Affimed - Q1 2022
June 1, 2022
Transcript
Operator (participant)
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 participants are on a listen-only mode. After the speaker's presentation, there'll be a question and answer session. To ask a question during the session, you'll need to press star one on your telephone. Please be advised that today's conference is being recorded. If you require any further assistance, please press star zero. I would now like to hand the conference over to Alex Fudukidis, Head of Investor Relations. Please go ahead, sir.
Alex Fudukidis (Head of Investor Relations)
Thank you, Norma, and thank you all for joining us up to 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 statement, even if new information becomes available in the future.
These forward-looking statements are subjects to risk and uncertainties, and actual results may differ materially from those expressed or implied in these statements due to various factors, including, but not limited to, those identified under the section entitled Risk Factors 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 Hoess (CEO)
Thank you, Alex. 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 backdrops like the global pandemic, geopolitical tension, and volatility in the capital market.
In the last few years, we have built a differentiated therapeutics pipeline of innate cell engagers, established clear 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 pre-treated patients with a combination of an innate cell engager and allogeneic natural killer cells.
We also recognize the need to build a solid financial base to allow our swift execution of our programs, and we're very pleased to have recently completed the EUR 103.5 million public offering. With these proceeds, we have the resources required to move our key wholly owned programs.
Just mention them here, AFM-13, AFM-24, and AFM-28, to important inflection points over the next 12-18 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 AFM-13 monotherapy. We expect to report the top-line data from this study in the fourth quarter of this year.
For the AFM-13 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 2 cycles of therapy at the recommended phase 2 dose and 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. As a result, MD Anderson has been enrolling additional patients with Hodgkin lymphoma and other CD30-positive non-Hodgkin lymphoma. We indeed had planned 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 H2 of this year. Moving on.
For AFM-24, 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're planning to present data in the H2 of this year. For AFM-28, 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 H2 of this year.
We're also continuing to make progress in our work with our partners at MD Anderson, Artiva, NKGen Biotech, and other third parties to ensure access to an off-the-shelf cryopreserved natural killer cell for further development with our ICE innate cell engager therapy. We expect to provide additional updates on our NK cell development strategy in the H2 of 2022. We are also advancing 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 Sciences, AFM-32 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 pharmaceutical 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?
Andreas Harstrick (CMO)
Yeah. 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 AFM-thirteen, as shown on slide 4. As you know, we are conducting two studies with AFM-thirteen. Our registration-directed study for AFM-thirteen monotherapy in patients with relapsed refractory peripheral T-cell lymphoma, also known as the 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-complexed with AFM-thirteen, followed by AFM-thirteen monotherapy in patients with relapsed and refractory CD30-positive lymphomas.
Let's turn to the study AFM-thirteen one zero four, the NK cell study first. At the recent AACR conference, Dr. Yago Nieto, the 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 two dose. Interestingly, and importantly, the rate of complete responses at the recommended phase two dose with the second cycle increased from 38%, as reported in December, to 62% at the final analysis.
The overall response rates remains at 100%. It's important to note here that 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. If after reviewing the side effects and learning that they are transient, 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. In fact, at MD Anderson, we are already treating patients with a third cycle. Durability data at the recommended phase two dose were also very encouraging.
Of the 8 patients who achieved a complete response, seven remain in complete response after a median follow-up of 6.5 months, including 2 patients in complete response for more than 10 months and two patients who were able to receive consolidation high-dose chemotherapy with stem cell transplant. If we turn to the other study, AFM-thirteen two oh two, 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 maturity 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 AFM-13. Let's now turn to AFM-24, and the clinical program is summarized on slide five. AFM-24 is the next most advanced innate cell engager in our pipeline, benefiting from the learnings of AFM-13. AFM-24, 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 elimination or CD16 receptor occupancy, as well as markers of NK cell activation, show a plateau between 320 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.
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. 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, the combination with atezolizumab, Roche anti-PD-L1 checkpoint inhibitor, we are now treating patients with non-small cell lung cancer, with EGFR wild type, gastric and gastroesophageal junction adenocarcinoma, and pancreatic, hepatocellular, and biliary tract cancers. In the second combination study, investigating the combination of AFM24 with autologous NK cells, SNK01. We are treating patients with non-small cell lung cancer, again, EGFR wild type, squamous cell carcinoma of the head and neck, and colorectal cancer.
Through the three ongoing studies, we will be evaluating safety and efficacy 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 H2 of 2022.
In addition, as shown on slide 6, at NK2022, held in mid-May, we presented an analysis of the longitudinal effects of AFM-24 for dose levels up to 480 milligrams, confirming the mechanism of action of AFM-24 on the innate immune system. There was an increase in Ki-67, a proliferation marker in peripheral 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 was the data that suggested also an activation of the adaptive immune system may be happening by AFM-24.
The analysis showed activation of cytotoxic T cells in the periphery and infiltration of T cells into the tumor bed by immunohistochemistry, suggesting stimulation of anticancer immunity beyond the innate immune system and a possible engagement of adaptive immune system. This data supports the rationale of AFM-24 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 the different AFM-24 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 AFM-28, 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 I study in the H2 of the year. As summarized on slide seven, at NK 2022 in May, we presented preclinical data demonstrating that AFM-28 induces lysis of CD123 positive leukemic blasts of AML patients, and that it effectively kills CD123 positive tumor cells, either pre-complexed or co-administered with cryopreserved NK cells.
This is an important finding, as it is the first time that we show data of AFM-24 in combination with cryopreserved NK cells. This is very exciting as it presents a promise for a potential off-the-shelf therapy targeting leukemic blasts and leukemic stem cells in patients with AML and MDS.
By combining AFM-24 with adoptive NK cell therapy, it is by redirecting these allogeneic NK cells to CD123-positive tumor cells, we believe that AFM-28 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-agent AFM-28 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 AFM-28, we recently announced that preclinical data will be presented in a poster session at the European 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 AFM-28. With this, I'll hand over the call to Angus, who will take you through the financials. Angus, please.
Angus Smith (CFO)
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 Standards 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 EUR 169.9 million, compared to EUR 197.6 million on December 31, 2021. The pro forma cash position as of March 31, 2022, including net proceeds before offering expenses from the April 2022 underwritten public offering, would be approximately EUR 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 EUR 28.4 million compared to EUR 16 million for the quarter ended March 31, 2021.
Included in our cash burn for the first quarter of 2022 was the milestone payment to MD Anderson for the initiation of the phase II portion of the AFM-13-104 trial, which was expensed in Q4 2021, and paid in Q1 2022. Total revenue for the quarter ended March 31, 2022, was EUR 8 million, compared with EUR 11.7 million for the quarter ended March 31, 2021. Revenue predominantly relates to the Genentech and Roivant collaborations.
Research and development expenses increased by 61% from EUR 11.4 million in the quarter ended March 31, 2021, to EUR 18.4 million for the quarter ended March 31, 2022. R&D expenses increased primarily due to increased expenses associated with the development of AFM-24 and the AFM-28 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 EUR 4.5 million in the quarter ended March 31, 2021, to EUR 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 EUR 5.5 million in the quarter ended March 31, 2021, to EUR 500,000 for the quarter ended March 31, 2022. Net finance income is largely due to foreign exchange gains related to assets denominated in US dollar as a result of currency fluctuations between the US dollar and euro during the year. Net loss for the quarter ended March 31, 2022, was EUR 16.7 million or EUR 0.14 per common share, compared with net income of EUR 1.4 million or EUR 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 US Securities and Exchange Commission. We'll now turn the call back to Adi for closing remarks. Adi.
Andreas Harstrick (CMO)
Yeah, thanks a lot, Angus. We're almost now halfway through the year, and
Adi Hoess (CEO)
We're very happy with the progress that we could make despite all the challenges out there. As we've shown, we are progressing now three wholly owned programs, AFM13, 24, and 28. All of them address major medical needs. With our three-pronged strategy, we have developed something 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 H2 of this year and on all three programs. Most importantly, we extended our cash runway into mid-2024, which enables us to reach these key inflection points for all our innate cell engagements. 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 their care, with the care of loved 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're now ready to take your questions. Thank you.
Operator (participant)
Thank you. As a reminder, to ask a question, you'll need to press star one on your telephone. To withdraw your question, please press the pound key. Please stand by while we compile the Q&A roster. Our first question comes from Daina Graybosch with SVB Securities. Your line is open.
Daina Graybosch (Senior Managing Director and Biotechnology Analyst)
Thank you for the question. One for me on the NK cell combination of AFM-13. Wonder if you could talk, as we're getting closer, about the questions that you plan to ask FDA in your 2022 meeting. A second question is, could you talk about any differences or unique questions that you're focused on in the collaborations on NK cell development with Artiva, NKGen, and MD Anderson?
Adi Hoess (CEO)
Yeah. Thank you, Daina. I'm gonna start out on that. In terms of questions for FDA, we're compiling those, the study which is ongoing with MD Anderson doesn't just deliver important additional information. 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 these high response rates.
But as we've said, we have just completed a second cycle and now able to add a third cycle. There's more to learn, in particular on durability, which indeed already looks very promising. All these elements contribute then to the strategy that we will discuss with the FDA in order to take AFM-13 forward. With that, I'll hand over to Andreas and see how he can answer your questions.
Andreas Harstrick (CMO)
Yeah, I think I cannot add significantly more. From the clinical side, as Adi said, we are gathering more experience with more patients, more follow-up, which clearly will frame our discussions. Focus from the clinical part clearly will be on accelerated approval pathways, as we believe that this is a treatment that needs to come to patients as soon as possible. As we have addressed also previously, of course, there will be some discussions on the NK cell and then CMC, which is normal for an FDA meeting. We are bringing all this together and then preparing for this meeting.
Adi Hoess (CEO)
Just to add on to your other questions relating to our collaborators. We're in close interactions with all of them. In case of AFM-13, we focus on an allogeneic NK cell product process that is planned to be developed in combination, as I said, with AFM-13. Here I cannot give you any further update at this stage as they are just a work in progress that we're conducting. We have made significant progress with many of our collaborators. I've received great support from them.
We're indeed quite confident that we can take such an innate cell product, a process that's also produced in reasonable quantities, so that eventually it's not just used for clinical grade clinical material, but also for commercial material. 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. That's the dialogues that we're having with some of these parties.
Daina Graybosch (Senior Managing Director and Biotechnology Analyst)
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 4 cycles around AACR, and just now I heard you say three. I wonder what the final protocol is for how many cycles you'll give the patients and what's been behind sort of that optimization of the number of cycles.
Adi Hoess (CEO)
Yeah. Sorry for that. I said three because we are now treating patients with a third cycle, but it's four cycles. This is correct, Andreas.
Andreas Harstrick (CMO)
Yeah, we can go up to four cycles. In individual patients, we could, you know, on an individual basis, even give cycles beyond four. I think four for now is a good number.
Daina Graybosch (Senior Managing Director and Biotechnology Analyst)
Thank you.
Operator (participant)
Thank you. Our next question comes from Kripa Devarakonda with Truist Securities. Your line is now open. Kripa, your line is now open.
Kripa Devarakonda (VP of Biotechnology Equity Research)
Sorry about that. Thank you so much for taking my question, and congrats on all the progress through this year. Just wanted to follow up on Daina's question. You know, 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 cycles needs to be?
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'd need before you talk to the FDA for a path forward for the combination? Thank you.
Adi Hoess (CEO)
Yeah, quite good questions. Andreas?
Andreas Harstrick (CMO)
Yeah. 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 MD Anderson, there initially has been quite a variability which was in part due to some logistic reasons, patient clinics. 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 28-56 days between cycles. 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 have said is that we want to discuss both aspects of a potential trial, which would be the clinical part, as well as the NK cell part, the CMC part. As Adi said, we are making good progress in identifying NK cell sources, so this will also be a gating factor for our interactions with the FDA.
Kripa Devarakonda (VP of Biotechnology Equity Research)
Great. Thank you so much.
Andreas Harstrick (CMO)
Hope this answers your questions.
Kripa Devarakonda (VP of Biotechnology Equity Research)
Yeah. Thank you.
Operator (participant)
Thank you. Our next question comes from Maurice Raycroft with Jefferies. Your line is now open.
Maurice Raycroft (Equity Research Analyst)
Hi, congrats on the progress, and thanks for taking my questions. 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.
Andreas Harstrick (CMO)
Yeah. 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.
Maurice Raycroft (Equity Research Analyst)
Got it. Okay, that's helpful. For the AFM-13 monotherapy study, are you waiting to see the data before starting a confirmatory phase 3? When do you anticipate speaking with FDA regarding the confirmatory study?
Andreas Harstrick (CMO)
Oh, yeah, as we said, we expect the high level data in the fourth quarter. Of course, this 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.
Maurice Raycroft (Equity Research Analyst)
Okay. Got it. 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? Do you see any dose-dependent response there or relationship with clinical benefit?
Andreas Harstrick (CMO)
That's a good question, and these data are very new, so we are currently in the process to analyze this. There's the obvious question, the correlation with clinical outcome, but we don't have the full data set yet. We'll give updates in the future.
Maurice Raycroft (Equity Research Analyst)
Got it. Okay, thank you for taking my questions.
Operator (participant)
Thank you. Our next question comes from Li Wang Watsek with Cantor. Your line is now open.
Li Wang Watsek (Equity Research Analyst)
Hey guys, thanks for taking the questions. I guess I wanted to ask about AFM-28. I know one of your peers showed some interesting data of NK cell AML. Just curious if you have any thoughts there. You think there is any way through to your program? And also where do you see the bar for success at? Thanks.
Arndt Schottelius (Chief Scientific Officer)
Andreas, you want to take that? I guess you're referring to the data that were recently published in ASCO.
Li Wang Watsek (Equity Research Analyst)
Yes.
Arndt Schottelius (Chief Scientific Officer)
In general, I would say we have seen activity of NK cells that were coming from different sources. We have seen activity of cells that were derived from peripheral blood cells and cord blood cells. Most of those results cluster in the range of 30%-40%. CAR-T data initially looks somewhat higher, but obviously here the n is still very small, so we're eagerly waiting for them to see more. What we know in general is that we can enhance the efficacy of NK cells quite significantly through AFM-28 in a preclinical study. I now hand over to Andreas in order to give you a little more insight from the clinical end.
Andreas Harstrick (CMO)
Well, I think you almost answered the question completely.
Arndt Schottelius (Chief Scientific Officer)
Okay.
Andreas Harstrick (CMO)
One of the rationales to really develop an ICE in AML MDS is the demonstrated sensitivity of AML cells to NK cells. 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 identity of the target.
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 our low expressing cells, to extend it to leukemic stem cells, which do express CD123 but would not express some of the other used targets. This, I would say, adds to our confidence there that AFM-28 could be a very, very potent program.
Li Wang Watsek (Equity Research Analyst)
Okay. I have an follow-up on AFM-24. I know you've shown some interesting biomarker data from the phase 1 trial. Just wondering if you can expand a little on perhaps the NK cell infiltration into the tumors and how it might engage the adaptive immune system as well.
Andreas Harstrick (CMO)
Maybe, Arndt, if it's a preclinical question.
Arndt Schottelius (Chief Scientific Officer)
Yeah, sure.
Andreas Harstrick (CMO)
Would you like to take it?
Arndt Schottelius (Chief Scientific Officer)
Sure. Happy to do that. Yes, you know, thanks for the question, Li. 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 NK cells.
We know by the destruction of the tumor cells, DAMPs will be released, activated dendritic cells, they, you know, move to lymph nodes, activate T cells. We feel that this is a apparently potent way to also activate the adaptive immune system. Obviously exciting because we have always thought in earlier models that we see that to some extent and to now see it in the patients. Now we need to be careful. It's small numbers.
We just discussed we still want to correlate with clinical activity. There clearly is a trend and we clearly it's also shown on the poster, you know, this one, non-small cell lung cancer, where you see, you know, 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 CD8 T cells with Ki-67, the potent proliferation and activation markers of the T cells. Other proof of the activation of circulating NK cells also by measuring a Ki-67 as one of the examples. Does that answer your question, Li?
Li Wang Watsek (Equity Research Analyst)
Yes. That's it.
Arndt Schottelius (Chief Scientific Officer)
Thank you.
Operator (participant)
Thank you. Our next question comes from Bradley Canino with Stifel. Your line is now open.
Bradley Canino (Director and Equity Research Analyst)
Good morning. Based on how enrollment for AFM-24 has progressed this year, can you expand on or offer any expectations for the degree of data that could be presented this year? You know, 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? 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. Thank you.
Arndt Schottelius (Chief Scientific Officer)
Andreas?
Andreas Harstrick (CMO)
Well, I can take this. 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 AFM24-103, 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 the limited number of patients. 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 combinations studies probably during H1 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.
Bradley Canino (Director and Equity Research Analyst)
Appreciate it. Thank you.
Operator (participant)
Thank you. Our next question comes from Do Kim with Piper Sandler. Your line is open.
Do Kim (Managing Director and Senior Research Analyst)
Hi. Thanks for taking my question. I was wondering if you could provide some additional details on the 720 milligram cohort for AFM-24. Any differences in AEs that you saw between that dose and the 480 milligram dose, any efficacy signals, that would be helpful. Thank you.
Andreas Harstrick (CMO)
Well, 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. In accordance to our previous guidance, we are putting the data together and then plan to submit more granular updated 101 scientific meetings.
Do Kim (Managing Director and Senior Research Analyst)
Okay, got it. A question on AFM-13 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?
Adi Hoess (CEO)
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. 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. That's open. Having said that, we have built up a commercial team that is doing all the background work as we move along. The work is fully proceeding and I just have to say at the moment, as we proceed, we haven't yet set a full-time line to this.
As we're proceeding, we can take the decision on which direction we're gonna go, if we partner or if we build up the commercial infrastructure on our own. Into this also plays the way how we proceed forward with AFM-13 in combination with the NK cells, which we then want to detail in the H2. This is an important milestone. I would say that once we have all that together, so the AFM-13 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 AFM-13.
Do Kim (Managing Director and Senior Research Analyst)
Okay. Thank you very much.
Operator (participant)
Thank you. Our next question comes from Yale Jen with Laidlaw & Company. Your line is open.
Yale Jen (Senior Managing Director and Senior Biotech Analyst)
Good morning, and thanks for taking the questions. The first question, just to tack on the previous one, that in terms of the N cohorts for the AFM-24, was there a minimum number of patients which could be different in different indications you need to have to make the initial assessment? I have a follow-up.
Adi Hoess (CEO)
Andreas, it's a question for you.
Andreas Harstrick (CMO)
Yeah. As we have discussed, I think, also when we presented the studies, all studies are basically built as Simon two-stage designs. Of course, the target response rate vary a little bit, but what I would say is if you assume like 10 patients ±2 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. Then, of course, if you meet your success criteria, each cohort has the potential to go up to 35-40 patients, which we believe would also be a critical number of patients to engage into meaningful discussions with FDA. As said, we have this first look at roughly 10 patients per cohort.
Yale Jen (Senior Managing Director and Senior Biotech Analyst)
Okay, great. That's very, very helpful. Maybe just another follow-up question here, which is that, given AFM-28 is already, you know, ready for the clinical study at the moment, question is that if you compared 28 versus the 13 both on the hematologic space, do you see any differences besides the indication or the targets that, you know, improve from the 13 or any other colors on that? Thanks.
Andreas Harstrick (CMO)
Yeah, that's a question for Arndt. Arndt, yeah.
Arndt Schottelius (Chief Scientific Officer)
Yeah, thanks for the question. You know, a few details we can share is that first, when you compare to thirteen, of course, twenty-eight is now more the IgG-like molecule with longer half-life. What hasn't changed is, I think the differentiation potential that Andreas already listed. What we see and shared on the poster is very specific killing CD123-positive cells, sparing of the progenitor cells that are CD123-negative, very strong activation of NK cells, superior to the Fc-enhanced antibodies, so basically talacotuzumab. What we are seeing across the board is preclinically so far that the strategy works out where we really strongly believe with our ICE technology, we can surpass activity seen with prior CD123 antibodies.
Yale Jen (Senior Managing Director and Senior Biotech Analyst)
Okay, great. That's very helpful. Appreciate the color, and thanks a lot, and congrats on the progress.
Operator (participant)
Thank you. Our next question comes from Nick Abbott with Wells Fargo. Your line is now open.
Nick S Abbott (Equity Research Analyst)
Good morning. Thanks. Thank you for your questions. Congratulations on all the progress. First one from me. For AFM13 plus NK cells, do you intend to file for breakthrough therapy designation before meeting with FDA?
Andreas Harstrick (CMO)
Regulatory. Wolfgang?
Wolfgang Fischer (COO)
Hi, this is Wolfgang. We would not 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, and then we take it from there.
Nick S Abbott (Equity Research Analyst)
Okay, thanks. Then, at that meeting, would you be presenting FDA with a registration-directed, you know, trial plan including CMC? Or is it more, here are the pieces, how do we put it together into a registration-directed trial?
Wolfgang Fischer (COO)
Our current
Andreas Harstrick (CMO)
As we have discussed.
Wolfgang Fischer (COO)
Our current thinking.
Andreas Harstrick (CMO)
Wolfgang, go ahead, please.
Wolfgang Fischer (COO)
Yeah, you go. No, you go, Andy. It's all good.
Andreas Harstrick (CMO)
No, no, Wolfgang. Thank you.
Wolfgang Fischer (COO)
Our current thinking is that we put that all together. The clinical perspective, but also the CMC perspective. We all know how important it is to have the CMC process in place, and therefore, this needs to go together from our perspective.
Nick S Abbott (Equity Research Analyst)
Just to be clear then, you would be proposing, "Here is our plan.
Wolfgang Fischer (COO)
Could you please repeat, Nick? I didn't get it.
Nick S Abbott (Equity Research Analyst)
Yeah. Sorry, Wolfgang. I'm saying just so, just to be clear then, you would go to FDA with a registration plan.
Wolfgang Fischer (COO)
Yes.
Nick S Abbott (Equity Research Analyst)
Okay, great. Thank you very much.
Operator (participant)
Thank you. As a reminder, ladies and gentlemen, that's star one to ask your question. I'm currently showing no further questions at this time. Thank you for joining Affimed's first quarter 2022 earnings and business update conference call. This concludes the conference. You may now disconnect. Everyone, have a wonderful day.