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

Welcome to Mendus Q1 report 2024. [Operator Instructions] Now I will hand the conference over to CEO, Erik Manting. Please go ahead.

Good afternoon, everyone, and thanks for participating in the Mendus Q1 report of 2024. As a listed 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 NorthX Biologics. ALLG is our Australian partner, the Australasian Leukemia and Lymphoma Group, with who we are involved in the AMLM22-CADENCE trial, and NorthX Biologics is a manufacturing organization based here in Sweden, who are our partner for large-scale manufacturing of our lead product vididencel. We also received in the first quarter Ethics Committee approval to allow for the start of the AMLM22-CADENCE trial, which is currently ongoing and we have progress in our NK cell program, which we presented at the Innate Killer Summit, which is a leading conference on that specific topic of NK cell therapies. We are 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 SEK 69 million through the exercise of that warrants and that provides us with cash runway until the third quarter of 2025 based on our currently planned activities. Vididencel, we've taken initial steps towards late-stage development. We reported end of last year, very positive data about the vididencel 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 are 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 have 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 company [indiscernible] trial is effectively run by ALLG 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 the initial positive feedback we received from the FDA on the steps we have planned towards that path. Also importantly, the manufacturing alliance with NorthX 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 vididencel 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 I trial in ovarian cancer. It is pursuing the same principle we are pursuing 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 6 vaccinations of vididencel, 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 ilixadencel. We have been preparing this product to reenter 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 benefit in different tumor settings. So this is a program that could in the future become a new pipeline program based on our in-house research. Vididencel 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, also deadly because they come back very quickly after initial treatment. Another reason to address low disease settings is the fact that vididencel 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. It just takes time to build up. Usually a couple of weeks, but we're also seeing in our own trial, 2 to 4 weeks and 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. Vididencel 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 NorthX. 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 that can be stored at bedside and injected by 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 [ motive action ] of the product as a vaccine. We have a strong regulatory dossier, including an [ATMP] certificate from the European authorities around our manufacturing process, orphan drug designations in the U.S. and Europe and a faster designation, which we obtained end of last year in the U.S. AML is devastating disease and is still largely unresolved disease. The 5-year survival has remained largely unchanged and is 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 a major barrier to long-term survival in adult AML. Another important element about maintenance therapy is that they have to be safe. And that is one of the elements that we feel makes vididencel a very competitive approach. It's a combination of training active immunity to result in long-lasting control of the disease, but also a product with a safety profile that is competitable 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 the initial chemotherapy relapse very quickly. Actually, the majority of patients, relapse is already within the first 3 months. With oral azacitidine, which is a small molecule chemical drug in a tablet form, you see that this curve shifts and the median relapse-free survival is 7 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 I, which showed that patients with a low disease burden had a chance of long-term durable remissions after treating -- treatment with vididencel. We started the Phase II trial, which is the currently ongoing ADVANCE II trial. And this trial was comprising 6 vaccinations of vididencel in patients that had successfully undergone initial chemotherapy. So we're in the first complete remission, but still were diagnosed with measurable residual disease, putting them at a high 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 at ASH is that the 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 2.5 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 vididencel. 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 vididencel. 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 [CINT] 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 vididencel 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 we're hardly able to build up immune responses. So that also explains why a set group of patients did not respond. Currently, we are addressing patients after high-dose chemo, so the chemo fit 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's 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 Venetoclax, leading to more patients in the complete remission in a group of patients that was recently deemed chemo-unfit 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 azacytidine alone or azacitidine with vididencel. 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 vididencel in combination with azacitidine, and we're extremely happy to do with ALLG, which is one of the leading research groups in this field worldwide with Andrew Way as the lead investigator. So how does it add up to our strategy for the clinical pipeline? As said, the ADVANCE II monotherapy trial is still a long-term follow-up. So we will continue to monitor the progress of the trial. The AMLM22-CADENCE trial is starting and will generate initial data in 2025, and particularly those data will reflect this initial safety, which we can see in that first patient group treated. In parallel, we are preparing for a global registration trial. And the preparation phase will comprise 2 parts. It's on the one hand, coming through 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 [ capacity wide 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 NorthX Biologics. Again, the facilities up and running, the preparation phase has been concluded, and we are now in so-called tech transfer phase, which will take us into 2025, 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 vididencel in AML. We have Ethics Committee approval allowing for the start of the AMLM22-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 IND in the U.S., allowing us to start trial activities in U.S. And now also with ALLG, we are 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 NorthX Biologics is on track for large-scale manufacturing of vididencel 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 are expected to be ready in 2025 second half. All developments are supported by a strong regulatory dossier around vididencel. And then for the other programs, we expect additional readouts from the ALISON Phase I trial in ovarian cancer, including the primary analysis in the second half of this year. And we continue to pursue ilixadencel 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.

[Operator Instructions] The next question comes from Chien-Hsun Lee from Pareto Securities.

So a few questions from me, could you elaborate a bit on the time line of the CADENCE trials? And how will the data be used in registrational trial? Would that be mainly safety data next year and does pivotal need to wait for the readout for CADENCE?

Sure. Thanks for joining Chien. The long story is -- 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 a Phase III registration path. It's not so that we are dependent on the data from CADENCE trial to start such a registration trial, but they will support the global registration dossier. Also, [Jeroen, do you want to add any statement.]

I think we are planning to set up the randomized Phase III trial and the CADENCE trial does not interfere with those time lines.

Okay. And maybe a follow-up question. So for the registration trial, do you think you will need the same amount of patients as registrational trial for overall [indiscernible] or you can potentially lower the patient number?

Yes, I think it's difficult to comment now on exact patient numbers. But yes, if you look at, say, the data, as you referred to, I think these are, say, sample sizes, which are, say, foreseeable, but it all, of course, depends on the effect size. 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.

The next question comes from Soo Romanoff from Edison Group.

Just a follow-on to what Chien asked for the CADENCE combination trial. I think we have some data for vididencel on the monotherapy and MRD-negative patients. Do you think regulators will want to see this data in the later stages of clinical development.

Sorry, Soo, can you -- maybe we can clarify the question? It 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 will 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 -- to be disclosed.

Yes. And also for vididencel once, I think in AML, we're looking forward to the update for the ovarian cancer program. I seem that do you intend to move directly into Phase II? Or do you think you'll need to prioritize for other indications?