Affimed N.V. (NASDAQ:AFMD ) Q1 2022 Results Conference Call June 1, 2022 8:30 AM ET

Alex Fudukidis - Head of Investor Relations

Adi Hoess - Chief Executive Officer

Andreas Harstrick - Chief Medical Officer

Arndt Schottelius - Chief Scientific Officer

Wolfgang Fischer - Chief Operating Officer

Angus Smith - Chief Financial Officer

Daina Graybosch - SVB Securities

Kripa Devarakonda - Truist Securities

Do Kim with - Sandler

Nick Abbott - Wells Fargo

Good day and thank you for standing by. Welcome to the Affimed First Quarter 2022 Financial Results Corporate Update Conference Call. At this time, all participant lines are in listen-only mode. After the speaker's presentation, there will be a question-and-answer session. [Operator Instructions] Please be advised that today's conference is being recorded. [Operator Instructions]

I would now like to hand the conference over to Alex Fudukidis, Head of Investor Relations. Please go ahead, sir.

Thank you, Norma, and thank you all for joining us for our call today. Before we begin, I'd like to remind everyone that we posted the relevant press release and presentation on the Investor Relations section of our website earlier today. On the call today, we have the members of our management team, including Adi Hoess, our Chief Executive Officer; Andreas Harstrick, our Chief Medical Officer; Arndt Schottelius, our Chief Scientific Officer; Wolfgang Fischer, our Chief Operating Officer; and Angus Smith, our Chief Financial Officer. The team will be available for the 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 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, and good day, everyone, and thanks a lot for joining us for this call today. I'd like to take a moment to review what we have achieved so far, especially against the challenging backdrop like the global pandemic, geopolitical tension and volatility in the capital market.

In the last three years, we have built a differentiated therapeutics pipeline of innate cell engagers, established the proof of concept for our three-pronged development strategy, reinforced our senior leadership team and strengthened our balance sheet.

More recently, we presented highly meaningful proof-of-concept data for our pioneering approach of treating heavily pretreated patients with a combination of an innate engager and allogeneic natural killer cells.

We also recognize the need to build a solid financial base to allow now swift execution of our programs and are very pleased to have recently completed the $103.5 million public offering. With these proceeds, we have the resources required to move our key wholly owned programs, just mentioned in here, AFM13, AFM24 and AFM28, to important inflection points over the next 12 to 18 months.

In the first quarter of this year, we announced the completion of enrollment of our REDIRECT study, which treats patients with relapsed/refractory peripheral T cell lymphoma with AFM13 monotherapy. We expect to report the top line data from this study in the fourth quarter of this year.

For the AFM13 study in combination with natural killer cells, following the compelling data that we reported in December of last year, we presented updated data at AACR, and we showed a strong increase in complete responses after two cycles of therapy at the recommended Phase 2 dose in very encouraging signs of durability. We believe these data continue to validate the program and the overall approach.

The data presentations in December 2021 at AACR have led to an increased interest by the pharmaceutical industry and treating physicians. And as a result, MD Anderson has been enrolling additional patients with Hodgkin lymphoma and other CD30-positive non-Hodgkin lymphoma. We indeed had plan to present new data from this study on additional patients, including important correlative science data at ASCO, which we now plan to present at a medical conference in the second half of this year.

Moving on to AFM24, our EGFR-targeting innate cell engager. We continue to enroll patients in all three clinical trials based on our three-pronged development strategy, and we are planning to present data in the second half of this year.

And for AFM28, our CD123 targeting innate cell engager, we're on track to submit an IND in June for clinical evaluation of patients with relapsed and refractory AML. We expect to initiate the Phase 1 clinical trial in the second half of this year.

We're also continuing to make progress in our work with our partners at MD Anderson, Artiva, NKGen and other third parties to ensure access to an off-the-shelf cryo-preserved natural killer celll for further development with our ICE innate cell engager therapy. We expect to provide additional updates on our NK cell development strategy in the second half of 2022.

We are advancing also our work with existing collaborators. In the case of Genentech, we have made good progress in various preclinical programs and handed over several programs to them for further preclinical development. Through our partnership with Roivant, AFM32 is currently being investigated in IND-enabling studies. We are eligible for additional proceeds from these key collaborations in the near term, including preclinical milestones as well as milestones based on early regulatory achievements.

We are also very encouraged by the data presented by our peers in the innate immune field and the interest from a pharmaceutics industry in therapies based on innate immunity. There is a growing recognition that engaging the innate immune system can play an important role in fighting cancer, and we are particularly proud to be among the first companies to have produced positive clinical data through this approach.

As our data have shown, our three-pronged approach has the potential to provide benefit to patients that have very limited treatment options and indeed urgently need novel treatment. We aim to bring our drugs forward to registration-directed studies in the near future. And we believe this is creating a strong commercial opportunity for each of our molecules.

With that, I will turn over the call to Andreas to give you more color on the progress on the program. Andreas?

Yes. Thank you, Adi, and also a warm welcome from my side. I will run you, as Adi said, through all of our development programs, and I'll start with AFM13 as shown on Slide 4. As you know, we are conducting two studies with AFM13: our registration-directed study for AFM13 monotherapy in patients with relapsed/refractory peripheral T-cell lymphoma also known as REDIRECT study; and our Phase 1/2 study that we are conducting in collaboration with MD Anderson and where we are evaluating cord blood-derived allogeneic NK cells that are pre complex with AFM13, followed by AFM13 monotherapy in patients with relapsed and refractory CD30-positive lymphomas.

Let's turn to the study AFM13-104, the NK cell study first. At the recent AACR conference, Dr. Yago Nieto, lead investigator at MD Anderson, reported the activity data of this approach after the second cycle of treatment for all patients at the recommended Phase 2 dose. Interestingly and importantly, the rate of complete responses at the recommended Phase 2 dose with the second cycle increased from 38% as reported in December to 62% at the final analysis. The overall response rate remains at 100%.

It's important to note here that the treatment is safe and very well tolerated. The main side effects were, in fact, associated with the lymphodepleting regimen, namely short-duration neutropenia and short-duration thrombocytopenia. I would highlight here the fact that these are mainly, I would say, laboratory side effects. Important to note is that they were not associated with any clinical consequences and we did not observe neutropenic fever or no signs of relevant bleeding. Also important, we did not observe any cases of cytokine release syndrome, any cases of neurotoxicity or graft-versus-host disease, which are often associated with T cell-based therapies.

So after reviewing the side effects, and learnings that we are transitioned, they did not lead to treatment delays or discontinuations. This led us and our colleagues at MD Anderson to believe that the safety and tolerability profile of this treatment will allow treating patients with more than the current two cycles. And in fact, at MD Anderson, we are already treating patients with a third cycle.

Durability data at the recommended Phase 2 dose were also very encouraging. Of the eight patients who achieved a complete response, seven remain in complete response after a median follow-up of 6.5 months, including two patients in complete response for more than 10 months and two patients who were able to receive consolidation high-dose chemotherapy with stem cell transplants.

If we turn to the other study AFM13-202, enrollment into the monotherapy study is now complete. More than 100 patients with relapsed or refractory peripheral T-cell lymphomas have received study treatment. And we expect, as Adi said, to report top line data in the fourth quarter of 2022.

The focus of this data release will be the overall response rate as assessed by blinded independent review committee and a preliminary assessment of duration of response, taking into account that the majority of duration of response data will depend on the actual duration of these responses.

In summary, we are very pleased with the continuing development of AFM13. Let's now turn to AFM24, and the clinical program is summarized on Slide 5. AFM24 is the next most advanced innate cell engager in our pipeline, benefiting from the learnings of AFM13, and AFM24, therefore, is also studied according to our three-pronged development strategy.

We presented data on the dose escalation up to 480 milligrams weekly as single agent at the recent AACR meeting. The data showed that the pharmacodynamic activity is present at doses of 160 milligrams and higher. Importantly, we also observed that the relevant pharmacodynamic parameters like target-mediated illumination or CD16 receptor occupancy as well as markers of NK cell activation show a plateau between 320 milligrams and 480 milligrams.

In the meantime, we have confirmed this finding with the data of the now fully enrolled 720-milligram cohort, again, seeing no relevant increases in pharmacodynamic markers with higher doses. These findings confirm our decision to define 480 milligrams as a recommended Phase 2 dose for the expansion cohorts. And as a consequence, the dose escalation part of the study has been finished, has been closed, and no higher doses will be investigated.

As I said, we are continuing to enroll patients in the expansion phase of the monotherapy study at 480 milligrams, and these expansion cohorts include patients with renal cell carcinoma, non-small cell lung cancer with EGFR mutations and colorectal cancer. We also continue to enroll patients in the dose escalation parts of the two combination studies, AFM24-102 and AFM24 103. In AFM24 102, a combination with talacotuzumab, Roche anti-PD-L1 checkpoint inhibitor, we are now treating patients with non-small cell lung cancer with EGFR white type, gastric and gastroesophageal junction adenocarcinoma and pancreatic hepatocellular and biliary tract cancers.

In the second combination study, instigating the combination of AFM24 with autologous NK cells, SNK01, how we are treating patients with non-small cell lung cancer, again, EGFR white type, squamous cell carcinoma of the head and neck and colorectal cancer. Through the three ongoing studies, we will be evaluating safety and efficiency of AFM24 in nine indication-specific cohorts with particular focus on non-small cell lung cancer, which is presented in all three studies; and colorectal cancer, which is represented in two of the three studies. As previously said, we expect to report initial data from these studies during the second half of 2022.

In addition, as shown on Slide 6, at NK 2022 held in mid-May, we presented an analysis of the longitudinal effects of AFM24 for those levels up to 480 milligrams, confirming the mechanism of action of AFM24 on the innate immune system. There was an increase in Ki-67, a proliferation marker in peripheral and NK cells and an induction of cytokines like TNF and interferon gamma over time. Importantly, and consistent with the pharmacodynamic data, these effects were more pronounced at higher dose levels of 160 milligrams and above.

A novel finding with the data that suggested also an activation of the adaptive immune system may be happening by AFM24. The analysis showed activation of cytotoxic T cells in the periphery and infiltration of T cells into the tumor bed by immune histochemistry, Suggesting stimulation of anticancer immunity beyond the innate immune system and the possible engagement of adaptive immune system. This data supports the rationale of AFM24 as monotherapy and the two combinations that are currently underway in the separate Phase 1/2a studies.

There will be three trial-in-progress posters at the upcoming ASCO conference that will further present background information and the design of three different AFM24 studies for patients with advanced EGFR-expressing solid tumors. We invite you to review these at the conference and connect with us if you happen to be at the conference.

For AFM28, our third wholly owned innate cell engager targeting CD123, we expect to submit an IND later in June and to start the first in-human Phase 1 study in the second half of the year. As summarized on Slide 7, at NK 2022 in May, we presented preclinical data, demonstrating that AFM28 induces lysis of CD123-positive leukemic blasts of AML patients and that it effectively kills CD123-positive tumor cells, either pre complex or co-administered with cryopreserved NK cells.

This is an important finding as it is the first time that we show data of AFM24 in combination with cryopreserved NK cells. This is very exciting as it presents a promise for potential of the cell therapy targeting leukemic blasts and leukemic stem cells in patients with AML and MDS.

By combining AFM24 with adaptive NK cell therapy, it is by redirecting these allogeneic NK cells to CD123-positive tumor cells, we believe that AFM28 can induce the depth of response necessary to meaningfully improve outcomes in patients with AML and MDS.

We plan to initiate a combination development with NK cells at the earliest possible time point as soon as adequate information about safety and tolerability of single aged AFM28 is available. The optimal strategy to initiate combination development will need to be discussed with regulatory agencies, and further details will be provided at a later point in time.

Finally, on AFM28, we recently announced that preclinical data will be presented in a poster session at the European heat Hematology Association Congress on June 10 in Vienna, Austria. This data will further summarize the preclinical proof-of-concept data and will demonstrate findings from our toxicology studies with AFM28.

With this, I'll hand over the call to Angus, who will take you through the financials. Angus, please?

Thank you, Andreas. Balance sheet and income statement highlights are shown on Slides 8 and 9 of the presentation. As a reminder, 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 currency. Therefore, all financial numbers that I'll present on this call, unless otherwise noted, will be in euros.

As of March 31, 2022, cash and cash equivalents totaled €169.9 million compared to €197.6 million on December 31, 2021. The pro forma cash position as of March 31, 2022, including net proceeds before operating expenses from the April 2022 underwritten public offering would be approximately €257.5 million. Based on our current operating plan and assumptions, we anticipate that our cash and cash equivalents, including the proceeds from the April 2022 public offering will support operations into mid-2024.

Net cash used in operating activities for the quarter ended March 31, 2022 was €28.4 million compared to €16 million for the quarter ended March 31, 2021. Included in our cash burn for the first quarter of 2022 was a milestone payment to MD Anderson for the initiation of the Phase 2 portion of the AFM13-104 trial, which was expensed in Q4 2021 and paid in Q1 2022. Total revenue for the quarter ended March 31, 2022 was €8 million compared with €11.7 million for the quarter ended March 31, 2021. Revenue predominantly relates to the Genentech and Roivant collaboration.

Research and development expense increased by 61% from €11.4 million in the quarter ended March 31, 2021, to €18.4 million for the quarter ended March 31, 2022. The R&D expenses increased primarily due to increased expenses associated with the development of AFM24 and the AFM28 program, an increase in costs associated with other early-stage programs and R&D infrastructure and an increase in share-based payment expense.

General and administrative expenses increased 57% from €4.5 million in the quarter ended March 31, 2021, to €7 million in the quarter ended March 31, 2022. The increase predominantly relates to higher share-based payment expenses and an increase in insurance premiums.

Net finance income decreased by 91% from €5.5 million in the quarter ended March 31, 2021, to €500,000 for the quarter ended March 31, 2022. Net finance income is largely due to foreign exchange gains related to assets denominated in U.S. dollars as a result of currency fluctuations between the U.S. dollar and the euro during the year.

Net loss for the quarter ended 31, 2022 was €16.7 million or €0.14 per common share compared with net income of €1.4 million or €0.01 per common share for the quarter ended March 31, 2021. The weighted number of common shares outstanding for the quarter ended March 31, 2022, was €123.4 million.

Additional information regarding these results is included in the notes to the consolidated financial statements as of March 31, 2022, which will be included in Affimed's filings with the U.S. Securities and Exchange Commission.

I will now turn the call back to Adi for closing remarks. Adi?

Yes. Thanks a lot, Angus. So, we're almost halfway through the year, and we're very happy with the progress that we could make despite all the challenges out there. And as we've shown, we are progressing now three wholly owned programs on AFM13, 24 and 28, all of them address major medical needs. And with our three-pronged strategy, we have developed funding that indeed can raise hopes within these patients.

As we're now showing on Slide 10, there are a lot more meaningful updates planned for the second half of this year and on all three programs. But most importantly, we extended our cash run rate into mid-2024, which enables us to reach these key inflection points for all our innate cell engagers.

With that, I'd like to thank you all for your continued support of our work. I'd like to thank patients and their families who entrust us with the care of lost family members and for our employees in the U.S. and Europe who are continuing to do the best they can in helping us to achieve our goal of bringing these innovative and differentiated treatments to patients who need them.

We are now ready to take your questions. Thank you.

[Operator Instructions] Our first question comes from Daina Graybosch with SVB Securities. Your line is open.

One from me on the NK cell combination of AFM13. I wonder if you could talk as we're getting closer about the questions that you plan to ask FDA in your 2022 meeting. And then a second question is. Could you talk about any differences or unique questions that you're focused on and the collaborations on NK cell development of Artiva, NKGen and MD Anderson?

Yes. Thank you, Daina. I'm going to start out on that. So in terms of questions for FDA, we're compiling those because the study, which is ongoing with MD Anderson does deliver important additional information. And so we have given you this snapshot now in AACR, where we have now treated in total 20 patients -- close to 20 patients and have seen this high response rate.

But as we've said, we have just completed the second cycle and now able to add a third target. So there's more to learn, in particular, on durability, which indeed already looks very promising. So, all these elements contribute then to the strategy that we will discuss with the FDA in order to take AFM13 forward. With that, I'll hand over to Andreas and see what -- how he can answer your questions.

Yes. I think I cannot add significantly more. So from the clinical side, as Adi said, we are gathering more experience with more patients, more follow-up, which clearly will frame our discussion's focus from the clinical part clearly will be on accelerated approval pathways as we believe this is a treatment that needs to come to patients as soon as possible. And as we have addressed also previously, of course, there will be some discussions on the NK cell and CMC, which is normal for an FDA meeting, but we are bringing all this together and preparing for this meeting.

And just to add on to your other questions relating to our collaborators, so we are in close interactions with all of them. In the case of AFM13, we focused on an allogeneic NK cell product cryopreserved that is planned to be developing combination, as I said, with AFM13.

And here, I cannot give you any further update at this stage as they are just work in progress that we're conducting. We have made significant progress with many of our collaborators and received great support from them. Indeed quite confident that we can take such an NK product cryopreserved that's also produced in reasonable quantities so that, eventually, it's not just used for the clinical grade or clinical material -- chemical material but also for commercial material.

So, that's the focus of our dialogues that we go beyond just looking at the clinical study but really have our focus on being able to execute this commercially, and that's the dialogue that we're having with some of these parties.

Maybe one follow-up for me on something you said in answer to the first question, Adi. I know we started with two cycles with this MD Anderson study. And then I think, last year, you were talking about up to six cycles. And then, I picked up that maybe you were talking four cycles around AACR. And just now I heard you say three. So, I wonder what the final protocol is for how many cycles -- give the patients and what's been behind sort of that optimization of the number of cycles.

Yes. Yes. Sorry for that. I said three because we are now treating patients with the third cycle, but it's four cycles. This is correct, Andreas.

Yes. We can go up to four cycles in the individual patients, we could on an individual basis, even give cycles beyond four. But I think four for now is a good number.

Our next question comes from Kripa Devarakonda with Truist Securities. Your line is now open.

Congrats on all the progress through this year. Just wanted to follow up on Daina's question. The multiple cycles that you're giving patients. So is there a better sense of what the duration between the treatment cycles is going to be? There was a range that you presented. When you go to the FDA, how much clarity would you need to have as to what the duration between the cycle needs to be? And in terms of data expectations for -- the data update from the combination, can you help set expectations as to what data we can expect, what level of maturity in terms of durability? And how much more do you need? You talked, Adi, about how you're going to have data from more patients. You're collecting more clinical data, but how much data do you think you need before you talk to the FDA for a path forward for the combination?

Yes, quite good questions. Andreas?

Yes. So in terms of interval between cycles, again, this is one of the open topics that we really would like to discuss with FDA. As you have seen in MD Anderson, there initially has been quite a variability which was in part due to some logistic reasons, patient planning. I think we are now getting much better to a standardized sequence of cycles where usually we will probably have it's hard to say, maybe 28 to 56 days between cycles. But again, there may be some variation here. And this is a topic that we definitely want to discuss with FDA.

Now in terms of how much additional data we need, again, what we said is that we wanted to discuss both aspects of a potential trial, which would be the clinical part as well as the NK cell parts, the CMC part. As Adi said, we are making well progress in identifying NK cell sources. So, this will also be a gating factor of our interactions with the FDA. Hope this answers your questions.

Thank you. Our next question comes from Maury Raycroft with Jefferies. Your line is now open.

Congrats on the. I have a quick follow-up on the combo as well. Just wanted to clarify if you're giving additional cycles to patients who are in a complete response? Or is it primarily to patients who are not in a complete response? I guess I'm wondering if you're giving additional cycles as a maintenance dose. Maybe if you can talk a little bit more about that.

Yes. So again, this is something where we gather experience. Our policy has been to give additional cycles also for patients who are in a complete response, at least one additional cycle, if you will, as a kind of consolidation in patients who go more slowly into a response like we have seen increase in quality of responses. Again, the primary goal is to get a patient into a complete response and then to probably get at least one consolidation cycle in.

Got it. Okay. That's helpful. And then for the AFM13 monotherapy study, are you waiting to see the data before starting a confirmatory Phase 3? And when do you anticipate speaking with FDA regarding the confirmatory study?

Yes. As we said, we expect the high-level data in the fourth quarter. And of course, these data will trigger all of the subsequent events. We have some plans how a confirmatory study could look like, and we will take this plan to the FDA probably at the time when we see the high-level data.

Okay. Got it. And maybe last question just for the increase in T cells that you're seeing in the tumor biopsies after AFM24 treatment, have you quantified that? And do you see any dose-dependent response there or relationship with clinical benefit?

That's a good question and these data very, very new. So, we are currently in the process to analyze this obvious -- the obvious question, the correlation was with clinical outcome, but we don't have the full data set yet, but we'll give updates in the future.

Thank you. Our next question comes from Li Watsek with Cantor. Your line is now open.

I guess I wanted to ask about AFM28. I know one of your peers showed some interesting data of [indiscernible]. Just curious, if you have any thoughts there? Do you think there is any [indiscernible] to your program? And also, where do you see the bar for success?

Andreas, do you want to take that? So I guess you are referring to the data that were recently published by Nkarta.

But in general, I would say we have seen activity of NK cells that were coming from different sources. So we have seen activity of cells that were derived from peripheral cells that were derived from cord blood cells. And most of the results cluster in the range of 30%, 40%.

Nkarta data initially looks somewhat higher. But obviously, here the end is still very small. So, we are eagerly waiting for them to see more. What we know in general is that we can enhance the efficacy of NK so quite significantly through a 2018 preclinical study. And I now hand over to Andreas in order to give you a little more insight from the clinical end.

Well, I think you almost answered the question completely. So, one of the rationales to really develop an ICE in AML, MDS is the demonstrated sensitivity of AML cells to NK cells.

So this, I think, is an important building block now. What we have said is that we believe that CD16A, especially when it's activating like we do with the ICEs with a very high affinity, very tight binding is probably the most potent way to activate NK cells. It also addresses problems with cells with very low target expression, where we have shown that we are largely independent of target or density of the target.

So, we believe that this is a very potent way to utilize the already demonstrated activity of NK cells in AML but really to boost it, to extend it to low-expressing cells, to extend it to leukemic stem cells which do express CD123, but would not express some of the other used targets. So this, I would say, adds to our confidence that AFM24 -- AFM28 could be a very, very potent program.

Okay. I just want to follow up on AFM24. I know you've shown some interesting biomarker data from the Phase 1 trial. So just wondering, if you can expand a little on perhaps the NK cell infiltration into the tumors and how inmate engage the adaptive immune system as well.

Maybe, Arndt, if it's a preclinical question? I'd like to...

Sure. Happy to do that. Yes, thanks for the question, Li. So we just discussed the T cells. I mean, how do we think the engagement of the adaptive immune system may happen. We don't have direct proof. But what we know, of course, from the cancer immunity cycle that we do engage in K cells.

We knew now by the destruction of the tumor cells, dams will be released, activated drilling cell. They move to lymph nodes, activate T cells. So, we feel that this is an apparently potent way to also activate the adaptive immune system, obviously, exciting because we have always started in earlier models that we see that to some extent into no [indiscernible] in the patients.

We need to be careful. It's small numbers. We just discussed, we still want to correlate with clinical activity. But that clearly is a trend, and we clearly -- it's also shown on the poster, this one, non-small cell lung cancer, where you see from 120 to 580. So, in some cases, quite significant, not all, but some cases.

So that's the mechanism of action. We have also seen and reported on the poster, of course, activation of circulating the CD8 T cells with Ki-67, the potent proliferation and activation markers of at T cells and other proof of the activation of circulating NK cells also by measuring Ki-67 as one of the examples. Does that answer your question?

Thank you. Our next question comes from Brad Canino with Stifel. Your line is now open.

Based on how enrollment for AFM24 has progressed this year, can you expand on, or I guess, offer any expectations for the degree of data that could be presented this year? Have there been any of the three therapies or cancer types that have enrolled better? Do you have a sense for the rough sample size? And I guess as well, will you be ready to make any go/no-go decisions at this update? I'm just wondering when you might be ready to narrow the nine-cohort approach.

I can take this. So, of course, enrollment differs between the three studies. The AFM24-101 study, here, we have three parallel cohorts open. We have identified the recommended Phase 2 dose. We are seeing enrollment into all three cohorts. It's probably a little bit too early to say whether one cohort will be faster or quicker enrolling than the others, but we should have adequate numbers of patients in all three cohorts.

Now for AFM24-102 and -103, we are a little bit earlier. As we have discussed, both studies have safety run-in phases, where we start with lower doses of AFM24 to address some of the authority comments to look at safety, at least in a limited number of patients. Here, we're in both studies, we are in the dose escalation part. So there will be mainly safety data that we will collect until the end of the year and activity data of the two combination studies probably during first half of next year.

Again, all these studies are open label. So depending on the degree of activity, of course, you can make decisions for further treatment or for discontinuation of certain cohorts at every part through the enrollment process.

Thank you. Our next question comes from Do Kim with Piper Sandler. Your line is now open.

I was wondering, if you could provide some additional details on the 720 milligram cohort for AFM24? Any differences in AEs that you saw between that dose and the 480 milligram dose? Any efficacy signals that, would be helpful?

I can take this also, again, the 720 milligrams, as I said, has been fully enrolled. We have not seen any dose-limiting toxicity, which is consistent with the other dose cohorts. We have not seen a change in the toxicity profile. And in accordance to our previous guidance, we are putting the data together and plan to submit more granular update at one of our scientific meetings.

Okay. Got it. And question on AFM13 monotherapy. If you do get accelerated approval, what are your initial thoughts on the size of the commercial infrastructure that you'll need, how big of a sales force? And does your cash guidance assume that you'll get approval and launch the product?

So the first question is on how big of an entity we would need to have to build in order to detail this product. We have not disclosed any details on that. And at the moment, the Company has not taken a final decision if we would detail the program as Affimed or if we would find a commercialization partner. So that's open.

Having said that, we have built up a a commercial team that is doing all the background work as we move along. So, the work is fully proceeding and I just have to say at the moment, as we proceed, we haven't yet taken a full time line to this. But as we're proceeding, we can take the decision on which direction we're going to go if we partner or if we build up the commercial infrastructure on our well.

Into this also plays the way how we proceed forward with AFM13 in combination with the natural killer cells, which we then want to detail in the second half. So this is an important milestone. And I would say that once we have all that together, so the AFM13 monotherapy data and how we can proceed with the combination of NK cells, then we can take this detailed step forward in order how we want to commercialize AFM13.

Thank you. Our next question comes from Yale Jen with Laidlaw. Your line is now open.

The first question just tag on the previous one that, in terms of the nine cohorts for the AFM24. Was there a minimum number of patients which could be different in different indications you need to have to make the initial assessment? Then I have a follow-up.

Andreas, a question for you.

Yes, as we have discussed, I think also when we presented the studies, all studies are basically built as a Simon two-stage design. And of course, there's the target response rate vary a little bit, but what I would say is if you assume like 10 patients plus/minus two or so for the first interim analysis and to make a first go/no-go decision. I think that gives you a reasonable ballpark how the design is laid behind these cohorts.

And then, of course, if you meet your success criteria, each cohort has the potential to go up to 35 to 40 patients, which we believe would also be a critical number of patients to engage into meaningful discussions with FDA. But as I said, we have this first look at roughly 10 patients per cohort.

Okay. Great. That's very, very helpful. And maybe just another follow-up question here which is that given AFM28, it's already ready for the clinical study at the moment. Question is that if you compare 28 versus the 13 both on the chemo space, do you see any differences besides the indication or the targets that improve from the 13 or any other colors on that?

That's a question for Arndt.

Yes. Thanks for the question. A few details we can share. First, when you compare it to 13, of course, 28 is now more the IgG like molecule with longer half-life. What hasn't changed is, I think, the differentiation potential that has already listed what we see and share the posters very specific killing CD123 positive cells, sparing of the progenitor cells better CD123 negative, very strong activation of NK cells, superior to the Fc-enhanced antibody, so basically talacotuzumab. So what we are seeing across the board is preclinically so far that the strategy works out where we really strongly believe that our ICE technology, we can surpass activity seen with prior CD123 antibodies.

Thank you. Our next question comes from Nick Abbott with Wells Fargo. Your line is now open.

Congratulations on all the progress. First one for me. So for AFM13 NK cells, do you intend to file for breakthrough therapy designation before meeting with FDA?

This is Wolfgang. We would apply for breakthrough designation before we talk to the agency with that program. We decided to first talk to the agency and discuss the data; and as Andreas mentioned before, from a clinical and also CMC perspective, then we take it from there.

Okay. And then at that meeting, would you be presenting FDA with a registration-directed trial plan, including CMC? Or is it more here are the pieces how do we put it together into a registration-directed trial?

Our current thinking is that we put that all together to the clinical perspective but also the CMC perspective. And we all know how important it is to have the CMC process in place. And therefore, this needs to go together from our perspective.

So just to be clear, then you would be proposing here is our plan.

Could you please repeat, Nick, I didn't get it.

Yes. Sorry, Wolfgang. And just to be clear then, you would go to FDA with a registration plan.

Thank you. [Operator Instructions] And I'm currently showing no further questions at this time. Thank you for joining Affimed’s first quarter earnings business and business update conference call. This concludes the conference. You may now disconnect. Everyone, have a wonderful day.