Dear live audience here at the studio, dear viewers of the webcast, I'd like to warmly welcome you to listen to Mendus's business update event today. We have for you today several excellent presentations on the company. My name is Antti Siltanen. I'm an equity analyst at Inderes, and I will be moderating the event and the Q&A session. Let's kick off the meeting and event with the CEO of the company, Erik Manting. Please, Erik.
Thanks, Antti. Thanks everybody for joining, both here in the room and online. Today we will present a business update. I'm together with the management team, but also importantly with a representation of two of our most important strategic partners, which is ALLG, the Australasian Leukaemia and Lymphoma Group , with who we collaborate to expand the clinical development of our lead product, and NorthX Biologics, a Sweden-based manufacturing organization, which is specialized in cell and gene therapies, and which is helping us move to a large-scale manufacturing where we can support also late-stage development and commercialization of our product. So two very important strategic partners, and we're very happy that they are willing to present together with us the next steps in the development of our lead product, vididencel.
I'll run you through a brief update of vididencel and our other pipeline programs at Mendus. We'll have a brief intermezzo on the financial outlook by our CFO, Lotta Ferm, before we move to a clinical update by our Chief Medical Officer, Jeroen Rovers, and also a presentation in the form of a video by Delaine Smith, who is the CEO of ALLG. We will talk about the vididencel manufacturing, both our Chief Technology Officer, Leopold Bertea, but also together with the NorthX Biologics team that's here present today. And I will complete the session with a summary and outlook, followed by a Q&A with obviously everybody involved to complete the session. We'll try to complete all of this in the first hour, at least with the presentations, followed by the Q&A.
So as an update, Mendus today, vididencel, we've seen end of last year a very important confirmation that our lead product, vididencel, may have potential large benefits for patients with acute myeloid leukemia, which is a devastating disease. It's still largely unresolved, and the fact that we saw long-term survival in the majority of patients, combined with also very strong immune responses, which were associated with those clinical responses, gives us a high level of confidence that this is a program that we want to move forward. Also, very importantly, we have obtained recently feedback from the U.S. FDA, so the regulatory authorities. We are in constant dialogue with the regulatory authorities, but in this case, we asked specifically guidance on all our main topics related to stepping up to late-stage manufacturing, but also, for example, scaling out the manufacturing to large-scale manufacturing process.
So all the steps involved are steps that you have to, align on with the regulators, and this was, for us, very important and encouraging feedback, and we believe it puts us in a position to start preparing for a pivotal stage trial. So then, with ALLG, we have provided guidance. We will start the trial in the first half of this year, and we are actually on track to realize that. We are still awaiting final ethics committee approval, so it's subject to that last step being taken. We have submitted everything already before the year end, but this is typical, an administrative process that has to take place, and we still expect to be able to recruit the first patients in April of this year.
Then, with respect to the other pipeline programs, we have, as you know, an ongoing trial in ovarian cancer. It's a phase I trial, so it's testing safety, feasibility. We've seen encouraging initial signals showing the formation of immune responses following vididencel treatment, but also the safety of the product in this indication was confirmed. And so we will expect further updates of that trial in the course of this year, including a so-called primary readout of the endpoints of the trial in the second half of this year. We have a second clinical program called ilixadencel. It's an intratumoral primer, so it's a somewhat different approach from the vididencel. That product, we have repositioned.
It was tested in a broad range of solid tumors, and we have decided to take that program forward in soft tissue sarcomas, and we have also made the manufacturing process of that product a lot more robust, which gives us a good confidence level we can move it forward. The preparations for that trial are ongoing, and we expect to conclude those preparations in the first half of this year and to announce the next steps for this program as well. And then finally, we have a preclinical program based on so-called natural killer cells, NK cells, and that is fueling our deeper product pipeline. And that program is on track, including the initial preparations for preclinical validation and the process development of this new approach. So what was the excitement end of last year? This is the data we presented at ASH.
It's a large hematology conference, a global conference. We were invited to present with an oral presentation, which is a big honor, but the reason was mainly that we saw these data in AML. AML is a very aggressive blood-borne tumor. Our CMO, Rovers, will talk about it more in his part of the presentation, but this is the kind of disease where relapse is, so the recurrence of the disease, very imminent. And we saw that initially with patients relapsing relatively quickly, but then all of a sudden we saw that 14 patients were, at the end of the trial, still alive, and in the long-term follow-up, are still all alive. And that is what you call a flattening of the curve.
So all of a sudden, after the first patients relapsing, we started to see that the majority of patients, in this case, 14 out of 20 patients, are now long-term in follow-up and still, and still in, alive and, and, and the majority also still in a, in a relapse-free, situation, so 11 patients being in a first complete remission. So this puts us in a position to expand the clinical development of vididencel. And last year, we have taken a few very important steps. First of all, we did a larger financing round of SEK 317 million in the form of a rights issue and a directed placement.
But also we announced two very important collaborations, which is on the one hand, the collaboration with NorthX Biologics, which allows us to step up the manufacturing, and I can't overstate the importance of that step, because your manufacturing has to be in place when you do late-stage development, and that process has to be aligned also in time with the preparations for your clinical trial. So the fact that we could take that step and basically immediately started working in that collaboration after the summer of last year, was a very significant and important step we could announce. And then end of last year, we announced that the Australasian Leukaemia and Lymphoma Group is willing to work with us on a very sizable randomized controlled trial, where we combine vididencel with oral azacitidine in the current standard of care.
So major steps have already been taken. Again, we did align with the FDA earlier this year to check on the different steps we have to take in order to be ready for late-stage clinical development. We got positive feedback from the FDA, so we now feel we are in a position to start preparing for the pivotal trial, and also, that outlook will be discussed in more detail by our Chief Medical Officer, Jeroen Rovers. So what was all the fuss about with immuno-oncology? And we're just trying to get back to the basics of why we believe this is a very unique approach to treat cancer. The big observation in immuno-oncology very early on was that you start to see long-term survival in patients.
So if you compare immuno-oncology, where the body is basically enabled to have prolonged immune control over disease, there is a chance that patients develop long-term survival in diseases that were previously untreatable, like melanoma and lung cancer, for example. It's different with targeted therapies. Targeted therapies slow down the disease, so you see an immediate effect briefly after the start of treatment, but in the end, all the patients become sick again. So the overall survival benefit is limited. So this is the big promise of IO, and that shift of the curve, which you see on the left-hand side in that top right figure, seems small, and it still is only the minority of patients responding to this type of therapy. But the significance, obviously, of treating patients in a way that leads to long-term survival is very large.
The leading drug, Keytruda, is now approved in more than 20 different cancer indications. It raised $25 billion in revenues last year, so it's a massive success. We were lucky to work with one of the people that were part of the discovery of Keytruda, Andrea van Elsas, who is in our board, and Andrea has been a very strong guiding figure in the early steps we took as a company when setting out our strategy. One of the very critical choices we made is that it already became clear that it's very difficult to improve on the checkpoint inhibitor. So after the initial success, showing long-term survival in, let's say, 10%-20% of patients in some tumors, the disappointment came to the...
out of the fact that it was very difficult in combination with other IO modalities, immuno-oncology modalities, to improve the success rate of the checkpoint inhibitors. So literally after thousands of trials, nothing has moved the needle significantly, and that's a conclusion we have to live with. So what we did early on is decide we would not go there. So the checkpoint inhibitors are improved in solid tumors. There's no checkpoint inhibitors in blood-borne tumors, so we are now with AML in a blood-borne tumor. With ilixadencel and also ovarian cancer with vididencel, we have decided to go to tumors where checkpoint inhibitors are not or poorly effective, because that gives us a chance to differentiate. So those guiding principles have been very important for us from the start of the company.
As a very important additional remark, cancer vaccines are very likely to only work in low disease settings. The cancer cells, what's known by now, have such a detrimental effect on the immune system, that basically the immune system is no longer able to build up an immune response, which leads to control of the disease. Also, other companies are now moving to low disease settings, and this is the reason we developed vididencel in a so-called maintenance setting. Patients have undergone initial high-dose chemotherapy. The disease is down to just residual disease levels, minimal or measurable residual disease, and that is where we hypothesized a vaccine approach could work, and where, where we now also start to see the data I just showed.
So I think it's important to position us in the field of immuno-oncology, and also, again, very grateful to have somebody like Andrea pointing us early on in the right direction. So blood-borne tumors incidence is still rising, and that's also the deaths related to blood-borne tumors. So there's still a very high unmet medical need to come up with better solutions for blood-borne tumors, and acute myeloid leukemia is a particularly aggressive tumor. It relapses basically in almost all patients, and the only curative approach is a bone marrow or hematopoietic stem cell transplant, which is unfortunately not available for many patients. So the five-year relative survival is still only around 30%, and this is in the U.S., which is, of course, a country with a well-developed healthcare system.
So the unmet medical need is that AML patients almost unavoidably will relapse after initial treatment, and to find novel treatments that will prevent that recurrence is what we're really after. And as an additional point of attention, those treatments have to be safe. After patients have already undergone very aggressive chemotherapy, maintenance treatments have to be safe and not impact health or quality of life, and that is what we are currently developing with vididencel. So-
...What's the basis of vididencel? It's basically a whole cell-based cancer vaccine. We manufacture it in a certain way. We administer it as an off-the-shelf product, so it's available to patients immediately when they need it. It's injected into the skin, where it triggers a very strong immune response, and that is something we have not only shown in a lot of pre-clinical work, but now also in a clinical trial. We've shown what happens, which is a very strong immune response initially in the skin, and then you see a broadening of the immune response or a very broad immune response, which you can pick up in the blood of the blood samples we have picked up in the trial.
Very important, there's a big difference between active and passive immunity, and I think the simplest way to explain it is if you go on a holiday and you need immediate protection, you will get antibodies, for example, against hepatitis. But if you want lifelong protection, you need a vaccination, and it's black and white. So the only long-lasting protection is active immunity, and that either comes from the disease itself, which is apparently very difficult in blood-borne tumors, which is why also maybe the checkpoint inhibitors don't work, or it comes from vaccination. Right? And that is where we play. We play an active immunotherapy in acute myeloid leukemia, again, in a low disease setting, meaning cancer maintenance therapy. So with that, I hope I've provided the context for the presentations going forward, and I'd like to invite Lotta to present our financial outlook for the year.
Yep. Thank you. Let me see. We don't talk about much about our profit and loss and so on. We don't have much of that. We don't have any revenue yet. But I would like to explain a little bit how we have used the money we got into the company after the capital raise last summer. We raised SEK 317 million. Out of them, we have to pay the advisors, the banks or lawyers, and other people twenty-four million. We used SEK 69 million to repayment of loans and accumulated interest, and then we used SEK 90 million for prepayment for the production, building up the production together with NorthX. So they were earmarked for that purpose.
And then there was SEK 134 million left, which was a cash injection into the company in August last year. And out of that, together with, with the cash position we already had at that moment, we have SEK 121 million left at the year-end this year, and that will cover all the cost we will have this year for the cash flow, for the cost. The cost will be higher when you look at the profit and loss, because we will have the cost for the production this year, but they are prepaid, so there will not be any cash flow for them. So it's, I will point out this difference between cash flow and cost. So if you look at our quarterly report and think, "Oh, we have high cost," but it doesn't mean that we need cash for all these costs.
That's the most important. This SEK 90 million, which we have prepaid for the production, they will cover not only the cost for this year, also the cost for next year. It will cover the cost until we have produced the GMP material for the pivotal trial we plan to start next year. The material for the trial we are starting this year, the CADENCE trial, it's already produced, so it's not included in the cost base for this year. And then, of course, if we got, we have warrants outstanding, as you all know about, that will prolong the cash runway into Q3 2025. So that's what I will, would like to say about this. So I hand over to Jeroen.
Yeah, thanks, Lotta. So, in the next few minutes, I will walk you through the development of vididencel as a maintenance treatment for acute myeloid leukemia. As Erik already indicated, it's one of the most aggressive and devastating diseases, unfortunately. I think what is the origin is that you have malignant cells growing in your bone marrow, and they basically suppress all the other cells. So that is the essence of acute myeloid leukemia. It needs to be treated as quickly as possible and often as hard as possible. But even with, say, the new treatments which we currently have or the very tough regimens of chemotherapy, which we already have for a longer time, a lot of patients remain to have residual disease, and the risk of relapse in acute myeloid leukemia is very high.
Measurable residual disease, which nowadays we can actually detect with the new technologies available, is a very clear indicator of the prognosis of these patients. That's why I think the main hurdle in AML is still the relapse, and trying to find a way to prevent that is, I think, what we are also trying to do with vididencel. So how do you typically treat acute myeloid leukemia? Well, like I said, as quickly as possible and as aggressively as possible. Preferred is to give a few cycles of high doses of chemotherapy, which is shown on the left-hand side, followed by, if there is a good response to that treatment, a bone marrow transplant. Bone marrow transplant today is still the only curative option for these patients.
In essence, it's actually the ultimate immunotherapy, I would say, because you replace the immune system, which doesn't control the disease, with a new immune system, which hopefully controls the disease. But there's still quite a number of patients who cannot find a donor or for whom the actual procedure of going through a bone marrow transplant is too severe, and they're left without a lot of options. Nowadays, and that's depicted here, there is the option of maintenance therapy with recently approved drug, oral azacitidine, and I'll show you a bit on the outcome of that. Other patients who can get high dose of chemotherapy have to rely on other regimens, like azacitidine in combination with venetoclax or targeted therapies, but that's only for a small portion of patients with a specific mutation....
So I think maintenance, trying to maintain a remission, which we induce through a very rigorous treatment, is a very important and still a very unmet medical need. So this is the data from the oral formulation of azacitidine, the branded name is Onureg. The drug has been registered, say, two years ago, also in Europe. And what you can see, this is the relapse-free survival in patients who are at the start of treatment, in complete remission after chemotherapy, but they still have residual disease, so they're MRD positive. And these patients were either given a placebo, that's the blue line in this graph, or they were given oral azacitidine. And what you see is that it shifts the curve. So patients with which were given placebo only had a median relapse-free survival of less than three months.
When given oral azacitidine, they benefit from treatment by shifting it to roughly seven months. But in the end, and I think if you look at the, say, five-year time point in this, Kaplan-Meier curve, you see that only a very small portion of these patients, it's about 10%, is still without a relapse and alive. And so there's a big unmet medical need to improve these results, and this is where vididencel is currently being developed in. So what have we done today to progress the development? Vididencel has been tested in a phase one study, a small study where high-risk MDS patients and acute myeloid leukemia patients were given a few doses of the drug to just test, is it feasible? Can you give it? Is it safe, and does it have a first sign of efficacy?
Yes, we saw it has a good sign of efficacy, but it was primarily in those patients which were in complete remission, so the patients who had already a low disease burden. Which makes sense from also the concept what we're trying to develop, like what Erik said, an active immunotherapy. So we need to rely on the immune system of the patient to work and to build up this defense or response, and that takes a little bit of time. If you have a lot of, say, circulating cancer cells, then that's just not feasible, of doing. The next step we took is to start a phase two trial, but now specifically in acute myeloid leukemia patients, which were already in complete remission, and so focusing on those patients with low disease burden.
but on top of that, these patients had signs of residual disease, so typically very high risk of getting the disease back within a very short time frame, and I showed you the data from this AML, QUASAR study. I think the schedule is, is shown over here. We injected intradermally four times, and then there's a short break, and then there's two further injections to boost the responses which we induce. This trial focused on looking at the efficacy of vididencel.
Before I show you that graph again, to again show what it does on the long term, I think it's also good to remember that during that whole process of development, we interacted with the regulatory authorities on a very frequent basis, which led to orphan drug designations, both in Europe and in the US for this product in acute myeloid leukemia. It also led for us to get a certificate from EMA on our manufacturing, and the way we manufacture vididencel also for the larger scale later on. And we most recently got a fast track designation from FDA, which again shows the unmet medical need for these patients to get new drugs developed. So this graph we just showed you already, and this is the data presented December last year at the American Society of Hematology.
And I think what Erik rightfully indicated, and if you look on the left, it's the relapse-free survival, is that you start to see that after the first period where there's still patients relapsing, that after the year, there's hardly any patient relapsing anymore. And I think that's something which is quite unique to see. We start to see this plateau in this Kaplan-Meier survival curve, which you don't see that often in aggressive diseases like acute myeloid leukemia. For the relapse-free survival, we were able to determine the what you call median relapse-free survival, which in the data readout in November last year, was 13 months. But for the overall survival, because we had still 14 patients alive, we were not yet able to establish that value, and so that's still work in progress.
But it's a promising sign, because it means these patients continue to do well, and so the later on follow-up will have to show how that develops itself. Another important part of this study was to also look in depth in what does the treatment do to the immune system. Do we trigger responses? Is the immune system changed by giving the treatment? And I think the answer is yes. We see, for instance, T-cell responses towards, say, the cancer antigens, which are carried by our product. And on the right you see the survival curve, and there's a clear correlation that the patients who show a lot of these T-cell responses, they do very well. So that's the patients on the blue line, and they all survive.
Patients who do not show an immune response, not a T-cell response, they do poorly, and that, that also makes sense. So the aim to try and get as many T-cell responses triggered, and then having a good, say, prognosis for these patients, is clear. Next to these T-cell responses, we saw broader activation of the immune system, with B cells going up, which is often a sign for a humoral response, but also increases in dendritic cells, and surprisingly, we saw some decrease in some of these suppressor cells. So the whole immune system is affected by the treatment we're giving. So how do we go from what we've shown you today to where do we want to go in the future? I think that's the development path which we put out here.
So like I said, the ADVANCE II study is still ongoing, so we're still following up survival of these patients, so we'll have later this year more data on that survival. But most importantly is we're taking the next step, and the next step is to combine vididencel with what is currently standard of care, oral azacitidine, so which is on the market, and that we do through the collaboration with the Australasian Leukaemia and Lymphoma Group . That's a randomized clinical trial, so patients will be randomized to either get vididencel with oral azacitidine or only oral azacitidine. The study is broken up in two phases. The first phase is really looking at, is this combination safe? And that's an important step, where we need to know if it's safe enough for any further development.
So the first 40 patients will be used to evaluate that, and then the study can move on into a phase where you much more look into the efficacy. But in parallel to that study, because it's only done with hospitals in Australia, we're preparing now for a pivotal phase for a global registration trial. Because when you want to register your drug, you need to collect the data also there where you want to register. So we need to get the hospitals involved, both in the U.S., both in Europe, and that's the expansion for this program. And so we're preparing that currently, the protocol is being designed. We're interacting, like we already just announced, with FDA, with EMA, to really align on that protocol in an aim to get that study started next year.
Why next year? Well, I think the main reason is that we need a larger amount of vididencel, and we need to produce that, and that's the work, of course, currently being done also in the alliance with NorthX, and that's shown on the bottom. So the transfer of that process aligns also with our starting and ability to start next year with that clinical trial. I think one of the other things which we continue to do is to talk to the treating physicians who come up with a lot of ideas on can we also use vididencel in this indication or that indication?
Our focus is to really look at AML maintenance, and see where that could potentially be expanded, and so if those discussions mature into a potential clinical trial plan, we're always open for that. I would now like to hand over to Delaine Smith, who's the CEO of ALLG. She recorded her presentation. Also due to the time difference, that makes much more sense. So, enjoy how she presents both our collaboration and the study we're gonna run with ALLG.
Hello, my name's Delaine Smith. I'm the CEO of the Australasian Leukaemia and Lymphoma Group , and it's my pleasure to speak with you today. Today, we're going to go through a little bit of the landscape of clinical trials in Australia, an overview of the ALLG, some background to our clinical trial program, and importantly, an update on the progress of our AML M22 Cadence collaboration. In Australia, the government and industry invest AUD 1 billion annually to advance clinical trials in Australia. Australia ranks in the middle globally for clinical trial activity per capita, and we are very well known for our reputation in excellence and transparency in the delivery of clinical trials. There are some features of the Australian environment that make it a good place for the conduct of clinical trials.
First of all, we have a universal healthcare system. We have Medicare for all Australians, regardless of socioeconomic status, and this enables the payment and support for standard of care tests, procedures, and some medicines. Our public hospitals are funded under a state government jurisdiction scheme, and that is also supported by our federal government. We have a national drug regulatory process through the Therapeutic Goods Administration and the PBAC. For clinical trials in Australia, we have a national program for a lead site ethics approval. This means that as a protocol from a sponsor is submitted to a lead ethics committee, all of the other subsequent hospital ethics committees that will adopt the trial will adopt the review and approval of the initial lead. There is also a uniform site contract in place for all Australian hospitals and sponsors to use.
These two things alone create for great efficiencies in the conduct in clinical trials, particularly in the study startup phase. Our hospitals in Australia also work under a national accreditation scheme, and this allows for high quality and standards in the conduct of clinical trials. Looking at our Australian data, you can see here, from our Australian and New Zealand Clinical Trial Register, that around 500,000 Australians a year participate in clinical trials. Not surprisingly, the cancer is the most studied area, and our average sample size of a clinical trial is getting smaller and smaller. Again, not surprising, due to the more that we are learning about the genetic mutation as the basis for targeting treatment. So the ALLG is a national cancer cooperative clinical trial group. We are a volunteer member-based organization.
So essentially, all of the qualified hematologists, research nurses, scientists, pharmacists in Australia that are in hospitals, involved in the treatment and the care of patients with blood cancers are volunteer members of our group. Through their membership with the organization, they're able to bring forward their research ideas, and me and my team in the ALLG office have the expertise to help them develop their research ideas into clinical trials, doing feasibility testing, analysis, et cetera. The ALLG itself as an organization has been around for, over 50 years now. Our annual operating budget is approximately AUD 10 million, and we have a really strong track record for delivering clinical trials across all types of hematological malignancies in Australia and New Zealand.
We've conducted over 160 clinical trials, we've put more than 13,000 patients on clinical trials, and we operate our trials from 94 accredited ALLG hospital sites around Australia and New Zealand. We're governed by a board of directors, and importantly, the Scientific Advisory Committee are the ones that are charged with driving our scientific research strategy and our clinical trial program, and we do this through utilizing the areas of interest and expertise of our key opinion leaders at the ALLG. Primarily, you'll see here, acute leukemia and the lymphoma clinical trial working parties are our flagship areas of research, and most of our clinical trials that we've conducted in the organization have originated from these two scientific areas.
Our Scientific Advisory Committee members are shown here, and some of them are, may be well known to you, but in particular here, Professor Andrew Wei has been leading our acute leukemia program for over a decade now. Our office structure is very similar to what you would see in a cooperative group model or in a academic institution that's conducting clinical trials or other types of research activities. We have a team that is dedicated to the development of clinical trials and also to the setup and the monitoring of trials. We have in-house quality, startup, data management, and monitoring expertise.
Our protocol development pathway that we've adapted, through refinement over the years, allows for a fast-tracking of process from the initial development and concept work through to study startup, and then through to our trial operations for the ongoing data collection and monitoring of patients on trial. We work with a number of international collaborative partners, primarily our European and UK colleagues and North Americans, and through this network of collaborations, we're able to have not only trials operating in Australia that are developed through our own individual members and their partnerships, but also through our peer groups, such as HOVON, that you can see here.
We collaborate with many industry partners across the diversity of clinical trials that we're conducting, and here you can see a snapshot of the number of drug companies that we work with and are working with this year for our clinical trial program. We work with a number of Australian affiliates as well that are involved in the foundation and patient care, and these are really important partnerships for us to have in order to help disseminate information about the clinical trials that are open for participation. Our acute leukemia research at the ALLG, we've conducted successfully 46 trials over our 50 years, and we have a number of trials in acute myeloid leukemia, MDS, and ALL open to recruitment at the moment.
Our snapshot of just some of the more recent active ones are shown here, and you can see there's a great diversity in early phase, phase II and phase III clinical trials that we're operating through the network of the ALLG sponsorship out to our member participating hospitals. One trial in particular is our AML M22 international AML platform. This has been led by Andrew Wei and has been up and going for a number of years now. The design of this trial is such that patients will enter a screening phase through our ALLG National Blood Cancer Registry, which is essentially a screening platform.
From here, patients are registered into the AML M22 trial, and we are monitoring them while they're going through their induction therapy, and when they get to their complete, first complete remission, they're then assessed for evaluability to come into the AML M22 trial, where they are further stratified according to their age and their cytogenetic risk factors across into the treatment arms that will be open, and those domains continue to evolve and grow as the trial program continues. One domain in particular that we're operating at the moment with the support of Mendus is Domain Four, Cadence. The name of this particular arm is Combining Oral Azacitidine and Dendritic Cell Vaccination vididencel in Maintenance, Cadence.
This trial, we've been developing over the past year, and we have a fully formed protocol that is now at the moment sitting with our national ethics committee for review. The way this study design works is, as you can see here, a standard clinical trial eligibility, eligibility listing. Our primary endpoint for the pilot phase is safety. Here we'll be undertaking to recruit 40 patients, randomizing 20 to each arm. We will treat and evaluate these patients for the safety component of the pilot study, and all being well, we will look to expand to a proof of concept stage, where we will be assessing event-free survival. The vididencel is an allogeneic leukemia-derived dendritic cell vaccine....
As you can show here, we are very interested in applying this in the AML setting to better understand the T cell reactivations. There has been data produced by Mendus through the ADVANCE II trial that shows some promising data that makes us very comfortable with operating this clinical trial in our clinical trial platform, AML M22. The study design is such that the cycle schedule is set according to the oral azacitidine schedule, which is administered orally, daily from day 1 to 14 on repeat every 28-day cycles. The vididencel treatment schedule involves a primary course of 4 vididencel intradermal injections on cycle 1, day 1, and day 15, and cycle 2, day 1 and day 15.
This will be then followed by a booster course of 3 additional injections on cycle 4, day 1, cycle 5, day 1, and cycle 6, day 1. We are also very interested in some of the exploratory research that we can conduct through the course of this clinical trial. We will be looking at the immune responses. We will be able to correlate flow cytometry MRD with molecular MRD, and we will be looking to evaluate mutational and clonal characteristics associated with relapse of AML. The timeline that we've been working towards is shown here. We've performed all of the protocol development work. We've now got the protocol sitting for lead site ethics review.
We are expecting the final review of the protocol in these coming weeks, and so therefore, we'll be expecting to be able to finalize and commence site activations during the course of April this year. The number of hospitals that we have interested in this study, in this particular domain, is very good. So we've been able to select out some key sites for the initial safety phase. So in Victoria, we'll have the participation of the Alfred Hospital and the Royal Melbourne Hospital. In Western Australia, we'll have the participation of the Fiona Stanley Hospital and Sir Charles Gairdner Hospital, which are the two largest centers in Western Australia. And in our New South Wales, Queensland region, we'll have the inclusion of Princess Alexandra Hospital.
So with being able to open and activate these sites in the April 2024 period, we'll be looking forward to having the first patient registered to participate in this particular domain, CADENCE, in mid-to-late April 2024. With the timeline of a 2-year recruitment period, we'd be expecting to close to recruitment as we come into the end of 2025 or very early 2026. We're very excited about the delivery of this trial. We certainly very content that we have all of the arrangements in place and set up and the track record to be able to deliver the results for this trial. So I'd like to thank you again for your support in this partnership.
The ALLG, as I said, has a very long and strong history in the conduct of clinical trials across all types of hematological malignancies, and we're certainly looking forward to the success of this one. Thank you very much.
Long-term survival data was actually in December 2022, so that's part of their preparation deck . So the data we showed are the updated ones from end of last year. And secondly, there's now 7 vaccinations, and the reason was that there was a relatively long period between the 4 vaccinations initially and then the 2 booster shots, and it simply gives doctors and patients more comfort if the pause is not so long, which is why we now have 7 vaccinations. Yeah, for those of you sharp enough to pick it up. So with that, I give it over to Leopold for the manufacturing part.
Thanks very much, Erik. I'm so excited every time I see this survival curve, it's highly motivating. So, let me give you a short update on manufacturing, on the technical side of things. First, I want to talk about our development teams in Leiden. So, all of our processes for all our programs have been developed in-house, so it's very important. So we have accumulated know-how over the years for both the process of Vididencel and the manufacturing process of Ilixadencel, our two, let's say, main projects. And we also have a third application of our platform, which is the application on NK cells. So these are, let's say, the three main activities in Leiden. And over the years, so the process for Vididencel has been optimized.
We have a current process, and the groups have developed a new process, which has a larger batch size and is able to supply actually the future needs, both for the pivotal trials to come and also for entering the market after expected market approval. So it's very important that we do all this work to not only prepare the pivotal trials, but to prepare the future of the project. And obviously, the team in Leiden has trained and done all the support and is doing all the support for the tech transfer and the production with our partners, which I will introduce after from NorthX. So the process for vididencel, it's very important that we understand certain things. So it's available off the shelf. That's very important.
It's not autologous, it was said before, so it's allogeneic. It's starting with a cell line, so we just take a few vials. We start the process, so it's every time the same quality, same thing. So this is really designed to be robust and scalable. So the current process is already a scaled up process, which is enough to supply the future, let's say, clinical trials, which will involve many patients. But for future needs, let's say in the next few years, we can just do the same as the big process and repeat it several times in parallel. So this is what we call scale out, and it has the big advantage that we will not change anything.
So the cells will see exactly the same things, so there will be no risk of comparability or similarity of this different process. Will be all the same. The logistics is very simple. The vials will be frozen off the shelf. They will be ready for the patient when the patient needs it. The patient doesn't have to wait for the dose, for the therapy to come, so this is also a very, very important feature of this process. Okay? I have talked about our manufacturing alliance with NorthX. So it's not only tech transfer, it's a manufacturing alliance, so this is very important. We have started this alliance in the summer, so end of the summer, and the two teams have really started working hand in hand.
Both, you know, the teams in Matfors, in the midst of Sweden. It's not in the north of Sweden, it's in the midst of Sweden. And the teams in Leiden. So it's a daily interaction, and the two teams have started, so there was a lot of work in Matfors. This will be explained in more detail by our friends from NorthX. And a big preparation work to design actually everything before it was actually constructed or modified. So there was a big preparation time for the concept of the tech transfer with tech transfer plans, concepts which really planned everything almost weekly from the start to the end.
So the project is really currently on track, completely on track, and we just started the implementation phase with the first technical batch last week. And everything is actually ready to be finished in time in 2025 at the beginning, where we will start manufacturing the first clinical batches for the pivotal trials. So we are very happy with this collaboration, and now I would like to introduce my friends from NorthX. So Eva-Karin , who will introduce also-
Thank you, Leopold. Thank you.
Tomas and Peter. Thank you very much.
So hi, guys. Firstly, I wanna say thank you to Erik and the team for inviting us here today. Really excited to be here and seeing all the beautiful data that you already present. So in the world of constant change, especially within the healthcare sector, it's really important to align with partners that are not only pioneers, but also bold and mature enough to actually change the way forward. And for us, it's Mendus is kind of pioneering partner. And we at NorthX, we wholeheartedly believe that this will actually pave the way and change the way of cancer treatment. So combining this innovation, because we heard now today that Mendus bring new data, new results that are just amazing, almost unbelievable, and combining this innovation with NorthX robustness and safe manufacturing, that's like the best combination, I think.
It's almost like writing a love, love story, but successful one, but within life science, and that's what we're doing now together in this manufacturing alliance. So who are we and what are we doing? So my name is Eva-Karin Gyllén, and I'm the CBO at NorthX Biologics, and I'm here today with my amazing colleagues, COO Peter Boman, and our Chief Quality Officer, Tomas Beck, and they will also present the progress of our project together with Mendus. So NorthX Biologics, as a company, we are a development manufacturing organization, and we are small enough to care and big enough to deliver, and I think that's more than a slogan because it's really true. Back in 2021, we were actually recognized and identified as a competence center and became a Swedish innovation hub, and supported by the Swedish government.
So we are beyond the CDMO. That's not a slogan. We are beyond the CDMO, and I think that this kind of alliance, manufacturing alliance that we have here today, that we're talking about, is a sign of that. And as Leopold said, we are in the middle of Sweden, right? We say up north, but in the middle of Sweden. So we have two different kind of manufacturing sites, and we started back in 1963, so we actually turned 60 years last year. So even though the brand is quite new, the, the legacy and our experience is for really, really long while, has been around for a long while. We're around 110 employees. We're two sites now. So in, in the summer of 2023, we actually acquired a new site in Stockholm area, close to the hospital as well.
I'm gonna leave it to my guys here-
Yeah.
Please go ahead.
Thank you. So, NorthX, what do we do? So, I mean, we're experts in producing biopharmaceuticals... and if you see this slide, it's, it, it might seem like we do a lot of different things, but in reality, we do almost the two things. We grow cells or bacteria, and then we purify something from the cells. It sounds quite easy, and sometimes it is, but normally it's quite a lot of hard work. Different cells work in different ways. Different bacteria needs different nutrients to grow, et cetera. So we are specialized in making these cells, this bacteria grow, and from these cells or bacteria, we either purify a product or the cell is the product, as is in the case with vididencel. We also have an unit where we can fill these cells for this protein in a vial in the end.
So we're spanning everything from proteins to viruses, to gene therapy, to cell therapy. Basically, everything you can do in the biopharmaceutical world. So for Mendus, I just need to start to say that Mendus, the contract is a very nice contract. Mendus knows that if you want to have a good source of your manufacturing, you need to invest in the right facility. So we had a very good start up in Matfors. We had lots of equipment, but all of these cell therapy manufacturing, they're quite special. So you really need the right rooms, the right equipment to grow the cells in the correct way. So that is what we have been procuring and rebuilding the last months. So we have an extremely nice facility to produce the vididencel product today.
As Leopold said, we started the first batch last week, and that was the first real training batch in the right facility. The staff has already been down to Leiden several times to practice with the experts who have developed the process. So that's been a very nice cooperation. We already talked about this, room for expansion. So, I mean, the process that we're running up in Matfors, it's already bigger than what has been produced before for vididencel. But if the product will be a big success, which we hope, then we actually have quite a lot of extra space to install more fermenters and make even more product without any significant investments.
The project is on time, which is great because you're always worried when you buy lots of equipment and you rebuild rooms, that something can happen, but it went very well. And the next sort of major goal we have now is the first GMP batch that is to produce early next year. So we have a few training batches and engineering batches to produce before the real GMP batch starts next year. Tomas?
This type of building a new facility doesn't come without challenges from the different authorities.
Tomas, your microphone.
Sorry. Sorry. So, again, coming back. This type of challenges with building a facility doesn't come without any type of challenges from the authorities. So where we are right now is that we have already achieved all the licenses ahead of time. So with this process, we need a specific X-ray license, and this we already have achieved. The equipment is already installed and validated. The next thing is, of course, regarding cells. We need to be able to manage the cells from a biosafety point of view. Not only do we have a dedicated biosafety officer, we also applied for the license to manage both cells in biosafety level one and also biosafety level two. So this has already been achieved. And the most important part is that we already are good to go with our manufacturing.
So we already achieved the ATMP, the Advanced Therapy Medicinal Product license from the MPA. That's Läkemedelsverket in Swedish, and also a license specifically for these type of dendritic cell therapy products. We also have a new fill finish line that we have a license for, and just only a couple of weeks ago, we managed to get our sterility testing, because these products need to be sterile. So that license has now been added to our portfolio. What is all this worth if we don't have the collaboration? And I'm so happy to see that the collaboration between Mendus and NorthX Biologics has been a tremendous success story. With thanking Leopold and the manufacturing team, we have close contact, we have the same type of ideas, same type of priorities. It's so easy to work together.
The alignment and the design of the laboratories, we almost spoke the first time in the car from Arlanda up to Matfors, a couple of hours, and then we ordered to design the facility. And actually, it came out exactly that way, both in the laboratories and also in the design of the clean rooms, and these are quite advanced clean rooms. We work with sterile products. We need really to work in spacesuits to do this, all the way through to the clinic to make sure we have sterility. The committee we have together leading the project forward, we meet regularly, and we had a meeting this morning, actually, to conclude, and there's no news there. We are on budget, we are on time with what Lotta explained before, and we have very good communication and really timely decision-making.
It almost brings me to tears, this type of very, very important therapy that we're building for the future and the extremely good collaboration, and I'm so happy to be here today. Thank you so much, and I hand back to Erik.
Fantastic. Thanks so much, Tomas, and Peter and Eva-Karin . Thanks. So I hope today made clear that this is actually... I'm presenting your slide now, the journey together, but I think it was pretty clear that that's, that's how we all feel. So today hopefully gave you a good overview of where we stand, what journey we have engaged in now with vididencel and AML, but also that we are not doing it alone. I think we have been making big steps in the course of last year, with the established European clinical network from the ADVANCE II trial, with the IND open in the US. The start now of the collaboration with ALLG, which will expand our global network towards the APAC region, so the Australian and Asian region.
But also that we have already established a very strong regulatory dossier related to both the development of the product and the manufacturing, right? And to see that all come together on a day like today is, of course, very important. We have recently checked with the FDA that we are on track also with respect to what regulatory authorities find important in preparing for late-stage development, and also how we can potentially use part of the data from the CADENCE trial for a go-global registration trial. But also how we can take the next steps in the large-scale manufacturing, as was also very nicely explained by the NorthX team, in alignment with what regulatory authorities would expect to see in a dossier, regulatory dossier for a product like this.
So for us, it's very encouraging that we also can continue to work on pivotal trial preparations with that basis. We will continue to work with the regulators to make sure we take the next steps in the right order. And of course, it's very important that the manufacturing of the large-scale GMP batches is ready and aligned also with the start of, in the end, the registrational trial, and that is coming together basically in the second half of 2025. So on the one hand, we have the trial preparations, the protocol development, the activation of sites that want to participate, but also making sure that everything is aligned with the regulatory authorities. But also very importantly, and I hope that's also something we have emphasized enough in the past, but certainly want to do today, it's a plan coming together, right?
So also the large-scale manufacturing, and this is why we were so happy mid last year that we were able to close the alliance with NorthX and could get started, because now you see how it comes together in time, and also how closely those two elements are aligned. So with that, I really want to thank everybody here and also online, NorthX and ALLG for contributing to this day, and we're open to a Q&A, for which I would like to invite the management team, the presenting management team, but also our CSO, Alex, who is also here today, to join me and then open up the Q&A with Antti.
Okay, we have several excellent questions received by email, so let's start working on those, shall we? Okay, so for the first question, I will quote your year-end report. "Based on the ADVANCE II data and data from the first stage of the CADENCE trial, Mendus expects to be in a position to get engaged in a global registration path for vididencel in 2025." So could you please elaborate a little bit on what do you exactly mean by this?
Yeah. So I hope it became clear today with how we presented, how things are coming together. So on the one hand, we made already big steps last year with the NorthX alliance and with the collaboration with ALLG, which of course is taking care of a very sizable trial in combination with oral azacitidine. I think what's also clear from today is that it's all supportive of what we want to do as a company, which is to make sure we are ready for pivotal stage development in the second half of next year, right? And there is overlap, so there is the possibility to use data from the Cadence trial also for the global registration dossier.
The path towards pivotal stage development is one that stands by itself, and that will bring together the different elements from the previous trials and the manufacturing side of things.
Great. The next thing... next question is also on the relationship of the Cadence trial and registration of vididencel. I think you touched a little bit on this already, but the question is that will the Cadence trial and the first 40 patients, and the readout of the first 40 patients guide the design of the pivotal study? And I could also add the same question about ADVANCE II. So how will they guide your future pivotal study?
Maybe that's one, Jeroen. Give you a chance.
Yeah, I think it doesn't really guide, say, the design, because I think that that's standalone, like how do you register the large phase three trial? And that's also needs to be a randomized clinical trial. But it's very important for us to get confirmation that we can safely combine these two treatments. Without that, you cannot progress into a larger trial, because then you risk that you have to stop the trial with unexpected, say, toxicities. So the Cadence trial provides a large and important, say, part of the information going forward, but that's the most important element there.
And the follow-up question on the same theme from the person who submitted the question is that: What do you believe regulators are specifically looking for? What does a clinically meaningful benefit for AML patients look like in a registration trial?
Yeah, I think that's no relapse. And so relapse-free survival is a very important endpoint and will probably be the most important endpoint for a registration trial, but in the end, it's gonna be overall survival. So everybody wants to see that patients will have a durable response and are able to survive as long as possible.
Do you care to speculate on the magnitude of the overall survival benefit?
No, I cannot speculate. No.
Well, I think what's most important is what we see, which is a durable response, right? And that makes a relatively large impact on, on overall survival as well. And what we've, I think, explained today is that in AML, relapse-free and overall survival are very closely related because it is such a deadly disease that relapse is followed very quickly by usually also, death related to the cancer. So that's why in AML, the medical need is very high, but also the, the readout with respect to relapse-free survival and in the end overall survival, is relatively quick. And where you see an effect like this, and maybe I will go a little bit further than you, Jeroen.
I know we have to be careful in speculating how exactly a trial will be designed and how big it will be, but it's clear that if you see an effect like this, it may not need such a big trial as, for example, BMS ran for the QUASAR trial, which was 500 patients. I think we can, we can deal with less patients than that. Maybe that's as far as we can go today.
Great. Okay. So when you first announced the collaboration with ALLG in December, you were expecting the trial, CADENCE trial, to start by year-end, and today you mentioned the recruitment will start in April. So, the question is that, what was the reason for the delay, and will that affect your plans and schedules going forward for the registration path?
Right. Well, the answer to the last part is obviously no, because we are not dependent on the completion of the CADENCE trial to progress into a pivotal stage trial. It will be important, of course, to get initial safety data from the trial. But what we stated end of last year is that we had submitted everything to allow for the start of the trial, eh? And the start of the trial would take place in the first half of this year, where we have some delay, but that's always a little bit of, however you want to call it, an adjustment with ethics committees and how quick they come back with questions. So you can't always fully control that first phase, but you have to take that hurdle in order to get started.
As stated also by Delaine Smith, CEO of ALLG, the trial is still ready to enroll first patients in April, and we do expect that final approval anytime.
Good. I will again quote your year-end report: "Additional trials may also allow Mendus to broaden the positioning of vididencel in AML maintenance and adjacent indications, such as myelodysplastic syndromes." So the first part of the question is, could you please elaborate how far you have come in analyzing these possibilities?
Well, it's an excellent question, Antti, and the reason we stated this more broader potential of the product is that we are refining our strategy. So initially, when we started, we had only one strategy, which is we're only gonna apply this product in low disease settings. And we looked very roughly into what disease areas are unmet medical needs, based on the criteria I showed in the beginning of the presentation, which is high need for maintenance therapies and no effects of immune checkpoint inhibitors. And we ended up with AML, but we also ended up with ovarian cancer because that has a similar dynamic, very deadly disease, because it comes back so quickly. Now, we are of course awaiting the trial data from ovarian cancer, and that will also guide us in that disease area, what we can and cannot do.
But we have, of course, a very high confidence level on the basis of the AML data, and that is refining now our strategy, which means that basically everything top of mind that we are doing is what we presented today, which is to make sure that we get on the right path to get vididencel into a situation where we can develop it for market registration in AML. Right? But there is such high unmet medical need, and like Jeroen also described, because the safety of the product is excellent and there is such benefit to be gained in the clinic, of course, there was a lot of interest to work with that product in the blood borne tumor setting, and we will not close our eyes for it.
So if there's opportunity, either with investigator-sponsored trials or smaller company-sponsored trials, to already start broadening towards other patient populations, we will take that into consideration. But it cannot become a distraction of the main path, which is to make sure that everything is in place for registration trial and AML maintenance in the current patient population.
Yes. And if we think about broadening, would you say it's primarily within AML to include more patients or to expand in other blood borne tumors or maybe even into solid tumors? So can you speculate a little bit on this?
Well, I think we started quite rough, again, with a very basic principle, which led us to AML on the one hand and ovarian cancer on the other hand. Refining of strategy comes once you've seen the initial clinical data, right? And I don't think... certainly, looking at the IO field as a whole, where sadly enough, a huge number of trials has not led to improvement on checkpoint inhibitors. That's a very hard lesson learned for the field as a whole, right? We have to adjust to that. So the fact that we first took that step and said, "Listen, we're gonna go where the checkpoint inhibitors are not working," and we now see data in AML, that was, until recently, not a given.
So we did see promising long-term follow-up already in December 2022, which is when we presented at ASH for the first time in an oral presentation. Now, we also have all immunomonitoring data showing that the product is doing what it's doing, and that it's also associated with the clinical benefit. So now we have nailed down everything we could get out of the phase 2 trial, and that is now a guiding principle. So that's also how we adjust as a company to the new reality as it surfaces. So where this will end, we don't know, with respect to what the breadth of the potential applications is of the product, but at a certain point, you also stop experimenting, right? For us, it's now.... So of course, we will await the data from the ovarian cancer trial. We have a few other pipeline programs.
We will not throw away valuable assets, but the mindset is now getting everything ready for registration trial.
Good. The next question is on the preclinical program and possibilities of the NK cells. So, this is now in preclinical phase. If the results are promising, are there plans to take this all the way to the pivotal stage? That's...
Well, I think I'm looking at Alex here. We're relatively early with the NK cell program. It is one of those deeper pipeline programs which we are developing. Alex is an NK cell expert. He was actually the founder of this discovery, like he is the founder of ilixadencel. So we are taking these programs forward, but again, it's a deeper pipeline program, right? And really too early to say if we're gonna do anything with it ourselves towards the clinic or if we do it in a partnership, but the program is on track. We have last year done a preclinical validation and also set up the initial manufacturing steps, 'cause otherwise it's not a product, right? If you can't manufacture it.
We have taken already very significant steps, but it's an early-stage program, which we can't compare directly with vididencel in terms of potential to enter pivotal stage development.
Yes. Okay, then the next question is on ilixadencel. Do you still expect to start the gastrointestinal stromal tumor trial with ilixadencel in H1 2024, and are there any changes or updates to these plans?
Well, maybe the only remark immediately to your question is we have already stated that we will look broader into the soft tissue sarcoma field, and the reason it's taken some time to prepare the product for re-entering into the clinic was twofold. First, we had to replace certain steps in the manufacturing process. The manufacturing process wasn't robust enough, but also some equipment that we used was taken off the market, so we had to redesign the manufacturing process. And also there, again, is a very simple rule: if we can't make it, we're not gonna proceed with it, right? So that was step one taken. Step two is you're always working in a competitive environment, and you have to see also now as a company with the data in AML at hand, how you balance that with your other investments.
So we do believe ilixadencel is a valuable product. We have looked into different options to run a clinical trial. In GIST, it's still a very competitive landscape, which is why we are now looking more broadly in the group of soft tissue sarcomas, which are all relatively poorly responding to currently available therapies. And we are progressing with those discussions, right? Which is maybe the explanation why it took a bit longer, but also repeating the statement that we are still dedicated to bringing that product back into the clinic.
Perhaps we can expand, expect some news during this year on what, on your plans.
We've said first half of this year-
Yes
W e will conclude these discussions, and they will either be successful, and I will announce it. If we're not able to find a valuable setting in the first half of this year, then, yeah, we may need to take other decisions, but right now we are dedicated to bringing it to a successful conclusion.
Yes.
First half.
You had a lot of information already on your progress with NorthX, but I will still repeat the question. Could you please comment briefly, how is it going with NorthX and the preparation for production? Is everything according to the plans?
Yes, so I can take that one. So yes, indeed, everything is according to the plan. It's really precisely according to the plan. So we started, we planned everything. Now, we started the implementation phase after the whole facility has been adapted and the rooms have been established, the equipment has been established. So now, as was explained also by our partners of NorthX, we started last week, the first technical run as planned. So precisely as planned.
Yes.
Yes, the answer is yes.
Very good. Has the entrance of Flerie Invest changed the situation for Mendus, and in what way so far?
Well, first of all, I'm very happy to see people from Flerie here. Ted is here, Carl is here from the team. I think the way we set up this collaboration could not have happened without Flerie, right? And they also stepped up at the time that it was necessary, when the markets were tough, when we needed a bit of extra success to raise the money we raised last year, and to not have any delays with the manufacturing. So I think there was a lot of good things coming together, and now we factually have two-thirds of our shares with large shareholders, being Van Herk, Flerie, AP4, who is also here today, and we're very happy with the support of those shareholders and by the way, all other shareholders, right?
I know this is a game that is always coming with risks and ups and downs, and share price moving in certain directions, which we don't always have under our control, but we feel very supported by our shareholders. That's the first thing I want to express, and I'm not sure, Ted, if I may ask you to add anything to what you saw as. Is there a microphone, maybe?
Yeah, there's one.
Yep.
Yeah, no, we've...
Ted is the CEO of Flerie, by the way.
Yeah. Hello, everyone, and hello, online. I can only reiterate, yeah, that we've been very supportive of Mendus. We've followed Mendus and Immunicum, and even DC Prime, for a long time before we invested, so this is an exciting field. We invest in cell therapies generally. We obviously have invested in CDMOs and manufacturing for a long time. Our founder, Tomas Eldred, who built up Recipharm, is, I think, very well known in the Swedish ecosystem. So I think the right steps have been taken. The data speaks for itself. I think it's unbelievable, actually, that so many patients are still relapse free. This is very difficult to do in this difficult space. So, yeah, I think we look forward to more good news in the coming weeks and months.
Yeah. Thanks, Ted.
Yes. Okay, and final question, you mentioned in today's news that you have received feedback from the FDA, and you have ongoing discussion with FDA and EMA. So can you add a little bit on color, or what are the topics that you have been discussing and are discussing, and what has the feedback been from the authorities?
I'll describe it in general terms, which will be understandable for everybody, and then if you want to add anything or Leo, they can say it. But what's super important is that you have a robust regulatory dossier, right? And that you check every element of that regulatory dossier, and regulatory authorities generally are willing to do that, right? As long as you plan your meetings carefully, and as long as you have also a good basis with respect to earlier interactions for when you ask for the next interaction. This time, we asked very broadly about everything which is relevant for our product, which relates to the manufacturing, which relates to element that we need to have in place as part of a registration trial, and basically ask confirmation on all these individual topics.
Particularly also making sure that we're on the right track in our thinking on how to design a pivotal trial, but also with respect to the next steps towards large-scale manufacturing. As you understand also from the presentation by NorthX and Leopold, there's a lot of steps to be taken, so you need to make sure that the regulators are happy with how you propose those steps and how you will next execute them, and that was the meeting we had earlier this year.
So that was all of the questions via email, and so thank you very much for the answers, and we can close the Q&A part.
There's maybe also questions in the room, and I also want to thank people for coordinating the questions via our email address. I know some people are very active in compiling what's going on with other investors and then sending the questions to us, so also much appreciated that they were part of the preparations for this session.
Yeah, and just a clarification, the material to be used in the CADENCE study, part one and two, has that already been produced in Leiden? So it's not NorthX.
Go, Leo.
Yeah, thank you for this question. So in fact, the material we are using, we have used so far, and we will use now for the CADENCE trial, has been manufactured not in Leiden, because in Leiden we have an R&D facility, so we are making... We're actually developing the processes and supporting the processes. But we work with the current CDMO for the small scale, let's call it the current scale manufacturing, and this is our source of current material. So this material is currently on inventory and waiting to be used. So it's ready to be used, and there will be no delays because of that. So it's, it has been manufactured at the CDMO.
Okay. And then from a clinical point of view, what maybe I should already know this, I have perhaps not read the data thoroughly enough, but what should one, an AML patient expect? Do some patients not at all have any success with vididencel, some a lot of success? And what should one expect on... Will this effect last, or will the cancer cells within a couple, three, four years circumvent the treatment? That's my question.
Yeah, maybe I can take part of it, and then I'll also leave part of it to Jeroen. What is related to, let's say, the outcome we are currently seeing, and which is what I also described early on, why was IO such a big breakthrough? It was actually two things. First of all, people thought that our immune system wouldn't work at all anymore after high-dose chemo, and now it turns out in solid tumors that it actually is still quite active. The big question is still: Why is only 10%-20% of patients responding, right? So that is one of the bigger themes now in immuno-oncology, but the fact that the immune system has a role in controlling disease and is maybe also the only way to get long-term cure or long-term clinical effects in cancer, is now established.
We're just entering a new phase in how to better work with that starting point. And where we have taken now in AML shows that it is possible to see an immunotherapy effect in AML. So I think that's the most relevant starting point, and the safety and benefit profile is also very positive. So the only side effect we've seen with the product is redness where we inject it in the skin, because there you get an immediate immune activation. But if that's the side effect of a cancer treatment, that's a very good starting point as well. So that's what we've seen.
What we've also seen in the clinic is that the patients that relapsed very quickly, and that's what Jeroen showed, basically had hardly any immunity left, and it was both at baseline, so before the treatment, but also after the treatment, we saw that their immune responses were very weak as compared to the majority of patients that responded much better. And whether or not we should exclude patients beforehand, on that simple basis, we currently don't foresee that. I think in hindsight, we can predict or we can at least explain why some patients have poorly responded, but I don't think in this indication you want to withhold treatment to anybody. And with respect to your question on, let's say, possible resistance, that's typically what you see when cancer cells have survived initial chemotherapy.
They tend to no longer respond to the same chemotherapy a second time. The other sort of resistance we see, particularly in rapidly evolving tumors like AML, is that if you have a very specific target, so one protein or one cellular pathway, there will be new clones very quickly developing, which don't have that particular protein on the surface, and then you will get what's called clonal escape. So then you get new cancer cells very quickly growing out again. Where we have designed our product as a whole cell based product, which carries a lot of antigens, at least it has the potential to have a much broader effect on the immune system, which we now see also translates into clinical benefit. That's as much as we can say, let's say from a fundamental perspective.
I'm not sure even if you want to add to the clinical picture.
You addressed all the points, so nothing to add from my side.
Does it answer the question?
Should one expect any differences in the way of or in the administration, how often you administer vididencel?
That's a very good question. I'll leave it up to you and-
Can you specify what do you mean changes of the ... For different patients, you mean?
Yeah, yeah. You could, you could, administer vididencel, twice a month and, and continue with that long term.
Yeah. Well, currently, we have a set regimen, and I think that's what we will continue to develop. Because otherwise, to make it, say, almost individualized, would require you to have a very good, say, readout on when to add another, say, injection and when not. And so that's work, which in the future, we might be able to provide a better insight in. But for now, we will just stick to the first, say, priming schedule, and then the boosting schedule, which we have introduced.
Thanks. I think that's the questions from the room, Antti.
Yes, thank you very much on my behalf. Excellent questions. So Erik, would you like to close up the remarks?
Just by saying thanks to everybody who contributed, so the NorthX team, ALLG, with recording by the Lane, of course, Antti as moderator, and all of you for being part of it, either here or online. And we look forward to keeping you updated on the next steps. Thanks.