Mendus AB (publ)

Good afternoon, everyone. Thanks for participating in the Mendes Q1 report of 2024. As a list of company, please pay attention to our disclaimer. To start with Q1, we made significant progress and we were proud to present that progress together with our business partners, ALLG and Northex Biologics. ALLG is our Australian partner, the Australasian Leukemia and Lymphoma Group, with who we are involved in the AML22 cadence trial. And Nordic Biologics is a manufacturing organization based here in Sweden, who are our partner for large-scale manufacturing of our lead product for the DEN cell. We also received, in the first quarter, ethics committee approval to allow for the start of the AML22 cadence trial, which is currently ongoing. And we have progress in our NK cell program, which we presented at the Aeneid Killer Summit, which is a leading conference on that specific topic of NK cell therapies. We were very happy to announce that our major shareholders as well as management and eligible board members announced their intention to execute the warrants that we issued as part of last year's financing. And in the end, we raised roughly 69 million Swedish krona through the exercises that warrants and that provides us with cash runway until the third quarter of 2025 based on our currently planned activities. With VitaDenso, we've taken initial steps towards late-stage development. We reported at the end of last year very positive data about the VitaDenso program in acute myeloid leukemia, and the data were, on the one hand, showing promising survival results, and at the same time also brought together a lot of the immunomonitoring data we collected as part of the trial. And those immunomonitoring data not only supported the mechanism of action of our product, as an immunotherapy that stimulates the immune system to act against residual cancer cells. It was also clearly associated with the clinical benefit we observed in the clinic. So, we were very happy with those data, which we presented at the ASH conference end of last year. Then, together with ALLG, the Australasian Leukemia and Lymphoma Group, we had prepared a trial with oral azacitidine, which is the current standard of care in AML maintenance. and we were awaiting ethics committee approval, which in the end we got in March and allowed us to start the trial. The registration trial, which we are planning to do in AML, is one that we are separately preparing for. So the trial is actually run by AMLG in collaboration with us, but the registration trial is a trial that you have to prepare for as a company-sponsored trial. That is a parallel track, and we are very much encouraged by initial positive feedback we received from the FDA on the steps we have planned towards that path. Also importantly, the manufacturing alliance with Northex Biologics is on track. So we started that collaboration after the summer last year. And now in the meantime, we have established a production facility, which is ready. And also the tech transfer process has started. So we've done the initial training run, including the filling of vials in the first quarter of this year. And now we are continuing with the tech transfer process, and we anticipate to be able to deliver the first GMP batches of Iterden cell based on this large scale production process mid 2025, which will also put us in a position together with the trial preparations to be ready for a pivotal stage trial. About the other pipeline programs, we have an ongoing phase one trial in ovarian cancer. pursuing the same principle we are pursuing in AML, which is after initial treatment, when the tumor burden is relatively low, we try to boost the immune system against residual cancer cells. In this case, it's ovarian cancer patients, which have undergone high-dose chemotherapy in combination with surgery. And then we provide our vaccination scheme of six vaccinations of vitidansel. And the primary endpoints of the trial are safety and immunogenicity in this indication. And we have already reported initial positive data. We will report also in 2024 on the trial, including a primary readout in 2024 second half. Our second clinical stage product is Elixir Denzel. We have been preparing this product to re-enter into the clinic after we had redesigned the manufacturing process, and we are still pursuing that route. It has faced delays. We were initially planning to enter into final negotiations around the trial end of last year. But we had to shift our focus towards another group of clinical centers and potential partners. And this process is currently ongoing. We are pursuing the program and we are aiming to conclude the discussions I just described in the first half of 2024. And then finally, we have a preclinical NK cell program, which we think is very promising because it is based on the expansion of so-called memory NK cells which are strongly associated with clinical benefits in different tumor settings. And so this is a program that could in the future become a new pipeline program based on our in-house research. Ritidansel is positioned as a maintenance therapy. And what is special about maintenance therapy is that it allows patients to stay in a disease-free state longer after initial treatment. And this is addressing one of the major challenges in cancer therapy today. So initial therapies that are, for example, including chemotherapy that address the initial tumor, they are generally successful. But the most deadly tumors, including acute myeloid leukemia or AML, are so deadly because they come back very quickly after initial treatment. Another reason to address low-disease settings is the fact that vitidan cell is an active immunotherapy. It means that it trains the immune system of the patient to build up long-lasting immunity over residual cancer cells. And that active immunity, which you can only build up through the disease itself or via vaccination, just takes time to build up. Usually a couple of weeks, but we're also seeing in our own trial two to four weeks in the first set of vaccinations is enough to start building up the immunity, but it does take some time and the immune system has to be in a good shape to be able to mount such an immune response. And this is building up to the concept which is depicted here, where we try to build up active immunity against residual cancer cells resulting in long-term relapse-free and overall survival for patients. Pilodensil has a competitive product profile. It is a cell-line-based product, which means we can affect scalable manufacturing, which we are currently, of course, carrying out together with Nortex. The nature of the product is so-called off-the-shelf. So we can make large quantities of the product, we store the product frozen, and it's ready to be shipped to hospitals on demand. Also, it's a relatively straightforward product. It can be thawed at bedside and injected via intradermal injection. And the only side effects we have seen is actually redness in the skin where we administer the product, which also supports the motivation of the product as a vaccine. We have a strong regulatory dossier, including an AT&P certificate from the European authorities around our manufacturing process, orphan drug designations in the U.S. and Europe, and a fast drug designation, which we obtained end of last year in the U.S. AML is a devastating disease and is still a largely unresolved disease. The five-year survival has remained largely unchanged, and it's only 30%. The main reason is that unless patients are able to undergo a bone marrow transplant, the disease unavoidably comes back, and disease relapse remains the major barrier to long-term survival in adult AML. Another important element about maintenance therapies is that they have to be safe. And that is one of the elements that we feel makes Svitodensel a very competitive approach. It's the combination of training active immunity to result in long-lasting control over the disease, but also a product with a safety profile that is compatible with the maintenance setting. The current standard of care for AML maintenance is oral azacitidine, and this is one of the data from the registration trial of oral azacitidine. And what you can clearly appreciate is that the blue line, which represents placebo, shows you that patients that have measurable residual disease after their initial chemotherapy relapse very quickly. Actually, the majority of patients relapse already within the first three months. With oral azacitidine, which is a small molecule chemical drug in the tablet form, you see that this curve shifts, and the median relapse-free survival is seven months. but it's still a very disappointing picture with the vast majority of patients relapsing and soon afterwards passing away very quickly. So a lot of room to improve on the current standard of care. What we have done is after a successful phase one, which showed that patients with a low disease burden had a chance of long-term durable remissions after treatment with the VitaDen cell, we started the phase two trial, which is the currently ongoing advanced two trial. And this trial, was comprising six vaccinations of fitodensil in patients that had successfully undergone initial chemotherapy, so were in a first complete remission, but still were diagnosed with measurable residual disease, putting them at a higher risk of relapse. This is the data we presented end of last year at ASH, and what you will appreciate is that after an initial group of patients relapsing and then also passing away relatively quickly, there was a remarkable large group of patients, being 14 out of 20, that was alive at the end of the active trial phase, which was a 70-week trial phase. And the great news we could report end of last year with ashes of those 14 patients were still alive end of last year. We are currently with the majority of patients alive, not at the point where we can determine an overall survival median. We do have a median relapse-free survival at the last readout of two and a half years. The most important part of this set of data is that you start to see durable remissions and durable overall survival in acute myeloid leukemia following treatment with vitidansil. Another important set of data we reported last year is so-called immunomonitoring data, whereby we study the immune system of patients. And first of all, this led to a lot of deeper understanding of how the immune system responds to vitidansil. But also very importantly, we saw that these immune responses correlated with the clinical benefit. And this is a kind of data that we continue to collect and also continue to report on, including this week at the CIMT conference. And this basically documents the immune responses, not only on the level of T cells against specific tumor antigens, but also other parts of the immune system, such as B cells, dendritic cells. And also we saw that, for example, suppressive immune cells were affected by the vitadent cell treatment, leading to lower levels of suppressor cells and increased levels of activated cells. Also, what was clear is that the patients that relapsed, unfortunately, had a very poor immune system and were hardly able to build up immune responses. So that also explains why a subgroup of patients did not respond. Currently, we are addressing patients after high-dose chemo, so the chemo fits patient population. And since oral azacitidine is now the approved drug, That is the first next step we will take. And we are doing this as we speak in collaboration with ALG and AMLM22 cadence trial. This is also the initial patient population that we will prepare a registration trial for. It is clear that also other AML patients will benefit from this treatment. And that is why we also consider to explore additional patient populations, including patients that have undergone a bone marrow transplant but are still at a high risk of relapse if they are still MRD positive, but also a new group of patients which is treated with a new drug called Hunitoclax, leading to more patients in a complete remission in a group of patients that was traditionally deemed chemo unfit, but with much higher remission rates that also creates a patient population that will benefit from maintenance therapy. So the CADENCE trial, as I said, is now starting with Ethic Committee approval out of the way. We have shipped material to Australia. We're starting up the clinical sites. The first phase of the trial will comprise 40 patients, equally divided over azacitidine alone or azacitidine with fitodensil. And then assuming no safety issues, that trial will continue to recruit another 100 patients. So this is a very significant trial in terms of data we expect it will generate of fitodensil in combination with azacitidine. And we're extremely happy do it with allg which is one of the leading research groups in this field worldwide with andrew y as the lead investigator so how does it add up to our strategy for the clinical pipeline i said the advanced to monotherapy trial is still a long-term follow-up so we will continue to monitor the progress of that trial the aml 22 cadence trial is starting and will generate initial data in 2025, and particularly those data will reflect the initial safety, which we can see in that first patient group treated. In parallel, we are preparing for a global registration trial, and that preparation phase will comprise two parts. It's on the one hand coming to a trial design and also interactions with the regulatory authorities that will allow us to come to a trial design that is also seen as the right one by the regulators. We are in regular interactions with both the FDA and EMA. So this part is the preparation phase we will do in-house. Then the other part is the manufacturing, and that is the project we are currently carrying out with Northex Biologics. Again, the facility is up and running. The preparation phase has been concluded, and we are now in the so-called tech transfer phase, which will take us into 2025. and which will release the first large-scale GMP batches hopefully mid-next year. So with that, I will come to the summary and outlook for 2024. Based on the positive data in the ADVANCE-II trial, we are moving forward to late-stage development of idudensal in AML. We have ethics committee approval allowing for the start of the AML22 cadence trial in collaboration with ALLG. We are, as part of the late-stage development strategy, building up a global network of clinical centers. We had already worked with 10 clinical centers in Europe for the ADVANCE-II trial. We have opened the IND in the U.S., allowing us to start trial activities in the U.S. And now also with ALLG, we're opening up a much broader network of clinical centers in Australia and New Zealand and a number of Asian countries. So an important addition to our global clinical trial network. The manufacturing alliance with Northex Biologics, is on track for large-scale manufacturing of VDDenCell for the clinical trial, the registration trial, but in the end also for commercial launch. And we are preparing for pivotal stage readiness based on the trial preparations and large-scale GMP manufacturing expected to be ready in 2025 second half. All developments are supported by a strong regulatory dossier around VDDenCell. And then for the other programs, we expect additional readouts from the Allison Phase 1 trial in ovarian cancer, including the primary analysis in the second half of this year. And we continue to pursue elixir denser as a program, which we want to bring back into the clinic in soft tissue sarcomas. With that, it's the end of my presentation, and we're open for Q&A.

If you wish to ask a question, please dial pound key 5 on your telephone keypad. To enter the queue, if you wish to withdraw your question, please dial pound key 6 on your telephone keypad. The next question comes from Chien-Hun Lee from Pareto Securities. Please go ahead.

Hi, good afternoon. So a few questions from me. Could you elaborate a bit on the timeline of the cadence trials and how would the data be used in registrational trials? Would that be a mainly safety data next year? And does the pivotal trial need to wait for the results for Cadence? Thank you.

Sure. Thanks for joining, Chan. The long story short is, yes, we are expecting some initial safety data from the trial. And that will support, of course, the preparations for phase three registration path. It's not so that we are dependent on the data from the cadence trial to start such a registration trial, but they will support the global registration. I think we are planning to set up the randomized phase three trial.

And the cadence trial does not say interfere with those timelines.

Okay, thank you. Maybe a follow-up question. So for the registrational trial, do you think you would need the same amount of patients as the registrational trial for overall other sites, or you can potentially lower the patient number?

Yeah, I think it's difficult to comment now on exact patient numbers. But if you look at, say, the data as you refer to, I think these are, say, sample sizes which are, say, foreseeable. But it all, of course, depends on the effect sites. And I think when we are, say, more advanced after the interactions also with regulators, we will be able to disclose more details on the potential registration trial.

Okay, got it. Thanks for taking my question.

Thanks, Jan.

The next question comes from Sir Romanef from Edison Group. Please go ahead.

Thank you for taking my question. You know, just to follow on to what Chen asked for the cadence combination trial, I think we have some data for Vividenzo on the monotherapy in MRD-negative patients. Do you think regulators will want to see this data in the later stages of clinical development?

Sorry, Sue. Maybe we can clarify the question. This was around MRD-negative patients, correct?

Yes, yes. So do you think that the regulators will want to see this data in kind of the later stages of the clinical development?

Well, I think just high level, it would go into how exactly we plan for our registration trial. So it would be too detailed to comment on that now. But your observation that the cadence trial also includes MRD negative patients is correct. And the reason is that MRD assessments are such that there's no false positive MRD, right? So when you pick up MRD is there, but there is false negative MRD. So also in the MRD negative patient population, relapse rates and overall survival are still disappointingly low, particularly in patients that cannot be transplanted. So your observation that the cadence trial indeed allows us to explore both patient populations, which we see as a positive, because it will generate a lot more additional data. that is correct whether or not we incorporate that in our late-stage registration trial that is still to be decided and to be disclosed.

Yeah, and also for Vivid Encel, I think in AML we're looking forward to the update for the ovarian cancer program. I've seen that, do you intend to move directly into phase two or do you think you'll need to prioritize for other, you know, for other indications.

Right. Well, I think it's a matter of means and focus, Sue. So when we started this exercise to see if it would be a potential treatment for low disease settings, we cast out the net quite wide, right, which is an AML, which is a very aggressive disease in terms of relapse rates and ovarian cancer, which is also aggressive, but somewhat slower diseases compared to AML. What we are seeing consistently is robust immune responses in both patient populations, and the primary readout of the ovarian cancer trial is actually safety and immunogenicity. So we have already indicated that those data start to look very positive. Whether or not we will see a strong enough clinical effect and also will have, let's say, enough breadth as a company in terms of means that we can put behind different trials and to pursue them, that's obviously still something we need to consider once we have a more, let's say, mature data set from that trial. But we are always taking data-driven decisions, right? So it starts with the fact whether or not we see enough promise in the data to take the program forward, and then we have to balance it with the additional opportunities. And the additional opportunities are not only, let's say, in solid tumor indications for both with the denso and elixir denso, But clearly also we see now the potential of the product to be broader positioned in the hemato-oncology space. So that's a more broader strategic question, which we're currently actively thinking about, obviously.

Okay. And my last question is really, thank you for that. My last question is really more housekeeping. The R&D was a lot higher than I thought it was going to be in the quarter, which kind of makes sense because there's been a lot of activity. What do you think the run rate is going to be going forward?

Well, the simple answer there, Sue, was we are starting up the cadence trial, right? So you will start to see that back in our R&D costs. And with respect to cash runway, we can just repeat what we stated, which is we have cash runway based on currently planned activities. So that includes also the start of the cadence trial until Q3 2025. Okay.

Thank you so much.

Thanks, Sue.

The next question comes from Auntie Siltanen from Indears. Please go ahead.

Good afternoon, and thanks for taking my questions. Some of them were already covered, but I just wanted to have a practical question on the cadence trial. Do you have any estimate or reasonable time frame on when the first 40 patients would be recruited, and also when would be the first readout of the cadence trial?

Yeah, so I think there's two parts to that question, Antti. Thanks for joining. The first part is we are starting of the trial as we speak, which means the material is safely arrived in Australia, luckily. But also, of course, we're starting up the clinical centers. And there's always a kind of hockey stick in the recruitment rate of a trial, right? So the first and most important parts, and that was what we were aiming for when we did the last business update, was to make sure we have ethics committee approval. Right now, we are starting up the trial. It's ALG who's running the trial, so we as a company will not make very specific comments about individual patients being recruited or patient numbers, but we will, together with the ALG, look at regular intervals with which we can monitor the trial. The most important readout we see, and this will also be, to a large extent, the initial benefit we see from the cadence trial, is the safety data in combination with azacitidine. We have limited data with azacitidine, from the phase one, but not in such a structured and randomized control way as we are now seeing from the cadence trial. So that is first and foremost what we're focused on, and that data will come in in the course of next year. I think much more important is then the second stage of the cadence trial, which will, of course, with larger patient numbers, allow us to evaluate the combination in terms of clinical benefits. Okay, thanks very much.

That's all from me for now. Thanks.

The next question comes from Christian Binder from Red Eye. Please go ahead.

Hi, and thanks so much for taking my question. I just have one follow up regarding registrational trials. You already mentioned that you can't elaborate too much right now, but if it's possible, When it comes to trial design, comparing to the second part of CADEN's registrational trial, are there any other key trial design differences that we should expect?

I think, like I said, Christian, we can disclose those details when we have had the interactions also with the authorities. Otherwise, it's preliminary to comment on it. But I think one of the things we could, of course, indicate is that there is the possibility for us to maybe focus on those patients with the highest need, which could be, say, patients which are clearly already positive as what we already selected within the ADVANCE-II study. So that could be one of these considerations from a design perspective to focus on those patients in highest need to show the benefit what we see also currently in ADVANCE-II.

All right, perfect. That was all from my side. Thank you so much.

Thanks, Christian.

The next question comes from Nils Andersson from Private Investor. Please go ahead.

Hello. I have a question regarding the GIST study. You partially answered it earlier in the presentation, but I would like you to elaborate on the answer a little bit. In mid-November last year you announced to the market that the study would start within six weeks. I guess that by that time preparations must have been very advanced and all sites must have been contracted as the study was expected to start in only six weeks. Now six months have passed since then and the study still hasn't started. So can you comment on what happened from mid-November to the end of December?

Right, yes, we put everything in place. Niels, thanks for joining, by the way, and asking your question. To be able to have a trial ready by the year end. And, yeah, in the, let's say, discussions with partners we were involved in at the time, things changed to the event to the extent that we decided to change course. And that related to both the discussions we were having but also more specifically just as an indication was a relatively narrow indication with a relatively large amount of competition. So we have shifted now to the broader soft tissue sarcoma indication, but also we had to find a new possibility to do that trial. And that is the events that came together, let's say end of last year. And that's also why we are now still pursuing that option, but in a different setting as compared to where we were end of last year. That's as much as I can say about it.

Okay. Thank you very much. Thanks.

There are no more questions at this time, so I hand the conference back to the speaker for any written questions and closing comments.

Thanks so much. Also, thanks for everybody joining online who did not ask questions. I think most of the questions that we received today are aligned with what we also saw coming in via our email address. So I think all the main questions have been answered. So back to the operator and have a great weekend, everybody.