Everyone, my name is Maury Raycroft, and I'm one of the biotech analysts at Jefferies. Thanks for joining us today. And I'd like to welcome our guest today, Adi Hoess, the CEO of Affimed. Thanks for joining us, Adi. We're going to do fireside chat format. So maybe to start off, for those who are new to the story, if you can give a one-minute intro. Yeah. Yeah. Thanks for inviting us here and giving us the opportunity to talk to you. So what does Affimed do? Primarily developing bispecific antibodies that are able to, on the one side, attach to a tumor antigen, on the other side, can recruit natural killer cells and macrophages. We do this with very high affinity, hence we're very distinguished from other approaches and have shown in the clinic single agent efficacy of our molecules in different types of lymphoma, in solid tumors, and are also approaching data in AML. Interesting is that we see the single agent responses in patients based on their own NK cells they can provide, but they have limits. They're usually not very active, meaning they also have low numbers. The other part we can do is that we have now established a regime, a combination regime that allows us to treat patients with bispecific antibodies, Innate Cell Engagers, as we call them, and allogeneic natural killer cells off the shelf. Got it. Yeah, it's a great intro. You've got a registrational study ongoing. Maybe talk about the design for that study, and you also had some FDA feedback recently on that, so maybe talk about that as well. Right. Yeah. Early in the year, we filed an IND, and that means in April, May, we got the IND approved by the FDA, which is a study that has been designed in basically accordance with guidelines of FDA, that this study can be a registrational directed study. FDA has commented at that time that they... let's call it, they have a certain request to modify the study, and this request and that was the recent interaction related to adding an additional cohort. So in detail, we have four cohorts in the beginning, ongoing, which we call run-in phase, that is testing two different doses of AFM13. From now on, I will call it acimtamig. That's the new INN name. acimtamig is either dosed to 200 mg or 300 mg, and this is either paired with 6 billion NK cells given as 2-2- 2, so three weekly installments, each 2 billion or 4-2- 2. So that makes two different doses of AFM13, two different doses of cells, which makes four cohorts, each six patients. That's the first data that we can publish next year, in the first half of next year. We have a fifth cohort, sorry, this cohort will treat Hodgkin lymphoma patients. A fifth cohort will investigate initially the efficacy of acimtamig and the Allo NK cell product in peripheral T-cell lymphoma. So that all was agreed when we submitted the IND. Now, we had to add a sixth cohort investigating just the NK cell alone as a comparator. We know that NK cells, in general, are not very active in particular aggressive lymphoma. So we, in the beginning, weren't sure if we should do so for ethical reasons or do it for practical reasons, meaning that you have a comparator. But we have just aligned with FDA that this modification has been done, and FDA has accepted our proposal. So this can be per protocol, 12 additional patients. We are rescuing these patients if they have no activity, which we mostly may expect, by then allowing the patients to cross over and receive acimtamig plus the NK cell. That's the most recent modification, meaning that we're now up and running the study, treating patients, and as we move along, we're publishing data. But we have fast track that also we received recently and have the opportunity to continue the dialogue with FDA because they have been pretty supportive in their communication to us to help us to bring this to market in a single-arm trial. So this is not a randomized controlled trial. That has not been requested, so we can move forward with a single-arm trial. And just to confirm this, FDA has given a few approvals this year just based on single-arm trials, and our efficacy has been very high in the proof of concept, with 90%+ response rate and over 70% CR rate. So with these high numbers, we are obviously qualifying for that kind of approvals. Yeah, makes sense. Yeah, I think the proof of concept data from MD Anderson, we'll talk more about that later, but that showed really good results, and now you've got this registrational study. You mentioned on the conference call yesterday that this single study could qualify for, for approval, based on the magnitude of benefit. I was wondering if you could just talk about that a little bit more, what that, that bar could be and if there's good reference data out there for that. Yeah. So most important, you have to pick the right patient population. So this is another agreement that we've achieved in terms of what's the right patient population you have to be in? And according to guidelines, FDA says you have to be in a patient population that has exhausted every established therapy, and you have quite some. In Hodgkin lymphoma, there's frontline chemo, there is Adcetris, and there are PD-1 checkpoints, either nivolumab or pembrolizumab. Interesting, all our data that we have generated to date already in this refractory patient population. I call it double refractory patient population for the simplicity, all our data has already been generated in this patient population. And in order to just emphasize that this is the right patient population, these patients that we have treated in the MD Anderson study all had a prior treatment where they were refractory to. So that means that they did not respond, and that's what you're currently, or you're what you're chasing for accelerated approval. So that's a strong data we already have, that we don't switch the patient population. We've been in there, that's why we have the strong data, and that's what we are now, that's what we're now doing. ... Got it. Makes sense. And, digging into that a little bit more, you mentioned that you did get some KOL feedback on what the bar could be. You mentioned 50%- Ah, okay. Overall response rate Yeah. -with a lot of CRs comprising that. Skipped over this answer, but I didn't do it intentionally, so. It's okay. Yeah, exactly. You do not get a strict feedback from FDA on what the bar is because they do their evaluation based on safety data. Ours looks very good, so we have a very, very good safety profile. They do it on efficacy and on the duration of response. We have only reported limited data for the duration of response, but this is the new update that's coming up at ASH. That's when we have 12 months plus follow-up on most of the patients. So stay tuned on, on this particular update because this will provide you PFS and durability data. In general, the bar for an accelerated approval, we're hearing 50%. So remember, we are above 90% with overall efficacy, and a good proportion of that needed to be partial responses. So let's say complete responses. So let's say at least 25%-30% should be complete responses. Again, currently, we sit on over 70%, and that's in over 30 patients we have tested, so it's already a significant large number. So that's probably the bar that we should hit, and then we may be successful with such an approach. Great. Yeah, so based on the data you've already shown, it's pretty reasonable, could be viewed as a low bar for what the KOLs want to see for- Yeah. -this. Yeah. For durability, I think you said six plus months for that. Is that for the CRs, or is that for-? Durability is on every response. So we are indeed in the particular situation that usually you have, like, a 40% response, and the durability is just counted on those patients that have a response, and you're neglecting the other 60%. We have a response rate with over 90%, 95%, so meaning, I think, except one patient ever responded. That means that our durability obviously moves a lot of patients on the positive end. Yes, so with six months, we have a lot of patients that have durations of nine, 12, and even longer. As I say, we'll report in ASH, but that's the lower end. Probably want to be anywhere in the eight to nine months range. That would be ideal. Got it. Makes sense. Yeah. And- Again, just to qualify that, there are other chemos out there that have efficacies in the range of 40%-50% and durabilities in the range of three to five months. So that's why you want to be above. Interesting is none of these chemos, so bendamustine or lenalidomide, they have never been tested in this double refractory patient population in a genetic study. So all their data is predating treatments with atezolizumab or PD-1, so they are in a far milder patient population, not as heavily pretreated. Right. Yeah, makes sense. And for your run-in update in first half of 2024, how many patients of the 24 do you expect data for in that update, and how much follow-up? Yeah. And what, what are you... In principle, as many as we, as we can. It's yet a little too early to really give you the exact number because we have just started this study, so we need about 5-10 sites up and running. Now, by that, the plan is to have this all concluded by December, so that if, if we're successful here, it looks pretty good because we have identified 25 sites overall that wish to participate. We have ranked those according to available patients, and that's the 5, 6 sites that we want to have initially. So we have high chances that all this will be on board, and then we should be able to recruit all that number, but we know more within the next four weeks. Interesting is those sites that are active, they all have immediately presented patients to us, not just one, but two, in one case, even four. So it seems that the early signs that we're seeing is quite encouraging on that end, and now we are executing. But we should say by JPMorgan, we should definitely know how far advanced we are. Got it. For the data that you get in the first half of 2024, will that be enough to inform your dose optimization part of the study? When could that start? Could that start second half of the year? That's the plan, that we start in the second half of the year. Exactly. And yes, that's sufficient data. So the requirement is to have one restaging done on all 24 patients, so it's a judgment on just objective responses. Interesting is, as I said, we expect that we see responses in all these cohorts as we are treating only with active doses. So it's... We have obviously a schedule and a decision path on which dose to select if they all look even. And so it all fall through in order to have a quick decision on which dose we're gonna pick in order to continue with stages one and two. Got it. Okay, and for the 25 sites, you mentioned probably five or six are gonna be higher-producing- Right ... sites. Would those be enough for the whole study, or do you anticipate having more sites? No, we continue. So most other sites will be then brought on in between, mostly February, March, April. So the first sites will be sufficient to run this, these initial patients, the 24, and then we add more for the stages 1 and stage 2. We're also exploring conducting the study in Europe, so we have parallel work ongoing. Why are we not yet in Europe? The IND or CTA for the cell is not yet filed in Europe. That's the next ambition we have, so to move with the cell into Europe, and as soon as that's allowed. That's probably available in the second half. So you see, once we're in stages 1, 2, we want to have Europe contributing. Got it. Okay. Makes sense. And for the expansion cohort, can you talk about what FDA will want to see as it relates to your decision to move into this part of the study with 1 or 2 doses? And can you talk about timelines here, depending on whether you need 1 or 2 doses? So as I say, we start with 4 cohorts, reduce it to 2, each 13 patients. Here, the decision is based on 2 cycles of treatment. Why that? Because cycle 1 at MD Anderson has shown that we have a high response rate, but the CRs were only at 35%. So with the second cycle, we moved the CRs from 35% to above 70%, and the third cycle did not much add in terms of response rate. So the CRs were the CRs. In that context, that's why we decided to take the decision after the 2 cycles. Obviously, again, the decision is then based on response rates at that time, and it will also be based on the magnitude of effect we're seeing. So the design we have, and that's what we have agreed with FDA, gives us a lot of flexibility. Can be roughly 70 patients on the lower end or 110 patients on the higher end. So we can, without going back and redesigning, readjusting, we can just add in these additional patients to move swiftly. That's the agreement with FDA. So it's dependent on the magnitude of effect we're seeing. Got it. Okay, makes sense. And for the update, first half of next year, you mentioned potentially around JPMorgan, you could have some line of sight into more granularity for when you can- In terms of recruitment. Recruitment? Yeah. Yeah. And then for the actual update, would that be at a medical conference or, you made that decision? Yeah, it's again, obviously, we wanna see and have first data before we submit an abstract. So again, that's being decided as we move along in the first quarter of next year, then we can decide. But yes, we're always aiming at medical conferences in order to present such data. That's the idea. Got it. Makes sense. And, for the update yesterday about the individual component contributions and this additional smaller cohort that you're adding to the study, for that cohort, how long do you think it would take to enroll that and get to an update? Yeah, it's... So we're still planning on when we exactly will start this cohort, so I can't give you any detail. That's just information that is super fresh. So we just got the feedback from FDA a couple of weeks ago, and now we're amending the study and then move forward. But it's not during the first 24 patients. That's what I can say. So we will not start with the cell-only dose. We will first generate data just on the active dose levels. That's the ambition. And then we have optionalities on when we'll bring it up. Got it. And if one of the patients or if a patient in that cohort progresses, they could get rescued with AFM13. Correct. Yeah. Okay. Yeah. With AFM13+ Allo NK. So the cell- Right ... is always required, the compound itself. Makes sense. And let's see. Wanted to talk about the MD Anderson data update at ASH in December. Maybe set the stage for that and what kind of update we should be looking for there. Yeah, obviously, I cannot say much because it's an oral presentation, so you're under embargo until that day. But, the content is, that we have longer follow-up. So we have, almost every patient by that time will have at least 12 months of, follow-up period, some range up to three years. We've already shown that there are very long-term, responders, in this group, and that's what it will mostly be about. Got it. And if you do see longer-term durability in this update, what are your latest thoughts on how that would translate to your current registrational study with AFM13+ AB-101? Yeah, it's what I would say mostly it's data what investors are interested in. The field somehow is criticizing durability for NK cells for me, for non-obvious reasons, because we're in a late-line patient population, as I said, that have passed through their most recent therapy. It tells you everything what that means to a patient, okay? That means that you may only live for two to three months. So anything above six months is a median. So median duration of response or median PFS is a big success for these patients. Seven prior lines is also telling you that these are incurable patients anyhow, but have a very aggressive underlying disease. And to treat aggressive patients is usually not what you want to start with in the first place, but that's the game in Hodgkin lymphoma. We also want to do PTCL, which is less aggressive in that context because they're only relying on a frontline therapy that only can, let's say, roughly cure half of patients. And if you, as a PTCL patient, move to second line, then you have no fully approved drugs available anymore. So with second line, you are on conditionally approved drugs that are left on the market despite low efficacy and only a medium durability, but there is nothing else there. So that's the second attempt that we're gonna have. We feel that we have a good chance also to be successful in peripheral T-cell lymphoma. Small number of patients have indicated that there is high efficacy as well, but it's only a couple of patients we have treated so far. And that gives us, interestingly enough, in Europe, U.S., a market opportunity that in Hodgkin lymphoma it can be a market opportunity is calculated as $1 billion. PTCL is even $2 billion. So the combined market opportunity in relapsed/refractory Hodgkin and PTCL is amounting to $3 billion. Got it. Yeah, I was definitely gonna ask about the market opportunity there. For PTCL, can you talk about timing for when you would start that, that cohort? Yeah. The ambition is that, we're gonna bring on site, as we speak, and then start in the first half of next year, treating that. Yeah. Got it. That's the idea. When we have data, we can let you know once we have started. That's the idea. You mentioned the $3 billion market opportunity. If you're successful here, is there a path to move to frontline setting for- In PTCL, definitely, because that's why I say the bar is not as high as it is in Hodgkin. Hodgkin's probably the ambition is to go to second line, so that's where the need is, where you can have with high CR rates, you can patient move to transplant. Indeed, the same for PTCL that the therapies are not strong enough in order to get patients on transplant, and that would be the same ambition in Hodgkin lymphoma. Hodgkin lymphoma frontline is, I would do it, but it's very challenging as you have very long-term studies that may last for si, 7 years. But because of the fairly high pricing, we can assume, so we're comparing pricing with CAR-Ts, and CAR-Ts comprise two sets of pricing: the drug acquisition, but also the associated therapy costs that are almost 50% of the drug acquisition cost. So you see that, for that reason, we can build this market opportunity even with not being in frontline Hodgkin. Got it. Makes sense. And, let's shift gears to AFM24. You're going to have an update from that program as well, in combination with atezo. Maybe talk about how many patients from the three different cohorts you could have data from and, what would go into go, no-go decision- Yeah for those. So, most important, we're still not finished with updating you on the monotherapy study. So that means that we have treated patients with AFM24 monotherapy, had used three cohorts: colon cancer, renal cell carcinoma, and non-small cell lung cancer. You have a mutant population. We have seen highest efficacy in the mutant population with partial responses and stable diseases. What you haven't yet seen is the PFS. As we had a good number of stable diseases, it's obviously very exciting to see durable, stable diseases. So that data is due in December and is already indicative of where we stand here. Because we have seen in patients that we do not only activate the innate immune system, so macrophages and NK cells, but we also see an uptake of T cells. That's where the synergy comes in with the checkpoint inhibitors, such as atezolizumab. So that's the underlying principle why we are very hopeful. So what you're gonna see is... Let's put it this way: we are treating four cohorts. Out of these two are lung cohorts. That's where we currently have the best data. We have gastric cancer and a vascular cohort, so we are reporting on three of the four cohorts. Mutant is behind because we added that just most recently based on the, on the mono data. And the data will be largely in 10-15 patients, so it's still a very early look, and then we can decide how we continue. It's also mostly on just the initial response rates, so we have limited follow-up yet in terms of how durable then the chances will be. That's why I believe that it's important also to see the durability of stable diseases with monotherapy. Got it. You mentioned the EGFR mutant cohort. When do you expect to complete enrollment of that cohort, and how many patients could you have in the first half of 2024 update? So, in essence, it's we have a very high chance to complete this enrollment still this year. So we're seeing a lot of patients being available, and so that's positive. Obviously, then just a minimum of, I would say, three to six months later, we're gonna have the data. So the first half of next year, when this data comes, again, trying to aim at the medical conference with this update. Got it. And do you have different expectations for EGFR wild type versus mutant as far as efficacy goes, based on what you've seen so far? Well, you always have to look at the individual treatment regimens available in these patients. Again, we're later lines, mostly in lung. It's third, fourth line, similar, wild type and mutant, and you just compare yourself to currently available treatments, which usually are in the current categories of three to four months of PFS. So it's a quite miserable disease to have, and as soon as we see the PFS trending usually in the ranges of five point five to six months, that's what you want to see. Then you're already in the ballpark where you have a strong story. Got it. So that's the, that's the, the view we have in non-small cell lung cancer. Okay, makes sense. And with the proof of concept efficacy that you've got so far from the platform with combining your bispecific with NK cell, how do you think about weighing factors that go into a partnership for AFM24 for an NK cell? Yeah. In general, what we have learned also from our initial investigations, NK cell can get to solid tumors and shrink tumors, so that's the important message that we have. These are patients only, NK cells. So we have seen in Hodgkin that we could jump from 15% single-agent efficacy, AFM13, to above 90% by combining in an NK cell. How far advanced are we? We have to find the right partner that is working with us in such an indication. We are focusing only on cells that are non-modified and are produced in larger quantities, so Artiva is amongst that in the mix here. But obviously we already have a study ongoing with them where we need a lot of NK cells, so it can also be another player. The other players are just developing their drugs to recommended phase two doses. So that's what is what we have to wait for. So again, with next year, we're gonna have additional opportunities. We are evaluating at the moment, these NK cells, so we're working together in order to see if they are working as well as we've learned with the Artiva cell, but that so far looks good. So we, we can have several options here. Got it. And yesterday on the conference call, you, you mentioned that, the 100 mg dose for AFM28 is completed and you're now in, the 200 mg Yeah ... dose cohort level four. How much higher do you anticipate going with the dose escalation, and when could you start to see clinical activity? Yeah. So at the moment, as you said, we're planning to jump from dose level four to five. That's the next step we have to take. And then we had been exceptionally fast in this clinical study, meaning that we have dosed the first patient in April, and here we are, we're almost finished with dose level 4, and we are fully recruited dose level 4 in just, like, six to seven months. But we only have usually done 2 patients per dose level. So that means it's very few. On dose level 4, we had a few more patients and dose level 5. So probably we need to assess dose level 4 and 5 in order to get a picture on where we are, because now we can not only see and measure PK, but also the receptor occupancy. That's usually our qualifier. So with dose level 4 and 5 finished, we can give you an update on that. So again, as we said, we guide to the next update on how we proceed early next year. Let me just finish here. Most important to us is to establish safety on AFM28. If we have a safe dose, even with efficacy or not, doesn't matter, we want to combine with NK cells. Got it. Makes sense. And I think we covered a lot of ground. Maybe to close out, if you want to, talk about cash position, current runway, and key catalysts ahead for the next, Yeah ... six to 12 months. We have multiple catalysts. To start out with the first one, December, we have two, both on AFM13 and AFM24, very important catalysts. And also first half next year, we're gonna have data on AFM13, AFM24, and AFM28. So catalysts rich, six months in front of us. Cash position is about $100 million at the end of Q3, taking us into 2025 without adjusting to anything what we do. So whatever I'm telling you is funded, so quite some good funding position, and that's where we are. Got it. Thanks so much for joining us today, Adi. Thank you, Maury.