Thank you for standing by, and welcome to Affimed's Clinical Data Update on acimtamig AFM13 and AFM24 conference call. At this time, all participants are on listen-only mode. After the speaker's presentations, there'll be a question and answer session. To enter a question at that time, please press star one one on your telephone. Please be advised that today's call is being recorded. I would now turn the call to your host, Mr. Alexander Fudukidis, Director of Investor Relations. Please go ahead. Thank you, Valerie. Good day, everyone, and welcome to Affimed's Investor Event during the 65th annual American Society of Hematology Annual Meeting and Exposition in San Diego. As a reminder, today's webcast is being recorded, and the recording will be available through our website later today. Before we begin, I'd like to remind everyone that we issued two press releases earlier today. One about our investigator-sponsored combination trial of acimtamig or AFM13, with cord blood-derived natural killer cells, data of which was presented earlier today at the ASH conference, and a press release on the progress we are making with AFM24, a solid tumor clinical asset. Both press releases may be found on the investor relations section of our website. On our site, you will also find a presentation which we'll be sharing with you today. We have our management team with us today to take you through the presentation. Adi Hoess, our Chief Executive Officer, and Andreas Harstrick, our Chief Medical Officer, will take you through the presentation, and the rest of the team will be available to answer questions during the Q&A session after the prepared remarks. Before we start, I'd like to remind you that today's presentation contains forward-looking statements regarding future events. These statements represent our beliefs and assumptions only as of the date of this event. 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 the section entitled "Risk Factors" in our filings with the SEC, and those identified under the section entitled "Forward-Looking Statements" in the press releases that we issued today and filed with the SEC. With that, I'll turn the call over to Adi to start the presentation. Adi? Yeah. Thanks, Alex. Thanks, all, for joining us today. Today in the morning, we issued press releases on two of our lead programs with, with novel data. The clinical data from both programs demonstrate that our innate cell engagers can drive a clinical benefit in, in patients, of high unmet need, and, provide a validation for our pipeline. The first update from our AFM13-104 clinical study, in collaboration with MD Anderson, demonstrates that we can deliver both unprecedented and durable responses, durable rates of responses in a cohort of Hodgkin lymphoma patients who have exhausted, indeed, all treatment options. In fact, none of the patients enrolled in the study had responded to the prior line of therapy, making the results even more remarkable. Separately, we released an update from our AFM24-102 study, where we are investigating the combination of AFM24 with a PD-1 checkpoint inhibitor, atezolizumab. This update demonstrates intriguing signs of clinical activity in EGFR-wild type non-small cell lung cancer, a large solid tumor indication where treatment options in the third line forward are currently insufficient. Andreas will provide the details of both clinical updates later in the call. Now, before we dive into the presentation, I'd like to again thank our employees for their unwavering commitment to delivering meaningful benefit to our patients, those that are in need for new therapeutic options. I'd also like to thank our study investigators and all patients who have participated in those trials. Now, together, we have reached a critical inflection point for our platform. We are pretty excited about the next steps towards bringing these meaningful treatments to patients who really need them. Now let me move over to acimtamig. With that, I'm going to go and dive into AFM13-104. What you see on slide five, we believe acimtamig, combined with, cord blood-derived natural killer cells, can fill a major void in the treatment paradigm for Hodgkin lymphoma and peripheral T-cell lymphoma patients, while addressing a significant market opportunity. Given the very high objective response rates and indeed, super very high complete response rate observed in AFM13-104, and the meaningful durability of these responses, we're moving ahead aggressively to bring this therapy to market. So our LuminICE-203 trial, geared towards generating an accelerated approval in Hodgkin lymphoma, also including an exploratory cohort in CD30-positive peripheral T-cell lymphoma, is now well underway. During 2023, we have made outstanding clinical and regulatory progress for the program, gaining Fast Track designation in September. Aligning with FDA on the approach to addressing contribution of the components in October, and now we're dosing patients in the first two cohorts of the study. All of this progress will allow us to present initial results from the running phase of the study during the first half of 2024. Now let's move on to slide six. I'll touch briefly here on the unmet need in Hodgkin lymphoma. Now, over the last decade or so, the treatment paradigm for Hodgkin lymphoma has indeed undergone a significant shift with the introduction of Adcetris and two checkpoint inhibitors into the market, called Nivolumab and Pembrolizumab. In both our AFM13-104, but also LuminICE-203 trials, we're treating Hodgkin lymphoma patients who indeed have progressed on both earlier treatments with Adcetris and the checkpoints. Following the introduction, these therapies have moved to earlier lines of treatment, and unfortunately, a large proportion of patients are not able to be cured by these therapies. Meaning, as a result, there is a relatively new clinical problem in Hodgkin lymphoma, which is that there are a number of patients who are refractory to both Adcetris and checkpoints. We refer to these patients as double refractory patients, and the treatment options available for these patients are limited, if there are any. In fact, one prominent Hodgkin lymphoma clinician told us that he views the treatment landscape for these patients as a wasteland. Slide seven, you can see here the treatment options for patients once they have progressed beyond Adcetris and checkpoints. The NCCN guidelines include several therapies for patients with three-plus lines of prior treatment. Importantly, none of these treatments were studied in double refractory patients yet. Nevertheless, you can see here that the CR rates and PFS for these therapies are quite low, supporting what we've heard from KOLs, that these patients have limited treatment options. Furthermore, there are not many therapies in development for these patients. The only ongoing novel development program that we're aware of is the pembrolizumab combination shown at the bottom of the slide. Here, again, you can see that the response rates in particular are not very impressive. So it's clear the double refractory patients are in desperate need of new therapeutic options. Now let me move to slide eight. The logical next question is: how many patients are there? And, on the left side of the slide, you can see that there are roughly 21,000 newly diagnosed Hodgkin lymphoma patients each year in the seven major markets. Roughly 13% or a little more than 2,500 patients will ultimately require additional therapies. This is the patient population we are indeed targeting with acimtamig now, acimtamig in combination with NK cells, and we believe it represents an initial market opportunity in excess of $1 billion. Now, we'll also have an exploratory cohort in LuminICE-203, investigating relapse refractory CD30 peripheral T-cell lymphoma patients. Here again, the unmet need is very high, as once patients progress beyond frontline treatment, the options are very limited and there is no fully approved drug indeed available for second-line patients. This indication is even larger, with 5,500 patients, roughly in the seven major markets, now representing a market opportunity indeed in excess of $2 billion. So in total, the initial patient populations we're targeting represent a commercial opportunity of $3 billion in the seven major markets, which is quite attractive. With that, I'm going to hand over to Andreas. Yeah, thank you, Adi, and also welcome from my side, and it's my pleasure to provide you an update on the clinical data that we have generated in both of our programs, AFM13 and AFM24. If we jump to the next slide, you see the high level data that were presented today by Dr. Yago Nieto, on the study with acimtamig in combination with cord blood-derived natural killer cells. And in order to put this data really into perspective, I think we should start on the right corner there in this little box and review again, the really unfavorable patients' characteristics that went into this trial. As you see, the median number of previous lines of therapy was seven, but more importantly, in addition to being refractory to combination chemotherapy, all these patients had a previous exposure to BV. All patients had a previous exposure to checkpoint inhibitors, which constitutes this new patient segment, these double or triple refractory patients. In addition, 63% of patients had a previous stem cell transplant, and Adi already highlighted the difficulties to compare this data with historical controls, as the prognostic factors have significantly changed and the pretreatment has changed. I think the most relevant data set is when you look at how did the patients respond to their most recent treatment. Again, taking into consideration that all these patients were treated at very experienced Hodgkin lymphoma sites, and therefore, you have to assume that physicians were really trying to do the best for the patients that was available to them. The response rate was 0%. Not a single patient derived any benefit or responded to the treatment that is currently available once they are triple refractory. Now, I think in this context, the data that we have presented today with our study are even more important and more compelling. In the 32 patients with Hodgkin lymphoma that were treated at the recommended phase II dose, which is the highest dose of cells of 1.1 x 10 to the eight cells per kilogram, all except for one patient responded, so 97%. And I think more importantly, especially for long-term prognosis, close to 80%, 78% of these patients achieved a complete response. Just a short reminder, what we did in our study. In the middle, you see the diagram of one cycle of treatment. So we start out with a standard lymphodepleting therapy. Then on day zero, patients receive one infusion of acimtamig that in this case was pre-complexed with AFM13. One dose of NK cells, pre-complexed with acimtamig. And then this is followed by three weekly infusions of acimtamig single agent. Tumor assessment is done on day 28, and in the initial phase, the first 20 patients were eligible to receive up to two cycles. When we saw deepening of responses, from cycle one to cycle two, we amended the protocol and allowed patients to be treated for four cycles. Let's move to slide 11 and review briefly the safety profile. The safety profile is remarkably good. In contrast to any approaches that try to utilize, for example, T cells, we have no cases of cytokine release syndrome, we have no immune cell-associated neurotoxicity, and we have no graft versus host disease. As expected and also shown in the presentation by Dr. Nieto today, the lymphodepleting chemotherapy results in the desired and necessarily reversible myelotoxicity. However, important to mention that this is not associated with clinical side effects. We have no episode of bleeding as a consequence of thrombocytopenia, and we only had one patient who experienced a short febrile episode that responded readily to antibiotics. Asymptomatic related side effects were also not frequent and were mild to moderate, with infusion-related reactions, the only worldwide side effect to mention, responding very well to treatment interruption, fluid replacement, and anti-inflammatory drugs. And no patients had to stop or discontinue treatment due to asymptomatic related side effects. On the next slide, you see the waterfall plot reiterating what we said. There's only one patient not responding. All other patients achieved a response, with the vast majority of patients achieving a complete response. Also interesting to note, that four patients, in addition to chemotherapy, BV, and checkpoint inhibitors, had received CAR T-cells, CD30 targeting CAR T-cells, and either not responded or relapsed after a very short period of time, and all four patients went also into a complete response. These are the updated data on slide 13, for the duration of response and the long-term effect. And what you can see is that 30% of patients have a response that lasts for 12 months and longer. Overall, the event-free survival was 9.8 months, the median duration of response, 8.8 months, and as I said, 30% of patients remain in remission for more than a year. As you can also see, it appears to be very important to achieve a complete response for long-term disease control. The gray bars on the bottom represent the PR patients. Some go out to six months, but ultimately all relapse. However, if you have a complete response, you really have a chance for long-term disease control, with first patients out now for more than two years. So this data enabled us to develop a regulatory strategy with the aim to bring acimtamig to patients as fast as possible. And as a process, we have gone through quite good discussions and productive discussions with FDA. This slide, slide 15, highlights the key messages. FDA supports that a single-arm study, non-controlled study in this area of high unmet medical need could support an accelerated approval, of course, always depending on the magnitude of clinical benefit. FDA is highly engaged and supportive in the progress and has actively suggested to have further discussions as we generate data. FDA also agreed, and that was the only questions I had to our original protocol, that our strategy to address the contribution of components is adequate. What you see on the next slide, slide 16, is the final design of our registration-enabling and directed LuminICE trial. As you see on the top, we are starting with a couple of different dose cohorts, which will be then narrowed down initially from four cohorts to two cohorts, to finally one cohort. And this addresses FDA's questions and need for information on the relationship between clinical benefit and exposure... As you see on the bottom of the slide, we have slightly modified the design of a cycle, so we use the same lymphodepleting regimen. However, instead of giving NK cells on one day only, we decided to fractionate these NK cells to one, day one, eight, and 15. But as in the MD Anderson study, this is followed by three weekly infusions of acimtamig, with disease assessment then done on day 43. To have the same duration of treatment, as we did in our 104 study, from these longer cycles, we will now give three cycles per patient. As you see in the middle, and as Adi mentioned, there is an observation cohort for patients with refractory PTCL that would enable us to also enter a development program into the PTCL area. And then the yellow box, this was cohort six that we added as a result of FDA feedback. This very small cohort of currently 12 patients, we will give patients initially a course of allo NK, so the cord blood-derived natural killer cells without acimtamig to see what the efficacy of a non-targeted NK cell would be. However, FDA also agreed that patients who are not developing a response to the first cycle of treatment can switch over to the acimtamig combination. So with this, I think the acimtamig program has come to a critical milestone. We clearly see that there is a void of viable agents for refractory patients, especially when they are refractory also to BV and checkpoint inhibitors. We have seen outstanding data with a combination of acimtamig and cord blood-derived natural killer cells. We now have a registration study that is agreed upon with FDA, up and enrolling patients in the first two cohorts. We believe that there is an important and attractive market opportunity, given the very high unmet medical need, both of refractory Hodgkin and PTCL patients. With this, I would like to switch to AFM24, our EGFR-targeting ICE in solid tumors. Just a reminder, AFM24 has a completely different mechanism of actions than currently available EGFR-targeting agents, as it does not interfere with the signaling pathway, but only uses EGFR to attach natural killer cells and macrophages to the target tumor cell. And these natural killer cells and macrophages are solely responsible for the tumor cell destruction. To summarize our program as we are today, in our early program with single agent and both also with combination, we demonstrated a very good safety profile. Again, with infusion-related reactions being the only worthwhile side effect to mention. We have seen antitumor activity in a monotherapy across a number of indications, meaningful clinical disease stabilizations, and some of these patients are still ongoing now for 12 months and longer. We also provided clinical validation that we are triggering both the innate immune system, as well as the adaptive immune system, which forms the biological basis to combine AFM24 with PD and PD-L1 inhibitors. What we, we share with you today are the efficacy data, very early efficacy data in non-small cell lung cancer, especially in combination with atezolizumab in a heavily pretreated patient population with an overall 73% disease control rate and four objective responses. We now go to the next slide, and this is just an update of the monotherapy. As you know, we started our non-small cell lung cancer with EGFR mutations as part of our monotherapy study. We provided the response data at ASCO this year with two partial responses. Now, with longer follow-up, we also have major progression-free survival data, which are close to 4.5 months, and therefore absolutely comparable with what you can expect in these patients with combination chemotherapy. So we believe that this really validates the efficacy of AFM24 in patients with non-small cell lung cancer. On the next slide, you see our combination study. Again, here we are combining AFM24 with atezolizumab. In the dose escalation, we could show that there are no additional new or potentiating side effects, and we can use both drugs at their individual single doses. We have four cohorts in this study, non-small cell lung cancer, both for EGFR mutant and EGFR wild type, and then gastric and HCC pancreatic. For today, we would like to focus on the non-small cell lung cancer data. On the next slide, you see the patient's characteristics. A total of 17 patients were enrolled with EGFR wild type non-small cell lung cancer. Two patients withdraw consent early before they went on to the combination treatment. So our final data set will now be 15 patients that we will discuss today. If you move down, you see that the median lines of prior treatment was two, so we are looking more at a third-line population here. But very important to mention, all patients had received prior, previously checkpoint inhibitors, and even though four patients had a short-lasting PR, all patients were progressive while still receiving a PD-1 or PD-L1 targeting therapy. On the right side, you see a short summary of the side effects. As said, very well tolerated, with only mild to moderate side effects and not treatment limiting. We move to the next slide. This is the waterfall plot. Again, very early data, but what we see is a good disease control rate, and more importantly, objective responses. Currently, one CR, three PRs. Now, in contrast or in addition to what we saw when we did this slide, we now have a second PR confirmed. So, as we keep patients on treatment, these data seem to consolidate. If we go to the next slide, this shows you the swimmers plot. Again, as you see, some patients out now for already six months, the majority of patients still on treatment. What you also see in the top two patients, these patients had a stable disease as their first assessment, that improved into a partial response with further treatment, and the top patient now has the PR also confirmed. Given the fact that we still have a significant number of patients with stable disease after the first assessment, I think there is a good chance that some of these patients may improve also into an objective response. To put this data into perspective, this is what we extracted from literature. What you can expect with atezolizumab monotherapy in patients who have been PD-1 pretreated or refractory. As you'll see, the response rate is basically not worthwhile to mention, roughly around 5%, and also median progression-free survival is around two to three months. And important to mention also, that even atezolizumab in PD-1 naive patients only results in a response rate of 15%, and again, in a very short median progression-free survival of roughly 2.8 months. This is just an overview of what currently can be used in patients with non-small cell lung cancer, even in second line. Again, standard of care would be ramucirumab and docetaxel, with very modest efficacy, overall response rate 23%, median progression-free survival 4.5 months. So we believe that the early data that we are seeing with the combination of atezolizumab and AFM24 compare well and provide a good safety, a good efficacy signal, an early signal, though, but we are highly encouraged with this early data that we are seeing. And we think this validates our approach of combining ICE with PD-1 or PD-L1 inhibitors. The market size, of course, in non-small cell lung cancer, both in EGFR wild type, as well as in EGFR mutant, is very significant. As you see, in second line, we have close to 200,000 patients that will require additional treatment if you look at the EGFR wild type cohort, and another 50,000-40,000 patients, roughly, in the EGFR mutant cohort. So what are the next steps? I think we have seen very encouraging activity signals in the combination with atezolizumab, with now two confirmed partial responses, one complete response, and one partial response that are awaiting confirmation. Disease control rate of 73%, close to 50% of patients with tumor shrinkage. This study continues enrollment, and also the study or the cohort with non-small cell lung cancer, EGFR mutant, is continuing enrollment, which will set us up for further data updates, including more mature progression-free survival and response data in the first half of 2024. With this, I would give the talk back to Adi for his concluding remarks. Yeah, thanks a lot, Andreas. So what you have heard is that the focus of the company is on acimtamig in combination with NK cells and AFM24, currently investigated in two cohorts. One is what we just presented, non-small cell lung cancer with wild type EGFR, and a second cohort that is treating patients with non-small cell lung cancer, EGFR mutant. And, as all these studies are ongoing, we have a number of data coming up in the first half of next year. So the new study for acimtamig is called LuminICE, and we have initiated the treatment of patients on this study, and there will be an update from the first patients. Could be up to 24 patients that we are currently treating. And, the second updates are coming from the AFM24-102 study. So again, treating patients that are relapsed from, mostly two lines of therapies, but also can have more with diseases, non-small cell cancer, divided up into wild type and mutant. So those data is going to come up. The mutant cohort is a little behind the wild type cohort, so roughly two months in terms of investigations. But we have on the mutant cohort patients fully enrolled and are awaiting data also to come up in the first half of next year, and longer follow-up data on the wild type cohort. Last but not least, to mention our last program, AFM28, that's CD123 targeting innate cell engager that's currently investigated in a dose-escalation study in AML patients, and we plan to give progress updates from the ongoing dose-escalation study, again, in the first half of next year. ...With that, I want to conclude the presentation and, check for questions. Thank you. Thank you, Andreas. Thank you, Adi. Valerie, we are ready now to take questions from investors and analysts who are participating in the call. Thank you. Thank you. Again, ladies and gentlemen, if you'd like to ask a question, please press star one one on your telephone. Again, to ask a question, please press star one one. One moment for our first question. Our first question comes from Srividya Deverakonda of Truist. Your line is open. Hey, guys. Thank you so much for taking my questions. For the LuminICE, you mentioned in the PR that you have completed enrollment of the run-in phase. Just confirming that 24 patients are now enrolled? And also, was this across multiple centers? Just, it seems like the time period between when you announced that we're starting to enroll and now is reasonably short. So, and also based on your trial design, looks like assessment will be done at 43 days. Is that sufficient for you to release the first tranche of data, or would you want to wait for additional confirmation of the response? Thank you. Yeah, thank you. So let's start with the first, and I'm not sure whether... I hope we did not said something wrong here. We have this first part of the study, which will be 24 patients. These patients are not fully enrolled yet. Okay. Yeah, we have started enrollment. We are actively enrolling into cohorts one and two. As you see on the diagram, there is a little bit of a staggering between one and two, which uses a lower cell dose and three and four. So this will be an active process that will be ongoing. Again, we are bringing more sites in the U.S. into the study as we speak. So basically adding a new site per week or so, and we see very active recruitment in these sites. And this, again, enables us to iterate our guidance or reiterate our guidance that first data from these patients will be available in the first half of next year. The focus, clearly, given the relatively short observation period that we will have for some patients, will be on response rate, and you will see a little bit more of a heterogeneous, pattern. So some patients may have one or two cycles, some patients may have completed all three cycles. But we believe that this will already give a very good indication, of the response rates that we are able to generate with the LuminICE study. Got it. Thank you. And then for the AFM, the EGFR wild-type cohort that you just reported, you said another. So two responses of the four that you reported are confirmed. Yeah. When do you think is the earliest we'll get confirmation of the remaining unconfirmed responses? Should we wait till the next medical conference before we can see that data? I can comment on the confirmation timelines. This will all happen within the next six to eight weeks. We should have confirmatory scans basically for all patients that are on the study. Now, we have not made a plan yet or not agreed on a plan when to, really, or at which venue to share these data. It could be a medical conference, could be, a company event. We still have to look at our options here. Got it. Thank you so much for taking my questions. Thank you. One moment, please. Our next question comes from the line of Daina Graybosch of Leerink Partners. Your line is open. Hi. Thanks for the questions, guys. The first one on the lung cancer data. Congratulations for the signal. I wonder now that you've stopped some of the other cohorts and other diseases and are focusing here, how you're thinking about exploring this signal. I'm sure as you and everyone knows, other companies with an IO signal in PD-1 relapse refractory have consistently elected to stay in that setting and add chemotherapy, given it's such a hard patient segment to treat or move into earlier lines, or I know you've considered a potential of adding a KRAS TKI. So how are you thinking about that, and when would you make decisions like that in terms of moving forward in the EGFR wild-type lung cancer? And then after that, I have a question on Hodgkin's. Yeah. So on the EGFR mutants, and these data are really very fresh. We have 15 patients now. Our intention is to increase this cohort to have a better and more robust signal. I think especially the PFS data that appear to emerge, responses are important, but I think especially in non-small cell lung cancer, also a good PFS is something that you will need for further development. And then we have a number of options. Again, if you look into the third line setting, this data could emerge as even better than anything that is available in third line, so you could stay with just this double combination. If you go earlier, of course, as you said, we have multiple, different options, so we can, we can have, patients in, in, in combination with either chemotherapy, we may even look into combination with some of the upcoming ADCs. And then if there's a target with a mutation, we may also look for combinations with, with specific mutation inhibitors.... But the first step, clearly, is to, corroborate the data, and then I think this gives you a lot of opportunities, to address the non-small cell lung cancer field from a multitude of different angles. To our knowledge, this is probably one of the only pure immune-based therapies that is providing such a signal, so this gives you a lot of combination partners. Just to clear, Andreas, started out saying EGFR mutant, but he meant the EGFR wild type. That's why we're adding additional patients. Yeah. Did I say EGFR mutant? Mm-hmm. Okay, thanks. No, I meant EGFR wild-type. As Adi said, the EGFR mutant cohort is fully recruited right now. It's also 15 patients, and here we are just waiting for the data. Thank you. Then a question on Hodgkin's. I think in the Dr. Nieto's discussion, you know, he separated out the two cycles and four-cycle patients, and showed that the 12-month EFS and OS is very similar, regardless of two versus four cycles. And I wonder how you're interpreting that. And, you know, we have, as we all know, a super impressive CR rate, and it would be nice to get more durability for more patients. And any path you could take forward to extend that durability that you're considering? Yeah. I mean, we have this comparison, two cycles versus four cycles. Again, it is a little bit difficult because we also saw, for example, the only non-responders in these patients who would be eligible for four cycles, and it's very small patient numbers. We think there is a slight trend for a better outcome with four cycles, but it's not more than a trend, so the question is still open. What we do in our LuminICE study, we have now three cycles of a longer duration. We are also spreading out the NK cells for multiple or for three infusions, which we think could offer some therapeutic benefit. We would say that 30% of continuous CR in a patient population that is basically without any treatment option is already an outstanding signal. Clearly, you always want to improve on that, but I think even this is already really, really good. So combinations that are thinking about maybe PD-1 maintenance after patients have gone into a complete response, something like that would be options to even increase the percentage of patients that remain disease-free of at one or two years. But overall, when, when you look at that, you're always saying the durability and then, so you have to look at this from another angle as well. It's how many patients are really staying within this remission, and we have 30% at the 12-month mark, and that's pretty exceptional for such a late-line treatment. So there are other drugs, obviously, given at some earlier lines, earlier point, and their numbers is also not looking much different. So the actual number that we're seeing that has a benefit of 12 months and longer is large. And that's really what also needs to be considered, not as a kind of a duration of response. In our case, we talk about 100% of patients. You know, duration of response is only important when you have smaller numbers, like 30, 40% of patients, reacting. Here, we have a very different view. We are really moving a large number of patients into 12 months and now even into two years. So we're not so much concerned, and I believe also the, the regulatory agencies will not so much be concerned about that. If it is nine, 10, or 11 months, it doesn't make a big difference here. And, as these patients, as we have said, have no options at all. So if you see a patient population that's 100% refractory to a prior treatment, that's quite dramatic because these patients otherwise would die. I think we have strong data and are not agreeing that the duration of response should just be longer, because that factor is just one way how you can look at the study, as I explained. Thank you. Thank you. One moment, please. Our next question comes from the line of Li Watsek of Cantor Fitzgerald. Your line is open. Hi there, this is Rose Marion for Lee. Thank you so much for taking our question. So I have one for each program. Firstly, for AFM24, I know the follow-up is still really early for these EGFR wild type guys, but can you comment on durability of these responses as well as what you think will be clinically meaningful in the future when you have more mature data? Not sure if you can hear me? Yeah. Adi, Andreas, you may be on mute. Sorry, can you hear us now? Yes. Yes. Sorry about that. Valerie, we're ready for the next question. Okay, she asked the question? Yeah. Rosemary, can you say that again, please? Oh, yeah, sure. So, the first question is on AFM24. Still really early data, but do you have any inklings on durability, and what would you say would be clinically meaningful when the data is more mature? Yeah, I think, we have basically two benchmarks. So what PD-1 provided in the second line, second setting, single agent PD-1 was roughly 2.5 months, 2.8 months, which at that time was already okay for approval. If you look into more complex combination regimens, either chemotherapy, chemotherapy plus VEGF, PFS consistently is roughly four months, but these regimens are significantly more complex and more toxic. I think any PFS that is in excess of five months, 5.5 months, six months, clearly positions you very well, against both combination chemotherapy and also PD-1. So this is, I think, a benchmark that would be extremely meaningful. Got it. Thank you. And then just one on AFM13, the combo, if you don't mind. So given the high CR rate, can you comment on using the combo to get it, the patients into transplant? And what proportion of patients do you think can potentially get to transplant? Well, this clearly will depend, of course, on the patient's conditions. In our regimen or in our study, a total of seven patients went on to transplant. If we look at the patients who are long-term disease-free, we have an even split, so five patients had a transplant, five patients are disease-free, even without a transplant. Now, I think when we look at the data, this very high complete response rate is a prerequisite to enable physicians to perform transplants. So what we may see is more patients going on to transplant after achieving a complete response to the NK cells plus acimtamig. And some of the physicians we spoke to are really, really enthusiastic about this possibility to get a patient that in his career never was eligible for transplant, to finally get to, into a transplant-eligible status. Got it. Got it. Thank you. Just to add to that, it's not unusual to see patients brought into transplants from other drugs that had CRs. Mm-hmm. So we also have longest responders in the Artiva study, which obviously was conducted in a much earlier line. But a certain percentage went into transplant, but also for the two checkpoints, a certain number went into transplant. So it seems for Hodgkin lymphoma, quite a good chance for patients, again, to have long-term cures and or long-term responses. So what we are seeing here with acimtamig is, at least in this early study, is not too different from what has happened also in the other context. And one reason why probably even more, not even more patients went into transplant, is that the insurances at that time already basically were exhausted to allow and pay for another transplant. So that was another challenge- Right We learned at the MD Anderson Center. But just imagine, and I, we, we cannot repeat it often enough, okay? These are seven prior lines, and these patients did not respond, although treated by the best experts on for these patients, and they just passed through this line. So can you imagine what a physician would do next if he already has chosen- Mm-hmm ... the best one? So it's really like, fishing in the dark for these patients to find another, another therapy. That's the, that's a really devastating situation for a patient. If somebody tells you, "I, I bring you another experimental therapy, but the chances you have are usually, let's say, very low." Now, we can with acimtamig and the NK cell and have changed that world. I think that's a huge achievement and, is, definitely appreciated from the patients. Now, what are we learning? The sites that we're bringing on, they immediately have patients. So I think that the physicians are already realizing the chances that acimtamig plus an NK cell is offering for these patients, because anything else they would give is just like a, a very low chance that they even can have some sort of a response. That's the reality for patients when they are, what we call them, double refractory. We have no drugs that are otherwise studied yet in this patient population, okay? There is other drugs in the guidelines, but you've, at the moment, not much of an idea how these patients ever would respond when they have these many- Mm-hmm ... and have really undergone all these prior therapies. So that's really new grounds that we had to establish. And I think when you look at, when you talk to physicians, when you talk to patients, for them, the world is changing in a dramatic manner. And now we're in a study that hopefully will take acimtamig plus the NK cell to the market. Surely. Thanks, Adi. Thank you. One moment, please. Our next question comes from the line of Maury Raycroft of Jefferies. Your line is open. Hi, this is Kevin on for Maury. Congrats on the updates. Just a couple of quick questions. Going back to the question on the presentation today, with the four cycles versus two cycles. You know, just looking at the swimmer plot here, I see there's a few more responders that are ongoing in the up to four cycles. Do you think that sort of survival or EFS could shift towards the higher cycles in a future update, potentially? And then also just maybe any comment on the, on the, the data for the blood levels of donor NK cells on cycles and sort of any learnings that you got from that MD Anderson study that you're, you know, taking with you into the LuminICE study? Yeah, thank you. I think as we discussed this question, two cycles versus four cycles, if you apply what we learned in lymphomas, treating it beyond a complete response, with one to two cycles to really consolidate such a response, historically has always led to better results. So we think that you need to give a critical number of cycles. We think in LuminICE with three cycles, but then three infusions of NK cells per cycle, we are probably addressing this question. And yes, we may see better or more long-term responses in those patients who have more treatment. Now, the data, I think, were also quite encouraging in terms of NK cell kinetics. When you see that you have a kinetic that is relatively short, which I think is a good thing for NK cells. They are different than T cells that really have to go directly into the tumor. This is where you want to have your NK cells. We have seen some NK cell engraftment in the lymph nodes in the MD Anderson study. So this is emerging data. Again, we will have or we'll do the same analysis for our NK cells, see how we can change or whether we change the kinetics. But it's important to see that also there was no sensitization effect. So the kinetics were comparable to cycle one, cycle two, cycle three, which I think is also very important. Great, thanks. And anything on the ongoing responses for the patients that are up to four cycles, if that might shift future? Yes, it may shift. It may turn out that those patients who have four cycles might in fact have a longer response duration. We just need a little bit more follow-up data for these patients, because historically, and this is why they currently may look still the same, this was sequential, this was not randomized. So by definition, the patients with two cycles, of course, have a longer follow-up, and therefore the chance to show a somewhat longer response rate. We introduced the change in the middle of the protocol, so currently the patients in the four-cycle cohort have a shorter follow-up time. Great, thanks. And just a brief one on AFM24. I know you said that all the patients had progressed on checkpoint inhibitors. I just wanted to check to see if you're saying, for those four responses, are those... Do you know if those are from refractory patients or if those are patients that responded and then progressed? Thanks. From the four patients that have a response right now, one patient had a very short-lasting partial response, but this was as a response to triple treatment. He, this patient got a chemo-cetuximab doublet t, plus PD-1, went into a PR, then progressed while still receiving PD-1. The other three patients had stable disease as their best response to previous PD-1, so they did not even respond to PD-1, and now we are seeing these good responses with the combination. Great. Thanks for taking my question. Thank you. One moment, please. Our next question comes from the line of Bradley Canino of Stifel. Your line is open. Hi, this is Bijan Owen for Brad Canino. Thanks for taking my question. The first is just to follow up on the durability question. You know, what's the durability benchmark for approval? And then what durability benchmarks do providers give to use a regimen like this? Yeah. For approval, FDA will never give you a concrete number. What we have worked with is a number of key opinion leaders that are also close to FDA. They say that duration of response of six months for them is meaningful, and this would encourage them to use this in clinical practice. We would believe that FDA is somewhat in the same ballpark. Again, maybe I can give this question of providers back to Adi. We did some market research, and would think that the profile that we are currently seeing is supporting our market projections, but- Yeah, but I think, I think you said it, Andreas. So that's the, the, the benchmark here. Again, I've mentioned that before, that, also for, other drugs, so in particular, Adcetris and, PD-1s used, some of these patients also went on a transplant. So I think that will be important because, they are, we're, we're seeing, the results, and, getting a patient on a transplant in Hodgkin's is probably another way of curing these patients. And, and that's a huge benefit. We see that our, therapy is enabling transplant. So there are different, views on that, but in general, the six months is, is, is, is the bar that, we need to cross. But I'm just repeating the point, the duration of response in our case, we're talking at least from the MD Anderson study, on 97% of the patients. So we have a far larger number that is indeed achieving 12 months and longer responses. And that larger number, this percentage we're having, is something that matters. So it doesn't come down simply to say this is six- ... eight months, 9nine months, 10 months. At the end of the day, if we have 30%, as in the MD Anderson study, that have a 12+ months and now even 24 months duration, that's what matters. So, and, Andreas has said, you know, now you can think if somebody is in these ranges of 18- 24 months, you can really start to consider these patients even having a longer-term cure. And that's very unusual for such a late therapy. And that's the values we're really adding. What we do not know, what is something that we may also want to understand, how patients may become responsive to other therapies. So this is something we have learned, also from, from PD-1s. When you treat with PD-1s, you again have a chance to provide, to retreat these patients also with, some sort of chemo. So that's another opportunity that may emerge and thereby significantly prolong overall survival of these patients. So, I would say that, we have opened new doors with this therapy, and, coming back now since over years, just on the duration of response, is somewhat meaningless in our minds because you need to look at the totality of the endpoints that are out there and not get hung up just on this single one. And as I said, with this high response rate, we're in a different category, then duration of response is not the right and most meaningful endpoint to look at. It is really that you are remission-free for 12+ months, these long-term responders that reach out to two years, and that's what we have been achieving. I think the overall picture is already very satisfying. Yeah. Yeah, I understand that. And just to follow up on some of your comments, for the transplant patients, I guess what were the characteristics of the patients who transitioned to transplant? And then what proportion of the relapsed refractory Hodgkin's patients do you think matches that? This was a very heterogeneous population, so we were not able to really isolate individual factor. We see again, if you have 80% complete response rate, it's very difficult to establish prognostic factors because your event, complete response, is happening basically in your whole patient population. And we have not seen any restrictions. So, for example, if patients have had a previous transplant, and we have a number of those who then, after getting a complete response to our treatment, got a second transplant. So even patients who have already failed transplant become re-eligible for transplant, given the very high efficacy of our regimen, which I think is again, it's an outstanding result. If you had talked to physicians or talked to physicians who say, "Okay, this patient has had the transplant, so I have nothing to offer him anymore." Now, we learned that with this type of treatment, we bring this patient to complete response, so they can get a second transplant. And some of them are now in disease control for 15, 18 months. So it's really a very powerful treatment. Again, there is no prognostic factor that would preclude a patient from getting a transplant or getting into complete response. So I think we can address basically the whole refractory lymphoma population that is out there. There are no restrictions. Importantly, we had patients in there that had bulky disease and metastatic disease. So there were bone metastases, there were liver metastases. So it's really a very unfavorable patient population that was then finally getting to be treated with acimtamig and an NK cells. So when you take all that together and you certainly don't have to stratify your patient population, you can just try it, and if your chances are as high as as seen in our study, 70%-80% of patients with a CR. I think that was a learning in the ongoing process, what happens in the ongoing study, what happens in the future. If, if you see the first CRs coming up, probably physicians will have a different view and prepare already earlier on what to do with these patients. So this is now something where you can plan a future therapy in a very different manner based on the learnings that we are currently seeing. So again, this study has, in our mind, and will open doors for patients that are very difficult to treat. And you may even then see them being eligible for our therapy at the stages when a physician has to decide to give this patient maybe a chemo versus achieving a CR and then allowing a transplant. So that is just something that nobody had expected, that these late-stage patients you ever have a chance to really reconsider to get a cure here. Got it. Thank you. Thank you. One moment, please. Our next question comes from the line of Yale Jen of Laidlaw and Company. Your line is open. Thanks, and appreciate to take the question. I've got two questions regarding the AFM24. The first one is a lot hypothetical and for your opinion. Do you see adding AFM24 is the activity mainly come from its own impact on the treating eliminating the cancer cell, or that actually also resensitize the cells to, again, you know, being for the PD-1, PD-L1? Then I have a follow-up. Yeah, I think what is happening is what we have seen in our monotherapy studies, we are increasing or seeing not only infiltration of NK cells into the tumor, but we are also seeing increased infiltration of T cells into the tumor. And when we look at the immunity cycle, the most likelihood hypothesis that we currently have is that we have initially a destruction of tumor cells by NK cells. We have liberation of new tumor-associated antigens. We are also activating the macrophage compartment, so we have a good processing of these new antigens to the T cells, and finally, you start to generate new tumor-reactive T cell clones. And these, of course, can be then augmented by PD-1. So this appears to be a real fundamental mechanism. We have to see synergy between natural killer cell activating agents and, PD-1 T cell activating agents. Just to remind you, when we, earlier studied acimtamig, we had this, combination study with pembrolizumab. And what we saw there is exactly the same thing. This was now PD-1 naive, but, if you look across the data, we were almost doubling the complete response rate by adding an ICE to PD-1. So I think it's a biological mechanism that may be true for all, ICE, for all drugs that are actively, engaged the NK cells, the macrophage compartment, that if, if you will, can sensitize these tumors to PD-1 again. Okay, great. That's very helpful. And maybe just one more follow-up here is that in terms of AFM24, you've got two cohort, patient cohort, you know, the indication cohort that you're not going to continue. Any updates in terms of, you know, what's the performance over there? And, thanks. Yeah, we will update this data, I think, in context also with the progress report of the lung cancer cohorts. We had very small patient numbers in these two cohorts. We also saw, which I quote it unfortunately, but we did see relatively bad patients. We had many patients progressing after only a couple of weeks of therapy, which did not really allow us to assess the responses in all patients. What I can say so is that we have seen objective responses both in the gastric and in the pan- in the biliary tract cancer cohort. But given where we are as a company, if you see such a strong signal in a so important tumor like non-small cell lung cancer, this is where you now want to focus your attention to. But we have seen responses, objective responses in all cohorts. Okay, great. That's very helpful. And again, thanks a lot and congrats on the data so far. Thank you. One moment, please. Our next question comes from the line of Yanan Zhu of Wells Fargo Securities. Your line is open. Hi, and thanks for taking our questions. I have two for LuminICE study. Just thinking ahead, towards the data at first half 2024, I was wondering whether that data from the four running cohorts could inform contribution of component, despite not having a contribution of component cohort in there, which is obviously cohort six. So I was wondering about, you know, whether there could be read-through from any dose response between the 200 μg and the 300 μg, the AFM13 arms, that could inform the presence or absence of a contribution from the AFM13. And, separately, the second question is also on that readout, is it obviously the AFM13-104 study set a very high bar on ORR. What might be the kind of go, no-go decision, so to speak, at that data readout? Is there an ORR, you know, a threshold that you hope to meet, at that readout? Thank you. Yeah. So to the first question, I don't think the first four cohorts are designed to really address the contribution of components, because all patients will get the NK cells, all patients will get acimtamig. This was why we are starting out with these four cohorts; we are testing a little bit higher dose of acimtamig. The reason here, and this was also something that we discussed with FDA, is that we are providing a very significant number of NK cells that have a very significant amount, of course, of CD16A receptors that need to be bound to acimtamig. So in this specific condition, FDA was interested to see whether a higher dose of acimtamig may be needed to really saturate all of the CD16A receptors that we are providing. But we are firmly convinced that you need both components. You will need acimtamig, and you will need the NK cells to really produce the results. In terms of response rate, we, of course, will aim to duplicate the data that we have seen with MD Anderson, but we have not set a firm threshold that we would need to reach. Again, with six patients, I think you look more at the totality of the data and look for trends, but we are convinced that this treatment will duplicate or replicate what we have seen with MD Anderson. Got it. That's very helpful. Thank you. Thank you. We're currently showing no further questions at this time. This does conclude today's conference call. Thank you all for participating, and you may all disconnect. Have a great day.