Affimed N.V.

I'd like to also welcome you all for joining us today for our second quarter 2021 results and operational update call. Before we begin, I'd like to remind everyone that we issued the relevant press release earlier today and that it can be found on the investor relations section of our website. On the call today, we have the following members of our management team. Dr. Adi Hirsch, our chief executive officer, Andreas Harstrick, our chief medical officer, Our chief scientific officer, Wolfgang Fischer, our chief operating officer, and Angus Smith, our chief financial officer. The whole team will be available for the Q&A session. Before we start, quickly to go through this safe harbor statement. Today's discussion 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 differ materially from those anticipated in the forward-looking statement, even if new information becomes available in the future. These forward-looking statements are subject to risks and uncertainties, and actual results may differ materially from those expressed or implied in the statement. And these statements, due to various factors including but not limited to those identified under the section entitled risk factors in our filings with the SEC, and those identified under the section entitled forward-looking statement in the press release that we issued today and filed with the SEC. With that, I'll turn the call over to Adi. Adi?

Yeah, thank you, Alex, and good morning, everyone. And thanks a lot for joining in for our second quarter update call. Today we're gonna provide an update on our pipeline, discuss the progress on our ongoing AFM13, AFM24 and AFM28 studies and our plan for what promises to be an exciting period over the next few months for our company. Before I do that, a quick summary of what we have accomplished so far. In the clinical and preclinical data confirm that our unique and innovative innate cell engagers are safe and have the potential to be effective in treating cancer patients, both as monotherapies, but also in combination either with natural killer cells or with checkpoint antibodies such as PD-1, maybe PD-L1. As we move the ongoing clinical trials forward, our efforts are now focusing on identifying and targeting indications where we believe our scientific discoveries will benefit patients by applying our three-pronged approach, monotherapy, therapies in combination with natural killer cells, and checkpoint inhibitors. We're very happy to report that our pipeline remains on track for our registration-directed study of AFM13 monotherapy in relapsed refractory peripheral T-cell lymphoma We are recruiting well and on track to complete enrollment of the study in the first half of 2022. And we expect to be able to provide further guidance about timing for data as we get closer to the completion of enrollment. In the investigator-sponsored clinical trial at MD Anderson Cancer Center, evaluating cold blood-derived natural killer cells pre-complexed with AFM13 we have completed the dose escalation part of the study with increasing doses. Indeed, there were three cohorts where we used either 10 to the 6 cells per kilogram, three patients that received 10 to the 7 cells per kilogram, and three patients that received 10 to the 8 cells per kilogram. We're currently enrolling additional patients at the highest dose, of 10 to the eighth cells per kilogram to gather robust data on safety and efficacy, what would form the basis for discussions with regulators about appropriate approval strategies. No dose-limiting toxicities have been observed during the dose escalation in any of the three cohorts, and we remain encouraged by the observed response rates. The next data update is planned for the fourth quarter at a major medical conference. Regarding our efforts to take forward the combination of AFM13 with natural killer cells into a registration-directed study, we have signed up a CDMO for the manufacturing of the NK cells and have generated additional data on cryopreserved natural killer cells pre-complexed with AFM13. As we have shared with you over the past few months, we view this car-like NK characteristics of our inertial engagers in combination with natural killer cells as a major advantage over monoclonal antibodies. The major difference being that when we look closer at the cell surface retention, our inertial engagers won't fall off in combined therapy for a very long time, including days later, whereas monoclonal antibodies are not retained for very long. As a result, our research shows that it is not possible to generate a pre-complex product with monoxone antibodies, but with innate and engaged cells only. Moreover, our research demonstrates that the engagement of our innate and engaged molecules with natural killer cells activate the natural killer cells to kill tumor cells. In our collaboration with the Karolinska Institute, we found that AFM13 when compared to a monoclonal CG30 antibody, mediated a more potent activation of natural killer cells, leading to a significantly increased number of natural killer cells that exerted engagement with multiple target cells, rendering these encasal serial killers. This exciting data has been accepted as opposed to presentation at the SITC annual meeting in November. In our ongoing trial with MD Anderson, it is our goal to generate a strong data package that would support discussions with the FDA and other agencies regarding next steps for the program, including a potential registration-directed study. Now let me turn over to AFM24, our EGFR-directed eNata engager. For AFM24, we continue to execute our three-pronged strategy of monotherapy, combination with natural killer cells, and combination with a checkpoint inhibitor PD-L1. Our goal in this program is to evaluate a broad set of solid tumor indications in parallel, supported all by a strong biological rationale. We expect multiple inflection points this year and plan to have multiple additional data readouts in 2022. Our monotherapy dose escalation study is on track. Based on current data, cohort five and six are pharmacologically active doses. Therefore, we have increased the size of cohort five, patients are dosed at 320 milligram, and cohort six, patients are dosed at 180 milligram, to generate additional pharmacokinetic and pharmacodynamic data that we expect will aid our selection of the recommended phase two dose. As of today, in each of the cohorts, five and six, five out of six patients are enrolled. It is important to mention that to date, in patients that have already completed the DLP period in each cohort, no dose-limiting toxicities were observed. So as just mentioned, we continue to see a good safety profile of AFM24. We confirm that we have not seen any of the classical EGFR-related side effects like apneiform skin rash or mucosal disease. This is in line with the distinct mechanisms of action of AFM24, which is very different from the mode of action of EGFR pathway targeting antibodies like Zituximab or Panetumumab. These findings also confirm the data from our pivotal toxicology studies in thymomolgus monkeys that indicated a different side effect profile for AFM24 versus the toxin. Infusion-related reactions remain the main side effect and are well manageable with symptomatic treatment and modifications of infusion rates. The ongoing dose escalation part includes patients with any EGFR expressing solid tumors. When assessing anti-tumor activity at those levels in the 320 milligram and 480 milligram cohort, we are encouraged to see that there were several patients on the study that experienced disease stabilization beyond eight weeks and were able to receive additional cycles. Biomarker analysis of the patients point to the activation of effector cells. shown by increasing expression of activation markers and a continuous secretion of cytokines. The supportive of this observation is a continuous occupancy of the CD16A receptor. We are enrolling patients in the monotherapy study, and independent of the selection of our recommended phase 2 dose, we plan to continue to increase the dose in non-selected patients to gather further insight into the exposure-effect relationship of AFM24, focusing on PD markers, and to confirm safety of AFM24 at even higher dose levels. Important now to note is, in addition, in line with our guidance, we expect now to start enrollment of indication-specific patients in the expansion course using single-agent AFM24 in the second half of 2021. These courts have been chosen based on a detailed analysis of the tumor biology, as we explained in the past, and will enrich for patients that we believe have a high likelihood to respond to single agent ASM24. These expansion courts will include renal cell carcinoma that fails standard of care, which includes TKIs and PD-1 targeted therapies. Second indication is non-small cell lung cancer, EGFR mutant, failing standard of care, TKIs. And the third indication is colorectal cancer, failing chemotherapy plus EGFR targeted antibodies. So we have selected three indications for the monotherapy study. In addition, we are now in the final stages of the setup phase for our combination studies of AFM24 with both atezolizumab study is called AFM24102, and the autologous NK cell product SNK01, this study is called AFM24-103. We confirm our guidance that we expect both of these studies to start enrolling patients in 2021. The tumor types we plan to study with the AFM24-Atezo combination are as follows. Non-small cell lung cancer, in this case, EGFR wild type, failing chemo and PD-1 targeted therapy. Gastric and GEJ cancer, failing standard platinum-based chemo. And a basket of EGFR-expressing tumors comprising pancreatic, hepatocellular, and biliary tract cancer, again, failing standard of therapy for the respective species. Now the tumor types we plan to study in the AFM24, SNK01, and K-cell combination study are as follows. Again, non-small cell lung cancer, EGFR wild type, squamous cell carcinoma of the head and neck, failing chemo and PD-1, and colorectal cancer, failing standard of care. The indications for each of the three studies have been selected carefully based on the biology of each tumor type. This approach allows us to investigate a broad set of solid tumors while also providing multiple shots on goal for the more prevalent tumor types, such as non-small cell lung cancer and colorectal cancer. In summary, we're very satisfied with the progress of the AFM24 program. The data show that AFM24 possesses a different mode of action compared to conventional EGFR-targeting antibodies. We see pharmacological activity based on CD16A receptor binding and NK activation markers. At these pharmacologically active doses, we see no classical EGFR-related side effects like skin mucosal toxicity. And in addition, we were seeing disease stabilization in these heavily pretreated patients at those levels 320 mg and 480 mg. We believe in the significant potential of AFM24, and with the planned expansion of the program, we're seeking to maximize this opportunity, addressing a broad set of major EGFR expressing tumor indications. And this strategy will allow us to provide a continuous flow of data. Now let me move to the third program, AFM28. For AFM28, we continue to advance the IND-enabling studies and have submitted an abstract with initial preclinical data for a major medical conference later this year. We plan to release information about the target and the indication once the abstract becomes available. We remain on track to submit the IND application in the first half of 2022, and our goal is to begin a clinical study in the second half of 2022. In addition to moving things forward in the clinic, we're continuing to publish data that supports our work. One such example is the recently published BRICLINICLE data that supported the IND filing, IND application of our inertial engager ADFM24 in the journal maps. Arndt, our CSO, will discuss the key takeaways from the publication. Arndt?

Thanks, Adi. And also for me, a very warm welcome to everybody on the call. As introduced by Adi, I would like to summarize the key preclinical data for AFM24 described in the recent publication in the journal MAPS. In this paper, we demonstrate the high affinity binding of AFM24 to CD16A on natural killer cells and macrophages. with strong binding values in the low nanomolar range. Importantly, AFN24 binds to CD16A on NK cells and macrophages with high affinity at a site that is distinct from binding of IgG, such that high concentrations of polyclonal IgG results in a minimal, only two-fold reduction in binding affinity. In contrast, binding of an FC-enhanced high-affinity anti-EGFR IgG antibody was significantly inhibited. These data again demonstrate the high surface retention of RICE molecules to NK cells, enabling the earlier described pre-complexing to NK cells with CAR-like NK cell properties, which are not possible with normal or FC-enhanced antibodies. We also show high-affinity binding of AFN24 in the nanomolar range to various EGFR-expressing tumor cells. AFN24 demonstrated to be highly differentiated from marketed anti-EGFR antibodies with its ability to potently and effectively kill tumor cells through antibody-dependent cell-mediated cytotoxicity, or ADCC, RNK cells. Moreover, this ICE mediated potent antibody-dependent cellular phagocytosis, or ADCP, biomacrophages in vitro. AFM24 was also shown to be effective towards a variety of EGFR-expressing tumor cells, killing these regardless of their EGFR expression level and irrespective of their KRAS or BRAF computational status. In addition, SA-124 has a lower affinity for EGFR and binds to a different epitope than cetuximab. It exerts an over 1,000-fold lower inhibitory activity on EGFR signaling, further underscoring its highly differentiated mechanism of action. Now, in terms of a devotator, in tumor mouse models, we have published at ASCR this year's ACR showing dose-dependent antitumor activity of AFM24 in combination with freshly isolated NK cells. This antitumor activity for AFM24 in combination with NK cells has now also been demonstrated with pre-complex and cryopreserved NK cells in vitro and in vivo within one of all preclinical collaborations. This exciting data gives us confidence that the NK cell product we used in combination with AFM24 retains its potent anti-tumor activity after cryopreservation in vitro and in vivo. Coming to the toxicology studies, in senile monkeys, also described in the paper, AFM24 was well-tolerated up to the highest dose of 75 mgs per kg when administered once weekly for 28 days. Remarkably, skin and other cytotoxicities which had been observed in these dose levels with cetuximab and comparable cinnamonkey studies were not observed here. Only transient elevation of interleukin-6 levels was detected at all dose levels, which returned to baseline after 24 hours. Moreover, an increase in circulating CD40 monocytes was observed after the first dose of AFAM24, concurrent with a decrease of circulating NK cells with doses of greater or equal to eight milligrams per kick. And our view showing the expected pharmacodynamic effect of this drug candidate. By taking together these results, emphasize the promise of our by specific innate cell engagers as an alternative cancer therapy and demonstrate the potential for AFM training core to effectively target tumors expressing various varying levels of EGFR regardless of their mutational status. Happy to answer any questions you may have about this in our Q&A. And for now, I'll hand the call over to Angus to review the financial. Angus?