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spk04: Good day, everyone, and welcome to AFI Med's first quarter 2024 earnings and corporate update call. At this time, all participants are in a listen-only mode. Later, we will conduct a question and answer session, and instructions will be given at that time. As a reminder, today's conference call is being recorded. I would like to introduce your host for today's call, Alex Vedakis, Head of Investor Relations at AFI Med. Please go ahead.
spk20: Thank you, Michelle, and thank you all for joining us today for our first quarter 2024 update call. Before we begin, I'd like to remind everyone that we issued the relevant press release and presentation on our website today, which you can find in the investor relations section. On the call today, we have members of our management team, including Andreas Harstrick, our chief medical officer and acting chief executive officer, Wolfgang Fischer, our chief operating officer, Denise Mueller, our Chief Business Officer, and Harry Welton, our Consulting Chief Financial Officer. Our financials today will be presented by our Vice President of Finance, Michael Wolff. The team will be available for Q&A after the prepared remarks. Before we start, I would like to remind you that today's presentation contains projections and forward-looking statements regarding future events. These statements represent our beliefs and assumptions only as of the date of this call. Except as required by law, We assume no obligation to update these forward-looking statements publicly or to update the reasons why actual results could differ materially from those anticipated in the future 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 and our filings with the SEC, and those identified under the section entitled forward-looking statements and the press release that we issued today and filed with the SEC. With that, I'll turn the call over to Andreas. Andreas?
spk15: Yeah, thank you, Alex, and good day, everyone, and thank you for joining us today for our first quarter 2024 earnings call. I'm excited to share with you today clinical data on all three of our clinical programs that as we believe are validating our approach of using the innate immune system as an additional tool to fight cancer. When we announced the strategic reorganization of AFIMED and our focus on the advancement of our clinical assets in January, We guided that our goal would be to generate meaningful data for all three programs in the first half of the year. I'm proud to say and thankful to all of my coworkers at AFIMED and to all our clinical investigators that today we can deliver on this guidance. As shown on slide three, we now have clinical validation for all three assets. For AFM24, we are advancing the combination study with atezolizumab in treatment refractory patients with non-small cell lung cancer, both in the EGFR wild type and in the EGFR mutant subgroups. Data that we shared at ASCO demonstrate durable responses in patients with EGFR wild type tumors with three or four responses ongoing now for over seven months. We also see meaningful and confirmed tumor responses in the EGFR mutant subgroup, a tumor type that is generally considered unresponsive to immunotherapy. We can also share exciting data for our clinical LUMINISE trial of a symptomic in combination with LONK cells in patients with refractory Hodgkin's lymphoma. Seven patients have had their CT scans meanwhile assessed by blinded independent read, which will be the primary endpoint of the study as agreed upon with FDA. In these patients, we see objective responses in six out of seven patients. for an overall response rate of 85.7%. Importantly, this includes four patients with a complete remission. Finally, AFM28, our CD123 targeting ICE for the treatment of refractory AML has shown remarkable clinical activity. At dose level five of our single agent dose escalation study, we have observed one complete response and five patients with stable disease. At dose level six, we see two patients with a complete response and a CRI respectively, and three patients with stable disease. Importantly, the complete response from dose level five is now ongoing and stable for more than five months, and five of the six patients at dose level six are continuing on treatment with a possibility for further deepening of their responses. Also importantly, no dose limiting toxicities were observed in dose level five and six, thereby establishing a safe and effective regimen for further development. Let us look at the data in some more detail. Today, I will start with a symptomic. As a reminder on slide five, you see the trial design as agreed upon with FDA. We now have completed enrollments into cohorts one and two and are actively recruiting cohorts three and four. We admit that there is still a slight delay in recruitment compared to our initial expectations as discussed on our last earnings call. This is mainly due to a higher rate of patient dropout during the screening period. However, with additional sites now active and more experience with the protocol at the site level, we expect to see further improvement in patient recruitment and a reduction in the dropout rate. In terms of safety, shown on slide six, The adverse event profile is in line with our previous experience with asymptomic and the combination of asymptomic and allogeneic NK cells, respectively. It is important to note that in the LUMINISE 203 study, we did not use steroids as part of the premedication for asymptomic, and therefore, we were expecting a slightly higher rate of infusion-related reactions compared to some studies with a symptomatic in which steroid premedication was routinely used. Four of seven patients developed a grade one or two infusion-related reaction slash CRS event. One of these four patients had a short-lasting grade three CRS, as assessed by the investigator, which manifested mainly by high fever and a decrease in blood pressure However, the patient responded readily to standard of care treatment. Importantly, in this patient, shortly after this event, there was also an acute CMV infection diagnosed, and thus the relative contribution of the infusion of a symptomatic versus acute CMV infection to the overall symptoms is not clear. Importantly, there were no treatment discontinuations due to side effects of asymptomic or LONK. Also, there were no instances of bleeding, ICANNs, or graft versus host disease. As a clinical activity of the combination is, I think, remarkable as shown on slide seven. Six of seven patients showed an objective response by independent read, including four patients with a complete remission. These data are directly comparable with the data that were reported by MD Anderson Cancer Center for a symptomic in combination with fresh pre-complexed NK cells, and thus indicate that co-administration of an ICE with allogeneic NK cells is active, that no pre-complexing is needed, and that cryopreserved NK cells seem to be comparable to fresh NK cells in terms of anti-tumor activity. Also, these results demonstrate that data from the single site study at MD Anderson are reproducible in a multicenter setting as these seven patients were enrolled by four different institutions. Slide eight shows the patient's characteristics underscoring that these patients are heavily pretreated with a median of four lines of previous therapy. All patients had failed combination chemotherapy, PD-1 targeting therapy, and brentuximab. In addition, five of seven patients had also failed after autologous stem cell transplant. On slide nine, you see an example of a patient with multiple manifestations of his refractory Hodgkin's lymphoma, including axillary lymph nodes, supraclavicular lymph nodes, spleen, and inguinal lymph nodes. The patient had failed all standard of care options, including stem cell transplant, and presented with B symptoms, which clinically is a very unfavorable prognostic factor. As you can see, all tumor manifestations resolved after only one cycle of therapy. Let's move on to AFM24. Since we presented the data in detail during our ASCO presentation, I will be brief here. As shown on slide 11, the combination of AFM24 and etizolizumab has meaningful activity in patients with heavily pre-treated EGFRY-type non-small cell lung cancer. In 15 evaluable patients, there were four objective responses and eight patients with stable disease. Of note, all patients had failed combination chemotherapy and PD-1 targeting therapy. All responders were documented progressive on previous anti-PD-1 treatment. Importantly, the responses and the tumor control induced by AFM24 atizolizumab appear to be durable, as shown on slide 12, where you see the long-term follow-up data. The progression-free survival for the whole study population is 5.9 months, which compares favorable to the 4.5 months, which is usually achieved in these patients with standard of care treatment. Even more encouraging is the fact that three of the four remissions are still ongoing, now at more than seven, more than eight, and more than nine months, respectively. It appears very unlikely that these data can be explained by atezolizumab activity alone. Even though there are occasional responses to PD-1 re-challenge after intervening chemotherapy, PFS data in these patients have been very short. Even in PD-1 non-pretreated patients, in platinum refractory non-small cell lung cancer, atezolizumab has shown a progression-free survival interval of only 2.8 months. Our recent results in patients with heavily pretreated EGFR mutant non-small cell lung cancer, as shown on slide 13, support the activity of the AFM24-Atezolizumab combination. In 13 patients that are response-evaluable, four responses and six patients with stable disease were achieved. Compared to the data that we reported at ASCO, meanwhile, all objective responses have been confirmed by follow-up scans, and all responses are ongoing. This is remarkable as EGFR mutant non-small cell lung cancer is in general regarded as unresponsive to immunotherapy. Slide 14 shows the market opportunity for drugs that are targeting refractory non-small cell lung cancer. In the seven major markets, there are 175,000 patients with EGFR-Y type non-small cell lung cancer, and roughly 35,000 patients with EGFR mutant non-small cell lung cancer annually who fail standard of care therapy and will need additional treatment options. Current treatment options for these patients are unsatisfactory, with PFS durations around 4 to 4.5 months. Also, many salvage regimens include chemotherapy, that is often difficult to tolerate for these heavily pretreated patients. The combination of AFM24 plus PD-1 could provide a chemotherapy-free alternative with meaningful activity and significantly better tolerability for these patients. Finally, let's review the most recent data of AFM28 our CD123 targeting ICE for the treatment of acute myeloid leukemia as shown on slide 16. Here we have escalated the dose through six cohorts up to 300 milligrams weekly. I think this study is also a good example of the ability of our organization to execute clinical studies. The first patient in this program was treated in March 2023 And the whole dose escalation trial over six cohorts was executed in only 15 months. The safety profile is shown on slide 16. For dose levels five and six, we did not see any dose-limiting toxicities. The most frequent side effects were infusion-related reactions, mainly of low grade. Only three patients had a grade two infusion-related reaction responding in all cases to symptomatic treatment, and there were no grade 3 or higher IRRs. One patient experienced a short-lasting self-limiting CRS of grade 1. Infections are characteristic manifestations of acute leukemia and were seen in half of the patients. However, none of the infections was considered treatment-related by the investigators. In addition, we observed meaningful target interaction at doses of 200 milligrams and above with near complete saturation of CD123 binding sites on the tumors and occupation levels of CD16A on the NK cells that in preclinical experiments result in potent NK cell activation. The clinical activity is displayed on slide 17. In dose level five, we saw one complete response and five patients with stable disease. All patients were heavily pretreated. Of note, the complete remission is still ongoing after more than five months. In dose level six, we saw two patients with a complete response and a CRI respectively, and three patients with stable disease. Five patients from dose level six remain on treatment with additional cycles, and thus was the option to deepen their responses. I think these results are remarkable. Most of these patients with advanced AML have very low numbers of own NK cells when they start treatment. So it appears that AML could be very sensitive to NK cell mediated killing if already low numbers of endogenous NK cells when directed to the leukemia cells by AFM28 can produce complete responses. These data taken together with impressive activities that we have seen with a combination of a symptomatic and allogeneic NK cells in Hodgkin lymphoma, support our strategic intent to pursue further development of AFM28 in association with a cryopreserved allogeneic NK cell product. With this, we would, again address an area of significant unmet medical need. In the seven major markets, we see over 14,000 patients per year who fail at least two lines of standard therapy and require a new treatment option. Many of these patients are elderly and show frequent comorbidities, thus limiting the use of aggressive chemotherapy. Immunotherapy has not been successful so far in AML. A treatment approach based on the activation of the innate immune system could therefore be an important additional strategy for the treatment of these patients. With this, I will close the overview of our clinical programs and hand over to Michael Wolf for a review of our financial data. Michael, please.
spk12: Thank you, Andreas. Balance sheet and income statement highlights are shown on slide 20 and 21 of the presentation. A quick reminder that AffiMate's consolidated financial statements have been prepared in accordance with IFRS as issued by the International Accounting Standard Board, or IASB. The consolidated financial statements are prepared in euros. Since our financials are described in detail in the press release, This morning, I will only provide highlights on this call. We ended the first quarter with cash, cash equivalents and investments of 48.5 million euros compared to 72 million euros on December 31st, 2023. Based on our current operating and financing plan, we anticipate that our liquidity will support operations into the second half of 2025. Net cash used in operating activities for the quarter ended March 31, 2024 was 23.8 million euros compared to 33.2 million euros for the quarter ended March 31, 2023. Total revenue for the quarter ended March 31, 2024 was 0.2 million euros compared with 4.5 million euros for the quarter ended March 31, 2023. 2024 was 19.2 million euros, compared with a net loss of 32 million euros for the quarter ended March 31st, 2023. Now I'll turn the call back to Andreas for final remarks. Andreas?
spk15: Yeah, thank you, Michael. For our concluding remarks, let's go to slide 22. I think this has been a very exciting and very successful quarter for AFIMED, in which we were able to obtain clinical validation of all three of our programs. I think the strongest conclusion that we draw from this data today is consistency. When you see a single data set in one study in one particular disease setting, of course, you may always think, could this be a chance finding? But what we are demonstrating today is consistent activity signals across three different programs that are all designed to leverage the power of the innate immune system to fight cancer. We see this in four different indications and with two different combinations. Initial results from our asymptomic and LONK program show remarkable activity which seemed to be on par with the data reported by MD Anderson. The difference is that we were able to generate this data with co-administration of the ICE and the NK cell, and with cryopreserved off-the-shelf NK cells. Those factors that enable the use of this approach in the real-world multicenter setting. For AML, we see that AFM28 can induce responses even in a setting where only very few NK cells are available to fight leukemia. I think it is very reasonable to expect a boost in activity if sufficient amounts of active allogeneic NK cells are added, as we have shown in our lumini study. Therefore, we are actively exploring ways to continue the AFM28 program in combination with off-the-shelf allogeneic NK cells. And last but not least, we see consistent activity for the combination of AFM24 and etesolizumab, the strategy that utilizes the crosstalk between the adaptive and the innate immune system. When we started this program, I think there were a lot of doubts where their innate immune system could even attack solid tumors, given the largely immunosuppressive environment that is found in many solid tumors. Meanwhile, we have demonstrated objective and durable responses in heavily pretreated EGFR-wide type non-small cell lung cancer patients, with the longest response now ongoing for 10 months in patients with prior documented progression on PD-1 targeting therapy. This data is supported by the observation of objective and confirmed responses in patients with heavily pre-treated EGFR mutant non-small cell lung cancer, a disease that historically has not been sensitive to immune-mediated treatments. Of note, we see these results with a regimen that does not include any chemotherapy and thus may be better tolerated in these heavily pre-treated patient populations. I think the totality of the data reported today support our strong belief that the innate immune system can be utilized to fight multiple types of hematological and solid tumors, and that AfiMed's proprietary IC molecules can provide the necessary targeting and activation. As guided, we will have additional important data readouts in the course of the year. AFIMED, with its portfolio of several potent NK cell engagers, and with its experienced and highly motivated clinical development organization, is well suited to advance the use of the innate immune system as an additional treatment option for patients in need. We will continue our path to advance these exciting programs and thereby bring value to our organization, our patients, and our shareholders. With this, I thank you all for your attention, and I'm happy to take questions. Operator, please.
spk04: Thank you. If you'd like to ask a question, please press star 1-1. If your question has been answered and you'd like to remove yourself from the queue, please press star 1-1 again. Our first question comes from Kripa Devarakonda with Truist Securities. Your line is open.
spk17: Hey guys, thank you so much for taking my questions and congrats on all the progress across the three assets you have. So I have a question about Luminize. You know, you talked, you mentioned that cohorts one and two were enrolled. Our assumption is that that's 12 patients. We saw data from seven patients today. I know you said you were going to see updates later. Just wanted to get clarification on the remaining five patients. Have they not reached the first scan, which if I remember correctly, seven weeks? And when we see the next update, you know, will we get durability data or have a sense of the longest duration of follow-up? Thank you.
spk15: Yeah, thank you, Kripa, for your question. So first, your conclusion is right. We have included 12 patients in cohorts one and two, so they are filled. We are actively recruiting cohorts three and four now. The reason why we have not shown the data of the remaining five patients simply is, as we mentioned, that we initially had a certain delay in recruitment. So these patients are in the middle of their treatment, their first cycle. As you rightfully say, we have our first assessment on roughly week seven, week eight. Now, what we also reported today is that we want all PET CT scans to be evaluated by blind and independent read, which is the FDA-prescribed final endpoint. So we wanted to make sure that data will really be consistent with the data sets that may go to FDA This may add another two to three weeks before you have your independent final readout data. So we will have the data of these 12 patients definitely in Q3. The question of follow-up, of course, is always when are the first patients treated. Again, we will have follow-up data, of course, of these 12 patients, but realizing that some of these patients have recently been entered The first follow-up will probably be like three, four, five months follow-up. Again, not due to the fact that we expect a lot of relapses, but simply patients have not been on treatment for longer. So if you want to have a real long-term follow-up where patients have the chance to be a year or so on this protocol, this probably will more be towards the end of the year.
spk21: Great. Thank you so much.
spk04: Thank you. And our next question comes from Dana Graybosh with Lyric Partners. Your line is open.
spk05: Yeah. A question for me, too, on Luminize 203, Andres. I wonder if you could talk about what was driving the screen failures dropout. I just wonder if there's any implications of that for the type of patients that could be treated by this going forward. And, yeah, let's take that.
spk15: Yeah, that's a great question. And we spent quite some time investigating what happened. I think there is still some training on the sites because physicians may have been over eagerly to enroll patients. So we had a couple of patients entered initially looked like they would fulfill all inclusion criteria. Then after review, we found out that, for example, One patient had no previous brantuximab treatment. One patient did not have a PD-1 treatment. One patient had a documented allergic reaction to CD3 targeting treatment. Then we have seen a couple of patients. Again, these are very sick patients who acquired viral infections. I believe we had two patients with an intervening COVID infection that made them drop out and In fact, we had one or two patients who withdraw informed consent when they considered significant commuting distances. Again, we only have like 10 sites open. So for some patients in the U.S., there is still a very significant commuting involved to participate in this trial. With more training on the trial side, I think at least we will see a reduction in patients who are not fulfilling all inclusion criteria. With more sites active, we can reduce the commuting issues, I think. The third issue, patients with Hodgkin's lymphoma with four or five previous treatments are more prone to virus infections. So we may still see some patients who acquire intermittent comorbidities or intermittent diseases while in the screening period.
spk10: Perfect. That's very helpful. Thank you.
spk04: Thank you. Our next question comes from Maury Raycroft with Jefferies. Your line is open.
spk16: Hi. Congrats on the progress and thanks for taking my question. Just based on your insights into enrollment and guidance for having another data update on the first two cohorts and third quarter, at this point can you project when you think you'll complete the run-in phase and start the randomization phase? I guess is there anything more on timelines that you're able to say about the study at this point? And then can you remind me if you need to go back to FDA to get feedback before you can start the randomized part of the study?
spk15: Yeah, so let's take the last question first. So we do not need to go back to FDA. FDA has approved the whole sequence of the study, so it's completely in our decision process. up to our decision to progress into stage one, stage two, also at which point to open the cohort for peripheral T-cell lymphomas. In terms of guidance, again, we have fully enrolled cohorts one and two. And as I said, we expect to have the data of the initial five patients in terms of responses in Q3. And then we will give updates at our earnings calls. We also intend to submit these data to the scientific conference. For cohorts three and four, we will do the projection once we are through the staggered period. Again, cohort three and four have the first three patients per cohort staggered. This has been a little bit of an uncertainty in cohorts one and two, so I think we don't have better guidance once we have completed the first six patients in cohorts three and four.
spk16: Okay, understood. And just wondering if you can clarify if the data are a mix of cohorts one and two, and at this point, do you have any view on how the two different dose cohorts are comparing as far as the dosing strategies go?
spk15: Yeah, again, it's limited number of patients. We have equal representation of cohorts one and two. I think we have four patients in one and three patients in two. Up to this point, we did not see any differences. Both cohorts have contributed responses and complete responses. Interestingly, we also have not seen any differences in side effects. So the 200 milligrams and 300 milligram uh symptomatic doses are absolutely similar in terms of their side effect profile okay okay thanks for taking my questions i'll hop back in the queue thank you our next question comes from lee watsik with cancer fitzgerald your line is open hey good morning uh thanks for taking my questions um i wonder if you can just
spk03: comment on, you know, the number of cycles that these seven patients being created. And I know the protocol allows up to three cycles. So just wondering if you can give some information there.
spk07: Yeah, currently we basically have everything.
spk15: So we have a couple of patients in the second cycle. We have patients who are now going into cycle three. We have a patient who is now going to stem cell transplant, incomplete response. So it's a mixture of cycles. Importantly, the treatment has been very well tolerated, so we have not seen any treatment discontinuations due to side effects, and all patients basically go as planned through their sequence of cycles.
spk03: Okay, and then maybe a follow-up question for the patient. baseline characteristics enrolled in the study versus the MD Anderson 104 study. Can you maybe just, you know, comment on prior lines of treatment and, you know, any response to most recent treatment for these patients? And I remember, I think, in the 104 study, we're looking at maybe seven prior lines of treatment versus here four. Maybe just talk a little bit about how should we think about patients enrolled.
spk15: Yeah, so here we have technically a somewhat shorter number or lower number of previous treatment lines, which I think is already reflecting what we expect to see also in the marketplace. I mean, patients, before we published the MD Anderson data, they simply did not have any alternatives, so physicians were trying quite exotic things which amounted to this high number of previous lines of therapy. Now, with this very active treatment available, physicians start to refer earlier patients to this treatment option because they also feel that this is by far the best chance of patients who have failed chemotherapy, et cetera, and PD-1. So it's a good development, I think, because patients get to potentially life-saving treatment earlier. It is good also in terms of market projection if we can establish this regimen in earlier lines of treatment. Importantly, the FDA was very clear on what defines a patient with unmet medical need. And that is failure of combination chemotherapy, failure to PD-1, and failure to etc. And all these patients fulfill the FDA required criteria for unmet medical need.
spk06: Okay, great. Thank you.
spk09: Thank you.
spk04: And our next question. comes from Yale Jen with Laylaw and Company. Your line is open.
spk02: Good morning and thanks for taking the questions and congrats on the progress. Just two quick ones here. The first one is for ASN 28. You guys are talking about seeking, adding NKCL to the study. What's the current progress and what was the option being considered at this moment?
spk15: Yeah, we are in an active process to identify an allogeneic cryopreserved NK-SAT product. These are discussions. These are ongoing, so I cannot share a lot of details here, but I think we are on a very good way.
spk02: Okay, great. Maybe one housekeeping question. We just noticed that for the last quarter, there's a $23 million cash used that you guided at the guidance in terms of runway to the second half of next year. Should we, for monitoring purpose, should we consider the expense going forward for the next few quarters will be reduced more? And that will be the projection. Would that be the projection? And thanks.
spk15: I think that's a question I would hand over to Harry or Michael.
spk18: No, I'm happy to answer this question. The cash guidance into H2 2025 is based on operational financial plans. So one element contributing to that is a significantly lower spend. As a matter of fact, we spend in Q1 2023, 10 million more than in Q1 this year. So we do have reduced spend based on the fact that we only have half the personnel. We significantly reduce costs regarding lease expense, et cetera. So that's one contribution. The other one, it includes certain amounts or payments to be made, be it with business development or be it with other financing transactions. And we continue to tightly monitor our spending. And so that's how this guidance came along.
spk08: Okay, great. That's very helpful. And thanks for taking the question. You're welcome.
spk04: Thank you. And our next question comes from Brad Canino with Stiefel. Your line is open.
spk14: Thank you.
spk13: Just to double-click on the dropouts question following Dana's question, I think the question when there are so many dropouts is always the potential for the results to have some form of bias from a selection of a narrow patient population and maybe those that are fit enough to wait as the enrollment process is being streamlined. It would be good to hear your view on whether or not this has occurred. And second, could you talk about your ongoing relationship with Arteva and both companies' commitment to the study as the program continues to advance now? Thank you.
spk15: Yeah. So for the dropout, as I said, we have not seen any pattern. And importantly, I do not see any indication of a selection bias. Again, it's a very mixed bag of reasons. Some are logistic. My belief is that that will be solved if we have even a broader geographic spread of participating sites. Some is that people were, I think, very enthusiastic, and we see this enthusiasm on our investigator side to enroll the patient. And some patients did not really fulfill all criteria for unmet medical need. As I said, we had patients who had not been pre-treated with etc. These patients are receiving etc. treatment now. They will have the option if they should fail etc. to go back into the study. We have a very clear defined population of patients, again, failing chemotherapy, failing PD-1 failing, et cetera. And if they are transplant eligible, they should also have received a transplant before. And so this is something that FDA agreed upon as an area of complete unmet medical need. And we will stick very closely to this FDA guidance. But I do not see any selection bias or any enrichment of certain patients. In terms of our relationship with ARTIVA, They are as enthusiastic about the data as we are. We have good relationship. We have strong support from the ARTIVA side to continue on this study and on this program. And so there's nothing else to report other than a real working relationship.
spk11: Great to hear the colleague. Thanks, Andreas.
spk04: Thank you.
spk09: As a reminder, if you'd like to ask a question, please press star 1-1. There are no further questions.
spk04: This does include the Q&A session. You may now disconnect. Everyone have a great day.
spk07: Thank you. Bye-bye.
spk04: You're welcome. you Bye. Thank you. Thank you.
spk00: Thank you.
spk04: Good day, everyone, and welcome to AFI Med's first quarter 2024 earnings and corporate update call. At this time, all participants are in a listen-only mode. Later, we will conduct a question and answer session, and instructions will be given at that time. As a reminder, today's conference call is being recorded. I would like to introduce your host for today's call, Alex Vedakis, Head of Investor Relations at AFI Med. Please go ahead.
spk20: Thank you, Michelle, and thank you all for joining us today for our first quarter 2024 update call. Before we begin, I'd like to remind everyone that we issued the relevant press release and presentation on our website today, which you can find in the investor relations section. On the call today, we have members of our management team, including Andreas Harstrick, our chief medical officer and acting chief executive officer, Wolfgang Fischer, our chief operating officer, Denise Mueller, our Chief Business Officer, and Harry Welton, our Consulting Chief Financial Officer. Our financials today will be presented by our Vice President of Finance, Michael Wolff. The team will be available for Q&A after the prepared remarks. Before we start, I would like to remind you that today's presentation contains projections and forward-looking statements regarding future events. These statements represent our beliefs and assumptions only as of the date of this call. Except as required by law, We assume no obligation to update these forward-looking statements publicly or to update the reasons why actual results could differ materially from those anticipated in the future 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 and our filings with the SEC, and those identified under the section entitled forward-looking statements and the press release that we issued today and filed with the SEC. With that, I'll turn the call over to Andreas. Andreas?
spk15: Thank you, Alex, and good day, everyone, and thank you for joining us today for our first quarter 2024 earnings call. I'm excited to share with you today clinical data on all three of our clinical programs that as we believe are validating our approach of using the innate immune system as an additional tool to fight cancer. When we announced the strategic reorganization of AFIMED and our focus on the advancement of our clinical assets in January, We guided that our goal would be to generate meaningful data for all three programs in the first half of the year. I'm proud to say and thankful to all of my coworkers at AFIMED and to all our clinical investigators that today we can deliver on this guidance. As shown on slide three, we now have clinical validation for all three assets. For AFM24, we are advancing the combination study with atezolizumab in treatment refractory patients with non-small cell lung cancer, both in the EGFR wild type and in the EGFR mutant subgroups. Data that we shared at ASCO demonstrate durable responses in patients with EGFR wild type tumors with three or four responses ongoing now for over seven months. We also see meaningful and confirmed tumor responses in the EGFR mutant subgroup, a tumor type that is generally considered unresponsive to immunotherapy. We can also share exciting data for our clinical LUMINISE trial of a symptomic in combination with LONK cells in patients with refractory Hodgkin's lymphoma. Seven patients have had their CT scans meanwhile assessed by blinded independent read, which will be the primary endpoint of the study as agreed upon with FDA. In these patients, we see objective responses in six out of seven patients. for an overall response rate of 85.7%. Importantly, this includes four patients with a complete remission. Finally, AFM28, our CD123 targeting ICE for the treatment of refractory AML has shown remarkable clinical activity. At dose level five of our single agent dose escalation study, we have observed one complete response and five patients with stable disease. At dose level six, we see two patients with a complete response and a CRI respectively, and three patients with stable disease. Importantly, the complete response from dose level five is now ongoing and stable for more than five months. And five of the six patients at dose level six are continuing on treatment with a possibility for further deepening of their responses. Also importantly, no dose limiting toxicities were observed in dose level five and six, thereby establishing a safe and effective regimen for further development. Let us look at the data in some more detail. Today, I will start with the symptomic. As a reminder on slide five, you see the trial design as agreed upon with FDA. We now have completed enrollments into cohorts one and two and are actively recruiting cohorts three and four. We admit that there is still a slight delay in recruitment compared to our initial expectations as discussed on our last earnings call. This is mainly due to a higher rate of patient dropout during the screening period. However, with additional sites now active and more experience with the protocol at the site level, we expect to see further improvement in patient recruitment and a reduction in the dropout rate. In terms of safety, shown on slide six, The adverse event profile is in line with our previous experience with asymptomic and the combination of asymptomic and allogeneic NK cells, respectively. It is important to note that in the LUMINISE 203 study, we did not use steroids as part of the premedication for asymptomic, and therefore, we were expecting a slightly higher rate of infusion-related reactions compared to some studies with a symptomatic in which steroid premedication was routinely used. Four of seven patients developed a grade one or two infusion-related reaction slash CRS event. One of these four patients had a short-lasting grade three CRS, as assessed by the investigator, which manifested mainly by high fever and a decrease in blood pressure However, the patient responded readily to standard of care treatment. Importantly, in this patient, shortly after this event, there was also an acute CMV infection diagnosed, and thus the relative contribution of the infusion of a symptomatic versus acute CMV infection to the overall symptoms is not clear. Importantly, there were no treatment discontinuations due to side effects of asymptomic or LONK. Also, there were no instances of bleeding, ICANNs, or graft versus host disease. As a clinical activity of the combination is, I think, remarkable as shown on slide seven. Six of seven patients showed an objective response by independent read, including four patients with a complete remission. These data are directly comparable with the data that were reported by MD Anderson Cancer Center for a symptomic in combination with fresh pre-complexed NK cells, and thus indicate that co-administration of an ICE with allogeneic NK cells is active, that no pre-complexing is needed, and that cryopreserved NK cells seem to be comparable to fresh NK cells in terms of anti-tumor activity. Also, these results demonstrate that data from the single site study at MD Anderson are reproducible in a multicenter setting as these seven patients were enrolled by four different institutions. Slide eight shows the patient's characteristics underscoring that these patients are heavily pretreated with a median of four lines of previous therapy. All patients had failed combination chemotherapy, PD-1 targeting therapy, and brentuximab. In addition, five of seven patients had also failed after autologous stem cell transplant. On slide nine, you see an example of a patient with multiple manifestations of his refractory Hodgkin's lymphoma, including axillary lymph nodes, supraclavicular lymph nodes, spleen, and inguinal lymph nodes. The patient had failed all standard of care options, including stem cell transplant, and presented with B symptoms, which clinically is a very unfavorable prognostic factor. As you can see, all tumor manifestations resolved after only one cycle of therapy. Let's move on to AFM24. Since we presented the data in detail during our ASCO presentation, I will be brief here. As shown on slide 11, the combination of AFM24 and etizolizumab has meaningful activity in patients with heavily pre-treated EGFRY-type non-small cell lung cancer. In 15 evaluable patients, there were four objective responses and eight patients with stable disease. Of note, all patients had failed combination chemotherapy and PD-1 targeting therapy. All responders were documented progressive on previous anti-PD-1 treatment. Importantly, the responses and the tumor control induced by AFM24 atizolizumab appear to be durable, as shown on slide 12, where you see the long-term follow-up data. The progression-free survival for the whole study population is 5.9 months, which compares favorable to the 4.5 months, which is usually achieved in these patients with standard of care treatment. Even more encouraging is the fact that three of the four remissions are still ongoing, now at more than seven, more than eight, and more than nine months, respectively. It appears very unlikely that these data can be explained by atezolizumab activity alone. Even though there are occasional responses to PD-1 re-challenge after intervening chemotherapy, PFS data in these patients have been very short. Even in PD-1 non-pretreated patients, in platinum refractory non-small cell lung cancer, atezolizumab has shown a progression-free survival interval of only 2.8 months. Our recent results in patients with heavily pretreated EGFR mutant non-small cell lung cancer, as shown on slide 13, support the activity of the AFM24-Atezolizumab combination. In 13 patients that are response-evaluable, four responses and six patients with stable disease were achieved. Compared to the data that we reported at ASCO, meanwhile, all objective responses have been confirmed by follow-up scans, and all responses are ongoing. This is remarkable as EGFR mutant non-small cell lung cancer is in general regarded as unresponsive to immunotherapy. Slide 14 shows the market opportunity for drugs that are targeting refractory non-small cell lung cancer. In the seven major markets, there are 175,000 patients, with EGFR-Y type non-small cell lung cancer, and roughly 35,000 patients with EGFR mutant non-small cell lung cancer annually who fail standard of care therapy and will need additional treatment options. Current treatment options for these patients are unsatisfactory, with PFS durations around 4 to 4.5 months. Also, many salvage regimens include chemotherapy, that is often difficult to tolerate for these heavily pretreated patients. The combination of AFM24 plus PD-1 could provide a chemotherapy-free alternative with meaningful activity and significantly better tolerability for these patients. Finally, let's review the most recent data of AFM28. our CD123 targeting ICE for the treatment of acute myeloid leukemia as shown on slide 16. Here we have escalated the dose through six cohorts up to 300 milligrams weekly. I think this study is also a good example of the ability of our organization to execute clinical studies. The first patient in this program was treated in March 2023 And the whole dose escalation trial over six cohorts was executed in only 15 months. The safety profile is shown on slide 16. For dose levels five and six, we did not see any dose-limiting toxicities. The most frequent side effects were infusion-related reactions, mainly of low grade. Only three patients had a grade two infusion-related reaction responding in all cases to symptomatic treatment, and there were no grade 3 or higher IRRs. One patient experienced a short-lasting self-limiting CRS of grade 1. Infections are characteristic manifestations of acute leukemia and were seen in half of the patients. However, none of the infections was considered treatment-related by the investigators. In addition, we observed meaningful target interaction at doses of 200 milligrams and above with near complete saturation of CD123 binding sites on the tumors and occupation levels of CD16A on the NK cells that in preclinical experiments result in potent NK cell activation. The clinical activity is displayed on slide 17. In dose level five, we saw one complete response and five patients with stable disease. All patients were heavily pretreated. Of note, the complete remission is still ongoing after more than five months. In dose level six, we saw two patients with a complete response and a CRI respectively, and three patients with stable disease. Five patients from dose level six remain on treatment with additional cycles, and thus was the option to deepen their responses. I think these results are remarkable. Most of these patients with advanced AML have very low numbers of own NK cells when they start treatment. So it appears that AML could be very sensitive to NK cell-mediated killing if already low numbers of endogenous NK cells when directed to the leukemia cells by AFM28 can produce complete responses. These data taken together with impressive activities that we have seen with a combination of a symptomatic and allogeneic NK cells in Hodgkin lymphoma, support our strategic intent to pursue further development of AFM28 in association with a cryopreserved allogeneic NK cell product. With this, we would, again address an area of significant unmet medical need. In the seven major markets, we see over 14,000 patients per year who fail at least two lines of standard therapy and require a new treatment option. Many of these patients are elderly and show frequent comorbidities, thus limiting the use of aggressive chemotherapy. Immunotherapy has not been successful so far in AML. A treatment approach based on the activation of the innate immune system could therefore be an important additional strategy for the treatment of these patients. With this, I will close the overview of our clinical programs and hand over to Michael Wolff for a review of our financial data. Michael, please.
spk12: Thank you, Andreas. Balance sheet and income statement highlights are shown on slide 20 and 21 of the presentation. A quick reminder that AffiMate's consolidated financial statements have been prepared in accordance with IFRS as issued by the International Accounting Standard Board, or IASB. The consolidated financial statements are prepared in euros. Since our financials are described in detail in the press release, This morning, I will only provide highlights on this call. We ended the first quarter with cash, cash equivalents and investments of 48.5 million euros compared to 72 million euros on December 31st, 2023. Based on our current operating and financing plan, we anticipate that our liquidity will support operations into the second half of 2025. Net cash used in operating activities for the quarter ended March 31, 2024 was 23.8 million euros compared to 33.2 million euros for the quarter ended March 31, 2023. Total revenue for the quarter ended March 31, 2024 was 0.2 million euros compared with 4.5 million euros for the quarter ended March 31, 2023. Net loss for the quarter ended March 31, 2024 was 19.2 million euros, compared with a net loss of 32 million euros for the quarter ended March 31st, 2023. Now I'll turn the call back to Andreas for final remarks. Andreas?
spk15: Yeah, thank you, Michael. For our concluding remarks, let's go to slide 22. I think this has been a very exciting and very successful quarter for AFIMED, in which we were able to obtain clinical validation of all three of our programs. I think the strongest conclusion that we draw from this data today is consistency. When you see a single data set in one study in one particular disease setting, of course, you may always think, could this be a chance finding? But what we are demonstrating today is consistent activity signals across three different programs that are all designed to leverage the power of the innate immune system to fight cancer. We see this in four different indications and with two different combinations. Initial results from our asymptomic and LONK program show remarkable activity which seemed to be on par with the data reported by MD Anderson. The difference is that we were able to generate this data with co-administration of the ICE and the NK cell, and with cryopreserved off-the-shelf NK cells. Those factors that enable the use of this approach in a real-world multicenter setting. For AML, we see that AFM28 can induce responses even in a setting where only very few NK cells are available to fight leukemia. I think it is very reasonable to expect a boost in activity if sufficient amounts of active allogeneic NK cells are added, as we have shown in our lumini studies. Therefore, we are actively exploring ways to continue the AFM28 program in combination with off-the-shelf allogeneic NK cells. And last but not least, we see consistent activity for the combination of AFM24 and etesolizumab, the strategy that utilizes the crosstalk between the adaptive and the innate immune system. When we started this program, I think there were a lot of doubts where their innate immune system could even attack solid tumors, given the largely immunosuppressive environment that is found in many solid tumors. Meanwhile, we have demonstrated objective and durable responses in heavily pretreated EGFR-white type non-small cell lung cancer patients, with the longest response now ongoing for 10 months in patients with prior documented progression on PD-1 targeting therapy. This data is supported by the observation of objective and confirmed responses in patients with heavily pre-treated EGFR mutant non-small cell lung cancer, a disease that historically has not been sensitive to immune-mediated treatments. Of note, we see these results with a regimen that does not include any chemotherapy and thus may be better tolerated in these heavily pre-treated patient populations. I think the totality of the data reported today support our strong belief that the innate immune system can be utilized to fight multiple types of hematological and solid tumors, and that AfiMed's proprietary IC molecules can provide the necessary targeting and activation. As guided, we will have additional important data readouts in the course of the year. AFIMED, with its portfolio of several potent NK cell engagers, and with its experienced and highly motivated clinical development organization, is well suited to advance the use of the innate immune system as an additional treatment option for patients in need. We will continue our path to advance these exciting programs and thereby bring value to our organization, our patients, and our shareholders. With this, I thank you all for your attention, and I'm happy to take questions. Operator, please.
spk04: Thank you. If you'd like to ask a question, please press star 1-1. If your question has been answered and you'd like to remove yourself from the queue, please press star 1-1 again. Our first question comes from Kripa Devarakonda with Truist Securities. Your line is open.
spk17: Hey guys, thank you so much for taking my questions and congrats on all the progress across the three assets you have. So I have a question about Luminize. You know, you talked, you mentioned that cohorts one and two were enrolled. Our assumption is that that's 12 patients. We saw data from seven patients today. I know you said you were going to see updates later. Just wanted to get clarification on the remaining five patients. Have they not reached the first scan, which if I remember correctly, seven weeks? And when we see the next update, you know, will we get durability data or have a sense of the longest duration of follow-up? Thank you.
spk15: Yeah, thank you, Kripa, for your question. So first, your conclusion is right. We have included 12 patients in cohorts one and two, so they are filled. We are actively recruiting cohorts three and four now. The reason why we have not shown the data of the remaining five patients simply is, as we mentioned, that we initially had a certain delay in recruitment. So these patients are in the middle of their treatment, their first cycle. As you rightfully say, we have our first assessment on roughly week seven, week eight. Now, what we also reported today is that we want all PET CT scans to be evaluated by blind and independent read, which is the FDA-prescribed final endpoint. So we wanted to make sure that data will really be consistent with the data sets that may go to FDA This may add another two to three weeks before you have your independent final readout data. So we will have the data of these 12 patients definitely in Q3. The question of follow-up, of course, is always when are the first patients treated? Again, we will have follow-up data, of course, of these 12 patients, but realizing that some of these patients have recently been entered The first follow-up will probably be like three, four, five months follow-up. Again, not due to the fact that we expect a lot of relapses, but simply patients have not been on treatment for longer. So if you want to have a real long-term follow-up where patients have the chance to be a year or so on this protocol, this probably will more be towards the end of the year.
spk21: Great. Thank you so much.
spk04: Thank you. And our next question comes from Dana Graybosh with Lyric Partners. Your line is open.
spk05: Yeah. A question for me, too, on Luminize 203, Andres. I wonder if you could talk about what was driving the screen failures dropout. I just wonder if there's any implications of that for the type of patients that could be treated by this going forward. And, yeah, let's take that.
spk15: Yeah, that's a great question. And we spent quite some time investigating what happened. I think there is still some training on the sites because physicians may have been over eagerly to enroll patients. So we had a couple of patients entered initially looked like they would fulfill all inclusion criteria. Then after review, we found out that, for example, One patient had no previous brantuximab treatment. One patient did not have a PD-1 treatment. One patient had a documented allergic reaction to CD3 targeting treatment. Then we have seen a couple of patients. Again, these are very sick patients who acquired viral infections. I believe we had two patients with an intervening COVID infection that made them drop out and In fact, we had one or two patients who withdraw informed consent when they considered significant commuting distances. Again, we only have like 10 sites open. So for some patients in the U.S., there is still a very significant commuting involved to participate in this trial. With more training on the trial side, I think at least we will see a reduction in patients who are not fulfilling all inclusion criteria. With more sites active, we can reduce the commuting issues, I think. The third issue, patients with Hodgkin's lymphoma with four or five previous treatments are more prone to virus infections. So we may still see some patients who acquire intermittent comorbidities or intermittent diseases while in the screening period.
spk10: Perfect. That's very helpful. Thank you.
spk04: Thank you. Our next question comes from Maury Raycroft with Jefferies. Your line is open.
spk16: Hi. Congrats on the progress and thanks for taking my question. Just based on your insights into enrollment and guidance for having another data update on the first two cohorts and third quarter, at this point can you project when you think you'll complete the run-in phase and start the randomization phase? I guess is there anything more on timelines that you're able to say about the study at this point? And then can you remind me if you need to go back to FDA to get feedback before you can start the randomized part of the study?
spk15: Yeah, so let's take the last question first. So we do not need to go back to FDA. FDA has approved the whole sequence of the study, so it's completely in our decision process. up to our decision to progress into stage one, stage two, also at which point to open the cohort for peripheral T-cell lymphomas. In terms of guidance, again, we have fully enrolled cohorts one and two. And as I said, we expect to have the data of the initial five patients in terms of responses in Q3. And then we will give updates at our earnings calls. We also intend to submit these data to the scientific conference. For cohorts three and four, we will do the projection once we are through the staggered period. Again, cohort three and four have the first three patients per cohort staggered. This has been a little bit of an uncertainty in cohorts one and two, so I think we don't have better guidance once we have completed the first six patients in cohorts three and four.
spk16: Okay, understood. And just wondering if you can clarify if the data are a mix of cohorts one and two, and at this point, do you have any view on how the two different dose cohorts are comparing as far as the dosing strategies go?
spk15: Yeah, again, it's limited number of patients. We have equal representation of cohorts one and two. I think we have four patients in one and three patients in two. Up to this point, we did not see any differences. Both cohorts have contributed responses and complete responses. Interestingly, we also have not seen any differences in side effects. So the 200 milligrams and 300 milligram uh symptomatic doses are absolutely similar in terms of their side effect profile okay okay thanks for taking my questions i'll hop back in the queue thank you our next question comes from lee watsik with cancer fitzgerald your line is open hey good morning uh thanks for taking my questions um i wonder if you can just
spk03: comment on, you know, the number of cycles that these seven patients being created. And I know the protocol allows up to three cycles. So just wonder if you can give some information there.
spk07: Yeah, currently we basically have everything.
spk15: So we have a couple of patients in the second cycle. We have our patients who are now going into cycle three. We have a patient who is now going to stem cell transplant, incomplete response. So it's a mixture of cycles. Importantly, the treatment has been very well tolerated, so we have not seen any treatment discontinuations due to side effects, and all patients basically go as planned through their sequence of cycles.
spk03: Okay, and then maybe a follow-up question for the patient. baseline characteristics enrolled in the study versus the MD Anderson 104 study. Can you maybe just, you know, comment on prior lines of treatment and, you know, any response to most recent treatment for these patients? And I remember, I think, in the 104 study, we're looking at maybe seven prior lines of treatment versus here four. Maybe just talk a little bit about how should we think about patients enrolled.
spk07: Yeah.
spk15: So here we have technically a somewhat shorter number or lower number of previous treatment lines, which I think is already reflecting what we expect to see also in the marketplace. I mean, patients, before we published the MD Anderson data, they simply did not have any alternatives, so physicians were trying quite exotic things which amounted to this high number of previous lines of therapy. Now, with this very active treatment available, physicians start to refer earlier patients to this treatment option because they also feel that this is by far the best chance of patients who have failed chemotherapy, et cetera, and PD-1. So it's a good development, I think, because patients get to potentially life-saving treatment earlier. It is good also in terms of market projection if we can establish this regimen in earlier lines of treatment. Importantly, the FDA was very clear on what defines a patient with unmet medical need. And that is failure of combination chemotherapy, failure to PD-1, and failure to etc. And all these patients fulfill the FDA required criteria for unmet medical need.
spk06: Okay, great. Thank you.
spk09: Thank you.
spk04: And our next question. comes from Yale Jen with Laylaw and Company. Your line is open.
spk02: Good morning and thanks for taking the questions and congrats on the progress. Just two quick ones here. The first one is for ASN 28. You guys are talking about seeking, adding NKCL to the study. What's the current progress and what was the option being considered at this moment?
spk15: Yeah, we are in an active process to identify an allogeneic cryopreserved NK-SAT product. These are discussions. These are ongoing, so I cannot share a lot of details here, but I think we are on a very good way.
spk02: Okay, great. Maybe one housekeeping question. We just noticed that for the last quarter, there's 23 million cash used, and you guided at the guidance in terms of runway to the second half of next year. Should we, for monitoring purpose, should we consider the expense going forward for the next few quarters will be reduced more? And that will be the projection. Would that be the projection? And thanks.
spk15: I think that's a question I would hand over to Harry or Michael.
spk18: No, I'm happy to answer this question. The cash guidance into H2 2025 is based on operational financial plans. So one element contributing to that is a significantly lower spend. As a matter of fact, we spend in Q1 2023, 10 million more than in Q1 this year. So we do have reduced spend based on the fact that we only have half the personnel. We significantly reduce costs regarding lease expense, et cetera. So that's one contribution. The other one, it includes certain amounts or payments to be made, be it with business development or be it with other financing transactions. And we continue to tightly monitor our spending. And so that's how this guidance came along.
spk08: Okay, great. That's very helpful. And thanks for taking the question. You're welcome.
spk04: Thank you. And our next question comes from Brad Canino with Stiefel. Your line is open.
spk14: Thank you.
spk13: Just to double-click on the dropouts question following Dana's question, I think the question when there are so many dropouts is always the potential for the results to have some form of bias from a selection of a narrow patient population and maybe those that are fit enough to wait as the enrollment process is being streamlined. It would be good to hear your view on whether or not this has occurred. And second, could you talk about your ongoing relationship with Arteva and both companies' commitment to the study as the program continues to advance now? Thank you.
spk15: Yeah. So for the dropout, as I said, we have not seen any pattern. And importantly, I do not see any indication of a selection bias. Again, it's a very mixed bag of reasons. Some are logistic. My belief is that that will be solved if we have even a broader geographic spread of participating sites. Some is that people were, I think, very enthusiastic, and we see this enthusiasm on our investigator side to enroll the patient and some patients did not really fulfill all criteria for unmet medical need. As I said, we had patients who had not been pre-treated with etc. These patients are receiving etc. treatment now. They will have the option if they should fail etc. to go back into the study. We have a very clear defined population of patients, again, failing chemotherapy, failing PD-1 failing, et cetera. And if they are transplant eligible, they should also have received a transplant before. And so this is something that FDA agreed upon as an area of complete unmet medical need. And we will stick very closely to this FDA guidance. But I do not see any selection bias or any enrichment of certain patients. In terms of our relationship with ARTIVA, They are as enthusiastic about the data as we are. We have good relationship. We have strong support from the ARTIVA side to continue on this study and on this program. And so there's nothing else to report other than a real working relationship.
spk11: Great to hear the colleague. Thanks, Andreas.
spk04: Thank you. As a reminder, if you'd like to ask a question, please press star 1-1.
spk09: There are no further questions.
spk04: This does include the Q&A session. You may now disconnect. Everyone have a great day.
spk07: Thank you. Bye-bye.
spk04: You're welcome.
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