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

Welcome, and thank you for joining this virtual investor event hosted by Immunicum. My name is Kajsa Söderberg from Direkt Studios, and I will be leading the Q&A session at the end of this event. Now I will give the floor to Sijme Zeilemaker from Immunicum, who is the Head of Communication and IR, and he will explain the event and the agenda.

Thank you, Kajsa, and thank you all for joining us live today or perhaps you're watching this event afterwards. It has been an eventful year for Immunicum with a lot of changes that have occurred. The goal of this event is, therefore, to show you a bit where we stand, where we're heading towards. And of course, also we have the chance to introduce you to some of the -- the new faces to some of you, the updated management team. So for today, on the agenda, we'll be starting off with a company overview that will be given by Erik Manting, our CEO; and Lotta Ferm, our Interim Chief Financial Officer. Then Alex Karlsson-Parra will be continuing. He will show as the Founder and Chief Scientific Officer of the company, the scientific leadership that we have been building and will continue to build. And then last of the team will be Jeroen Rovers as the Chief Medical Officer. And he will, of course, show the clinical results so far, but also the plans moving forward. Now we have, of course, also received some questions over the last few weeks. We've been compiling them and gathering them in some of the more general topics. So they will be answered at the end. We've also been receiving questions from analysts that have been following us. So we're also trying to make sure to address them. And of course, there's still the possibility to ask questions in the live chat. So please do so. We'll try to address as many as possible within the time that we have. So without further ado, I would like to hand over to Erik to start the presentation. Thank you.

Thanks, Sijme. Thank you, everybody, for joining. Also thanks to Direkt for hosting this event. As some of you may know, I joined Immunicum, first as a Director of Business Development; and a deputy CEO, following the merger with DCprime. And today, I'm Immunicum's CEO, and it's a pleasure to address all of you today in that new role, together with the rest of the management team. Immunicum today is a company with complementary therapeutic approaches. Those approaches are based on allogeneic dendritic cell biology, about which I will say a bit more why that is such an important element of connection for the company as a whole. Also, the company has a strong pipeline, which is both in solid and in blood-borne tumors. The pipeline delivers near-term newsflow, but also we have a deep research pipeline that will fuel further pipeline development. The corporate profile has become more international with now a location in the Netherlands and in Sweden, but certainly with the ambition to grow this further into a global biopharmaceutical company. And we have by now realized an integrated organization. About allogeneic dendritic cell biology, what does that mean? Dendritic cells are an important part of the immune system. Basically, they are the cells which tell the immune system to respond to infections to other troublesome events like, for example, cancer. And basically, they send signals to the immune system allowing the immune system to respond to those infections or tumor cells. What is specific about allogeneic dendritic cell biology is that the cells that we apply as a therapy are not from the patient him or herself, but are from another source. And that requires a specific understanding of the biology behind that. And there's other pathways which dendritic cells use besides the exact match with the immune system. And those relate, for example, to the production of pro-inflammatory cytokines, about which Alex will tell a lot more in detail, but it simply means that they activate other cells of the immune system. But also they use other antigen-presenting cells to send their signals to the immune system. Or that's the type of biology which is really specific for the platforms we are working on and where Immunicum is world-leading in its research and certainly, in a combination with DCprime, which is now the combined company, we have a very deep and diverse understanding of what the biology comprehends. There's another side to the allogeneic dendritic cell strategy of the company. And that has to do with the production of this type of products. One of the recent events in cancer immunotherapy is that cell-based therapies have become an important part of the therapy landscape. And those cell-based products are often based on patient material, which means that they have to be harvested from the patient. They have been manipulated into a product and then they have to be given back to that same patient. On the one hand, these therapies like CAR-T, for example, have proven very effective and have really been innovating the cancer therapy landscape. But on the other hand, it's also still held back to a certain extent due to these complex manufacturing and logistic processes associated with them. So a next wave of development is the so-called allogeneic cell-based products, and that is where we are positioned as Immunicum. Ilixadencel is a product which is derived from donor material, which means that a healthy donor donates the cells that form the basis for the product. And next, we are able to manufacture multiple doses out of this donor material, serving multiple patients. So that already is a big step forward in terms of logistics and in terms of manufacturability. But next to that, we also have a platform called DCOne, which is a cell line, combined with the proprietary manufacturing process, which allows for further scaling up and also even more centralized manufacturing because it starts with a central cell bank, which we call a working cell bank, and that is basically the start of the manufacturing process. As an allogeneic cell-based therapy company, I think 2 elements are important to emphasize, which is, first, you need to understand the biology of your products, and that is something specific for each product, and that is where we have strong leading science, both in-house and in our research network. And secondly, you have to have control over your process development. In other words, how you develop the manufacturing of your products. And that is something that we try to integrate as a company into the overall corporate strategy. In terms of the therapeutic positioning of our products, there are 2 important challenges in cancer therapy today. First of all, there are hard-to-treat established tumors. And these tumors either respond poorly to existing cancer therapies or they are tumors that have recurred after initial therapy and have basically become resistant against the original therapy. And this is, of course, the biggest fear of cancer patients that tumor that was treated comes back. Those tumors, but also tumors that are generally unresponsive to current standard of care, require novel approaches. And this is where we have immune primers, ilixadencel, as a possible solution. We administer the product into the tumor where it not only inflames the tumor, and it creates a more susceptible environment for the immune system, but also leads to the release of tumor antigens into the immune system and thereby triggering immune cells to be specific against this specific tumor of the patient. So that is one way to approach the cancer therapy field. The other important element is to prevent tumor recurrence. And that is something which we do with an approach we call relapse vaccination. We do that currently with the product called, DCP-001. This is a vaccine that carries in itself tumor associated antigens, which makes use of the strong immunogenic properties of dendritic cells, and which is injected in the skin, where it triggers an immune response against the residual tumor cells and hopefully, thereby delaying or preventing tumor recurrence. An important element of both ilixadencel and DCP-001 is the excellent safety profile of these products. And this allows for 2 important elements, which is one, positioning in combination with other cancer therapies, which is necessary for these hard-to-treat tumors. And secondly, it allows us to position these products in the maintenance window, which is the phase where patients have been treated with an initial treatment are still at the high-risk of tumor recurrence. But at the same time, not able to bear other very aggressive cancer therapies. And a product with a relatively benign safety profile like DCP-001, for example, could be a great benefit to those patients, again, with the aim to prevent tumor recurrence. The pipeline of Immunicum is the result of long combined research and multiple clinical trials that have been completed or that are currently ongoing. Jeroen Rovers, our Chief Medical Officer, will say more about the details of these trials and the progression of this pipeline going forward. For now, I think it's an important fact that the company has multiple indications as an opportunity to pursue and based on promising initial clinical data. As key value inflection points for the company moving forward, we have 2 clinical studies with an important readout. Again, Jeroen will say more about the details. But one of the studies which is ongoing is the ILIAD study, which we'll read out in the third quarter of this year. And we will provide an update on safety and feasibility out of the trial during the third quarter. The other study, which is ongoing, is the so-called ADVANCE-II study in AML for which we expect to be recruiting all of the patients in this quarter in the second quarter, and we'll provide a more advanced update of the data of that study in the fourth quarter of this year. Of course, research is an important element of any biotechnology company, and I'm particularly proud of the research team, which is now headed by Alex Karlsson-Parra, but also the network of collaborations we have in place that really support us being in the front of the field. But also generating additional ideas to potentially take to the clinic and develop novel therapies that could become part of our future pipeline. Also, we are developing combination approaches with other cancer therapies. And this research basis, therefore, is a very important pillar under the company as a whole. As an ambition, we want to grow into an integrated global biopharmaceutical company. With integrated, I mean, that we try to capture as much as value out of our research, out of our clinical development, but also certainly out of our process development in-house. And that is something we are now able to do with offices in Sweden and facilities in Leiden, which also comprise research and process development, and for which we announced earlier this year, we will also move to a new facility early next year, which will be a center of excellence for this type of research. And that is an important part of creating the value for all stakeholders going forward so that we have more under control, under our own roof. And for example, with respect to our own products, we really capture the value in-house. Of course, it's an international organization with actually people not only from Sweden and the Netherlands, but certainly with 2 locations being Stockholm and Leiden, but also with the ambition to further internationalize the company, including preparing ourselves for a presence in the U.S. Finally, of course, we are listed on NASDAQ Stockholm, and we have a strong investor base, which includes AP4 and Van Herk Investments, who is a renowned European investor that was the shareholder of DCprime and is now the largest-single shareholder in Immunicum. The shareholders will be supportive together with the whole shareholder base and everybody, hopefully, who has been part of the Immunicum shareholder base, and we'll be moving forward and realizing this ambitious goal. About the management team, on March 16 of this year, we announced the new management team. I've said it maybe before, but I'm thankful to Sven Rohmann to making possible the merger of the both companies. We had a rather big management team as a result of the merger. We had to, of course, sort out the CEO role. And this is typically the kind of processes that companies do prior to a merger and then very often the merger doesn't happen because there's too much struggling over this. I think we set a very good example because we believe in this combined company by realizing this process and then taking care in a step-wise process, together with the Board and I would say, with a very positive attitude towards the outcome to make possible the shift towards the new management team. This new management team is, I think, a very competent team. It is lean. It is for people, which is, I think, of sufficient size for the company to provide for strategic and operational directionality. Lotta, our CFO, will tell a bit more about the details of the organization. But for now, I would like to thank everybody involved of being part of this process and leading to the current management team. The same is true for the Board. We have a good mix of people with a medical scientific background and a business background and even also some financial markets expertise. So I couldn't wish for a better Board, but also very importantly there, the Board has really grown together from the 2 companies coming together being DCprime and Immunicum into 1 combined Board for Immunicum as a whole, and they have been very supportive throughout the process. Also a great thanks to them. With that, I would like to hand it over to Lotta Ferm, our CFO, to say a bit more about the organization structure.

Hi. I'm Lotta Ferm, and I'm the CFO of Immunicum. And I've been in the company since February this year. And during this time, we have been working with -- put 2 organizations together to 1 operational unit. So we don't look at it as 2 separate companies. We are working together over the borders. And you see now the picture of the organizational chart. You have the management team. We are 4 members of the management team. It's a lean management team, so we have several responsibilities within the team. So I'm -- for example, I'm heading the Finance department, the HR, also Office and IT. Jeroen, who is CMO, is Head of Clinical, Regulatory and Pharmacovigilance. And then, of course, we have Alex still in the company. He's very important for the company, and he is Head of Research and IP. And then we have Erik, who is the CEO. And he also responsible for Quality, CMC, Business Development and IR. But the teams is mixed from both Holland and Sweden. With the finance, we have been -- put a lot of energy to look which cost synergies we can find out with the new organization. And we have found someone. And we also -- it has also made it possible to in-source some activities, which was still -- which was earlier outsourced. And that's why we now have started to build up CMC operation in Leiden because we think it's important for the company to have control over this process. Cash runway is also an important topic for us. And as it looks now, we have cash into 2022. And of course, financing is something which is high on the agenda for the finance department. And that's something we constantly discuss and evaluate. And we are always looking for the best possible way forward. And of course, we have help from Erik, which is former investment banker. And that's good for the company as well. And one aim with the financing is also to broaden the shareholder base.

Yes. I think that was it for our part of the session. Back to you, Kajsa.

Well, now, we're going to head over to the people that we have on teams. We have Alex Karlsson-Parra, right?

So if we go to the Slide #17, just to show these 2 well-established clinical candidates. First of all, my name is Alex Karlsson-Parra. I'm Chief Scientific Officer at Immunicum. So on Slide 17, 2 well-established clinical candidates, ilixadencel, is a pure immune primer. And we have DCP-001, which actually is an immune primer but also contain tumor-associated antigens, which means that by definition, it's a full-blown vaccine. Next slide, please. So what's the role for anticancer immune primers/adjuvant? And actually, it's to recruit and activate. To make it short, it's to recruit and activate dendritic cells that efficiently cross-present captured tumor antigens to CD8+ T cells. So if you look into the figure to the left, we have the tumor containing tumor antigens. This tumor will be captured by dendritic cells and the tumor antigens will be cross -- we call it cross-presented on the outside of these cells on MHC class I molecules. If the cells become properly activated, they will migrate to the lymph node, where they will educate tumor-specific CD8+ T cells by presenting the antigens to the T cell receptor. Next slide, please. So how to properly activate these into mature and migratory cells that efficiently cross-present or cross-prime CD8+ T cells. I think we have to go to the viral space because it's well-known that viral infection -- strong viral infections, they create strong cytotoxic CD8+ T cell response. I usually mentioned the success of smallpox vaccination, which for me is like the king of vaccines, eradicating smallpox worldwide. And about the mechanism of action, and then you have this figure to the left showing Edward Jenner performing the first vaccination, taking material from the cowpox lesion from this milkmade and transferring it to this poor little boy, 8 years old, who got this inoculation of cowpox into the skin. 6 weeks later, he was challenged with a real smallpox virus and actually, he show to be immune against this infection. So to us years later, Miller et al conducted a clinical study published in Immunity, where they vaccinated healthy persons with this vaccinia vaccine and actually could show this fantastic increase of very specific CD8+ T cells within 2 weeks. So after 2 weeks, you can see it's like 15% of all CD8+ T cells, they are reactive towards the vaccine antigen. And even 3 months later, you still have a substantial number of vaccinia specific T cells in the peripheral blood. And the traditional way to explain this immunological effect is that vaccinia virus or the virus particles that will infect the dendritic cells. By this infection, the dendritic cell will become activated due to the receptors that are recognizing noncell foreign microbial structures. This will lead to maturation and subsequent migration into the draining lymph node where they will present the antigens to CD8+ T cells. However -- next slide, please. So now we are on Slide #22. But when looking into this proposed mechanism, but like 15 years ago or 20 years ago, it was Steinman, the one who got the Nobel Prize for the DC discovery together with Nina Bhardwaj. They were trying to look into the mechanism in the test tube. And what they found was actually that when dendritic cell became infected by the vaccinia virus, they became disabled, those antigen presenting cells. They couldn't migrate. So they continue the work and found out that actually, what happens is that the infected DC produced inflammatory factors that recruits and activates bystander immune cells, including NK cells and what we call bystander DCs. Next slide, 23. So by producing this factor and recruiting NK cells and DCs, the NK cells will become activated. They will kill the infected tissue cells, including dendritic cells, which will lead to release of viral antigens that are captured by the bystander cross-presenting DCs. And these ones that are harboring the antigens, but not deadly infected, they will be the one migrating to the lymph node and cross-presenting the antigens to the CD8+ T cells. Next slide, please. So here in the center, we have this infected DC, this pro-inflammatory DC. And what we are doing, we are -- instead of infecting our ilixadencel DCs with the vaccinia virus, we are stimulating them with a very potent cocktail of inflammatory factors. It's something called Toll-like receptor ligands. Ligands for Toll-like receptor 3, 7 and 8 together with interferon-gamma. And if we take next slide, so if we inject ilixadencel into the tumor, the production of these pro-inflammatory factors will actually neutralize tumor immunosuppressive environment and open up for recruitment of fresh new bystander DCs and NK cells into the injection site. And by activating the NK cells, these will kill locally tumor cells that will lead to release of tumor-associated antigens and tumor-specific antigens. They will be captured by these bystander DCs. And to the right, you see when they subsequently migrate to the lymph nodes, they will then activate the CD8+ tumor-specific T cells, leading finally to eradication of the tumors systemically. So to Slide 26, just shortly, this cocktail is partly developed not by us, I mean, it was presented at least a combination of Poly I:C and R848 in [ immunology ] some years ago. But what you can see is that by combining Poly I:C and R848 to Toll-like receptor ligands and stimulating DCs, you have a huge increase of inflammatory factors, including IL-12, 50 fold increase. And then if we look for all other types of pro-inflammatory factors like chemokines and cytokines, you can see very high production of these factors. So the next Slide 27, just to show what we have a lot of data from [indiscernible] studies showing that ilixadencel induce a huge NK cell activation. They produce a lot of interferon-gamma. They become tumor-killing NK cells. And the factors produced are also affecting bystander DCs by inducing what we call phenotypic maturation of these DCs. Next slide, Please, 28. So ilixadencel has shown promising preclinical efficacy. To the left at the top, you have [ A-II ] tumor model in mice, where you let the tumor grow for 14 days. So you have rather big tumors, 100 cubic millimeters and then you start a treatment. If you have anti-PD1 antibodies, you have no clear-cut effects on tumor progression. However, if you add ilixadencel to PD1, then you see a clear sign of delay of tumor progression. And if you treat with CTLA4, anti-CTLA4, so monotherapy, that has a clear-cut impact on tumor progression. It's clearly delaying tumor progression. And if you add ilixadencel, you have this huge synergy leading to 70% of mice become cured. And the others, they have delayed tumor progression. And when we rechallenging these 70% of mice with the new tumor -- with the same tumor, but at a later time point, they are totally immune against this tumor that will react to it immediately. Then we take Slide Number 29. So now we go to DCP-001 as immune primer and the mechanism of action. So when you are using the DCP-001 as a vaccine or an immune primer, you inject it intradermally. And in this situation, you have an environment that is not immunosuppressive. Instead, you have a lot of tissue-resident memory cells within the epidermis called tissue-resident CD8+ and CD4+ T cells. And they will become activated by the DCP-001 because it's another [ allogeneic cell ]. This reaction will lead to production of inflammatory factors that will actually be the ones recruiting the NK cells and bystander DCs. So in the ilixadencel situation, the DC cells and ilixadencel are producing these inflammatory factors. In this intradermal administration of DCP-001, the DCP-001 indirectly induced this inflammation by activating tissue-resident T cells. And that will lead for -- to recruitment of NK cells and bystander DCs. And since this DCP-001 also contain tumor antigens, they will be captured by the incoming bystander DCs. And these DCs will then mature and migrate to the lymph node, whether we will educate tumor-specific T cells. Next slide, Slide #30. So I mentioned this mixed leukocyte reaction. And here, we have -- what happens if we do it in the test tube. If we combine DCP-001 with [ allogeneic DCs ]. To the left, you can see that the DCP-001s are actually derived from DCOne progenitor cells. So by a specific differentiation and activation of these cells, they start to upregulate all types of well-known co-stimulatory factors like CD70, CD80, CD86, CD40, CD83. So when they are mixed with [ allogenic CDs ], including T cells, they induce a huge proliferation and activation of these cells. And that is exactly what we believe is happening in the skin when we inject the DCP-001 into the skin, unreactive tissue memory cells will react to this injection. Next slide, Slide #31, just to show that the alloreactive T cells that start to proliferate upon recognition of DCP-001, we are just not proliferating. They're also producing a lot of factors. And actually, all kind of factors that are needed for NK cell and DC recruitment and for NK cell and DC activation. Let's see now we have Slide #32. This is just to show from the published data from the first Phase 1 -- started Phase I-II study in AML patients treated with DCP-001 or DCP-001 vaccinations, showing that after vaccination, you could monitor the development or increase of tumor-specific T cells in peripheral blood. And to the left, you can see that you've got increased numbers of T cells recognizing tumor-associated antigens that are actually expressed on DCP-001, indicating that this vaccination led to a tumor-specific immune response. And to the right, we have additional data also showing that this vaccination leads to something called epitope spreading because we also saw increase on tumor-specific T cells that recognize antigens that are only expressed on the tumor that are treated not DCP-001, which is actually a very good sign. And then just to exemplify this in the mouse tumor models in this Slide #33, where compared DCP-001 vaccination with standard of care treatment in humanized mouse model. And as you can see, just monotherapy with DCP-001 is equal to the combined treatment with 5-Aza and Venetoclax. But when you combine these 2 drugs or 3 drugs, you have an even better delay of tumor progression. Slide 34, another model. First, to the left, we have shown that by incubating DCP-001 with T cells from patients with ovarian cancer. This [indiscernible] test indicate that the interaction between DCP-001 and [indiscernible] from these patients induce tumor-specific T cells in the test tube. And to the right, you have a mouse model showing that DCP-001 suppresses tumor growth in a humanized mouse model for ovarian cancer. Okay. So could we use it for more than just vaccination with monotherapy or combined with different drugs? Well, we believe we have interesting data indicating that DCOne could be used as a combination platform for T cell-based therapies. For T cell-based therapies, there is certain challenges. The T cell-based therapies, they are, of course, powerful, have shown great success. But despite the success, there's some challenges remaining and that is due to the durability of clinical responses and manufacturing and relapse, they are common. So 30% to 50% of patients receiving CAR-T are relapsing within a year. Ex vivo and in vivo T cell quality, quantity and persistence are actually major predictors of CAR-T cell failures. And we have actually very interesting data from our preclinical studies, we have data indicating that using DCOne for expansion of T cells and CAR-T cell appears to be a very optimal way to induce CAR-T cells that have a long [ patient ] system, memory T cells that will survive for a long time. And that is most likely due to that DCP-001 is expressing all types of co-stimulatory molecules compared to the expanders that are commonly used now because they used artificial APCs expressing like 1 or 2 co-stimulatory molecules. In our case, we have a cell-based artificial [ lesion ] that is expressing a lot more of co-stimulatory molecules. And we also believe that by combining CAR-T cell treatment with DCP-001 vaccination could have a synergistic effect. Then we go to next slide. And that is actually the deep pipeline expansion opportunities. There's -- Lotta -- I mean Erik presented this lamp with old potential pathways. Saying that therapeutic combination with standard of care cancer therapies, yes, we have data, at least from the ilixadencel studies where we have anecdotal data indicating that when we combine ilixadencel with doxorubicin as we did in the patient with bile duct cancer. This patient responded very well and lived for 41 months instead of expected 11 months. We have a kinase inhibitors, some of these sunitinib and lifirafenib in the GIST study and axitinib in the mRCC study. And actually, we have this preclinical data on hypomethylating agents. And then we could also combine our drugs, of course, with checkpoint inhibitors. We have interesting data from the preclinical mouse tumor models. We have -- we'll get data from the ILIAD study, that is ongoing. And we believe that our drugs or vaccines immune primers could also be combined with antibodies and T-cell engagers. And moreover, there could be synergy when combining, of course, our cells with CAR-T cells and NK cells, moreover improving CAR-T and other adopted cell therapies. I think that the manufacturing of CAR-T cells could be some and very interesting area for our future development. And we're also talking about development of next-generation immune primers. And then, of course, we'll favor, I'm favoring this development of something that you could call ilixadencel 2.0 and mixed-generation ilixadencel. And finally, we have a novel immunotherapy concepts based on tumor independent antigens. And that's actually to vaccinate, to induce a stronger viral -- antiviral response and then to decorate tumors with the viral antigens in order to have this expanding viral specific T cell attacking the tumor that will express the viral antibodies. Yes, I think I'll stop there. Thank you.

Thank you very much, Alex. Now we're going to head over to the Chief Medical Officer, Jeroen Rovers.

Thank you, and it's my pleasure. My name is Jeroen Rovers, and I'm happy to walk you through the clinical pipeline of the company and we go to the first slide. And already expressed by Alex just now, but to reemphasize, I think we've got 2 great products at this clinical stage of development. We have, on the one hand, ilixadencel, which, as Alex explained, is in its mechanism of action. It's an immune primer, which works for solid tumors. And in this case, specifically, it is useful for all those tumors where you can inject the product directly into the tumor. It activates locally the immune system and priming, of course, the whole system, immune system for the tumor antigens, which are present in those tumors. And the studies which have been conducted, have tested this approach already in kidney cancer, in intestinal cancers, in this case, in liver cancer, and we'll come back to that a little bit. On the other hand, we also have DCP-001, which is immune primer which you administer more systemically. So intradermal administration and where you activate then the immune system and you prime it with the tumor-associated antigens, which are already an integrated part of the product. This has been, of course, something you want to use in those cases where you cannot find a bulky tumor to inject into. Hence, also the liquid tumors or in other words, the blood-borne tumors. Studies have been conducted in acute myeloid leukemia, one of these aggressive leukemias, and I'll come back to that one as well. So we'll go to the next slide. And we jump into ilixadencel. So like I said before, so we have an off-the-shelf product. This product is easily distributed. It's stored and then can be injected. It has been already injected into more than 100 patients. And it has shown to be safe and well-tolerated. And it triggers then the immune response to those antigens, which are present within the tumor, which as a result of the immunological response, which is induced, will give you this primer. The proof-of-concept of this has been established by doing a larger randomized Phase II trial in renal cell cancer, which I will just show to you later. I will also through the interactions we have with regulators where we really indicated to be of sufficient interest to give us RMAT Designation, for instance, or other designations. We go to the next slide, please. So I think the audience has been informed on several occasions already about the Phase II study, which the company has conducted and, which is still ongoing with follow-up. So that's the Phase II MERECA study where ilixadencel is combined with a kinase inhibitor, in this case, sunitinib. The study has read out thus far with a more mature data set of a minimum follow-up of 36 months, and that was recently also presented. What we see is that there is 2 major things coming from the study. One is that -- and I'll show you that on the next slide, but the response rates to ilixadencel in combination with sunitinib are better than only treating patients with sunitinib. That's one big advantage. And the other that results in an overall survival, which seems to be extended. So the median overall survival for ilixadencel plus sunitinib treatment arm was almost 36 months versus only 25 months for those patients who were only given sunitinib. The study is still ongoing, like we said, and more survival follow-up data will emerge next year, but it's a promising sign that we have seen this increase in median overall survival for these 10 months. If you combine ilixadencel for these patients with renal cell cancer. And if we go to the next slide. And like I said, I think the major observation already earlier on communicated was that ilixadencel really increases the number of patients which react to the treatment. You see that in the left-hand corner, where ilixadencel plus sunitinib gives an overall response rate of 42% with a certain number of patients who have a complete response meaning there's no disease detectable anymore. Whereas in sunitinib group, there was only an overall response in 24% of the patients, and there were no patients who had complete clearance of their disease. If we look on the right-hand side, of course, we have to always balance that, with potential toxicity you add. And what we've seen in all the studies with ilixadencel and always clearly emerging from this study, which was caused in a larger patient population, is that we do not add any toxicity to other treatments. And on the top one, you see the overall number of adverse events, which is reported, which is not more in the ilixadencel group than sunitinib-only group and specifically the more severe one. So the Grade 3 and the serious adverse events, they do not increase when we add ilixadencel to the treatment of these patients. And that's, like I said earlier, of course, confirms a very benign safety profile, which makes also the treatment easy to combine with other treatment modalities. Can we go to the next slide, please. So that is a positive result from that study. However, study was combined with sunitinib in first-line in renal cell cancer. And over time, the whole, say, treatment landscape of renal cell cancer has changed substantially. And what we see, and that's not only in renal cell, but I think in general, the introduction of immunotherapy is highly effective in a lot of diseases. And in renal cell, this has also resulted in the checkpoint inhibitors. So coming into this first and also second line very rapidly. And what we see in this slide is that if you look at the first line but also the second line, regimens currently used for the metastatic renal cell cancer patients is that the majority of those involved a checkpoint inhibitor. That means that going further into rental cell cancer, you have to be prepared to combine it. And I think the good news for us is that what Alex showed earlier in the presentation, combining ilixadencel cell with a checkpoint inhibitor or a combination of different checkpoint inhibitors is actually even more beneficial and we see the results. In their preclinical model, increased tremendously if we combine ilixadencel with checkpoint inhibitors. But as a good preclinical rationale to do the same for ilixadencel. I think that's where we're going, of course, with the readout of the MERECA study and also the ILIAD, which I'll come back to in a minute, and that has to lead to a further definition of the studies we are planning to do also in the renal sub cancer space. We then go to the next slide because one of the other indications where there's great opportunity for us. That is in the Gastrointestinal Stromal Tumors. So just in short, company has run a Phase I study, and that's the data shown over here in a limited number of patients being six, but interesting enough, of those 6 patients we saw there was a response to treatment in 2 of the 6. And these were patients which have been treated before on the kinase inhibitors to be used. So in first line, that's imatinib, but those patients progressed. So normally, the only opportunity then is to switch from 1H from 1 kinase inhibitor to another, where you hope that the response will come back again. But the majority of patients have a very limited response. This study is also a follow-up, meaning the real survival follow-up will the data will emerge over time. So we have to see if the responses, which we see translates in the durable, say, survival. But that's news to come. But this is one of these indications, which is of great interest. And why? I'll show you in the next slide. So we'll go to the next slide. This landscape in the GIST treatment. It looks, of course, totally different than what I just showed you before in renal cell cancer. In first line, these patients are typically being treated with imatinib as the preferred choice of the TKIs. But if that fails, there's only the possibility to use one of the other TKIs, such as sunitinib, et cetera. So our experience already in combining ilixadencel with sunitinib gives us a great advantage to potentially use, in this case, ilixadencel for the second line in these patients and knowing that the response rates are very low. We know that there's a very high medical needs to improve these response rates. And improve also progression-free survival there. So if we go to the next slide. So those were 2 indications to highlight. And currently, we are awaiting the first results of the ongoing Phase Ib study where we combine ilixadencel with a checkpoint inhibitor. Like I said, I think from the experience in renal cell cancer, it is very important for us to know can we safely combine these 2 immunotherapy approaches. And the answer will follow over summer because we are collecting the data to be further analyzed and hope to report on that, like I said before, in the third quarter of this year. What we are testing, of course, here is if you inject ilixadencel at the same time, when patients are being treated with a checkpoint inhibitor, in this case, specifically, pembrolizumab or KEYTRUDA as a brand name, will that be safe to apply? And I think the reason in the beginning why this study [ recruiting ] quite slow, but also a general concern of regulators that combining different approaches to stimulate your immune system might actually lead to over stimulation or additional toxicity, which is completely unwanted. And that, of course, is why initially patient by patient by patient had to be tested before we were allowed to further enroll multiple patients at the same time for testing. We have reported that all the 21 patients have been recruited. And like I said, we will read this study out in the third quarter of this year. But the main expectation from our side, of course, is that we want to see, can we safely apply ilixadencel in combination with a checkpoint inhibitor. So if we go to the next one. So summarizing this as our clinical strategy for ilixadencel, I think it's a very rich source for us, of course, that we have multiple studies conducted in the past. So 3 Phase I studies completed in renal cell and GIST and in hepatocellular carcinoma with the ongoing, of course, Phase 1 to test the safety of the combination of ilixadencel with a checkpoint inhibitor. Like I said, the Phase II data in renal cell from the MERECA study is giving us a comfort that we see efficacy of this approach. But to apply it in first-line in renal cell, we need to test this potentially in combination with the checkpoint in invertor. So that's one of these options we're currently working on, but we want to wait, of course, confirmation of safety of such a combination, which is we're planning to set up a Phase II study to see whether this initial quite promising result in these 6 patients can be actually generated in a larger group of patients to show that actually, the response rates are increasing if you combine ilixadencel with, in this case, sunitinib. So if you go to the next one. Now we're jumping, of course, from the 1 primer versus solid tumor indications to the primer of, in this case, the blood-borne tumors and residual disease. And DCP-001 is same like ilixadencel tested in more than 100 vaccines, which were given so far. And it has shown also to be very benign in safety profile. And so the side effect profile, DCP-001 is limited to the intradermal injection. And hence, of course, the side effects we see in skin there and luckily not to any systemic effect. It's easy to use. Also this product is delivered to the hospital at the bed side and then inject it into the skin. And we have conducted a Phase I study in AML and currently are running a Phase II study in AML and have just initiated the Phase I in a different indication or variant. So I'll quickly run through those. I think one of the key opportunities for this way of primary immune system and in this case, and specifically of DCP-001 is that if we are able to trigger an immune response, we might be able to gain control over the disease. And in acute myeloid leukemia it's very important. Most of these patients, unfortunately, will relapse. Even if you have a very effective treatment at the beginning, that the disease will not disappear totally. But the only option to get rid of the disease is to, say, replace your immune system by going through a quite hefty procedure or the bone marrow transplant. So the observation is that even if you are treated effectively, the residual disease, which you might still have will indefinitely lead to relapse. But that's also an opportunity where in patients with minimal residual disease, we can actually see whether our approach could reduce that. So can we deepen the responses to any treatment? And by that also prolong, of course, the disease-free period of these patients. So can we go to the next one? So if you look at the whole positioning of DCP-001 in AML, you need to understand a little bit on the complexity of the treatment paradigm patients with acute myeloid leukemia. And I think what is listed over here will not go through all the details. But the key is that once a patient is diagnosed with an aggressive disease, such as AML, you have to treat as soon as you can. And I would always say as hard as you can. So patients are being given high dose of chemotherapy to see whether you can reduce the amount of blasts in the -- in blood to a degree where the disease seems to be initially under control, a definite solution for those patients who will reach an [ initial complete ] remission state has to be done through either consolidating this through additional chemotherapy regimens. And ultimately, like said, by going to a bone marrow transplant. The latter, the bone marrow transplant is unfortunately not available for everyone. And also the procedure is coming with a certain amount of toxicity and mobility, that it's not tolerable for everyone. At least, also quite a large population of patients with an initial response, but not with a definite solution. That's one. I think currently, we are investigating the use of, in this case, the immune priming and DCP-001 to try and trigger an immune response, which will give lasting control over the disease. And so in the maintenance space of this disease. Another proportion of patients cannot even get high dose of chemo because they're not strong enough to tolerate those, and those will be treated with lower intensity regimens and also with hypomethylating agents in these cases. Their response rate, unfortunately, are then lower, and so there's a lot to improve there. So if we go to the next slide. So the company has run a Phase I study in the past, testing the feasibility of this approach in patients with acute myeloid leukemia. 12 patients were recruited and treated, and some patients were in complete remission, which means that the number of blasts which were detected in bone marrow was less than 5%, but there was also half of the population, where the number of blasts were above that limit for those patients who are not under control. The observation was clearly that in this case, the vaccination strategy, where the patient is getting 4 vaccines with 1 week apart. That it led to a disease control in those patients who were vaccinated when the number of, say, blast was low. So when the disease is under control in a complete remittance state, the vaccination seems to increase the survival tremendously, and that's shown on the right-hand side where the relapse-free survival in those patients was 14 months and the median overall survival 36 months, and we want patient even surviving for 71 months. And that's for acute myeloid leukemia. Astonishing results. So if you go to the next slide. And this has led to the current Phase II. So the company is now running an international multi-center Phase II study, where patients are being recruited after initial response to treatment. So they are in a complete remission state. They have still signs of residual cancer, and that's what we call MRD positive. And so those patients have a very poor say prognosis because an MRD-positive state means high-risk of relapse. And what we're targeting is to see does the vaccination DCP-001 has an effect on this MRD status. In other words, are we able to compare those patients from being positive, MRD positive to MRD negative. And that means can we deepen their response? And then also give them a better chance to have a longer period of life without the disease. On top of that, of course, we're testing what kind of immune responses we trigger in those patients when we apply this strategy. So we go to the next slide. And we had some initial data presented end of last year at the annual meeting of the American Society of Hematology. It was presented by Professor van de Loosdrecht from the Amsterdam University Medical Center. We were there able to present on the subset of patients. We have recruited by then 15 patients in this study. And 7 patients, we were able to look at the minimum residual disease and how the vaccination would impact that MRD assessment. And we observed it from those 7 patients, 2 patients became actually MRD negative. And that means that the vaccination led to non-detectable disease anymore, where before the vaccination, the disease was still detectable. And 3 other patients, we actually saw that there was a reduction of the load of detectable disease. But it wasn't just yet at the level where it's deemed to be MRD negative. If we look at, say, the responses, and that's very, very preliminary work, we saw that there was an increase in circulating CD8+ T cells. And like what Alex said, this is what you want to see after vaccination. And we saw some specific responses to the tumor-associated antigens, which we know are carried by the vaccine, WT-1, PRAME & RHAMM. Very promising, but it's a subset. And the study is still recruiting patients. We hope to report before the summer that the enrollment has been completed and to present some more results towards the end of the year when one of these conferences is held again. We go to the next one? So this whole principle, can we take control over residual disease goes further than acute myeloid leukemia. One of these diseases, where we know that this is happening is, for instance, ovarian cancer, thereafter intensive treatment and, say, surgical debulking of the cancer. You cannot say physically see the disease per se, but you know there is probably residual things. And those patients are also very highly likely to relapse, and that's where the relapse vaccination could have a potential effect, and that's what we're testing in the Phase I. So we go to the next slide. And this study has been initiated, and we're waiting for the first patient to be enrolled. It's a single center study with an academic center in Groningen in the Netherlands. And we're looking here for a systemic response to the antigens, which we know are there and see whether that leads to control of recurrence. So we'll be brief on this one. And we hope to report more next year on what the first findings will be from this approach in ovarian cancer patients. So again, to summarize, what is the strategy here for DCP-001. We, of course, will continue to explore this in acute myeloid leukemia, where currently, with the advanced 2 study, still recruiting and delivering this data. That will lead, of course, to a further understanding of what the outcome is of this approach. And helps us to define, say, the further steps there. And the expansion of this program into combining it with modalities such as the hypomethylating agents, or even a combination of these with venetoclax, as shown by Alex preclinical data suggest that if you combine the vaccination with 5-Aza and venetoclax you get even a much better result. That has to be defined after we can read out the initial results of this study. The advantage we have, of course, in the acute myeloid leukemia is that the registration trials might be relatively a small in size due to younger medical need, and we can actually use the surrogate endpoints such as MRD for a potential registration there. And in ovarian cancer, we are at the very early stage. And the data, we'll have to see how we can progress in Phase II with this indication in this application. And I will leave it to that and more than welcome for questions.

Thank you very much, Jeroen, for that presentation. Like you said, it's time for the Q&A session. And thank you guys for sending in so many questions. I will do my best to get answers for them all. And let's begin with quite a summarizing question, and it's going to come to you, Erik. What are your corporate goals for Immunicum?

Well, let me start with a summary of what the most important deliverables are for the company going forward. And that has to do with the execution of the clinical development plan. As Jeroen explained, we have multiple options to take clinical programs forward. We have had quite some interesting data already out of the pinnacle studies that are still ongoing or have been completed. But we also have 2 very important value inflection points and clinical milestones coming up this year, which is, one, the combination of ilixadencel with checkpoint inhibitors, which I think has become clear today, is an essential combination to position ourselves optimally in the broader cancer immunotherapy field. Secondly, we have important data out of the ongoing ADVANCE-II study to hopefully confirm that DCP-001 is a suitable product in the AML maintenance window. So to treat patients that have achieved complete remission, but due to their MRD status are still at a high-risk of tumor recurrence. So 2 very important clinical milestones this year that will support the clinical development of our programs in the future. But next to that, also a very important strategic consideration, which is how we position ourselves optimally in the broader cancer immunotherapy space. And this is a competitive space. So we need to listen carefully to the doctors we work with key opinion leaders or KOLs. We need to keep a good track of what industry parties are doing, who is moving to the front in what indication. And we have to adjust our corporate strategy to that. So to start with that, the clinical development strategy, the execution of that and the positioning of our clinical trials moving forward. It's a very crucial part of our corporate development strategy. Secondly, to build an integrated biopharmaceutical company is also something we have clearly stated to be part of our corporate development strategy. And this is putting together all the expertise we have in the company. But also from the teams that we have and the physical presence that we have, make sure that we have everything in place to take care of our own research, our own process development and potentially also at least part of our future manufacturing. But this is a step-wise and longer-term process with the aim to capture maximum value for the company and its stakeholders. Finally, we are a global company. This is a global business. We have a presence now in 2 European countries. We want to internationalize further. The U.S., for example, is not only an important market, but also a very important country in terms of clinical and nonclinical research. So we certainly also are keeping an eye on that and preparing the company for expanding our presence in the U.S. So that's, in a nutshell, our answer to that question or set of questions you got.

Thanks, Erik. And I can see here in the live chat, that there's a lot of questions about the stock price. And I can say also that since September last year, there's been a drop in by nearly 50%. So I wanted to ask you, Erik, what are your thoughts on the stock price?

Yes. I've also seen quite some questions about that. And I understand the frustration to a certain extent. I also extend, of course, people being disappointed with the share price, and I can also not deny that I'm disappointed by it. The fact of the matter is, the share price is the only thing I can't control. What we can control is to deliver value for the company, which is exactly what we are doing. This is not an overnight thing. So I can't promise anything to happen quick or quick fixes for this. This is really something that requires dedication and execution discipline, which is exactly what we are about. That's one part. And yes, just to also maybe address a few related questions, we saw coming in, Kajsa, about insider participation. I am shareholder, a large part of my personal wealth is in the form of Immunicum shares. Also, Alex has quite a significant shareholding, a few members of the Board, including Dharminder and Sven Andreasson. So I think in that sense, there's multiple people with exposure to the share price. But again, we do not influence it.

Let's move on with the next question. It's about financing, Lotta. What is the financing strategy moving forward?

Yes. We have -- we are financed in until 2022, into 2022. We -- at this stage, we evaluate different ways of financing further. And we will use the best value for the company.

Erik was mentioning in the beginning that you are a global company and that you want to expand maybe into the U.S. Will you seek a new listing on the U.S. NASDAQ.

We are listed in Sweden and Stockholm NASDAQ today, and we are happy about that. And what's more important for us is to broaden and expand our shareholder base. So where we are listed is not that important. But of course, we are considering all different alternatives.

Erik, back to you. Could you talk a little bit more about your business development strategy, please?

Sure. Yes. I think we also saw some questions coming in of that nature. So let me say the following. We keep track of the field. And there's, of course, multiple industry parties, both, let's say, larger pharma companies, but also competitors moving into those indications. We are also active in. So that's one important element. We always keep an eye on. And to a certain extent, that determines our focus and priorities. But I think that is something which is given on a day-to-day basis. Where I think we have an active business development strategy is with respect to the earlier-stage pipeline because we cannot take everything into clinical development ourselves. Sometimes also you need expertise from other companies to create more optimal outcomes. We have a few ongoing collaborations, for example, with PCI Biotech, a Norwegian company; with Glycotope, a German company. And these are all about sort of risk sharing, also opportunity sharing collaborations. And that is, let's say, an active [ BDE ] strategy that we follow. And finally, as Alex explained, we are developing a combination platform for T cell-based therapies. And that could also create additional business development opportunities because that's typically a space that we cannot develop ourselves. It's already quite a mature industry, but where we think we have added value towards the current approaches, and that could also deliver some more business development opportunities.

We're going to move on, and I want to ask, this is about the clinical development plan. So let's ask that question to Jeroen, what exactly are your clinical development plans?

I think what I tried to outline in the presentation is that there is, of course, 2 different strategies for the 2 different pipeline products. But I think we're in a lucky situation that we have 2 products currently in Phase II of its clinical development and where we have the opportunity to get, like Erik said, more mature data during this year. And that, of course, we'll have to need to further say a definition of, which is the most appropriate study also in relationship to what is the field currently showing. And I think for ilixadencel, it's clear that we are very anxious to see if a combination with a checkpoint inhibitor, which will allow further, say, progress into not only renal cell, but also other indications, whether that combination is safe enough to apply. And in the meantime, of course, we will further explore in GIST in combination with sunitinib, we were able to set up a protocol, which feels to the KOLs as well. And in the use of DCP-001, the monotherapy data currently in AML will, of course, show how strong the effect might be of this vaccination approach and whether we can push that forward. So I think in bottom line, I think we are in the lucky situation to have 2 ongoing studies for both products, which will deliver data from which we can further define the way forward for either.

We have also received a question from Niklas from Redeye. This is also addressed to you, Jeroen. He's asking about the ILIAD study. He wants to know what patients have been included so far.

Yes. I think the short answer could be, well, patients who are in need of treatment with checkpoint inhibitors. But I think he's alluding to the potential different indications for which this is being used. We came today, and of course, not to report on that. I mean, like I said, the data is still emerging and only say, in the third quarter, we will report on this study. And that's also when we will, of course, report in more detail on the type of patients enrolled into that study. But I think the major focus and objective, of course, is to see whether this combination is safe and whether there's no additional toxicity if you combine a checkpoint inhibitor and, in this case, immune priming approach with ilixadencel. And I think that's independent to a great extent on which underlying indication is being treated.

We also have a final question to you, Jeroen. This is from Jonas at Edison Healthcare. He's asking if there are any other indications with high relapse rate other than AML and ovarian cancer that you have identified that would be amenable to DCprime's platform?

The answer is yes. I think there's a lot of cancer indications. Unfortunately, where we know that after an initial response to any treatment, there's still a risk of the disease coming back. I think if we look at, for instance, in the hematology/oncology area, we know for sure that there are diseases such as multiple myeloma and other lymphoma-related diseases where this is applicable. And actually, multiple myeloma is something we have already tested DCP-001 in a preclinical study, which was published together with university in Boston, U.S., where we know that combining DCP-001, in this case, with treating patients with multiple myeloma will give you a better result than otherwise. So that is preclinically a goal. But clinically, we have not explored that yet. But these options are there. And the same holds, of course, for say other diseases where residual disease is known to potentially lead to relapses on a short term.

Thank you very much for that, Jeroen. We're going to move on here. We have another question, and this is to Alex, and we -- the people want to know what are the differences in terms of scientific approach between ilixadencel and DCP-001.

Well, as I tried to explain that you should see the ilixadencel as an immune primer actively producing factors that inhibit immunosuppression. So when you inject it into the tumor, it will like inhibit the immunosuppression and open up for recruitment of DCs and NK cells, while DCP-001 is not actually producing a lot of the inflammatory factor itself, but it comes in contact with an allogeneic T cells. We have seen that in the test tube, and we have indication that the same will happen when we inject it into the normal skin, they will meet unreactive memory cells in the epidermis that will lead to production of inflammatory factors. So I can say that basically, ilixadencel is a direct primer and DCP-001 as an indirect primer.

Thank you very much, Alex, for answering my question. And let me have a look at the live chat. There are also quite a lot of questions about the time-to-market. Do you have any comments on that?

Well, I think time-to-market is always difficult to predict in the sense that clinical trials take time and the design of the clinical trials is also determining the development time. There are certain opportunities where we can look into to accelerate the approval of our drugs, and we have already put in place certificates or regulatory documents that help us to, for example, accelerate the approval or get more attention from the regulatory authorities when we want to interact with them, like the RMAT, for example. So I think from that perspective, we are facilitated. But again, it is all about the design of the clinical studies, and you have to do them in the best possible way. And that is something which I think we can provide more clarity on as we move forward and have the critical readouts in place that we expect for this year. But for now, I cannot comment more specifically, Kajsa.

Thank you, Erik, and I look forward to hearing more about that. And thank you guys for tuning in today, and thanks for all the questions in the live chat. Bye-bye.