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spk17: Good day, everyone, and welcome to AFAMED's second quarter 2023 earnings and corporate update call. As a reminder, today's conference call is being recorded. I would now like to introduce your host for today's call, Alex Soutikidis, head of investor relations at AFAMED. Please go ahead.
spk02: Thank you, Chris, and thank you all for joining us today for our second quarter 2023 update call. Before we begin, I'd like to remind everyone that we issued the relevant press release and presentation earlier today, which can be found on the investor relations section of our website. On the call today, we have the members of our management team, including our chief executive officer, Adi Hurst, Andreas Horstrich, our chief medical officer, Arantxa Tilius, our chief scientific officer, Wolfgang Fischer, our Chief Operating Officer, and Denise Mueller, our Chief Business Officer, and Angus Smith, our Chief Financial Officer. The team will be available for Q&A after the prepared remarks. Before we start, I'd like to remind everyone that today's presentation contains projections and forward-looking statements regarding future events. These statements represent our belief and assumptions as 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?
spk06: Thank you, Alex. Good day, everyone, and thanks for joining us today.
spk07: I'm delighted to welcome you all to our second quarter results and business update call for 2023. I will take a moment to reflect on the good progress that we have made at AFIMET over the past few months. Let's move to slide five, please. First and foremost, I'm pleased to share with you that we are continuing to make significant progress across all of our pipelines. We have three ongoing clinical programs and we have the potential to generate meaningful data over the next 12 months. As presented, our inertial engager molecules are capable of delivering single-agent activity and show a benign safety profile in a broad number of heme and solid tumor indications. This benign safety profile now allows us for a number of different therapeutic combinations, and our focus is on combinations with allogeneic NK cells and checkpoint inhibitors. Now, for both combinations, we have generated impressive proof-of-concept data with AFM13. The success of AFM13 in combination with N-Casel in Hodgkin lymphoma patients who have exhausted any of its prior treatments has been outstanding. We're now leveraging this valuable experience in the AFM13-203 or LUMINAIS-203 study where we will combine AFM13 with the allogeneic encasal product AB-101. This promising combination holds tremendous potential for revolutionizing treatment for Hodgkin's and T-cell lymphoma patients. We continued our discussions with the FDA, and based on their feedback, we have requested a Type C meeting to further discuss the requirements for an accelerated approval based on the Luminize 203 study. Our FDA-approved protocol includes Q-learnings from earlier clinical studies. Now to AFM24. We announced at ASCO that going forward, we will be focusing our development efforts on the combination with atezolizumab. The data we presented from our monotherapy study created optimism within the medical community, and we are working to capitalize on this momentum. We have seen activity of AFM24 mono in all three indications tested, EGFR mutant non-small cell lung cancer, renal cell carcinoma, and colon cancer, including partial responses, tumor shrinkage, and or durable stable diseases. The activity now of AFM24 was most pronounced in the EGFR mutant non-small cell lung cancer cohort with two partial responses and five stable diseases observed in only 15 patients. And just to remind us, these are heavily pre-treated patients. From the phase one to mono study, we have further learned that there's not only an activation of NK cells, but also of T cells. And both are redirected now into the tumor upon AFM24 therapy. This is why we have added an additional expansion cohort to the Arteza-Lisa-Malcombo study to investigate EGFR mutant NSCLC with this combination. In fact, we have received a regulatory approval, and the new cohort is now open for recruitment in Europe and the U.S. Now, we believe this new expansion cohort will bring us valuable data that demonstrate the potential of 24 in this very difficult-to-treat solid tumor indications. Shifting gears again, I'm now pleased to share with you that our third eMedZen engager in the clinic, A from 28, is advancing rapidly through dose escalation. We have successfully completed the second dose cohort without any dose-limiting toxicities, and we're now actively treating patients in the third dose cohort, which is a flat dose of 100 milligrams once weekly. Finally, we continue to be in a good position. We have ample cash to execute our business plan into 2025, and this financial stability provides us with the freedom to pursue our focus goals without compromise while we continue to drive innovation in cancer treatment. Now, as we move forward, we're eagerly anticipating several upcoming election points. The next two months hold the promise to further revealing the potential of our therapies to provide clinically meaningful benefit in difficult to treat cancer. For AFIM-13, we're expecting to have further discussions with the FDA regarding the suitability of the LUMINAIS-203 study to support the potential accelerated approval. Next, we are expecting initial efficacy data from this study in the first half of 2024. We're also expecting more mature data from AFM13104 to be presented by MD Anderson and ASH in December. For AFM24, we are expecting to report data on the combination of AFM24 with atezolizumab at a company event in the fourth quarter of this year. And with AFM28, we are developing a novel therapy for one of the most in need patient population in relapsed refractory AML. Our recent progress with the dose escalation is very promising, and we will continue to update you as we proceed. In our view, we've made solid progress and look forward to meaningful updates over the next few months. With that, let me turn the call over to Andreas, who will provide to you additional insights. Andreas?
spk14: Yeah. Thank you, Adi, and also welcome from my side. Thanks to everyone on the phone for listening in. I'm happy to give you an update of the clinical progress of our three programs. And here I will start with the progress in AFM13. As we told you on our last call, we have received clearance from the FDA to proceed with the initiation of a Phase II clinical trial in which AFM13 will be evaluated in combination with EB101 the allogeneic NK cell product. We have made significant progress towards our goal of getting the study up and running and have generated interest from over 25 sites in the U.S. to participate, showing our commitment and dedication to advancing this innovative treatment. We are now in the final stages of site activation and expect to have the first sites open for patient recruitment in the September-October timeframe. Importantly, we believe that this will enable us to report initial data from the study in the first half of 2024. As all patients will be treated with active doses of AFM13 and AB101, even in the initial cohorts, we believe this initial data update will provide already a meaningful insight into both efficacy and safety of this treatment regimen. Furthermore, as Adi mentioned, we have taken proactive steps to follow up and engage with FDA and have requested a Type C meeting with the agency. The purpose of this meeting is to further discuss the requirements for an accelerated approval based on the LIMINISE 203 study. Based on FDA guidelines, we expect the meeting to be scheduled in the fourth quarter of 2023. Our proposed clinical study design is shown on slides seven and eight. As shown on slide seven, the study will commence with four cohorts evaluating two different doses of AFM13 and two different doses of AB101, focusing on patients with relapsed and refractory classical Hodgkin's lymphoma. It's important to note that all four cohorts will use doses of AFM13 and AB101, respectively, that we believe are active doses. Two of these four doses will then be selected for the next step, the first part of the assignment two stage design. And finally, our intention is to select one schedule for the final expansion part. This design addresses FDA's guidance to generate data on different doses early in the course of clinical development. and to make informed decisions on the dose that will be fully developed for the market, as for example outlined in the Project Optimus guidelines. In addition, we plan to start a fifth cohort treating peripheral T-cell lymphomas, CD30 positive, and this cohort should commence next year. On slide eight, you see the design of an individual treatment cycle of the study. After lymphodepleting therapy with modest doses of cyclophosphamide and flutarabine, a regimen that has been tested and demonstrated to be safe even when used multiple times, patients will receive AB101 cells and AFM13 on three consecutive weeks once weekly, followed by three weekly applications of AFM13 single agent. It is planned to give up to three cycles in patients who show a response. This design builds on experience from other NK cell studies and on our experience with AFM13 in the AFM13104 study. The weekly application of NK cells may offer more and longer exposure to the tumor to NK cell-mediated cytotoxicity. Of note, early data of AB101, again given weekly, in combination with rituxan, has shown good safety profile and promising activity in patients with refractory B-cell lymphomas, as recently published at ASCO. The application of weekly AFM13 for three additional weeks is based on data from the 104 study, where it could be shown that free AFM13 is capable to load repopulating patients' own NK cells thus providing a dual attack on the tumor. We are also reducing the interval between cycles, thereby preventing regrowth of tumor cells between cycles. Taken together, we think that the study design gives us the best chance to produce deep and lasting remissions in these difficult-to-treat patients. Additionally, as I already mentioned, as far as the 104 study is concerned, We expect MD Anderson to present updated data from this study at ASH later this year. This data will provide a comprehensive analysis of the efficacy, durability, and safety outcomes observed in patients with CD30-positive lymphomas, further demonstrating the potential of AFM13 in combination with NK cells. And now if we turn to AFM24, as announced during ASCO, We will focus our clinical development program with AFM24 on the combination with atezolizumab in the near term. In our AFM24 monotherapy study, as you know, we investigated AFM24 in patients with colorectal cancer, renal cell carcinoma, and EGFR mutant non-small cell lung cancer. Important to note that in this study, we were treating late-line patients that have often failed multiple prior lines and have no further treatment options. As shown on slide nine at ASCO, we presented data that showed clear signs of activity across all three cohorts. We are particularly encouraged by the partial responses tumor shrinkage and stable diseases that AFM24 could produce in heavily pretreated patients with EGFR mutant non-small cell lung cancer, including two confirmed partial responses and five patients with stable disease, which includes additional three patients with tumor volume reduction. Importantly, AFM24 exhibited a favorable safety profile, with manageable infusion-related reactions being the most common side effect. AFM24 did not induce severe EGFR-mediated toxicity in the skin or mucosa, which is commonly associated with other EGFR-targeting agents. As said earlier, the study also investigated patients with colorectal cancer and renal cell carcinoma. And again, the data demonstrated tumor shrinkage or reductions in target lesions across both tumor types. Some of these patients showed prolonged stability of their once-progressive disease, including, for example, one renal cell carcinoma patient achieving a substantial 28% reduction in target lesions just shy of another partial response. As shown on slide 10, based on the very encouraging activity of AFM24 monotherapy in EGFR-mutated non-small cell lung cancer, we have added a fourth cohort to the ongoing combination study with atezolizumab. Based on an amendment filed earlier with regulatory agencies, this cohort is now open for patient enrollment. Moving forward, we believe that AFM24's role in activating the immune system by specifically triggering NK cells and macrophages to destroy tumor cells and liberate tumor-associated antigens is crucial. These antigens can then be processed by macrophages and dendritic cells, leading to the activation and clonal expansion of tumor-reactive T cells, as shown in our earlier studies. The combination of AFM24, which activates innate immune system, with artesolizumab, which enhances the adaptive immune system, therefore has a logical rationale. As Eddie also mentioned, we plan to present an update from the ongoing combination trial with artesolizumab at the company event in the fourth quarter. Finally, data from the dose escalation portion of AFM24 in combination with the autologous cell product SNK01 was recently presented at ASCO Breakthrough. In this study, seven patients with a mean number of five prior lines of therapy received the combination of AFM24 and SNK01. No unexpected or dose-limiting toxicities were observed. and the PK properties of AFM24 were similar to AFM24 monotherapy. We believe that this first human study of an ICE in combination with adoptive and case head transfer established the feasibility of this novel combination approach. Of note, the stabilization of disease in heavily pre-treated patients with microsatellite-stable colorectal cancer was considered by our lead investigator, Dr. Elkhoury, as clinically meaningful. Based on the learnings from this study, we are evaluating options to advance AFM24 with an allogeneic off-the-shelf NK cell product, which we believe will better be suited for the combination with AFM24. Let's now turn to AFM28. And on slide 11, we are providing the update of AFM28, which was specifically designed to address CD123, positive myeloid malignancies, including acute myeloid leukemia. We have made significant progress in advancing the clinical development of AFM28. First, we have successfully cleared the second dose cohort, administering 50 milligrams of AFM28 weekly to patients with heavily pretreated AML without encountering any dose-limiting toxicities. Building on these data, we have now started the third cohort where we are administering a 100 milligram flat dose once weekly to AML patients. This positive development highlights the favorable safety profile and tolerability of AFM28. Moreover, we were also encouraged by data presented at ASCO with a different NK cell engager, also targeting CD123, that validated this target as a druggable target and showcased an acceptable safety profile. This is of importance as many other CD123-directed approaches, such as T-cell engages, CAR-Ts, or antibody drug conjugates, have shown high toxicity, including fatal cases at low doses, leading often to terminations of these programs. In our assessments, the new data likely mean that targeting CD123 is possible with NK cell engagers with manual toxicity. This is important as CD123 is considered a highly promising target, being expressed not only on leukemic blasts, but also on leukemic stem cells. We believe these results further emphasize the potential of AFM28 as a therapeutic target for AML patients. Additionally, preclinical data presented at the European Society for Blood and Marrow Transplantation Conference earlier this year highlighted the promise of AFM28. The data demonstrated the effective induction of NK cell-mediated lysis of AML blasts and leukemic stem cells. Notably, AFM28 exhibited activity even at low CD123 expression levels, and remained unaffected by the CD64 expression on leukemic cells. We believe these characteristics distinguish AFM28 from other approaches and suggest the possibility of deeper anti-tumor activity, more frequent remissions, and associated with a safe toxicity profile. Given the aggressive nature of AML and the urgent need for viable treatment options, we are diligently working to expedite the availability of AFM28 for relapsed and refractory AML patients. With this, I will conclude my update on the clinical progress and turn the call over to Angus to update you on the quarterly financial numbers. Angus, please.
spk12: Thank you, Andreas. Balance sheet and income statement highlights are shown on slides 13 and 14 of the presentation. A quick reminder that AFM28's consolidated financial statements have been prepared in accordance with 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 numbers that are mentioned in the call, unless otherwise noted, will be in euros. As of June 30th, 2023, cash and cash equivalents totaled 120.1 million euros, compared to 190.3 million euros as of December 31st, 2022. Based on our current operating plan and assumptions, we anticipate that our cash and cash equivalents will support operations into 2025. Net cash used in operating activities for the quarter ended June 30th, 2023, with 33.3 million euros compared to 26.5 million euros in the second quarter of 2022. Operating cash flow for the quarter was adversely impacted by a change in working capital of 7.5 million euros, which included 4.3 million euros for changes in trade and other payables, and 2.7 million for changes in other assets and prepaid expenses. The change in trade and other payables was driven primarily by payment of manufacturing costs for AFM 13 and AFM 24 that were expensed in prior periods, while the change in other assets and prepaid expenses was driven by 3.1 million of prepayments associated with the Luminize 203 trial, partially offset by a reduction in the amount of certain insurance prepayments. Total revenue for the quarter ended June 30th, 2023 was 1.4 million euros compared with 7.3 million euros for the quarter ended June 30th, 2022. Revenue predominantly relates to the Roivant and Genentech collaborations. R&D expenses for the quarter ended June 30th, 2023 increased by 21.3% from 20.8 million in the quarter ended June 30th, 2022 to 25.3 million in the quarter ended June 30th, 2023. The increase was primarily due to higher expenses associated with the development of AFM-13 and AFM-24, a result of increased costs related to the scale-up of production of AFM-13 for commercial purposes, as well as costs incurred for procurement of clinical trial material, increased clinical trial costs, and manufacturing costs, and an increase in costs associated with other early-stage programs and infrastructure. G&A expenses decreased 25.1% from $8.4 million in the quarter ended June 30, 2022, to $6.3 million in the quarter ended June 30, 2023. The decrease was due to a decline in legal, consulting, and insurance expenses, as well as share-based payment expenses. Worth noting is that total operating expenses for the second quarter were down 15% as compared to the first quarter of 2023. We expect to see a continued reduction in operating expenses over the next several quarters due to the reorganization that we announced in May, the completion of our work on the Genentech and Roivant collaborations, and the completion or wind down of certain clinical activities such as AFM 13202, AFM 13104, AFM 24101, and AFM 24103, as well as the timing of certain manufacturing expenses for AFM 13, which were weighted towards the first two quarters of 2023. Net finance income and costs for the quarter ended June 30th, 2023 decreased from income of 2.3 million euros in 2022 to income of 47,000 in the quarter ended June 30th, 2023. Net finance income costs are largely due to foreign exchange gains and losses related to assets denominated in U.S. dollars as a result of currency fluctuations between the U.S. dollar and the euro. Net loss for the quarter ended June 30th, 2023 was 29.4 million euros or 20 cents per common share compared with the net loss of 19.4 million euros or 13 cents per common share for the quarter ended June 30th, 2022. The weighted number of common shares outstanding for the quarter ended June 30th, 2023 was 149.3 million. Additional information regarding the results is included in the notes to the Consolidated Influence Financial Statements as of June 30th, 2023. which are included in APIMED's filings with the U.S. Securities and Exchange Commission. I will now turn the call back to Adi for closing remarks. Adi?
spk07: Thanks a lot, Angus. Let's move to slide 16. On this slide, now we show a snapshot of all our programs and upcoming milestones. In summary, as I already introduced, we have multiple meaningful milestones that we can meet within the next 12 months. This includes the initiation of Luminoids 2 or 3 targeting relapsed refractory Hodgkin and peripheral T-cell lymphoma patients. Our data already has shown that we can achieve high response rates in patients that have exhausted all prior approved treatments. Our deep and careful analysis shows furthermore that about 10,000 relapsed refractory Hodgkin and peripheral T-cell lymphoma. Patients comprise this market opportunity. So, however, as we've learned from the KOL and the payer landscape study, the data from AFM13 in combination with alloying K cells was so intriguing that this may offer prices at or even above CAR T's. With this, I'd like to express my sincere gratitude to our dedicated team whose tireless efforts have propelled us to where we stand today. Their unwavering commitment and passion for improving patient outcomes have been the cornerstone of our success. Together, we will continue to push the boundaries of medical innovation and bring hope to those cancer patients who need it most. Thank you all for your support, and I look forward to an engaging and informative session today. We're now ready to take questions. Operator?
spk17: Thank you. To ask a question, please press star 1 1 on your phone and wait for your name to be announced. To withdraw your question, please press star 1 1 again. Stand by as we compile the Q&A roster. And one moment please for our first question. Our first question will come from Maury Raycroft of Jefferies. Your line is open.
spk15: Hi, good morning and thanks for taking my questions. I had a question on the AFM 13203 study. So the Type C meeting is expected to happen in fourth quarter. Based on your timeline, what data from the 203 study could you show to FDA by that point? I know it would be early, but could you potentially have initial overall response rate and safety data from the run-in phase by the time of that meeting?
spk07: I'll hand this question over to Wolfgang, please.
spk09: Yeah. Hi, Mary. This is Wolfgang. As you might know from our previous discussions and disclosures, the Type C meeting is about to address the request from the FDA, which makes our LUMINI study feasible to be an accelerated for registration directed study for accelerated approval. And we had interactions with the FDA, and the FDA let us know that they are requesting the contribution of the single agents. That's their question. And based on this, right, we put together all the documents, et cetera, and submitted a Type C meeting request where we will discuss with the FDA how to best address these requirements for an accelerated approval based on our LUMINISE 203 study. And once we have had that meeting and aligned with the FDA on the approach, right, we will disclose that. Does that answer your question?
spk15: Well, I think so, but it sounds like you may not have initial data from the 203 study to discuss at that point. Is that fair?
spk09: This is not the objective of this Type C meeting, right? Also, our questions are around the contribution of the single agent. And as Andreas mentioned in his part, right, we are about to activate the study sites. September, September, October. And, of course, as soon as we have that, right, we will start recruitment of patients.
spk15: Understood. That makes sense. And what are your base case expectations at this point in terms of what a registrational study could look like?
spk09: I mean, when you also what we discussed and disclosed earlier, but the FDA granted us that study, and we clearly asked for or requested that registration-directed trial. And the FDA said there is open questions from their side. And then we clarified that in the request for clarification. And the result was that they're asking for the contribution of the single agent. And that's now what we are following up.
spk15: Understood. And last question, and then I'll hop back in the queue. For the first half of 24 update for the 203 study, How substantial would that update be in terms of number of patients, what stage of the study, and how much follow-up could you potentially have?
spk14: Andreas? Yeah, so as you see from the trial design, the focus clearly will be on the patients who are treated in the first four cohorts, so four times six patients that go initially on study. Given that, as Wolfgang said, we will start or we have trials... Sites open in October. I think the main focus of this initial update will be clearly safety, but also response rate. Of course, by the nature of when we start the study and then when we want to give the updates, the follow-up at this point in time will be relatively limited. So focus will clearly be on response rate and safety.
spk15: Got it. Okay. Thanks for taking my questions. Thank you.
spk18: One moment, please, for our next question.
spk17: Our next question will come from Dana Graybosh of Lerink Partners. Your line is open.
spk01: Hi, thank you for the question. I'm going to ask more about FDA's request on contribution of components, so a multi-part question on that. When they asked about contribution of components, Which components are they inquiring about? Obviously, AFM13 and the NK cells. Are they also including IL-2, which is new, and asking about contribution of components? That's the first question. And the second question is, how are you proposing to FDA that you show contribution of components of the NK cell specifically? And then maybe you could also address how you're going to show contribution of component for AFM 13. Thank you.
spk09: Yeah. Okay. Hi, Dana. This is Wolfgang. So, number one, yes, the FDA asked for contribution of single agents, including AFM 13, AB 101, and IL-2. But the way how we are proposing that, I mean, we have a proposal and sent that to the FDA. And, of course, we first want to discuss with the FDA whether that approach is feasible, right? And then, of course, we disclose. In particular, when you ask for AFM13, right, for AFM13, we have, I do not know how many patients, but way more than 100 patients treated in Hodgkin lymphoma, where we clearly know what the contribution of the single agent is. And we know that the... the response rate is between 11 and 16%. So this is, does that answer your question?
spk01: Yes, I agree. The ASM 13, I think, is pretty clear on contribution. I think what's less clear is the AB 101 and the IL-2, how you're going to demonstrate that. So I was interested in those proposals.
spk09: Yeah. No, we have a proposal, right, and that's also what we sent to the FDA. And as soon as we have an alignment here, we are going to disclose that.
spk01: Maybe one follow-up question. Which group at FDA is primarily asking these questions and leading the review? And which groups are involved in advising?
spk09: Yeah, so it's cyber and CIDR. Both of them are involved, right? So they gave that feedback together.
spk18: All right. Thank you.
spk17: Sure. Thank you. One moment please for our next question. Our next question will come from Lee Watzek of Cantor Fitzgerald. Your line is open.
spk11: Hey. Hey. Good morning. Thank you for taking our question. I guess just follow up on the type C meeting for ASM 13. And then in terms of the confirmatory state, can you just clarify if that will be part of the conversation at the meeting? And then in terms of, you know, communication to the street about the feedback, would you wait for meeting minutes? Or if so, should we still expect to hear back from you guys this year?
spk18: Wolfgang, you want to take this again?
spk09: Yeah, the last question, whether you will hear from us this year, yes, because we expect the feedback according to the FDA guidelines in Q4 this year. But we all know what we experienced in the past, where there was some delay. But according to the FDA guidelines, as I said, we expect that in Q4, definitely. And then, could you please repeat your first question? I didn't get that completely. Sorry.
spk11: In terms of the confirmatory study, just wondering if that will be part of the conversation as well.
spk09: The confirm, no. That's all, it's really about the contribution of the single agents, right, because the confirmatory will then come after that. Okay.
spk11: And then in terms of, you know, study starts for the phase two study, I guess, you know, what are the guiding steps here to sort of dosing the first patients in the next couple months? I mean, you mentioned there are 25 sites are interested. So just trying to understand, you know, where you are in that and, you know, anything you can do to accelerate the process.
spk06: Andreas?
spk14: Yeah, we are taking all possible measures already to accelerate the process. But as you may know, once you go to site initiation, there are certain legal contractual steps that you have to do on the site level. There's often additional review committee involved. So we are working through all these steps. We are having very close contacts to our primary investigators. So I think we are probably as fast as we can, but there are certain things in site initiation that just cannot be shortcut. But as we said, we have high interest from sites, and we expect to have a substantial number of sites open in the fourth quarter, and this has resulted also in our guidance that we are comfortable to provide first data updates first half of next year.
spk11: Okay, thank you.
spk17: Thank you. And one moment, please, for our next question. Our next question will come from Yale Jen of Laidlaw and Company. Your line is open.
spk10: Good morning, and thanks for taking the questions. I just wanted to follow up a little bit in terms of the first half 24 data release of Toll 3 study. Given that you would start the first two cohort first and then subsequently the second, the next two cohorts later, as well as the patient was sort of stacking between the first and second initially. So what, obviously, depending on the pace of enrollment, but what should we anticipate in general for the data release in the first half of next year, what level of patients we should be anticipating? Andreas, you want to take that?
spk14: Yeah. I mean, to some degree, of course, depends on the speed in which we can initiate the sites. As I said, we feel that we are on a good way here. Now when you carefully look at the study design, these four cohorts are overlapping, so we only have a staggered approach for the first two cohorts, and here also not for all patients. So basically once we have a couple of patients in the first two cohorts, all four cohorts can start to enroll patients more or less simultaneously. So we think that we should have all 24 patients
spk10: enrolled and for the majority of these patients we should have as i said safety and response data okay great that's very helpful and maybe just one more housekeeping question but you guys indicated that the two partnerships are you know going to renegotiate or discuss the future uh collaborations so should we anticipate that uh at least in the short term For example, starting next quarter or the third quarter, the revenue will be substantially reduced, or how should we look at that for a modeling purpose?
spk12: Yeah. Yeah, it's Angus. Let me just correct something you said. We didn't say anything about, you know, renegotiating partnerships. What we said is that we have completed the work that we were contractually obligated to do under Genentech and Roivant collaborations and handed the molecules over to them. So, from that perspective, we made that comment to highlight the fact that our expenses per contract under those collaborations are now substantially complete. The go-forward development of the molecules that have been handed over are at the discretion of our partners. And as we've said in the past, you can get a pretty good sense for what we expect to recognize in revenue from those collaborations over the next 12 months by looking at the current portion of our contractual liabilities. But since we recognize revenue on a percent of completion basis for each of those collaborations, and we have now substantially completed our work, it's fair to assume that the revenue recognized under those collaborations will be lower than in past periods. But again, as a reminder, that revenue is non-cash, and it's recognition of upfront payments that were received under those collaborations.
spk10: Okay, great. That's very helpful, and best luck and congrats on the progress.
spk18: Thank you. One moment, please, for our next question. The next question will come from Yanin Zhu of Wells Fargo.
spk17: Your line is open.
spk08: Thanks for taking our questions. I wanted to follow up a little bit on the FDA question. In terms of your response, would the response involve modification of the study design, for example, including more cohorts with varying doses of each component? Or would your response be mainly focusing on things like maybe preclinical evidence or literature research? And also, is there any evidence in the literature that suggests NK cells alone
spk06: even with io2 could have any efficacy in hodgkin's lymphoma thanks yeah um thank you for you shall i andreas do you want to take that question first on the um yeah so on the efficacy part um this i think is an ongoing discussion uh
spk14: To our knowledge, there has not been a data set generated, a clinical data set that specifically looks at non-targeted NK cells in Hodgkin's lymphoma. There are several data sets for quote, quote, non-targeted NK cells in non-Hodgkin's lymphoma, which consistently show very modest activity, if activity at all. Targeting really appears to be essential in this lymphoma tissues. And this will be one of the discussions with FDA whether FDA would want to see a specific clinical testing of NK cell plus IR2 or whether they basically acknowledge the experience and the data that had been generated in the non-Hodgkin lymphoma setting. So that is one of the, I think, key questions that will be discussed. As I mentioned in my introductory remarks, we have already taken into account some guidance when it comes to different doses and schedules, so we are addressing the Optimus initiative of FDA. As you see, we start out with four, basically, cohorts with different doses, schedules narrowed down to two, and finally, based on the data, narrowed down to one. we would not expect that the dose and scheduling question comes up with FDA. So I think the negative case will be the key point that will be discussed with FDA.
spk08: Got it. Thank you. That's very helpful.
spk17: Thank you. One moment, please, for our next question. Our next question will come from Srivipa. Devaram Konda, Truist Securities. Your line is open.
spk13: Hey, guys. Good morning. Thank you so much for taking my question. So regarding the Type C meeting, I have a follow-up question. In terms of the package that you need to submit, do you already have that ready to go? I think you need to submit it a few weeks ahead of the meeting. And what is the likelihood that the FDA might say, you know, wait for early preliminary data from part one or stage one of the study before they think it is meaningful to have this discussion. And on the partnership with Genentech and AppEvent, you've completed your part of the work. Is there a timeframe before which the partners are required to make a go, no-go decision on these assets? Thank you.
spk09: Yes, so I'll hand it over to Wolfgang again. I start with the type C meeting. Yes, you are correct, right? You need to submit your package briefing book, et cetera, before the meeting. And yes, we are preparing that, and we are on track to submit that in due time. That's the first question. You said, what is the risk that the FDA say, wait until you have first data before we discuss We think that risk is small because it's really a specific request from the FDA. And the FDA invited us for an interaction for a Type C meeting to discuss that with them. So therefore, it's our belief that this risk is very small, if at all.
spk18: Does that answer your question? Yes.
spk06: No, that's very helpful. I guess you want to speak about the collaborations.
spk12: Yeah, in terms of the collaborations, I mean, no specific timeframe in which the assets would have to move forward. Again, as we said, the decision to move that forward is at the discretion of the partners, as well as at this stage of the collaboration, the communication around moving forward is also at the discretion of the partners.
spk13: Thank you.
spk12: There are standard, you know, kind of commercially reasonable effort type of clauses as well.
spk17: Thank you. One moment, please, for our next question. Our next question will come from Andy Chen of Berenberg. Your line is open.
spk05: Hey, thank you for taking my question. So, another question about the Type C meeting with the FDA. Is the FDA just curious about single-agent contribution, or do they require single-agent contribution for accelerated approval to be possible? Just, like, if you don't know, like, I'm wondering if you can speculate on, like, why the FDA is asking for this information and what they're thinking in their head.
spk09: Thanks for the question. Thanks for the question, Andy. The FDA is requesting that, right? And also, when you read the FDA guideline, right, it's also there that when you have combinations the contribution of single agents need to be investigated, right? So that's, it's a request. It's not, they are not just curious.
spk05: Okay. So it needs to be investigated, but it doesn't need to be like strongly positive, right?
spk09: Correct. You need to, you need to provide a plan. You need to provide an idea how you, how you demonstrate that contribution of the simulations, right? And that's what we are going to do and to discuss with the FDA during the type C.
spk05: Got it. And the other question is about Arteva's ASCO data. So they saw, I think, two out of 15, well, out of 15 patients, they saw two cases of CRS at 1 billion cells, single dose. And I'm wondering, because you're, like, for your Luminize trial, you're going to be doing higher doses and multiple cycles. And I'm wondering, like, how do you think about the risks of doing that in the trial? Andreas? Can you take that question?
spk14: Yeah, I think, and I would have to go back to the original data from the poster, but as far as I recall, these were very mild cases of CRS, often very difficult to distinguish from a classical infusion-related reaction. Overall, I think the cell so far has shown a remarkably good safety profile. And, of course, we will take somewhat higher doses Again, not higher than the doses that are tested now. As you may know, Arteva is currently looking at 4 billion NK cells per infusion, so per week. And we have not heard any indication of new or unexpected toxicity. So our current belief is that this approach will be very safe and it could be administered for multiple cycles.
spk18: Thank you. Thank you.
spk17: And again, one moment, please, for our next question. Our next question will come from Foyam Pakola Ramakath of HCW. Your line is open.
spk03: FOYAM PAKOLA RAMAKATH Thank you. This is RK from HCW. Good afternoon, Adi and Andreas. I've been juggling between calls, so I apologize if these questions have been answered before. Just in terms of AFM28, In terms of the monotherapy part of the study, what sort of data should we expect from here to the end of the year? And in terms of the combination part of the study, what else needs to get done before you could start that trial?
spk14: I just want to make sure you're meeting AFM28 because you said also combination part of the study, which AFM28 does not have. But let's start with the first question. So, as you know, we are in a dose escalation study. We have moved very quickly through the first two dose escalation cohorts, have not seen any dose-limiting side effects. We are currently enrolling into our third cohort. The study has a Bayesian dose escalation design, so we cannot predict at this point how many dose escalations that we will finally take. And as we said, we will provide you with updates on the progress as we go along during the course of the year. Now, I'm not sure what you mean with the combination study, because as far as FN28 is concerned, currently we only have the dose escalation study in our portfolio. As we said, we actively look also into options to combine with an NK cell, but this is a strategic effort that the company is currently undertaking without a firm protocol yet.
spk03: Thanks, Andreas. My apologies. What I meant was your plan to see whether the combination is feasible. That's what I meant. I apologize for that.
spk06: Andres?
spk14: Whether the combination was feasible, we believe it's feasible based on all that we have seen. Again, the first strategic effort that we have is to identify an NK cell that we could take forward into our FM248 program.
spk03: Thank you. Thanks for taking the questions.
spk17: Thank you. One moment, please, for our next question. Our next question will come from the line of Bradley Canino of Stiefel. Your line is open.
spk16: Hey, good morning. This is Bajano for Brad Canino. Thanks for taking my question. Another question on the FDA Type C meeting. Is it going to require multiple FDA meetings to get clarity on the requirements for registration and the confirmatory strategy, or do you expect to have answers for the both of those after this 4Q meeting?
spk09: Yeah. Thanks for the question. As we said before, right, the Type C meeting is really focusing on the contribution of the single agent and to discuss with the agency how we can address that best to make Luminize feasible for registration directed study for accelerated approval. That's the focus of the Type C meeting. Now, when it comes to a confirmatory study, no, the confirmatory study will not be discussed at that Type C meeting. That will be separate.
spk16: Got it. And just one more question. On the AB101 ASCO poster, what are the takeaways from that poster that give you confidence it'll produce a similar effect in combination to MD Anderson's NK cells? Andreas?
spk14: Yeah, I think, of course, it's very early data. When you look at the ASCO poster, it's with very low numbers of cells. but still even in patients who were coming from CAR-T treatment, they have seen complete and partial responses. Our confidence is not only based on the ASCO poster, but also on all of the extensive preclinical work that we have done with the AB101 cell. Again, hard to test head-to-head against the MD Anderson cell, as MD Anderson is a fresh cell product which could not be shipped, so we were not able to run a head-to-head comparison, but in very comparable models, and Arndt probably can speak more to that, but in every model that we tested this cell, we have seen at least comparable activity compared to the data that we have generated with the MD Anderson cell.
spk04: Yeah, just to quickly add this to John, this is Arndt. As Andrea said, when we compare co-dosing to pre-complexing, You remember in vitro, we actually saw that slightly better than the pre-complexing. And the models we have done with serocore administration are absolutely equivalent to the ones that we have done with MD Anderson. And you may remember of seeing the ICML poster where we again showed we have full saturation of 13 on AD101 after cryopreservation. Very important that also is possible after cryopreservation and have shown that convincing mouse model going there.
spk18: Appreciate the answers.
spk17: Thank you. I see no further questions in the queue. This will conclude today's conference call. Thank you all for participating. You may now disconnect and have a pleasant day.
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