Good afternoon, everyone, welcome to Affimed's Investor Event to discuss our announcement today and the development of AFM13, our CD30-positive lymphoma-targeting immune cell engager at the 64th American Society of Hematology Annual Meeting and Exposition. I'm Alexander Fudukidis, Head of Investor Relations at Affimed. As a reminder, today's webcast is being recorded and the recording will be made available on our website later today. Before we begin, I'd like to remind everyone that we issued two press releases earlier this afternoon. One about our REDIRECT study, the monotherapy study of AFM13 in relapse refractory PTCL patients, and the other about the investigator-sponsored trial of AFM13 in combination with cord blood-derived NK cells in CD30-positive Hodgkin lymphoma and non-Hodgkin lymphoma patients. Both press releases may be found on the investor relations section of our website. On our site, you will also find the presentation which we'll be sharing with you today. Today, we have the following members of our Management Team with Adi Hoess, our Chief Executive Officer, Arndt Schottelius, our Chief Scientific Officer, Denise Mueller, our Chief Business Officer, and Angus Smith, our Chief Financial Officer. Our Chief Medical Officer, Dr. Andreas Harstrick was unfortunately not able to travel to the U.S. to be with you today, with us today because he was ill. Our Chief Operating Officer, Wolfgang Fischer, is joining us virtually. The whole team will be available for Q&A, obviously, after the presentation. Before we start, I'd like to remind you that today's presentations contains projections and forward-looking statements regarding future events. These statements represent our beliefs and assumptions only as of the date of this meeting/call. Except as required by law, we assume no obligation to update these forward-looking statements publicly or to update the reasons why actual results could differ materially from those anticipated in the forward-looking statements. Even if new information becomes available in the future. These forward-looking statements are subject to risks and uncertainties, and actual results may differ materially from those expressed or implied in these statements due to various factors, including but not limited to those identified under section entitled "Risk Factors" in our filings with the SEC, and those identified under the sections entitled "Forward-Looking Statements" in the press releases that we issued today and will be filed with the SEC. The presentation today is video webcast, and you will be able to ask questions by participating in the webcast portion of the call by following the link that we made available to you in our press releases and on our website. You have the option of dialing into the presentation to listen to the call, but in order to ask a question, you will need to submit your questions via the chat function of the webcast. We will first take questions from the people who joined us in our live event here in New Orleans, followed by questions from members of the financial community who are joining us via webcast. I think that covers everything. I will turn the call over to the team to walk you through the presentation. Adi will start. Adi, our Chief Executive Officer, obviously. Yes. Thank you, Alex, and good evening. Thanks for coming by from an exciting ASH. I trust, at least, people who were watching soccer were pretty excited today about what was happening. I was seeing more people outside in the streets watching it with nice weather, and that's how soccer needs to be. We are, however, here in order to give you insights into newest data and also the outlook of what we're gonna do with such data. In our minds, in my mind, for me, I believe it's a very helpful day for patients that are suffering from recurrent lymphoma. We know that these patients are receiving multiple therapies and are undergoing multiple relapses. If you know our vision, it's about speaking not just curing cancer, it's also preventing the derailing of the lives of these patients, but also of the lives of the entire families. What we have been showing today is new data of our monotherapy study of AFM13 in peripheral T-cell lymphoma, that's the REDIRECT study. The second dataset that we presented today or indeed was presented by Dr. Yago Nieto from MD Anderson. He presented the data of AFM13 in combination with natural killer cells, cord blood-derived natural killer cells in mostly Hodgkin lymphoma. Overall, the study is however open to CD30-positive lymphoma, and you're gonna see also the first patients treated in this context. Interesting is when you look at this at the patient population. The recurring tumors that these patients have, and if you look at their history, you can see that these patients are extremely difficult to treat. When they come into a study such as ours, often many therapies have been applied and everything has been exhausted. Obviously we have to accept this as a consequence that the patients are not really having a functional immune system. That's one of the aspects still. We have developed a drug, AFM13 that can recruit NK cells and macrophages, and can activate these cells, and thereby, we are seeing anti-tumor responses. Very important what we learned is that this is a very safe proposition. It appears to have a very well managed safety profile and patients do not really suffer from multiple side effects. That's in contrast to of the many other therapies that these patients have to undergo before. They take chemotherapies, are going through this through these many toxicities that come along with these high-dose chemotherapies and then that. We always need to think about that. These patients, they need to, and they want to live a normal life. Our ambition is to bring these therapies forward, not only make them highly effective, but also bring back to these patients that they can live their normal life. This is why we have been starting to work with investigating the activation of innate immunity many, many years ago. Obviously, with such data that we have presented today, this is very rewarding when you see that you find your way into getting high response rates in patients. Now, after a longer follow-up, we also see that these can be quite durable. Dr. Nieto presented data where he showed that over 90% of patients have an objective response after one cycle of therapy. There's this one dose of NK cells in combination with AFM13 and then three AFM13 monotherapeutic doses. We see already this high response rate, but there are still many patients that have a partial response and not yet a complete response. When we add a second cycle, we see a large number of these responses also becoming complete responses. What was reported today is 70% of patients now have a complete response. What, in my mind, very interesting is when you look at these data, we have here a comparison. On the one side of AFM13 monotherapy, it's active as a single agent. It's modestly active. Around 20% of patients show a response. Very few have a complete response. We have studied that very intensely, tried to understand what is the reason that some patients can respond and others not, and it all came down to two reasons. It's a dysfunctional NK cell compartment, but also low numbers of natural killer cells. In essence, if you have a technology that's bispecific, can connect cells, but doesn't have enough effectors, you know that you will only see limited activities. Still, it was very safe, but there was a very, very important second learning. It's not just that we activate the innate immune system. We have now evidence with additional drugs that you also can activate the adaptive immune system. Some early study we have done with AFM13 was combining AFM13 with a checkpoint PD-1 inhibitor. The idea is that AFM13 is preparing kind of the attack in the tumor by delivering not only NK cells but also T cells, and then you set it free with a checkpoint, in this case, PD-1. Our results, this was a study where we tested, investigated, this combination, 24 patients, showed that we indeed double the complete response rates of Keytruda. It went up from 20% to the mid-forties. To the very right on this graph, you see now the newest data with a very high response rate that I just mentioned. What we saw in peripheral T-cell lymphoma, Arndt will guide you through that, is that we also have single-agent efficacy. In a very heterogeneous patient population, peripheral T-cell lymphoma comprises many, many sub-indications. We are seeing, again, single-agent efficacy of about 30% and again, 10% have a complete response. Here for us the picture is emerging. We can use the efficacy of the monotherapy, the activity of the monotherapy, and now in principle, beef it up either with a checkpoint or with a cell, NK cell. That's what we have said earlier today. This will be the strategy of the future for AFM13. We will entirely focus our development on the combination of AFM13 plus natural killer cells. Are we moving? Important is now to understand the two indications that we are pursuing. I will show you later that there are multiple indications that are CD30- positive. The two indications we have been focusing on mostly in the past years was either Hodgkin lymphoma or peripheral T-cell lymphoma. We have been investigating patients only that had undergone all standard therapies plus additional therapies. That means for Hodgkin, it's frontline chemo, it's brentuximab vedotin, it's PD-1. Once all that is exhausted, we see such patients and then we treat them with, as described before, with a cell and a mix of AFM13 monotherapy. That's where we wanna focus on. With the benefit we're seeing at the moment, we believe that this could be sufficient for a registration-directed study. That's what we plan to initiate as a as a next step. We've already mentioned that we've been applying for a meeting at FDA, a Type B meeting. We are expecting feedback in the first quarter of early in the first quarter of next year. We got pushed out a little bit. With what we're assuming positive feedback, we can file the IND in the first half of next year. The same is planned for peripheral T-cell lymphoma. Indeed, peripheral T-cell lymphoma is already part of this clinical study that we intend to initiate with in Hodgkin lymphoma. In parallel, we will investigate Hodgkin lymphoma and peripheral T-cell lymphoma with a mix of a combination of AFM13 plus the cell and always AFM13 monotherapy. Now, you're realizing I'm mentioning AFM13 monotherapy being part of our clinical, being part of our clinical strategy. The data that we're seeing in these studies in Hodgkin and peripheral T-cell lymphoma are obviously very important to inform us that we can not only activate donor-derived cells, but we can also activate patients own NK cells. In the therapy that we're doing, we believe this is important and can be an important contributor. This sets us up for initiating now the studies in the what's called later lines. In Hodgkin, it will be 3+ lines. In peripheral T-cell lymphoma, it will be 2+ lines of therapies. Eventually, we are planning to move to earlier lines, but the focus at the moment is to get the studies up and running where we believe we can do this with a registrational intent. The market opportunity, we believe, is quite meaningful. That's shown on the next slide. Overall, we see in the U.S., in the main major European countries, but also Japan, about close to 50,000 patients that are annually diagnosed with CD30- positive lymphoma. Obviously, there are more lymphoma patients out there, but it's 50,000, close to 50,000 patients that are annually diagnosed. Many of them, indeed, end up still in the relapsed refractory case. About a third of these patients require additional treatments. Once you are there, it becomes tricky for these patients because very often at that stage, you're not really curable anymore. As you can see, we're focusing on peripheral T-cell lymphoma and Hodgkin lymphoma. Those two relapse refractory groups comprise about 10,000 patients. Essentially, that's where we focus on in terms of T-cell lymphoma, but also cutaneous T-cell lymphoma. We also have ambitions to run earlier, stage studies. The focus where we are aiming for, registration will be, peripheral T-cell lymphoma and Hodgkin lymphoma. This, I'll hand over to Arndt to now give you the details of the two clinical studies that we press released today. Thank you, Adi. Also from me, very warm welcome. It sometimes may get a little loud because we're close to the street, so hopefully at the right moments here. Let me see if this works. Okay. Just as a reminder, you know, I think everybody in the room realizes that PTCL is a really difficult-to-treat patient population with a high medical need, limited treatment options, and very poor survival outcomes. When you look at the treatment options in second line, as you know, this includes combination chemotherapy that may also include brentuximab vedotin. Patients in second line and beyond that have a dismal prognosis with a PFS around two to three months and survival around six to seven months, as you can see on the graph on the right-hand side. With that backdrop, let me go through the design of the REDIRECT study, monotherapy AFM13 in PTCL. Very pleased to present those results. A key inclusion criteria, as you can see on the slide, was CD30 expression demonstrated by immunohistochemistry. Patients must have received at least one prior line of systemic therapy. They could have also received more than one prior line. Patients with systemic anaplastic large cell lymphoma histology were also required to have failed or be intolerant to previous production of vedotin. The primary outcome activity was assessed by independent review committee. Initially, we had actually started with two independent cohorts with high and lower CD30 expression. Just remember at the time when we started the study, there was actually no clinical available with low CD30 expression out there. As you know, after the planned interim analysis with 20 patients per cohort, these cohorts were combined because we saw very comparable activity in both of these cohorts. Here's the music. I'm not sure if it's fitting right here, but we'll go with it. It's nice song, actually. When we go with the baseline and demographics, let me just review this. This was a heavily treated patient population. Noteworthy is the relatively high percentage of previous brentuximab vedotin treatment, 46% of patients. This is really clearly different from studies from [inaudible], where basically there was no previous brentuximab vedotin, of course then, and not yet approved. On the next slide, we'll go through the responses that we had seen. Actually one back. Okay. What we have observed is a really robust clinical activity with an overall response rate of 32.4%. This is, I will show you this in the context with the other approved therapies of PTCL at the upper end, what you would expect with other relapsed refractory PTCL therapies, which are usually around 25%-29%. We saw that the PFS at 3.5 months, very comparable with other relapsed refractory PTCL therapies, and we think very encouraging. We saw an overall response rate of 13.8 months, and the duration of response was at 2.3 months. If we look at the safety profile. Next slide, please. Let me just advance this. Could you advance the next one or, yeah, thank you very much. The safety profile was clearly well managed with drug-related serious adverse events of 8% and treatment emergent adverse events leading to discontinuation of 12%, which is clearly below the levels observed for other approved agents in relapsed refractory PTCLs. The IRRs that we've seen are occurring roughly one-third of the patients. They were all manageable, very well manageable with symptomatic treatments such as interruption infusion, antipyretics, or a fluid substitution. The next slide. Let me put that in the context of other approved and previously approved therapies in PTCL. What does this mean? What are we seeing? We see clearly a robust response rate, good safety profile as a novel mechanism of action. What we see when you compare to the other therapies, clearly the opportunity to build on these results with the combination with NK cells. We will thus focus our further development of PTCL on the combination with NK cells, where the strong synergy was demonstrated in Hodgkin lymphoma, and we'll review those data as updated today. The next slide, let me move to the update, the AFM13-104 study. One slide further, please. Which, as you know, was the first study to really combine an innate cell engager with allogeneic NK cells and in CD30-positive lymphomas. Let me just briefly start with briefly reviewing the objectives and the design of the study. The initial phase I was, as presented previously, consisted of dose escalation parts with three cohorts. This established 1 times 10 to the 8th NK cells as the recommended phase II dose. Today, though, we will focus on the expansion of this dose as it was designed, which was designed to describe the activity. Patients received a single dose of AFM13 pre-complexed NK cells, which was followed by three weekly doses of free AFM13, as you can see on the design. As we had, as you know, as previously described, seen monotherapy activity, the single agent activity, this could now further enhance the efficacy after the cell infusion. As you can also see, we are using a moderate dose of only 300 mg per meter square of cyclophosphamide, where many other programs are using 500. Why is that important? Because we believe this enables us to give multiple rounds of lymph depletion. As you will see, actually the study started with allowing two cycles. With the new protocol after patient 19, up to four cycles. There's good actually precedent in the literature in CLL, where a dose of 250 mg per meter square cyclophosphamide was being able to give up to 6 times with really any serious side effects. The first patients, 19 patients, as I just pointed out, were limited to receive two cycles. The protocol was amended to receive up to four cycles. This study is in progress and the data of four cycle is not mature yet, as we will review. The study is actively as on the lower end of the slide here, recruiting into the two expansion cohorts up to a total of 40 patients. One cohort with Hodgkin lymphoma patients and one with CD30- positive lymphoma, lymphomas at the cell dose recommended phase II dose 1 times 10 to the 8th AFM13 pre-complexed NK cells. Now let's go to the patient population. It's reviewed here. Again, you can see here a heavily pre-treated patient populations. All patients were pre-treated with BV, and all patients except of two had also previous PD-1. In addition, quite remarkable, more than 75% of patients had previous stem cell transplant, and four patients had previous CD30 T-cell therapy. Importantly, all of the patients had not previously responded to their previous line of therapy, which of course characterizes a very bad prognosis for these patients. Let me summarize the antitumor activity in the next slide. When we review the antitumor activity study, we observed an outstandingly high overall response rate of 97% in Hodgkin lymphoma. The CR rate in Hodgkin lymphoma is now at 77%. Remember when we did the last updated ASCR, patients were only able to receive two cycles. We reported a complete response rate of 62%, now up to 77%. While the experience in non-Hodgkin lymphoma is still limited, so far we have four patients that have been treated. The antitumor activity of these patients is very encouraging, with an overall response rate of 75%, complete response rate of 25%. One patient of those four incomplete remission, that patient is a PTCL patient. Very encouraging. It's also remarkable that all four patients previously on CAR T-cell therapy had a complete response on this study. I would also like to highlight that nine patients with a PR during the first cycle actually converted into complete response after the second cycle. Really that demonstrating that additional cycles are able to deepen the response. Very important. Now, let's come to the outcomes. The median follow-up of seven months. As you can see that the median follow-up of seven months at the recommended phase II dose at six months is 61%. As you can also see the event-free survival on the graph beyond six months is still immature. Many patients of these have an ongoing response. You see that kind of with the tick marks between zero and six months. The overall survival in these patients at six months was 85%. In terms of looking at the durability of responses, on this slide, quite a busy slide with the swimmer plot, many errors indicating of course that there many patients have an ongoing response. The message, the slide is that the patients with a CR, it appears durable. Indeed, 17 of 25 patients with a CR have an ongoing CR, several responses out to 12 months. We also see a 63% CR rate at six months in the 24 patients with at least 6 months of a follow-up. When we look at the lower part of the slide, you can see, becomes clear follow-up is still needed. It's still relatively short, and responses are still ongoing. We will now have a look at those patients with a longer follow-up at the next slide. With a nice jazz music in the background. Bourbon Street is maybe moving closer here, kinda. Importantly, when we look at the 13 patients treated at the recommended phase II dose with only two cycles, four of the eight CRs lasted for at least 12 months of the initial therapy. Three are still ongoing, Three patients with a complete response received consolidating stem cell transplant. Remarkably, we have one patient from dose level one, which is not shown on this slide, who now is in response for almost two years. We go to the next slide. Safety, remarkably well managed. The combination of cord blood derived NK cells, very good safety. No cases of cytokine release syndrome, neurotoxicity or graft versus host disease. A very low rate, mostly mild infusion related reactions. Moderate myelotoxicity after lymphodepletion, with no cases of bleeding and only one case of neutropenic fever. Importantly, also no dose-limiting toxicities observed. In closing, let me just summarize. Results of this study really reinforce our strategy to address the unmet needs in Hodgkin lymphoma by focusing on further development of 13 in combination with NK cells. The study, as you've just seen, shows remarkable clinical results, high overall response rate, complete response rate and durable responses. The encouraging six months durability of 63%, with several responses lasting more than 12 months. We've also seen CD30- positive NHL patients also benefit with the first PTCL patient showing a complete response. Our goal is now to expedite clinical development 13 with NK cells to make this treatment more broadly available to patients with no other treatment options. With that, I'll be glad to hand over to Adi to discuss the further treatment strategy of AFM13 and start, stop with closing thoughts. Thanks a lot, Arndt. Yeah, innate immunity is upcoming. We see it here with the data today. We also see other companies that are developing CAR NK approaches. There's quite some significant investment ongoing into this area. What we are learning is in my mind, that the redosing of patients, in particular bringing on this allogeneic NK cells It's not only a novel approach, but also an approach which I said in the beginning could be very helpful for patients. Here are the two achievements. The one achievement is we have established monotherapy in the indications investigated with AFM13, both in Hodgkin and in peripheral T-cell lymphoma. At the same time, we are seeing and confirming the results, the early results in the combination of AFM13 with natural killer cells, meaning that the first responses were still a surprise to us that that could be the case, and then it continued, and it continued, and continued. It was just like massive to see that you can take patients that are very sick, even patients out of a hospice, and can bring them forward into responses. The goal is to bring the two learnings together, which is setting up the studies that I described earlier. We will do this in partnership with Artiva, a deal that we announced about four weeks ago. Artiva, as you may be aware, is a company that is developing a cord blood-derived NK cell. I'll show you in a minute what drove us in order to work together with Artiva. Important is where do we stand with this approach? We already requested a Type B meeting at FDA back in September. We have the briefing books all has been submitted. We're now expecting feedback, as I said, early next year, in the first quarter of next year. That will give us then the opportunity to file for the IND and then get the studies up and running. Again, just to remind you, currently we're working with a cell, cord blood-derived cell, produced at MD Anderson, that's produced at a small scale. Indeed, it's also a fresh product. We knew that eventually we need to move forward and have a product that's really off-the-shelf, meaning it's cryopreserved. We had looked broadly into all options out there that are currently developed. We learned that the most important driver in terms of why a cell is really synergistic with our engagements is the expression of CD16. The expression of CD16 on the Artiva cell on AB101 is very high. Arndt knows the accurate number, but I believe it's in the range of 90%, so it's really one of the highest expressor of CD16. It's manufactured at a large scale, so at the moment we can make a handful of doses at MD Anderson and treat the patients. They can make thousands of doses with a single manufacturing run. Important, we were studying not only this cell, but also other cells, checking for their viability in a variety of assays. A long time, we already entered into a collaboration with Artiva. We had already a two-year ongoing collaboration where we could learn how this cell is really functioning and it serves really well. It is producing very nice in vitro results, as I said, based on the high expression of CD16, based on a particular phenotype that they are generating. It's a strong killer, and you can see this on the right side when you look at the animal studies that we have been conducting. With the combination of AFM13 and AB-101, you're pretty much wiping out the tumors in these animals. It's a highly active cell, and it's investigated in the clinic, so it has an open IND. They have treated already a good number of patients, so we know about the safety profile. This, for us, sounded like an ideal partnership, and we were very happy to have announced this a couple of weeks ago. That, I guess, brings me to the very end of this presentation. We've shown to you that CD30-positive lymphoma is an indication with high medical need, a substantial patient number out there. We have been working very hard in order to come up with this data today, in particular, the combination of AFM13 plus the NK cells. The profile we have is a little different to what you can do with an engineered cell. The beauty is we're not engineering the cell, so it comes in as is from cord blood derive. You activate it, you basically amplify it, then we can use it as it is. That's a big advantage. We have worked in testing it as a pre-complex cell, but also co-administered. All these work equally well, there's no difference if you take the one or the other variation of it. It worked a lot faster for us to move forward when we decided to go for the co-administration way because to develop a pre-complex product would have taken, again, a longer while. Speed was of essence, and we could eliminate the risk by investigating all this preclinically. As we have said, the monotherapy activity is still important for us in Hodgkin and in T-cell lymphoma for the reason that we intend to give not only a single shot of cells with AFM13, but multiple. At the moment, there are either three or four infusions possible. We're using the monotherapy again to drive back in the patient's own NK cells and macrophages in order to then have an effect on the durability. What Yago showed today very nicely when they analyzed the cells in the patient, so they can distinguish the donor-derived cells from the patient's own NK cells, and then they checked for the presence of AFM13. Indeed, you'll find AFM13 bound not only to the donor-derived cells, but they also are occupying and strongly binding to the patient's own NK cells. That distinguishes us from what you can do with engineered cells. We have a different strategy, and thereby we can prolong those cycles beyond what is four weeks. We believe that these cycles will be probably twice as long. That's what we are discussing with FDA, and then we can either come with three or four cycles. This brings me to the end. I wanna thank you for your attention, for being here, listening to us and seeing our data on AFM13. Thank you very much. Thank you. We'll take some questions from the people in the room now. All right. May I ask you to please identify yourself and the firm that you're with or the bank? All right. Thank you. Daina Graybosch from SVB Securities. Good. I have some questions on the T-cell lymphoma data, particularly the duration of response. It's notable that the duration of response seems lower than one might infer from the PFS and OS. I wonder if you could tell us the range of duration of response. Are we seeing, you know, a long tail of longer duration? Whether you have this data split by CD30 expression. Thank you, Daina. The split is, not sure if it's on the slide. I mean, there was some, have to look that up actually. We have not done the analysis yet with CD30. A lot of the analysis is actually ongoing. We plan to present those results. You're right. The 2.3 months is, in a way, lower than one could expect with the other PFS and overall survival data that we have seen. You know, one of the explanations that we have, as we know from Hodgkin lymphoma, innate immunity is not fully functional. We have studied that ourselves. It's described in the literature. We think that's very similar in PTCL, that while there is a good single agent antitumor activity, that the duration of response, in a way, is hampered by the non-existing innate immune system. Which kind of further for us, makes a good argument to really combine with allogeneic NK cells. The other part of your question is if we see a longer-lasting responses. Yes, there are patients in there. We're gonna publish all that at a medical conference. That's why we have limited data available today in order to reserve it, because there is a lot more information obviously available that we're then gonna share at one of the next major conferences. Daina, do you have a follow-up question? Here you go. Thank you so much for taking my question. Kripa from Truist Securities. One of the things that immediately pops up is timelines. You know, people were expecting if this were to look as good as the expectations were for the monotherapy, that you would take it forward, and now you're going to have to wait a little bit longer with the pivotal. Can we have a sense of what the timelines for a confirmatory trial could be? The second question from Dr. Nieto's presentation was, one of the things he talked about from a safety perspective was that with multiple cycles of lymphodepletion that you're seeing, I think, accumulating thrombocytopenia, is there anything that, in terms of the gap between the timing between the lymphodepletions that you could do to reduce that? Yeah. Thank you. On the latter thing is obviously we're just learning this. We have now started to treat the first patients with three and four cycles. This is clearly in the observational period. We'll again, with the next presentation at one of the major conferences, we can provide an update there. In terms of timing, obviously, we have said that we're gonna wait for the feedback of FDA. If, as mentioned earlier, our plan is to have the IND filed in the first half of this year and then move forward. To your question about moving forward with monotherapy or moving forward with the NK cell, it's very clear that the NK cell has much of an upside. We're not gonna start a confirmatory study, obviously, because in peripheral T-cell lymphoma, others have tried it's gonna take very long. What we want to do is now move forward with the NK cell and bring this, as I said, forward not only in Hodgkin, but also in PT cell. The study that we intend to do will cover both, will cover both indications. On this way forward, we are currently looking into the best option where we would run a confirmatory study. As I said before, we have synergy with a checkpoint inhibitor. In particular, pembrolizumab and nivolumab are available in Hodgkin lymphoma. These are potential options that we're currently evaluating. The focus will be entirely on the cell combination. Yes, we're in the meantime, obviously, addressing this to move forward very fast with the NK cell combination. The cryopreserved will allow us, so the cryopreserved cell will allow us not just to work in tertiary hospitals, but also go to community centers. We have to see on how that all will be set up and executed, but we believe that we can get to patients in a different manner, not just through the major hospitals. Initially, we are focusing in the U.S. We are currently working with Artiva also to bring it over into Europe, their cell, and then we can broaden these clinical studies from the U.S. also into Europe. There is a broad activity behind that in order to make this happen. In terms of timelines, we can't say because we also need to learn about the patient number that we have to do. This could be as low as 60, but also could be as high as 100, similar to what we have done. All these will be factors that are contributing, but we should have this information pretty soon. Just to add, Kripa, quickly, as you rightly noticed, with increasing cycles, neutrophils kind of, you know, stayed, but thrombocytes are slightly lower. Importantly, we have not seen any events of bleeding, as Yago Nieto also said, there's no functional relevance to them. Just one quick follow-up question. Given what you've seen with the AFM13, do you think with the rest of your assets, you will have to see whether it was a monotherapy or is now the understanding that you will need the combination of? Yeah. Or Yeah. Yeah. Every indication is a new start. Every molecule is a new start. We can speculate about that and, but we don't know it. That's why we are investigating AFM24 as the next asset in development. We're currently running the phase I, phase II in as monotherapy. Again, we'll have an idea. We have picked two indications where we believe we have a higher chance of seeing single agent efficacy, which is lung and renal. If things go as planned, we're gonna have readouts next year, through 2023. We have now a third asset that will move towards clinical studies, which is AFM28 targeting CD123, so we're in leukemia. Again, this will be investigated initially as a single agent to learn about the single agent efficacy. We always need that, okay? That is the basis that you're going to be asked anytime and dependent on the response rates. Again, in leukemia, our ambition is also to move forward with the NK cell. Leukemic cells are sensitive to natural killer cells, in particular, donor-derived. They usually show an efficacy already of 30%, 40%. Again, here durability is okay with, let's call it naked cell, non-modified cell. Coming up, coming in with an engager, mixing it with the NK cell can drive up hopefully the efficacy, but also then create the respective durability. You see the cell will play a major role. It's different than what it was like two, four years ago. We always have to understand that the NK cell field is a novel field. Many companies have recently started developing their product at scale. This is why now is the right time to think broader, and this is why we could make the step. Even if we would have wanted to do this two years ago, there was just no cell product out there in order to move forward, and that's changing. Essentially, I believe that there will be cells on the market in some future time, and any immune cell engager will take the advantage of basically using the synergy between these two drugs. Thank you. All right. Thanks for the update. Li Watsek from Cantor. I guess, can you talk a little bit about your plan maybe to share the monotherapy data with the agency? How do you think it can address maybe the question of contribution of parts, with this data set for your NK combo, given the relatively short, duration of response? Yeah, great question. Thank you, Li. Obviously, as Adi said, we have a pre-IND meeting package be submitted. We'll get a written response beginning of the year, as we said. We will then, also fully engage with the agency, sharing all of the data. I think where you're getting is, you know, what does the relatively short duration of response contribute? I mean, what we see, maybe just to reiterate, I think we feel we see robust single agent activity as antitumor activity. There is limited durability that from today's perspective, we think is better served with the combination of NK cells, and that will be a discussion with the agency. I mean, from our perspective, we are clear the direction that we want to go. I think your question is how will the agency kind of see the contribution? I mean, I would say from my perspective, that's why we wanted to give you also the benchmark. You know, in most of the parameters, actually, there is a good comparison, which we believe is a really excellent foundation to build further with the combination of NK cells. It's, as I introduced, it's a mix between looking at the clinical utility of AFM13 mono and the market opportunity on the other side. All our analysis show that we can be, in terms of addressing population, we can become much larger as soon as we bring forward the NK cell combination. We now need to focus on this. Again, if you go in PTCL with one strategy, you cannot in parallel do the other strategy. You have to make up your mind and have to take a decision. The decision we believe is the right decision to go for higher, basically higher efficacy, better durability. That's the conclusion from Hodgkin lymphoma, which we're seeing, and then trans-transferring this now over into peripheral T-cell lymphoma. We increase the chance of moving ahead in the, in the lines of therapy. This is also being investigated in parallel, and we just believe that what we're seeing here and the data show us that the combination with AFM13 plus NK cell is the strategy to move forward. Right. My second question is on the NK combo. I guess once these patients get into CR, can you talk a little bit about what are the subsequent treatments? It looks like the OS curve sort of plateau, like, from the plot. Can you just, you know, tell us, like, what's driving that? Except for one patient at the moment that we know he has received, for no reason, a PD-1 maintenance. That decision was taken because Dr. Nieto wanted to bring this patient forward to a transplant. That's why he decided to move. There was no medical reason. None of the other patients at the moment have received additional therapies. As long as they are in response, okay. Whatever happens afterwards, we would know we don't have any follow-up on these patients beyond the relapse. Many relapses are, sorry, many of the responses, complete responses are yet ongoing, so we're gonna learn over time. The only event we are having is, at the moment, the transplant. That's particularly important for these patients, as some of them had already a transplant which failed or couldn't get to a transplant. So the CR rates that we have generated help these patients to basically have a chance for cure. And we're seeing that some of those that are transplanted, they're ongoing. As we've said, the very first patient, now it's over two years. I think it's at 27 months this patient is in remission. I t had never achieved that before. So that's something we just see as a, uh, as a big win for the patient lives, and that's why we're doing it essentially. So in essence, uh, we have a fairly good, uh, overview on, in particular now with the third and the fourth cycle, that simply prolongs the treatment periods. That's beautiful if we can do that, because in our study we will also have three or four cycles. We can treat these patients now much longer, and then eventually receive long duration of responses, both in Hodgkin and in PTCL. Thank you. This is RK from H.C. Wainwright. I have a couple of questions. The first one being from Dr. Nieto's presentation this afternoon. Do you folks have an idea of how long the NK cells persisted after the first dose of the combination? The second question is on the monotherapy. We see a differential in the OR between Hodgkin lymphoma and non-Hodgkin lymphoma. I believe 32% versus 18%. What does that tell us regarding is it indication or is it the drug or, you know, is there something else that we should be thinking about? Thank you. Yeah. Yeah, thank you. First, persistence of NK cells. You know, a few interesting messages. We've now seen data up to four cycles, important at the same kind of height, PK pattern, if you so want, right? There is no sensitization, very important. Usually what we see is that they, you know, persist two to three weeks, very consistent with the other NK cell fields out there, right? That after lymphodepletion, patient's own immune system kind of kicks in, and they kind of, being removed. Again, that level can be reached again by multiple dosing, making the, another point that not only the regimen that we use allows multiple lymphodepletions, we also see the same levels of NK cells. In terms of the question response rate between, I think there was a question kind of the non-Hodgkin lymphoma and Hodgkin lymphoma. You know, I would be careful to state, while we use numbers, but let's face it's four patients, right? Yes, it's nominally 75%. Very encouraging. I mean, we have a PT cell patient that's complete response. We really feel encouraged, but I think it's just too premature to really make conclusions. I would say in its entirety, that's what we, you know, sets the right basis where we see a good basis to transport the high response rate that we see in Hodgkin lymphoma, non-Hodgkin lymphoma. Thanks very much. Zhi Xu from Berenberg. I have a question on when you have. You can treat patients up to four cycles. Can you comment on the patients who received the third and fourth cycle? What's the kind of additional benefit from those? I think I recall it's 11 patients in total from the presentation. I would say it's very difficult to give you any additional benefit. Only. We have deepening from cycle 1 to cycle 2. After cycle 2, in particular, the Hodgkin patients in these, in that group that could receive now third and fourth cycle, only three patients were there that had a PR. In terms of deepening, we are not able to detect that anymore because almost every patient already has a CR. What we are assuming is the following: that when you do these measurements in these patients, the FDG PET and CT, it can. When it says complete response rate, it means just that there are no detectable tumor cells anymore there. However, there are still tumor cells there. We know this for the reason that patients eventually can relapse. With the additional cycles, we are basically targeting the invisible. That means that the remaining immune cells could be removed through such a strategy, so the expectation is that, you may end up with an even longer durability. That's the idea behind that. It's safe. As I say, patients are treated, outpatient. In that context, and thereby it's probably been feasible to see many patients ending up with three or four cycles. Great. Just a quick, I guess, biology question on the back of the data. If you do some back of envelope calculation on the monotherapy 2.3 duration response, 3.3 month duration response, plus the scan, six weeks there, it's about 3.8 months treatment for the monotherapy. I guess that's sort of equivalent to about one to two cycles of your 204 study. I wonder, do you need to have a, to have mismatched HLA count NK cells in order to achieve CRs and PRs long duration there? Well, the mismatch is one aspect you can look into. We know that the patients are only having dysfunctional cells. A tumor is, in principle, the result of a mutagenized tumor tissue, but also a certain, I call it weakness in the immune system. Usually, innate immune system would take care of aberrant cells, it cannot. Thereby, the tumor cells is allowed to grow. You see that a basically, a tumor is not just a one-sided activity, it is also using some weakness in the immune system. The idea then to activate the patient's own immune system and bringing this forward, we believe is a great idea, as it not only produces in case of a macrophage activity, but it also we see this infiltration of T-cells. You need to see that the innate immune system is preparing the setup in order then to either come in with NK cells or with checkpoint inhibitors. That's the, that's the strategy that we're pursuing. As I said, we're gonna have additional data next year, in particular for AFM24, demonstrating that that could be a viable approach. For AFM13, we have already seen this, that that could work. Hi, it's James Shin from Wells Fargo. The focus now is on combos, obviously. The preclinical data you've shown for Artiva cells and MD Anderson cells shows marginal differences, but there are some differences. MD Anderson cells are pre-activated. Artiva cells are cryopreserved. AFM13-104 is pre-complexed. The trial with Artiva cells will be co-administered. To Daina's point, I think the DOR and PFS is a little bit disconnected or decoupled from the durational response. You put all that together cumulatively, is your expectation for your combo trials that you're gonna be now using with AB-101, should we expect the same level of efficacy, durational response, depth of response, as you've shown from AFM13-104? Yeah, great question. Lots of parts. Let me start maybe kind of the basis that the data also that I'll start with that Adi shared. You know, we carefully looked at the different types of NK cells. I think what's evolving is that NK cells are quite similar in what, you know, what they can do, untargeted and targeted. Untargeted AML, lots of data, quite comparable, can be improved certainly with a targeting. Now, what we've done clinically, pre-clinically, to the one first difference you rightly point out, pre-complexing co-administration. We in vitro see that's very comparable. Actually, when you look at the data, this is accumulation of actually several independent repeated experiments, slightly better co-administration. I wouldn't make much out of that, but it's comparable. In different mouse models, we've done that. We've shown that, published 2024, pre-complexing co-administration also quite comparable. There's probably pros and cons for both. We don't have time to go into, from that standpoint, we believe we really see very comparable efficacy. The cells, both cord blood-derived. Artiva also different, but also in a way cytokine activated. Adi mentioned that very high consistent CD16 expression, fully saturated. We really have great confidence that this is the right cell. From the patient's perspective, moving away, you know, can I predict? Of course not. You know how that exactly will predict in PR and CR rates, maybe that's not so much the point. I think the point is we see great data, we expect to see very high response rates also with the Artiva cell. That would be my expectations. We cannot predict exact numbers. It's a cell that's ready to go. It's off-the-shelf. It's very stable. Has all the right receptors. Artiva has beautiful publications. You know, you find in the presentation when it's upscaled, it has all the right receptors. It's ready to kill. It's a very good cell to be selling. It can be used in multiple centers. That's why we did, you know, really thought biologically and from a cell and CMC perspective, applicability in clinical trials is the right to go. Do we know exactly how it will pan out? No, but we have great confidence that this is really a adequate cell that will deliver great results. On the cryopreservation, we have seen earlier studies with NK cells that were used fresh. Now every company has switched to use cryopreserved cells. Just recent data of in CAR T-cell fate. The cryopreservation was something to be solved in manufacturing, but it's addressed. We're not seeing cells that are completely dysfunctional or because of cryopreservation do not work. That aspect, we have studied also in-house, quite extensively, and we have not seen the cryopreservation is really impacting the activity of the cell in any manner, let's put it this way. That's fine. In terms of co-administration and pre-complexing. What we know from our data, For full activation of an NK cell, 100% receptor occupancy. Do you know the exact number? It's a small percentage of what you need to have occupied of CD16 A receptor. Yes, exactly. It's a low number. We have also learned this from the study of AFM24. You know, how we determine the recommended phase II dose. We could see that the receptor occupancy, again, is in the range of 20-30% when the cells are extracted, treated at the recommended phase II dose. When we test this in vitro, again, the number what we need is much lower. We have again seen today at the other presentation that AFM13 is binding to patient's own cells. This is an indirect evidence or is a direct evidence, I should say, that AFM13 reaches the cell, occupies it, and as long as CD16 is there, this is leading to activity. That could also be a topic when you look at the cells that are found in the patient that they have CD16, but it's lower. It's not as high as it is on the donor-derived cell. This is why. There's a contribution of factors, it's number, it's activity of the cell, but also the CD16 expression are the important drivers of what we feel is the efficacy. Now we can give multiple doses. What we do as a single dose, we now will spread likely over three or four doses and then the multiple cycles. I think we can have good confidence that that approach is gonna result in meaningful efficacies in any kind of CD30- positive lymphoma. As Hans said before, with our technologies developed in a way that we can target cells with low target expression. As we've said, for AFM13 in the clinical study, as monotherapy, we didn't see a difference between the high expressers and low expressers in terms of responders. That is basically the clinical evidence. Pre-clinically, we can see. We will have a post on Monday, by the way, on another drug called AFM28. Here we are studying 10, 12 different cells with different expressions of CD123, compare it to an FC enhanced antibody, and you're gonna see a very dramatic difference between how high of an expression you need for an FC enhanced antibody and at the same time, how low you can go with an Innate Cell Engager. We need really tiny numbers of receptors expressed and still see the full activity of our technology. These are the evidences that we have brought together in vitro, in vivo, in the clinic, and thereby gives us a good piece of confidence now to put all this sources, resources behind the combination with NK cells. We have a couple of questions from a couple of our friends in the financial community. Our analyst, Maury Raycroft from Jefferies, is asking, who couldn't be here with us today, is asking, "For the combo, could you talk more about data specifically in patients that went through more than two cycles? You're seeing a higher six months event-free survival. Are there any other metrics or biomarker data you can share or leverage going forward?" That's his first question. there's Yeah, thank you. Maury, you're online. A great question. As Adi said, we are still analyzing the data. We don't wanna, you know, share great detail here. This be publications. We're looking at different markers, you know, across the board that was in the protocol. Maybe, maybe we'll wait to share that when we have that in the publication. Okay. The next question he's asking is: Are there any new learnings from the ongoing Rituximab Artiva combo study, and how is that informing your combination planning? Yeah. Artiva will publish the data subsequently. At the moment, the disclosure of those data is due to them. The study is what we're seeing. It's recruiting well, so it's going well, and they have happy faces. Thank you. Our analyst, Yale Jen, at Laidlaw is asking, by comparing prior mono versus natural killer cell combo data in Hodgkin's lymphoma with substantial differences, do you see a natural killer cell combo in PTCL future study? Could you see similar differences? Can these be reflected in the durability of response? Yeah. That's what we are believing exactly based on the data, based on what we have been studying. We have too few patients in the study with MD Anderson yet to make a claim, but we see again activity in the CD30- positive lymphoma patients. if I may add one more. Can you talk about latest thoughts on what is factoring into event-free survival, including how stem cell therapy is impacting results? Well, you know, the stem cell therapy is counted as an event, right? Is not counted as event, right? Okay. More details at this time, we can't share. Okay. Those were, Oh. Hi, Do Kim from Piper Sandler. I just wanted to ask about the one Hodgkin lymphoma patient that progressed and didn't respond to treatment. He seemed to progress really quickly, just blew through therapy. Was he just one of those patients that had too aggressive disease and too late to treat, or was there anything particular about the patient that didn't allow him to respond? It's interesting that you're asking a question about the single patient, Hodgkin lymphoma patient that didn't respond. Usually, you would ask the question, a single question for that patient that had responded, it's, yeah. Rewarding. Can we talk about that, why that would have happened? No, we have no info on this particular patient, what exactly has happened, what the reason is, and so we have to follow up with this. This was a very recent finding just so that's something that happened in the past weeks only, and we are still in the follow-up. We had full focus on preparing the presentation this time and did not really pay attention to the single patient that did not have a response. We don't have any more questions coming from the people who are participating on the webcast. Do we have any more questions here in the room? This is a really strange question. I think that you've answered it before. In the last day, I should say, since I've been here at ASH, at least three or four people I've talked to about Affimed were confused about the Artiva economics. Can you remind people of the Artiva economics? Yes. 'Cause they have the impression that you gave a lot away. Can you just remind people? Thank you. That's an impression that people can have if they want that. I think. No, I think they have the wrong numbers. For us, what's important is, Artiva has, and it's, company where the technology is coming from, Green Cross has made a massive investment in this manufacturing, okay? We have calculated that through, and if we would have done this on our own, it would have basically taken up a big chunk of the cash available. We don't have to make that investment because Artiva has made it, and on top we get pretty much the sales for free. That is a massive gift to us in this context as we now can move forward. Now to the economics. We will conduct the phase II study, so the so-called phase II registration-directed study. As soon as it comes to any confirmatory study, Artiva will match our expenses, so we will pay 50/50. We all know that our studies that are far larger. This already points to why there is a expectation on Artiva to receive economics and not just a small percentage. We're splitting it up. Two-thirds will remain with Affimed, and one-third will remain with Artiva. Each party is responsible for its own COGS in insofar for its own manufacturing. We then will eventually split. I can make it up as a number. If we sell the drug for $300, we keep $200 and Artiva gets $100, and each party is responsible for marketing its own product. Okay. We don't have any more questions. We will conclude the virtual section of the event today. The team will be here for a little bit longer if you wanna hang out and discuss with our team. Be happy to answer any more questions that you may have. Thank you very much all for joining. Thanks a lot, and good night.