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spk01: The conference will begin shortly.
spk06: Thank you for standing by. Welcome to today's third quarter earnings and business update conference call by AffiMed NV. As a reminder, all participants are in listen-only mode. A question and answer session will follow the formal presentation. Please note this conference call is being recorded. I would now like to hand the call over to your host for today, Alex Flutakese. Director of Investor Relations at S&Med. Please go ahead.
spk14: Thank you, Shannon. And thank you all for joining us for our call today. 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. On the call today, we have members of our management team, including Adi Hirsch, our Chief Executive Officer, Andreas Harstrick, our Chief Medical Officer, Arne Stratelius, our Chief Scientific Officer, Wolfgang Kirchhoff, our Chief Operating Officer, Denise Mueller, our Chief Business Officer, and Angus Smith, our Chief Financial Officer. The team will be available for a Q&A after the . Before we start, I'd 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 statement, 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?
spk16: Thanks, Alex. Good day, everyone. And thanks for joining us for the third quarter update call. Let me start with the most important update that we announced earlier this month. As we are showing on slide four, after an extensive evaluation of the available apps, on November 3rd, we announced a new collaboration with Arteva, building on our already established relationship to take the combination treatment of AFM13 and Arteva's Chiropracept, of the Schroes-Koplak-derived encasal product candidate called AB101, forward quickly. For us, this collaboration is a natural evolution of the AFM13 Plus and Casel program as we move this therapy from an early stage into late stage development and begin to position the combination for commercial success. According to our analysis, this partnership represents the fastest option to make this combination therapy available to patients. We're convinced that we made the right choice for AFM13. Now, through this collaboration, we have gained access to a highly active NK cell product. As shown on slide five, we've generated preclinical data showing the highly synergistic anti-tumor activity of the combination of AFM13 with AV101. Overall, based on the preclinical data generated as well as our previous experience of administering AFM13 with a cold blood-derived encasal product in our AFM13-104 study, we're confident that AFM13 administered in combination with AV101 has the potential to generate a robust ADCC response and clinical activity in patients with relapsed or refractory Hodgkin lymphoma and CD30-positive peripheral PC lymphoma. Other factors were considered when selecting AB101, and this included the fact that AB101 is already in clinical development with a cleared IND and is a cryopreserved off-the-shelf product. It demonstrates consistent and high CG16A expression. A GMP-grade manufacturing site with the right scale for clinical trials and future commercialization is available and the product has viable cost structure moving to slide six it shows that the terms of the deal with arteva allow us to accelerate the development of the combination therapy now by leveraging the financial resources of the two companies ultimate will initially pay for the clinical trial cost of the phase two study and arteva will supply av101 and R2 for the study at their cost. Cost of any conservatory study will be shared 50-50. And all the revenues will be shared with ultimate now receiving 67% of the revenues of the combination therapy. In our efforts to move forward quickly, we're also making progress on the regulatory front. We already requested a pre-IND meeting with the FDA in early September, and the agency has indicated that they will provide feedback to us by the first quarter of 2023. This is a little later than the usual 60 days, which the agency has informed us is caused by a significant backlog due to COVID. Still, our goal is to submit an R&D for the combination study in the first half of 2023 and begin the clinical study later in the year. We believe that we'll be able to move into the clinic quickly because of the robust clinical and preclinical data that has been generated for each product on its own. The preclinical data that we have collected from our over two-year collaboration and the very good safety profile that we have seen in our combination study with AFM 13 and cold blood-derived allogeneic incasor. So as you can appreciate, we are at a very exciting point in the development of our company. In addition to the data and business updates we provided in the last few weeks, we are preparing to announce key catalysts that could have a meaningful impact for our company and the patients we serve. These include top line data from the phase two redirect study of AFM13 in peripheral T cell lymphoma in mid-December. and data from the combination of ASM13 with in case of . Now, to tell you more about our clinical program and some of our recent data, I'll hand over the call to Andreas. Andreas?
spk11: Thank you, Adi, and also a warm welcome from my side to everybody on the call. I would like to take the opportunity and provide an update on our clinical programs and the progress that we have achieved. Let us start with our AFM13 program on slide nine. Our registration-directed monotherapy study of AFM13 in relapsed and refractory peripheral T-cell lymphoma, also known as redirect, has completed enrollment earlier that year. As previously communicated, we expect to report data from the study in mid-December. The study has enrolled more than 100 patients with relapsed or refractory CD30 positive peripheral T cell lymphoma. And the focus of the initial data release will be on the overall response rate as assessed by a blinded independent review committee, which is the primary endpoint of the study, and a preliminary assessment of the duration of responses, as well as an analysis of safety. As a reminder, peripheral T-cell lymphoma is a disease with still significant unmet medical need. In our estimates, there are about 1,500 patients in the U.S. alone with relapsed refractory PTCL, and treatment options remain very limited, and the prognosis for these patients is poor. As also previously communicated, we plan to initiate discussions with the FDA following our analysis of the data. The second AFM13 study that is ongoing is our Phase I-II study AFM13-104 in collaboration with MD Anderson Cancer Center, evaluating cord blood-derived national killer cells pre-complexed with AFM13 given as one infusion, followed by three single-agent AFM13 treatments in patients with relapsed and refractory CD30-positive lymphomas. On slide 10, you can see the highlights from the ASH abstract from a couple of weeks ago. We showed that as of July 31st, the cutoff date for the analyzers that provided data for the abstract, 24 patients have been treated at the highest NK cell dose of 1 times 10 to the 8 NK cells per kilogram body weight. This represents an increase of 11 patients since the data reported at AACR earlier this year. To highlight, the overall response rate at this dose has been maintained at 100%, and the complete response rate increased to 70.8%. An improvement over the 61.5% CR rate as reported earlier this year at AACR. As announced in our press release, Dr. Yago Nieto, Professor of Stem Cell Transplantation and Cellular Therapy at the University of Texas MD Anderson Cancer Center, and principal investigator of the study, will provide an update from the ongoing phase two trial at ASH on December 10. Now let's turn to AFM24. As you can see on slide 11, we show that we are continuing to enroll patients in all three ongoing studies, including the expansion cohorts of our monotherapy study and the dose escalation cohorts for the combination studies with atesolizumab and SNK01, the autologous NK cell product from NKGEN, respectively. In the AFM24 monotherapy trial, we are continuing to enroll patients in the expansion phase at the recommended phase two dose of 480 milligrams weekly. The expansion cohorts include patients with renal cell carcinoma, non-small cell lung cancer with activating EGFR mutations, and colorectal cancer, which are KRAS-wide type. In the combination studies, we are continuing to enroll patients in the dose escalation phases of the two studies. As a quick reminder, the primary purpose of the dose escalation phase of these studies is to establish the safety of the two combinations and identify the recommended phase two dose for further testing. In AFM24102, the combination study of AFM24 given weekly with atezolizumab at the recommended dose given every two weeks. We are enrolling patients with non-small cell lung cancer, which are EGFR wild type, gastric or gastroesophageal junction adenocarcinoma, and pancreatic hepatocellular and biliary tract cancers. We completed the first dose escalation cohort of 160 milligrams weekly of AFM24 without any dose-limiting toxicities. Furthermore, the first three patients at the 480 milligram dose have now been enrolled and completed their dose-limiting toxicity period without DLTs. According to protocol, we are enrolling additional three patients at this dose to confirm 480 milligram as the recommended phase two dose for this combination. The second combination study, AFM24103, is investigating the combination of AFM24 with EDSNK01, the ex vivo expanded and activated autologous NK cell therapy from NKGen Biotech. In this study, both agent AFM24 and the NK cells are given weekly to patients with non-small cell lung cancer, EGFR wild type, squamous cell carcinoma of the head and neck, and colorectal cancer. In this study, we have completed the first dose escalation cohort, which treated patients at 160 milligrams of AFM24 with no dose-limiting toxicities. We are currently enrolling patients at the 480 milligram dose of AFM24. On slide 12, we are showing a summary of two presentations that were presented at CITC Immunotherapy Congress last week. For the monotherapy study, correlative science data from the dose escalation portion of the study provided interesting insights into the mechanism of action of AFM13. Findings showed that starting at low doses of AFM24, and K-cell activation could be seen in the peripheral blood. CD16A receptor occupancy also increased in a dose-dependent manner at lower doses, but levered off at a dose of 320 milligram and above, indicating that at this dose, receptor occupancy was saturated. We could also demonstrate activation of cytotoxic T cells in the periphery, pointing to a simultaneous activation of the adaptive and the innate immune system. Furthermore, when we looked into tumor biopsies by immune histochemistry and gene expression profiling, translating the findings from the peripheral blood to the tumor, we saw that NK cells and cytotoxic T cells increased in the biopsies of AFM24-treated patients, indicating that cytotoxic cell function of both NK and T cells are increasing significantly. These data demonstrate that AFM24 activates the innate and the adaptive immune system in the periphery and in the tumor microenvironment and paves the way for combinations with checkpoint inhibitors and NK cells. This brings me to the combination study with atezolizumab the phase one dose escalation study. Here we showed that clinical activity was observed in two patients in the first dose escalation cohort of 160 milligrams of AFM24 weekly. As you can see on the slide, one of the patients was a patient with gastric cancer. This patient had already been treated with Pembrolizumab and chemotherapy combination in first line. followed by three lines of various chemotherapy regimens before included into the trial. Importantly, to the pembrolizumab-hemotherapy combination in first line, the patient had only achieved a very short-lasting partial response, which was followed by progression of metastasis while still on pembrolizumab treatment. It is important to note that this represents a patient profile where a response to single agent PD-1 re-challenge is very unlikely. The second patient, a patient with pancreatic adenocarcinoma, exhibited stable disease on the combination of AFM24 plus atezolizumab after showing progressive disease on three different previous chemotherapy regimens. We are expecting to submit data from all three AFM24 studies to major scientific conferences in the second and third quarter of 2023. On slide 13 for AFM28, we announced an abstract at ASH which will describe the preclinical in vitro models using a panel of AML lines showing efficiency and antibody-dependent cell-mediated cytotoxicity against CD123 positive tumor cells by a combination of allogeneic NK cells and AFM28. This combination induced highly potent and selective lysis of CD123 positive leukemia cells and included cytotoxicity against leukemic stem cells and progenitor cells. We believe that this is an important finding as the ability to eradicate leukemic stem cells is associated with durable responses and the potential for long-term remissions in patients with refractory or relaxed AML. Given the aggressive nature of the disease and the need for viable treatment options, the AFM28 program is of high priority for AFIMED, and we remain committed to being able to offer this treatment options for relapsed and refractory AML patients as quickly as possible. Accordingly, we moved quickly to file clinical trial applications in a number of European countries, with Spain and France leading the way. Additional filings in different jurisdictions are expected in the next few months. With that, I will turn the call over to Angus to update you on the quarterly financial numbers. Angus, please.
spk15: Thank you, Andreas. Balance sheet and income statement highlights are shown on slides 15 and 16 of the presentation. APIMED's consolidated financial statements have been prepared in accordance with the IFRS as issued by the International Accounting Standards Board, or IASB. The consolidated financial statements are prepared in euros, which is the company's functional and presentation currency. Therefore, all financial numbers that I'll present in this call, unless otherwise noted, will be in euros. As of September 30, 2022, cash and cash equivalents totaled €222.9 million compared to €197.6 million on December 31, 2021. Based on our current operating plan and assumptions, we anticipate that our cash and cash equivalents will support operations into mid-2024. Net cash used in operating activities for the quarter ended September 30, 2022, with 19 million, compared to 25.6 million for the quarter ended September 30, 2021. Total revenue for the quarter ended September 30, 2022, was 14.9 million euros, compared with 18.7 million euros for the quarter ended September 30, 2021. Revenue predominantly relates to the Genentech and Roivant collaborations. Research and development expenses increased by 27% from 20.6 million euros for the quarter ended September 30th, 2021, to 26.1 million euros for the quarter ended September 30th, 2022. The increase was primarily due to higher expenses associated with the development of the AFM 13 and AFM 24 programs, a result of an increase in procurement of clinical trial material, clinical patient trial costs, and manufacturing costs. an increase in costs associated with other early-stage programs and infrastructure, and an increase in share-based payment expense. G&A expense increased 19% from 6.8 million euros in the quarter ended September 30th, 2021 to 8.1 million euros in the quarter ended September 30th, 2022. The increase predominantly relates to higher personnel and share-based payment expenses and an increase in insurance premiums and higher consulting costs. Net finance income increased from 1.5 million euros for the quarter ended September 30th, 2021 to 2.7 million euros for the quarter ended September 30th, 2022. Net finance income is largely due to foreign exchange gains related to assets denominated in US dollars as a result of currency fluctuations between the US dollar and the Euro during the year. Net loss for the quarter ended September 30th, 2022 was 16.5 million euros or 11 cents per common share compared with a net loss of 17.1 million euros or 14 cents per common share for the quarter ended September 30th, 2021. The weighted number of common shares outstanding for the quarter ended September 30th, 2022 was 149.3 million. Additional information regarding these results is included in the notes to the consolidated financial statements as of September 30th, 2022, which will be included in APIMED's filings with the US Securities and Exchange Commission. I will now turn the call back to Adi for closing remarks.
spk16: Thank you, Angus. Now, if you've seen our most advanced program, it's called AFM13, and it's validating our three-pronged approach. It has shown very good safety profile with broad activities. Now, if everything works out as planned, we expect to take the drug forward as monotherapy, as well as in combination with natratilazole, which could create significant value for patients and investors. As shown on slide 18, with monotherapy and encasome combinations, we can initially address the needs of about 3,500 patients in the US only, and indeed far more when developed in the EU and Japan, with relapse and refractory CD30 positive Hodgkin and peripheral T-cell lymphoma. And we can even expand beyond to address about 7,500 patients Now, again, just in the US only, again, it will be more in Europe, Japan, by moving to earlier lines. Considering the likely value base on current data of the AFM13 in casal therapy to patients and the payer feedback, we believe we can make AFM13 a major commercial opportunity for our companies. Now through the partnership with ARTIVA, we've achieved a major milestone that enables us to pursue this substantial market opportunity. As you have heard in parallel, AFIM-24 is moving forward in all three studies, indeed addressing multiple major solid tumor indications. Important overall, the safety of AFIM-24 is monotherapy, and inclination looks quite favorable. which now allows us to treat patients at the 480 milligram dose across all three studies. The first date of April 24 in combination with ATISO presented at CITSE is highly encouraging. And as shown on slide 19, we are on track to provide additional data updates throughout 2023 at major medical conference. Our pipeline is further enhanced through April 28, which is in the filing stage for a clinical phase one study outside the U.S. Also, our ongoing partnerships are moving forward. In the case of Genentech, we have made good progress in various pre-clinical programs and handed over several programs to them for further pre-clinical development. In our second collaboration, Roybent just presented a poster at SISI which showed that AFM32 represents a novel approach to treating folate receptor-alpha-expressing tumors by engaging the innate immune response for safe and effective tumor cell care. Roivind announced that it is expecting to enter into Phase I TMA trials in 2023. We're therefore eligible for additional proceeds from these key collaborations in the near term, including preclinical milestones as well as milestones based on early regulatory achievements. With this, I'd like to thank you all for your continued support, the patients and their families, and for our employees in the US and Europe who are continuing to do the best they can in supporting our efforts to move things forward. We're now ready to take questions. Operator?
spk06: Thank you. To ask a question, you will need to press star 1-1 on your telephone. In the interest of time, we ask that you please limit yourself to one question and one follow-up to permit time for others to ask. Please stand by while we compile the Q&A roster. Our first question comes from the line of Kripa Devarakonda with Truist. Your line is now open.
spk09: Hey, guys. Thank you so much for taking my questions, and congratulations on the poster presentations at SWTC. The AFM24 PD-L1 poster that you presented, the patient where you recorded a PR in gastric cancer, it's clear from the poster the impact on the cutaneous lesions. Can you tell a little bit, sorry if I missed it, about the impact on the primary tumor itself? And also, it looks like you continue to see reduction in lesions with multiple doses. Can you remind me how long these patients are expected to be treated at this dose? Thank you.
spk11: Andrea, please. Yeah, I can take this. So the patient's manifestation was mainly skin metastases, which were, as you have seen on the poster, quite bulky. The patient also had a primary tumor, which was in the gastric wall. However, due to the difficulty to really objectively measure thickening of the gastric wall, this lesion was more regarded as an evaluable lesion, but not as a real measurable lesion. We also saw some reduction in the gastric wall again with a limitation that it's very difficult to measure. But again, a major reduction of the skin metastasis which represented the vast bulk of the tumor load in this patient. In terms of duration of treatment, the protocol is designed that we can continue treatment as long as the patient derives clinical benefit, so there is no upper limit of possible cycles that can be given.
spk09: Got it. Thank you so much.
spk06: Thank you. Our next question comes from the line of Mari Raycroft with Jefferies. Your line is now open.
spk05: Hi. Congrats on the progress, and thanks for taking my question. Just wanted to check on regulatory path going forward for AFM13 and PTCL. So, given some of the regulatory updates with other oncology companies in the space as it relates to accelerated approval path and confirmatory studies, can you talk about your plan for PTCL based on the redirect study and FDA feedback that gives you confidence from your accelerated approval path?
spk16: Wolfgang, can you take this question?
spk12: yes sure hi mary this is wolfgang the once we will have the data we will consult with the fda discussing the path forward right because currently we do not know what the data look like and this will also include a registration directed study yes we are aware that the fda is also talking to other companies right and we just heard last week or the week before about that company and that they are requesting that a consummatory study is underway. However, we do not know what other factors have been considered here, right? So, we think we go with our data and discuss with the FDA.
spk05: Got it. That makes sense. And maybe one follow-up just for AFM28. If you do the dose escalation in Europe or start looking at combinations in the EU, How do you eventually plan to pivot back to development in the United States?
spk16: Andreas?
spk11: Yeah, I think we will generate initial data, initial safety data as we have announced in the European jurisdictions. Now the requirement for FDA to use foreign data is that the patient population and treatment algorithms should represent the standard of care and the Usual population in the U.S., I think both factors are given by the selection of the countries that we have. So I mentioned Spain and France will lead the way. So I think as soon as we have cleared initial dose cohorts and have demonstrated also the clinical safety of the program, we should be able to revert back to the U.S. and then embark onto a global development program that will include U.S. as well as Europe.
spk05: Okay, thanks for taking my questions.
spk06: Thank you. Our next question comes from the line of Dana Graybosh with SVB Security. She wants to open.
spk08: Yes, I want to ask a question about the ASM24 response in gastric cancer. The cutaneous lesions are obviously a very clear response, and I wonder if there's something about cutaneous lesions and the mechanism of targeting EGFR, that's notable. And of the other cancers that you're going for, if there's any similarity, either in the monotherapy, PD-1 or NK cell combinations with manifestations of cutaneous lesion.
spk16: Thank you. Thanks, Dana. Andreas?
spk11: Yeah, so thank you for the interesting question. I mean, this patient, as you have seen, happened to have skin metastasis And skin, of course, is an area where you have a high EGFR expression. Now, biologically, we think that this is not connected as the EGFR expression would be limited, the high EGFR would be limited to the normal keratinocytes, the normal cells. The gastric cells still maintain their EGFR expression pattern that they have in the primary tumor. So to my knowledge, there's no indication that EGFR on tumor cells is upregulated when they home into the skin. So, as we announced previously, we have conducted a very specific and very detailed analysis of the tumor microenvironment of a number of very different tumor histologies, which formed the basis for selecting certain indications for monotherapy for combination with PD-1 and for combination with NK cells. But skin metastasis or the likelihood of skin metastasis was not part of the consideration. Again, we believe, and most biological data show that tumor cells, irrespective to where they metastasize, will maintain their biological fingerprint or footprint. And therefore, I think a gastric cancer cell that homes to the skin is biologically not very different from a gastric cancer cell that may go to the liver or to the bones or other more frequent metastasic locations.
spk08: I have a follow-up. I mean, do you see any impact potentially? You know, other companies will target normal or stromal cells around the tumor, let's say with FAP. Do you see any indication that other cells in the tumor microenvironment or surrounding normal could have an impact in your sort of mirroring and in vitro models?
spk11: I think for the in vitro models, I could hand over to Arndt. I think clinically, again, the NK cell reactivity is very specific to the cell where the NK cell attaches to and then to the microenvironment. I would not see a difference between skin locations of tumor cells or other locations, but Arndt, maybe you can take the in vitro question.
spk10: Yes. Let me see if I got the question correctly. I mean, if you talk about cells in the vicinity in the tumor microenvironment, of course, what we know and, you know, we talk a lot about NK cells. Of course, we have also quite clear growing data on macrophages. Of course, in terms of attempts, they will be recruited. We don't have evidence of other neighboring cells. Of course, the bulk of the data is for the NK cells, and as Andreas pointed out, these indications have also been carefully selected to see that, you know, the innate immune system is accessible or actually the cells of the innate immune systems are there. I mean, above we have also seen, as Andreas described in the talk, that the SITC poster, we do see the activation of the innate and the adaptive immune system. which we think is a very natural physiological way to get both systems going in the immune oncology cycle. So in a much more natural way, getting adaptive immune cells in there as well. Not sure if that answers your question. We'll be happy to do follow-ups also.
spk08: Well, that's good. Thank you.
spk06: Thank you. Our next question comes from the line of Doe Kim with Piper Sandler. Your line is now open.
spk13: Hi. Thanks for taking my question. I also have a question on the AFM24 Atezo poster that you presented at CISI. In the patient who had the partial response in gastric cancer, knowing that the patient failed PEMBRO prior, do you think atezo is contributing to the anti-tumor activity? And does this partial response change how you think about the monotherapy or give you more confidence in advancing that monotherapy study?
spk16: Andrea?
spk11: Yeah, so let's start with the pembrolizumab, atezolizumab question. Again, the literature is quite quite limited. We have not found meaningful data for gastric carcinoma. Most of the experience really comes from retreatment attempts with PD-1, PD-L1 in patients with non-small cell lung cancer. And if you look across the literature, what you see is that a response is possible to PD-1 re-challenge, but these responses are largely limited to patients who have either stopped pembrolizumab or any PD-1 inhibitor while still in a response, or who had to stop temporarily because of immune-related adverse events. If you look at patients who have a demonstrated progression while receiving PD-1, especially when this PD-1 was also given in combination with chemotherapy, the response rates of PD-1 re-challenge are extremely low, and in many studies they are 0%. So we do not think that this patient belongs to a patient group that would have responded to PD-1 re-challenge alone. We attribute this activity clearly to the combination of AFM24 and PD-1. And as Arndt just said, I think this is also increasingly supported by our preclinical and clinical data now that we really show also in the patient and activation of the adaptive immune system. So, and now I have a long answer and forgot your second question. Could you repeat, please?
spk13: Yeah. The second question was, does this response change how you think about monotherapy, or do you think that Ateza was important in getting to this partial response in the gastric patient?
spk11: Well, for monotherapy, we are currently collecting the data. And as we said, we will report initial data into a major scientific conference next year. Whether it really changes our belief, I think our belief from the get-go is that AFM24 is an extremely potent drug that can recruit NK cells, and as Arndt mentioned, can also very potently activate macrophages. So clearly, the combination with a PD-1 or PD-L1 inhibitor is very promising. Again, we believe that there are certain tumor indications out there where the NK cell infiltration into the tumor microenvironment could be sufficient enough to support monotherapy activity. But we will learn more as we are generating more data. But again, for combination with any PD-1 inhibitor, this is now the second data point in addition to the AFM13 studies that we have seen in combination with pembrolizumab. where we saw a significant increase in complete response rate and overall response rate. I think a combination with PD-1, PD-L1 inhibitors, and ICEs in general look extremely promising.
spk13: Thank you. That was very helpful.
spk06: Thank you. Our next question comes from the line of Lee Watson with Cantor. Your line is now open.
spk07: Thank you for taking my questions. Maybe just two from this. I guess first regarding maybe the confirmatory study of, you know, AFM13 plus AB101 combo, I guess is it sort of part of the discussions that you are having with FDA right now aside from the trial design of the potential Phase II study? And then second is, you know, in terms of the site selection for the potential Phase II trial of this combo, Can you give us a sense of, you know, what parameters that you're looking for? Would the sites mostly be at the academic centers, perhaps with self-therapy experience, or are you looking at some community sites as well?
spk16: Andreas, you want to take this question?
spk11: Yeah. So, let me start with a second question. So when we are in terms of sites that we are anticipating to have on our combination trial, on our phase two trial, we are not limiting these sites to academic sites or sites with NK cell or cell therapy experience. Simply based on our experience with the MD Anderson trial, which showed a remarkably good safety profile. In fact, most of the patients receives their treatment on outpatient basis. So other than other cell therapies like CAR-T. So we do not think that this is a treatment that will be restricted to academic centers. We believe that this can very well be given also in experienced community hospitals. Now in terms of our discussions with FDA, as Adi mentioned, we have already submitted the pre-IND requests. containing a lot of also clinical questions. This will be, of course, followed by an IND then. And as we are planning to discuss with FDA an accelerated approval option and accelerated approval pathway for this treatment, also discussions of potential confirmatory studies, I think, will be part of these interactions with FDA. Okay. Thank you.
spk06: Thank you. Our next question comes from the line of James Shin with Wells Fargo. Your line is now open.
spk03: Hey, good morning, guys. Thanks for taking my question. For AFM13104, can you share whether you think the memory-like phenotype of the cells may be contributing to the response? And then secondly, given AB101 will be co-administered, do you think the lack of IL12, 15, and 18 poses somewhat of uncertainty or risk of matching what you've seen in Hodgkin's lymphoma?
spk16: Yes. Thank you. So I'll start here in terms of we have obviously very intensely looked at NK cells and the way how they are produced and what we have learned from, in particular, working with Artiva is they do have a pre-activation of a cell with cytokines as well. It's a little different to what MD Anderson does. Overall, from our internal experiments, we have seen almost no differences between different cell types. So we have studied cells that are derived from the periphery from cold blood, also iPSCs, and there was one key denominator that was truly important. it is the CD16A expression. So as long as these cells, when manufactured, express a significant level or a good level of CD16A, these cells synergize extremely well with our inner cell engagers. We have the high affinity to cover them in very high quantities. As you know, when this is established, you can't really wash it off, so it forms a stable complex, and then these cells become active. So our own learnings being that there has been very little differentiation amongst many different cell types with the one denominator that it expresses CD16A. So the pre-activations that you were mentioning, we did not see an outstanding activity as compared to other cell types. So this is important, and that's what gave us great confidence that we indeed have a number of options where we wanted to partner with, and our option, basically our choice with Artiva has been because they are so far advanced in the manufacturing, and that could indeed induce or start, initiate a phase two clinical study fairly quickly with product that's very similar to the product that we eventually want to commercialize. That was important, and that's what Artiva is basically bringing to us in this partnership. Now, the other question I'll hand over to Arndt and see what he wants to add.
spk10: So let me see if I understand what the other question was. I think maybe referring to the, James, the preclinical data that we have shared and maybe most relevant, the mouse model. And I just want to interrupt you quickly.
spk16: It was about co-administration and pre-complexing. Sorry.
spk10: Yes. So, the, what we have seen, James, you know, and we shared that at the call, and we have it summarized on one of the slides today, when we look in the CD30 positive CARPA cells and directly compare pre-complex and co-administration AB101 with 13, we saw, yes, there was a slight better cytotoxicity with co-administration, but we see that in the same ballpark, very comparable. And when we review again the mouse model that we did with co-administration, we see a very excellent tumor growth inhibition. And referencing back to your initial question, while that was not done side by side, very similar results, you know, tumor, the total tumor growth abrogation as we had seen with the MD Anderson cells. So all taken together, in addition to what Adi already said, is we really do not see a difference preclinically, just feel very confident with moving forward with AB101 in the co-administration setting.
spk16: So, there are two additional data sets. One is published. It's that we can determine the receptor occupancy of AE from 24 when it's used as monotherapy. So, this shows that we can basically, our inner cell engages, get to the encasals in the body, So this is a kind of not following the co-administration because here the patient is bringing the NK cells, but we can detect A from 24 and binding to CD16A. That's our published data. So that gives us, again, very good confidence. And you know why we're seeing this strong binding. It's for several reasons. One is the very high affinity that our engagers have onto CD16A. plus they're binding an epitope that is not impacted by circulating IgG. So this is the advantages, and that's why we believe with co-administration, we can achieve a very solid binding of the entasels that we infused, in this case, AB101. A second data set we have never published yet, but we have also looked at A from 13 inpatients. If it's binding to entasels, then again, we can see A from 13 bound on patient-owned entasels. So those set of data give us a reasonably good basis to follow through with the strategy of co-administration. On top, we have generated, obviously, a multitude of pre-chemity data that confirms that co-administration and pre-complexing results in basically similar data with similar activity.
spk03: Thank you for the detailed response. Very much appreciate it.
spk06: Thank you. As a reminder, to ask a question at this time, please press star 1-1 on your touch-tone telephone. Our next question comes from the line of Yeo Jin with Laidlaw and Company. Your line is now open.
spk02: Good morning, and thanks for taking the questions. I know you mentioned a lot of similarities between the MD Anderson and the Ativa cells. Do you speak with, going to speak with FDA, do you anticipate that could be some sort of bridging study needed before you move to the, you know, the full phase two study for the potential accelerated approval?
spk12: That's welcome. Yeah. So, how the FDA looks at these differences, right, we can't say before we have to talk to them, so that's important. But we believe that we have a good data set showing the similarity comparability between these cells, right? All as mentioned by Ant and Andreas and Adi before. I mean, the preclinical studies in vitro, in vivo, demonstrate the similarity, right? So, we do not anticipate that we have to under-bridging study. However, we can give more guidance once we have spoken to the FDA.
spk02: Okay, great. Maybe just a follow-up on this one. Let's assume if a bridging study might be needed, are you guys, in your mind, have any sort of setup or design to fulfill that request if that happens? And thank you. Yeah, yeah.
spk12: Of course, in preparing for the FDA interaction, we are evaluating all potential ways. And yes, we are thinking about all these different paths and look for solutions for that.
spk16: When you look at the clinical study of Arteva, they already started with a billion cells as the first dose. and are adding in now also rituximab, and they will only do one dose escalation to 4 billion. So with non-modified cells, you have far less hurdles in terms of running dose escalations in this context. So you can do a run-in, and that's what the most likely scenario will be, that you may have just to treat initially three patients, see if this is safe, and then you can continue to recruit the larger number of patients. This is our assumption, and as Wolfgang said, the assumption is based on a number of experiments that we've conducted. We have just, to make this understanding, is treated over 200 patients with AFM13 as monotherapy and also in combination. So we have a very thorough data set. On top, we have shown a very good safety profile in combination with in case also already. So our base case assumption is that there is a safety run and then we can start recruiting these patients. So there should not be any separate studies being conducted. But as Wolfgang said, obviously, we're prepared to react to anything because we believe that there is a high chance that this treatment is coming through in an accelerated approval study. it can really make patient lives very different just based on the data that you've seen in the ASH abstract. Thank you.
spk02: Okay, thank you.
spk06: Thank you. Our next question comes from the line of Chi-Chung with Chu with Berenberg. Your line is now open.
spk04: Hi, good morning. I want to ask Also on FM24 in combination with the tesolizumab, I'd like to ask about the two pancreatic patients you reported. One, I think, has some durable stable disease. I wonder, from disease biology standpoint, any color can provide on why NK engager or macrophage engager should work in this sort of cold tumor situation? Thanks very much. Andreas?
spk11: Yeah, you're right. Pancreatic is probably one of the most difficult to treat tumors with immunotherapy. Now, given the mechanism of action of AFM24, we believe that we could be able or should be able to really get initial NK cells into these cold tumors. We also believe that we have a chance to activate macrophages in these cold tumors. And I think increasingly our data indicate that this could kickstart really a concerted action of the innate and the adaptive immune system. So pancreatic cancer was selected based on these assumptions that we provide a completely different mechanism of action with both parts of the immune system activated. And it's an area of very significant unmet medical need. No immunotherapy has really worked here. So we wanted to give these patients really a chance. And again, I think we have some quite good preclinical rationale that even pancreatic carcinoma could drive some benefit from the unique mechanism of action of AFM24.
spk04: Great, thank you. And maybe a quick follow-up on your out-licensed AFM32 foliar receptor alpha program. I guess, can you remind us the economics over there and given, you know, foliar receptor alpha ADC is just recently approved, I guess, you know, any upside from that program that you see going forward? Thanks.
spk15: Yeah, Angus here, I could probably chime in on that. We have, as you're aware, we have licensed ASM32 to a subsidiary of Roy Vance as part of that deal. And through that deal, that subsidiary will be responsible for funding the clinical trial costs. And in return, we're entitled to milestones and royalties on that sales.
spk04: Great, thank you.
spk06: Thank you. I'm showing no further questions at this time. Thank you all for your participation. This does conclude today's call. You may now disconnect. Thank you.
spk16: Thank you.
spk01: The conference will begin shortly. To raise your hand during Q&A, you can dial star 11.
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