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

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

Thank you. Welcome, everybody, to this morning's webcast. Of course, end of last year, we had an exciting update of the ADVANCE II monotherapy trial. And more recently, we announced how we want to move forward with the program that comprises, on the one hand the clinical path forward and on the other hand an important manufacturing alliance, which we announced with NorthX. Today, we will guide you through an overview of what that means and how we will move forward from here. Next slide is the disclaimer, which is also on our website. And the next slide is today's program and speakers. I will give a brief introduction about Mendus, which you would be familiar and then hand it over to Ted Fjällman, who is a board member at NorthX and CEO of Flerie to say a few words about NorthX and also Flerie's investment model. And then I will hand it over to my colleagues. First, Leopold Bertea, our Chief Technology Officer, to say more about vididencel manufacturing and the importance of [indiscernible] program. And then over to Jeroen Rovers, our Chief Medical Officer, to guide you through the plans for the vididencel clinical development. After a brief summary, we will go over to the Q&A with the analysts that are part of the call and also the questions that have been sent in, in advance to us that we will also guide you through. With that, I want to go to the next slide, which is an overview of Mendus and the way we are pioneering cancer maintenance therapy. As most of you will be familiar with, most cancer-related deaths are the result of the recurrence. So it's not the primary tumor that kills patients. It's actually the fact that the tumor is very often and in certain diseases very quickly come back and are done very difficult to treat. So what we are trying to do is to prolong disease-free periods by reducing tumor recurrence, and that's called cancer maintenance therapy. Our lead program, vididencel is positioned in acute myeloid leukemia, where also the data were collected I just referred to last December, a monotherapy trial in AML patients in need of maintenance therapy, particularly because they have measurable residual disease, which puts them at a high risk of tumor recurrence. And also, we have a second program in ovarian cancer, which is also characterized by very fast and imminent recurrence in the majority of patients. Then we have our intra-tumoral primer ilixadencel, which is positioned to treat hard-to-treat established solid tumors. It's a product that's injected into the tumor microenvironment. And lastly, we have a new program, which is a preclinical program based on so-called natural killer cells or NK cells, which we believe also holds additional therapeutic potential and which is the most important program of our preclinical pipeline. Next slide is a part of an overview [Technical Difficulty] pipeline chart, which is the program in acute myeloid leukemia. The ADVANCE II trial is a monotherapy trial, again, aimed at cancer maintenance therapy for AML patients that suffer from residual disease, which puts in at a high risk of tumor recurrence. And what we have made as a principal decision is to move forward in combination with oral azacitidine in that setting. Oral azacitidine is currently only approved drug in this indication. And that's why it's also the most logical step to take forward. And Jeroen, our Chief Medical will describe it in more detail. Then I said we have the ovarian cancer trial ongoing. It's a Phase I trial, also with already some successful readouts on safety and feasibility based on immune responses against the vaccine, but also with additional updates expected in the second half of this year and early '24. And then we have the ilixadencel program, which will be positioned in the field of soft tissue sarcomas, which is a broader group of tumors and where we have had initial clinical success in the treatment of gastrointestinal stromal tumors, and this is the basis to move that program forward. And then finally, the NK cell program is based on a specific application of our DCOne platform, our technology platform that allows us to expand therapeutic quantities of NK cells. Now as a basic principle, next slide, please, Mario, the principle of cancer maintenance therapy. Again, the vast majority of cancer-related deaths is due to recurrence of the disease. And that's particularly related to residual cancer cells that remain after, for example, chemotherapy and in some cases, also surgery and radiotherapy. These residual cells are responsible for recurrence of a tumor that's an also very often difficult to treat. And so what we try to do is to provide for maintenance therapy based on immunotherapy, whereby we stimulate the immune system to basically regain control over the residual cancer cells and thereby reducing the cancer recurrence. Also very importantly, the safety profile of our products is tuned to maintenance therapy, meaning that we work with products that have a relatively benign safety profile, which is also very important for patients that have already undergone quite harsh cancer treatments in prior lines of treatment. Very importantly, the last data we presented from the ADVANCE II trial in AML maintenance was last December, where we not only saw that the majority of patients was alive after the active study period but also that they remained disease-free in the long-term follow-up, which ranged from 16 to 47 months. So with that, I think we've nicely demonstrated the principle on which we will now build out the further development of vididencel in the clinic, but also very importantly, by scaling of the manufacturing of the products. For that, we have recently closed and announced an alliance with NorthX Biologics, the customer manufacturing organization based in Sweden. And also we announced in the financing transaction -- as part of a financing transaction and investment by Flerie. And we're very happy to be joined by Ted Fjällman, who is on the board of NorthX and he was also CEO of Flerie Invest and to say a few words about NorthX and about Flerie. Ted, over to you.

[Foreign Language] I'll continue in English. Very happy to be here. And we, of course, want to help Mendus to prevent recurrence with vididencel and to bring that to as many patients as possible. And how will we do that? Well, NorthX will do that through scaling up the manufacturing process that [Technical Difficulty] to prevent recurrence of cancer in as many patients as possible. My name is Ted Fjallman. I'm a Board member at NorthX Biologics and I'm also CEO of Flerie, which is an investment firm that will soon be a shareholder in Mendus. Next slide, please. Little bit about NorthX. We specialize in the GMP manufacture of biologics, as the name suggests, and we do that mostly for clinical trials, a little bit for commercial. And we also have largest [Technical Difficulty] therapy manufacturer in Northern Europe. Many people are getting to know us now because we've been around with this name for about 1.5 years but we're still young with the name, but not at all young when it comes to our experience. We've been making GMPs for over 30 years, making GMP manufacture. We were also recognized as a Swedish national innovation hub for GMP manufacturer of advance drugs such as ATMP in October 2021 and this, of course, is also [indiscernible] expertise that goes all the way back to the 60s actually on the site just outside of [indiscernible] Central Sweden. We have a lot of ambition to grow and then do more things. And in fact, we have a lot of experience, some of us in NorthX from having built [indiscernible] over many decades. And if we go to the next slide, you will see that, in fact, man on the right-hand side here, Thomas Eldered, who's now [indiscernible] Biologics. And we were recognized as the new NorthX Biologics by the then Minister of Enterprise in the center of the picture Ebba [indiscernible] as basically the Swedish GMP manufacturing innovation hub for Advanced Biologics, also together with Darja Isaksson, who is the General Director of Vinnova, the Swedish Innovation Agency. And this was right when we launched the name NorthX Biologics in October 2021. We have been quite a tough [Technical Difficulty] from all over the world. And on the previous slide, you're pretty clear read that we, of course, have all the quality capabilities to take on almost any project in the cell and gene therapy space and very happy enough to do so with Mendus. Next slide, please. A little bit about the main facility that we have. It's a 7,000 square meter facility. You see it in the picture on the right-hand side there, that's the winter picture. We have [Technical Difficulty] 2,500 square meters of flexible queen rooms. Obviously, we do service and support in manufacture of biologics used in vaccines, but we focus a lot in cell and gene therapy and also can take on other advanced applications, anything in the biologics field. We also do more than just following the process of our customers. We help them with innovation and process development support. And that we do mostly to this innovation [indiscernible] track that is also [indiscernible]. We have expanded operations already and now really looking forward to expand operations to produce [indiscernible] cells for Mendus. It fits very well into the clean rooms and the expertise of the stocks that we have at NorthX. A little bit more about that on the next slide. What we bring together between Mendus and NorthX is, of course, Mendus has the dividend for a specific know-how and we have the ability to scale that up [Technical Difficulty] and grew that with Mendus [indiscernible] towards commercialization. Mendus has the manufacturing process and analytical methods in place that they've developed with previous partners and themselves. We have the in-house process and analytical development capability to, again, create whatever new requirements will be needed for future trials and also, of course, for a changing regulatory environment. Mendus has the clinical development expertise. And of course, you'll hear from Jeroen Rovers about that. We [Technical Difficulty] want to begin ready for the pivotal trial, again, through the scale-up of the manufacturer. And definitely, I want to point out that what attracted me also CEO of Flerie to Mendus is that Mendus is a trail bracer in the dendritic cell therapy field. There are a few people in the world, not just in Europe, that have the understanding of dendritic cell biology. Mendus really is a front runner here. And I think it's a very, very exciting field. [Technical Difficulty] procedures, so you can have a fantastic science. But what you need is the ability to translate that science into something that can be scaled and done in a very quality control process so that the patients get a very robust product. And of course, Mendus was seeking a long-term manufacturing partner, and that is precisely what we want to be as NorthX Biologics. We do have [Technical Difficulty] as well, but the ability to grow with client [indiscernible] Mendus has been a very, very good fit for us. Now switching gears a little bit on the next slide to Flerie and our active ownership model. So as I mentioned on the CEO of Flerie, we are a very active owner in our companies. We have 30 companies. We sit on 28 out of 30 companies' boards. That means we're very active Board engages. We don't just turn up to board meetings. We actually work with the CEOs and with the management teams [indiscernible] part of our active ownership model and just some examples is that we have had companies who've made really good deals with big companies such as KAHR Medical in Israel with Roche and Prokarium in the U.K. with Ginkgo Bioworks in the U.S.A., where they've also had over $20 million of investments. So we, as Flerie really want to help Mendus also to expand their investor and collaborator base, and we do that in an active way. [Technical Difficulty], of course, becomes a part of our network Flerie and peers. We've had many CEOs of our companies come together, both on satellite events at conferences and so on. But we actually actively work on a bringing the CEOs together in small groups in a very tight knit sort of weekend or 3 or 4 days activity where they share a lot of experiences. And this has led to our CEOs getting to know [Technical Difficulty] sometimes lonely at the top as the CEO of biotech companies. You have a lot of different stakeholders to take care of. It's useful for different CEOs within a similar field to exchange views and do that in an area relaxed atmosphere and we facilitate that as Flerie. That has led to many interactions and that's the last pillar, collaborations and synergies between our companies and of course, NorthX Biologics being a CDMO is [Technical Difficulty] we've actually initiated R&D collaborations with each other within our network because our network is so big and also just a set of companies. We have 30 companies within Sweden and Europe and the U.S. and Israel, that really creates a lot of opportunities for collaboration. Thank you very much for this. And I'll pass it on now to Leopold Bertea.

Thank you, Ted.

Thanks, Erik. Thanks, Ted, for this introduction. So I would like to bring you through the manufacturing of vididencel. First, on the first slide with the background of the vididencel manufacturing, we would like to give you some -- some, let's say, elements on vididencel. So what is vididencel? Vididencel is actually a whole cell-based vaccine, so a cancer cell-based vaccine which is derived from a cell line, which is a leukemic cell line, which we call DCOne. So this cells are reprogrammed to actually express dendritic cell co-stimulatory molecules which happens during the manufacturing steps of the process. I will show you a bit more about the process later on. Actually, this product is -- this process brings a product which is very highly immunogenic and the administration is intradermal. So it's an intradermal injection. We developed a process, which actually yields a high quality and constant quality product, which actually comes from the fact also that the starting material is a constant quality material. So it's a cell line. It's not from donors and not from patients. So it's really of the shelves and the product is off-the-shelf. The product can be stored as virus and they are ready to be shipped to hospitals on demand. So how do we supply this product? We have developed a proprietary manufacturing process. We very recently have received an ATMP certification from EMA. So it's Advanced Therapy Medicinal Product Certification. And we have finalized the process scale-up at our R&D teams and the process is -- so the new process is ready for transfer to a GMP provider such as NorthX. And we have actually signed very recently an agreement with the NorthX Biologics, as was explained by Ted just before. So what are the next steps? The next steps are clearly to execute now this technology transfer to the new facility and to actually execute the introduction of the new process and manufacture the supplies for the upcoming pivotal clinical studies and eventually the product launch. Next slide, please. As pictures say more -- much more than words, I would like to show you these nice pictures, which show actually what the process is about. As you see on the left-hand side, the upper left-hand side, we have the cells. So these are myeloid cells, which are frozen and they are [ sold ]. They are proliferated. And the process is very closed process which is a stepwise process using up-to-date equipment and the result is the frozen vials of vididencel, which you see on the bottom, obviously, the number is not representative of the batch size, but it shows you that we can actually make as many vials as we want and we can -- and I will show you that later, we have scaled up the process, we'll make it bigger. But in the future, we can just make the same many times, and that's what we call scale out. So the result is an available off-the-shelf product, which we can bring to the patient when it's needed, hence, the manufacturing can really be scaled out. So as we need the more vials, we just do the same many times, and we don't need to change the process anymore. So the result is really no waiting time for the patient. Next slide, please. How did we develop this process? So we did it over several years with the know-how on dendritic cells, know-how on process and analytical development. The first steps of the process are based on an expansion of the DCOne cells. Then there is a transformation of the cells and activation and the results are this dendritic cells, major dendritic cells, what we call the MDCs, which actually is the product vididencel and obviously, the [Technical Difficulty]. Last but not least, the very important step for the safety of the product, which is an irradiation. So we use an irradiation step to ensure the safety of the cells and that these cells are really safe to be injected in the patient. This has been proved and we have actually really scaled up this process, and it's now ready for transfer. Obviously, our development approach is a holistic approach. So we have this so-called quality by design approach, which is going step by step to define the critical parameters and critical quality parameters, et cetera. And really, the very important aspect of this strategy is that we invested a lot of efforts to scale up the process. And that's what you see on the bottom, so we make it bigger but now the next steps will be very easy, and we call this scale out. And as I told you before, we can do it many times and enlarge the number of vials as much as we want. Next slide, please. The whole development work is done in [ Liden ] in our very modern labs. In this labs, we can develop the process steps for all our products, so not only for vididencel also for ilixadencel and we have actually a very, very tough team of technicians and PhDs who actually do all the work of developing the analytical steps and the process development of the product. We also work on the new platform as was introduced by Erik, the NK cell program, and this is also based on our DCOne cell line. Next, please. We are very proud about the latest announcement. One is the ATMP Medicinal Product Certificate for the quality of vididencel. This is really a stamp on the quality of our process and a recognition. And we're also very proud of, obviously, the press release of our new collaboration with NorthX Biologics, which I visited and they really have a great plant in Matfors, which we are very happy to start this new collaboration with these new partners. Next slide, please. As a summary of this part of the presentation, vididencel is manufacturing is based on the DCOne cell line. So it's off-the-shelf product is ready for on-demand delivery to patients. It's based on a proprietary manufacturing process. It's based on our know-how on dendritic cell biology and our CMC expertise. We just received an ATMP certificate from EMA, which provides a stamp of quality for our process. We have actually very important goal forward to establish a large-scale vididencel manufacturing. The current process is enough for our current needs, clinical needs and now the next step is really key so that we set up this new large-scale manufacturing with our new partner, NorthX Biologics. It's very important, and we are very happy that Flerie Invest will initially invest SEK 90 million in our collaboration with NorthX Alliance. The planned investments will actually cover all activities until almost end of 2025, which actually will include a lot of the steps, which include adjustment of the facility, but also obviously the scale up, the installment of the equipment, the training of the teams and manufacturing of the first clinical batch. The manufacturing alliance with NorthX will really help us translate our cutting-edge oncology know-how, vaccine know-how and cell therapy competence and we are really happy to start this new collaboration. Thank you very much.

Thanks, Leopold. Next up is Jeroen, our Chief Medical to talk you through [indiscernible] clinical development plans. Jeroen, over to you.

Yes, Erik, thanks. So we move to the first one. So I'll focus for this presentation on acute myeloid leukemia because that's the lead indication in which we are developing vididencel currently. Acute myeloid leukemia is a very aggressive blood cancer, and it's characterized by formation [Technical Difficulty] by suppressing your hematopoiesis and giving all the signs and symptoms. So what is required for treating these patients is to immediately start treating them to eliminate and reduce the blasts in the bone marrow and blood as much as possible. This is typically done in patients who are fit for intensive therapy with high doses of chemotherapy, so the so-called induction therapy, followed often by 1 or 2 additional cycles of chemotherapy to consolidate the possible effects generated. If patients are not fit for intensive treatment, they will also be given a combination of azacitidine and venetoclax or specific kinase inhibitors for some types of AML mutations. Even with current treatments today, the risk of relapse is still very high. And specifically, if not all the disease has been eradicated. So when there's presence of residual disease, what we call measurable residual disease, there's a very high risk of the disease coming back again very short. And I think disease relapse, as indicated earlier also by Erik, remains still the major barrier for long-term survival in these cancer patients. So if we move to the next slide. And the relevance of residual disease is actually shown by this meta-analysis. So patients who are after treatment still with residual disease do far less than patients who are without, so MRD-negative patients have a better prognosis than the MRD-positive patients. And this comes back in several studies. It's after first chemotherapy treatment, but also after other regimens it's also after, say, transplants, any sign of residual disease is unfortunately a poor prognosis. So if we move to the next one. And this has actually led to a further focus on trying to find ways and methods to maintain a remission. So we've been very effective in the past, say, 10 years to develop new compounds for induction and consolidation. So to actually [Technical Difficulty] into completion, but it is now the challenge to keep them into remission. I think for that, it is very important to find treatments which are effective, so they can actually extend relapse-free survival and overall survival, but we do not add to, say, a potential burden of treatment. So no additional toxicity and so no reduction of your quality of life. If we look at patients who have been treated with chemotherapy, the so far registered maintenance treatment in U.S. and Europe is actually oral azacitidine that has been registered in the past, say, 2, 3 years in both these territories. And I'll show you a bit on the results of that in the next slide. So these data are from the registration trial from oral azacitidine and the study was called the QUAZAR study. And on the right-hand side, within the green box, you actually see the results of the study in patients who had residual disease or MRD-positive patients. On the top, it's the overall survival and below, it's the relapse-free survival. And what is quite apparent is that the addition of oral azacitidine has actually increased, say, the prognosis for these patients with extension of overall survival and median also relapse-free survival. However, most of these patients continue to still be at risk to relapse and die in the end. I think that also emphasizes the high medical need, which we currently still see in trying to provide additional effects in keeping these patients into remission. If we go to the next slide. So what have we done so far with vididencel? And I think the most recent data we published was at ASH in December last year on our ADVANCE II. So that was a monotherapy study, Phase II study, where we treated patients who were in complete remission after chemotherapy, but who had signs of residual disease, and that was determined by both the multicolor flow cytometry and molecular assays. These patients also had no planned bone marrow transplant, which otherwise would, of course, you prefer -- would be your preferred choice for a potential cure. We looked at the [ circuit ] endpoint for effect being the result of treatment on the residual disease, so the MRD and we also then looked, of course, on the outcome parameters as relapse-free survival and overall survival. And with the maturing study, we were able to show more of that data. How did we treat these patients has shown on the right-hand side, where we injected vididencel 4x biweekly. So that's the first schedule of vaccinations. Then there was a short pause, and then patients were given 2 booster vaccinations. And we measured MRD at the beginning, then at week 14, week 20 and week 32. Then all patients were subsequently further followed up until week 70 before they entered into a long-term follow-up phase. So we move to the next one. Just to show you the results, which were published before on the MRD responses. Again, all these patients were MRD-positive at the start. So when we started treating. And we actually saw that 7 out of the 20 patients had a reduction or a complete conversion to an MRD-negative status. So 5 converted to become MRD-negative and 2 had a more than 10-fold reduction in the MRD levels being also regarded as a responder. We also had 7 patients who were still in complete remission, but with residual disease. And 6 patients had relapsed within this 32-week period. So if we move to the next one. And this is then what we were able to show in December last year, how that translates into survival. In this case, relapse free survival. This Kaplan-Meier still shows, of course, the patients which were in follow-up. But as you can see, we had not yet passed the median relapse free survival at 50%. We estimated at that time that the 12-month relapse free survival would be 70.7% and 24 months would be 54%. The median overall survival was read out as 30.9 months. And on top of, say, the survival data, this study also provided us with data on T-cell responses, and we observed that vididencel-induced T-cell responses in the majority of patients, 17 out of 20. And that there was actually also a significantly higher number of these T-cell responses induced in patients who, in the end, remained in complete remission. So we move to the next one. And what I showed you earlier on maintenance, I think is, of course, very applicable also to what we're developing vididencel and that's the balance. The balance of what you add as an effect versus what you add as a toxicity. And on that respect, the toxicity profile of vididencel is still very favorable. We've done more than 100 intradermal vaccinations with vididencel thus far. And basically, the most reported side effects which are related to the treatment are injection site reactions, rashes, et cetera. So these patients are actually showing we're in the site where we inject the drug, swelling and redness like any other, say, trigger of the immune response in the skin. We didn't have any unexpected serious adverse events and one serious adverse event reported, which was not related. So let me move to the next. So coming back again to how we see vididencel in the whole treatment diagram of patients with a acute myeloid leukemia. And specifically, how does it fit as an AML maintenance treatment? So like I said, you have to really look at the AML treatment schedule in 2 different categories. One is the category of patients who are what we would call chemo-fit, so they're actually fits to undergo intensive treatment. Those are the patients who get an induction therapy with high dose of chemotherapy, followed by some consolidation treatment. And nowadays, like indicated, oral azacitidine as an option for maintenance. The other part of these patients, they will go if they have a donor available and can actually are fit enough to undergo the procedure. They will go to a bone marrow transport. So our current strategy is to continue the development of vididencel in those patients who are in complete remission after chemotherapy treatment and who are in need of maintenance treatment. In this case, would be qualified to get oral azacitidine and we plan to add vididencel into that treatment schedule for these patients. However, I think the broader application is also shown on this graph on this diagram, patients who have undergone the bone marrow transplant and who are still having residual disease, they are also potentially eligible of course, for any maintenance treatment and vididencel might be a future option for them as well. Likewise, in the other part of the schedule, patients who have been treated with a combination of, for instance, azacitidine and venetoclax, they might also be in need of additional maintenance treatment for the longer duration. But these are developments, which are for future. And our focus, like I said, is now currently on combining vididencel with oral azacitidine. So if we move to the next slide. So what is the rationale to combine it with oral azacitidine? Well, one, like I said, it has been now established as the standard of care or the approved treatment in that patient population. But additionally, we've done preclinical experiments testing the combination and what we have observed, and that's what we shown on [Technical Difficulty] vididencel with, in this case, azacitidine and venetoclax, which is one of these core treatment regimens currently used in AML that we can actually improve the results of the AML treatment. There's a synergy between the vaccination and the treatment with these compounds. And that provides, of course, a good basis to actually explore that in clinical use as well. So we move to the next one. So how do we progress? So like what Erik said, the ADVANCE II is a monotherapy study. And the study is still ongoing, and we are following up these patients because to remind you, in December, we still had 14 patients, which were alive in this study, and we're following up how their disease status is and we'll report in the second half on the outcome of that follow-up. And we're now planning to set up the combination study. This will initially be a smaller group of patients, which will expose to vididencel in combination with oral azacitidine. And we will randomize that against patients who will only get oral azacitidine that will allow us to have a very good view on the potential additional or, in this case, not additional toxicity we expect in this kind of combination and give us a first sign of the potential efficacy, which is added with combined vididencel and oral azacitidine. The study will be designed in such a way that it will be possible to extend it into a larger trial and the time lines are given here as well. That is the focus for the next, say, 2 years, at least. But we will not exclude, of course, that there might be additional explorations in other AML maintenance indications in the future. And with that, I will just leave it and open to all questions. I give it back to you, Erik.

Thanks, Jeroen. So if we could move to the summary and conclusion slide to wrap it up, maintenance therapy, is the new barrier in the treatment of cancers and particularly in aggressive cancers like AML, where successful maintenance therapy, we believe, will have a very significant benefit for patients. The ADVANCE II data published end of last year or presented at the end of last year show that vididencel has the potential to deliver relevant survival benefit as a monotherapy and that it has a competitive product profile based on the durability of response, combined with an excellent safety profile, which, as you Jeroen alluded to, is very important for maintenance therapies. The only currently approved drug in AML maintenance is oral azacitidine, also leaving sufficient room for additional drug leading to further improvement of survival benefits and this is the main combination we will test in the next trial and also as the main route towards an end pivotal stage development. Finally, we are, of course, very happy with the alliance with NorthX as the manufacturing of the product will have to be aligned with the clinical development, and we have full confidence that this collaboration will result in the end in large-scale manufacturing of vididencel for pivotal stage development and in the end commercialization. So the main pillars are in place for late-stage development of vididencel. And with that, I'd like to go over to the Q&A. There's a number of analysts on the line who will ask their questions. We've also collected questions from people via the IR e-mail address, which we also want to answer. So I'll hand it over to the operator with the current request to the analysts to stick as much as possible to 2 questions per person. Also keeping an eye on the time and the fact that we have a hard stop at 11. Thank you.

[Operator Instructions] We will now take the first question. It comes from the line of Chien-Hsun Lee from Pareto Securities.

Congrats with the progress of vididencel, and thank you for the presentation. So yes, 2, maybe a few questions from my end. So in the upcoming combo trial with oral aza, will you still focus on the more severe MRD-positive patient? Or would it make sense to improve the more general AML population?

Thanks, Chien. I'll hand it over to Jeroen.

Yes, thanks for the question. I think it's a very good remark. I think if you look at, of course, the registration for azacitidine, that's broad. So that isn't limited to either MRD-positive or MRD-negative patients only. And in the first part of what we plan to do, and I think we will just follow the label of oral azacitidine. For this feasibility and safety, we plan to test it in the broader population of both MRD-positive and MRD-negative patients.

Okay. And maybe a follow-up. So how many patients are you thinking about for this upcoming combo trial and as well as if you combine vididencel, like how many patients are you thinking about considering the overall aza registration trial, they have enrolled more than 400 patients?

Yes. I think the exact numbers on a pivotal trial, of course, always depend on the effect size, which you observed. So the combination -- sort of the first part of what we plan to do, as indicated, it's a smaller study where we randomize patients to get either vididencel in combination with oral azacitidine or only oral azacitidine and that will be a smaller number of patients, and then it will be decided how the, say, larger part of the study would look like based also on the observed efficacy.

Okay. And maybe another question. So what's your general view on the competition? So [indiscernible] other candidates that are being developed for maintenance therapy in late stage?

Yes. Thanks, Chien. I'll take that. Without going into, let's say, very specific competitors or specific competitor molecules, the currently available compounds are either relatively safe but lack durability of response or they are relatively toxic which is useful to reduce the disease burden, very difficult to manage in the maintenance. I think that's the general picture, you will see when you look into, let's say, ongoing trials, but also to a certain extent, approved drugs like azacitidine and venetoclax. A lot of the novel approaches, which are currently being developed are based on specific molecular targets, which could be cellular pathways or specific antigens. This limits the patient population on the one hand, but also there is a certain risk of so-called coronal escape or tumor escape, whereby specific mutation is basically avoided by the tumor. Vididencel has shown durable responses in the monotherapy trial, which we showed last December. Also, the safety profile, of course, is very good. But also, it's an important element as far as we are concerned that it is a product that has a broad antigen profile, which makes it less dependent on specific mutations as compared to competition. That's why the combination of factors leads us to believe that vididencel has a competitive profile with potential broad applicability as a novel AML maintenance treatment.

It comes from the line of Luisa Morgado from Van Lanschot Kempen.

This is Luisa from Van Lanschot Kempen dialing in for Suzanne. I wanted to ask you first. So with this new NorthX alliance, how long do you think the tech transfer will take? And more or less, when do you expect to be ready to start manufacturing vididencel?

Leopold, you want to take the question?

Yes, I can take that. Thank you for this question. So tech transfer is a stepwise process. To make it very short. It will take less than 2 years, but it will to have really the batches ready for the clinical trial, it can be somewhat quicker, but that's -- so let's say, between 1.5 and 2 years, something like this. So this is, let's say, the broad range that we expect from the start. And I would like to add that we have sufficient supplies with the current partner to cover our current clinical study needs.

Okay. Very clear. And well, with this new investment from Flerie, where does your cash position stand now also in terms of debt? And how far does this cash position take you to?

Yes. Thanks, Luisa. I'll take that one. So the estimated cash runway with respect to the financing that we're currently raising will be until the end of '24. And with the warrants also being exercised, assuming that will happen, we'll extend the cash runway until the end of the third quarter of 2025. The direct placement towards Flerie covers the costs, as Leopold described, for the manufacturing part, which were run in parallel to the clinical development part.

[Operator Instructions] It comes from the line of Soo Romanoff from Edison Group.

On the heels of the positive ADVANCE II study results, how do you plan to build on the prior data with the planned Phase II combination study of vididencel with [indiscernible]? And do you think that we could see vididencel being approved as a higher line therapy?

Yes, Soo, thanks for the question. I think what the ADVANCE II study did is that it's focused, of course, on the monotherapy effect. And we're very glad to see, of course, that by just using vididencel that we see this effect emerging. And the next step is to combine it with current say only approved AML maintenance, which is oral azacitidine, because like what we showed also in this, oral azacitidine has provided, say, an additional benefit to patients by shifting, say, relapse-free and overall survival, but it has not led to say a durable response that doesn't lead to cure. And so we feel that actually this combination could benefit patients even more. Does that answer your question, Soo?

Yes. No, that's great. Could I ask a little more, please? Yes. So assuming we have some positive results on the combination study. Maybe you could comment on the future clinical development path for vididencel. How will the data -- data to date on the ovarian cancer influences?

Yes. Well, thanks for the question. I think the ovarian cancer project is separate, of course, from what we do in AML and I think there, we have this Phase I study exploring whether we could actually generate similar immune responses in this case, solid tumor patients, but it's not at a stage where we can currently already draw conclusions on the potential effect on the long run. That takes time. So whatever happens in the ovarian cancer study doesn't influence our development in AML. And I think our AML development is purely driven by the positive results we see from the ADVANCE II study. And as a reminder, we showed you the reader free survival curve. And this plateau, which we start to see is a very, say, typical immune therapy kind of response, but it has not yet really been observed in other studies in acute myeloid leukemia. So our focus is to really see whether that can translate in combination with oral azacitidine in a prolonged and durable control of the disease for these patients.

We will now take the next question from the line of Christian Binder from Redeye.

Just one follow-up. Regarding your recently granted ATMP certificate, do you think that will have any benefit for the planned clinical development now? I wonder whether you can just elaborate on that.

So yes, definitely, yes. The answer is yes. This certificate and especially also the preparation of the work to get this certificate was very useful for us because on one hand, we have, let's say, generated and accumulated a lot of process data and analytical quality data as well and also preclinical data, which we have presented, and we had in-depth discussions and reviews with the authority to review this data. And the fact that we get now the certificate is really helping us in the next steps of the development. So it will help us also interact with the authorities. They know now a lot of the details of the manufacturing of the [indiscernible] and this will actually accelerate the further, let's say, technical development of this product.

So are there any more questions, operator?

There are no further questions on the telephone line. I would like to hand back over to Erik Manting for questions on the e-mail.

Yes. Thanks. What I will do is I will read out the questions and then either answer them myself or ask my colleagues to answer those questions that were collected prior to the call. First question, what provides you with confidence that vididencel has an effect on MRD and survival AML? That's for you?

Yes. I think it's a bit reiterating what we presented and what we said before, but I think AML is still a highly deadly disease. And unfortunately, there's quite a proportion of patients even after initial successful treatment who relapse. I think what we did in the ADVANCE II study, we actually treated those patients, which were at highest risk. And so we treated patients who had residual disease, which if left untreated, would probably relapse within a year. I think the fact that we are now observing that what we presented in December that 14 out of these 20 patients were still alive and long-term follow-up is ongoing. And like I said, we will report later this year what the status is. I think it's a very strong sign that vididencel has the potential to add a new treatment modality for AML. On top of that, this study has given us evidence by looking at T-cell responses and other say, immune responses that the proposed mechanism of action is actually contributing to this effect. And the treatment will improve the controlled disease and specifically of the residual disease. So that provides us with the comfort based on the outcome of the advanced study thus far.

Second question, how is the decision to move forward with vididencel balanced versus the other programs, particularly ilixadencel? Well, I think what's clear is that particularly the data we presented last December for vididencel provided us with the confidence level to move forward with vididencel AML. For ilixadencel, actually, we have gone through 2 major steps, which was first to reposition the clinical development because the landscape in renal cell carcinoma, which was our lead indication in the past has dramatically changed with checkpoint inhibitors now being first-line treatment. So therefore, we have chosen to tap into the broader group of soft tissue sarcomas, based on the data we have observed in the subgroup of sarcoma called GIST. But secondly, and that's been a major investment by the company, actually, we have invested significantly in improving the ilixadencel manufacturing process, which resulted in a much more robust process and also, for example, extended the shelf life of our current inventory and that was all due to efforts in 2022 and also the first quarter of this year. So we are now in a position to move ilixadencel forward. So I would say that the decision to move forward with vididencel has not hurt ilixadencel. Actually, we have invested quite a lot in the program, which now in itself has a good basis to move forward. The third question is what were the design the combination trial with [indiscernible] look-like? What does it practically mean that it is a step up to pivotal stage development? That's one for you.

The design of the next study, which we plan to start with vididencel is, of course, like just at a randomized study from the beginning. So we will randomize in a smaller group of patients to either get vididencel in combination with oral azacitidine or oral azacitidine alone. This allows us to really have a good idea on the safety and efficacy with the smaller group. And of course, that has to determine what the pivotal stage study will look like effect size wise, that's one. And so like shown, it will probably take us 18 to 20 months [indiscernible] looking for after which we can progress and that ties in also with, of course, the manufacturing as just indicated, which by that stage should be also ready for pivotal stage development.

Question 4. Does a choice for oral azacitidine as the next trial means your approval strategy targets, this combination and not vididencel as a monotherapy?

Yes, that's correct. Or [indiscernible] is approved as AML maintenance. And when we added on top of that, I think we believe that it might provide additional benefit for patients. And that will, of course, then -- if that's a registration study lead to the label of combining it with oral azacitidine. However, it doesn't exclude it in other indications or other, say, AML maintenance populations, we might still explore the use of vididencel as a monotherapy.

Thanks. Question 5. Were there more alternatives than the cooperation with NorthX and Flerie and for what reasons was this alternative chosen? That's for Leopold.

Thank you. So yes, indeed, we have evaluated broadly the possibilities for manufacturing of vididencel with more than a handful of potential providers. And NorthX was selected because of the good technical fit and the available capacity also they have and also and really the willingness to grow with the project. And also as an additional element, we have a joint ambition to be part of the expansion of the cell therapy production capabilities here in Sweden.

Thanks. Number 6. Why did the new financing not play significantly earlier? We clearly cannot comment in detail on the timing of our financing efforts, except for the fact that we are constantly evaluating all available options to us. But what we can clearly state also is that it was important to first to find a path forward for our key programs, not only for vididencel, but also ilixadencel, including the progress we made on the manufacturing side and the extension of shelf life and the NK cell program, which is also shaping up, which all had major advances in the fourth quarter of 2022 and the first quarter of 2023 and which provides the basis for the financing efforts. Number 7. Is the [indiscernible] relationship still active? And should we expect further tranches in the future? The [indiscernible] financing was part of a bridge financing, which also involves shareholder loans from our largest shareholder from [indiscernible] and this bridge financing allowed us to reach key advances for vididencel and our other pipeline programs as just explained, as main pillars for our next financing round. For the announcement with respect to the financing, we have clearly stated that there are currently no outstanding bonds to [indiscernible] and also that we have entered into an agreement with Pareto as our adviser for the financing transaction not to exercise any further financing from [indiscernible] arrangement. Next question, is there a possibility for a partnering deal in the near term? Similar to financing, we can't go into a lot of details about our partnering efforts. But clearly, partnering is an integral part of our strategic considerations. And what we are particularly looking for is potential broadening and acceleration of the development of our assets but that will have to be balanced also by the value such a collaboration brings versus the value that we don't need to share with the partner. Next question. You recently announced ATMP certificate for the vididencel program, how does this correlate with the previous ATMP press release you did in '21? And is this certificate valid under the framework with NorthX as well?

So thank you. So I start with the end. So yes, the certificate is valid under the framework with NorthX, of course. And the link to the previous announcement in '21, it was just the classification of vididencel as a ATMP. So the class of products by EMA and the recent ATMP certificate of quality and nonclinical data is based on much more detail data and review of this data and on the manufacturing process. So it represents a further, let's say, confirmation of the robustness of the manufacturing process development and preclinical data we have submitted.

Thanks. Last question, how much would the manufacturing process with a different provider cost if you were not to use NorthX?

Of course. So yes, so basically, the CDMO market is quite efficient and the prices are -- there are some differences, but it's not very big differences. So the decision is basically -- we don't really spare money or pay more money with this collaboration. It's really that we have actually asked for multiple cohorts and the proposals were quite of the same, let's say, order of magnitude. So it's not so much about saving cost, but much more important is about the chance of success of this collaboration. And therefore, we choose NorthX and actually, it starts also with a well-designed process, which we have been developing over many years. And now actually, we will transfer this via a very close collaboration, a trained team of NorthX, use their GMP environment and experience. And this is what we call the tech transfer process. So it's a very important phase and basically, this is very critical as I told before. We are talking about 1.5, 2 years of complete process from scratch to provide clinical batches ready to be used by Jeroen and his team for the pivotal trials.

Great. So this was the end of the Q&A session. With that, I'd like to hand it over to the operator, and thank everybody for being part of this very important update for the company.

That concludes today's conference call. Thank you for participating. You may now disconnect.