Great, great. 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?

Yes, 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 basic adverse events that we have seen. But also, I think, as you probably noticed, we don't have EDSS or disability data or brain atrophy data here, which I; 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 their effect on disability, relapsed independent disability and on EDSS progression. Hopefully, we can present at least first data.

It's 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 visibility progression and also on brain atrophy data.

Great. And congrats on the results and look forward to the presentations in September.

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

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 -- and 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 set will show me in terms of how these are distributed between the treatment arms, I don't think 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?

PML.

Okay. So I think at the moment, mostly we'll just thinks that Aubagio being a DHODH inhibitor and DHODH inhibitor displaying broad antiviral properties and for teriflunomide, Aubagio, this has already been shown in different viruses and there are publications around this. And we have also presented the data, especially when we started the COVID-19 trial and in our R&D Day, we 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'm thinking 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 even no or very low risk. But usually, I think there's even publication that basically point out that teriflunomide, because being a DHODH inhibitor have no PML risk. And given the broad antiviral 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 100,000s 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 3/4 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, you probably know that a lot of these placebo-controlled clinical trials in MS have shifted towards resource -- countries with not 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 basically used a patient population that is specific for the countries that we are -- that where you can do these trials.

And when you look at the previous Phase II trials, for example, it was done, and that I think also I looked, when we looked at the illustration with the other Phase II trials, have used a very similar population or because there was already the shift to maybe Central Eastern European countries for these Phase II trials. And I think this is surely a reflection of the countries that we were in.

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 effect 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. Urinalysis was at 70% at 24 weeks. So is there a -- is there any insight that you have that if you could have gone longer, you could have seen a better efficacy or stronger efficacy than you saw, even though 70% is phenomenal? And I have 2 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 II 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 have also done every 6 weeks in MRI, up to 36 weeks. They had shown that the basic differentiation between the treatment groups and 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 may be helping you in terms of the variability of the data and basically having more or having less confidence in (inaudible) and so forth that helps your statistics. However, I think it doesn't change the proportion of lesion suppression to my mind. Every other Phase II trial is similar in design to our trial has shown that a longer treatment duration or source doesn't lead to a different proportion of patients that have lesion suppression or have no lesions or I think that these endpoints look very similar when you look at different time points.

But in this slide, I really want to point out, and I took the main statistical analysis for the Phase II trial in the slide that I presented, just to make sure that we really compare the main statistical analysis for which the p values that 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 them -- for the primary analysis.

So yes, I think you have follow-up questions.

Andreas, the second one is, thank you for the careful analysis of the liver enzymes and 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 these black box warning come after you have cases of acute liver failure.

However, I think the agency has been very adamant about, just for example, these Hy's Law 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 had done this biomarker in Phase I trials and really could show that we had no increase of the miR-122 biomarker. We have shown that we have no elevated risk of liver enzyme elevations. We have no Hy's Law 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's required.

And I think given that we have a much larger Phase III program than the Phase II program that I just presented, I think we will have to continue collecting these data that we have collected here in the Phase II trial and continue collecting these data in more patients. And I think this will probably give the regulators a little bit more confidence to avoid the black box warning.

Maybe I can -- Yasmeen, this is Daniel. Maybe I can add something here. So there's another aspect, and that's why we put in the chemical structures of teriflunomide and of 838 in this presentation, I don't see a very close structure similarity. And therefore, that's also in that 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 this wonderful data on safety, and we really want to be very transparent on the liver effect here. And I think so far, it looks really very good. And firstly, I think there's a high chance that we don't have that problem.

And then one last question. I know we're awaiting granular data for diarrhea, alopecia and neutropenia. But if you look at the totality of the events, and you compared it to the component study, are they in line? Is there any reason why maybe those side effects would maybe differentiate or show up in the RRMS 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 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 0, and some of them were 1 or 2 that showed up in this trial. So even in the worst case, if you would assume they're all in one treatment arm, it's absolutely no signal expected on these adverse events.

Congratulations again.

Thank you, Yas.

And the next question comes from Ram Selvaraju with H.C. Wainwright.

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 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 is more variability at week 6, yes, because I think with (technical difficulty), 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 averages over time. But the separation of the placebo and IMU-838 treatment curves comes basically already at the first time. But that's actually consistent with other drugs. You have seen it for teriflunomide, like I pointed out, but we've also seen it from other drugs that have a very early separation right away in terms of MRI activity. I hope that's all right.

I mean, with the data that our coordinating investigator will present, probably the time course of these effects, we will have more data on that as well. But I think the data really proportional for all of the time points.

Okay. That's very helpful. And then also with respect to the 30-milligram versus the 45-milligram. 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 III? Or if you haven't made a decision yet regarding that? Or if indeed, you intend to take forward both doses into Phase III?

So I think one question is easy. We haven't made the final decision yet because we would have to wait until we have the whole data. I think from all the data that I've seen so far, the clear statement that's 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 III 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 III design, and I understand that this is potentially a premature inquiry, but can you give us a sense of what kinds of potential comparators might you envision using? I believe that in your previous prepared remarks regarding the Phase III 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 III 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 III trials. But I think -- I'm sorry, I can't say more at this point because I think it would be premature to really 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 III development program.

And do you continue to expect that the Phase III would potentially be done with a partner on board? Or are you considering all options at this point, including conducting the Phase III (inaudible).

Yes. Good point, Ram. I think, first of all, this is great data, and I think this gives us much more options than we had 2 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 we are -- I think we are starting dialogue with everybody who is interested in joining forces here.

I think it's a low-risk way forward for everybody who is interested in that space. It could be an interesting option for a lot of companies, so. It's too early to say what is our priority here, but we are open for any kind of discussion.

And congrats again on the data.

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

I'll echo, congrats on the data. Explains how quickly this set enrolls. 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 the other question on the efficacy, which kind of looks comparable to Aubagio based on the MRI analysis. But any thoughts about perhaps seeing greater efficacy relative to Aubagio when you look at EDSS or any of the analyzed reads later on?

So I think I -- unfortunately, I think I have to say, we had 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 this 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 the comparator should be in Phase III. And I think it would be hard to make any prediction of -- in 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 -- and on the PK side, we are very confident that IMU-838 is considerably more convenient and offers a much better profile for patients in RRMS than teriflunomide. Whether we can establish an efficacy, I think, depends a little bit more on the data that we get over the next weeks.

And then just a quick follow-up here. You mentioned perhaps accelerating Phase III 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 II data, once we have all the data, the next step would be an end of Phase II meeting with both FDA and EMA. And that's definitely something that we are accelerating right now based on these data reviews. We have good data to show them. There's also a lot of other things that you have to prepare for going into Phase III. We have really, I think it's been very good, and we presented this on the R&D data in terms of manufacturing, I think we had done great steps forward towards Phase III and there's additional data that we'll expect over the next weeks to come from other areas, so that we complete the Phase II pack -- end of Phase II package. I would assume that an end of Phase II meeting, maybe something that's happening in -- early in 2021, but I think I can't give you more detailed guidance on that.

And the next question comes from John Newman with Canaccord.

And my congrats on a very clean data set. Just have 2 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 wonder 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 had about a 6-month washout period, whereas this agent does not?

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 RRMS patients are very consistent to our previous data, so I -- we don't see any difference there.

And then the first question was the -- sorry, remind me again, I'm too old to remember 2 questions. Don't do this to me.

No, I'm sorry. So I believe the study design also involved measuring patients after 12 weeks.

12 weeks. Yes. Sorry, 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 performance statistical analysis on week 24. Of course, I have seen how, for example, [TOA] lesions or gadolinium lesions develop over time. And as I said before, it's a linear event, a proportional event. We see separation of the curves at 6 weeks and at 12 weeks already. And if you look at the 12th week, I think you see a very clear treatment difference and also before that.

But you asked for 12 weeks, do you see in 12 weeks a numerical difference between placebo and very consistent numerical difference between placebo and the IMU-838 treatment arms, but these were not tested statistically. And I think we need to be careful that -- yes, that we are not running further into trading hours here.

And as that 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 listening on the great, 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.