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

Hi, and welcome, everyone. Today, I have the pleasure of interviewing Erik Manting, CEO of Mendus. Erik, thank you so much for being here.

Thanks, Christian.

Now to start off with, you've recently presented new data from ADVANCE II and ALISON at EHA and ESMO cytological cancers. To get everybody on the same page, can you just elaborate on which data did you present and especially which new data points were presented?

Yes, with pleasure. To start with the ADVANCE II data we presented at the European Hematology Association Congress. What we have brought together is actually 2 data sets. One is the data set that we had collected end of last year about the survival of AML patients in that trial. And as you know, we saw a striking pattern with some patients relapsing and also passing away very quickly, which was 6 out of 20 patients, but then 14 patients having a remarkable long survival curve at the time we measured the long-term follow-up medium was already 37 months. And that's very unique in AML because it's a very aggressive disease. It disturbs the bone marrow and the blood compartment. And yes, certainly when the disease comes back, usually within a half year, it leads to death. So it's a devastating disease. And the fact that we saw these 14 patients alive and long-term follow-up, that was a very important signal for us that vididencel, our lead product, has an effect in this patient population. But then we also collected blood samples to actually look into the immune system in more detail. And initially, we reported T cell responses or T cells are a specific part of the immune system. They recognize specific antigens. And we just chose the most known or the best described antigens in AML, and we could already show that patients have responses against these antigens. The majority of patients had responses against these antigens. And also that there seems to be a correlation between the patients that fell ill very quickly. They had hardly had any of such responses and the patients that were in the long-term survival curve that did show those responses. And now we actually looked in a lot more depth into the immune system with so-called deep immune profiling. And it means that you use all kinds of markers for immune cells to distinguish different subsets of immune cells. And what was striking was that the patients that had immune responses following vididencel administration, not only had T cell responses, but also B cell responses, for example, and a few other nuances that will be in too much detail for now. But the simple explanation is that there's different compartments of the immune system involved in immune response against the vididencel vaccine. And that is very important for disease control. And that's not only something as a concept, which we had hypothesized that you need this kind of broad-acting vaccines to protect against residual cancer cells or to enable the immune system to control these residual cancer cells. But it's not also something we could show convincingly. So we looked at so-called confirmed T cell responses of patients having T cell responses at multiple time points. But we also looked at the relative level of B cells in the way the B cells increased following vaccination. And it was a striking picture. So the patients that had these immune responses also were all in the long-term survival curve, whereas the patients that were lacking these responses, they were showing poor survival. So it clearly shows that the immune responses that we induce during the vaccination period result in a long-term clinical benefit. And that is exactly what you want to do with this kind of approach because it confirms that you're training what's called active immunity, which means that your own immune system builds up immunity against the residual cancer cells and therefore, also able to have long-term control of these residual cancer cells. So that was coming together at EHA. For the ALISON trial, we are a bit earlier. So we have done initial immunomonitoring data in ovarian cancer patients. What -- the idea was behind the trial was to test if vididencel, which is of a leukemic origin. So it's a leukemic cancer cell line would also be able to trigger potentially relevant immune responses in a different tumor setting, in this case, being ovarian cancer. And the reason is that the cancer cells express a lot of tumor antigens that are basically shared between different types of tumors. So in this case, we selected antigens that have been documented to be relevant for ovarian cancer. So somewhat different antigens as compared to the ones we checked in the ADVANCE II trial. And we could show that in the majority of patients, we started to see very robust T cell responses against one or more of these antigens. So that is -- and of course, we also provided an intermediate analysis on survival and could show the majority of patients was still disease or progression free at the last point we measured. But it's too early to draw conclusions from that. That's also something I would like to emphasize. Ovarian cancer is a very different disease as compared to AML. AML is so aggressive that there's either AML or there's no AML, there's nothing in between. In ovarian cancer, women are treated with surgery combined with chemotherapy and then sent home basically. In our case, they got the vaccination, and were sent home. And they come back to the hospital when they have complaints, right? And then you don't know exactly what happened in between. And the only thing you know is usually the complaints -- physical complaints means that the tumor is back, and then you can, of course, assess if it has grown versus previous scans or if there's new tumors, et cetera. So that trial will simply take more time to read out in terms of potential survival benefit that we see in those patients. So that's why we are now following up these patients with long-term follow-up. And the additional readout we will generate by the end of this year is to do the immunomonitoring for the whole patient population, which is 17 patients and to also show more detail how those evolve for the total patient population. And what we have already shown now in the first 15 patients that we checked that there was a new responses in the majority of patients and that the product is very safe, which is a good starting point.

Perfect. And you already discussed a little bit in terms of both T and B cell responses. I think a lot of people might only think, all right, if you have a vaccine, you need to induce CD8 T cell response, for example, and they will kill the cancer cells. Can you elaborate a little bit on why is it so important that you have a well-rounded immune response?

Yes, I think it's a perfect question. And what I think has been explored a lot in the biotechnology industry is the concept of using antibodies, which are produced by B cells for specific targets. So then you use the target and you try to find an antibody that may have a therapeutic effect based on binding to that specific target. So a lot of the antibody companies try to approach the use of antibodies in that way. That is what's called passive immunity. So it means that you inject something in the bloodstream or so nowadays also subcutaneous, but you inject into the body. Antibodies that have a specific target to which they bind, that may slow down or reduce the disease. That's called passive immunity. It's not long lasting. You have to repeat the dosing of those antibodies. Traditionally, vaccines were very much oriented towards antibodies because you could measure those antibodies in the blood and you could show that antibodies against the vaccine were induced and therefore, also people were protected for example, against infectious diseases. So that is something which we now see also in the ADVANCE II data. So the T cell field has moved a lot more towards specific tumor-associated antigens. We [ feed ] the immune system with a full repertoire of tumor associated antigens, right, because they're part of original cancer cell that we just made immunogenic for vaccination purposes. So we do pick -- it's encouraging to see that we do pick up T cell responses against these individual antigens. But the fact that we also see, let's say, the classical B cell response against a vaccine and that that's also strongly related to the clinical benefit shows that for an effective antitumor response, it's actually optimal if you have a much broader activation of the immune system as compared to, let's say, single target vaccines or vaccines that only track T cell responses. So I think the finding is highly relevant, and we could now also show that it actually does contribute to the long-term survival benefit of those patients that have a robust immune response.

Very interesting. Now both Advance II and ALISON had relatively small sample sizes. So do you think these data are rather conclusive? Or do you expect that you will have to confirm them, so to speak, in larger trials?

Well, I think the data in itself are conclusive because they confirm the proposed mechanism of action of the product and also the outcome of the trial being the majority of patients alive in long-term follow-up is a very strong signal. And the fact that these 2 are correlated, that makes a compelling conclusion of this trial. We will have additional readouts that patients are still a long-term follow-up. But I think this coming together makes a very strong conclusion out of this Phase II trial. What I think is the main next challenge is how to optimally position the product for further clinical development. And that relates to 2 things. It's on the one hand, which patients do you address? How big do you need to make your next trials. As you know, we have started now a trial with ALLGs or the oscillation leukemia in the former group, which goes up to 140 patients. That's also a number -- yes, you should have in mind roughly with respect to what the registration trial would mean in this indication, but then you need to make other choices like do you only include patients that are of a very high risk status so that have residual disease measures -- MRD positive, as we call them. Or should you approach the broader AML patient population because also MRD-negative patients have very high relapse rates. Where are you exactly positioned following chemotherapy. So in the current trial, we allowed patients basically at any stage after the chemotherapy into the trial as long as they were MRD positive, and as long as they were still in their first complete remission. In the CADENCE trial, for example, we have a much more standardized time window following chemotherapy when we apply the vaccination, right? And that is also something we would consider for a registration trial. So I think that is where the real challenge will be to design a good set of trials that will allow us to get the product registered. But also to see if we can further broaden the application of the product in additional AML maintenance populations. And that is something we are also currently considering and that will also mean we're going to test this concept in different settings, for example, in the post-transplant setting, where patients get vaccinations after the immune system has been reconstituted. So patients get stem cells back. They grow out into a new immune system, but you need to train the immune system. And what typically happens is at a certain point patients get childhood vaccinations to boost the active immunity against those infectious diseases. But that is a window we could also use to vaccinate against the leukemic cells. So that's one example of where we think we can broaden the positioning of the product. And that is now, I think, really where we have to confirm that it holds up in different clinical settings. So I think for the basic concept of can you induce active immunity in AML, can you show that it leads to long-term survival benefit. That is a crucial step we have taken, but are now translated more broadly in expanding clinical development setting, that is going to be the most interesting part of the journey.

Right. Got it. Now as we already talked about, you've shown data on both T and B cell responses in AML. In ovarian cancer, you primarily focused on T cell responses thus far. Do you have any data yet on potential B-cell responses in ovarian cancer?

Not yet. No. And the simple reason is -- we did the same thing with the ADVANCE II trial in AML. The initial T cell responses against individual antigens are relatively easy to pick up because you do what's so-called ELISpot assays. So basically, you test for T cells that become activated when you expose them to the antigens that you test against, that's a relatively quick assay. So the fact that we pick up these responses in ovarian cancer with that assay is encouraging, but it's a start. And the deep immune profiling when you really look into individual immune cell subsets, that simply takes a lot more time and effort. So it will follow.

Perfect. And looking a little bit more broadly. During the last couple of years, you've presented a lot of immunomonitoring and efficacy data. Looking back, would you say that your picture of vididencel's mechanism of action has evolved in any way? Or has it primarily confirmed what you already expected at the start?

Well, I think the mode of action of the product was quite well documented in the preclinical setting and also to the point that we did in C2. So with live human skin experiment. So we knew that when we inject the product into the skin that the antigen-presenting cells in the skin, basically phagocytose or eat it or processes or if you want to call it, but phagocytosis is the scientific term. So they will be loaded with antigens, and we could also show that they become activated. So the expectation that these cells which are basically in the skin of the patient, would activate a broad immune response that was a quite logical assumption. But what I think is new is that we really start to see now how broad the immune response is, but also that it's quite remarkable that -- and that was the big question that patients that have undergone not only AML as a disease, which is very disruptive for the blood compartment and the bone marrow, but also very high-intensity chemotherapy are still showing these responses. That is remarkable. And I think that was the start of cancer immunotherapy as a whole. For a long time, people thought that chemotherapy and other similar cancer therapies would destroy the immune system to the point it would no longer have a role. So the checkpoint inhibitors as a class of drugs have changed their picture and have shown that the immune system can play a role also in the treatment of cancer. And I think we've taken it to one of the most challenging settings where also, for example, checkpoint inhibitors have not shown any effect in acute myeloid leukemia. So the fact that we are now seeing these responses in these patients, again, that have had this aggressive disease and that have had very high-intensity chemotherapy. That is, I think, very encouraging in opening up a whole new spectrum of possibilities.

Great. And obviously, for you as a biotech company, it's also important to attend these congresses and conferences because there are a lot of academic and industry participants. So can you elaborate on what kind of feedback have you received when you presented these data?

Well, let's separate it into 2 categories. I think for the academic contacts that we have, key opinion leaders, we have already established a very valuable and also high-quality network of centers that we work with. So in Europe, we work with 10 of the leading academic hospitals. And also in Australia, with Professor Andrew Way, we have teamed up with one of the world leading KOLs in the field. And what is particularly attractive is that people really want to work with the product because we see these compelling data, combined with the fact that it's very safe. So to try this in different settings and see how this will play out in different patient populations is something that people are very keen on doing. And that helps us because it will make it easier to get people engaged in trials and to potentially also broaden towards additional patient populations. With respect to industry, yes, I think we know the players quite well. They know us. The long story short is, I think that, yes, the data look very interesting. They are also rather compelling to the point that the scientific part of it, which we just discussed and the outcome in this patient population holds up. But typically, yes, pharma companies want to wait a bit longer, see a bit more data, derisk as much as possible. And what has also changed and impacted the field a lot is that most of the recent immunotherapy trials have failed. So there have been a number of large pharma companies trying to develop either existing or novel checkpoint inhibitors in acute myeloid leukemia as a potential long-term cure, but it has simply not materialized. So also people are now looking for new indications that it could or could not work in AML to develop immunotherapy. And I think that's where we have, on the one hand, a very unique approach, right, also showing that this active immunity, which you boost with this product contributes to long-term survival. But also there's a kind of risk-averse attitude currently in the industry because so much was tried and failed, right? So I think what we need to do as a company is make sure we continue to collect these data and continue to keep a close finger on the polls with potentially interested industry partners. And at the same time, make sure we don't lose space, right? So what we have mentioned is that we will do everything to be ready for a registration trial by mid next year, third quarter, mid-third quarter next year based on the trial protocol being ready and also having the large-scale manufacturing in a GMP facility with our partner NorthX setup because that will also be very important for any potential partnership, right, that you keep on moving forward that you have a clear plan that the manufacturing is sorted out. So that's in a nutshell or strategy of the company. So we make -- we continue to collect data. We make the product more attractive. We will collect data from the ongoing trials, prepare for a new trial and potentially broaden towards additional AML patient populations. And, at the same time, make sure that everything in the program is well on track. And that's, I think, the way we will also interact with potential pharma partners.

Perfect. Let's talk a little bit about how the presented data will guide your later-stage development. Has it, for example, influence how you think about designing later-stage trial, which immunological assays to run, et cetera?

Well, it's a good question. And I think we've skipped maybe one part of the immunomonitoring data that we have collected in the past 6 months, and that was also data we presented at earlier conferences, including CIMT. And it is that at baseline, you do see differences between patients that respond and that do not respond to the vaccination. So baseline means before you do the first administration of the vaccine. And that relates to the steps of the immune system. And that in turn also seems to relate to the disease. So the disease is suppressive of the immune system, actually, the cancer cells themselves act as suppressor cells for the immune system. And we did see that in patients that poorly responded, there were, for example, elevated levels of what's called LAG-3 positive T cells. So it's a specific subgroup of T cells that are suppressive and not actively involved in an antitumor or effectively involved an antitumor response. But the effects were not black and white. So the combination of seeing relatively encouraging immune responses in the majority of patients, combined with a very strong safety profile. Yes, initially, does not lead to, let's say, exclude any patients. Actually, we should treat as many patients as possible, like what you also see with the immune checkpoint inhibitors, right? So they show long-term survival benefit in, yes, roughly 10% to 20% of patients in responsive tumors, but still everybody gets them because there is no harm, right? And that's also how we see vididencel where also with the feedback we're getting from KOLs, for example, that are dealing with very high unmet medical need, both, by the way, in hemato-oncology and in ovarian cancer. There's very little effective treatment for patients after initial treatment success. Yes, they will not hold back because there's no harm, right? It's a relatively safe product. So in that sense, we don't see a clear reason why we would or would not include or exclude certain patients. The only thing is that it's good to confirm afterwards that the immunomonitoring data also point in the same direction. So that's something we will continue to do also in our upcoming trials.

Great. Now to round off, you already touched on it a little bit, but I think a lot of people, they see kind of oncology or cancer as one disease, but if you're actually a little bit more involved, you recognize that each different type of cancer is kind of its own disease, so to speak. So based on the data that you've collected to date, what can you say about potentially differing effects in different indications?

Yes. So I think there's 2 sides of the medal, right? One is the immunogenicity. I think in principle, and we're testing it now in ovarian cancer, we don't see any reasons why if there is immunogenic overlap between our product and antigens expressed by other tumors, it would not lead to an effective immune response. But that is something we are currently testing, for example, in the ALISON trial, but which we also keep in mind for the broader hemato-oncology field. And the other side of the medal is the tumor. And tumors have very different microenvironments. So blood-borne tumors, they are also different amongst each other with respect to dynamics and also sometimes whether or not they're in bone marrow or in other places of the immune system. But generally speaking, there are in a liquid compartment. With solid tumors establishing a microenvironment of their own. So the cancer cells are embedded in the tumor mass and the tumor masses sometimes also infiltrated with other cells that suppress the immune system. So, also in ovarian cancer, we look to go to as low as possible disease setting to hopefully give the immune system in the upper hand in controlling the residual disease. But the tumor microenvironment in a solid tumor is very different, and it also varies a lot from tumor to tumor. So it's hard to predict what exactly will happen. But yes, we always take data-driven decisions. And that is why we have experimented a lot. And now with the fruits being what we start to see in AML, right? And also that was not something that was easy to predict as being potentially successful. So, I think for now, the main focus of the company is where we see the strongest data which will be in hem-onc. And yes, with the other pipeline products, we will just wait and see how they play out, either as monotherapy or maybe potential future combination therapies that we can develop by ourselves or in partnerships, et cetera. But I think the most important message, Christian, is that where we see the strongest data, we will put most of our efforts, which is currently in AML.

Perfect. Certainly looking forward to future additional readouts and business development activities. Erik, thank you so much.

Thanks, Christian.