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Good day, and thank you for standing-by. Welcome to Affimed N.V. Third Quarter 2023 Earnings and Business Update Conference Call. [Operator Instructions] Please be advised that today's conference is being recorded.I would now like to hand the conference over to your speaker today, Alex Fudukidis, 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 we 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 Hoess, our Chief Executive Officer; Andreas Harstrick, our Chief Medical Officer; Arndt Schottelius, 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 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 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 thank you all for joining us today also from my [ side ]. And we have entered a very important and exciting phase for Affimed. 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 3 clinical programs and are now in a period where we plan to report data frequently over the next weeks and months.Moving to Slide 5. We recently announced that the new name for AFM13 will be acimtamig. Acimtamig is developed in combination with Artiva's AlloNK product in the LuminICE-203 study. We are now actively include Hodgkin lymphoma in [ Ph 2 ] LuminICE-203 and preparing to report efficacy and safety data from the study in the first half of [ 2024 ]. As a reminder, during this phase of this study, we will be treating 24 patients with Hodgkin lymphoma in 4 cohorts, and all these cohorts will use active doses of acimtamig and AlloNK.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 LuminICE-203 study designed based on FDA feedback and guidelines puts us in a very good position to pursue accelerated approval.The LuminICE-203 study builds on the unprecedented results observed in AFM13-104. The investigator-sponsored clinical trial we have been running in collaboration with MD Anderson. Updated data from that study will be presented by Dr. Yago Nieto, the lead investigator at the ASH Meeting -- Annual Meeting 2023 on December 11. Affimed 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 data.Now turning to AFM24. We remain on track to provide an update on the first 3 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 innate cell engager acimtamig in combination with PD-1 is able to double the complete response rate of PD-1 alone in rehab refractory Hodgkin lymphoma patients.During the third quarter, we also initiated enrollment in the non-small cell lung cancer, EGFR mutant cohort and have begun treating patients. Again, as a reminder, AFM24 as 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 AFM28 monotherapy dose escalation. During the third quarter, we completed treatment of patients in the third dose cohort without any limiting dose escalation [Technical Difficulty] and completed enrollment of patients in the fourth dose cohort, now administering a flat dose 200 milligram weekly.On Slide 6 and 7, we provide important background on the treatment of the indications we're targeting with LuminICE-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, the 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-based chemo and bendamustine or even targeted agents such as lenalidomide or mTOR inhibitor are listed in the NCCN guidelines. But it's important to note that these therapies were studied in relapsed/refractory Hodgkin patients before the introduction of BV and checkpoint inhibitors. And limited information is available on their efficacy on -- in the double-refractory population. But even still they are characterized by low CR rate and [indiscernible].We believe this is where acimtamig plus NK cell therapy has the potential to transform the treatment landscape for double-refractory patients. The response rates reported from AFM13-104 are outstanding, and in particular, with CR rate of 70-plus percent is higher than the CR rate of other treatments, even in less heavily pretreated patients. At ASH next month, we'll provide a definite view on the duration of response and event-free survival for the therapy for NHL patients treated at the recommended phase.LuminICE-203 further includes relapsed/refractory PTCL patients. PTCL has a very high need with more than half of patients moving to second one, which now offers only agents with limited efficacy and still no full improvement. Based on our market results, with atezolizumab [indiscernible] for acimtamig plus NK cells in double-refractory Hodgkin lymphoma alone is in excess of [ 1 billion ]. And with the inclusion of second-line relapse refractory PTCL, this would increase to over [ 3 billion ] combined.Finally, during the quarter, we saw a significant reduction in our operating cash burn has come to the first 2 quarters of the year, a result of the actions we implemented during the first half of the year to focus our investments on our 3 clinical programs.With that, I'll turn the call over to Andreas, who will provide additional insights on the progress we are making in our pipeline. Andreas?
Yes. 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 acimtamig going forward. We are pleased to update you on the progress that we have made regarding the development of acimtamig in combination with AlloNK or is it also known AB-101 from Artiva. After receiving the clearance from FDA to proceed with the initiation of the Phase II 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 9. In September, we received Fast Track designation for acimtamig. And in October, we got a written feedback from FDA on our Type C meeting request.On Slide 10, we show the updated LuminICE study design. In accordance with FDA's feedback, we will now add a cohort to the LuminICE-203 trial, which will treat patients with relapsed or refractory Hodgkin's lymphoma with AlloNK 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 acimtamig if they don't show a response to their initial treatment.We believe that the study, which is 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. Yago Nieto, the lead investigator of the original study that investigated the combination of acimtamig 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 II 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 II dose. The treatment regimen continues to demonstrate a good safety and tolerability profile with no cases of cytokine release syndrome, immune effector 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. And 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 acimtamig in combination with allogeneic NK cells. On the same day, Affimed plans to host an investor call to provide additional information about the status of the LuminICE-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, AFM24-102, we are treating patients with AFM24 and atezolizumab. In the ongoing study, the original 3 cohorts included patients with non-small cell lung cancer, EGFR-wildtype, 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 in 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 AFM24, which activates the innate immune system with atezolizumab, which impacts the adaptive immune system, therefore, has, in our opinion, a very good logical rationale. As Adi mentioned, we will report data on the first 3 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 4, 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 II dose based on correlative science and initial clinical activity. After that, for us, there are 2 options: either to develop AFM28 as single agent or in combination with allogeneic NK 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 Affimed's consolidated financial statements have been prepared in accordance 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, 2023, cash, cash equivalents and financial assets totaled EUR 97.5 million compared to EUR 190.3 million 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 30, 2023, were EUR 18.2 million compared to EUR 19 million 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 30, 2023, was EUR 2 million compared with EUR 14.9 million for the quarter ended September 30, 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 Affimed, 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 3 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 and 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?
[Operator Instructions] Our first question comes from the line of Maury Raycroft of Jefferies.
This is James on for Maury. Congratulations on the progress. For the Type C meeting, did the FDA provide any more specifics on the magnitude of clinical benefit? And did they see more focus on ORR or durability measures? And then after I have a quick 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 no -- as you may know, when you talk with FDA, they will never give you a fixed number of what I 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 a 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 a duration of -- or even progression-free survival of 6 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 in follow-up do you need to adequately address the contribution of single components in the AlloNK/IL-2 cohort that you reported today?
Again, that is a question that basically -- or 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 a 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 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.
Our next question comes from the line of Srikripa Devarakonda with Truist Securities.
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 this -- the Type C meeting, can you move ahead with Part 2 of the study? Or following Part 1, is there any need to meet with the FDA again? I know you guys have -- you can have multiple meetings with the FDA, given your designation, Fast Track designation.
Wolfgang, I can take this as well or do you want to take...
I can take it. So 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, AlloNK cells 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 AlloNK/IL-2 cohort needed for accelerated approval submission?
When we spoke to the FDA during IND process and also during Type C, right, 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.
Our next question comes from the line of Li Watsek with Cantor Fitzgerald.
Maybe just a follow-up for 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 calm these patients in the total and to support the efficacy as well?
Wolfgang, do you want to take?
Yes. I can take that question. Yes, these patients, right, when treated with AlloNK/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 and enrolling patients. Just can you give us some stance in terms of how many sites do you need to fully enroll the running portion?
Andreas, do you want to take the question?
Yes. I mean, for the running portion, as you know, there is somewhat of a staggered approach, especially for the first 3 patients per cohort. So our current assumption is that we probably need 5 to 6 good recruiting sites for the initial 4 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 first half of 2024.
Our next question comes from the line of Daina Graybosch with Leerink Partners.
Two questions for me. One on the new AB-101 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, it's included 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 benefit. 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 the study now that this arm [ has ] a possibility?And then my second question is on AFM24. And there's -- 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 combined with chemotherapy and if you're considering that in the form of an ADC going forward?
Andreas...
Yes. I can take both questions. So yes, so the AlloNK/IL-2 arm, as you mentioned, is an arm that we added also after discussion with some of our clinical advisory and key opinion leaders, probably the only way to make such an arm -- recruiting arm is what we implemented now that we give patients the option if they do not have a response after cycle when they can immediately cross over to the combination treatment. So they will have the option to receive what we believe is a 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 AlloNK 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. So combination either with TKIs, for example, in the EGFR mutant field or with ADCs, both in the non-small cell lung cancer EGFR wild-type and EGFR mutant fields are definitely options that we would look at after we have completed our 102 study.
Our next question comes from the line of Yanan Zhu with Wells Fargo.
Great. Two questions on the AFM13 program. The first one is how is the infusions of the NK and AFM13 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 2 infusions?The second question is about how you select the 2 cohorts for Stage 2. Would that be based on 2 cohorts having to have the same NK component, NK dose or having -- or these 2 cohorts having to have the same AFM13 dose or it doesn't matter just the two cohorts with the best-performing ORR?
Andreas?
Yes. So in terms of administration and then how the trial currently is designed, we start on the days where we gave AFM13, acimtamig and NK cells with the acimtamig infusion, initial infusion duration is 4 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 1-hour break, and then we have the NK cell infusion, which usually is a pretty short 15-minute to 30-minute infusion. This is based on the previous experience, especially with rituximab in 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 pre-specification, so we do not necessarily have to use the same cell dose or the same acimtamig dose in the 2 cohorts. We will do a good assessment or a thorough assessment of the risk-benefit profile, both looking at efficacy and safety. And based on that, we'll select to most appropriate cohorts for the part 2 of the study.
Our next question comes from the line of Brad Canino with Stifel.
I had a 2-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 guess, I want to ask, do you expect the MD Anderson presentation, which I think will include the final follow-up for the 3 to 4 cycle patients to be a definitive demonstration of the durability of your potential commercial product? Or would you tell us to wait for the LuminICE-203 data to start rolling in?
Andreas?
That's 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 quite significant number of patients in follow-ups. So there could be a further follow-up data with even longer duration of responses or survival. Now how these data translate into the LuminICE 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 AlloNK cell is very active and the core administration if it all trends to be even a little bit more potent than the precomplexing, again, with a 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 AlloNK cell and acimtamig.
Our next question comes from the line of Yale Jen with Laidlaw & Company.
You have introduced the concept or the phenomenon of double-refractory patients. So my question is, does the LuminICE-203 study only include patients with this designation or this phenomena? Or you will have single-refractory patients as well?
No, I can take this. All patients that are recruited into LuminICE have to be double-refractory. So the requirements they have at least Phase I combination chemotherapy regimen. They have failed BV and they have failed PD-1. So if you will, it's more just 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 entire need for active treatment.
Okay. That's very helpful. And in terms of MD Anderson studies with the cord blood cells, most of the patients also being categorized into this category or some sort of single refractory patients? So I just wanted to get some sense of how to think about that data versus the future readout you have in first half of next year?
Yes. So in the MD Anderson trial, it's the patients with Hodgkin lymphoma all fall into this category of double-refractory. So all patients or BV and PD-1 refractory. As you remember, we also had a very small group of 5 patients of non-Hodgkin lymphoma as PD-1 is not approved for all non-Hodgkin lymphomas. We have 2 patients in the non-Hodgkin lymphoma cohorts that have not been exposed to PD-1 but have been exposed to BV. But again, the core population, the Hodgkin lymphoma population, all patients have been double-refractory to BV and checkpoint inhibitors.
[Operator Instructions] Our next question comes from the line of Sean Lee with H.C. Wainwright.
I was just wondering if you could provide a bit more color on what type of data do we expect from AFM24 at ASH? You mentioned in things like the first 3 cohorts.
Andreas?
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 you can expect from ASH for AFM24 from the first 3 cohorts, I think as you mentioned.
Yes. So AFM24, will not be at ASH, but will be a separate disclosure of the data will happen in December. Now as we've said, we have these 3 cohorts, which is EGFR-wildtype non-small cell lung cancer, gastric cancer and so the basket cohort that was HCC pancreatic and biliary tract. And we have about 10 to 15 -- it varies a little bit from cohort to cohort response rate 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 6 months, but we should have quite robust response data for these 3 cohorts.
I am currently showing no further questions at this time. And this concludes today's conference call. Thank you for your participation. You may now disconnect. Everyone, have a wonderful day.