Mendus AB (publ)

Good morning, everyone. Thanks to Mendes Q2 2024 Business Update. My name is Erik Menting, CEO at Mendes, and today I'm joined by our Chief Medical Officer, Jeroen Rovers, and our CFO, Lotta Ferrum. As a summary of the second quarter of 2024, we raised roughly 69 million Swedish krona in April through the exercise of warrants that were associated with the financing that we carried out in 2023. 2023, sorry, with participation of all major shareholders, management and eligible board members. We're very happy with our current shareholder basis and also with the fact that they all contributed to this part of the financing. We also had some board changes and importantly, a new chairman of the board in the person of Sven Andreas von, we're very happy Sven was willing to step up to this role. He is someone with a very broad experience, both in Europe and the US, and has been on both sides in the pharmaceutical industry and the biotech industry, and brings a lot of also business development expertise. So we're happy with Sven as new chairman. Very importantly, in the second quarter, we did a lot of immunological research on the samples we collected in the ADVANCE2 trial. And we presented those data at the CIMT and EHA conferences, and they confirmed proof of concept that Fetidensel acts as an active immunotherapy in AML. And we'll spend some time in the coming slides on what that exactly means. Also, very importantly, we announced in the first quarter a collaboration with the Australasian Leukemia and Lymphoma Group, AOLG, and also ethics committee approval to start the AMLM22 cadence trial, which is a combination trial with our product Fetidensel and current standard of care. Following the ethics committee approval, we immediately engaged in starting up the trial, which means that we ship material to Australia and we work with the clinical centers to make them ready for including patients in this trial. And we'll provide an update in the coming slides. We have, as a very important part under the late-stage development strategy for VD-DenCell, engaged in a manufacturing alliance with North X Biology. which is a manufacturing organization based in Sweden. The reason it's so important is that we need to be ready for large scale production to support our clinical trials going forward and also in the end for commercial launch. And you want that to be the same process. So working with Northex Biologics to establish a large scale manufacturing facility and in the end also large scale GMP manufacturing is something that is a very important pillar under our strategy. And we have in the first half of the year already completed the manufacturing facility, but now also performed the first large scale runs, which we completed successfully as part of setting up this facility. We presented positive data from the Allison trial in ovarian cancer at the asthma gynecological cancers conference. We'll discuss those in detail. And also in July, we announced that we have established a collaboration with ,, which is a leading cancer center in France, to study our intratumoral primer in soft tissue sarcomas. As financial highlights, we have a strong cash position of 130 million sec. which has provided us with cash runway into the third quarter of 2025 based on current activities, which means also the activities we will discuss today. We had a relatively limited cash burn of 22 million Swedish krona in the second quarter. And the reason it is lower than the net result is that the investments that we have made to establish the manufacturing with the manufacturing alliance with Nortex Biologics have been prepaid. So they are as we are progressing that alliance costs, but they don't weigh on our cash burn. And finally, we carried out the reverse stock split, which was resolved at the annual general meeting and effectuated in June. Moving to our lead program, VDDenCell and AML. Acute myeloid leukemia, or AML, is a very aggressive bolt-borne tumor. The only way to suppress it is with very intense chemotherapy. and also there's hardly any cure. The only cure actually or treatment that is potentially curative is completely replacing the patient's immune system with a donor immune system that's called hematopoietic stem cell transplant or bone marrow transplant. The biggest problem with AML is actually relapse due to residual cells and patients that are not able to undergo a transplant are particularly sensitive to relapse and that's related to residual disease or measurable residual disease in short, MRD. And even after transplant, patients relapse. So relapse is also the main reason for transplant failure. Five-year survival is very low in AML, and it means that there is a big need for therapies that will basically maintain disease-free periods for these patients much longer than what's the current situation. So we are developing VD-DenCell as an AML maintenance treatment. It's meant to provide longer periods of relapse and overall survival. And also very importantly, maintenance therapies should be able to deliver this without harming health or quality of life. There's currently no approved immunotherapies in AML. There is a big impact of immune checkpoint inhibitors in solid tumors. It's a class of drugs that does provide for long-term survival in a range of solid tumors, but they have simply not been effective in blood-borne tumors. And that's why there's such a high medical need for new immunotherapies that could address this need for novel maintenance treatments. The ADVANCE-II trial, as a summary, is a trial that was treating 20 AML patients in a first complete remission after high-intensity chemotherapy, but still with measurable residual disease. We treat patients with six intradermal injections of filidenzo, And we did this trial with 10 participating hospitals throughout Europe. The active study phase has already been completed and patients are now in long-term follow-up. This is the data we last presented. It's at a median follow-up of 31.6 months. And what you will appreciate is that a large group of patients is actually in long-term survival. Actually, the majority of patients is still alive in the long-term follow-up. and median relapse-free survival currently stands at two and a half years. What we have now performed in the last months and presented at the CIMT and IHA conferences is a much more detailed analysis of the immune responses following VDDen cell treatment. And what we were able to show is that VDDen cell has a very broad impact on the immune system. We had already in previous presentations at conference has shown that the product leads to T-cell responses against specific tumor-associated antigens like WT1, PRAME, and REM in the majority of patients. But what we were now able to show is that, first of all, there is a difference between patients that respond very well to the treatment and patients that relapse despite the treatment. And that has to do with the baseline health of the immune system. But what we were also able to show is that generally improves the immune status of patients. And finally, and this is the data we presented at IHA last June, we could show that those patients that have good immune responses, meaning T cell responses at multiple time points, but also above median levels of B cells, so the cells that make antibodies, they were all in the long-term survival And this is very important because it provides proof of concept that VDN cell indeed acts as an active immunotherapy in acute myeloid leukemia and that the immune responses are relevant because they result in long-term survival benefits. As a summary of that concept, it's important to understand the difference between active and passive immunity. Active immunity is something your own immune system builds up. It also comes with immunological memory and it provides long-term protection against disease. It's very different from passive immunity, which you get from injecting antibodies or, for example, also immune cells that have been manufactured outside the body. They will deliver an immediate response, but they're not long-lasting. Now, the fact that we see after VDDM cell treatment these broad immune responses associated with durable disease control in the majority of patients is proof of concept that VDDM cell indeed acts as an active immunity, leading to long-term immune protection in, in this case, the majority of patients in the ATRANS2 trial. Currently, the only approved AML maintenance treatment is a drug called oral azacitidine. It's a chemical drug. And what you see here is a picture from the registration trial, phase three trial for oral azacitidine. And what you see is that there is a discrepancy between the placebo treated group, the blue group and the red group. So the azacitidine treated group but it's a temporary difference so that the chemical drug slows down the disease, but it doesn't cure it. There is an attractive side to azacitidine, and this is documented in literature, but azacitidine has an effect on cancer cells and makes them more immunogenic. And that is a good combination with immunotherapy such as 3D-Denso. And therefore, we expect a potential synergistic effect in the combination. And we've also seen initial promising data in our own preclinical work Uh, and also some initial positive data in our Facebook. So there's a good basis to combine. So, in therapy. Uh, and a big step forward, we have set up a collaboration with the oscillation, leukemia, lymphoma group. It's a very renowned clinical research group. It's a big group of Australian and New Zealand-based, but also a few Asian centers that are collectively called ALLG. They were also one of the leading research groups in the trial we previously showed that got oral azacitidine approved. And they have already set up a large trial that allows companies to do research in combination with oral azacitidine. And Mendes is now one of those companies that is working with ALLG And we are combining Hididanzole with oral azacitidine in the AMLM22 cadence trial, or a short cadence trial. The cadence trial is a two-stage trial design. Initially, we aim to open up nine clinical centers in Australia and treat 40 patients for an initial safety analysis of the combination Hididanzole and oral azacitidine. Subject to a positive safety evaluation, that stage will be followed by another 100 patients for efficacy signals. So this is a large trial. We're working with one of the best centers in the world. So we're very happy that we've entered into this collaboration. And what I mentioned earlier in the second quarter, we have been particularly focused on getting the trial up to speed. So following ethics committee approval, the clinical team and the regulatory team has worked closely with the hospitals and the CMC team has made sure that the material is in Australia ready free patients, and we expect the first sites to open in September. Now, it adds up to a path to market that we are preparing for. So we have the monotherapy data, the proof of concept data from ADVANCE2. We are entering into the start of the CASINS trial, and that will deliver a larger set of data in combination with current standard of care, with OLA as cited in. In parallel, we are preparing for pivotal stage development. And the reason we do this is we want this product to be ready for pivotal stage development. We are currently in the preparation phase, which means that we are preparing the eventual registration trial protocol. We're also seeking regular feedback from the regulatory agencies, so the EMA and the FDA. And we want this program to be translated into a clinical trial protocol by mid next year. In parallel, we are developing the large scale manufacturing. So the manufacturing has to be there in order to not only support the trial, but also in the end to allow for commercialization. And we are currently in the implementation phase of moving our process. That is a large scale manufacturing process we have developed at Mendes. to the manufacturing facilities at Northex in Sweden. One of the other things we did in the first half of the year is extensive market research. We looked into the maintenance opportunity for VDM cell in acute myeloid leukemia using both public sources, but also a broad series of interviews with key opinion leaders. doctors, experts in the field in both Europe and the US. We came to an estimated addressable market based on the current therapeutic setting of around 3.7 billion US dollars and this is an indication that the market is sizable. The reason is that the need for maintenance therapies is so broad and also that so far we have not seen any restrictions related to our product in the type of patients we can treat. So it's not limited to, for example, specific mutations. This is really a drug that can address the broader maintenance market and also comes with an attractive market opportunity. And then next to the current setting, which is the setting after chemotherapy, there's also additional maintenance populations that we could address, and that includes the setting post-transplant. Again, also after transplant, there's a lot of relapse. It's actually the main cause of transplant failure in AML. And also there's a new group of patients which is not treated with high-dose chemotherapy, but with a combination of azacitidine and a new drug called Venetoplex. And also those patients now have a better chance of a first complete remission and would require maintenance therapy. So there's a broader market opportunity next to the current already attractive market opportunity. So as a summary and outlook for the AML program, the proof-of-concept data that is a combination of the survival data and the immunotherapy data, sorry, the immunomonitoring data that I just described, support the mode of action of EDM cells and active immunotherapy in AML. We are already in the process of expanding clinical development in combination with current standards of care, or as I cited in the collaboration with and the first sites of the AMLM22 cadence trial will open in September for recruitment of patients. In parallel, we are preparing the registration trial protocol for VDDenCell and AML, including the feedback from regulatory agencies. It's supported this exercise by an already strong regulatory dossier, and we are implementing the large-scale manufacturing in our collaboration with NorthX Biologics. We should be ready or let's say entering the program into late stage clinical development, which is something we can do by ourselves. We're in a partnership. We want the program one way or the other to be ready mid next year. The near term milestones from the AML program are the survival update from the advanced two trial that we expect to announce in the fourth quarter. So we are still following up those patients in the long term follow up phase of the trial. The start of the patient recruitment of the cadence trial with the first sites open in September. Moving to ovarian cancer. As a general principle, we were just interested to see if we could make VitaDentCell work as a product in an indication outside of AML. And we chose ovarian cancer because it's one of the deadliest gynecological diseases, again, due to tumor recurrence. So initial treatment, chemotherapy, and surgery is generally not enough to get rid of the disease. So together with the University Medical Center in Groningen, we've set up a trial with 17 ovarian cancer patients to see if we could trigger relevant immune responses in ovarian cancer. We provided an update of that trial in June at the Asthma and Gynecological Cancers Conference. The trial is fully recruited with 17 patients. And at week 22, the majority of patients that was treated, so 10 out of 17, still had stable disease. The other seven had image-confirmed recurrence. We're following up those patients now in long-term follow-up to see potential clinical benefits from the treatment. What we have established in the meantime is that filidansel is triggering immune responses against a broad range of antigens that have been shown to be relevant for ovarian cancer, and the product also has a confirmed very good safety profile in this indication. The part of immunogenicity and safety is very good, and we also aim to have the primary analysis based on the immunomonitoring of all 17 patients in the fourth quarter of this year. Clinical benefit is dependent on the long-term follow-up, and we will of course also provide updates on how that is developing. As a summary, the safety and feasibility of eludanacel in ovarian cancer is confirmed already in the ongoing phase one trial, the ELISIN trial. The immunomonitoring data are positive. We are seeing tumor-directed immune responses in the majority of patients treated. Primary readout in the fourth quarter based on the immune evaluation of all treated patients and the potential survival benefits dependent on what we will see in the long-term follow-up of these patients, which is ongoing. Then shifting to Elixir Denzel, it was a product that already had shown safety and signs of clinical efficacy in a broad range of hard to treat solid tumors. We had two challenges with the product, which was one, we wanted to improve the manufacturing, which we have taken care of. But secondly, also, we needed to reposition the product. And the main reason was, and that's a broader lesson learned for the field as a whole, the cancer immunotherapy field, is that it is very difficult to improve on the immune checkpoint inhibitors as a class of drugs. Immune checkpoint inhibitors have made a big impact for the cancer immunotherapy field. Then a lot of trials were performed to see if other immunotherapies could improve their efficacy, and that has not materialized. So we need to think different on how to approach solid tumors with immunotherapy. And what we have done with elixirdenzo, which is an intratumoral primer, is we've basically learned all the lessons from the trials we have performed, which is both monotherapy data, but also data in combination with other drugs like tyrosine kinase inhibitors and checkpoint inhibitors. It's safe in those combinations, but also we've taken that other lesson into account, meaning that we were looking for tumors that are currently not responding to immunotherapies, specifically immune checkpoint inhibitors. And soft tissue sarcomas is one of those tumor types that is in that category and which could benefit from elixir den cell as a means to engage the immune system in the treatment of those tumors. in combination potentially with other drugs. That was the background. We have been looking for a long time to do a good quality trial with Elixir Densel to prove this concept in soft tissue sarcomas, and we've now taken a major step in the collaboration with the Institut Bergogne, which we announced last July. I will hand it over to our chief medical officer, Jeroen Rovers, to describe in more detail the collaboration and the trial.

Yeah, thank you, Eric. So it's a pleasure to be able to give a bit of the background of the next clinical trial, which we're initiating in collaboration now with a group of French cancer centers. So they are, say, collaborating in this what we call regimune trial, but I'll give you a bit of the background in the next slide. Again, soft tissue sarcomas, to reiterate what Eric was just saying, is one of these tumors which is still very hard to handle. It's a rare type of tumor. which arises mostly from soft tissue like fat muscles, blood vessels, etc. And typically, they are not discovered at an early stage, but slightly later. So often, they are already, say, metastasized, which makes them even more difficult to handle. When they're small, you can still resect them through a surgical procedure, for instance, or irradiate them. But unfortunately, the majority of these tumors is not, say, eligible for that. So this cancer often recurs. And it's poorly responsive to the available therapies such as chemotherapy. And it also has shown thus far to be poorly responsive to say immunotherapy. So this is typically one of these indications where we feel that the intratumoral immunotherapy approach, which we are able to provide through elixir and cell, might make a difference. So we announced mid-July, so just before the holiday period in most countries, that we are initiating this collaboration with the Institut Bergogne. This is an institute in Bordeaux, France, and I'll show you some of the details later. The collaboration means that we will add a cohort to an existing trial, which is run by Institut Bergogne and several other cancer centers in France. This is the RegImmune trial, and that's a phase one, two trial, where they are combining already two existing and approved drugs in solid tumors, which are Regarafinib, which is a TKI, the tyrosine kinase inhibitor, and Avelimab, which is an immunotherapy. So it's a checkpoint inhibitor, a PD-1L inhibitor in this case specifically. So if we look at the collaboration, then like I said, the Institut Bergogne is one of the leading cancer centers in France. In this case, it's in Bordeaux. um and this trial is a multi-center trial so it's a collaboration of seven major french cancer centers where they are recruiting patients in for different say indications into this regimune trial and in in the trial it the the intent is to see how the combination of a tyrosine kinase inhibitor and a checkpoint inhibitor might improve say cancer results and this trial is already then supported by the providers of these two say, approved drugs. So Regorafenib by Bayer and Merck provides Avelimab. And Mendes will provide, say, Elixir Denzel to set up a cohort where we combine these three products. So it actually means that Elixir Denzel will be administered to soft tissue sarcoma patients twice while they are being also treated with both the TKI Regorafenib and also the checkpoint inhibitor Avelimab. we feel confident that the combination is feasible in applying, based also on the fact that we have already previously conducted clinical trials where we combined elixir and cell with regorafenib, for instance, but also with a checkpoint inhibitor. And the latest of that is, of course, the IDIOT trial, where we combined elixir and cell with a checkpoint inhibitor and shown that it's safe to have these two different immunotherapies work together. So in summary, for elixirin cell, like Eric already explained, we have conducted in the past several clinical trials. It was shown sign of clinical efficacy in typically some hard-to-treat solid tumors like the renal cell cancer. And we're now moving into say, the clinic again with elixirin cell to try to show the effect of elixirin cell in soft tissue sarcoma, which is a very hard-to-treat tumor, as indicated. And the collaboration with the Institute of Burgundy will evaluate this combination, and we will prepare in the next few months, together with Burgundy, for this trial to be, say, this cohort in this trial to be approved so that we can start treating patients next year. And I will hand over back to Eric for the continuation.

Thank you. As concluding remarks, we now see, as a combination of the survival data and the immunomonitoring data, a very important proof of concept for VDDen cell in AML, where it provides a potential solution for a very high medical need for novel maintenance treatments. And particularly important is the fact that VDDen cell acts as an active immunotherapy with a good safety profile that is able to deliver durable clinical responses in AML. That drives us to prepare the program for pivotal stage readiness. That will be an important catalyst for our corporate development, and that includes also the manufacturing side of things, but also it's an important catalyst for potential . for the registration trial to make sure we have the protocol ready and to make sure that the program is ready to enter that phase is currently top of our mind. The market research we performed in the first half of the year confirms the attractiveness of the AML maintenance market for VD Denzel. And also there's a potential to broaden that market potential by addressing additional AML maintenance populations. And then our other pipeline programs which is the ovarian cancer program and the elixir-dense cell clinical program that we described today, but also our preclinical and case cell program are all well positioned to deliver all additional upside. We have multiple milestones until the year end, which is the survival update of the advanced two trials and the long-term follow-up update of the patients in the trial. The start of the patient recruitment in the cadence trial and the primary analysis of the Allison trial, but also in the background, of course, there's a lot more activity ongoing related to our manufacturing alliance and related to the preparations for the pivotal trial for VDT-MSL. So with that, I would like to conclude the update and hand it over for Q&A.