Affimed N.V.

Good day, and thank you for standing by. Welcome to AFIMED NV Third Quarter 2023 Earnings and Business Update Conference Call. At this time, all participants are in a listen-only mode. After the speaker's presentation, there will be a question and answer session. To ask a question during the session, you'll need to press star 11 on your telephone. You will then hear an automated message advising your hand is raised. To withdraw your question, please press star 11 again. please be advised that today's conference is being recorded. I would now like to hand the conference over to your speaker today, Alex Futakidis, head of investor relations. Please begin, sir.

Thank you, Norma, and thank you all for joining us today for our third quarter 2023 update call. Before we begin, I'd like to remind everyone that he issued the relevant press release earlier today, which can be found on the investor relations section of our website. The presentation is also on the website. On the call today, we have the members of our management team, including Adi Huss, our Chief Executive Officer, Andreas Harstreich, our Chief Medical Officer, Arne Stupelius, our Chief Scientific Officer, Wolfgang Fischer, our Chief Operating Officer, and Angus Smith, our Chief Financial Officer. The team will be available for Q&A after the prepared remarks. Before we start, I would like to remind you that today's presentation contains projections and forward-looking statements regarding future events. These statements represent our beliefs and assumptions only as of the date of this 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 actually 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 statement and the press release that we issued today and filed with the SEC. With that, I'll turn the call over to Adi. Adi?

Thank you, Alex. Good day, everyone. And thanks a lot for joining us today, also from my side. We have entered a very important and exciting phase for us in it. Our investors and patients that do require novel options in order to prolong their lives so that they can spend more time with their families and friends. We have been progressing well with all three Kennedy programs and are now in a period where we plan to report data frequently over the next weeks and months. Moving to slide five, we recently announced that the new name for ACE-M13 will be Asymptomic. Asymptomic is developed in combination with Arteva's Allo-NK product in the LUMINIZE-203 study. We're now actively recruiting Hodgkin lymphoma patients in the LUMINIZE-203 and preparing to report efficacy and safety data from the study in the first half of . As a reminder, during this phase of the study, we will be treating 24 patients with Hodgkin lymphoma in four cores. and all these cores will use active doses of asymptomic and allo-NK. In addition, our interactions with the FDA have been very productive. In September, we announced that we received fast-track designation, and today we announced that we received positive feedback from the FDA in their responses for our Type C meeting, which Andreas will discuss in just a moment. But from the FDA's written responses, we believe that the LUMINOIDS-203 study design, based on FDA feedback and guidelines, puts us in a very good position to pursue accelerated approval. The LUMINOIDS-203 study builds on the unprecedented results observed in AFM13-104. The investigator-sponsored clinical trial we have been running in collaboration with Andy Anders. Updated data from that study will be presented by Dr. Iago Nieto, the lead investigator at the ASH annual meeting 2023 on December 11th. AFIMIT will host a dedicated call for the financial community to provide an in-depth insight into this important update, which will include longer follow-up dates. Now turning to AFM24, we remain on track to provide an update on the first three expansion cohorts from the combination study of AFM24 with atezolizumab in December. This combination is based on findings that AFM24 activates both innate and adaptive immune cells, and the idea now is to enhance efficacy by combining AFM24 with atezolizumab. As a reminder, we already have seen that our inertal engager, asymptomic in combination with PD-1, is able to double the complete response rate of PD-1 alone in relapsed refractory hot conformer patients. During the third quarter, we also initiated enrollment in the North Muslim lung cancer EGFR mutant cohort and have begun treating patients. Again, as a reminder, EFIM24 is a single agent showed partial responses and durable stable diseases in this indication. Data from this expansion cohort is expected in the first half of 2024. And last, we continued to make good progress in our ASM28 monotherapy dose escalation. During the third quarter, we completed treatment of patients in the third-dose cohort without any limiting dose-limiting facilities and completed enrollment of patients in the fourth-dose cohort, now administering a flat-dose 200-milligram weekly. On slide six and seven, we provide important background on the treatment of the indications we're targeting with Luminize 203. In Hodgkin lymphoma, BV and PD-1 checkpoint inhibitors have changed the way patients are treated. As these therapies move to earlier lines of therapy, a patient population with high unmet medical need has emerged, their BV and PD-1 double refractory population. Now let me quickly talk about which therapies exist in general for relapsed refractory Hodgkin lymphoma. For this patient population, cytotoxic agents such as platinum chemo, impendimustin, or even targeted agents such as linoleumide or mTOR inhibitors are listed in the NCCN guidelines. But it's important to note that these therapies were studied in relapsed refractory heart patients before the introduction of PV and checkpoint inhibitors. And limited information is available on their efficacy in the double refractory population. But even still, they are characterized by low ZR rate and poor peers. We believe this is where a symptomatic plus in case of therapy has the potential to transform the treatment landscape for double refractory patients. The response rates reported from AFM 13-104 are outstanding. And in particular, the ZR rate of 70 plus percent is higher than the CR rate of other treatments, even in less heavily pre-treated patients. And as next month, we'll provide a definite view on the duration of response and event-free survival for the therapy for HL patients treated at the recommended phase. Luminize 203 further includes relapsed refractory TTCL patients. TTCL has a very high need with more than half of patients moving to second-line, which now offers only agents with limited efficacy and still no full recruitment. Based on our market results, we believe the market opportunity for asymptomic plus-in-case cells in double-refractory Hodgkin lymphoma alone is in excess of 1 billion. And with the inclusion of second-line relapsed refractory TTCL, This would increase to over 3 billion combined. Finally, during the quarter, we saw a significant reduction in our operating cash burn as we come to the first two quarters of the year, a result of the actions we implemented during the first half of the year to focus our investments on our three clinical programs. With that, I'll turn the call over to Andreas, who will provide additional input on the progress we're making in our pipeline. Andrea?

Thank you, Adi, and also welcome from my side to everyone on the phone. I would like to start my clinical overview with our progress that we made with AFM13, as Adi said, now called asymptomic going forward. We are pleased to update you on the progress that we have made regarding the development of asymptomic in combination with LONK or is it also known AB101 from ARTIVA. After receiving the clearance from FDA to proceed with the initiation of the phase two clinical trial earlier this year, we made significant progress towards our goal of getting the study up and running. And we now have the first sites open and we are actively recruiting patients. Furthermore, as shown on slide nine, In September, we received fast-track designation for asymptomic, and in October, we got a written feedback from FDA on our type C meeting request. On slide 10, we show the updated Luminize study design. In accordance with FDA's feedback, we will now add a cohort to the Luminize 203 trial which will treat patients with relapsed or refractory Hodgkin's lymphoma with LONK plus IL-2 only. This will address the contribution of individual components in the combination. This cohort will be designed as an observation cohort with the option available to patients to cross over to the combination with the symptomic if they don't show a response to their initial treatment. We believe that the study, which was designed based on FDA's recommendation and guidelines, puts us on track for regulatory approval pending the final assessment of the magnitude of clinical benefit. We are very encouraged with the outcome of the FDA interactions and look forward to continuing our discussions with the agency as we are generating data from the study. As announced, we expect to report initial safety and efficacy data from this trial during the first half of 2024. In addition, as Adi mentioned, Dr. Jagunieko, the lead investigator of the original study that investigated the combination of asymptomic with cord blood-derived NK cells at MD Anderson Cancer Center, will present updated data in an oral presentation at the ASH 2023 Annual Meeting on December 11. The abstract for the presentation was published earlier this month. As shown on slide 11, at the cutoff date for the abstract, a total of 42 relapsed refractory CD30 positive Hodgkin lymphoma and non-Hodgkin lymphoma patients were enrolled in the study, with 36 of these patients treated at the recommended phase two dose. Important to mention that all patients were heavily pretreated and refractory to their most recent line of therapy with active progressive disease at the time of enrollment. Of note, all of the Hodgkin lymphoma patients were double refractory to BV and PD-1. The combination treatment achieved an overall response rate of 94.4% with a complete response rate of 72.2% at the recommended phase two dose. The treatment regimen continues to demonstrate a good safety and tolerability profile with no cases of cytokine release syndrome, immune effect of cell-associated neurotoxicity, or graft versus host disease of any grade. At a median follow-up of 14 months, The overall survival rate was 76%, and the median overall survival has not been reached. An in-depth analysis included updated event-free survival and overall survival data will be presented during Dr. Nieto's oral presentation, including a comprehensive analysis of efficacy, durability, and safety outcomes. demonstrating the potential of a symptomatic in combination with allogeneic and K cells. On the same day, AFIA met plans to host an investor call to provide additional information about the status of the LUMINIZE-203 study, the treatment landscape in Hodgkin lymphoma and peripheral T cell lymphoma, and the respective market opportunities. Now, let me turn to AFM24. As shown on slide 12, in the ongoing study AFM24102, we are treating patients with AFM24 and atesolizumab. In the ongoing study, the original three cohorts included patients with non-small cell lung cancer, EGFR wild type, gastric and gastroesophageal junction adenocarcinoma, and pancreatic hepatocellular and biliary tract cancers, respectively. Based on the promising activity seen with AFM24 in our monotherapy study, we added also a cohort for EGFR mutant non-small cell lung cancer patients that is now actively treating patients. We believe that AFM24's role in activating the immune system by specifically triggering NK cells and macrophages to destroy tumor cells and to liberate tumor-associated antigens is crucial. These antigens can be processed by macrophages and dendritic cells with the possibility to activate tumor-reactive T cells. The combination of AFN24, which activates the innate immune system, with a tesolizumab, which impacts the adaptive immune system, therefore has, in our opinion, a very good logical rationale. As Eddie mentioned, we will report data on the first three cohorts, of 10 to 15 patients per cohort in December, and we plan to report the data on the non-small cell lung cancer EGFR mutant cohort in the first half of 2024. If we turn to AFM28 on slide 13, we show the progress for our third clinical program. AFM28 is targeting CD123 in acute myeloid leukemia. In this program, we have completed treatment of patients in the third dose cohort of our ongoing dose escalation trial, using a dose of 100 milligram FLAT once weekly. As mentioned, we have not seen any dose-limiting toxicities at this dose cohort, and we meanwhile have completed the enrollment of patients in dose cohort four, treating patients at 200 milligrams weekly. Now, where do we go with AFM28? The first step is to complete the dose escalation study and to identify a safe recommended phase two dose based on correlative science and initial clinical activity. After that, for us, there are two options, either to develop AFM28 as single agent or in combination with allogeneic and K cells. We are planning to provide the next progress update on this during the first half of next year. Now, thank you again for your attention, and with this, I will turn over the call to Angus to update you on the quarterly financial performance. Angus, please.

Thank you, Andreas. Balance sheet and income statement highlights are shown on slides 15 and 16 of the presentation. A quick reminder that Appymed's consolidated financial statements have been compared with IFRS as issued by the International Accounting Standard Board or IASB. The consolidated financial statements are prepared in euros. Since our financials are described in detail in the press release we issued this morning, I will only provide highlights on this call. As of September 30, 2020-2023, cash equivalents and financial assets totaled 97.5 million euros compared to 190.3 million euros on December 31, 2022. Based on our current operating plan and assumptions, we anticipate that our cash and cash equivalents along with our financial assets will support operations into 2025. Net cash used in operating activities for the quarter ended September 30th, 2023 for 18.2 million euros compared to 19 million euros for the third quarter of 2022. Importantly, our operating cash burn for the quarter reflected a 45% drop from the previous quarter and is reflective of our efforts to carefully manage our cash burn going forward. Cash flow from investing activities for the quarter reflects the fact that we allocated a portion of our cash resources to short-term government bonds during the quarter in an effort to diversify and get access to higher interest rates on our excess liquidity. Total revenue for the quarter ended September 30th, 2023 was 2 million euros compared with 14.9 million euros for the quarter ended September 30th, 2022. Total revenue predominantly relates to the Roivant and Genentech collaborations and the reduction as compared to the prior year period is due to the fact that we have now completed our obligations under both collaborations and therefore recognize the significant majority of the associated revenue. We remain eligible for future milestone payments under both collaborations based on the advancement of the licensed molecules, which is at the discretion of our partners. I will now turn the call back to Adi for closing remarks. Adi?

Thank you, Angus. Let's move to slide 18. Here you see the details of our upcoming milestones for all our programs. As I said in my intro, we have entered a very important and exciting phase For us at Afimet, our investors and in particular patients that do require novel options in order to prolong their lives, to be able to spend more time with their families and friends. We have been progressing well with all our three clinical programs and are in this period where we plan to frequently report data over the next weeks and months. Thank you all for your continued support and trust in our mission to make a difference in the lives of patients. We look forward to sharing more exciting developments with you in the very near future. We're now ready to take questions. Operator?

Thank you. As a reminder, to ask a question, you'll need to press star 11 on your telephone. To withdraw your question, please press star 11 again. Please wait for your name to be announced. Please stand by while we compile the Q&A roster. One moment for our first question, please. Our first question comes from the line of Maury Raycroft of Jefferies. Your line is now open.

Hi, this is James on for Maury. Congratulations on the progress and thank you for taking our questions. For the Type C meeting, did the FDA provide Any more specifics on the magnitude of clinical benefit? And do they seem more focused on ORR or durability measures? And then after that, I'll click follow on.

Andreas, do you want to take that question, please?

I can take it, or Wolfgang, who I think is also on the line, but I can probably start. So now, as you may know, when you talk with FDA, they will never give you a fixed number of what they consider is a meaningful magnitude of effect. However, when we look at the landscape and when we talk to key opinion leaders, and we have done quite a number of interviews right now, I think the consensus seems to focus on 50% response rate or higher, with the majority of responses being complete responses. And when you look at time-related factors, I think it's probably duration of or even progression-free survival of six months or longer for these very heavily pretreated patients. Now, again, I have to stress this is more feedback from key opinion leaders. FDA will always tell you it's a review issue, and we expect that FDA will look both at overall response rate as well as time-related factors like either duration of response or event or progression-free survival. I hope this addresses your question.

Yes, that's helpful. And the second question is, how many patients and follow-up do you need to adequately address the contribution of single components in the IL-2 cord that you reported today?

Again, that is a question that probably will be answered by the data. We expect that the response rate for a non-targeted NK cell will be relatively low So we will see or we expect to see already very significant differences in the response rates, which clearly will diminish the importance of long-term follow-up. If you only have a couple of responses compared to a response rate, which is in excess of 50%, 60%, I think the magnitude of differences would be sufficient.

So how many patients do you think you would need?

Again, this is something that we will discuss further with FDA. The initial design is somewhere between 10 and 20 patients.

Great. Thank you so much for answering the question. I'll hop back into the queue.

Thank you. One moment for our next question, please. Our next question comes from the line of Sri Rippa Devarakonda with Truist Securities. Your line is now open.

Great. Hey, guys. Thank you so much. I have actually a follow-up on the previous question. Just to confirm, were there any changes to the protocol that the FDA asked for just broadly? And also, based on the type C meeting, can you move ahead with part two of the study or following part one, is there any need to um meet with the fda again i know you guys have um you know you can have multiple meetings with the fda given your designation fast track designation takes us as well or do you want to take sure i can take it hi so the first the first question whether there have been changes to the protocol requested by the fda the answer is no

But as Andreas mentioned before, we are going to add this one cohort alone. That's the first question. And the second question, there is no need for us to go back or consult with the FDA to proceed with our study. So that means we can proceed from the beginning to the end as approved by the FDA.

Got it. And also just another clarification, is this ALO and KIL-2 cohort needed for accelerated approval submission?

When we spoke to the FDA during IND process and also during Type C, the contribution of single components is important to the agency. And therefore, the assumption is, yes, this is something which we need to get accelerated approval.

Great. Thank you so much.

You're welcome.

Thank you. One moment for our next question, please. Our next question comes from the line of Lee Wasik with Cantor Fitzgerald. Your line is now open.

Hey, thanks for taking my questions. Maybe just a follow-up for the, you know, the new NK cohort. Can you just clarify, do these patients need to progress before they can cross over? Maybe just a little more color on the criteria for crossover. And then can you count these patients in the total and to support the efficacy as well?

Yeah. I can take that question. Yes, these patients, right, when treated with LONK IL-2, If they are not responding, that means if they are not showing a partial response or a complete response, they will have the opportunity to cross over to the combination treatment. Now, this brings me to your second question, whether these patients then could go cross over into the analysis cohort for the primary endpoint. And the answer is no, because there could be a bias. So what we are having, right, is that we say, they can cross over to the combination treatment and will be treated but not be part of this analysis for the primary endpoint.

Okay, got it. And then you mentioned earlier you had the first site open enrolling patients. Just can you give us some sense in terms of, you know, how many sites do we need to fully enroll the rung-in portion?

Andrea, do you want to?

Yeah. I mean, for the run-in portion, as you know, there is somewhat of a staggered approach, especially for the first three patients per cohort. So our current assumption is that we probably need five to six good recruiting sites for the initial four cohorts, and then we will bring more sites on board as the study progresses or continues. But we are in an active process to add sites. But as we said, we are on track to provide the initial safety and efficacy data for the first half of 2024.

Okay, thank you.

Thank you. One moment for our next question, please. Our next question comes from the line of Diana Graybush with Learing Partners. Your line is now open.

Thanks. Two questions for me. One on the new AB101 arm. I think you had known that it was a possibility that FDA would want an arm like this for contribution of components. But initially, my understanding is didn't include it in the design because KOL feedback that they were hesitant to enroll patients into such an arm given the preclinical data suggesting NK cells alone wouldn't have benefits. I wonder how have your conversations gone with KOLs and sites, and what can you do to ensure enrollment into this arm and enrollment overall to this study now that this arm is a possibility? And then my second question is on AFM24. And, you know, just particularly in EGFR mutant lung cancer, but also across your indications a lot of interesting data with antibody drug conjugates. And I wonder whether there's potential down the road after you show benefits that combine with chemotherapy and if you're considering that in the form of an ADC going forward. Thank you.

Andrea.

Yeah, I can take both questions. So, yeah, so the LONK-IO2 arm, as you mentioned, is an arm that we added also after discussion with some of our clinical advisor key opinion leaders. Probably the only way to make such an arm a recruiting arm is what we implemented now that we give patients the option if they do not have a response after cycle one, they can immediately cross over to the combination treatment. So they will have the option to receive what we believe is the more active treatment. And again, as I said, we believe that the number of patients in this arm will be relatively small, as we are not expecting to see a very high response rate here. So this is, I think, a good compromise that most of our clinical sites believe is acceptable to patients. If you would have an arm that has only LONK cells without the option to cross over, I think you would have quite significant challenges to recruit in such an arm. As for AFM24, yes, we have a number of indications, especially in the non-small cell lung cancer field, where we do see ADCs coming up, and we believe that the mechanism of action of AFM24 could fit very well with ADCs. combination either with TKIs, for example, in the EGFR mutant field, or with ADCs both in the non-small cell line cancer EGFR wide-type. And EGFR mutant fields are definitely options that we would look at after we have completed our 102 study.

Great. Thank you. Thank you. One moment for our next question, please. Our next question comes from the line of Yanan Hu with Wells Fargo. Your line is now open.

Great. Thanks for the questions. Two questions on the AFM 13 program. The first one is how is the infusions of the NK and AFM 13 handled on the day of infusion? I was wondering, since this is not a pretty complex product, which component is infused first and what is the space of time between the two infusions? The second question is about how you select the two cohorts for stage two. Would that be based on two cohorts having to have the same NK component, NK dose, or these two cohorts having to have the same AFM13 dose, or it doesn't matter, just the two cohorts with the best performing ORR? Thank you.

Andrea? Yeah, so in terms of administration and how the trial currently is designed, We start on the days where we give AFM 13 or symptomatic and NK cells with the symptomatic infusion. Initial infusion duration is four hours for the first cycle but with the option to reduce the duration of the infusion if there are no infusion related reactions. Then we have a one hour break and then we have the NK cell infusion which usually is is a pretty short 15 to 30 minute infusion. This is based on the previous experience, especially with rituximab and B-cell lymphomas where I think in all programs rituximab was given first to allow some distribution of rituximab throughout the body and then followed by the NK cells which has quite well worked in the B-cell field. So this is how the regimen would be handled. And the second question was around selection of the appropriate cohort. Again, there is no specification, so we do not necessarily have to use the same cell dose or the same symptomatic dose in the two cohorts. We will do a good assessment or thorough assessment of the risk-benefit profile, both looking at efficacy and safety and Based on that, we'll select the two most appropriate cohorts for the part two of the study.

Great. Thank you.

Thank you. One moment for our next question, please. Our next question comes from the line of Brad Canino with Stifel. Your line is now open.

Hi. Thanks for the question. I had a two-parter. One of them was answered about your view on the durability when it comes to the accelerated approval previously. So on top of that, I just want to ask, do you expect the MD Anderson presentation, which I think will include the final follow-up for the three to four cycle patients, to be a definitive demonstration of the durability of your potential commercial product? Or would you tell us to wait for the Luminize 203 data to start rolling in? Thank you.

Andrea?

That is a very difficult question. I think what we will show at ASH is clearly an update of both EFS or PFS survival and overall survival. I would not say this will be the final, as we already indicated in the abstract. There are still a quite significant number of patients in follow-up, so there could be a further follow-up data with even longer duration of responses or survival. Now, how these data translate into the LUMINI study is a little bit more difficult to answer. We believe that the 104 study is a very good proof of concept study, which I think indicates the magnitude of clinical effect that you could expect. Based on all our preclinical data, we have shown that the LONK cell is very active, and the co-administration, if at all, tends to be even a little bit more potent than the precomplexing. Again, with the caveat that this is preclinical data, but we believe that 104 is probably a very good indicator of what can be achieved with an active CD16A positive LNK cell and asymptomic.

Thank you.

Thank you. One moment for our next question, please. Our next question comes from the line of, Yelei Jin with Laidlaw and Company. Your line is now open.

Good morning, and thanks for taking the question. You have introduced the concept or the phenomenon of double refractory patients. So my question is, does the Luminescent 203 study only include patients with this designation or this phenomenon, or you will have single refractory patients as well?

No, I can take this. All patients that are recruited into Luminize have to be double refractory, so the requirement is that they have at least failed one combination chemotherapy regimen, they have failed BV, and they have failed PD-1. So if you will, it's more or less triple refractory. So it's chemotherapy refractory, PD-1 refractory, and BV refractory. So this is the patient population where we believe there's absolutely no medical alternative, and these patients are in dire need for active treatment.

Okay, that's very helpful. And in terms of MD Anderson studies with the corpulent cells, Most of the patients also have been categorized into this category or some sort of single refractory patient. So I just wanted to get some sense of how to think about the data versus the future readout you have in first half of next year.

Yeah, so in the MD Anderson trial, the patients with Hodgkin lymphoma all fall into this category of double refractory. So all patients, are BV and PD-1 refractory. As you remember, we also had a very small group of five patients of non-hot skin lymphoma. As PD-1 is not approved for all non-hot skin lymphomas, we have two patients in the non-hot skin lymphoma cohort that have not been exposed to PD-1 but have been exposed to BV. But again, the core population, the hot skin lymphoma population, all patients have been double refractory to BV and checkpoint inhibitors.

Okay, great. That's very helpful, and thanks and congrats on the progress.

Thank you. As a reminder, to ask a question, you'll need to press star 11, and please wait for your name to be announced. One moment for our next question. Our next question comes from the line of Sean Lee with HC Wainwright. The line is now open.

Good morning, guys, and thanks for taking my question. I was just wondering if you could provide a bit more color on what type of data can we expect from AFM24 at ASH? You mentioned you can expect the first three cohorts.

Andrea?

Sorry, I had a little bit of a disconnect. Can you repeat your question?

Sure. I was just wondering if you can provide a bit more color on the type of data that we can expect from ASH for AFM24 from the first three cohorts, I think, as you mentioned.

So AFM24 will not be at ASH, but will be a separate disclosure of the data. It will happen in December. Now, as we said, we have these three cohorts, which is EGFR, Y-type non-small cell lung cancer, gastric cancer, and then the basket cohort that was HCC pancreatic and biliary tract. And we have about 10 to 15, varies a little bit from cohort to cohort, responsive valuable patients where we will show mainly response rates. I think it's too early to have long-term follow-up data as many of these patients were recruited over the last six months, but we should have quite robust response data for these three cohorts.

Got it. Thanks.

Thank you. I am currently showing no further questions at this time. This concludes today's conference call. Thank you for your participation.