Earnings Call Transcript - IMUX Q2 2020

Jessica Breu, Head of Investor Relations and Communications

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 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 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.

Dr. Daniel Vitt, CEO and President

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 diagnoses are emerging in the second and third decades of life. Therefore, persistence and compliance are very important factors for helping patients with MS. Commonly used treatments have shown substantial 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-based medication for MS patients with a 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 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.

Dr. Andreas Muehler, Chief Medical Officer

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 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 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 of the reasons for 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 where 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 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 they are gadolinium-enhanced or lesions seen 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 to analyze these data for the 45 milligram IMU-838 dose was the key secondary endpoint with the use of 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 with 45 milligrams IMU-838 over 24 weeks suppressed an average of 62% of CUA MRI lesions as compared to placebo. You can picture the endpoint as showing, for example, that while placebo patients show an average of 10 new MRI lesions – these are not the actual numbers, just for illustration. Patients treated with 45 milligrams IMU-838 show an average of 3.8 new MRI lesions over 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 weeks as compared to placebo. Taking my example again for placebo patients having 10 MRI lesions – again, this is for illustrative purposes, that means 30 milligram patients only show three new MRI lesions over the 24-week period. The analysis showed us that this group statistically significant superiority of 30 milligrams IMU-838 over placebo with a p-value of less than 0.0001. The analyses of the primary and key secondary endpoints represent the main statistical analysis for this trial as prescribed and a preplanned statistical analysis plan. All other endpoints of this trial will only be analyzed descriptively in agreement with general regulatory guidance that 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 2 trials for other first-line oral medications currently commercially available for patients with relapsing-remitting multiple sclerosis. Although comparison between trials are often difficult as we point out, some of the differences are on the slide. Immunic believes that the MRI lesion suppression of IMU-838 compares favorably to other established first-line oral medications in relapsing-remitting MS. The next slide is intended to show that MRI lesion reduction data are predictive of relapse reduction, an end point that is usually used in Phase 3 clinical trials in relapsing-remitting MS. A very large meta-analysis, including 54 published trials had shown that there's a robust association between the effect of MRI lesions and the effects of the same treatment on relapses with a high correlation factor. Let's continue with 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. Those 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 advantages of the IMU-838 treatment arms over placebo. This slide summarizes the data on the relapse-related endpoints of this Phase 2 trial. As relapse events are much less frequent than some of the occurrences of new MRI lesions, which was the assessment being the primary objective of 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 a much longer follow-up period than the 24 weeks of this trial. Therefore, the study was not powered to make any more meaningful relapse-based assessments. However, and despite those limitations of the study, a positive signal was already detected that would indicate a lower relapse rate and more relapse-free patients in the IMU-838 treatment arms. Given the limitations of such small and short-duration trials, we're extremely pleased with what we have already observed concerning the signals related to 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 2 trial of IMU-838 in relapsing-remitting MS patients. Primary and secondary end points were met with high statistical significance. We also believe that there's equal efficacy of both dosages used in this trial, 30 and 45 milligrams 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 inhibition of MRI lesions are very encouraging and compare favorably to other first-line oral medications. So let's 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's no noticeable trend for higher rates of adverse events with higher doses of IMU-838. There were only three 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. Additionally, 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've already shown the low overall discontinuation rates 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, three patients in the placebo group and only two 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 discontinuation rates from this trial with some of these data from again the same first-line and oral medications that are currently commercially available for patients where it's 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 how 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 relapsing-remitting MS medications. Immunic has always considered this a potential area for differentiation of IMU-838 and has very closely monitored liver events and liver enzyme elevations. Thus far, no signal for hepatotoxicity anywhere in the IMU-838 development program has 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 two approved doses of teriflunomide as compared to placebo. The label also has a very specific requirement for laboratory-based monitoring, particularly during the initial treatment periods. Immunic has previously reported the detailed safety results of the COMPONENT trial and 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 thorough analysis of liver and also renal events in this Phase 2 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 treatments over 24 weeks as compared to placebo. But let's dive in a little bit deeper. We also looked at the rates 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 and AST, two of the major different enzymes, are very low. Additionally, there was no increase in the rate of liver enzyme elevations in either IMU-838 treatment arm as compared to placebo. But let's go to another important analysis, which 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 normal 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. There's approximately 650 patients exposed to the data. 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, 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 you through summarizing the safety-related results of the top line data of this Phase 2 trial. Consistent with prior data sets in other patient populations, administration of IMU-838 in this trial was observed to be well-tolerated, data also providing further evidence of the favorable safety profile of IMU-838 in this relapsing-remitting patient population. In general, the safety profile is comparable to the placebo group. We have seen a very low rate of treatment discontinuations – in IMU-838 discontinuation rates compared favorably to many other oral and first-line medications already available in relapsing-remitting MS. In summary, we believe that a favorable safety profile of IMU-838 was observed. There was no increase in liver or renal events as compared to placebo, and there's no signal for any 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 2 trial data is ongoing beyond these top line data that are currently available that presented to you in full. 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 at the analysis of the core data set. However, once we obtain and analyze the full data set of this trial to 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 3 program some time ago. And given the availability of the Phase 2 data, we are continuing preparations for such Phase 3 program. We will provide more guidance on the intended Phase 3 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.

Dr. Daniel Vitt, CEO and President

Yes. Thank you, Andreas, and I really love these 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 to take care of that.

Jessica Breu, Head of Investor Relations and Communications

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

Operator, Operator

Yes. Thank you. And the first question comes from Liana Moussatos from Wedbush.

Liana Moussatos, Analyst

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?

Dr. Andreas Muehler, Chief Medical Officer

So thank you for this question. I think that taking the meta-analysis that I have presented that is available, which 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 we hope to kick off soon.

Liana Moussatos, Analyst

Thank you.

Operator, Operator

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

Matthew Kaplan, Analyst

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 your advisors as well?

Dr. Andreas Muehler, Chief Medical Officer

Yes, we believe that we will adhere to the guidelines and recommendations stemming from our regulatory meetings, of which we have conducted several. We intend to present studies that align with regulatory guidance as pivotal trials, but we also believe that a head-to-head trial with an active comparator is important as a supportive element. However, I prefer to hold off on further comments until we have more clarity after analyzing the complete data and concluding discussions with our clinical, statistical, and regulatory advisors regarding this information.

Matthew Kaplan, Analyst

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?

Dr. Andreas Muehler, Chief Medical Officer

Certainly, I believe we need to explore the safety data further to provide more details. We currently lack data on EDSS or disability and brain atrophy, which were collected during the trial but are not included in these top-line results. This aspect is a key differentiator for the DHODH drug compared to other MS treatments, particularly regarding its impact on disability, relapse-independent disability, and EDSS progression. We hope to present at least preliminary findings soon. The same applies to relapse data; a larger and longer study would have been necessary to yield meaningful results. Nevertheless, we are eager to see any indications regarding EDSS disability progression and brain atrophy data.

Matthew Kaplan, Analyst

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

Dr. Andreas Muehler, Chief Medical Officer

Yes. Thank you, Matt.

Jessica Breu, Head of Investor Relations and Communications

Thanks, Matt.

Operator, Operator

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

George Farmer, Analyst

Hi, good morning and my congratulations as well. Very clean data set. I was wondering if you could comment on the 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?

Dr. Daniel Vitt, CEO and President

So I can only answer what I've already said here is that, of course, we had 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.

George Farmer, Analyst

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?

Dr. Daniel Vitt, CEO and President

So you said PML.

Jessica Breu, Head of Investor Relations and Communications

Aubagio.

Dr. Andreas Muehler, Chief Medical Officer

Currently, most neurologists believe that Aubagio, as a DHODH inhibitor, exhibits broad antiviral properties. This has been demonstrated in various studies involving different viruses, particularly highlighted during our COVID-19 trial, where our R&D presented extensive antiviral data. It is generally thought that teriflunomide poses either no or very low risk of PML. Assessing the situation can be challenging because many MS patients experiencing PML have typically been treated with multiple medications, making it complicated to attribute the condition to a specific drug. Nonetheless, there is consensus that teriflunomide carries a minimal PML risk, with some publications asserting that, due to its nature as a DHODH inhibitor, there is no associated PML risk. Given the broad antiviral action observed with IMU-838, we hope to replicate this in clinical data. However, as PML is a rare event, it will require a significant number of treated patients to draw definitive conclusions regarding PML risk.

George Farmer, Analyst

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?

Dr. Andreas Muehler, Chief Medical Officer

A significant number of placebo-controlled clinical trials in multiple sclerosis have increasingly been conducted in resource-limited countries, where there are not enough medical resources to carry out these trials while still achieving high participation rates. Your observation is absolutely correct. This situation highlights how these trials have specifically targeted patient populations in countries where they can take place. For instance, the previous Phase 2 trial was conducted in those regions. Additionally, when reviewing the illustrations from other Phase 2 trials, they involved a similar patient demographic, as there has been a noticeable shift towards Central and Eastern European countries for these trials. This certainly reflects the locations involved in our studies.

George Farmer, Analyst

Okay, great. Thanks, Andreas.

Dr. Andreas Muehler, Chief Medical Officer

Yes. Thank you for the question.

Operator, Operator

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

Yasmeen Rahimi, Analyst

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.

Dr. Andreas Muehler, Chief Medical Officer

Thank you, Yas. I have to manage your expectations a bit because looking at the data from other Phase 2 trials, such as those involving teriflunomide, we've seen that the cumulative number of MRI lesions over time shows a consistent differentiation between treatment and placebo groups at various check-in points. They've demonstrated separation at 6 and 12 weeks, and analyzing the data at different intervals would yield results similar to the final outcome of a 61% reduction in lesions at week 36. While a longer trial duration can enhance data reliability, it doesn't fundamentally alter the proportion of lesion suppression observed. Other Phase 2 trials with similar designs have indicated that extending treatment duration doesn’t change the percentage of patients experiencing lesion suppression or having no lesions; outcomes appear similar across different time points. In my presentation, I focused on the key statistical analysis for the Phase 2 trial to ensure clarity in comparing the main results, which have been published, rather than interim data available through graphs. Those graphs often lack essential details regarding primary analysis. So yes, I welcome any follow-up questions you may have.

Yasmeen Rahimi, Analyst

Thank you, Andreas. The next question is about the careful analysis of the liver enzymes in Hy’s Law. What additional data do you think is needed to avoid a potential black box warning similar to what has been observed with teriflunomide? Are there any other studies that the agency might require?

Dr. Andreas Muehler, Chief Medical Officer

I believe it's primarily about having more patients involved. The black box warnings usually arise from instances of serious events, such as acute liver failure linked to these medications, rather than just liver enzyme spikes. While these enzyme elevations signal concern, most warnings emerge only after cases of acute liver failure have been reported. The agency has been quite firm on this, particularly regarding Hy's law cases, and a biomarker named miR-122, which indicates the risk of acute liver failure. Although this biomarker isn't fully validated yet, the FDA considers the data associated with it. In our Phase 1 trials, we demonstrated that there was no increase in the miR-122 biomarker, and we showed no elevated risk of liver enzyme elevations or any unfortunate cases. Ultimately, more patients are needed to replicate these results and confirm that there are no acute liver failure incidents, which is necessary. With our significantly larger Phase 3 program compared to the Phase 2 program I just discussed, we aim to continue gathering the data we’ve already collected in Phase 2 and further expand our patient pool. This should help instill a bit more confidence in regulators and potentially mitigate the risk of a black box warning.

Dr. Daniel Vitt, CEO and President

Maybe I can add something here. There's a reason we included the chemical structures of teriflunomide and IMU-838 in this presentation. I don’t see a very close structural similarity, and because of that, you cannot expect a class effect here. The term "class" really refers to the chemical class of molecules. Andreas presented excellent data on safety, and we want to be very transparent about liver effects. So far, it looks very promising, and I personally believe there's a high chance that we won’t encounter that problem.

Yasmeen Rahimi, Analyst

Thank you, team. And then one last question. I know we're waiting on 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 in line? 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, that would be very helpful.

Dr. Andreas Muehler, Chief Medical Officer

Yes. So the quick answer is no. I'm absolutely confident that there's nothing to be shown. And I feel unfortunate 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.

Yasmeen Rahimi, Analyst

Thank you team and congratulations again.

Jessica Breu, Head of Investor Relations and Communications

Thanks, Yas.

Operator, Operator

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

Raghuram Selvaraju, Analyst

Hi. Thank you for taking my questions and congratulations on the impressive data. I would like to inquire about curve separation in the study. Looking at earlier time points before the 36 weeks, specifically the 24 weeks, can you provide insight on when you initially observed separation between the treatment arms and placebo concerning the lesion endpoint?

Dr. Andreas Muehler, Chief Medical Officer

I can only say that the data I have seen so far indicate a proportional effect at all time points starting at week 6. However, there is more variability at week 6 because, over time, the differences among patients become less pronounced. Some patients may have more lesions at one time point than another, which averages out over time. The separation between the placebo and treatment curves appears to occur early, which is consistent with observations from other drugs, including teriflunomide. As our Coordinating Investigator presents additional data, we will gain more insight into the timing of these effects. Overall, I believe the data are proportionate across the various time points.

Raghuram Selvaraju, Analyst

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?

Dr. Andreas Muehler, Chief Medical Officer

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 milligrams 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.

Raghuram Selvaraju, Analyst

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?

Dr. Andreas Muehler, Chief Medical Officer

You could use any comparator, but it is likely that you will select comparators that show superiority in some trials. Additionally, you might consider an oral option as a comparator in these Phase 3 trials. However, I can't provide further details at this time as it would be premature to disclose more information. I apologize for this and wish I could share more, but let's wait a bit longer. We will update you soon about our Phase 3 development program.

Raghuram Selvaraju, Analyst

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?

Dr. Daniel Vitt, CEO and President

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

Raghuram Selvaraju, Analyst

Thank you very much and congrats again on the data.

Dr. Andreas Muehler, Chief Medical Officer

Thank you.

Dr. Daniel Vitt, CEO and President

Thank you, Ram.

Operator, Operator

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

Zegbeh Jallah, Analyst

Good morning. I will echo congrats on the data. It 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 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 analysis later on?

Dr. Andreas Muehler, Chief Medical Officer

I believe it's necessary to state that we need to be at least as effective as teriflunomide, and our results indicate that we have achieved that. Specifically, our 30 milligram dose shows a higher rate of lesion suppression compared to Aubagio. However, it's important to analyze more data from this trial, including the EDSS data and brain atrophy data, which will enhance our confidence moving forward. This should be assessed in Phase 3. At this moment, making a prediction regarding a comparison to teriflunomide is challenging based on the current data. What I can confidently say is that regarding safety and tolerability, IMU-838 appears to be significantly more convenient and offers a superior profile for patients compared to teriflunomide. The ability to establish efficacy will depend on the data we receive in the coming weeks.

Zegbeh Jallah, Analyst

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?

Dr. Andreas Muehler, Chief Medical Officer

With the Phase 2 data we have, the next step will be an end of Phase 2 meeting with both the FDA and EMA, which we are looking to expedite due to the positive data. We also need to prepare for various aspects of Phase 3. We've made significant progress in manufacturing as we approach Phase 3, and we anticipate additional data in the coming weeks to complete the end of Phase 2 package. I expect that the end of Phase 2 meeting may occur in early 2021, but I cannot provide more specific guidance at this time.

Zegbeh Jallah, Analyst

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

Dr. Andreas Muehler, Chief Medical Officer

All right. No, thank you.

Jessica Breu, Head of Investor Relations and Communications

Thank you, Zegbeh.

Operator, Operator

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

John Newman, Analyst

Hi, guys. Thanks for taking the question and add my congrats on a 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 drug does not.

Dr. Andreas Muehler, Chief Medical Officer

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 with 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.

John Newman, Analyst

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

Dr. Andreas Muehler, Chief Medical Officer

Yes. 12 weeks.

John Newman, Analyst

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

Dr. Andreas Muehler, Chief Medical Officer

Yes, it’s my turn now. I just need a moment sometimes. Regarding the 12 weeks, there hasn't been a formal statistical analysis conducted. As I mentioned, we’ve done formal statistical analysis at week 24. I've observed the development of CUA lesions over time, which is a linear event. We notice the separation of the curves in terms of events at both 6 and 12 weeks. At 12 weeks, there’s a clear treatment difference, and this can also be seen earlier, but we specifically request data at 12 weeks. There is a numerical difference between the placebo and treatment groups at 12 weeks, though these differences were not subjected to statistical testing.

John Newman, Analyst

Great. Thank you.

Operator, Operator

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

Dr. Daniel Vitt, CEO and President

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.

Operator, Operator

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