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spk02: Good morning and welcome to Munich's third quarter 2021 earnings call. My name is Jessica Brue, Head of Investor Relations and Communications at the Munich. I will also be the moderator on today's call. Please note, all participants will be in listen-only mode and this event is being recorded. Speaking on today's call are Dr. Daniel Fitt, our Chief Executive Officer and President, as well as Glenn Whaley, our Vice President of Finance and Principal Financial and Accounting Officer. After today's presentation, there will be an opportunity to ask questions. If you join the webcast via the Zoom client, there are two ways to submit your questions. You can either submit your questions in writing via the Q&A tool of the Zoom Portal, or if you would like to speak with us directly, please use the raise hand function of the Zoom Portal to queue your question. If you join today's webcast by phone, please press star nine to queue your question. Before we begin, I would like to remind you that this presentation may contain forward looking statements. Such statements can be identified by words such as may, will, expect, anticipate, estimate or words with a similar meaning. And such statements involve a number of risks and uncertainties that could cause Immunix actual results to differ materially from those discussed here. Please note that these forward-looking statements reflect Immunix'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 Immunix's SEC filings for a more detailed description of the risk factors that may affect Immunix's results and these forward-looking statements. I now would like to turn the call over to our CEO and President, Dr. Daniel Fitt, to start with the presentation. Daniel, please go ahead.
spk07: Yeah, thank you, Jessica, for opening the call. I also would like to welcome everybody on Immunix 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 continue 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 2022. 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 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 one trial later this year. Additionally, we just have started part C of the phase one 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 one trial of INU856 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 raw gamma T inverse agonist, IMU935. We presented very encouraging preclinical data showing that IMU95 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 IMU95 for the treatment of metastatic castration-resistant prostate cancer. Based on the strength of this data, we expect to initiate an open-label phase one 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 runway through multiple value inflection points into 2023. In September, we signed an in-license agreement with University Medical Center Göttingen in Germany, covering the combination of DHO-DH inhibitors and nucleoside analogs to treat viral infections. At the same time, we published remarkable preclinical data showing that certain DHO-DH inhibitors, including IMU828, strongly synergize with selected nucleoside analogs to inhibit SARS-CoV-2 replication in vitro. This powerful reduction was demonstrated across multiple SARS-CoV-2 variants, including alpha, beta, and delta, and 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, Göttingen, Ruhr University, Bochum, Universitätsklinikum Erlangen, Utah State University, and MBM Science Bridge for their tremendous work. In September, we enrolled the first patient in our Phase II Caliper Trial of IMU828 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 IMU828's neuroprotective potential. We believe that if the trial is successful in showing a beneficial neuroprotective effect of IMU828, 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 Immunik. In October, we also dosed the first psoriasis patient in Part C of our ongoing Phase I trial of IMU9C5. This represents the first time patients are treated with our oral IL-17 inhibitor, IMU9C5. 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 two trial of IMU838 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.
spk04: 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 30th, 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 reflect a 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 two 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 30th, as compared to 2.5 million for the same period last year. For the nine months ended September 30th, GNA 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 non-cash 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 76 cents per share, based on 25.3 million weighted average common shares outstanding. compared to a net loss of approximately 12.9 million, or 70 cents 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 30th 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, Immunic AG, signed with 4SC AG in March of 2021. Immunic AG settled this remaining obligation of a 4.4% royalty on net sales of IMU 838 for 17.25 million. The payment was made 50% in cash, 50% in shares of Immunix common stock. No further payment obligations remain between Immunix and Forest CAG. With that, I'll turn the call back over to Daniel for an outlook on our upcoming clinical milestones. Daniel.
spk07: Yeah, 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 IMU838 into active phase three development with the first relapsing MS patients expected to be dosed very soon. The insure program comprises twin phase three designed to evaluate the efficacy, safety, and tolerability of IMU838 in RMS patients. We have targeted an enrollment of approximately 1,050 patients in each trial. Dosing will be either 30 milligram daily dose of IMU828 or placebo. The primary endpoint for both trials is time to first relapse up to 72 weeks. One of our biggest milestones in 2022 will be the readout of our phase two 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 one trial of IMU0935, we recently completed the experimental phase of the multiple ascending dose part in 15 healthy volunteers. We anticipate to receive unblinded safety, pharmacodynamic, and pharmacokinetic data from both the single and multiple ascending dose parts still in the fourth quarter of 2021. Also for IMU95, we expect initial patient data from the third portion of the phase one trial in moderate to severe psoriasis to be available in the second quarter of 2022. For IMU95, this will be a major value inflection point as the data will provide us the first time hints about IMU95's safety and efficacy profile in a patient population. Staying a little bit with our IMU935 program, in July, we announced that we anticipate to begin an open-label phase one dose escalation trial of IMU935 in patients with progressive metastatic castration-resistant prostate cancer. The trial is designed to establish a recommended phase 2 dose and to assess safety, trollability, anti-tumor activity, biomarkers, and pharmacokinetics of IMD-95 in CRPC. We were very honored that Professor Johann de Bono from Royal Marston Hospital in London agreed to be the principal investigator of the trial. Just recently, we received approval by the relevant authorities in the UK to conduct the trial, which we expect to start in the fourth quarter of this year. Finally, we anticipate unblinding safety data from the single and multiple descending dose parts of IMU856 in healthy volunteers in the third quarter of 2022. Initiation of patient part of the phase one 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.
spk02: Thank you, Daniel and Glenn, for walking us through the third quarter 2021 earnings presentation. We will now begin the question and answer session. As a reminder, if you joined the webcast via the Zoom client, there are two ways to submit questions. You can either submit your questions in writing via the Q&A tool of the Zoom portal, or if you would like to speak with us directly, please use the raise hand function of the Zoom portal to queue your question. if you join today's webcast by phone please press star 9 to queue a question 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 mueller our chief medical officer patrick walsh our newly appointed chief business officer and inderpal singh our general counsel at this time we will pause momentarily to assemble our rooster The first question comes from Yasmin Rahimi at Piper Sandler. Yasmin, please unmute yourself and go ahead.
spk01: Good morning, team. Thank you so much for taking my questions. I have a number for them. Maybe I would like to start off as we think about the CALDO 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 and endoscopy healing. 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 endoscopy reading, and then I have a follow up.
spk06: Very good. Thank you, Yas, for the question. This is Andreas, the chief medical officer. Regarding our CALDOS-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 Dr. Daniel Ziblatt- endoscopic remission to be achieved at the same time at week 10. So when we designed the study, Dr. Daniel Ziblatt- both regulators and also international clinical experts that we work with Dr. Daniel Ziblatt- had really indicated that we needed to find an endpoint that Dr. Daniel Ziblatt- Reduces the variability of the outcomes in placebo is known from the history of trials and IBD that that there is some variability between trials in 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 trial, 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 IMU838. 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 have also used the composite endpoints of very similar even identical composite endpoints where you see that the placebo response is below 10 percent or or much below 10 percent and the active treatment arms of of these drugs that we know are active uh been found somewhere in the range of 15, 20, 25% for the active treatment arms. And I think that's also our expectations 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 of placebo. So that's that's the the first question. Yes, and the and the second question, the clinical execution of of endoscopy and histology. So, as with many other trials, I think it's now a state of the art that the endoscopy Christian Lebiere, The screening endoscopy, but also we have endoscopies, of course, at week ten for the primary endpoint, and we have an endoscopy at week fifty at the end of the double-blind maintenance period after the induction after remission was achieved that all of those endoscopies are done by a central blinded reader. So this is not done locally, but it's done by a central binary reader. And there was also an adjudication of the week 10 endoscopy. That means that they have been read at least twice. And if they're not concurrent, Christian Lebiere, then an adjudication was done, so I think this is what we've done, I believe, is really state of the art to what's 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 a gita score that's also the histology store that's that's used that of course is also done in a blinded fashion which is of course much easier because it's it's done often by a it has to be done by a central lab that that is completely independent of the execution of the trial hopefully yes i i addressed your your questions um no that was that was perfect thank you andreas
spk01: and maybe one more follow-up for you would be with will you be reporting a top line also just the individual rates for clinical remission and then the second question is as we are awaiting the data from the sat and map portion of 935 should we be looking at certain biomarkers that will help us sort of provide translation into the 1B psoriasis cohort. And thank you again for taking my long list of questions.
spk06: Yeah, no, no, that's fine, yes. So I think for the UC trial, the CALDOS-1 trial, we will, of course, the top-line data will not only include the primary data, but it also includes the individual rates of clinical remission, clinical improvement and endoscopic improvement, endoscopic remission. So I think there will be these individual data as well, not just the composite data. I think because also I think it provides a better understanding of comparability to other UC drugs and phase two trials. So I think that for us was important as well to be part of the top line data. In terms of 935, that's a very good question. Do we have in the part A and B that includes healthy volunteers any chance to have biomarkers that will hint on efficacy or on activity in the psoriasis part later on? I have to say that's very difficult. We have thought about this quite a lot, and it's very difficult to do because you wouldn't have to look at um for example cytokines or some other biomarkers that are not elevated in these healthy volunteers because they're they're very carefully selected to be really healthy volunteers and and uh have no medical history and so forth so i unfortunately i have to say i don't think with the data that we will present to you before the end of the year in terms of the safety pharmacokinetics unblinded uh laboratory findings and so forth i don't think that will give too much credence on efficacy activity readouts. So I don't think that's possible with this healthy volunteer population.
spk01: Thank you so much for taking my question.
spk02: Thank you, Yas. Our next question comes from Gobind Singh at JMP. Gobind, please unmute yourself and go ahead.
spk00: Hi. Is this working?
spk02: Yes.
spk00: Wonderful. Thanks. So two for me. First on IMU 838 and progressive MS. Wondering if there's 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 neurofilaments and what have we seen 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 Caliper trial? And then one follow-up from me.
spk06: Dr. Alexander De Juan- I go I go and thanks for the question this Andrea is again chief medical officer, so I think in terms of the btk we're carefully looking, of course, at at the btk inhibitors. Dr. Alexander De Juan- And how they present themselves and in this space, especially in progressive Ms, but also in general in the MS space and, to be quite honest, I think i've seen the. the presentations by the companies developing it. And at the moment they are focusing very much on still the immune component of their reaction and the upregulation of the BTK. um in immune related cells in the brain which surprised a little bit because i think if you uh if you have to uh if you if you uh want to develop this for secondary progressive you you have to to my mind or to our mind you have to address also um Juergen Etzlstorfer- mechanisms of disability worsening that are unrelated to to the primarily unrelated to the immune system, so I think the BTK inhibitors have focused on on microglia, for example. We believe that the mechanism of action of IMU-A38 is much broader than that and can address different things that, of course, involves, for example, antiviral effects. It involves also having an effect on, which is known for other DHO-DH inhibitors, on actually the metabolic status and mitochondrial stress in actually neuronal cells, so non-immune-related cells, which I think... we believe is contributing to a efficacy in a phase of MS that's not primarily driven by immune mechanisms. So in that respect, I see clear difference. in the way that IMU838 can act in secondary progressive MS or in primary progressive MS than the BTK inhibitors. On the other thing, I also feel very strongly that our safety profile that we have shown in phase two in the relapsing remitting and also that we see now in the continued open label phase of this phase two study. And we have more than 200 patients of this phase two trial still on drug, still on treatment in this open label portion. And we see very little drop off in basically patients on treatment, which we take as a very good sign in terms of the general tolerability profile for this drug. So I think we feel very strongly that we can achieve a very good differentiation versus BTK inhibitors, even in this progressive MS population.
spk00: 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, you know, about a 20% reduction compared to placebo. Might we see an update in the open label this year? And then one follow-up on COVID-19, you know, with everything going around with Merck and the excitement there and the data that you guys have presented in the combo setting, X vivo for the potentially improved reduction in Sarko V2. Is there anything there that you can comment on at this point about maybe resuming clinical development or otherwise?
spk06: Yeah, Gobind, so just the question for you, basically neurofilament. I have to hear in public uh present ignorance on my part that i don't really have a good understanding of what newer filament is doing in ptk inhibitors so i know you you're very interested in it and i'll do my best to to update myself a little bit better next time And maybe for the question about the synergistic effect between DHO-DH with other drugs in the COVID setting, I would hand over to Daniel.
spk07: Yeah, I think we just recently announced and you have seen we signed this collaboration or a licensing agreement with the University of Göttingen and it was based on exactly that synergy observed. We think the potential is broad and goes definitely beyond COVID-19. So I think this principle should be used on a broader level on targeting antiviral or having new antiviral, very potent antiviral treatments. However, we clearly said in the past already that we are not planning to go ahead into phase three in with 828 and COVID-19 and we didn't change our plans yet. I think we are focusing the company really on the important things here. We are still interested in the combination and in the antiviral properties, but that should be done in a collaboration or in an independent way forward. And I'm not in a position to give more details on the discussion status here, but I think clearly there is an interest in this world in potent antivirals, and there will be a way forward for that molecule, but it's unlikely that we start in clinical trials soon.
spk00: Thank you.
spk02: Thank you, Gobind. Our next question comes from Thomas Smith at SVB Liering. Thomas, please unmute yourself and go ahead.
spk09: Hi, everyone. This is Mike on for Tom. Can you hear me all right?
spk02: Yes, hi Mike.
spk09: Sure.
spk02: Hi there.
spk09: Thanks for taking our questions. Two on our end. The first is just, can you provide some color on how you're thinking of overall competitive landscape in IBD, and specifically what kind of impact you see the recent labeling updates for the JAK inhibitors having? And I have a follow-up.
spk07: That was well, it's a mixture of question for andres and myself. Um, of course it's an interesting time in that space, and specifically given that um and and that that's not a secret that the Fda had some some question questions around safety and durability of jack inhibitors recently. So that's, of course, impacting the whole set of therapy developments in that space. And for us, it underlines that there's a high unmet medical need. We nicely fit in. And just to repeat, and I mentioned that in our company presentations a couple of times, A3A provides something from a mode of action point of view, something new for patients with ulcerative colitis, which is, on the one hand, being a selective immune regulator and targeting specifically hyperactivated immune cells. On the other hand, having antiviral properties protecting patients from viral reactivations. I think these are two features which are urgently needed from patients in that space.
spk06: um not sure unless if you want to add some some more color on this on on the competitive landscape from your point of view just from the medical point of view yes and of course i when we started the phase two program for for imu 838 um there was when we when we talked to our medical advisors and and experts there was cause they had a lot of focus on the jack inhibitors because they had a an advantage to the market um to um in establishing this new category of these novel immune modulators that are between the traditional immune modulators and the biologics. And what I've seen now is really, I think that with more and more drugs coming, there was the hope that that what's called more selective JAK inhibitors would behave differently or would have less challenges, which I think in general didn't materialize. And so I think the whole class of drugs really has to certain different degrees, of course, the different drugs, but have the same Juergen Etzlstorfer- I think reputational problem, then also for the medical community, we also have seen that there was especially about the jack inhibitors a lot of discussions about the increases of infections during treatment and virus reactivations. and especially zoster reactivations. And I think we clearly see here that our antiviral properties really has helped us that we have, in our clinical trials, never seen an increase of infections and infestations versus placebo. We have not seen these viral reactivations. And in that respect, we feel very strongly that the time advantage that these jack-in-the-headers had coming into the market will not play out well for them, to my mind, and we have a very good chance with IMU838 to create a very successful drug in ulcerative colitis.
spk09: Got it. That's very helpful. Thanks. And then just quickly, with respect to the Ms. Program, has anything changed recently in the phase three trial assessment? And how do you plan on mitigating potential impact of Covid in the study?
spk06: So I'm not sure anything has changed. No, I. I'm just thinking what you could mean, because we are just executing as quickly as possible the plans that we had. And so I think it's a very large program. These phase three programs are very complex in terms of the different assessments with different vendors that you have to do. our team does do extremely good work in terms of preparing these phase three trials, but nothing has changed in the execution of the phase three trials.
spk07: And 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.
spk06: I think we have the experience from the, from the CalDOS trial, the IMU A38 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 in our part, the COVID impact on IMU 838, because we had been in very close contact with all of the investigators during the COVID period, highlighting the broad antiviral property. Dr. Alexander De Juan- At a time when we didn't know that we had actually activity in covert 19 as we found out later on with the color trial. Dr. Alexander De Juan- We focus that this does not put patients at risk, like many other immune modulators with that actually put patients at risk, which is very well known now for a more severe course of the of the covert 19 disease and once we had to call it. Dr. Alexander De Juan- Data in covert. We actually also informed them that 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 I think assurance to the investigators that that they should continue this trial. That's what you had seen at least in the Caldos trial. We, of course, take preventive matters, especially in terms of providing study drug 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 more robust infection numbers in the future here in this winter for COVID-19.
spk09: Great. Thanks very much and congrats on the progress.
spk06: Thank you, Thomas.
spk02: Mike, Mike, Mike. So our next two questions come from Zach Bejala 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 Munich, including MS, you see psoriasis, et cetera. And even your investigator sponsored studies like MCRPC are all blockbuster indications. However, they are also indications for which there are multiple competing drugs. You've shown success in MS. How are you thinking about competitiveness of your programs in UC and psoriasis?
spk07: Well, this is a very important strategic question for the company. And first of all, I agree with the success in the MS space. That's a good problem to have. They are big indications. And I think the company is addressing high unmet medical needs. We may not be in a position to continue with all the programs through phase three our own. So it's likely something where we are open for partnering. And in that context, you can also see that we just recently strengthened the team with Patrick Walsh joining us in October as chief business officer to balance the exposure here and also strengthening our discussions here with potential farmers for the future. But of course these are big markets and they are driven by big unmet medical need.
spk02: The second question is about our interest in partnerships and are you likely to also independently take your UC and psoriasis programs into phase three like you have with the MS program or are you open to partnering ahead of the initiation of pivotal studies?
spk07: Patrick, would you like to?
spk03: to comment on that? 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.
spk02: Thank you, Patrick. Just as a reminder, if you have a question, please use the raise hand function of the Zoom portal, or if you joined by phone, please press star 9. Our next question comes from Matt Kaplan at Leidenberg-Talman. Matt, please unmute yourself and go ahead.
spk10: Hi, good morning. Can you hear me?
spk02: Yes. Hey, Matt.
spk10: um thanks for taking the questions up just one a couple a couple of questions uh first a follow-up on on yasmin's question um in terms of the sad and mad data for 935 i guess um not that not that we're looking for a read-through to the psoriasis but can you describe uh the pd data that we should be looking for as that as that reads out later this year So, Matt, are you meaning what's in the part A and B that we're… No, just from a pharmacodynamic point of view, what are some of the things you're looking for, not really beyond PK, I guess, in the SADMAD data?
spk06: So pharmacokinetic, of course, data we will have extensively because, of course, in this part A and B, we did single-dose pharmacokinetic. We had multiple-dose pharmacokinetic over 14 days in these patients. And these were healthy volunteers, sorry. um we also explored different dosing options um once daily versus twice daily i think to to see how they address um certain needs for example or how they would allow us certain configurations for for these patients so both are done and we also in this part a and b did evaluation of food effect, for example, on the pharmacokinetic. So that's what you should expect all to come. And I think I just have to stress what I told you. Yes, I think the amount of Dr. Michael Doan- pharmacodynamic data that you can get this relevant to really our indication and that exceeds what we had done in vitro, because we had done the in vitro data with human lymphocytes and release based on different concentrations of i'm in 935, so this was done in vitro and the. felt that there's very little that you can do in healthy volunteers that would exceed really the value of the in vitro experiments that we had done with human lymphocytes.
spk10: Okay. That's very helpful. Thank you. And then a second question, just wanted to focus a little bit on your other program, IMU 856, which targets the intestinal barrier function. Can you give us a sense in terms of what role this molecule could play and what indications you're excited about potentially pursuing after your after you announce the sad and mad data, I guess, in the third quarter of next year.
spk06: I think Matt, these are very good questions. The thing with the, and you know this as well as I do, that the mechanism of action addresses the barrier dysfunctions in the gut that is responsible for so many diseases, symptoms and pathophysiology for different diseases. Yes. And that's as much as good news as bad news. Yes. Because I think the company has to focus to find its indication where we believe we can show proof of concept relatively quickly with the 28 day dosing similar to psoriasis. um where you have a medical need and where you also have the ability to execute quickly towards um with with endpoints that are accepted by the fda and with this this discussion is ongoing but i think um i can promise you we i have a lot of these interesting discussions and we will relatively soon uh present our our plans for that but at the moment we we haven't fully been able to make this public yet.
spk10: Okay, fair enough. Well, thanks for taking the questions and congrats on all the progress.
spk02: Thank you, Matt. Next question comes from Bubalan Pachayapan at H2 Rainrite. Bubalan, please unmute yourself and go ahead.
spk08: Hi, can you hear me? Yes, hi. Okay, awesome. So just a few, thanks for taking my question, 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 NSHE trial and maybe future pivotal trials in advanced MS patients?
spk06: Hi, Bubulan. This is Andreas again, the chief medical officer. So I think this goes way beyond the Munich, yes, because I think the, not only the MS community, but the community of doing, clinical research on in neurodegenerative diseases this is beyond ms i really found that the biomarker neurofilament correlates to the amount of damage to neurons and independent necessarily independent of the disease process that that's involved and we have seen this in in several diseases and in ms also we've seen a very good correlation not just in our trial but also um in other trials in the last years that um the the treatment effect in preventing the the damage to neurons and endurance neurons dying and having less lesions and having less relapse activity always translates into neurofilaments. And we have shown this just with the ECTRIMS poster, I think, two months ago, last month. that it correlated very well with the patients who had relapse. For example, in our phase two trial had more of a more resistance to nfl decrease than patients who didn't have a relapse. But you're also asking a good question, because I think there's a predictability. It doesn't mean that there's not overlap in the individual patients. So I think NFL is a good marker for groups in terms of, or populations in terms of therapy control, or a therapy relation to success of therapy. But we have also seen that, and that we have also published in this ECGEMS poster, is that those patients who at baseline, for example, at start of therapy, have a relatively high neurofilament that they're having more activity in a trial. They tend to have more activity, but it's also a little bit more, this is a prediction and may not help you on the individual patient level, but on the population, that's true. We will not use a stratification or a inclusion-exclusion criteria for neurofilament in the Phase III because we believe, I think, also that what we have seen from the Phase II data, and that was part of the poster as well, that the treatment effect of IMU838 is independent of what baseline neurofilament level you have. So I think it would unnecessarily diminish our phase three population. And also we don't need to basically enrich a more active or a population that is expected to have more relapses for this trial, we believe. So it's something that is a very good marker. for damage to neurons. And especially to your, you come back to your last question in terms of progressive MS. There are over the last one or two years, and this ECTRIMS again last month was also no exception. There are now more data because I think the marker started with relapsing MS data, but we have now more data in progressive MS and they absolutely mirror what we know from relapsing MS that neurofilament also is a very good the treatment predictor and correlates with activity of drugs in secondary progressive and patients who have a more aggressive form of progressive MS have a higher neurofilament in serum than those patients who have a less severe disability progression or brain atrophy. And this has been shown over and over again. So it thinks this is a real effect. And that's why we're also using neurofilament as part of our interim analysis for our CALIPER trial. And we believe that this could be predictive in terms of the overall results to expect at the end of the trial.
spk08: Sanjay Gupta, Ph.D.: : I found just that's really, really helpful so your candles one study is completed enrollment So what are your baseline expectations for this trial. Sanjay Gupta, Ph.D.: : And what what would be the minimum placebo adjusted clinical remission rate you'd like to see to carry the program forward, and do you think the candles one results impact the upcoming Crohn's disease trial.
spk06: Dr. G R Narsimha Rao, So I think. Dr. G R Narsimha Rao, I know that's a very good question in terms of whether you have a. a hard threshold or a hard parameter on which to decide whether to go forward in phase three. Usually, I think these phase three decisions are not related to statistical significance or to a certain outcome, or I think you need to justify it on the on the entirety of the data, because I think there's also some benefit risk that you have to consider where you have to put the safety versus the gain and efficacy activity that you see. So I personally think that you need to look at the entirety of data. For example, Bertrand de La Chapelle, I just want to remind you of the face to try and talk about seven and two topics in it like Pfizer that there was really I think as far as I remember. Bertrand de La Chapelle, There was no statistically significant outcome in the primary or key secondary outcomes and. and clearly it's an active drug in UC. And Pfizer took it forward. So I think the expectation should be really to look at the entirety of the data and make an assessment of benefit risk and also what the dosing level is that is supported by activity and the safety. And so far what we have seen, I think, we have uh and that was this true for the phase two study in ms that we could have taken any of our doses forward that we had in phase two in terms of safety but yeah then you have to decide what's the um the lowest effect of those that that should be going to phase three and that's how we chose the the 30 milligram dose it was not a assessment of a certain statistical outcome from the phase two, to be quite honest. So it was, I think, more consideration span. But I think the outcome, of course, in the main efficacy endpoints, of course, have a huge effect on how this benefit risk is. But I think it's wrong to have a, well, it's not advised to have a very hard criterion for that, to my mind.
spk08: 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? Thank you.
spk07: So maybe this is more an overall question for the pipeline and the balance. And we decided to park it for a little bit because we have identified CRPC as a very attractive indication. prioritize crpc a little bit over of a gps and given that we will see data from the sad mad safety part towards end of the year and first in first efficacy hints from the psoriasis patient cohort in the second quarter next year coming from psoriasis i think this will this will help us to get the full picture and also will help us on supporting going forward for example in gps as well
spk08: Okay, thanks so much for taking my question. Really appreciate your time. Thank you.
spk02: Thank you, Gubalan. Our next question comes from Andreas Aguridis at Wetbush. Andreas, please unmute yourself and go ahead.
spk05: All right, good morning, and thank you for taking our questions. Just a quick one, and this is a nice segue from the Prostate Cancer Program 935. Can you provide additional color on the study, such as how many doses will be assessed at the start of the trial? What biomarkers do you plan on measuring?
spk06: Yes. Hi, Andreas. I think it was a little bit lower volume, I think, than the rest. So I just say, repeat the question for if somebody had a hard time hearing the question. So you want a little bit more color, how the study will be done in CRPC for IMU 935. So this... first of all, in general, this study will have a dose escalation part. That means that we have several cohorts where we try to escalate the dose and potentially find a dose limiting of toxicity. This is something that we have not done in the Dr. Daniel Ziblatt- Phase one trial in the general phase one trial for i'm your 935 because we know that the dose limited toxicity is way beyond the therapeutic necessary doses for immunology diseases so in that respect. Dr. Daniel Ziblatt- This will be different, of course. Juergen Etzlstorfer- Before the oncology indication, where you have to try to dose up to the dose limiting toxicity, so this will be done with several courts we don't know how many. Juergen Etzlstorfer- So it depends a little bit of, of course, how quickly you find that those limited because he or whether you're not find that we have a maximum dose also identified, where we will stop because it's we believe that. You don't need to go beyond that. And then we have a second part that's an expansion part where we take one or two doses that we identified as potential phase two doses or that basically are where we have seen maybe some hint of activity in the dose escalation part to expand cohorts to allow a more a thorough assessment of activities in those parts. The study will look at biochemical markers, of course, PSA, yes, as a biochemical output. We are looking at imaging. We're looking at circulating tumor cells. So everything that you know about prostate cancer, and especially about casterization and prostate cancer from the prostate cancer working group. Now, recommendation three, I think we have implemented. So I think when you read the Andreas Schleicher, Ph.D.: : prostate cancer working group document you basically find the biomarker that we're also looking at the following the recommendations as. Andreas Schleicher, Ph.D.: : You and the bonus one of the authors of this prostate cancer working group document and really had set the guidelines, I think. Andreas Schleicher, Ph.D.: : You more or less have to follow these. Andreas Schleicher, Ph.D.: : These guidelines, then.
spk05: Great all right appreciate the color thanks and congrats on all the progress. Andreas Schleicher, Ph.D.:
spk06: : Thank you address.
spk02: Thank you, Andreas. This concludes our question and answer session. I would like to turn the call back over to Daniel for any closing remarks.
spk07: Yeah. Thank you, Jessica. And thank you all for the great questions and the lively discussion today here. 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 IMU828 in alternative colitis and the initial patient data from IMU935, 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.
spk02: Also from my side, thank you for joining in Munich's third quarter 2021 earnings call today. The conference has now concluded. You may now disconnect.
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