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

[Operator Instructions] Now, I will hand the conference over to the speakers, CEO, Erik Manting, and CFO, Lotta Ferm. Please go ahead.

Thank you, and welcome, everybody, to the Q3 webcast and also the business updates that we can provide at this point in time. As a summary of Q3 and also some of the significant events that we reported after the reporting date, we have opened the first clinical centers for the AMLM22 CADENCE trial. This is a trial run by the Australasian Leukemia and Lymphoma Group and they opened up the first centers in Australia, which we also communicated via LinkedIn yesterday, but we're happy that the trial is finally open for recruitment. We have worked with Northx, our manufacturer with whom we have a manufacturing alliance for implementation of the large-scale manufacturing of our lead product, vididencel. It's a crucial part of our preparations for pivotal stage readiness. And we're happy to report that alliance is on track. The collaboration we announced in July with Institut Bergonié, allows us to reenter into the clinic our second clinical stage product, ilixadencel, and we will study this program in soft tissue sarcomas. We'll provide more background of that indication and the trial during the call. We will have a presentation today supporting the combination of ilixadencel and avelumab at the SITC conference in Houston, Texas. And we have already published a press release yesterday with a summary of the main data supporting the combination of ilixadencel and avelumab. And avelumab is also the antibody used in the REGOMUNE trial with Institut Bergonié. So, it's very relevant data for that trial. We have also announced this week that we will present multiple abstracts at the upcoming Conference of the American Society of Hematology, ASH, which is from December 7 to 10, but with the most important update being the survival updates of our ongoing Phase II trial, the ADVANCE-II trial on December 8, for which we will issue a press release on Monday morning on December 9 with a summary of the updated survival data. Then also as a final remark, as an update, we have extended our cash runway. So, we've taken measures to further improve our cost efficiencies. Lotta, our CFO, will comment in more detail. But it's important for us that we are preparing for Phase III readiness mid next year, but also that we have now enough cash runway to deliver that milestone. And this is an improvement versus earlier guidance of having cash runway until the third quarter of 2025. As a summary for the financial information, I would like to hand it over to Lotta.

Thank you, Erik. Yes, the net result for the Q3 amounted to minus SEK 23 million. And for the first nine months, the net result was SEK 96.9 million. Cash flow from the operating activities, which normally is quite close linked to the net result amounted to SEK 20 million for the Q3 quarter and to SEK 73.1 million for the first nine months. The difference between the cash flow and the net result is mainly operating costs. We have a small income and sometimes from grants. The main difference is then related to the cost we have for the manufacturing alliance with Northx, which is prepaid. And therefore, it will have no effect on the cash flow. So, the cash flow will be lower also for coming months than the cost. The cash position at the end of Q3 amounted to SEK 109.3 million. And, as Erik said before, we have looked into some cost savings we can do to run the business more efficient. We have lower clinical trial costs because you might be aware of that we planned for another trial for ilixadencel, but then we got opportunity to shift to one. We are now starting up with Institut Bergonié., and that's a more cost-efficient trial. And then we are also optimizing the cash management, and we are looking for grants, which can fund some of the development costs. So, yes, that's everything for me.

Thanks Lotta. So, as the next part of the presentation, we will provide some context about the cancer immunotherapy landscape and how our programs are positioned within the cancer immunotherapy landscape. There's two reasons for that. One, we have taken early on decisions that are a general guiding principle for our programs, which we would like to explain in this part of the presentation. But also there have been major learnings recently in the cancer immunotherapy landscape, which I think are good for general awareness about also the positioning of our programs. So, one of the main conceptions within the treatment of cancer has long been that the immune system is basically suffering so much from treatments like chemotherapy that it has no role in the treatment of cancer. However, checkpoint inhibitors or immune checkpoint inhibitors have revolutionized that fault. So, when they were initially discovered, this class of antibodies showed long-term survival in solid tumors that were very difficult to treat, such as melanoma and lung cancer, for example. The picture that you see on the bottom left shows what immunotherapy does if you compare it to chemotherapy or targeted therapies based on small molecules or antibodies. Targeted therapies have an immediate effect on cancer cells because they basically slow down the growth of the cancer cells. So you see an immediate effect, but it's not a permanent effect. The effect is temporary and it lasts as long as the treatment is working and is being applied. Immunotherapy, whereby you stimulate the immune system, simply, we're talking about active immunity, which is built up by your own immune system. That leads to the formation of immunological memory and it leads to long-term survival benefit. That was a major finding. It holds up across many different tumor types. And for example, the largest selling checkpoint inhibitor, KEYTRUDA has been approved in over 20 solid tumor indications and realized $25 billion of global revenues in 2023. However, only the minority of patients respond to checkpoint inhibitors. And that has been a major exercise of the industry to see if we can improve the efficacy of checkpoint inhibitors by making more patients respond to them and for example, combining them with other immunotherapy modalities. The tough, but in the end, final conclusion is that it has been extremely difficult to improve the efficacy of the checkpoint inhibitors where they are effective. So, somehow that shifts from the green line on the top right slide to the blue line has not materialized. The survival of patients being treated with immune checkpoint inhibitors is still only benefiting in 10% to 20% of patients. And some tumors are completely unresponsive to checkpoint inhibitors. So, we decided quite early on that we would not pursue tumors that are already responding to checkpoint inhibitors because it has turned out to be so difficult, and we're talking about thousands of trials to elevate the level of patients responding to checkpoint inhibitors and also the other way around where the checkpoint inhibitors are effective, it's very difficult to beat them because they are an effective immunotherapy. So, we took a decision early on to focus on tumors that do not respond to checkpoint inhibitors, and that positions us in blood-borne tumors, where we have vididencel as a lead product and also to a certain extent, in solid tumors that today respond very poorly to checkpoint inhibitors and for which checkpoint inhibitors have not been approved. Active immunity is immunity built up by our own immune system. It's also the only long-lasting form of immunity. It takes some time to build up because the immune system has to recognize, in this case, a vaccine or an earlier disease. It takes time to build up an immune response and then to build up immunological memory or cells that have long persistence and that can always quickly respond when the disease comes back. So, you need to do this in a low disease setting. That's also been one of the major choices we've made as a company with respect to our positioning. We focus on low disease settings where there is a big risk of recurrence, but where also the immune system still has a chance to build up sufficient immunity to provide for immune control over a longer period of time against the residual disease. The market of blood-borne tumors is very sizable. So, when we look into the current market for immune checkpoint inhibitors, that's only in solid tumors, we're talking about a market of a total size of around $47 billion. When we look into the addressable blood-borne tumor market and this is an exercise we did in-house with external consultants, but it has been quite extensive market research. We assess the market to be roughly $16 billion in the blood-borne tumor space only for vididencel. We are currently, of course, only addressing a small part of that market. So, we're addressing acute myeloid leukemia. As a blood-borne tumor, we are addressing patients that have undergone chemotherapy in acute myeloid leukemia, but still that is a very sizable market because the need for this kind of treatments in blood-born tumors, including acute myeloid leukemia. This provides some context of how we think and how we have positioned our programs. So, let's now move to the actual programs. Vididencel is addressing AML and particularly the need for maintenance therapies in AML. AML is a very aggressive tumor, actually, the only way to reduce the disease is with high-intensity chemotherapy and nowadays also with a new drug called Venetoclax, which is also a very toxic compound, but it takes down the number of circulating cancer cells. However, the big problem with AML and the reason why it's such a deadly disease is relapse. So basically, if you stop treatment, relapse is almost immediate. The only way to permanently get rid of acute myeloid leukemia is through a hematopoietic stem cell transplant or a bone marrow transplant. And even there, half of the patients suffer from a relapse, which is also the main reason for transplant failure. So, it's a very deadly disease. You need to keep it under control. And for long-term control of the disease, you need what's called maintenance treatment. Another very important element of maintenance treatment is that it is safe. You can't provide more toxic treatments after patients have already suffered from very toxic treatments like high-intensity chemo, like Venetoclax to get the disease down. So, maintenance treatment needs to deliver durable responses, but also it needs to preserve health and quality of life. That's where immunotherapy can make a difference. This is the survival curve that you know. We presented them before, but in the context of what we just described, you can appreciate what's going on. We see a number of patients. In our case, we treated 20 patients and 6 patients relapsed and then also passed away relatively quickly after treatment. Those were patients that had poor immunity; poor immune responses and we are unfortunately not able to build up immunity against the residual disease. The promising part of the trial is that 14 patients were alive at the end of the trial at 72 weeks, and we are now following up these patients in long-term follow-up. The long-term follow-up that you see is in years. So, we get a really different picture for these patients that have a good immune response and that translates into the control of residual disease and long-term survival with 11 out of 20 patients still in the first complete remission without further treatment. What we've also confirmed in the first half of this year is that the immune responses and the general status of the immune system is associated with the clinical benefit, which is a very important element of the proof of concept for this product as an active immunotherapy in AML. And, what you see is that all the patients that have good levels of B cells that have good levels of T cell responses are in the long-term survival part of the curve, confirming that the immune responses we pick up actually translate into survival benefits. This is a chemical drug called azacitidine, it's now approved as a maintenance treatment in the form of a doublet, oral azacitidine; and here, you see a very different picture. So, this is a picture of MRD-positive AML patients. We also, in our ADVANCE-II trial, we just discussed, only treated patients with measurable residual disease, or MRD, which puts patients in a high-risk patient category. This is from a Phase III trial run by BMS, the large pharmaceutical company. And what you see is that patients with an MRD-positive status have a very poor prognosis, and this is after high-intensity chemotherapy, median relapse-free survival, so the time until patients get sick again is 2.7 months. So, more than half of the patient is already sick again within 3 months. With azacitidine, you slowdown that progression. So, it shifts to 7 months. But, in the context of what we just discussed about the relevance of immunotherapy, you can see what's happening. This is a slowing down of the disease, and it's not leading to long-term survival benefit. This is the only approved maintenance therapy today. There's a good medical rationale to combine vididencel with oral azacitidine, and that is also supported by data we have generated in-house, part of which we will also present at ASH this year that azacitidine is actually synergistic and is also not negatively affecting the mode of action of vididencel. So, the two drugs can be quite well combined and they also both have a very good safety profile, making the combination suitable for maintenance therapy. The trial we have engaged in with the Australasian Leukemia and Lymphoma Group is called trial, or in short, the CADENCE trial. This trial is run by ALLG, it's important to emphasize, it's not our trial. We facilitate for the trial. We provide vididencel for clinical use. We provide some financial support for the logistics involved in the trial. But in the end, ALLG is responsible for the execution of the trial. For us, this brings two important elements, which is, one, this is a relatively large trial, up to 140 patients. It's 2-stage trial, first 40 patients for safety analysis and then another 100 patients for a proof of concept or feasibility stage. Secondly, the data from this trial can be used for our global registration dossier of the product, particularly the safety data will be good to have because this is the first trial where we directly combine oral azacitidine with vididencel. Yesterday, we did some social media effort around it based on a release by ALLG. But also, in the Q3 report, you can see we announced that the first sites are now open also, we should say that it's a little bit later than we had hoped for. We had already achieved ethical committee approval in March. But again, it's up to ALLG to execute on the trial. We can only facilitate, and we are very happy that they are very motivated to do this trial and have now opened the first clinical centers to allow for patient recruitment. The overall picture is this. We have the ongoing ADVANCE II trial of which we showed the survival curve. The next survival update will be on December 8 during the ASH conference. Again, the press release will be on the morning of December 9, but that is an important update. There's also an abstract already available on the ASH website, but that is the update with the data we could collect up to May of this year. So, the actual data by the year-end and also the actual summary of the survival data that we can make will be made available on December 8 and then next press release on December 9. The AML CADENCE trial, as I explained, is now open for recruitment. It will be a very valuable trial in terms of size, but also in terms of the data that we can get out of that trial to benefit our global registration dossier. But, the biggest effort currently for the company is in the preparation of a pivotal stage development program, which means this is the last phase that you need to go through with the product to get it registered for in the end commercialization. And the reason it takes some time is that it comprises different steps. On the one hand, we are working on a clinical trial protocol, and we're asking the regulators like the EMA and the FDA for feedback on the protocol. But also, we need to make sure that we have the final production process in place, and we have actually manufactured the first GMP batch for clinical use based on that large-scale manufacturing process before we can engage in the pivotal stage development trial. And the reason is that during such a trial, you want to change as little as possible in your manufacturing process. So, we are now working on that with our manufacturing partners at Northx. That's why it's also so important that manufacturing alliance is on track. And also in the Q3 report, we have asked our Chief Technology Officer, Leopold Bertea, to give an interview to give a bit more color on how that collaboration is working and also what the relevance is for the further development of vididencel. Now, based on all the preparations, the alignment with the regulators and being ready for large-scale GMP manufacturing, we estimate to be in a position to be pivotal stage ready, meaning the product is ready to enter the pivotal stage trial by mid next year. And then, of course, we have to engage in such a trial, either by ourselves, with the partner or a combination of both. And that is the next step. For now, we are fully focused on executing towards this pivotal stage readiness. Then as a last remark about the development path for vididencel. The maintenance population in AML is much broader than the post-chemo patients. And we are considering additional AML maintenance indications. And also, we are doing some exploratory work to look into adjacent indications like, for example, chronic myeloid leukemia. This is the kind of data we are currently investigating and accumulating in our research labs and which we will also, to a certain extent, present at the upcoming ASH conference. So, this is the overall AML treatment landscape. Like I said in the beginning, there's high-intensity chemotherapy for patients eligible, which is roughly 50% of the total AML patient population. This is the patients we are currently treating. Importantly, transplants are the only potentially curative option, but they're not available for the majority of patients. So, all the patients that are not or not in time able to have access to a transplant, they can be treated with our product, and we will now do that in combination with oral azacitidine, and we have already initiated the CADENCE trial to explore that combination, but that will also be the basis for the registration trial moving forward that we are preparing for ourselves. Then also in the post-transplant setting, the post-HSCT setting, patients have a high risk of relapse. So, it could be a rationale to boost those transplants with an anti-leukemic vaccination, which is what we provide for with vididencel. So, that's another part of the patient population in AML that could benefit from this product. And then finally, we have the patients that are classified as chemo unfit who are today treated with a combination of azacitidine and venetoclax, with venetoclax being quite an effective drug to drive more patients into a complete remission, but being also relatively toxic. So, those patients will have much better chance today with Venetoclax being available of reaching a complete remission. But in the end, also those patients will require maintenance therapy. And this is one of the reasons we also did preclinical work to explore the combination of azacitidine and venetoclax with our product, vididencel, and we're able to show very nicely at ASH that there's a good combination rationale between the two therapies. So, there is venetoclax on the one hand and vididencel on the other hand. Then moving to the other programs. The ovarian cancer trial we have ongoing with the University Medical Center in Groningen is going well. We have established in the majority of patients, immune responses and also very good safety of the product. What we will do in the fourth quarter of this year is to evaluate immune responses in all patients treated, and that's also the primary readout of the trial. So, we aim to collect those data via the University Medical Center in Groningen before the year-end and report those top line data before the year-end. I should also say because I read from some of the analysts covering us that, that would already be the long-term survival. That's not the long-term survival follow-up. So, where we are now also looking back to the introduction I provided about cancer immunotherapy is in the initial phase. So, we've treated all the patients. We've gone as far as week 22 in the analysis of patients responding, and we saw that 10 out of 17 patients had stable disease at week 22. We have established that in majority of patients, there is immune response that are directed against relevant tumor antigens and that the product is safe. Now, we need to look long-term if the patients are responding and are becoming more stable as compared to what you may expect in this indication. And that's the phase that will be next, right? So in the fourth quarter, we will not report long-term survival data, but we will report the outcome for all the patients treated to date. And then we will look for, of course, the long-term follow-up of these patients to see if there's actually a number of patients benefiting with long-term survival benefit after treatment with vididencel. So in this indication, initial data look good. We have to look more carefully for an efficacy signal. Then moving to ilixadencel. Ilixadencel is an intratumoral primer. It's a different kind of product. Ilixadencel is based on a cell line, and we can grow large quantities of these cells, which we then transform into the final product, which has a dendritic cell phenotype. Ilixadencel is actually derived from healthy donor monocytes from healthy donor blood, from which we derive the product, and then we inject these activated dendritic cells intratumorally and they improve the intratumoral inflammatory environment. So, it facilitates the immune system to act against tumor cells and also facilitates the presentation of tumor antigens to the immune system. Now, we've tested this concept in a wide range of tumors, and all of these tumors are very difficult to treat. And as part of the strategy I summarized earlier on, we have now shifted towards an indication that is not responding to checkpoint inhibitors currently. And that is soft tissue sarcoma. So, the rationale to explore ilixadencel in soft tissue sarcomas, it's a very difficult-to-treat tumor type. It's also a very aggressive tumor. So, particularly when there's first-line treatment failure, these tumors become very irresponsive to currently available therapies, including immune checkpoint inhibitors, but also progression and eventually death is actually quite a very aggressive tumor. Now, one of the encouraging elements of soft tissue sarcomas, and this is also a study done with authors from Institute Bergoniér, so the institute we are working with, including Professor Antoine Italiano, is that you do see a survival benefit in patients that have high numbers of infiltrating lymphocytes and particularly it's called tertiary lymphoid structures, which are associated with functional immune responses and also that show improved clinical outcomes in soft tissues are associated with improved clinical outcomes in soft tissue sarcoma patients that are treated with immune checkpoint inhibitors. Now, that makes a very logical combination with ilixadencel because it will create a more pro-inflammatory immune environment inside the tumor. It will attract more immune cells inside the tumor. We've also shown already that ilixadencel is safe and can also act potentially synergistically with immune checkpoint inhibitors, including anti-CTLA-4 and anti-PD-1 antibodies. The latter we did in the ILIAD trial, of which we will publish the data soon. But that trial is completed. It was with a positive safety readout. What we are now presenting today at SITC is the combination with avelumab. And avelumab is an anti-PD-L1 antibody and what we will show at SITC is that there's a strong synergy between ilixadencel and avelumab and actually the addition of avelumab leads to better activation of NK cells, other immune cells and also the activation of bystander dendritic cells, which facilitate for a systemic immune response against the tumor antigens that are part of the tumor. So, in that sense, we have built up, I think, a strong case to support this trial, and we're looking forward to go ahead with this trial. We announced a collaboration with institute Bergonié in July. It will be a multicenter open-label Phase I/II trial. There's a large number of leading French hospitals involved. The trial is supported by Bayer that provide regorafenib and Merck that provide avelumab. What we will do is provide ilixadencel specifically for the study arm addressing soft tissue sarcomas and allowing Bergonié to, as part of the REGOMUNE trial treat up to 43 soft tissue sarcoma patients. We are currently in the preparation phase, which we aim to complete by 2024, Q4, so this quarter. It means that we are submitting all the regulatory documents that we need to get the trial started in the first half of next year. And of course, also that we make sure we have enough study material and we work closely together with Bergonié to get this trial started. So a summary and outlook, the ADVANCE-II data, the combination of the survival data and immune monitoring data provide proof of concept that vididencel acts as an active immunotherapy in AML, and I hope we also provided some additional context about the meaning and the importance of that statement. We are combining with oral azacitidine in the AMLM22 CADENCE trial that is run by the Australasian Leukemia and Lymphoma Group. But very importantly, we are not dependent on this trial. We are benefiting from this trial, but we are separately preparing for a registration trial for vididencel in AML. And that includes the feedback from the regulatory agencies. It includes the implementation of large-scale manufacturing, and we aim to be ready to enter into a Phase III trial in the second half of next year. It is supported this will exercise by a strong regulatory dossier, including orphan drug designation and Fast Track designation, but also, for example, an ATMP certificate issued by the EMA for the manufacturing process and the preclinical data of the product. It's a very important validation of our approach towards manufacturing. And we will have a next survival update of the ADVANCE-II trial on December 8 at ASH. And then I hope we also provided a good picture today that the other programs, that's the ESMO trial, is the ilixadencel program and also our preclinical pipeline program based on NK cells are well positioned to deliver additional upside. With that, it's the completion of the update for Q3 and business update, and the meeting is open for questions.

[Operator Instructions] The next question comes from Chien-Hsun Lee from Pareto Securities.

So, a few questions from me. According to the ASH abstract you published earlier this week, I think it's quite encouraging to see there's only one additional death and the median overall survival has not been reached yet. But for the survival update that you are going to present in December, is it fair to assume that the new data cutoff will be until November?

Chien, thanks for joining. Yes. So, one patient passed away in the trial and yes, that was years after the initial treatment success, by the way. But, of course, there's multiple reasons why patients can in the end pass away and often these patients are also somewhat older. But the overall picture that you see now in the ASH abstract is indeed the data we collected in May from all the hospitals that are following up the patients in long-term follow-up. So, these patients come to the hospital at least twice per year. And that is also then the moment we can collect the data from all the hospitals. So the actual update at ASH, but you have to submit the abstract at ASH already in early June. So, that's why the best thing we can do at that point in time is to provide the intermediate update that we can collect in May. The real update we will present at ASH is based indeed on the data we have collected from all the hospitals and which we are currently compiling to present at ASH.

And I also noticed that there are three patients seems to undergone the stem cell transplant. So, how are you thinking of presenting the data? Will you exclude this patient in the next update?

Excellent question, Chien. What we do also in the survival curve that we presented during this webcast call is, we censor those survival plots, the Kaplan-Meier plots for the transplanted patients. So, it's a conservative way to do it. What you often see is that studies do not discriminate between the transplanted patients and the non transplanted patients. But in our case, we really wanted to look at monotherapy efficacy. What happened was all the patients that were recruited for the ADVANCE-II trial were at the time of recruitment not eligible for transplant or there was no transplant available. And what happens if after vaccination with vididencel or treatment with vididencel, patients have more time. So, they recover, their health is better. They're in a relatively stable phase, then yes, doctors sometimes just don't want to take the chance and they look for a transplant and they do the transplant. The good news is that the transplants were successful. So, it's also important for us to know that we don't harm a potential curative option for AML patients with our products. The transplant went well. But what we do typically is we clearly mark how we report the numbers and also in the case of our current overview. And you can see that 11 patients are still the first complete remission. The 14 patients, which are now three patients alive included the transplanted patients, but we will also clearly, let's say, make a difference in the way we report the outcome of the trial.

The next question comes from Christian Binder from Redeye.

[Technical Difficulty]

The next question comes from [ Arun Akar from Edison Group ].

Noticed in the results that R&D expenses were notably lower than in Q1 and Q2. I'm curious to know to what extent this is due to the Northx technology transfer nearing completion? And if so, what might we expect this trend to continue in Q4?

Yes, I can take that question. It is like this with the R&D cost and it's where we report the cost for the tech transfer. It goes up and down according to activities. And in the Q3, we have the vacation period. So, Northx have closed the factory for two weeks for maintenance stop and so it was lower activity in the Q3. So, it's not always that you can compare the quarters to each other.

My second question, looking really at the ALISON and ADVANCE II readouts, which we're looking forward to, just curious to know that given that AML is the strategic priority, what might the next steps look like in ovarian cancer following the ALISON readout? And I think you touched upon it, but after the subsequent long-term survival data. Just curious for a bit more color on how these might be prioritized moving forward.

Yes, absolutely. I think, like I said, ovarian cancer is aggressive disease, but the slower disease is AML. AML, you have an immediate outcome because there's no half AML. Patients are either healthy or they relapse and pass away very quickly, usually within 6 months after the relapse. With ovarian cancer, we're looking at a very different picture. So, women are either healthy or they come back to the hospital and they don't feel good, and then you have to look at whether there's tumor recurrence or if already present metastases have grown. So, it takes more time to read out such a trial. And also, given that we have our major efforts currently ongoing in AML, that's the clear priority for the company. And for the ovarian cancer trial, we'll just see if we can pick up a clear sign of survival benefit, in which case that could be an interesting indication to pursue either with the product as monotherapy or in combination, for example, with other drugs which are currently being developed for ovarian cancer. But first and foremost, we want to see if we can really pick up survival benefit before we take other decisions. And that will take at least another 12 months.

My last question is just looking at the CADENCE trial. Given the sort of slight pushback, which you touched upon, which we appreciate comes from ALLG mainly, given that they're in control. But just curious to know if this has any influence on the planned time lines for the registrational trial. I think the current guidance is consistent with your previous communication. Is it fair to say now that the sites are active, we can assume a reduced risk of any other possible delays?

Sure. Thanks for asking the question. Well, first of all, again, the trial is in the hands of ALLG. We're very happy with the collaboration. They're a very high-quality research group and also high-quality clinical centers supporting ALLG. What was a bit of a delay versus our earlier expectation was the time between the ethics committee approval and the actual opening of the hospitals, and that had to do with organizational elements with communication elements. But one way or the other, ALLG is committed to the trial, and they've now, of course, opened the first center. So, we expect and they've also stated in their own social media post yesterday that they will continue to open up additional centers, and we stated in the past up to 9 clinical centers to support the first stage of the trial. So, I think we've taken the first and most important step, which is that the hospitals are opening up now. There is no correlation between the tempo of the CADENCE trial and the Phase III trial. That's the other element I wanted to emphasize and will emphasize again. We are full speed on track in preparing for a Phase III trial. We prepare that trial on the basis of the ADVANCE II data that we discussed today. We will benefit from the CADENCE trial, but we are not dependent on it. The preparations for the Phase III trial are dependent on II important elements, which is one, the trial design and the alignment with the regulators. And it's II, the completion of the large-scale GMP manufacturing in our alliance with Northx. Those 2 elements coming together will make us pivotal stage ready. That's not dependent on the CADENCE trial.

The next question comes from Christian Binder from Redeye.

I'm sorry for the initial technical difficulties. But just a follow-up on CADENCE. As mentioned, it's not your trial, it's ALLG's. But given the slight delay in site activation, can you give any updated indications in terms of when we might see initial readouts?

Well, I don't think we are, at this point, thinking about delayed readout. There's 2 reasons for that, Christian. One is you typically see a kind of hockey stick effect. So it takes most time to get the first sites initiated and to get the doctors and study nurses work with the product, et cetera, and creating patient awareness. Next week is a very important week because it is the week of the ALLG scientific days. There will be a plenary presentation of the AMLM22 CADENCE trial. You started to see this week, actually yesterday that ALLG starts communicating about the trial. So, it's a combination of actually opening the hospitals, training the personnel to work with the product, creating awareness that is usually taking most of the time in the start-up phase of such a trial. But at this point, we do not expect that it will, let's say, result in further delays. I think we've now taken the first steps, and we will follow up and see ALLG follow up with opening up of additional clinical centers and starting the patient recruitment. So, I think we will still stick to the idea that we will have the initial data in the first half of 2026. It's also an open-label trial. So, the first stage is immediately delivering data on the safety of the combination, Vididencel, oral Azacitidine, and that's particularly the information that we are looking for also to get more comfort, let's say, in advance of the Phase III trial about the combination. So, in that sense, we're also not dependent on actually completion of the first stage of the CADENCE trial, though data that relate to, let's say, the safety of the combination will come in basically from the start of treating patients.

And then just one follow-up on your cost-saving measures. You mentioned low clinical trial costs primarily because you're doing the REGOMUNE trial now instead of doing an in-house trial with ilixadencel. So, just to clarify, I guess you didn't really scale back your ambitions there. It's just that, that form of trial means lower cost to you.

Yes. I think that's exactly the right summary, Christian. And we actually looked into different ways to do a sizable trial with ilixadencel. Obviously, we also keep an eye on the priorities that we need to follow as a company based on available data. And with Ilixadencel, I think we have collected a lot of promising but early clinical signs of efficacy. And, yes, that makes the program that we want to pursue. But we have to balance it with our efforts to prepare the AML program where we now see a very clear efficacy signal for Phase III. So, we were initially thinking about the company-sponsored trial, then we shifted to an investigator-sponsored trial, and we were initially talking to another hospital. And then came the connection with Bergonié and the possibility to be part of this great trial, which is the REGOMUNE trial also in the combination of drugs that we are very happy with because already we had shown synergies with TKIs, including regorafenib and ilixadencel. And now we, of course, also have more specific avelumab preclinical data. But the trial setup, the indication being soft tissue sarcoma and the fact that we can work with Bergonié was a tremendous opportunity. Also, what we hope to show today is the Bergonié is a center that knows a lot about the immunology and also particularly the intratumoral immunology of this kind of indication. So, it was a perfect setting, first of all. And secondly, because the trial is up and running, we only contribute the study drug. So, that makes it a very cost-efficient trial. So, the combination of a high-quality trial, a very decent size of number of patients we can treat in that trial and the cost made this the best possible setting to move forward with the product.

There are no more questions at this time. So, I hand the conference back to the speakers for any written questions and closing comments.

Thank you, operator. I think there's one specific question in the activity feed about the Nomination Committee press release we just issued and whether or not specific parties are part of that or not. I think that is their discretionary decision, whether or not they want to spend the time on the Nomination Committee, yes or no. So, I can't comment on that in more detail. But thanks for asking the question. I don't see any further questions in the activity feed. So, with that, I would like to close this call and thank everybody for their participation.