Mendus AB (publ) (IMMU) Earnings Call Transcript & Summary

Good day, and thank you for standing by. Welcome to the Immunicum webcast conference call. [Operator Instructions] Please be advised that today's conference is being recorded. [Operator Instructions] I would now like to hand the conference over to your speaker today, Erik Manting. Please go ahead, sir.

Thank you. Welcome, and thank you for joining the Immunicum webcast, which relates to the update of our ADVANCE-II clinical trial. Today's webcast is hosted by myself; and by Jeroen Rovers, our Chief Medical Officer, and as an introduction, please have a look at Slide 4 for what the main topics are for today. In today's webcast, we will be reviewing the interim results from the ADVANCE-II study of DCP-001, our cancer relapse vaccine and the press release that was a summary of the main data reported was released this morning. In today's update, we will focus on 2 main topics: One, the primary endpoint of the trial is measurable residual disease; and secondly, we will give a first impression on how the MRD relates to the relapse-free and overall survival. Before we move to Jeroen to present the data, let me say a few things about the ADVANCE-II trial. First of all, the trial is a monotherapy trial, so we're looking at single drug activity in AML maintenance therapy, which is a high unmet medical need and also as Jeroen will also explain in his session, it's a very aggressive disease. So the fact that we are aiming for monotherapy data in this therapeutic setting, means that we have data that we believe very much and strongly relate to the product. What also makes us a unique trial is that it was a rather large consortium of 10 participating clinical and academic centers in different European countries, being the Netherlands, Germany, Sweden, Norway and Finland, and that the trial was supported by a Horizon 2020 grant after EU. That not only supported the trial, but it also supported the setting up of a broader research network and the development of our process development and manufacturing capabilities. So with that as a background, I will hand it over to Jeroen for the AML maintenance therapeutic landscape and then the presentation of the data.

Thank you, Erik. So I will first walk you through a bit of the background of acute myeloid leukemia, specifically maintenance treatment in acute myeloid leukemia and also on measurable residual disease because that's the primary endpoint we report on today, and just give a bit of a background how to interpret MRD nowadays. So on Slide 6, we showed you a diagram of treatment of acute myeloid leukemia patients at the moment. This is still a disease diagnosed typically at an elderly age, and yearly, we see about 55,000 patients diagnosed with this disease. Those who are fit for chemotherapy will go and receive chemotherapy as soon as they can. And the success rates there are about 65% of patients who reach a status of complete remission, which means there's less than 5% of the leukemic blast detected in the bone marrow. When you reach that level, so when the initial chemotherapy has been successful, then it's a matter of trying to see whether you can really eradicate all the disease. Nowadays, we know that we can detect residual disease, and that has become a much more important parameter like I will show later. But for those patients who have reached complete remission, the standard currently is to go for a more definite solution, which is a bone marrow transplant or abbreviated often by HSCT. That is a procedure where, of course, bone marrow is eradicated and replaced by the donor bone marrow, but it's not available, unfortunately, for everyone. You either need to be able to go through that procedure, so you need to be in a condition which allows you to be transplanted, but maybe as important, you also need to have a donor available, which is not everywhere in the case. Those patients who do not have a chance to go for a bone marrow transplant, they need to be followed up carefully and see whether the disease returns and act upon or -- and that's the space where we currently will talk about more, get some form of treatment to maintain the remission status. And the quote we provided from Professor Platzbecker in Leipzig actually supports that this has become a new area where we try to find solutions for patients. We need to try and maintain patients into complete remission because we know that we'll guarantee their longer survival. So if we go to Slide #7, what I just mentioned is that with more patients now in complete remission, it becomes also more important to see whether they still have residual disease, and that's where we talk about a measurable residual disease. And we see that MRD is also in clinic, an accepted endpoint or at least an accepted parameter to monitor carefully. We've seen a publication just recently on the relevance of MRD in AML patients, which was a metanalysis in more than 11,000 patients which again supported the conclusion that achieving MRD negativity is really associated with superior long-term survival. And that's clearly shown in the figure on the left-hand side where the patients who are MRD negative have a better relapse-free survival, as you can see, versus those who are MRD positive. So if we go to Slide #8, our lead investigator in the ADVANCE-II study, Professor van de Loosdrecht, also actually has shown -- has indicated that this is one of the key parameters which nowadays, we need to look at. Specifically in early studies, MRD is a relevant parameter to see if you can have an effect on residual disease, and that translates towards the future in a better relapse-free and overall survival. And I think the data we start to see emerge as what we will show you in a little bit later, is also indicating this. So we move to Slide #9. And this slide actually gives a bit of the background on the current landscape in treatment of acute myeloid leukemia, specifically maintenance. It wasn't until, say, 2 years ago that there was a lot of choice for patients who went into complete remission because there was hardly any maintenance treatment, except for regular monitoring of these patients to see if they are still in remission, yes or no. But since then, we've had the introduction of oral azacitidine, which was approved through a larger Phase III study called QUAZAR study. So on this slide, we're showing you some benchmarks from that Phase III study where oral azacitidine was actually compared against placebo in acute myeloid leukemia patients who were brought in complete remission through chemotherapy treatment. And in this case, we are also looking at the subset of patients who had still residual disease. This is the same patient population as where we are conducting the ADVANCE-II study, hence, the relevance for the data we will show you a little bit later. On the left-hand side, you see there the MRD responses where you see that in both the oral azacitidine group and in the placebo-treated group, there are MRD responders. It's 37% in the oral azacitidine and 19% in the placebo. It needs to be clear that in this study, patients started with either of these treatments immediately after the chemotherapy treatment, so their induction and consolidation therapy treatment which is the most likely explanation for seeing an effect of this chemotherapy transpire into the placebo group. And that's clear because most of those MRD responders are actually within a short time after the start of this treatment. At a later stage, it's hardly unlikely to see in at least in this placebo group patients to still have an MRD response that's relevant to still bear in mind. On the right-hand side, this gives you the relapse-free survival. And it's also very clear to see here that there is still a high medical need for patients who reach a complete remission, but who still have residual disease. And that's shown by the placebo-treated patients who have a median relapse-free survival of just 3 months. And the patients treated with oral azacitidine have a median of 7 months. And although that's an improvement for both these patient groups, you see that within, say, the first 2 years after diagnosis, about 80% to 90% of these patients still relapse. I think that indicates, as Erik just also indicated, the high unmet medical need, in our view, for finding additional solutions to maintain complete remission for these patients. And on Slide 10, that's actually how we look at it from our side, how we develop and position DCP-001, because this is a vaccination where we aim to boost the antitumor immunity after the initial successful treatment with chemotherapy in order to try and control this residual disease and to reduce and delay the relapse of these patients. So this was the background, which I wanted to briefly introduce before going into interim results of the ADVANCE-II trial, what I will do now. So on Slide 12, we're showing you how this study looked like. So it was a Phase II study designed to validate the DCP-001, as a novel maintenance therapy in AML. This was a multicenter study where we recruited 20 patients which were available for the primary endpoint. The primary endpoint was measurable residual disease. Specifically, in this case, up to 8 months after start of the treatment. Additionally, safety and tolerability was an important primary endpoint and the immune responses, which might be triggered through the vaccination. What we have read out and what we report on now is the effect on measurable residual disease and secondary endpoints of this trial will follow later being, say, survival, like relapse-free survival, overall survival. For reference, how did we treat these patients? Well we've vaccinated these patients, and it's an intradermal vaccination approach with 4 vaccinations scheduled biweekly. Then there was a small pause and then 2 boost of vaccinations were given. And the total time follow-up for patients to look at MRD was at least 8 months or 32 weeks, but the study continues to follow up patients for their survival. If we move to Slide 13, then we briefly give you a snapshot of the safety profile of DCP-001, which we see emerging in the ADVANCE-II study. We've given more than 100 intradermal vaccinations with this product, and thus far, we've not seen serious adverse events, which were reported to be related to the vaccination. And what we have saw reported related to the vaccination were primarily injection site reactions. So there where we do the intradermal injection, we see that the patients develop redness or swelling. So really as a clear sign of an activation of the immune system. So I think overall, this supports the use of AML -- of DCP-001 as an AML maintenance treatment because we don't seem to add any toxicity to this patient population. And the feedback so far has been that patients are tolerating this treatment extremely well. Then if we move to the next one, Slide 14, I think that's the key for today, next to the slide, which we'll show after this. So what have we seen on MRD responses? So we've seen that of those 20 patients, which we were able to determine MRD responses after the vaccination, 5 responded completely, meaning we had patients turning MRD negative after the vaccination. We had 2 patients where MRD actually was reduced by more than tenfold, which are generally also accepted to be regarded as responders. Then we had 7 patients where MRD remains stable, and these patients continue to be in complete remission. And within the first 32 weeks, we saw 6 patients that had a disease relapse. So to summarize MRD responses we saw in 7 out of the 20, and we had stable disease for MRD on 7 additional patients. On the right-hand side, you see a snapshot of the patient population. And I think the most important to show is that the median follow-up. Today, when we read out the data, was already 436 days or more than 14 months. So the data set is maturing quite nicely, but like I said, we are further looking into the survival of these patients in the months and years to come. So if we move to Slide #15 next to the responses, we also want to give you a slight insight on the onset when do these responses occur and how durable are they. Well, we saw that in all these patients where we had an MRD response in the MRD converters, that happened after the 4 initial vaccinations. So it's relatively quick after the start of the vaccinations, within the first 14 weeks that we see these responses occurring, and they were durable. So in 4 out of the 5 patients, MRD negativity was maintained up to the 8-month time follow-up. What is important to note is that the time between start of the vaccination and the initial treatment of acute myeloid leukemia, so the induction chemotherapy, that was 295 days. So these patients are at least a month or 10 after start of their chemo. So the effect of potential chemo treatment is less likely at this time. If we look at then the survival and of course, this is not read out yet, we can only give you the status as of the database cutoff. And we saw that in total so far, even beyond, say, the 32 weeks, we had 7 patients who relapsed. For the median relapse-free survival and the overall survival, we've not been able to read that out. So patients have just survived too long yet to be able to conclude on that. But we have been able to estimate the probability of relapse-free survival at 6 months. That was 83.7%. And if we look at the probability of overall survival at 6 months, that was 97%. So I think to summarize, the interim results suggests that the DCP-001 treatment of these MRD-positive AML patients leads to a reduction of residual disease, which seems to translate into a survival benefit. And with that, I'll hand over to Erik Manting.

Thanks, Jeroen, for the background and the presentation of the data. So if you move to Slide 17, let us look ahead with the update of today, what the next steps will be. First of all, these data are very encouraging. I think it's a first sign of efficacy, not only on the MRD level but also on how the effects on MRD translate into relapse-free and overall survival benefit. But of course, we will continue to follow the secondary endpoints and continue to report on how the relapse-free and overall survival data will shape up. Secondly, as part of the study, we are not only following the residual disease, but also quite in detail the responses of the immune system, so meaning the immunomonitoring data. They take a bit longer together for technical reasons. But as soon as we have more immunomonitoring data, we also hope to add those to the total update of the study. Of course, we have been presenting at multiple medical scientific conferences. We presented at ASH, we presented at EHA and also a number of other conferences both the data from the ADVANCE-II trial, but also the preclinical data that we have obtained with DCP-001, and we will continue to do so. As a midterm outlook, we feel very much encouraged by today's result and that the ADVANCE-II study will provide for a base for late-stage development of DCP-001. So next to the data updates that we will continue to provide to the market, we are preparing in parallel our manufacturing strategy. And in that context, we are very happy that Leopold Bertea joined us recently as Chief Technology Officer, and he will be in charge in setting up a commercial stage manufacturing infrastructure. What was also recently published at the medical scientific conference is the combination potential of our product with azacitidine and Venetoclax, which are 2 established drugs in AML treatment, where azacitidine, like Jeroen explained, is also particularly positioned in AML maintenance, the oral azacitidine. But we've also published end of last year a paper demonstrating the combination potential of our product with CD47 antagonist, which is another upcoming class of therapies. So I think overall, we have put in place next to the clinical data, quite a broad package of research supporting the combination potential of DCP-001 in the broader AML maintenance space. With that, we'd like to conclude the presentation of today, and hand it back to the operator to introduce the Q&A session.

[Operator Instructions] Your first question today comes from the line of Jacob Mekhael from Kempen.

I just want to say congrats on the set of results. They're very interesting to see. But I'm just curious if you've had any feedback from the regulator about the percentage of MRD conversion that would be deemed sufficient.

I think that then centers around the question, would this data set be of acceptable quality to go for marketing authorization. And we don't expect that, to be honest, at the moment because it's a small data set. But I think what we've shown here briefly about what is acknowledged more and more by not only the clinical, but also the regulatory environment is that MRD is really a very good surrogate and it translates into survival. So if you are able to eradicate the residual disease, a patient really relapse far less and they survive much better. Having said that, so any next trial will, of course, look at MRD and also effects on MRD, but the discussion here with the authorities, I think were not, per se, centered at MRD as being the endpoint. I think the survival endpoints like relapse-free survival are as important. And what's shown in this graph from this Phase III trial is, of course, also very evident is that relapse-free survival is very poor still in this specific MRD-positive patient population. So we expect that both on MRD, but also on relapse-free survival, for instance, we would be able to generate sufficient data to discuss that with the authorities.

Okay. My next question, I was also curious, do you expect to see any more MRD conversions going forward? Or do you think that, that sets for now? Or are you going to be subtracting those going forward?

No, we've now looked at MRD up to week 32 old study, meaning about 8 months. And as the therapy was given initially and what we indicated as well, we see the MRD responses happening early on. And then they seem to be doable, but we don't expect at a much later stage for these MRD conversions to still take place. And we also are not, say, collecting additional MRD data. We collect additional data on the disease status, meaning relapse-free survival and overall survival, but not anymore in MRD.

I have a few more questions also. So we have the readout that's coming in Q4 this year on the RFS and OS data. What kind of levels are you expecting to see -- or again, what levels would you want to see for the benefit of DCP-001 to be deemed sufficient?

Well, what I expect to see, it's difficult to comment on. But I think if you relate it to also what we've just shown in this presentation, so patients who are treated only with a placebo who are, say, in complete remission after initial chemo who are MRD positive, their median relapse-free survival is 2.7 months. It's clear from the data we showed you now is that's going to be better for our patient population in this study for sure. Where we will in the end land with our median relapse-free survival, I cannot predict. But I think given the maturity of the follow-up and the data set and current status of relapse which we were able to report, I think you should be able to have a good estimate on where this might go. And I think the only thing I can say, I'm looking extremely forward to later this year to be able to read the further, say, survival data.

And one final question, if I may. So in terms of plans with DCP-001 going forward, is there a new trial plan? And if so, what are the time lines? And what would the design of the trial be like?

Maybe Jeroen, you can give the first part of the answer, and then I will add some funding perspective.

Yes. I think the next steps, of course, would be to see how you can make this work best for patients with AML. And I've shown, I think we've seen an incremental benefit of treating these patients. And so not doing anything, just waiting and watching is not the solution. So adding oral azacitidine into the treatment of those patients has shown to relate to a better, say, survival, a relapse-free survival and overall survival of these patients. And we feel that by adding maybe DCP-001, into that treatment regimen, we could even step up so we could even improve those results. Recently, of course, we showed that preclinically, we did experiments by combining DCP-001 with an approach like azacitidine or Venetoclax. And we see that actually we are able to add additional benefit. And that's what we probably will go for in the next clinical trial combining DCP-001 with the standard of care at that time, which could, of course, be oral azacitidine.

And just to add briefly to that, Jacob. Of course, the data are still shaping up and the better the data will look like at the end of the year, the more aggressive we can be in the strategy moving forward. So we are looking into different scenarios at the moment, but at the same time also, of course, keeping an eye on the further maturation of the data. So please bear with us. I think we can say more about the way forward as soon as we have further maturation of the data at hand. Thanks so much for your question, Jacob. Maybe if you have any further questions, we can also take it offline, but it would be also good to give a few others the opportunity to ask one more questions. Thanks so much.

Your next question comes from the line of Christian Binder from Redeye.

Most of them have actually already been answered, but just picking up on what's just discussed in terms of potential late-stage trials, so as you said, it depends somewhat on the data. But in terms of trial design, do you think there will be a possibility of directly going into a Phase III trial? Or do you think it would be more structured like a, for example, Phase II free trial? How do you think about that?

Well, I think it goes back to the question from Jacob also, Christian. Of course, the design of the trial will be, to a certain extent, dependent on the strength of the data, which, of course, we are very much encouraged by on today's update, but how big the differentiator will be and how strong the data will be will also determine to a certain extent, how much we can accelerate. Of course, we will also have to discuss it with the regulatory agencies. As Jeroen stated, MRD is a very important endpoint for this trial, but we are not sure at this point whether it will also be recognized as an endpoint of further clinical development on a conservative side of things we would expect not. And so there are still a lot of moving parts, but we do feel with today's data that we are well positioned to start working on the next trial design and without wanting to be too speculative on what that will look like. But of course, with the intention to keep you updated as much as possible as we go.

And then one last question regarding looking at AML as a whole as an indication outside of maintenance, which specific other indications do you think could be addressed with DCP-001 longer term?

Well, first of all, we have a combination of the products which, as you know, is a wholesale-based vaccine. We believe that, that is not a trivial element of it. It carries a lot of endogenous antigens, and it triggers the immune system in a natural way through a combination of cancer cell and dendritic cell biology. And that creates a much broader immune control over the disease. So we think that is one important element which is inherent to the product. But the positioning of the product, which means that the immune system is recovering from previous lines of chemotherapy, but also that a lot of the suppression mechanisms that tumors generally cause have been taken out, actually provides for a natural window for vaccination because you have some time for the immune system to respond to the vaccine. The disease burden is relatively low. So I think that, to a large extent, determines the positioning of the product. So a natural way to go about this is, first of all, we focus on the current positioning, which is in AML in post-remission patients for patients that have undergone high-dose chemo. But as you look into the broader AML field, you already see that the maintenance window will become a lot broader. So with Venetoclax now on the market, driving more patients that are not eligible for high-dose chemo into a state of clinical remission, also leaves more patients in that roughly half of the total AML population for maintenance therapy. And finally, also, after transplantation, patients sometimes still suffer from MRD. So also in the post-transplant setting, there will be room to treat MRD-positive patients. So as the broader picture shapes up, we believe the maintenance window will only become broader and bigger. And that is the most immediate element that we wish to address. And after that comes everything else, meaning also potential other indications but we believe that there's more than enough room to grow in the immediate vicinity of the current trial.

[Operator Instructions] Your next question comes from the line of Harry Shrives from Edison Group.

It's Harry here from Edison. Congratulations on those results as well. The data is shaping up quite honestly there. Yes. So I just wanted to ask, is there any difference between the 2 dose costs that you've got that we should be aware of?

Thanks for the question. No, I think at the moment, we don't see any difference between the 2 dose cohorts. And that's also the reason why we feel comfortable pooling them altogether and also in analyzing going forward, the survival data, but neither on responses or neither on side effects, we've seen a difference. What we are, of course, looking into whether there might be differences based on immune responses, if we look really in-depth into immunomonitoring. And like what Erik was indicating, that data is still to follow, and we hope to report on that later this year.

So secondly, I was just thinking, is there -- do you guys anticipate any read across from these results in the ADVANCE-II study to the other study in ovarian cancer, the ALISON study.

No, I think that's too early to say. I think what it indicates in AML, of course, is that if you're able to take control over residual disease, you hope to really reduce relapse and extend survival. If the same concept holds in ovarian cancer, of course, that's to be seen, but the first step we're taking there is to really see that we are triggering immune responses, which we deem to be relevant for potential control. So that's what we hope to read out as soon as we can. So the safety of applying it in a different cancer indication and whether, of course, we see the expected, say, immunological responses. And then as a next step, but that will take a slightly more time, of course, if that also is then relating or translating into less relapses in that specific disease indication.

And I think to add to that, Harry, there is, of course, a more general point of validation. As you know, we have published end of last year's a very detailed paper about the mode of action of the product, which relates to indirect priming mechanisms of the immune system with crosstalk between dendritic cell compartments and with exchange of antigenic material, and that is, we believe, not only very attractive biology from the scientific point of view, but it's actually crucial for the triggering of relevant immune responses. And that is increasingly being recognized. It was also, by the way, the reason for the merger between DCprime and Immunicum because we felt we could build leadership in allogeneic and dendritic cell biology, which relates to this type of mode of action. So in that sense, of course, with these being relatively maturing clinical data, we do believe that the concept also -- or the data also underlines the concept that we are pursuing.

So finally, I just wanted to ask, I know that direct comparisons between trials are not always objectable and the data is still quite young. But can you explain how you see this data stacking up against sort of main competitors like Onureg in the market.

Yes. And I think the first -- if we take, say, the Onureg study, so that's this Phase III study, QUASAR AML-001 study, if we take that as a reference, and it is a very valuable reference for us in this whole development, of course. I think the first reference is those patients treated with the placebo because that's indicating if you don't give anything else, what would happen to these patients. And what was mentioned earlier, we see that those patients still relapse very quickly after the initial treatment. So the median relapse-free survival there was 2.7 months. How does it compare to what we're currently seeing? Well, I think we've shown you that with a median follow-up here of about 14 months, we've not yet been able to read out the immediate relapse-free survival. So I think compared to that, I think I'm quite comfortable to say our median relapse-free survival will be much better than those patients treated only with the placebo. Comparing to oral azacitidine, well, I think the reference there is a median relapse-free survival of 7.1 months, and I hope later this year, we were able to show you where we stand. And so -- but thus far, like I said, our median relapse-free survival has not been able to read out in this patient population at this data cutoff. So let's wait and see. And we're quite excited to see where it will end, but we're very comfortable.

Congratulations again on the results.

There are currently no further questions. I will hand the call back to yourself, Erik, for any closing remarks.

Thank you. Well, with that, this concludes our webcast of today. Thank you so much, everybody, for participating. Thanks for all the covering analysts for your questions, and we look forward to keeping you and the market updated on the further progress of the data.

Thank you. This concludes today's conference call. Thank you for participating. You may all disconnect.