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spk26: Good day, everyone, and welcome to AFIMED's first quarter 2023 earnings and corporate update call. At this time, all participants are in a listen-only mode. After the presentation, there will be a question and answer session. To ask a question during the session, you'll need to press star 1 1 on your telephone. You'll then hear an automated message advising your hand is raised. To withdraw your question, please press star 1 1 again. As a reminder, today's conference is being recorded. I would now like to introduce your host for today's call, Alex Futakidis, Head of Investor Relations at Appamed. Please go ahead.
spk06: Thank you, Liz, and thank you all for joining us today for our first quarter 2023 update call. Before we begin, I'd like to remind everyone that we issued two relevant press releases 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 Adi Hirsch, our Chief Executive Officer, Andreas Harstreich, our Chief Medical Officer, Arne Schotelius, our Chief Scientific Officer, Wolfgang Fischer, our Chief Operating Officer, 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 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 those 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 subjects to risk 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 and of 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'd like to turn the call over to Adi. Adi?
spk11: Thank you, Alex, and good morning, everybody. Thanks for joining our call today. I'll start with reviewing key highlights. And as Alex has already mentioned, I'm very pleased to report that we continue to make progress on our key priorities across the pipeline. As you can see now on slide five, First, we are extremely excited to announce the FDA clearance of our investigational new drug application for the combination of AFM13 with AB101. And we will call this study LUMINOIS-203. Indeed, this is a significant achievement for our company as it enables us to move forward with a Phase II study of this promising therapy. I'd like to thank all colleagues at AFIMED and Artiva who worked diligently in the past few months to make this possible. This treatment now will build on the findings that we have generated in the AFM13-104 study of AFM13 in combination with coblast-derived natural killer cells. Data which was presented by Dr. Iago Nieto from MD Anderson Cancer Center at the ASH conference back in 2022. Across our organization, we're committed to advancing the development of this therapy as fast as we can. The efficient and quick execution of this trial, assessing the combination therapy of AFIM13 and AV101 is a key focus for our company. Wolfgang Fischauer, Chief Operating Officer, will go into the details of the study design and timing late in the call. Andreas Hartstrick, our chief medical officer, will update you on the rest of our clinical programs. Second, we have continued to advance AFM24 clinical studies towards data milestones. AFM24 is our novel inner-cell engager targeting EGFR, and we believe it has the potential to be a transformative therapy for many patients with EGFR-expressing solid tumors. We now plan to present interim data from the monotherapy expansion cohort at the upcoming ASCO meeting on June 3. Specifically, we will be presenting data from the non-small cell lung cancer cohort, which has been accepted for poster presentation, and data from the colorectal cancer cohort, which has been accepted for online publication. The data will include about 15 patients from each court. The full text of the abstracts will be published later this week and will only include data as of the December 2022 cutoff date. The data in the NSCLC poster will include data from a later close date. We plan to host a call with the financial community to review the monotherapy data in more detail, as well as provide a strategic update on the AFM24 program. The virtual event will be held on Saturday, June 3. Details of the call will be included in our abstract release on Thursday. Finally, our phase one study of AFM28 monotherapy is proceeding quite rapidly. We're pleased to announce that the first dose cohort has already been cleared, and the study is now actively recruiting patients in the second dose cohort, which means all our pipeline programs have significant potential to address unmet medical needs and improve outcomes for a variety of hematological and solid tumor indications. With this, we are quite uniquely positioned to drive shareholder value in the near term. Before now I hand over the call to Wolfgang, I'd like to mention that considering the current market conditions, AffiMed has had to make a difficult decision to control our operating expenses by reorganizing our company to focus our efforts primarily on our Kennedy programs. As a result of the reorganization, we have reduced our full-time equivalent headcount by approximately 25%. We took extra care to ensure that this reorganization will not impact the development of our three clinical programs, and we believe we are well positioned to meet key data milestones for all three programs within the next three to 15 months. This now includes data from AFM13 in combination with AB101, data from all three AFM24 clinical studies, and data from AFM28 mono in AML as we continue to make progress with the dose escalation. And with that, let me turn over the call to Wolfgang, who will provide additional insights on the progress we're making in our pipeline.
spk09: Wolfgang?
spk17: Thank you, Adi. Good morning, everybody. As Adi mentioned, we now have the IND clearance from the FDA to take AFM13 into a phase two study in combination with the AB101 and KSAR from Activa. This study will build on data from the AFM13-104 study, which we reported at ASH in December 2022. Very briefly, as shown on slide seven, At ASH, we reported data from the Phase I-II study of ASM13 combined with co-blood-derived NK cells in patients with relapsed refractory CD30-positive lymphomas. Data from the study showed a 94% objective response rate and a complete response rate of 71% in 35 heavily pretreated CD30-positive Hodgkin lymphoma and non-Hodgkin lymphoma patients treated at the recommended Phase II dose. 63% of the patients treated at the recommended phase 2 dose with at least six months follow-up after the initial infusion remained in complete response for at least six months. In addition, the treatment was well-tolerated with no cases of cytokine release syndrome, immune effector cell-associated neurotoxicity, or graft-versus-post disease observed. Since we disclosed the data from the AFM13-104 study, we have had conversations with treating physicians, and we know that there is a lot of interest in the medical community about the possibility of having such treatment available to patients. In the past, we have also shared with you information about why we are confident in the combination of AFM13 with AB101, as outlined on slide eight. We believe Antivas AB101 and K-cell has all key features that will allow for similar clinical results as those we saw with the combination of AFM13 with the MD Anderson and K-cell. And very importantly, it meets critical commercial requirements. A new IND is for phase two clinical study to investigate AFM13 in combination with AB101 from Arteva in patients with relapsed refractory Hodgkin lymphoma who have exhausted all standard of care therapy, including chemotherapy, rentuximab, vedotin, and the PD-1 checkpoint inhibitor. As is shown on slide nine, the primary endpoint of the study are to assess the antitumor activity by objective response rate, including complete responses and partial responses. Secondary endpoints of the studies are to assess efficacy, durability of response, safety and tolerability, as well as immunogenicity of the combination therapy. Now, on slide 10, we introduce the design of the clinical study, which, as I mentioned before, will be called Luminize 203. The study will begin with a safety running phase. During this phase, we will evaluate different combination doses of AB1N1 and AFM13 in four cohorts of six patients each. Now let's go through the cohorts. Cohort one will evaluate a dose of 2 billion AB1N1 cells administered weekly combined with AFM13 200 milligram weekly. Cohort two will be exactly the same. except that the AFM13 dose will be 300 milligrams. Cohort 3, there we will evaluate the dosing regimen of AB101 of 4 billion cells in week 1, followed by two weekly doses of 2 billion cells, in each case combined with 200 milligram AFM13. And finally, cohort 4 will be the same as cohort 3, except that we will administer AFM13 300 milligram weekly. During the run-in phase, we will evaluate the safety and preliminary efficacy of these dosing regimens with the goal of selecting two dosing regimens for the dose optimization phase, which follows assignment two stage design. The study has then the potential to continue with one for both cohorts from the optimization phase into the expansion phase. The trial will enroll up to 140, 134 patients, and currently all our clinical sites are located in the United States. As you can see, there is also an exploratory cohort with CD30-positive PT-CL patients, which will include another additional 20 patients. On slide 11, we show the treatment regimen. In Luminize 203, patients will be treated with lymphodepleting doses of fluorarabine, 30 milligram per square meter per day, and taclofosfamide, 300 milligram per square meter per day, prior to the first AFM13 AB101 dosing. This dose and schedule of lymphodepleting chemotherapy is based on other cell therapy studies that have demonstrated the safety and effectiveness of this regimen, including our own study, AFM13-104. As you can see on the slide, one treatment cycle will consist of three weekly co-administered doses of AFM13 and AB101, followed by three weekly doses of AFM13 monotherapies. Up to three cycles of treatment may be administered. Looking ahead, as outlined on slide 12, we are very focused to get the study up and running in Q3 2023. During the IND process, we requested feedback from the FDA on the suitability of the study to support an accelerated approval in Hodgkin's lymphoma. As a recommendation of the FDA, in parallel to advancing the study, AFIMED will have further discussions with the agency on the requirements for registration application in the U.S. Finally, we expect to be able to share data from the safety run-in phase during the first half of 2024. As a final note of this discussion about the combination of AFM13 with AB101, many of you have asked us questions about when ARTIVA plans to share data from AB101 in B-cell lymphoma. We wanted to bring to your attention that ACIVA is planning on presenting data from the AB101 rituximab combination study in a poster presentation at ASCO on June 5th. Now, I'll hand over the call to Andreas to discuss the updates for our other clinical programs. Andreas.
spk22: Thank you, Wolfgang, and also welcome from my side to everyone on the call. Let's now move to AFM24. And as we show on slide 13, at ASCO, AFIMET will present initial data from two expansion cohorts of the monotherapy study of our EGFR-targeting innate cell engager AFM24. As mentioned by Adi, we have been accepted to present interim results from the EGFR mutant non-small cell lung cancer cohort in a poster presentation. And in addition, interim results from the colorectal cancer cohort have been accepted for online publication. As you will be aware, full abstracts for ASCO and for both of our cohorts will become available on May 25th. So for today, we are limited in what we can share with you. However, what we can tell you is that the data reported on May 25 in the abstracts will have a cutoff date of December 2022. At ASCO for the non-small cell lung cancer cohort, we will share updated data with a significantly later cutoff date. Specifically, we will present data from 15 patients from each of the non-small cell lung cancer and the colorectal cancer cohorts. As Adi mentioned, we are also planning to host a call with members of the financial community to discuss the data and to review our AFM24 strategy going forward. Our second AFM24 study, the combination of AFM24 with atezolizumab, we are continuing to treat patients with non-small cell lung cancer, EGFR wild type, gastric and gastroesophageal junction adenocarcinoma, and pancreatic, hepatocellular, and biliary tract cancers in three separate cohorts. The dose escalation portion of the study is complete. And we have confirmed the 480 milligrams weekly dose of AFM24 as the recommended phase two dose. Enrollment in the expansion cohort is ongoing, and the treatment continues to show a well-managed safety profile. As shown, we plan to provide data from this ongoing study in the second half of 2023. The second combination study of AFM24 is investigating the combination of AFM24 with SNK01, the ex vivo expanded and activated autologous NK cell product from NKGen Biotech. Here, both agents 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. We continue to enroll patients in the dose escalation phase of the trial and expect to have this completed within 2023. Also, for this trial, we plan to provide data in the second half of 2023. Now, moving to AFM28 on slide 15, we show the exciting progress that we were able to make with our I.C.E. designed to bring a new immunotherapeutic approach to patients with CD123 positive myeloid malignancies, which include acute myeloid leukemia and myelodysplastic syndrome. In our phase one study, we treated the first patient in March, and since then we have been able to complete the first dose cohort of 25 milligrams once weekly. without encountering dose-limiting toxicity. This has allowed us to open the second dose cohort at 50 milligrams weekly, in which we are currently actively recruiting patients. Given the aggressive nature of this disease and the need for viable treatment options, we are working diligently to bring this treatment option to refractory and relapsed AML patients as quickly as possible. With this short summary, I will turn the call over now to Angus to update you on the quarterly financial numbers. Angus, please.
spk29: Thank you, Andreas. Balance sheet and income state highlights are shown on slides 17 and 18 of the presentation. As a quick reminder, AFIMET'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, which is the company's functional and presentation currency. Therefore, all numbers that I will present on this call, unless otherwise noted, will be in euros. As of March 31st, 2023, cash and cash equivalents totaled 155.8 million euros compared to 190.3 million euros on 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 March 31st, 2023 was 33.2 million euros compared to 28.4 million euros for the same period in 2022. Total revenue for the quarter ended March 31st, 2023 was 4.5 million euros compared with 8 million euros for the quarter ended March 31st, 2022. Revenue predominantly relates to the Genentech and Roivant collaborations. Research and development expenses for the quarter ended March 31st, 2023 increased by 60.7% from 18.4 million for the same period in 2022 to 29.5 million in 2023. The increase was primarily due to higher expenses associated with the development of AFM 13 and AFM 24. resulting from increased procurement of clinical trial material, increased clinical trial costs, and increased costs associated with other early stage programs and infrastructure. General and administrative expenses decreased 2.8% from 7 million euros in the quarter ended March 31st, 2022 to 6.9 million euros in the quarter ended March 31st, 2023. An increase in personnel costs were offset by a decline in legal consulting and insurance expenses. Net finance income and costs for the quarter ended March 31st, 2023 decreased from income of about half a million euros in the quarter ended March 31st, 2022 to costs of about half a million euros in the quarter ended March 31st, 2023. As a reminder, net finance income or costs are largely due to foreign exchange gains or losses related to assets that are denominated in U.S. dollars as a result of currency fluctuations between the U.S. dollar and the euro during the year. Net loss for the quarter ended March 31st, 2023 was 32 million euros or 21 cents per common share compared with a net loss of 16.7 million euros or 14 cents per common share for the quarter ended March 31st, 2022. The weighted number of common shares outstanding for the quarter ended March 31st, 2023 was 149.3 million. Additional information regarding these results is included in the notes of the consolidated financial statements as of March 31st, 2023, which will be included in AFTIMED's filing with the SEC. I'll now turn the call back to Adi for closing remarks. Adi?
spk11: Thanks a lot, Angus. Now moving to slide 19, we show a snapshot of all our programs. And we're very excited on behalf of patients that could benefit from the combination treatment of AFM13 with AB101. And we're now looking forward to getting the study started and bringing new updates as we make the progress. We also are looking forward to our call with you on June 3 to discuss the findings from the non-small cell lung cancer and colorectal cancer studies. during which we are also planning to update you on our broader plans for AFEM 24 going forward. And as you've heard, we are indeed quite excited about the progress we are making with AFEM 28 in AML, which we believe has a huge potential, as we mentioned in the past, that NK cells can play a major role in AFEM 28 as a very pronounced activity redirecting NK cells. We're also thankful for the support and efforts of our employees who have pulled together to move things forward. It is through their dedication and the support from you and the patients and their families that gives us inspiration to continue our work of bringing these life-saving therapies to the market. We are now ready to take questions, and I hand back to the operator.
spk26: As a reminder, if you'd like to ask a question at this time, please press star 1 1 on your telephone and wait for your name to be announced. To withdraw your question, please press star 1 1 again. Our first question comes from the line of Maury Raycroft with Jefferies.
spk25: Maury, your line is now open.
spk05: Hi, thanks for taking my questions. Question on the Luminize study. Presumably the Simon2 stage design part of the study is open label. Just wanted to clarify that. And then also wondering what is the bar for success on overall response rate and duration of response? And is there anything additional you're saying on powering for the study?
spk11: Yeah, thanks, Maureen. Good morning. So, handing this question over to Wolfgang. Wolfgang?
spk14: Okay, and you may be on mute.
spk17: Yeah, thanks, Angus. Hi, Marie. As you can see on slide number 10, the dose optimization, right, we have two cohorts selected from the safety run-in, 13 patients per cohort, and each of these cohorts will follow assignment stage 2 design. So that means we are evaluating each of these cohort separately, right, to a futility, whether to move forward, yes or no. That's number one. The other question was the bar success, right? Based on the data we have generated with AFM 13-104, right, we believe that the bar or that we can achieve very high response rates, very similar to what we have seen in the 104 study. And the third question, I do not remember. Could you please repeat?
spk05: If you're saying anything additional on powering for the study.
spk17: Do you want to take that question regarding the power of the study?
spk22: Yeah, I can take this question. As Wolfgang has said, and I think it's also depicted on the slide, the second part of the study, which starts with two doses selected from the initial four cohorts, and then the option to continue basically into the expansion, consists of two separately powered Simon2 stage cohorts. So there is no direct comparison on a statistical level between the different cohorts. And on the totality of the data, we can decide to either move one or two cohorts until the final number of 55 patients per cohort. This was something that specifically came out of our discussions with FDA, and I think it's also in line with FDA's attempt to have more data available on dose optimization and the effect of different doses on the outcome. So again, these two arms are separate Simon 2 stage arms, which do not have a statistical comparison between the two arms.
spk05: Got it. Makes sense. And anything else you can tell us about the nature or timing of FDA discussions to be had on registration or requirements? I guess would that be first half 24 after you get the run-in data, or would that be later on? And can you say if you've spoken with FDA at all about the feasibility of doing a randomized study as opposed to a single-arm study?
spk21: Oh, yeah. Go ahead.
spk17: Yeah. So we have designed that study with the intent for an accelerated approval. very clear, right, and also following also the draft guidance from FDA from March 2023, where it still very clearly says that single-arm study is still feasible in certain senses. So, we asked the FDA for that feedback, and the FDA came back to us and recommended that we continue that discussion in a separate meeting with them. So basically, they recommend it while starting the study, reaching out to them for further discussions. During these interactions with the FDA, the FDA did not provide us specific guidance or feedback regarding their concerns.
spk05: Got it. Okay. Makes sense. Thanks for taking my questions.
spk26: Our next question comes from the line of Lee Wacek with Cantor Fitzgerald.
spk24: Hey, guys. Thank you for taking our questions. Maybe just follow up on, I guess, the registration application, understanding that, you know, you're still in the process of that with the agency. Can you give us a sense of what kind of, you know, different scenarios that you're preparing for here?
spk17: I mean, we are in constant contact with our project manager at FDA, and we'll determine the next steps. Once agreed with the timelines, we will provide further guidance. We also believe that it's currently too premature to discuss or to speculate what is the FDA's position and what are different scenarios.
spk24: Okay, got it. And then just for the safety and running portion, I guess do you need to discuss with the agency before you proceed to the optimization service portion or it will be pretty seamless And I guess for the safety running portion, how long is the follow-up?
spk17: The first question, right, these patients are treated as outlined on the slide we have provided. I guess it's slide number 11. and also these patients can receive up to three cycles. The assessment for selecting two dose cohorts moving forward into the optimization phase will happen after the first assessment. And the first question was whether we need to go to FDA before moving forward. No, the FDA provided full commitment to that study. Okay, thanks.
spk26: Our next question comes from a line of Sri Kripa Devarakonda with Truist Securities.
spk31: Thank you so much, guys, for taking my question, and congrats on getting the IND cleared. Quickly, you know, what else needs to be done in order for you guys to get the trial going? You said third quarter, you should be able to get it going. And Based on the trial enrollment that you saw with your previous partnership with MD Anderson, how confident are you that we'll have enrollment and we'll be able to see data from the run-in patients? It's about 24 patients in first half. And is there any likelihood that we could also see enrollment in stage two by then? Not data, but at least enrollment. Thank you.
spk17: Yeah, so 1st question we are, we are preparing for 1st patients. 1st patient in in Q3, 2023. And we are, we are fully on track on on that. So we are interacting with the zeros. We are interacting with the site, et cetera, et cetera. So that's all fine and and on track for Q3, 2023. Regarding the 1st, the data. Yes, we plan to provide a first data from the safety run-in, so from the 24 patients in H1 2024.
spk14: Did you have another question?
spk17: Sorry, maybe I missed it.
spk31: Oh, sorry. Sorry, I was on mute. Okay. I was just wondering By the time you have the data, should we expect enrollment to already begin in stage two of the trial as well?
spk17: I mean, we will start with stage two of the trial, so with the optimization phase, as soon as we have finished basically the safety run-in right after the first assessment, as I said before, because that's the basis for moving forward. And as soon as we have completed that, we will start with the stage two. When that exactly will be, I can't say.
spk30: Okay. Thank you. That's helpful.
spk26: Our next question comes from the line of Brad Canino with Stiefel.
spk33: Hi. Thanks for the updates. I'm looking at slide 10 here for the dose expansion portion where it says you'll select one or two cohorts depending on the interim clinical data. I'm wondering, can you comment on what length of follow-up will be required for the interim data to make that decision to move into the pivotal period?
spk12: Wolfgang, again?
spk17: Yeah. So, after the dose optimization, a patient will be follow-up for two treatment cycles. And after these two treatment cycles, right, the decision will be made, the interim analysis will be made, and then the decision based on the Simon 2 stage design to move forward or not to move forward. So after two treatment cycles, two assessments.
spk33: Okay, thank you. And then as you continue the FDA discussions, can you help us understand how much your partner is included in these? You know, particularly I'm thinking about how much buy-in they might have if one of the decisions being to run a concurrent confirmatory study along with this single arm study. Thank you.
spk17: Yeah. So, Eddie, I take that, at least the first part, and then I give it to you for the second part. The partnering with ATIVA is going very well. It's a very nice and very good collaboration. on a team level, on a joint steering committee level, and we are all aligned in our interactions with the FDA. We align before we discuss and have a common path forward. So that's going really well. Regarding the confirmatory study and their commitment, I will hand over to Adi. Adi, please.
spk11: Yeah, contractually, as you know, this is a shared study in terms of costs. And we have not yet started the details of this discussion as we're fully focused on getting the IND cleared. And obviously, ARTIVA has played a major role in submitting the IND and input into this product design. So as we're now through with the IND clearance and can start the study, we will now take up and move to the next steps on what kind of confirmatory studies we were contemplating. We have already mentioned in the past that we have, obviously, a number of options in Hodgkin and Fulmer where we can place it, but we also focus in terms of moving forward with the PTCL, at least initially based on the findings within the 20-patient cohort. That's our plans, yeah. Okay.
spk14: Appreciate the comments. Thank you.
spk26: Our next question comes from the line of Dana Graybosh with SBB Securities.
spk07: Hi, this is Rabib online for Dana. The questions we have are surrounding ASCO in particular, especially in regards to Arteeva. What are you looking for for this first disclosure and clinical data from Arteva, given that this product is being used for the Luminize 2 or 3 trial, as opposed to the Anderson product from previous data? And then what are we looking for in the AFM24 monotherapy data in CSD1 and in CL3? that give us confidence for future readouts in second half 23 with the combination of NK cells and or PD-L1.
spk11: Yeah, thanks for the question. I'll hand over to Andreas, please.
spk22: Yeah, so it's a difficult to answer question because it relates basically in all parts to data that will be published at ASCO. As you know, for ATIVA, ATIVA has an ongoing study that evaluates both of the AB101 cell as a single product, so without targeting agent. And here they are looking at a couple of different dose levels in patients with B-cell malignancies. And they also have the combination of AB101 cells with rituximab, so a targeting agent in B-cell malignancies. And they will provide update on the current status of their study. Again, given that this is an upcoming ASCO presentation, we cannot go into more details as all of the, especially the updated and newer data are under ASCO embargo. For AFM24, again, we will show updated data for the patients with EGFR mutant non-small cell lung cancer treated with single agent AFM24. We will also have an online publication for the colorectal cancer cohort. Again, those will have updated data compared to the abstracts that come available or become available later this week. And as we said, after our poster presentation, we will also host an investor event to discuss or to have a comprehensive discussion of the AFM24 strategy, of course, taking into account the new data that we will show at ASCO. But I think until then, I unfortunately cannot share more details with you.
spk07: Just a short follow-up. We've heard that companies are permitted to provide updated data after the abstracts are released if the data are different than what was written in the abstract. Is that something you can look for from ACOBIT?
spk29: Yeah. Adi, maybe I can take that one. So, thank you for the question. It's something we've obviously looked very, very closely at. ASCO is unique in this regard. Ultimately, since we have a poster presentation at ASCO, out of respect for our investigator who will be at the poster, our decision was to provide the updated data at ASCO itself on June 3rd, and as Adi and Andreas mentioned, to then host an investor call subsequent to the poster discussion to provide further updates on ASM24. That was the decision. That's kind of what went into our decision to wait until June 3rd. And as was mentioned, the abstracts with the December cutoff date will be published on Thursday.
spk32: Thank you so much.
spk26: Our next question comes from the line of Gail Jen with Laidlaw.
spk14: Good morning, and thanks for taking the questions.
spk16: Good morning.
spk15: Good morning.
spk16: Good morning. How are you? Sorry. My first question is that you guys mentioned that in the press release that you're going to have preclinical data presented at the ICML. My question is that what should we anticipate from that data sort of data release, Do you show anything in comparison to the cobalt cell-derived NK cell as well?
spk09: Andreas, you want to take the question, please?
spk22: When it's relating to preclinical, I think Arndt would probably be the right person to respond.
spk02: Okay, sorry.
spk20: Happy to take the question, Gail. Very nice to... Thanks for your question. So you will have noticed we have not given any specifics because we want to also respect the embargo for this conference. But as you can assume, we will show preclinical data, the combination of the products, and some of that we had actually previously shown also at some investor conferences. So we will show the preclinical data
spk16: basis for moving into the clinic so you can expect that uh you know there's synergistic activity to be shown but i i cannot share more more specifics that will be that will be shared at the conference i'm sure you'll understand sure uh not problem and thanks for that and maybe just one more housekeeping questions that also in the press release you indicated that uh the genentech uh uh collaboration at least for the time being seems completed, you handed out the product. So just from a modeling purpose, should we anticipate the revenue be slightly lower going forward as you at least assume there's only one collaboration panel at the moment until otherwise?
spk29: Yeah, I can take that. As you mentioned, Greg, the work that we were responsible for under the Genentech collaboration has now been completed, and the targets that we were developing on their behalf have been handed over to Genentech. So, that's good news on that front. As you know, we've been recognizing revenue which is associated with the upfront payments we received under that collaboration over time based on a percentage of completion basis. Naturally, we have now recognized the bulk of the revenue from the upfront payments we received. There will be a small tail on that for certain upfront payments that are recognized on a time basis, but as we've disclosed in our financial statements, you can certainly assume that the revenue we'll be recognizing, which is non-cash, by the way, will be lower than what we've recognized in previous quarters as a result of now the completion of our work under those projects. The same will hold true eventually for Goivant as we have moved forward towards completion of the work we have there and now recognize a large proportion of the upfront payments we've received under that collaboration. An easy way to sort of tell what may be coming in the next 12 months is to look at the contract liabilities that we have, the short-term portion of the contract liabilities we have, and that should give you an estimate for what we would expect to recognize over the course of the next 12 months.
spk16: Okay, great. That's very helpful and detailed, and thanks and congrats for all the progress.
spk26: Our next question comes from the line of Jiting Xu with Barenburg.
spk19: Hi, thank you for taking my question. This is Andy on for Z. Regarding your phase two trial, it looks like you're doing four cohorts, two doses for AFM13, two doses for NK cell therapy. Can you please remind us how were those doses selected and which level of confidence behind those doses chosen? And my other question is regarding the restructuring, 25% of your employee, How is that going to affect your operating expenses going forward? If you can provide some guidance, please. Thank you.
spk11: Thanks for asking. I will hand over the second question to Angus and then move back to Angus. Sure.
spk29: So, I mean, looking at the reorganization, you know, on its own in a vacuum, I mean, the reduction in headcount costs that we would expect on an annualized basis is in the range of about 5 million euros. Obviously, that won't be recognized immediately. There are notice periods and severance obligations that will come with that. But we do expect to begin to recognize savings this year and then next year start to see the full impact on an annualized basis. So, on its own, the reorganization will have, you know, roughly a 5 million annualized impact. on operating expenses that will be spread across R&D and G&A. And then obviously within that context, there are other investments that in the, you know, for primarily in the early stage pipeline that'll be reduced. So over time, we do expect to see, you know, both in particular, the R&D number start to come down. We've actually, we're kind of at a period here as a company where we have overlapping programs. You know, the AFM 13202 study winding down our work, as mentioned, on the Genentech and Roevent collaborations now winding down with those molecules being handed over to our partners. So operating expenses beyond the reorganization should start to come down as we go through the rest of this year.
spk13: And now moving back to Wolfgang.
spk17: Okay. The question was the dose selection for the safety run-in cohort. But let's start with AFM13. And for AFM13, we have a recommended phase two dose of 200 milligram FLAT, right, which has been used also in the PTCL trial, but which we also used in the AFM13-104 trial. And we decided also to evaluate a higher dose, namely 300 milligram after discussion and feedback from the FDA. And this decision is driven basically by the fact that when we add additional than case cells that we are providing meaningful higher number of CD16A binding sites. And therefore, higher doses of AFM13 may be needed to optimize receptor occupancy. This has been the reason for the 200 milligram and the higher dose of 300 milligram. When we move to the AB101, these two doses have been selected, of course, after discussion with the colleagues from Arteva. And these are based on initial data from the ongoing phase one study, which Andreas mentioned earlier. The initial data from this study will be presented at ASCO, as he said, and therefore are under embargo at that time. Therefore, we cannot further comment on this. Does that answer your question?
spk18: Yes, thank you. Congratulations again. Thanks. Thank you.
spk26: Our next question comes from the line of with HC Wainwright.
spk03: Thank you. This is from HC Wainwright. So most of my questions have been answered. Just want to understand on AFM 28 and see what update you can provide in terms of how the phase one studies currently enrolling and, you know, should we expect any data in 2023?
spk10: Andreas, you want to take that, please?
spk22: Yeah. So, the study is, I would say, running very well. As I said, we only started in March to recruit first patients. We have already completed the first dose cohort, which were two patients. However, these patients are required to receive four infusions of AFN28 to be dose-limiting toxicity-evaluable. So as we said, we don't have seen any DLTs, which allowed us to open the second cohort. So currently we are enrolling patients at 50 milligrams, and we are extremely satisfied with this kind of speed. Again, we have not made detailed plans whether and in which form to release data from the initial cohorts, but that's something that we will provide guidance, I would say, in the very near future.
spk14: Thank you. Thanks.
spk26: As a reminder, that is star 1-1 to ask a question. Our next question comes from Yanan Zhu with Wells Fargo Securities.
spk08: Hi, thanks for taking the questions. Two quick ones on the phase two trial. One is, the first one is on the cadence of enrollment. Do you have to have safety evaluation for each patient or a group of patients before enrolling the next group of patients within the same cohort? Then another question is about the FDA regulatory discussion. Since you mentioned there seems to be additional discussion needed. for determining the accelerated approval path. I was wondering, do you think that discussion will require data from the Phase II trial? Yeah. Thank you. Okay.
spk17: Now, to the first question, right, that's the study design. And if you look at slide number 10, You can see that cohort 1 and 2 start in parallel, and then cohort 3 and 4 start in parallel. What we do, the first patient of each cohort will go first, and then there is a staggering, and we wait seven days before we start with the second patient. So there is, for the first patient, there is a staggering of seven days. Now, the second question, the additional discussion, whether it will require phase one data or not, currently we can't say. As I mentioned before, right, we are in close interaction with the FDA to determine next steps and then move that forward. But we do not know and cannot speculate, right, on the position of the FDA. And therefore, we cannot comment on that. currently because it's too premature. Thanks for understanding.
spk08: Understood. Thanks for the answers. Welcome.
spk26: That concludes today's question and answer session. This concludes today's conference call. Thank you for participating. You may now disconnect. you you Thank you. Thank you.
spk27: Thank you. Bye. Thank you.
spk26: Good day, everyone, and welcome to AFAMED's first quarter 2023 earnings and corporate update call. At this time, all participants are in a listen-only mode. After the presentation, there will be a question and answer session. To ask a question during the session, you'll need to press star 1 1 on your telephone. You'll then hear an automated message advising your hand is raised. To withdraw your question, please press star 11 again. As a reminder, today's conference is being recorded. I would now like to introduce your host for today's call, Alex Futakidis, Head of Investor Relations at Appamed. Please go ahead.
spk06: Thank you, Liz, and thank you all for joining us today for our first quarter 2023 update call. Before we begin, I'd like to remind everyone that we issued two relevant press releases 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 Adi Hirsch, our chief executive officer, Andreas Harstrick, our chief medical officer, Arne Schertelius, our chief scientific officer, Wolfgang Fischer, our chief operating officer, 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 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 those 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 subjects to risk 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 and of 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'd like to turn the call over to Adi. Adi?
spk11: Thank you, Alex, and good morning, everybody. Thanks for joining our call today. I'll start with reviewing key highlights. And as Alex has already mentioned, I'm very pleased to report that we continue to make progress on our key priorities across the pipeline. As you can see now on slide five, First, we are extremely excited to announce the FDA clearance of our investigational new drug application for the combination of AFM13 with AB101. And we will call this study Luminize 203. Indeed, this is a significant achievement for our company as it enables us to move forward with a Phase II study of this promising therapy. I'd like to thank all colleagues at AFIMED and artiva who worked diligently in the past few months to make this possible this treatment now will build on the findings that we have generated in the afm 13 104 study of afm 13 in combination with coblast derived natural killer cells data which was presented by dr jagonieto from andy anderson cancer center at the ash conference back in 2022. Across our organization, we're committed to advancing the development of this therapy as fast as we can. The efficient and quick execution of this trial, assessing the combination therapy of AFIM13 and AV101 is a key focus for our company. Wolfgang Fischauer, Chief Operating Officer, will go into the details of the study design and timing late in the call. Andreas Hartstrick, our chief medical officer, will update you on the rest of our clinical programs. Second, we have continued to advance AFM24 clinical studies towards data milestones. AFM24 is our novel innate cell engager targeting EGFR, and we believe it has the potential to be a transformative therapy for many patients with EGFR-expressing solid tumors. We now plan to present interim data from the monotherapy expansion cohort at the upcoming ASCO meeting on June 3. Specifically, we will be presenting data from the non-small cell lung cancer cohort, which has been accepted for poster presentation, and data from the colorectal cancer cohort, which has been accepted for online publication. The data will include about 15 patients from each court. The full text of the abstracts will be published later this week and will only include data as of the December 2022 cutoff date. The data in the NSCLC poster will include data from a later close date. We plan to host a call with the financial community to review the monotherapy data in more detail, as well as provide a strategic update on the AFM24 program. The virtual event will be held on Saturday, June 3. Details of the call will be included in our abstract release on Thursday. Finally, our phase one study of AFM28 monotherapy is proceeding quite rapidly. We're pleased to announce that the first dose cohort has already been cleared, and the study is now actively recruiting patients in the second dose cohort, which means all our pipeline programs have significant potential to address unmet medical needs and improve outcomes for a variety of hematological and solid tumor indications. With this, we are quite uniquely positioned to drive shareholder value in the near term. Before now I hand over the call to Wolfgang, I'd like to mention that considering the current market conditions, AFIMED has had to make a difficult decision to control our operating expenses by reorganizing our company to focus our efforts primarily on our community programs. As a result of the reorganization, we have reduced our full-time equivalent headcount by approximately 25%. We took extra care to ensure that this reorganization will not impact the development of our three clinical programs, and we believe we are well positioned to meet key data milestones for all three programs within the next three to 15 months. This now includes data from AFM13 in combination with AB101, data from all three AFM24 clinical studies, and data from AFM28 mono in AML as we continue to make progress with the dose escalation. And with that, let me turn over the call to Wolfgang, who will provide additional insights on the progress we're making in our pipeline.
spk09: Wolfgang?
spk17: Thank you, Adi. Good morning, everybody. As Adi mentioned, we now have the IND clearance from the FDA to take AFM13 into a Phase II study in combination with the AB101 and KSAR from Arteva. This study will build on data from the AFM13-104 study, which we reported at ASH in December 2022. Very briefly, as shown on slide 7, At ASH, we reported data from the Phase I-II study of ASM13 combined with co-blood-derived NK cells in patients with relapsed refractory CD30-positive lymphomas. Data from the study showed a 94% objective response rate and a complete response rate of 71% in 35 heavily pretreated CD30-positive Hodgkin lymphoma and non-Hodgkin lymphoma patients treated at the recommended Phase II dose. 63% of the patients treated at the recommended phase two dose with at least six months follow-up after the initial infusion remained in complete response for at least six months. In addition, the treatment was well tolerated with no cases of cytokine release syndrome, immune effector cell associated neurotoxicity, or graft versus host disease observed. Since we disclosed the data from the AFM13-104 study, we have had conversations with treating physicians, and we know that there is a lot of interest in the medical community about the possibility of having such treatment available to patients. In the past, we have also shared with you information about why we are confident in the combination of AFM13 with AB101, as outlined on slide eight. We believe Antivas AB101 and K-cell has all key features that will allow for similar clinical results as those we saw with the combination of AFM13 with the MD Anderson and K-cell. And very importantly, it meets critical commercial requirements. A new IND is for a phase two clinical study to investigate AFM13 in combination with AB101 from Arteva in patients with relapsed refractory Hodgkin lymphoma who have exhausted all standards of care therapy, including chemotherapy, rentuximab vedotin, and the PD-1 checkpoint inhibitor. As is shown on slide nine, the primary endpoint of the study are to assess the antitumor activity by objective response rate, including complete responses and partial responses. Secondary endpoints of the studies are to assess efficacy, durability of response, safety and tolerability, as well as immunogenicity of the combination therapy. Now, on slide 10, we introduce the design of the clinical study, which, as I mentioned before, will be called Luminize 203. The study will begin with a safety running phase. During this phase, we will evaluate different combination doses of AB1N1 and AFM13 in four cohorts of six patients each. Now let's go through the cohorts. Cohort one will evaluate a dose of 2 billion AB1N1 cells administered weekly combined with AFM13 200 milligram weekly. Cohort two will be exactly the same. except that the AFM13 dose will be 300 milligrams. Cohort 3, there we will evaluate the dosing regimen of AB101 of 4 billion cells in week 1, followed by two weekly doses of 2 billion cells, in each case combined with 200 milligram AFM13. And finally, cohort 4 will be the same as cohort 3, except that we will administer AFM13 300 milligram weekly. During the run-in phase, we will evaluate the safety and preliminary efficacy of these dosing regimens with the goal of selecting two dosing regimens for the dose optimization phase, which follows assignment two stage design. The study has then the potential to continue with one for both cohorts from the optimization phase into the expansion phase. The trial will enroll up to 140, 134 patients, and currently all our clinical sites are located in the United States. As you can see, there is also an exploratory cohort with CD30-positive PT-CL patients, which will include another additional 20 patients. On slide 11, we show the treatment regimen. In Luminize 203, patients will be treated with lymphodepleting doses of clorharabine, 30 milligram per square meter per day, and cyclophosphamide, 300 milligram per square meter per day, prior to the first AFM13 AB101 dosing. This dose and schedule of lymphodepleting chemotherapy is based on other cell therapy studies that have demonstrated the safety and effectiveness of this regimen, including our own study, AFM13-104. As you can see on the slide, one treatment cycle will consist of three weekly co-administered doses of AFM13 and AB101, followed by three weekly doses of AFM13 monotherapies. Up to three cycles of treatment may be administered. Looking ahead, as outlined on slide 12, we are very focused to get the study up and running in Q3 2023. During the IND process, we requested feedback from the FDA on the suitability of the study to support an accelerated approval in Hodgkin's lymphoma. As a recommendation of the FDA, in parallel to advancing the study, AFIMED will have further discussions with the agency on the requirements for registration application in the U.S. Finally, we expect to be able to share data from the safety run-in phase during the first half of 2024. As a final note of this discussion about the combination of AFM13 with AB101, many of you have asked us questions about when ARTIVA plans to share data from AB101 in B-cell lymphoma. We wanted to bring to your attention that ACIVA is planning on presenting data from the AB101 rituximab combination study in a poster presentation at ASCO on June 5th. Now, I'll hand over the call to Andrea to discuss the updates for our other clinical programs. Andrea.
spk22: Thank you, Wolfgang, and also welcome from my side to everyone on the call. Let's now move to AFM24. And as we show on slide 13, at ASCO, AFIMET will present initial data from two expansion cohorts of the monotherapy study of our EGFR-targeting innate cell engager AFM24. As mentioned by Adi, we have been accepted to present interim results from the EGFR mutant non-small cell lung cancer cohort in a poster presentation. And in addition, interim results from the colorectal cancer cohort have been accepted for online publication. As you will be aware, full abstracts for ASCO and for both of our cohorts will become available on May 25th. So for today, we are limited in what we can share with you. However, what we can tell you is that the data reported on May 25 in the abstracts will have a cutoff date of December 2022. At ASCO for the non-small cell lung cancer cohort, we will share updated data with a significantly later cutoff date. Specifically, we will present data from 15 patients from each of the non-small cell lung cancer and the colorectal cancer cohorts. As Adi mentioned, we are also planning to host a call with members of the financial community to discuss the data and to review our AFM24 strategy going forward. Our second AFM24 study, the combination of AFM24 with atezolizumab, we are continuing to treat patients with non-small cell lung cancer, EGFRY type, gastric and gastroesophageal junction adenocarcinoma, and pancreatic, hepatocellular, and biliary tract cancers in three separate cohorts. The dose escalation portion of the study is complete. And we have confirmed the 480 milligrams weekly dose of AFM24 as the recommended phase two dose. Enrollment in the expansion cohort is ongoing, and the treatment continues to show a well-managed safety profile. As shown, we plan to provide data from this ongoing study in the second half of 2023. The second combination study of AFM24 is investigating the combination of AFM24 with SNK01, the ex vivo expanded and activated autologous NK cell product from NKGen Biotech. Here, both agents 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. We continue to enroll patients in the dose escalation phase of the trial and expect to have this completed within 2023. Also, for this trial, we plan to provide data in the second half of 2023. Now, moving to AFM28 on slide 15, we show the exciting progress that we were able to make with our designed to bring a new immunotherapeutic approach to patients with CD123 positive myeloid malignancies, which include acute myeloid leukemia and myelodysplastic syndrome. In our phase one study, we treated the first patient in March. And since then, we have been able to complete the first dose cohort of 25 milligrams once weekly. without encountering dose limiting toxicity. This has allowed us to open the second dose cohort at 50 milligrams weekly, in which we are currently actively recruiting patients. Given the aggressive nature of this disease and the need for viable treatment options, we are working diligently to bring this treatment option to refractory and relapsed AML patients as quickly as possible. With this short summary, I will turn the call over now to Angus to update you on the quarterly financial numbers. Angus, please.
spk29: Thank you, Andreas. Balance sheet and income state highlights are shown on slides 17 and 18 of the presentation. As a quick reminder, AFIMET'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, which is the company's functional and presentation currency. Therefore, all numbers that I will present on this call, unless otherwise noted, will be in euros. As of March 31st, 2023, cash and cash equivalents totaled 155.8 million euros compared to 190.3 million euros on December 31st, 2022. Based on our current operating plan of assumptions, we anticipate that our cash and cash equivalents will support operations into 2025. Net cash used in operating activities for the quarter ended March 31st, 2023 was 33.2 million euros compared to 28.4 million euros for the same period in 2022. Total revenue for the quarter ended March 31st, 2023 was 4.5 million euros compared with 8 million euros for the quarter ended March 31st, 2022. Revenue predominantly relates to the Genentech and Roivant collaborations. Research and development expenses for the quarter ended March 31st, 2023 increased by 60.7% from 18.4 million for the same period in 2022 to 29.5 million in 2023. The increase was primarily due to higher expenses associated with the development of AFM 13 and AFM 24, resulting from increased procurement of clinical trial material, increased clinical trial costs, and increased costs associated with other early stage programs and infrastructure. General and administrative expenses decreased 2.8% from 7 million euros in the quarter ended March 31st, 2022 to 6.9 million euros in the quarter ended March 31st, 2023. An increase in personnel costs were offset by a decline in legal consulting and insurance expenses. Net finance income and costs for the quarter ended March 31st, 2023 decreased from income of about half a million euros in the quarter ended March 31st, 2022 to costs of about half a million euros in the quarter ended March 31st, 2023. As a reminder, net finance income or costs are largely due to foreign exchange gains or losses related to assets that are denominated in U.S. dollars as a result of currency fluctuations between the U.S. dollar and the euro during the year. Net loss for the quarter ended March 31st, 2023 was 32 million euros or 21 cents per common share compared with a net loss of 16.7 million euros or 14 cents per common share for the quarter ended March 31st, 2022. The weighted number of common shares outstanding for the quarter ended March 31st, 2023 was 149.3 million. Additional information regarding these results is included in the notes of the consolidated financial statements as of March 31st, 2023, which will be included in APMED's filing with the SEC. I'll now turn the call back to Adi for closing remarks. Adi?
spk11: Thanks a lot, Angus. Now moving to slide 19, we show a snapshot of all our programs. And we're very excited on behalf of patients that could benefit from the combination treatment of AFM13 with AB101. And we're now looking forward to getting the study started and bringing new updates as we make the progress. We also are looking forward to our call with you on June 3 to discuss the findings from the non-small cell lung cancer and colorectal cancer studies. during which we are also planning to update you on our broader plans for AFEM 24 going forward. And as you've heard, we are indeed quite excited about the progress we are making with AFEM 28 in AML, which we believe has a huge potential, as we mentioned in the past, that NK cells can play a major role in AFEM 28 as a very pronounced activity redirecting NK. We're also thankful for the support and efforts of our employees who have pulled together to move things forward. It is through their dedication and the support from you and the patients and their families that gives us inspiration to continue our work of bringing these life-saving therapies to the market. We are now ready to take questions, and I hand back to the operator.
spk26: As a reminder, if you'd like to ask a question at this time, please press star one one on your telephone and wait for your name to be announced. To withdraw your question, please press star one one again. Our first question comes from the line of Maury Raycroft with Jefferies.
spk25: Maury, your line is now open.
spk05: Hi, thanks for taking my questions. Um, question on the alumni study, presumably the assignment to stage design part of the study is open label. Just wanted to clarify that. And then also wondering what is the bar for success on overall response rate and duration of response? And is there anything additional you're saying on a powering for the study?
spk11: Um, yeah, thanks. Morning. Good morning. So, um, ending this question over to Wolfgang Wolfgang.
spk17: Yeah, thanks, Angus. Hi, Marie. As you can see on slide number 10, the dose optimization, right, we have two cohorts selected from the safety run-in, 13 patients per cohort, and each of these cohorts will follow assignment stage 2 design. So that means we are evaluating each of these cohorts separately, right, to a futility whether to move forward, yes or no. That's number one. The other question was the bar success. Based on the data we have generated with AFM13-104, we believe that the bar or that we can achieve very high response rates, very similar to what we have seen in the 104 study. And the third question, I do not remember. Could you please repeat?
spk05: If you're saying anything additional on powering for the study.
spk17: Do you want to take that question regarding the power of the study?
spk22: Yeah, I can take this question. As Wolfgang has said, and I think it's also depicted on the slide, The second part of the study, which starts with two doses selected from the initial four cohorts, and then the option to continue basically into the expansion, consists of two separately powered Simon2 stage cohorts. So there is no direct comparison on a statistical level between the different cohorts. And on the totality of the data, we can decide to either move one or two cohorts until the final number of 55 patients per cohort. This was something that specifically came out of our discussions with FDA, and I think it's also in line with FDA's attempt to have more data available on dose optimization and the effect of different doses on the outcome. So again, these two arms are separate Simon 2 stage arms which do not have a statistical comparison between the two arms.
spk05: Got it. Makes sense. And anything else you can tell us about the nature or timing of FDA discussions to be had on registration requirements? I guess would that be first half 24 after you get the run-in data Or would that be later on? And can you say if you've spoken with FDA at all about the feasibility of doing a randomized study as opposed to a single-arm study? Oh, yeah.
spk21: Go ahead. Yeah.
spk17: Yeah. So we have designed that study with the intent for an accelerated approval. Very clear, right? And also following also the draft guidance from FDA from March 2023. where it still very clearly says that single-arm study is still feasible in certain senses. So, we asked the FDA for that feedback, and the FDA came back to us and recommended that we continue that discussion in a separate meeting with them. So, basically, they recommended, while starting the study, reaching out to them for further discussions. During these interactions with the FDA, the FDA did not provide us specific guidance or feedback regarding their concerns.
spk05: Got it. Okay. Makes sense. Thanks for taking my questions.
spk26: Our next question comes from the line of Lee Wacek. with Cantor Fitzgerald.
spk24: Hey, guys. Thank you for taking our questions. Maybe just follow up on, I guess, the registration application, understanding that, you know, you're still in the process of that with the agency. But I guess, can you give us a sense of what kind of, you know, different scenarios that you're preparing for here?
spk17: I mean, we are in constant contact with our project manager at FDA, and we'll determine the next steps. Once agreed with the timelines, we will provide further guidance. We also believe that it's currently too premature to discuss or to speculate what is the FDA's position and what are different scenarios.
spk24: Okay, got it. And then just for the safety running portion, I guess do you need to discuss with the agency before you proceed to the optimization service portion or it will be pretty seamless? And I guess for the safety running portion, how long is the follow-up?
spk17: So the first question, right, these patients are treated as outlined on the slide we have provided. I guess it's slide number 11. And also these patients can receive up to three cycles. The assessment for selecting two dose cohorts moving forward into the optimization phase will happen after the first assessment. And the first question was whether we need to go to FDA before moving forward. No, the FDA provided full commitment to that study.
spk14: Okay, thanks.
spk26: Our next question comes from the line of Srikripa Devarakonda with Truist Securities.
spk31: Thank you so much guys for taking my question and congrats on getting the IND cleared. Quickly, what else needs to be done in order for you guys to get the trial going? You said third quarter, you should be able to get it going. And based on the trial enrollment that you saw with your previous partnership with MD Anderson, How confident are you that we'll have enrollment and we'll be able to see data from the run-in patients? It's about 24 patients in first half. And is there any likelihood that we could see, we could also see enrollment in stage two by then? Not data, but at least enrollment. Thank you.
spk12: Again, Wolfgang?
spk17: Yeah. So first question, we are preparing for first patient in in Q3 2023. And we are fully on track on that. So we are interacting with the CROs. We are interacting with the sites, et cetera, et cetera. So that's all fine and on track for Q3 2023. Regarding the first data, Yes, we plan to provide a first data from the safety run-in, so from the 24 patients in H1 2024. Did you have another question? Sorry, maybe I missed it.
spk31: Oh, sorry. Sorry, I was on mute. I was just wondering if by the time you have the data, is there Should we expect enrollment to already begin in stage two of the trial as well?
spk17: I mean, we will start with stage two of the trial, so with the optimization phase, as soon as we have finished basically the safety run-in right after the first assessment, as I said before, because that's the basis for moving forward. And as soon as we have completed that, we will start with the stage two. When that exactly will be, I can't say.
spk30: Okay. Thank you. That's absolute.
spk26: Our next question comes from the line of Brad Canino with Stiefel.
spk33: Hi. Thanks for the updates. I'm looking at slide 10 here for the dose expansion portion where it says you'll select one or two cohorts depending on the interim clinical data. I'm wondering, can you comment on what length of follow-up will be required for the interim data to make that decision to move into the pivotal period?
spk17: So after the dose optimization, the patient will be follow up for two treatment cycles. And after these two treatment cycles, right, the decision will be made, the interim analysis will be made, and then the decision based on the Simon two stage design to move forward or not to move forward. So after two treatment cycles, two assessments.
spk33: Okay, thank you. And then as you continue the FDA discussions, Can you help us understand how much your partner is included in these? In particular, I'm thinking about how much buy-in they might have if one of the decisions being to run a concurrent confirmatory study along with this single-arm study. Thank you.
spk17: Yeah. So, Adi, I take that, at least the first part, and then I give it to you for the second part. The partnering with... Artiva is going very well. It's a very nice and very good collaboration on a team level, on a joint steering committee level, and we are all aligned in our interactions with the FDA. We align before we discuss, right, and have a common path forward, right? So that's going really well. Regarding the confirmatory study, right, and their commitment, I will hand over to Adi. Adi, please.
spk11: Yeah, contractually, as you know, this is a shared study in terms of costs. And we have not yet started the details of this discussion as we're fully focused on getting the ING cleared. And obviously, Arteva has played a major role in depicting the ING and input into this product design. So as we're now through with the ING clearance and can start the study, we will now take up and move to the next steps what kind of confirmatory studies we were contemplating. We have already mentioned in the past that we have, obviously, a number of options in Hodgkin and Fulmer where we can place it, but we also focus in terms of moving forward with the PTCL, at least initially based on the cohort findings that, on the findings within the 20-patient cohort. That's our plans, yeah. Okay.
spk14: Appreciate the comments. Thank you.
spk26: Our next question comes from the line of Dana Graybosh with SBB Securities.
spk07: Hi, this is Rabib online for Dana. The questions we have are surrounding ASCO in particular, especially in regards to Arteeva. What are you looking for for this first disclosure and clinical data from Arteva, given that this product is being used for the Luminize 2 or 3 trial, as opposed to the Anderson product from previous data? And then what are we looking for in the AFM24 monotherapy data in CSD1 and in CLC? that give us confidence for future readouts in second half 23 with the combination of NK cells and or PD-L1.
spk11: Yeah, thanks for the question. I'll hand over to Andreas, please.
spk22: Yeah, so it's a difficult to answer question because it relates basically in all parts to data that will be published at ASCO. As you know, for ATIVA, ATIVA has an ongoing study that evaluates both of the AB101 cell as a single product, so without targeting agent. And here they are looking at a couple of different dose levels in patients with B-cell malignancies. And they also have the combination of AB101 cells with rituximab, so a targeting agent in B-cell malignancies. And they will provide update on the current status of their study. Again, given that this is an upcoming ASCO presentation, we cannot go into more details as all of the, especially the updated and newer data are under ASCO embargo. For AFM24, again, we will show updated data for the patients with EGFR mutant non-small cell lung cancer treated with single agent AFM24. We will also have an online publication for the colorectal cancer cohort. Again, those will have updated data compared to the abstracts that come available or become available later this week. And as we said, after our poster presentation, we will also host an investor event to discuss or to have a comprehensive discussion of the AFM24 strategy. Of course, taking into account the new data that we will show at ASCO. But I think until then, I unfortunately cannot share more details with you.
spk07: Just a short follow-up. We've heard that companies are permitted to provide updated data after the abstracts are released if the data are different than what was written in the abstract. Is that something we can look for from AccoVet?
spk29: Yeah. Adi, maybe I can take that one. Yes, please. Thank you for the question. It's something we've obviously looked very closely at. ASCO is unique in this regard. Ultimately, since we have a poster presentation at ASCO, out of respect for our investigator who will be at the poster, our decision was to provide the updated data at ASCO itself on June 3rd, and as Adi and Andreas mentioned, to then host an investor call subsequent to the poster discussion to provide further updates on ASM24. That was the decision. That's kind of what went into our decision to wait until June 3rd. And as was mentioned, the abstracts with the December cutoff date will be published on Thursday.
spk32: Thank you so much.
spk26: Our next question comes from the line of Gail Jen with Laidlaw.
spk14: Good morning, and thanks for taking the questions.
spk16: Good morning.
spk15: Good morning.
spk16: Good morning. How are you? Sorry. My first question is that you guys mentioned that in the press release that you're going to have preclinical data presented at the ICML. My question is that what should we anticipate from that data sort of data release, Do you show anything in comparison to the cobalt cell-derived NK cell as well?
spk09: Andreas, do you want to take the question, please?
spk22: When it's relating to preclinical, I think Arndt would probably be the right person to respond.
spk02: Okay, sorry.
spk20: Happy to take the question, Gail. Very nice to... Thanks for your question. So you will have noticed we have not given any specifics because we want to also respect the embargo for this conference. But as you can assume, you know, we will show preclinical data, the combination of the products and some of that we had actually previously shown also at some investor conferences. So we will show the preclinical basis for moving into the clinic so you can expect that you know there's synergistic activity to be shown but i i cannot share more more specifics that will be that will be shared at the conference i'm sure you'll understand sure uh not problem and thanks for that and maybe just one more housekeeping questions that also in the press release you indicated that uh
spk16: The Genentech collaboration, at least for the time being, seems completed. You handed off the product. So just from a modeling purpose, should we anticipate the revenue be slightly lower going forward as you at least assume there's only one collaboration panel at the moment until otherwise?
spk29: Yeah, I can take that. As you mentioned, Greg, the work that we were responsible for under the Genentech collaboration has now been completed, and the targets that we were developing on their behalf have been handed over to Genentech. So that's good news on that front. As you know, we've been recognizing revenue, which is associated with the upfront payments we received under that collaboration. over time based on a percentage of completion basis. So naturally, we have now recognized the bulk of the revenue from the upfront payments we received. There will be a small tail on that for certain upfront payments that are recognized on a time basis. But as we've disclosed in our financial statements, you can certainly assume that the revenue we'll be recognizing, which is non-cash, by the way, will be lower than what we've recognized in previous quarters as a result of now the completion of our work under those projects. The same will hold true eventually for Goivant as we have moved forward towards completion of the work we have there and now recognize a large proportion of the upfront payments we've received under that collaboration. An easy way to sort of tell what may be coming in the next 12 months is to look at the contract liabilities that we have, the short-term portion of the contract liabilities we have, and that should give you an estimate for what we would expect to recognize over the course of the next 12 months.
spk16: Okay, great. That's very helpful and detailed, and thanks and congrats for all the progress.
spk26: Our next question comes from the line of Jiting Xu with Barenburg.
spk19: Hi, thank you for taking my question. This is Andy on for Z. Regarding your phase two trial, it looks like you're doing four cohorts, two doses for AFM 13, two doses for NK cell therapy. Can you please remind us how were those doses selected and what's your level of confidence behind those doses chosen? And my other question is regarding the restructuring, 25% of your employee, How is that going to affect your operating expenses going forward? If you can provide some guidance, please. Thank you.
spk11: Thanks for asking. I will hand over the second question to Angus and then move back to Wolfgang. Angus?
spk29: Sure. So, I mean, looking at the reorganization, you know, on its own in a vacuum, I mean, the reduction in headcount costs that we would expect on an annualized basis is in the range of about 5 million euros. Obviously, that won't be recognized immediately. There are notice periods and severance obligations that will come with that, but we do expect to begin to recognize savings this year and then next year start to see the full impact on an annualized basis. So, on its own, the reorganization will have, you know, roughly a 5 million annualized impact. and operating expenses that will be spread across R&D and G&A. And then obviously within that context, there are other investments that in the, you know, primarily in the early stage pipeline that'll be reduced. So over time, we do expect to see, you know, both in particular, the R&D number start to come down. We've actually, we're kind of at a period here as a company where we have overlapping programs. You know, the AFM 13202 study winding down our work, as mentioned, on the Genentech and Roevent collaborations now winding down with those molecules being handed over to our partners. So operating expenses beyond the reorganization should start to come down as we go through the rest of this year.
spk13: And now moving back to Wolfgang.
spk17: Okay. The question was the dose selection for the safety run-in cohort. But let's start with AFM13. And for AFM13, we have a recommended phase two dose of 200 milligram FLAT, right, which has been used also in the PT-CL trial, but which we also used in the AFM13-104 trial. And we decided also to evaluate a higher dose, namely 300 milligram after discussion and feedback from the FDA. And this decision is driven basically by the fact that when we add additional than case cells that we are providing meaningful higher number of CD16A binding sites. And therefore, higher doses of AFM13 may be needed to optimize receptor occupancy. This has been the reason for the 200 milligram and the higher dose of 300 milligram. When we move to the AB101, these two doses have been selected, of course, after discussion with the colleagues from Arteva. And these are based on initial data from the ongoing phase one study, which Andreas mentioned earlier. The initial data from this study will be presented at ASCO, as he said, and therefore are under embargo at that time. Therefore, we cannot further comment on this. Does that answer your question?
spk18: Yes, thank you. Congratulations again.
spk17: Thanks.
spk18: Thank you.
spk26: Our next question comes from the line of with HC Wainwright.
spk03: Thank you. This is from HC Wainwright. So most of my questions have been answered. Just want to understand on AFM 28 and see, you know, what update you can provide in terms of how the phase one studies currently enrolling and, you know, should we expect any data in 2023?
spk10: Andreas, you want to take that, please?
spk22: Yeah. So, the study is, I would say, running very well. As I said, we only started in March to recruit first patients. We have already completed the first dose cohort, which were two patients. However, these patients are required to receive four infusions of AFN28 to RB dose limiting toxicity evaluables. So as we said, we don't have seen any DLTs, which allowed us to open the second cohort. So currently we are enrolling patients at 50 milligrams. And we are extremely satisfied with this kind of speed. Again, we have not made detailed plans whether and in which form to release data from the initial cohorts, but that's something that we will provide guidance, I would say, in the very near future.
spk26: Thank you. Thanks. As a reminder, that is star 1-1 to ask a question. Our next question comes from Yanan Zhu with Wells Fargo Securities.
spk08: Thanks for taking the questions. Two quick ones on the phase two trial. The first one is on the cadence of enrollment. Do you have to have a safety evaluation for each patient or a group of patients before enrolling the next group of patients? within the same cohort. Then another question is about the FDA regulatory discussion. Since you mentioned there seems to be additional discussion needed for determining the accretory approval path. I was wondering, do you think that discussion will require data from the Phase II trial? Thank you. Welcome.
spk17: Yeah. Okay. Now, to the first question, right, that's the study design. And if you look at slide number 10, you can see that cohort one and two start in parallel, and then cohort three and four start in parallel. What we do, the first patient of each cohort will go first, and then there is a staggering, and we wait seven days before we start with the second patient. So, there is, for the first patient, there is a staggering of seven days. Now, the second question, the additional discussion, whether it will require Phase I data or not, Currently, we can't say. As I mentioned before, right, we are in close interaction with the FDA to determine next steps and then move that forward. But we do not know and cannot speculate, right, on the position of the FDA. And therefore, we cannot comment on that currently because it's too premature. Thanks for understanding.
spk08: Understood. Thanks for the answers. You're welcome.
spk26: That concludes today's question and answer session. This concludes today's conference call. Thank you for participating. You may now disconnect.
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