Good day and thank you for standing by. Welcome to the ATHIMED First Quarter 2021 Financial Results and Corporate Update Conference Call. At this time, all participant lines are in listen only mode. After the presentation, there will be a question and answer session. Please be advised that today's conference may be recorded.
I'd now like to turn the conference over to your host today, Mr. Alexander Fudakidis, Head of Investor Relations at Avamed. Please go ahead.
Thank you, Liz. I'd like to welcome and thank you all for joining us today for our Q1 2021 results and operational 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 our management team, doctors Adi Hurst, our Chief Executive Officer Andreas Harstrich, our Chief Medical Officer Ansche Tielias, our Chief Scientific Officer Wolfgang Fischer, our Chief Operating Officer and Ms. Denise Miller, our Chief Business Officer and Angus Smith, our Chief Financial Officer. The whole team will be available for the Q and A session.
Before we start, I will quickly go through the 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 even if new information becomes available in the future. These forward looking statements are subject to risks and uncertainties, And actual results may differ materially from those expressed or implied in these statements due to various factors, Including, but not limited to, those identified under the section entitled Risk Factors in our filings with the SEC and those identified under the section entitled Forward Looking Statements in the press release that we issued today and filed with the SEC. With that, I'll turn the call over to Adi.
Adi?
Thank you, Alex. Good day, everyone, And thanks a lot for joining us today for our Q1 update call. I will provide updates on our pipeline And discuss the progress of our ongoing studies, in particular for AFM13 and AFM24 and our plans for the remainder of this year. I will also speak briefly about the announcement of our partnered BCMA program with Genentech. I'm very pleased to report that we are maintaining our momentum by continuing to execute well across all of our wholly owned programs.
We are leveraging the unique features of our innate cell engagers, which we also call ICE, across different programs And have continued to publish data that support the multi pronged approach of our development strategy, which includes development of our ICs as monotherapy and in combinations with natural killer cells and in combination with PD-one or PD L1 checkpoint inhibitors. Our AFM13 and AFM24 clinical programs Let me start with the registration directed study of ASUM-thirteen. This study is conducted as monotherapy in relapsedrefractoryperipheral T cell lymphoma and it continues to enroll patients following the positive interim analysis outcome, which we reported in March of this year. Today, we announced that we expect complete enrollment of about 110 patients in the first half of twenty twenty two And that we expect to be able to provide guidance about timing for data as we get closer to the completion of enrollment. We're also very pleased with the progress in the enrollment of the Phase I study at MD Anderson Cancer This study is evaluating increasing doses of cold blood derived natural killer cells Pre complexed with AFM13.
Today, we reported that the dose escalation cohorts are now fully enrolled And that we expect MD Anderson will have a data update from this study at a major medical conference in the second half of this year. In the current protocol of this study, patients can receive up to 2 cycles of therapy. Acyclic consists of 1 infusion of AFM13 pre complex with cord blood derived naturotol, followed by 3 weekly administration of 200 milligram of AFM13 monotherapy. The dose of natural killer cells is 10,000,000 per kilogram of body weight in Cohort 2 and 100,000,000 per kilogram of body weight in Core 3. In April, Doctor.
Rezwani of Endosynthesenter presented data on the first four patients that were treated with this therapy And each experienced significant disease reduction, with 2 complete responses and 2 partial responses, And objective response rate of 100%. In May, we announced the publication in clinical cancer research Supporting the therapeutic potential of AFM13 in combination with neutrinocell. Arndt, our Chief Scientific Officer, will discuss The key takeaways from the publication and some of our other preclinical work in just a few minutes. Important to us, IASM 13 continues to validate our 3 pronged development strategy for our innate cell engager molecules. We've now demonstrated that we can drive responses as monotherapy in indications where the innate immune system is functional.
Here specifically, we mean peripheral T cell lymphoma. We further published data on the combination of AFM13 with pembrolizumab that demonstrated synergy between AFM13 and PD-one and inhibitor in Hodgkin. And we have emerging data and emerging data set around the combination of ADFM13 with core blood derived NK cells that has demonstrated exciting initial results in CD30 positive lymphoma. The data we've now generated from AFM13 is informing the way we develop the rest of our pipeline, notably AFM24 and AFM28. Let me turn to AFM24.
Development of AFM24 is on track. In our ongoing monocarative The dose expansion phase It's intended to collect preliminary evidence of efficacy in specific indications and to further confirm As announced today, we have now completed dose cohort 5 at 3 20 milligram And recruitment of patients into Cohort 6 has begun at a dose level of 4 80 milligrams, which is a 50% increase in dose from cohort 1. The decision to increase to 4 80 milligram was driven by data derived from the cohorts 1 to 5. Specifically, our decision was informed by pharmacodynamic data from cohorts 1 to 4 and pharmacokinetic data from cohorts 1 to 5. Key and indeed very encouraging findings are Exposure is now correlated with increases in activation markers on natural killer cells and CD16A receptor occupancy.
Importantly, we have not observed signs of intangental exhaustion. In terms of safety, no medical relevant drug related side effects have been reported other than infusion related reactions, which are managed to standard pre medication. We have indeed not seen any of the classical EGFR related toxicities through Cohort 5, such as kin or other organ toxicity. Subject to additional dosing steps, we plan to determine the recommended Phase And we are expecting to begin the expansion cohort in the second half of this year. Now in parallel, We are making progress towards our goal of beginning 2 additional combination clinical studies, which would include the investigation of AFM24 in By leveraging now Both the innate and the adaptive immune system, we believe we can potentially show synergistic effects like we already did for AFM13, And this could provide a very meaningful benefit to patients.
We expect to dose the first patient in a Phase IIIa study evaluating in the second half of twenty twenty one. In addition, we expect to initiate a Phase IIIa study for the combination of AFM24 24 with NKGen Bio's autologous NK cell product in the second half of this year. We are committed to pursuing our multipronged development strategy development approach for AFM24, which we believe will enable us to target a broad range of EGFR expressing tumor types and population, indeed, all at the same time. For each of our 3 AFM24 studies, we plan to have expansion cohorts in at least 2 to 3 different indications. In total, the AFM24 program will target a broad range of EGFR expressing tumors, providing us with multiple opportunities for clinical success.
We expect to disclose more details about the indications for these studies later this year. Let me talk about quickly about the AFM 28, our 3rd program. For AFM 28, we continue of 2022. And our goal is to begin our clinical study in the second half of twenty twenty two. This morning, we also announced an update on the development of RO-seven twenty nine-seven thousand and eighty nine by our partner Genentech.
This is the BCMA targeting units in Engager. Genentech has completed the dose escalation portion of the Phase 1 study. No Those limiting toxicities were observed during the study. However, due to a broader portfolio consideration, Genentech decided to stop the Phase 1 As a reminder, this program was only the first of multiple targets under development with Genentech, And they may be clear to us that this decision does not have any implications for our platform or impact the continued development of the other targets. So we should remain confident in our collaboration with Genentech and look forward to progressing the additional targets towards clinical development.
Now I'd like to leave you with a message Today, we are very proud and excited to be able to play a leading role in developing cancer therapies based on innate immunity. As we have shown at multiple events, we believe that our innate cell engager molecules offer unique advantages over other immunotherapy. They do this by binding to a unique epitope in PD-six DNA, which allows us to show a reduced competition with plasma IgG, leading to a far more effective tumor Okay, with ABCC and ABCC. They have superior binding and retention on NatGen killer cells, which have been shown to persist over several days. They are able to kill tumor cells independent of the level of antigen expression, And it's now been shown that NK cells preloaded or pre complexed with our high affinity eNotes and ENGAGERs show improved muscle We have positioned Affimed in a unique place in the innate immune cell therapy landscape.
We have developed the differentiated drug platform that generates innate cell engager molecules, enabling NK cells and macrophages to locate the tumor and once they do to eliminate it. Furthermore, as we are learning for cellular NKTRAL based approaches, These require the specific targeting of NK cells to recognize the tumor. We're addressing this important need
With that, I'll
hand over the I'll turn the call to Arnd. After Arnd, Angus will give you an update on our financials. Arnd?
Thank you, Adi, and good morning, everyone. Also warm welcome from me. As Adi mentioned in the past few months, We have generated exciting preclinical data with our IC molecules, which I'd like to share with you today. On AFM24, we presented a preclinical poster of this year's AACR. In the poster, we were able to demonstrate that AFM24 in combination with adoptive NK cells Leads to a AFM24 dose dependent tumor regression in a mouse synograft model, establishing a strong This important finding was further supported by data demonstrating At AFM24's ability to tightly bind to NK cells as well as its cytotoxic potential to kill each of our Such toxic potential, which was greatly diminished by competing IgG.
The poster further showed that AFM24 induces a very prominent ADCP response or killing through macrophages against EGFR positive tumor cells, is a highly differentiated drug candidate. On AFM13, in a collaboration with Bjorn Urnsfeld At the Karolinska in Stockholm, we generated data demonstrating that the addition of AFM13 to NK cells renders these NK cells serial killers. If you look at Slide 6 in your presentation that shows Microscopy pictures of a single well containing a single NK cells and multiple tumor cells In the absence and presence of AFM13, on the top row, you can see that a single naked and undirected NK cell, which is shown in blue, It's not able to kill CD30 positive tumor cells, those are shown in red, over time period of 12 hours. The addition of AFM13 moves around in an undirected fashion without killing tumor cells in stark contrast and as shown on the lower line of pictures, The addition of AFM13 clearly increased the ability of that NK cells not only to kill 1, but several tumor cells. They are turning from red to green when they're being killed, demonstrating that the innate cell HRM13 effectively directs Next, I would like to summarize the key findings of our collaboration with the labs of Acadia Ruslan, MD Anderson, Todd Feininger, Washington University School of Medicine, which was recently published in Clinical Cancer Research.
In this paper, we were able to show That AFM13 strongly binds to MK cells, including cytokine activated or cord blood derived MK cells, resulting in enhanced tumor recognition and ADCC, so antibody dependent cellular cytotoxicity. This exciting data formed the basis for the successful IND of the ongoing Phase 1 study With pre complex cord blood derived NK Cells at MD Anderson in patients with CD30 positive lymphomas. The schematic on Slide 7 shows that cord blood derived NK cells were pre activated in the presence of IL-twelve, $15 $18 for $16 all were left untreated before being further co cultured with a feeder cell, Resulting in expanded cord blood NK cells shown on the top of the schematic or resulting in pre activated And expanded or abbreviated later as P and E, P plus E, cord blood derived NK cells, just shown on the bottom. As you can see on the next Slide 8, on the right, the cytotoxic efficacy of Pre activated and expanded cord blood derived NK cells shown in green is substantially enhanced By the combination with AFM13 over the cytotoxicity of only expanded cord blood NK cells, which are shown in light blue. Importantly, the surface expression of CD16 remains unaltered in both treatment groups as you can see on the graph on the left.
We go to Slide 9. It shows you on the right that the long retention on NK Cells after preloading These with AFM13 leads to a substantially higher degree of specific killing of CD30 positive tumor cells over a period of 72 hours when compared to unloaded NK cells. This potent ability to kill tumor cells remains unaffected by washing the AFM13 preloaded NK cells And this is the comparison between the blue and the red bars. The graph on the left shows that this Also on this graph, we can clearly see that the degree of ADCC is much higher in AFM13 preloaded versus unloaded pre activated and expanded cord blood wrapped NK cells. And again, that washing the NK cells Complexed with AFM13 does not affect their ability to kill, demonstrating the ability of our IC molecules to bind Strongly and durably to CD16A and NK cells and forming stable CAR like complexes Without the need for any substantial engineering, indeed we can generate these CAR like NK cells in just 1 to 2 hours.
I will now turn the call over to Angus to provide an update on our financial position and quarterly results. Angus?
Thank you, Arndt. Affimed'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 presented in euros, which is the company's functional and presentation Therefore, all financial numbers that I will present in this call, unless otherwise noted, will be in euros. We ended the Q1 of 2021 with cash and cash equivalents of €240,700,000 compared to 146 €900,000 on December 31, 2020. The cash balance includes the net proceeds from our January 2021 underwritten public offering and the $10,000,000 we received from the 1st tranche of the Silicon Valley Bank loan.
Based on our current operating plan and assumptions, including the proceeds from the recent financing, anticipate that our cash and cash equivalents will support operations into the second half of twenty twenty three. Net cash used in operating activities for the quarter ended March 31, 2021 was €16,000,000 compared to €16,500,000 in the Q1 of 2020. Total revenue for the Q1 ended March 31, 2021 was €11,700,000 compared with €5,100,000 for the quarter ended March 31, 2020. Revenue for the Q1 of 2021 mainly comprised of collaboration revenue from Research and development expenses for the Q1 of 2021 remained flat at €11,400,000 compared to the Q1 of 2020. General and administrative expenses for the Q1 of 2021 increased 27.3% to €4,500,000 from €3,500,000 in the Q1 ended March 31, 2020.
The increase relates largely to higher personnel expenses, higher This increase is largely due to foreign exchange gains related to assets denominated in U. S. Dollars as a result of the strengthening of the U. S. Dollar against the euro during the Q1.
Net income for the quarter ended March 31, 2021 was €1,400,000 or 0 point 0 $1 per common share compared with a net loss of €8,300,000 or a loss of $0.11 per common share for the quarter ended March 31, 2020. The weighted number of common shares outstanding for the quarter ended March 31, 2021, was 116,200,000. I will now turn the call back to Adi for closing remarks. Adi?
Thanks a lot, Angus. So the second half of twenty twenty one could be rich with data based on our pipeline and our research. We're focused on execution We have the financial strength to bring our programs forward with cash runway now into the second half of twenty twenty three. Key upcoming milestones for our pipeline are as follows. For AFM13, we expect to complete enrollment In this study, in the first half of twenty twenty two, and to provide guidance for the timing of the data release closer to the time When we complete enrollment in this study.
For the study of A13 pre complexed with NK cells, We expect that the team at the MD Anderson Cancer Center will report additional data at our major medical conference in the second half of this year. For AFM24 monotherapy, we're now recruiting in dose cohorts and are on track We further expect to initiate 2 Phase Ietwoa Combination studies for ATOM24 in the second half of this year, including the study with NKGen's SNK-one And K cell therapy and our study in combination with Roche Defentriq. For AFM 28, we expect to disclose the target for this program and publish initial preclinical data at Amelite's conference in the second half I'd like to reiterate our appreciation and gratitude to our investigators and clinical We would now be happy to take any questions that you may have.
Our first question comes from Maury Raycroft with Jefferies.
Hi, good morning, everyone, and thanks for taking my questions. So first question is just if you can talk more about where you're at with PD In Cohort 4 for AFM24, I guess if you use a positive control or think about maximum NK cell activation markers in CD16A Where are you at for with PD for Decimal 4 and how much more room do you have to go?
Andreas, can you take this question, please?
Yes, sure. So what we have said is That we see significant increases in exposure, which is more than dose proportional And that the activation markers that we are looking at that include CD16 Receptor occupancy, but are clearly not limited to CD16 receptor occupancy, show a good correlation with the exposure. So as we go up, we expect to get into the range of the pharmacodynamically optimal dose. That was one of the reasons why we decided to go to in a smaller step now. So instead of 100% increase, we selected With a 50% increase, again, we are very happy with the safety profile.
As we have announced, we have not seen any of the typical organ toxicity, most notably skin toxicity or any other Medically relevant toxicities. So we are titrating the dose to really define the optimum biological dose. And this was the reason why We decided to go into smaller steps.
Got it. That's helpful and makes sense. And based on your objectives for AFM24 Higher doses until you see a safety issue or sees exhaustion of NK cells or are there specific efficacy parameters that you're looking at with the monotherapy
Yes. Good question. So as we said previously, based on the mechanism of action and the Preferiential activation of NK cells in tumor tissue, we would not expect and also in line with our cytomolgos We would not expect to encounter any classical dose limiting toxicity. So we will probably not escalate To see toxicity because this is probably a very unrealistic high dose. What we will monitor closely are the pharmacodynamic markers.
As We have a mixture of markers that indicate activation of CNK cells looking at CCD16 receptor occupancy, But also monitoring NK cell exhaustion and we will titrate the dose so that we get a maximum And this will guide us in our selection for our dose that goes forward into the Phase 2 and into the expansion cohorts.
Got it. That's really helpful. And then last question, based on the PD data from Cohort 4 and the PK data from Cohort 5,
I think it's a little bit too early. As we said, we believe that we should be able to define a recommended Phase 2 dose second half of this year, whether this is cohort 5 or maybe 1 dose cohort above will still depend on the data that we are seeing.
Got it. Okay. Thank you for taking my questions.
You're welcome.
Our next question comes from Dana Graybosch with SVB Leerink.
Hi, thank you for the question. I'd like to talk more about the Genentech decision. And I guess one logistical question or process question and one science question. So I'll start with the process question. Do you can you do you plan to take this program back as ASM26?
And will we will Genentech present the dose escalation results for the medical conference?
Yes. Thank you, Dana. I'll hand over to Denise to see if you can still stay in contact with GNSX.
Yes. Hi, Dana. Thanks for the question. This is really early news for us and we haven't discussed with Genentech what the future of the program could look like, including whether or not rights could revert back to Affimed. So it's just too early on that.
But what we do know is Genentech will be planning on Publishing the data at a medical conference later this year.
That's helpful. And then and scientifically, it Struck us to remember that we've seen or we haven't seen promising results of NK cell therapy, adopted cell therapy in multiple myeloma. I believe Gamida Cell had a cohort of their NK cell therapy combined with elotuzumab that they never presented, but suggested that the results weren't particularly promising. I wonder if you could scientifically put this in context For what we've seen for other NK cell either NK cell therapy or NK cell directed therapies in multiple myeloma.
Yes, I'll turn this over to Arnd and Andreas. Andreas? Yes, I can then I
can start. Okay, Andreas, please.
Yes. I think it's a good question. I think what is important to note is that We do not know anything about the efficacy of the Phase I study. So we have not seen the full data set other than our So that's probably a little bit too early to speculate about efficacy or loss of efficacy. In general, I would agree multiple myeloma appears to be a difficult area for immune based therapies.
It's not only the NK cell approach so far where we're not so successful. We also can recall the failure of PD-one in multiple myeloma. So it appears to be a very specific biology, Really, probably differing a little bit from biology and other lymphoid malignancies. But again, As we do not have the full data set, it would be premature to speculate really here.
Got it. So we should have assumed
go ahead.
No, no. Dana, please you go well.
I'd like to hear what you were going to add and I just wanted to summarize that we really shouldn't assume the efficacy
I mean just one thing I would add, the GANIDA, it's interesting. I would say it's Probably accepted olituzumab is not one of the stronger antibodies kind of in the field with NK cells, so that Could have a bearing there and really nothing to add what Andreas has beautifully explained about also immune function in mouse melanoma.
Great. And then one last question here. Do you have any sense of when we could learn the target or when you will announce the targets for other programs in the Genentech collaboration?
Hi, Dana, Denise. We're prohibited from disclosing anything related to the targets with Genentech. And I guess it would become apparent when they take one of the next molecules into the clinic, at which point in time it will be apparent. But unfortunately, we're not able to What I can tell you is, it's a mix of solid and hematologic targets that we're working on with them.
Great. Thank you very much for answering the question.
Our next question comes from Nick Abbott with Wells Fargo.
Good morning. Thanks for taking my question. On AFM24, I seem to recall In preclinical models at least, and this is, I guess, a general observation with the innate cell engagers that you see cleavage of CD16 And so as you look at the data that you're accumulating the PD data, And I don't know, I can't remember if that leads to soluble AFM24CD16 Okay. So soluble CD16 FM24 complex, but are you seeing this? Are you able to look at this and look at that Expected cleavage event.
And then allied to that, are you seeing evidence of any NK cell margination? And how you think about sort of total NK cells versus circulating NK cells or the circulating pool As you think about optimizing that pharmacodynamic
endpoint.
Mike, can you take that question?
Sure. Yes. Nick, great question. Thank you. First of all, we can to some degree look at cleavage Not so clearly in the patient, but what we have seen, as you noticed in preclinical models, that that is not affecting.
First of all, it doesn't really we don't see that to a certain degree. It's not affecting the efficacy of the molecules. Quite in contrast, we have commented previously, we believe that some degree of cleavage That we have observed is probably good biologically because it enables also the NK cell to disengage and engage again. Again, when we look at what we have seen and now really describing with Bjorn Urgentfeld, and this is just a preview of something we will want to publish More substantially towards the end of the year, we see the ICEs render the NK cells serial killers. And that again, I think has also to do to some extent with the ability to disengage and some amount of cleavage.
Now To your question about, margination of NK Cells overall numbers, What we have seen, let's start with the preclinical studies. If you maybe recall the monkey data, we have Seeing that the peripheral levels transiently go down, we believe that is most likely Margination with the cells coming back. It also, we believe, is a sign of The NK cells actually being led into the tumor. So also more generally, we think there's 2 mechanisms of action. Of course, that would be expected, 1, the innate cell engagers leading the NK cells from the periphery into the tumor And the innate cell engagers also taking the NK cells in the tumor microbe and really engaging them to Let me stop here just to make sure that I'm answering your questions.
Yes. I think we're definitely Getting a lot of good information. But as you sort of think about that threshold that you want to see in PD, Do you are you able to account for these different pools, the tissue the NK cells in tissue So is it circulating NK cells and that movement presumably between those two pools?
Yes, we are I think we have said that with looking at CyTOF as we look at the activation markers, exhaustion Mark has, of course, looked at all of the NK cell populations very actively in the study. We will also be able to Thank you, Nick.
Our next question comes from Yale Jen with Laidlaw and Company.
Good morning and thanks for taking the questions. My first question is that a little bit forward looking one. In terms of AFM13 monotherapy, once you complete a current study, my understanding is that you will Later conduct a PIP a confirmatory study. My question is that, Would you potentially start a confirmatory study before you have the readout of the current study or you would do that
Andreas, that's a question for you.
Yes, we have not finalized this. As you know, we are targeting an accelerated approval with Swiss 202, which Would require us to start or to have a confirmatory study at the time of a BLA submission. So This was something I think where we started to engage with FDA into discussions not only about the monotherapy But again about the broader AFM13 development strategies that could include NK cell based therapies as well as monotherapy. So it's something that we need to do as we are approaching the completion of the enrollment phase, but we have not made a final decision here.
Okay, great. And maybe 2 quick questions. The first one is that although I understand The AFM13 NK cell combo study is still ongoing, but given that this study is an open label Juan, so is there any read through at this point for your design for the AFM24 NK cell combo study at the moment?
At the moment, we are pursuing to different strategies. As you know, AFM13 uses allogeneic Product and we are employing preloaded NK cells. For AFM24, We use autologous NK cells, so the SNK-one product from NK GEN, which has already established Safety profile has also shown some preliminary activity. Here we are really looking at coadministration, So parallel infusion, we are giving the NK cells much more frequently. We're giving NK cells on a weekly basis.
We also have Significantly higher total number of NK Cells. So if you will, we are more or less Exploring the broad spectrum that you could think about from 1 NK cell infusion allogeneic preloaded to multiple NK cell infusions,
Okay. Maybe the last question, you mentioned about checking the NK cell exhaustion marker, Probably the important one across the board at this point. Would you provide a little bit more color in terms of What specific sets of biomarkers are the key for investors to pay attention to? Thanks.
Arnd, do you want to take that question?
Yes, happy. So great question, Yale. I know As a case of our expert, you will be interested as everybody else. We are not disclosing that at this time. Also, please understand that could have also IP implications and of course we want to share that entirety.
We can tell you that of course we all that's a pretty broad panel It includes all of the markers that you would traditionally expect in terms of activation and all exhaustion. So that's as much as we can say at
Okay. I really appreciate that and I really fully understand that. And again, congrats for heading to the second half of this
I'm showing no further questions in queue at this time. So that will conclude today's question and answer session. Ladies and gentlemen, this concludes today's conference call. Thank you for participating. You may now disconnect.