Immunic, Inc. Q3 FY2021 Earnings Call

Hello. Good morning, and welcome to Immunic's Third Quarter 2021 Earnings Call. My name is Jessica Breu, Head of Investor Relations and Communications at Immunic. I will also be the moderator on today's call. This event is being recorded. Speaking on today's call are Dr. Daniel Vitt, our Chief Executive Officer and President; as well as Glenn Whaley, our Vice President, Finance and Principal Financial and Accounting Officer. After today's presentation, there will be an opportunity to ask questions. Before we begin, I would like to remind you that this presentation may contain forward-looking statements. Such statements can be identified by words such as may, will, expect, anticipate, estimate or words with 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 revision to these forward-looking statements in light of new information or future events. Please refer to Immunic's SEC filings for a more detailed description of the risk factors that may affect Immunic's results and these forward-looking statements. I now would like to turn the call over to our CEO and President, Dr. Daniel Vitt, to start with the presentation. Daniel, please go ahead.

Yes. Thank you, Jessica, for opening the call. I also would like to welcome everybody on Immunic's Third Quarter 2021 Earnings Call. Earlier this morning, we announced our financial results from the third quarter of 2021, and highlighted recent milestones as well as upcoming updates to our clinical development pipeline. During today's call, we will talk through our third quarter 2021 and subsequent highlights, financial and operating results as well as anticipated milestones. Before we close the call, you will have the opportunity to ask questions. During the third quarter, we continued to make great progress in advancing our three product candidates through the clinic, setting the stage for several important data readouts in the fourth quarter of 2021 and '22. Most importantly, we expect to start patient enrollment in our Phase III program in relapsing multiple sclerosis still this quarter. Another major milestone will be the top line data from our Phase II trial in ulcerative colitis, which we anticipate in the second quarter of 2022. We just recently announced the completion of patient recruitment with 263 patients randomized in total. For our second program, IMU-935, we expect unblinded safety data from the single and multiple ascending dose parts of the Phase I trial later this year. Additionally, we have just started Part C of the Phase I trial in psoriasis patients and expect initial human data from this patient population in the second quarter of next year. Finally, we also hope to see first clinical data from the ongoing Phase I trial of IMU-856 in the third quarter of next year. But let me walk through the third quarter 2021 and subsequent highlights in more detail first. In July, we hosted a virtual R&D Day to provide an update on the preclinical and clinical development of our RORgamma t inverse agonist, IMU-935. We presented very encouraging preclinical data showing that IMU-935 may inhibit both the generation of Th17 cells and the production of IL-17 cytokines that are responsible for the development of autoimmune diseases without impairing thymocyte development. We think that this may avoid a potential risk for lymphoma that has complicated third-party programs in this space. At the R&D Day, we also presented further new preclinical data highlighting the potential of IMU-935 for the treatment of metastatic castration-resistant prostate cancer. Based on the strength of this data, we expect to initiate an open-label Phase I dose escalation trial in CRPC during the fourth quarter of this year. Also in July, we successfully completed a $45 million follow-on offering, which extended our cash run rate through multiple value inflection points into 2023. In September, we signed an in-license agreement with the University Medical Center Goettingen in Germany, covering the combination of DHODH inhibitors and nucleoside analogues to treat viral infections. At the same time, we published remarkable preclinical data showing that certain DHODH inhibitors, including IMU-838, strongly synergized with selected nucleoside analogues to inhibit SARS-CoV-2 replication in vitro. This powerful reduction was demonstrated across multiple SARS-CoV-2 variants, including alpha, beta, and delta, thereby highlighting the independence of this approach to mutant virus forms. I once again would like to thank our research partners at the University Medical Center, Goettingen, Ruhr-University Bochum, Universitätsklinikum Erlangen, Utah State University, and MBM ScienceBridge for their tremendous work. In September, we enrolled the first patient in our Phase II CALLIPER trial of IMU-838 in patients with progressive MS. The trial will run concurrently with our twin Phase III ENSURE trials in relapsing MS and is thought to be a supportive trial to underline IMU-838 neuroprotective potential. We believe that if the trial is successful in showing a beneficial neuroprotective effect of IMU-838, we may be able to clearly differentiate IMU-838 versus other oral MS medications and carve out a very attractive commercial positioning in the MS landscape. In October, we are very pleased to welcome Patrick Walsh as our new Chief Business Officer. Patrick is a seasoned BD executive, and I very much look forward to leveraging his experience here at Immunic. In October, we also dosed the first psoriasis patient in Part C of our ongoing Phase I trial of IMU-935. This represents the first time patients are treated with our oral IL-17 inhibitor, IMU-935. We expect initial psoriasis data in the second quarter of next year. October was a month of clinical milestones for Immunic. We also completed patient randomization in our Phase II trial of IMU-838 in moderate-to-severe ulcerative colitis. In total, 263 patients were randomized. We now eagerly await the top line data of the trial in the second quarter of next year. For the next part of our presentation, I would like to hand over to Glenn for the financial overview.

Thank you, Daniel. We will now review the financial and operating results for the third quarter of 2021. Let me start with the cash overview. We ended the quarter with $110 million in cash and cash equivalents, which we anticipate to be sufficient to fund operations into 2023. Now let's review the operating results. Research and development expenses in the third quarter were $15.5 million as compared to $11 million for the same period in 2020. For the nine months ended September 30, R&D expenses were $42.7 million as compared to $27.5 million for the same period in 2020. The increase in costs for both periods reflects the continued ramp-up of our clinical expenses related to our three clinical programs, as well as increased personnel expenses as a result of hiring more people to support the company's growth. The increases were partially offset by decreased costs related to our Phase II clinical trial in COVID-19 that was finished in the first quarter of 2021 and decreases in drug supply costs for IMU-856. General and administrative expenses were $2.9 million for the three months ended September 30 as compared to $2.5 million for the same period last year. For the nine months ended September 30, G&A expenses were $10 million as compared to $7.3 million for the same period in 2020. The increase in costs for both periods was primarily due to noncash stock compensation expense as well as smaller increases in costs across numerous categories. Net loss for the third quarter 2021 was approximately $19.3 million or $0.76 per share based on 25.3 million weighted average common shares outstanding compared to a net loss of approximately $12.9 million or $0.70 per share based on 18.4 million weighted average common shares outstanding for the same period in 2020. Net loss for the nine months ended September 30 was approximately $71.8 million or $3.33 per share based on 21.6 million weighted average common shares outstanding compared to a net loss of $32.9 million or $2.35 per share based on 14 million weighted average common shares outstanding for the same period in 2020. I would like to remind everybody that our year-to-date net loss was impacted by the settlement agreement of our subsidiary in Immunic AG signed with 4SC AG in March of 2021. Immunic AG settled its remaining obligation of 4.4% royalty on net sales of IMU-838 for $17.25 million. The payment was made 50% in cash, 50% in shares of Immunic's common stock. No further payment obligations remain between Immunic and 4SC AG. With that, I'll turn the call back over to Daniel for an outlook on our upcoming clinical milestones.

Yes. Thank you, Glenn. As mentioned in the beginning of the call, we have a wealth of milestones coming up in the next couple of months, and I'm happy to walk you through these. Still in the fourth quarter of this year, we anticipate advancing IMU-838 into active Phase III development with the first relapsing MS patients expected to be dosed very soon. The ENSURE program comprises twin Phase III design to evaluate the efficacy, safety, and tolerability of IMU-838 in RMS patients. We have targeted an enrollment of approximately 1,050 patients in each trial. Dosing will be either a 30 milligram daily dose of IMU-838 or placebo. The primary endpoint for both trials is time to first relapse after 72 weeks. One of our biggest milestones in 2022 will be the readout of our Phase II trial in patients with moderate-to-severe ulcerative colitis. We currently expect the top line results of the induction phase to be available in the second quarter. For our Phase I trial of IMU-935, we recently completed the experimental phase of the multiple ascending dose part in 15 healthy volunteers. We anticipate receiving safety, pharmacodynamic, and pharmacokinetic data from both single and multiple ascending dose parts still in the fourth quarter of 2021. Also for IMU-935, we expect initial patient data from the third portion of the Phase I trial in moderate-to-severe psoriasis to be available in the second quarter of 2022. For IMU-935, this will be a major value inflection point as the data will provide us with the first insights into IMU-935's safety and efficacy profile in the patient population. Staying a little bit with our IMU-935 program, in July, we announced that we anticipate beginning an open-label Phase I dose escalation trial of IMU-935 in patients with progressive metastatic castration-resistant prostate cancer. The trial is designed to establish a recommended Phase II dose and to assess safety, tolerability, and tumor activity, biomarkers and pharmacokinetics of IMU-935 in CRPC. We were very honored that Professor Johann de Bono from Royal Marsden Hospital in London agreed to be the principal investigator of the trial. Just recently, we received approval by the relevant authorities in the U.K. to conduct the trial, which we expect to start in the fourth quarter of this year. Finally, we anticipate underlining safety data from the single and multiple ascending dose parts of IMU-856 in healthy volunteers in the third quarter of 2022. Initiation of the patient part of the Phase I trial in intestinal barrier function associated diseases is expected in the first half of 2022. This brings me to the end of the presentation. Jessica, please open the call for the Q&A session.

Thank you, Daniel and Glenn, for walking us through the third quarter 2021 earnings presentation. For the Q&A session, we also have our broader management team on the call. In addition to Daniel and Glenn, we have Dr. Andreas Muehler, our Chief Medical Officer; Patrick Walsh, our newly appointed Chief Business Officer; and Inderpal Singh, our General Counsel. The first question comes from Yasmeen Rahimi at Piper Sandler.

I have a number of things. Maybe I would like to start off as we think about the CALDOSE study that is upcoming. So I think a frequent question that we're getting from our clients is to understand how we should be thinking about the composite endpoint, which is symptomatic remission endoscopy healing. So if you could provide us some color on what bar in your view is considered success? And then second, I would love to also learn a little bit more in terms of the clinical execution of reporting these histological and an endoscopy reading. And then I have a follow-up.

Thank you, Yas, for the question. This is Andreas, the Chief Medical Officer. Regarding our CALDOSE-1 trial in moderate-to-severe ulcerative colitis patients, yes, I think you're absolutely right. I think we use a composite endpoint that entails both symptomatic remission and endoscopic remission to be achieved at the same time at week 10. So when we designed this study, both regulators and international clinical experts that we worked with had really indicated that we needed to find an endpoint that reduces the variability of the outcomes in placebo. It is known from the history of trials in IBD that there is some variability between trials in a placebo response, and patients actually can get better even under placebo or no treatment in this indication. And this variability has contributed to some of the failures of clinical trials in the past of drugs that we know to be active. So when we designed this drug, this composite endpoint was designed to minimize any placebo response. So we do expect a very low treatment response in the placebo group. But also, I think this will have influence in what to expect in terms of the response in the active dose groups for IMU-838 when we have three dose groups, 10, 30, and 45 milligrams in this trial. So I think there should be the expectation. That's very similar to very recent trials that were also used on identical composite endpoints, where you see that the placebo response is below 10% or much below 10%, and the active treatment arms of these drugs that we know are active have been found somewhere in the range of 15%, 20%, 25% for the active treatment arms. And I think that's also our expectation that this would be a desired outcome and a good outcome for this kind of trial where we use this very stringent composite endpoint in order to reduce the variability of placebo response. So that's your first question, Yas. And the second question, the clinical execution of endoscopy and histology. So as with many other trials, it's now state-of-the-art that the endoscopy, the screening endoscopy, but also we have endoscopies, of course, at week 10 for the primary endpoint, and we have an endoscopy at week 50 at the end of the double-blind's maintenance period after the remission was achieved, that all of those endoscopies are done by a central blinded reader. This is not done locally but this is done by the central blinded reader. And there was also an adjudication of the week 10 endoscopy. That means that they have been read at least twice. If they are not concurrent, then adjudication was done. So I think this is what we've done, I believe, is really state-of-the-art to what is currently done in IBD trials. In terms of histology, we have a histology assessment at screening at week 10 and at week 50 that will allow us to do the EDSS, that's also the histology score that's used, and of course, this is also done in a blinded fashion, which is, of course, much easier because it's done often by a central app that is completely independent of the execution of the trial. Hopefully, Yas, I addressed your questions.

No, that was perfect, Andreas. I have one more follow-up for you. Will you be reporting a top line along with the individual rates for clinical remission? Also, as we await the data from the SAD and MAD portion of 935, should we focus on certain biomarkers that could help translate into the Ib psoriasis cohorts?

Yes, that's fine, Yas. For the UC trial, the CALDOSE-1 trial, the top line data will include not just the primary data, but also the individual rates of clinical remission, clinical improvement, endoscopic improvement, and endoscopic remission. Including these individual data points is essential, as it allows for better comparability to other UC drugs and Phase II trials. In terms of 935, it’s a good question. In Parts A and B, which include healthy volunteers, it's challenging to identify biomarkers that might indicate efficacy or activity in the psoriasis segment later on. We've considered this extensively, and it's difficult because the healthy volunteers are carefully selected to ensure they have no medical history or elevated biomarkers. Therefore, I don’t believe the data we present before the end of the year, regarding safety, pharmacokinetics, and laboratory findings, will provide much insight into efficacy activity readouts. I don't think that's possible with this healthy volunteer population.

Our next question comes from Gobind Singh at JMP.

So two for me. First, on IMU-838 in progressive MS. Wondering if you have any comments about the recent hype from large pharma to kind of develop their own BTK in this space and also RMS, of course, but if why BTK is in MS and now? And is there any relation to neurofilament? And what are we seeing there? And is there any way to kind of use that as a bar for what could be coming from the interim readout from the CALLIPER trial? And then one follow-up for me.

Thank you for your question, Gobind. This is Andreas, the Chief Medical Officer. Regarding BTK inhibitors, we are carefully examining their role, particularly in progressive MS and generally within the MS field. I must admit that I have observed the presentations from the companies developing these inhibitors. Currently, their focus remains largely on the immune response and the upregulation of BTK in immune-related brain cells, which I find somewhat surprising. In my opinion, for the development to be effective for secondary progressive MS, it is essential to address mechanisms of disability worsening that are largely independent of the immune system. BTK inhibitors have concentrated on microglia, but we believe that the mechanism of action of IMU-838 is broader and can tackle various aspects, including antiviral effects. Additionally, it also affects the metabolic status, particularly mitochondrial stress in non-immune-related neuronal cells, which we think plays a role in the efficacy for MS phases not primarily driven by immune mechanisms. Consequently, I see a notable difference in how IMU-838 functions in secondary and primary progressive MS compared to BTK inhibitors. Furthermore, our safety profile demonstrated in Phase II for relapsing-remitting MS, as well as what we are observing in the ongoing open-label phase of this trial, is encouraging. With over 200 patients still on treatment, we are seeing minimal drop-off, which indicates a favorable tolerability profile for this drug. We are confident that we can establish a significant differentiation from BTK inhibitors, even within the progressive MS population.

One follow-up on that. Have we seen with any of the BTKs, what it's doing on neurofilament? And then on the open-label part of the trial, might we see any updated data longer term, perhaps improvements in neurofilament? I believe the last results you guys presented there was almost about a 20% reduction compared to placebo. Why would we see an update in the open label this year? And then one follow-up on COVID-19. With everything going around with Merck and the excitement there and the data that you guys have presented in the combo setting ex vivo for potentially improved reduction in SARS-CoV-2, is there anything there that you can comment on at this point about maybe resuming clinical development or otherwise?

Yes. Gobind, just a question for you, basically neurofilament. I have to hear in public present ignorance on my part that I don't really have a good understanding of what neurofilament is doing in BTK inhibitors. So I know you're very interested in it, and I'll do my best to update myself a little bit better next time. And maybe for the question about the synergistic effect between DHODH with other drugs in the COVID setting, I would hand over to Daniel.

We recently announced that we signed a collaboration or licensing agreement with the University of Göttingen, which is based on the synergy we've observed. We believe the potential goes beyond just COVID-19 and should be applied more broadly to target antiviral treatments, particularly highly effective ones. However, we have previously stated that we do not plan to proceed with Phase III trials of 838 for COVID-19, and our plans remain unchanged. Our focus is on important priorities within the company. We are still interested in the combination and the antiviral properties, but that work should be pursued through collaboration or independently moving forward. At this time, I can't provide additional details regarding the discussions. Nonetheless, there is a clear interest in effective antivirals, and we will find a path forward for that molecule, although it is unlikely we will initiate clinical trials in the near future.

Our next question comes from Thomas Smith at SVB Leerink.

This is Mike on for Tom. Two on our end. The first is just can you provide some color on how you're thinking of the overall competitive landscape in IBD? And specifically, what kind of impact you see the recent labeling updates for the JAK inhibitors having? And then I have a follow-up.

It's a combination of a question for Andreas and me. It's an interesting time in that area, particularly because the FDA has recently raised concerns about the safety and tolerability of JAK inhibitors. This situation is affecting the entire range of therapy developments in that field. For us, it emphasizes a significant unmet medical need where we fit well. I want to reiterate, as I've mentioned in our company presentations several times, that 838 offers something novel for patients with ulcerative colitis. It acts as a selective immune regulator that specifically targets hyperactivated immune cells, while also providing antiviral properties to protect patients from viral reactivations. These two characteristics are urgently needed by patients in this area. Andreas, do you want to share more insights on the competitive landscape from a medical perspective?

Yes. When we initiated the Phase II program for IMU-838, we consulted with our medical advisers and experts who highlighted the significant interest in JAK inhibitors. They believed these drugs had a competitive edge in establishing a new category of immune modulators that bridge traditional immune modulators and biologics. However, as I observe now, more drugs are entering the market. There was hope that more selective JAK inhibitors would function differently or face fewer challenges, but that expectation has not generally come to pass. Thus, the entire class of these drugs faces varying reputational issues within the medical community. We've also noted considerable discourse regarding JAK inhibitors and their association with increased infections and viral reactivations during treatment. In contrast, our clinical trials have demonstrated that IMU-838's antiviral properties have not resulted in any rise in infections and infestations compared to placebo. We have not observed any viral reactivations. Therefore, we are confident that the initial advantage JAK inhibitors had in entering the market will not benefit them in the long run, and we believe we have a strong opportunity with IMU-838 to develop a successful treatment for ulcerative colitis.

Got it. That's very helpful. And then just quickly, with respect to the MS program, has anything changed recently in the Phase III trial assessment? And how do you plan on mitigating potential impact of COVID in the study?

I'm not sure anything has changed. I'm just considering what you might mean because we are executing our plans as quickly as possible. These Phase III programs are quite complex due to the various assessments required with different vendors. Our team does an excellent job preparing for these Phase III trials, but there has been no change in their execution.

Maybe just on COVID, I think we talked about it, given that we have seen antiviral properties of 838, we clearly see not a big issue with the ongoing COVID pandemic on recruitment. That's priced in basically in our estimates.

I think we have the experience from the CALDOSE trial, IMU-838 trial in ulcerative colitis that of course had a lot of activity during the whole COVID period. And yes, there are a few sites usually that makes monitoring harder and also that we have accessibility problems for patients. But this was really, I think, very minimal on our part, the COVID impact on IMU-838 because we have been in very close contact with all of the investigators during the COVID period, highlighting the broad antiviral property at the time when we didn't know that we had actually activity in COVID-19 as we found out later on with the CALDOSE trial. We focus that this does not put patients at risk like many other immune modulators that actually put patients at risk, which is very well known now for a more severe course of the COVID-19 disease. And once we had to cover data in COVID patients, we actually also informed them that we have seen some activity in this trial that would support that we actually might be helpful for these patients in case they get infected. So I think this all had very good assurance to the investigators that they should continue this trial and that's what we have seen at least in the CALDOSE trial. We, of course, take preventive measures, especially in terms of providing study drugs to patients when they're not allowed to access the site. But in terms of enrollment, I don't think we see a significant impact even with maybe a more robust infection numbers in the future here in this winter for COVID-19.

So our next two questions come from Zegbeh Jallah at ROTH Capital, and I will actually read them because they came in via the Q&A tool. First question, most of indications being pursued by Immunic, including MS, you see psoriasis, et cetera, and even your investigator-sponsored studies like MCRPC are all blockbuster indications. However, there are also indications for which there are multiple competing drugs. You've shown success in MS. How are you thinking about the competitiveness of your programs in UC and psoriasis?

This is a crucial strategic question for the company. I agree that achieving success in the MS space is a positive challenge to have, as there are significant indications involved. The company is addressing a pressing medical need, but we might not be able to advance other programs through Phase III independently. Therefore, we are open to partnerships. Recently, we bolstered our team with Patrick Walsh joining us as Chief Business Officer to enhance our outreach and discussions with potential partners moving forward. These are large markets driven by significant unmet medical needs.

The second question is about our interest in partnerships. And are you likely to also independently take your UC and psoriasis programs into Phase III like you have with your MS program? Or are you open to partnering ahead of the initiation of pivotal studies?

Yes, happy to, and good morning, everyone. This is Patrick Walsh. I'll summarize it this way in that we are actively exploring many options across the portfolio, and we have not made any decisions with respect to the types of arrangements that we will or won't consider, but certainly excited about the evolution of the data for all of our programs here. So looking forward to that.

Thank you, Patrick. For the next question comes from Matt Kaplan at Ladenburg Thalmann.

Just one question. First, a follow-up on Yasmeen's inquiry regarding the SAD and MAD data for 935. While we're not seeking a direct correlation to psoriasis, could you explain the PD data we should anticipate as it becomes available later this year?

So Matt, we are looking for information related to Parts A and B of the study. We will have extensive pharmacokinetic data because we conducted single-dose and multiple-dose pharmacokinetic studies over 14 days with healthy volunteers. We also explored various dosing options, such as once daily versus twice daily, to understand how they meet certain needs or allow for specific configurations for patients. Both of these studies were completed. Additionally, in Parts A and B, we evaluated how food affects pharmacokinetics. This data is what you can expect in the future. I want to emphasize that the amount of pharmacodynamic data we can obtain is not particularly relevant to our indication, as it exceeds what we have accomplished in vitro. We have conducted in vitro studies using human lymphocytes and assessed the release at different concentrations of IMU-935. We believe there is little that can be learned from healthy volunteers that would surpass the insights from our in vitro experiments with human lymphocytes.

Okay, that's very helpful. For my second question, I would like to focus on your other program IMU-856, which targets intestinal barrier function. Can you provide some insight into the potential role of this molecule and the indications you are considering pursuing after announcing the SAD and MAD data, which I believe will be in the third quarter of next year?

Yes, Matt, that's a great question. The mechanism of action addresses the fundamental barrier dysfunctions in the intestines that contribute to various diseases, symptoms, and pathophysiology. This is both good and bad news because the company needs to focus on identifying its indications where we believe we can demonstrate proof of concept relatively quickly with the 28-day dosing, similar to psoriasis. This area has a medical need and allows us to move quickly toward endpoints that the FDA accepts. This discussion is ongoing, and I can assure you we are having many interesting conversations. We will soon share our plans, but for now, we haven't been able to make this information public yet.

Next question comes from Boobalan Pachaiyappan at H.C. Wainwright.

Okay. Awesome. So just a few from our end. So just curious to hear your thoughts on NFL, especially these two questions. So firstly, how do NFL levels in RRMS patients compare with healthy adults? And secondly, do you think utilizing NFL as a biomarker may streamline patient recruitment for your upcoming ENSURE trial and maybe future pivotal trials in advanced MS patients?

Boobalan, this is Andreas again, the Chief Medical Officer. I believe this extends beyond Immunic because both the MS community and those involved in clinical research on neurodegenerative diseases are affected. The biomarker neurofilament correlates with the extent of neuronal damage, regardless of the disease process involved. We have observed this correlation across various diseases, including MS, where there has been a strong connection not only in our trials but also in other trials over the past few years. The treatment's effectiveness in preventing neuronal damage, reducing the number of lesions, and decreasing relapse activity consistently translates into neurofilament levels. Our ECTRIMS poster from last month highlighted that patients with relapses in our Phase II trial experienced a greater reduction in neurofilament than those without relapses. You raise a valid point regarding predictability; however, individual patient overlap may still exist. Neurofilament serves as a good marker for groups concerning therapy success. Our published ECTRIMS data also indicated that patients with higher neurofilament levels at baseline exhibited more trial activity, but this is more of a general prediction rather than applicable to individual patients. In our Phase III trial, we won't use neurofilament as a stratification or inclusion/exclusion criterion because we believe that the treatment effect of IMU-838 is independent of baseline neurofilament levels. This would unnecessarily limit our Phase III population, and we do not need to select a population expected to have more relapses for the trial. Neurofilament is a significant marker for neuronal damage. Regarding your earlier question on progressive MS, more data has emerged over the last couple of years, including at ECTRIMS last month. Initially focused on relapsing MS, we now have significant data on progressive MS, which parallels what we understand from relapsing MS. Neurofilament is also an effective treatment predictor for secondary progressive MS, and patients with a more aggressive form of progressive MS tend to have higher neurofilament levels in serum compared to those with less severe disability progression. This finding has been consistently demonstrated, affirming that neurofilament's predictive ability is real. Consequently, we are incorporating neurofilament into our interim analysis for our CALLIPER trial, as it may help predict the overall results we anticipate at the trial's conclusion.

Okay. Awesome. One last one from me. So what are some of the gating items remaining to initiate the GBS program, Guillain-Barre syndrome? And where do you see opportunities for value creation given there are multiple players in the clinical development space?

So maybe this is more of an overall question for the pipeline in the band, and we decided to pocket for a little bit because we have identified CRPC as a very attractive indication and we prioritize CRPC a little bit over GBS. Given that we will see data from the MAD safety part towards the end of the year and first efficacy hints from the psoriasis patient power in the second quarter next year coming from psoriasis, I think this will help us to get the full picture and also will help us on supporting going forward, for example, in GBS as well.

Our next question comes from Andreas Argyrides at Wedbush.

Just a quick one. I know there's a nice segue from the prostate cancer program, 935. Can you provide additional color on the study and such as how many doses will be assessed at the start of the trial? What biomarkers do you plan on measuring?

Yes, Andreas. I think there’s a bit less interest overall, so let me reiterate the question for anyone who might have had difficulty hearing it. You’re asking for more details about how the study in CRPC for IMU-935 will be conducted. This study will include a dose escalation component, meaning we will have several groups where we will try to increase the dose to potentially identify a dose-limiting toxicity. We haven’t conducted this in the Phase I trial for IMU-935 because we know that the dose-limiting toxicity is significantly above the therapeutic doses necessary for immunological diseases. Therefore, this approach will differ for the oncology indication, where we aim to escalate to the dose-limiting toxicity. The study will involve several cohorts, although the exact number is uncertain and will depend on how quickly we can find that dose-limiting toxicity, or if we do so at all. We have also determined a maximum dose at which we will stop, as we believe there’s no need to exceed that level. Following that, there will be an expansion phase where we evaluate one or two doses identified as potential Phase II doses, where we may have observed some signs of efficacy during the dose escalation. The study will assess biochemical markers, including PSA levels, as well as imaging and circulating tumor cells. We are looking at all relevant aspects of prostate cancer, particularly in relation to castration-resistant prostate cancer, following the guidelines set out in the prostate cancer working group's latest recommendations. One of the authors of this document, Johann de Bono, contributed to establishing the guidelines, which we will adhere to closely.

This concludes our question-and-answer session. I would like to turn the call back over to Daniel for any closing remarks.

Yes. Thank you, Jessica, and thank you all for the great questions and the lively discussion today here. I very much enjoyed that. I hope you can feel our excitement about the operational progress Immunic has made this year and the multiple catalysts to come in the next couple of months. We very much look forward to seeing clinical data from our clinical programs next year, in particular, the Phase II data of IMU-838 in ulcerative colitis and the initial patient data from IMU-935, both in the second quarter of next year. With this, I would like to close today's call. Thank you very much for joining, and we are very happy to answer any additional questions in one-on-ones.

Also from my side, thank you for joining Immunic's Third Quarter 2021 Earnings Call today. The conference has now concluded. You may now disconnect.