Affimed NV (AFMD) 2020 Q4 法說會逐字稿

Good day, everyone, and welcome to Affimed's Fourth Quarter and Year-end 2020 Financial Results and Corporate Update Conference Call. (Operator Instructions). As a reminder, today's conference call is being recorded.

I would now like to introduce your host for today, Mr. Alex Fudukidis, Head of Investor Relations at Affimed. Please go ahead.

Thank you, Tracy. I'd like to welcome and thank you all for joining us today for Affimed's Fourth Quarter and 2020 Year-end Financial Results and Operational Update Call.

Before we begin, I'd like to remind everyone that we issued our release earlier today and it can be found on our Investor Relations section of our website. On the call today, we have our management team, doctors, 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 then Ms. Denise Mueller, our Chief Business Officer; and Angus Smith, our Chief Financial Officer. The whole team will be available for the Q&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 publicly or to update the reasons why actual results could differ materially from those anticipated in the forward-looking statements, even if this -- 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 projected 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?

Yes. Thank you, Alex. Good day, everyone, and thank you for joining us for our fourth quarter business update call in 2020.

Today, we will briefly review the key developments of the company, including our recent updates on the AFM13 monotherapy, interim futility analysis. The findings presented by Dr. Katy Rezvani at AACR from the investigator-sponsored clinical trial at the MD Anderson Cancer Center, which is treating patients with a pre-complex combination of AFM13 and cord blood-derived NK cells. And we will provide an update on the clinical progress of AFM24 and our other programs currently in development.

I will then hand the call over to Angus to discuss our fourth quarter financial results. We will conclude the call by highlighting some of our key milestones we expect or estimate for the rest of this year.

We are very excited to share groundbreaking clinical data with you on our programs and demonstrate progress we are making across our pipeline, which has undergone an incredible evolution in 2020 in the early part of 2021. Affimed has been a pioneer in leveraging the innate immune system to fight cancer. We have spent a good part of the last decade developing our technology, the ROCK platform, and innate cell engagers, and we're seeing increasing evidence that our technology can result in meaningful benefits for patients in the clinic.

A very rewarding experience for patients, their families, the doctors who treat them and for us as well.

Over the years, we have established what we believe is a unique position for Affimed to develop best-in-class molecules by engaging our first-line of defense, our innate immunity, including natural killer cells and macrophages to guide these cells to the cancer where they can do what they are naturally intended to do and protect them from disease. We have conducted a lot of preclinical work to support our development strategy and to identify indications where we believe our innate cell engagers have the best chance of success. We believe that we are now beginning to see the results of all of these efforts.

As we've shared with you in the past, we believe that our innate cell engagers are strongly differentiated vis-à-vis competing platform and approaches to helping patients fight cancer. Our innate cell engager molecules, as you'll know, bind to CD16A on natural killer cells and macrophages with high affinity. And the unique binding epitope on CD16A reduces competition with plasma IgG, and leading to an effective tumor cell killing via ADCC and ADCP, which are acronyms for cytotoxicity and phagocytosis. Innate cell engager show superior binding and retention on natural killer cells, which have been shown to persist over -- which has been shown to persist over several patients. They are able to kill tumor cells independent of the level of antigenic expression. In addition, NK cell is pretty complex with our high affinity innate cell engagers show improved tumor cell killing, which is fully maintained after freezing, thawing and washing.

A very important and unique advantage is that no matter how you design the effective cells, cord blood-derived iPSCs, or autologous, common need of all these platforms is that they need targeting. Our innate cell engager enable natural killer cells to locate the tumor independent of target expression level, and we believe that this is where our technology has a strong advantage.

If you look at the different tumor targeting approaches, we believe our technology is the best way to target whatever NK cell programs you work with.

Over the last several months, we have been able to demonstrate that the [clinical] science behind our technology can produce highly encouraging clinical results.

The recent announcement about the positive interim analysis of our AFM13 monotherapy trial. The data presented from the study at MD Anderson on AFM13 combination with NK cells. And the data from the combination of AFM13 with pembrolizumab, we believe provides validation for what we have been saying about our science and the advantages of our innate cell engager. Furthermore, these findings help validate our 3-pronged development strategy, which leverages monotherapy in specific indications with a high chance of innate cell involvement, focuses on combination with NK cells in indications where the patient's innate immune system is dysfunctional and sees, aims at activation of both innate and adaptive immune system by combining innate cell engagers with anti-PD-1 or PD-L1 checkpoint inhibitors.

I would now like to briefly review the news we reported on AFM13 in the last few weeks. Last month, we reported a positive outcome of the interim futility analysis for AFM13 as monotherapy in patients with CD30-positive peripheral T-cell lymphoma. As a reminder, the interim analysis demonstrated that Cohort A, representing patients with at least 10% of tumor cells expressing CD30 achieved the predefined futility threshold. And that Cohort B, which includes patients whose tumors have lower CD30 expression, defined as from 1% up to less than 10% positivity for CD30 showed sufficient comparability to Cohort A. Importantly, we noted that on complete and partial responses in both high and low expressing CD30-positive peripheral T-cell lymphoma patients.

As a result, this monotherapy study will continue by combining the 2 cohorts into 1 for all patients with CD30 positivity. The outcome of the interim analysis was encouraging on many fronts. We now have a drug candidate that has the potential to deliver benefits to patients with PTCL, who have exhausted options after undergoing multiple therapies, including experimental therapy. And AFM13 could have the standard for accelerating our drug discovery efforts with our in-house ROCK platform, leveraging the power of the innate immune system.

As mentioned, we believe we have the first and best-in-class innate cell engager platform with a validated approach and broad potential that allows our drug candidates to be developed to find a wide range of diseases, addressing high unmet needs in CD30-positive lymphomas and EGFR expressing solid tumors as well as other solid tumors in hematologic cancers.

Earlier this week, Dr. Rezvani, of the MD Anderson Cancer Center presented data at a major symposium of the AACR annual meeting from the investigator sponsor trial of cord blood-derived natural killer cells pre-complexed with AFM13. In the first cohort of that study in which patients were treated at the lowest dose of 10^6 cells -- the NK cells per kilogram pre-complexed with AFM13, we reported that all 3 patients experienced significant disease reduction with 2 partial responses and 1 complete response. The first patient dosed in cohort 2, now we're using 10^7 pre-complexed NK cells per kilogram was assessed with a complete response rate after a single cycle of therapy.

In total, we have observed an objective response rate of 100% to date. Dr. Rezvani also discussed with you yesterday what she believes that the opportunities are for this treatment. Importantly, we see the results from this study so far as validating the benefits of a CAR-like NK approach with high affinity binding of our innate cell engager molecule to natural killer cells, delivering meaningful benefits to patients. Our plan now is to continue to develop and customize approaches that leverage the unique and differentiating features of our molecules in combination with adoptive NK cell transfer to provide options for treating a variety of hematologic and solid tumors in the future.

The study is currently recruiting and treating patients in the second cohort with 10^7 NK cells per kilogram. We expect Dr. Rezvani and her colleagues at MD Anderson will continue to provide updates on the study and update us on the success story with patients throughout the year.

Finally, late last year, we published final data from the Phase Ib study of AFM13 in combination with Merck's PD-1 checkpoint inhibitor KEYTRUDA in blood, the Journal of the American Society of Hematology. The data showed an objective response rate of 88% at the highest treatment dose as well as a complete response rate of 46%. This data publication was another very significant step forward for Affimed as it was the first time that the combination of one of our innate cell engager molecules with an anti-PD-1 checkpoint inhibitor demonstrated disease reduction and the ability to be safely administered with manageable side effects.

The high objective response rate and complete response rates in this proof-of-concept study indicated that our approach of harnessing the activation of innate immunity could improve upon current therapy. This growing clinical evidence from AFM13 in our monotherapy trial in the combination trials with NK cells and other immunotherapies, we believe provides correctly validation and confirmation about our innate cell engager activity. Furthermore, it provides us with critical knowledge and clinical experience that we are now leveraging and are applying across our development program.

We now have clinical data from the AFM13 program to support our development strategy by demonstrating that our innate cell engagers can generate meaningful monotherapy efficacy, show substantial synergy with checkpoint inhibitors and work-in-concert with adoptive NK cells to drive responses even at low doses of natural killer...

The data we have generated from AFM13 is thus informing in the way we develop any other pipeline candidates, notably AFM24 and AFM28. Here, too, we are making very good progress. On -- our ongoing AFM24 monotherapy trial is currently in the dose escalation portion of our Phase I/IIA clinical study in relapsed/refractory patients with any EGFR expressing solid tumors. We announced this morning that we have completed Cohort 4, which was dosing patients at 160-milligrams and we're now recruiting and treating patients at a dose of 320 milligrams, which is Cohort 5. The objective of the dose escalation portion is to evaluate the safety and tolerability of AFM24 at various doses and to establish a recommended Phase II dose that we can use in the expansion phase of the trial.

At this stage, we don't yet have any information to indicate that we are yet at a pharmacodynamically active dose nor have we reached a maximum tolerated dose. And we plan to continue to do dose escalate. We'll have further updates on the progression of the dose escalation on our next earnings call. The dose escalation phase of the trial is enrolling all comers, and is not yet enriched for any specific tumor type. In the expansion cohorts, we will enroll patients into specific indication with known innate cell involvement, and this should enable us to evaluate the efficacy of AFM24. We expect to start the dose expansion phase of the trial in the second half of this year.

We have also continued to make good progress with the initiation of a combination study of AFM24 with adoptive NK cells. We recently announced that the IND for the combination of AFM24 with NKGen autologous NK cell product as NK-01 was cleared by the FDA. We expect to initiate a Phase I/IIA study for the combination in the second half of 2021. We're indeed very excited about the potential for this combination given the initial clinical data from MD Anderson with AFM13. Hence, the exciting clinical data shown on our AFM24 poster at this year's AACR conference.

In that poster, we were able to demonstrate that AFM24 in combination with adoptive NK cells, leads to a dose-dependent tumor regression in a mouse treatment graph model, establishing a strong preclinical proof-of-concept for this promising combination. This important finding was further supported by data demonstrating that AFM24's ability to tightly bind to a natural killer cell as well as it's cytotoxic potential to kill EGFR expressing tumor cells was unaffected by the presence of competing polyclonal IgG. In stark contrast, rituximab cytotoxic potential was greatly diminished by completing IgG. The poster further showed that AFM24 induces a very prominent ADCP response activation of macrophages against EGFR positive tumor cells irrespective of the presence of KRAS mutations, further adding to the reasons to believe for this highly differentiated drug candidate. Thirdly, we have also accelerated our plans to investigate AFM24 in combination with Roche atezo and anti-PD-L1 checkpoint inhibitor.

We believe the combination of AFM24 with atezo could leverage the innate and adaptive immune systems in the fight to kill cancer. We expect to dose the first patient in a Phase I/IIA study evaluating the combination in the second half of 2021.

Now our third wholly owned innate cell engager, AFM28, continues to advance through IND-enabling studies, and we plan to release more details about this program later this year, including information obviously about the target and then the IND-enabling preclinical data.

Looking at our collaborations. We have also continued to work closely with Genentech and Roivant as they move their programs forward. We're very happy with how these 2 partnerships are developing. Recall, we announced last August that 0789 -- 7089, the former AFM26, which is CD16A BCMA targeting innate cell engager, entered Phase I clinical step. And as we said in the past, presenting details of the trial are dependent on our partnership. As far as the Roivant partnership is concerned, we are collaborating with them to move preclinical work for AFM32 forward. And just in case, you missed it...

(technical difficulty)

I think we lost Adi, but just to finish up and then move to the financials. Adi was mentioning that just in case you missed it, Roivant now announced today, AFM32 is being directed towards solid tumors. And in addition, we have -- want to highlight that through several recent transactions, we have strengthened our balance sheet, and I will cover that in just a moment.

Overall, we are encouraged with the progress that we and our partners have made and are looking forward to a promising 2021.

So this is Angus Smith, Chief Financial Officer of Affimed. I will now review our fourth quarter 2020 financial results.

Affimed's consolidated financial statements have been prepared in accordance with IFRS as issued by 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 will present in the call unless otherwise noted will be in euros. As Adi mentioned, through several recent transactions, we have been able to significantly strengthen our balance sheet, extending our cash runway while enabling us to accelerate our multipronged development approach for our innate cell engager molecules.

We ended 2020 with cash, cash equivalents and current financial assets of EUR 146.9 million compared to EUR 104.1 million for December 31, 2019. The cash balance does not include the net proceeds from our January 2021 underwritten public offering or the EUR 10 million we received from the first tranche of the Silicon Valley Bank loan. The pro forma cash position as of December 31, 2020, including net proceeds from our January financing activity, would be approximately EUR 244.5 million.

Based on our current operating plan and assumptions, including the proceeds from the recent financing, we anticipate that our cash, cash equivalents and current financial assets will support operations into the second half of 2023.

Net cash used in operating activities for the year ended December 31, 2020 was EUR 19.4 million compared to EUR 29.1 million in 2019. Cash flow from operating activities improved in 2020 due primarily to proceeds received from the Roivant and Genentech collaborations, partially offset by an increase in our net loss.

Total revenue for the year ended December 31, 2020 was EUR 28.4 million compared with EUR 21.4 million for the year ended December 31, 2019. The revenue for 2020 and 2019 predominantly relate to the Genentech collaboration. Collaboration revenue of EUR 19.7 million for the year ended December 31, 2019 was from the Genentech collaboration. Collaboration revenue for the year ended December 31, 2020 amounted to EUR 27.8 million or $26.2 million from the Genentech collaboration and EUR 1.4 million from the Roivant collaboration.

Research and development expenses for 2020 increased 14% from EUR 43.8 million in 2019 to EUR 50 million in 2020 due to higher expenses for AFM24 and other programs as well as infrastructure investments. General and administrative expenses increased 34% from EUR 10.3 million in 2019 to EUR 13.7 million in the year ended December 31, 2020. The increase predominantly relates to higher personnel expenses due to the increase in headcount in 2020 and to higher legal, consulting and audit costs.

Net loss for the year ended December 31, 2020 was EUR 41.4 million or EUR 0.50 per common share compared to a net loss of EUR 32.4 million or EUR 0.50 per common share for the year ended December 31, 2019. The weighted number of common shares outstanding for the year ended December 31, 2020 was 83.5 million. As of March 31, 2021, our common shares outstanding were approximately 119 million. We encourage shareholders to also review our 20-F filing for the year as filed with the SEC this morning.

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

Yes, I'm back again. Sorry for this. I was just disconnected. But thank you very much, Angus, for jumping in.

In closing, I would like to reiterate our excitement at Affimed for our very important achievements in 2020, the strong start to 2021 and all of the progress we are looking forward to in the coming months. We've advanced our strategy of exploring our innate cell engager as monotherapies and we're now exploring opportunities in novel combinations with NK cells through partnerships we secured with NKMax or NKGen, as they are called now, and Artiva.

We are moving our AFM13 monotherapy study forward with both high and low expressing CD30-positive PTCL patients. We are expecting that in the combination of AFM13 with NK cells at MD Anderson as the trial moves through the cohort, our collaborators, they will present their findings at scientific conferences throughout 2021. For AFM24, we expect to complete the dose escalation phase in our ongoing monotherapy study and initiate the dose cohort expansion phase in the second half. We are working quickly and efficiently to prepare for further investigation of combination therapies of AFM24 in solid tumors, first, with NKGen Bio, SNK01 autonomous cell product as well as in combination with atezo Roche PD-L1 inhibitor.

We expect to be dosing patients in both of these studies in the second half of 2021. For our preclinical asset, AFM28, we expect to report data from preclinical IND-enabling studies later this year and then subsequently file the IND in the first half of 2022.

Finally, there is upside -- we believe there is upside in our collaborations with Genentech and Roivant because we have the opportunity to provide further meaningful update. Updates on these programs will remain largely, however, at the discretion of our partners, and we will continue to work and support them as they move their respective innate cell engager molecules through the clinic.

Now before we open the call for Q&A, I would like to say thank you to really a lot of people. So thank you again to the patients who entrust us with their health. Very important, I want to thank all Affimed employees who are working, indeed, very hard and very diligently to ensure that our progress -- our programs continue to progress. And welcome and thank our new and old investors who continue to believe in us and support our scientific efforts. As always, we have the whole team on the call today. And look forward to your questions. Thank you very much. Operator?

(Operator Instructions) Your first question comes from the line of Do Kim from Capital Markets.

Adi, you said that there wasn't any pharmacodynamic activity at the dose level for AFM24, how does that align with your expectations for the dose escalation? And is there a dose level where you would stop that if you still don't see activity and just shift the development focus to combination strategies?

Yes. Thanks for this question. I want to hand this over to Andreas to explain where we are. But what I must say is we've just finished the expansion of the cohort 4 and now are moving into 5. So we haven't really analyzed cohort 4. But I'll let Andreas explain you where we are.

Yes. Thank you, Adi. And yes, the answer is in line with what Adi said. We have not analyzed most of the pharmacodynamic readouts. In fact, for those cohorts, 3 and 4, we are using beta analysis here. Some of the assays like CD16A receptor occupancy are quite new. So we will process the data that we have collected or the samples that we have collected. So what Adi said is we currently do not have the data to say whether we are already at a pharmacodynamically active dose week. It's a possibility that we need to evaluate over the next couple of weeks.

Now coming back to the overall strategy, as Adi has shown, if we take AFM13 as a blueprint, we have seen meaningful clinical activity as a single agent in combination with PD-1 as well as in combination with NK cells. According to our analysis of tumor biology, especially in the EGFR expressing tumors, we expect to see exactly the same picture or the same pattern. So we believe there are distinct disease types, which will benefit from a single agent approach as these patients have sufficient numbers and sufficient functionality of their own NK cells. We expect patients to benefit from PD-1-based approaches. And then ultimately, there will be tumors or there are tumors where the patients' own NK cell number and NK cell functionality is limited, at least initially. So these were patients who will be targeted with our NK cell-based approaches possibly on the long run in combination with either single agent or PD-1 plus ICE maintenance. So there's a lot of flexibility, but we believe that we will see, as I said, the same picture with tumor entities differing in their biology, and they will need accordingly different treatment approaches.

Great. And I have a follow-up question on the pipeline. Given that you saw such strong responses with the MD Anderson study, how are you thinking about other opportunities in blood cancers and possibly revisiting CD19 but with a innate cell engager or going after CD20 or CD38?

I think these are all options that are open. Now again, CD19, CD20 is probably a field that is very well-served. We see the medical need, clearly right now, in other areas, CD30 is an important area. What we just learned from the study. And then when we look closer as that CD30 expression is not only limited to T cell lymphomas and Hodgkin's. We do see CD30 expression on B cell, especially diffused large B cell. We also see CD30 expression in a very significant chunk of acute leukemias, which gives additional options for CD30-based therapy. And as you know, we are in collaboration with Roivant and Genentech, where we have not disclosed the target. So I think the ROCK platform offers the versatility to address a number of different clinical situations. And this opportunity will expand as we go along, either in-house with our new candidates or in collaboration with our partners.

Your next question comes from the line of Brad Canino from Crédit Suisse.

Still committed to disclosing first clinical data this year? And if so, what are the factors that you're considering to determine when to present it? And then just to be clear, it sounds like you're going to continue to a cohort 6 in the dose escalation for beyond, if needed, would that be 640 milligrams?

Andreas, did you get the full question? I missed the first half.

Yes. I missed also -- probably the first. But maybe I'll start to answer from the back end, and then we see what we are missing. So first of all, again, we are currently accruing at cohort 5, 320 milligrams. And as I said, we will have to analyze our pharmacokinetic and pharmacodynamic markers from the 2 previous cohorts. This will give us a picture where we stand in terms of pharmacodynamic activity, and this will guide our decision whether to enroll additional cohorts.

Now as we have also said, the relative increase of the steps, the relative increasing steps from cohort to cohort is guided by a Bayesian assessment model, which will suggest the relative increments from cohort to cohort based on the totality of the data we have seen over the cohorts as well as the data that we have seen in the previous cohort. So 640 is a possibility. But again, as we will collect data from cohort 5, this may change to either a larger or a smaller increment depending on the Bayesian analysis.

Okay. Great. And the first question was just, are you still committed to disclosing first clinical data this year? And what factors are you looking at to consider when to present?

There is, yes, a certain element of insecurity is still in there. We believe that by end of this year, we should have defined our pharmacodynamically active dose. And as Adi said, we are also committed to start to enroll into expansion cohorts. As we said, once we have defined this pharmacodynamically active dose, we'll disclose the data of the whole dose escalation part, including patients' characteristics, patients' responses as well as the pharmacokinetic and pharmacodynamic data that defines its dose selection. So our best estimate, I would say, that this all will happen within this year.

I just want to reiterate, so we have just finished cohort 4. What does this mean? So what we take about 4 weeks for the last patient then to finish the dose escalation. At that stage, we can determine the safety, and we can open to move to the next cohort. However, the assessment of such a patient is only done after 8 weeks. So currently, we are analyzing data of cohort 3 and cohort 4 because we pull those, and that's what's been ongoing over the next weeks. So in essence, the way how this has moved forward is determined by really understanding the safety, getting to meaningful doses and then in parallel do the assessment. So just to give you a little bit of an explanation of where we currently stand. And such data then could be the basis of further communications.

Your next question comes from the line of Yale Jen from Laidlaw & Co.

Again, congrats on the yesterday's fantastic results. I have 2 questions here. The first one is, again, based on yesterday's report, do you anticipate also that for the AFM24 and SNK01 study that later on, you may actually preload the NK cell with the engager or you feel this is not necessarily something that relevant for the AFM24 in solid tumor development?

So we have currently disclosed the 3 approaches forward with monotherapy, with combination with the autologous cell product and with the anti-PD-L1 antibody from Roche. So any other activities -- so we're considering a number of additional options for AFM24 at this stage. Amongst this, obviously, the combination with an allogeneic cell project. So once we are -- have fully validated all these steps forward, we will disclose that.

Okay. Maybe one more question on AFM13. That last year, because of the COVID, you have sort of paused the development in PMF. I just wonder what your current balance sheet and maybe a better environment, would you resume that study going forward? Or do you have any other thoughts?

So currently, we have not reopened this particular arm as in most countries where we are active in, COVID is still massively around. You can read this all over Europe. That's where the majority of the sites are. So we are still in the midst of a wave and not after a wave. So the situation hasn't changed at all.

Your next question comes from the line of Daina Graybosch from SVB Leerink.

I'm going to start actually asking about the AFM24 pharmacodynamics and dosing a little bit more to make sure that I understand. So I think last time you spoke about this, the planned cohort 5 was going to be 1,000 milligrams, and now you're down at 320. I presume what you said earlier that you have this Bayesian approach has changed what you had previously expected. And I wonder if you can get more into the details, specifically what changed from your expectations now as you actually have the data and what might explain that change? And then just to clarify on the pharmacodynamic data. So you have not done the pharmacodynamic analysis of cohort 3 and 4. Is that correct? But you did not see pharmacodynamic engagement in cohort 2? And can you clarify specifically what the pharmacodynamic assays you are completing?

Andreas, do you want to take the questions?

Yes, this is a lot of questions. So yes, I think we initially had planned, and this was when we first presented the study, a relatively aggressive dose escalation step, which would have brought cohort 5, as you said, to 1,000 milligrams. Now already in cohort 2, and we diminished the relative increments as we wanted to make sure that we have more granularity and it really can titrate the recommended dose. If you will or if you look at the relative increments, we are at -- basically doubling the dose starting in cohort 2. So it was really driven by the consideration that we need a better titration and that the initial steps might be too big.

Now in terms of the pharmacodynamic, pharmacokinetic markers, what we said is that on the pharmacodynamics field, we will look at a number of cytokines and the profile of cytokines over time. We will use assays looking at the occupancy of CD16A receptors in circulating our target sales as well as some of the subsets and activation markers within the NK cells.

So this is the pharmacodynamic panel that we are using. And as it was many questions. I don't know whether I missed one, but -- yes.

I'll help you out here, Andreas. So why not yet -- what have we seen on cohorts 1 and 2, so we consider those cohorts to be below the -- a meaningful dose or a relevant dose. And that's why we have been focusing on the analysis on starting with cohort 3 and 4. So that's also the relevance that we started fairly low with the dose escalation. Again, AFM24 is a first-in-class innate cell engager to be developed in a solid tumor indication with a more promiscuous target.

As in effect, we've not seen any of the side effects that were previously reported for TKIs or monoclonal antibodies at the dose levels investigated. We've been moving straighter along in this study. Again, this was all started in COVID. Somehow we need to -- COVID because the vaccination around, but it did impact the original cohort in terms of how fast we could recruit. So I guess, we have made the progress for our Phase I program that's been, at least, at the level of where others have been and others indeed have reported much more difficulties of starting Phase I study during COVID.

So I guess that there is -- we're pulling our expectations. And just now at the level in order to look deeper into what we have achieved. But you're correct. Now we are in cohort 5 and the data is just coming in now.

Great. And then one other question for me. Can you talk about the rationale for an autologous NK cell therapy, which is relatively less experienced in the academic literature for autologous? And also confirm what your starting dose will be for that combination. And if you'll be dose escalating both AFM24 and the cells or you'll be holding them constant?

I'll hand over to Andreas again.

Yes, I can take that. So let's start with autologous. Yes, you're correct, there are clearly less experience and less literature about autologous. Now when we look at the data that NKGen, or previously, NKMax has generated. What we saw first is they had established safe dose of their autologous NK cell product. And they have developed their manufacturing, their expansion capabilities in a way that allows us to use relatively high doses of NK cells on a frequent basis and can continue treatment for a pretty prolonged period of time. I believe in their current Phase I single agent studies, some patients have been on study in excess of half a year.

Now what we also saw, remind you, there was a small Korean study published at ASCO in patients with non-small cell lung cancer, where we evaluated their autologous NK cell product in combination with pembrolizumab compared to pembrolizumab single agent, again, very small patient numbers. But if I recall the data right, there were about 4 responses in treatment-refractory non-small cell lung cancer patients with autologous NK cells plus pembrolizumab.

Now we also looked at the sales in some of our in vitro assays, found them to be very suitable to work in combination with our ICE engager, specifically it was AFM24. So taking all these data together, we believe that it is potential expansion of our opportunities. We have an NK cell product that is safe in the clinic, has an established dose, has shown activity preliminary in an EGFR expressing tumor, which is non-small cell lung cancer. And gives us another opportunity and basically opens a new field. So we believe it's worthwhile also to explore autologous NK cells in addition to allogeneic NK cells.

Now in terms of how the study is designed. The -- currently, the NK cell dose is fixed, 4x10 to the 9 NK cells, which is a dose that was established by NKMax and their single agent studies and we will have a titration of AFM24. Again, we do not necessarily have to wait for the establishment of a recommended Phase II dose in our single agent study, our starting dose here for the NK cell study will be a dose level that has cleared the safety in the single-agent study.

And again, we will have to assess where we are once we are ready to initiate the NK cell study, which what we said will be in the second half of this year.

Your next question comes from the line of Nick Abbott from Wells Fargo.

Congratulations on all the progress. The first one is on the preloaded NK cells. And hopefully, I've got my math right here, but at dose level 1, you've got 100% response rate at a dose that's at the low end of approved CAR-T. So how do we think about this given that CAR-T efficacy is tied to expansion of CAR-T?

Andreas, do you want to take that?

Yes, I can start, and happy if you chime in. So yes, I think what also Katy said yesterday on her call, these data are extremely encouraging because already with a very low cell dose pre-complexed with AFM13 and then followed by AFM13 single agent. You see -- I would really say striking responses given also the pretreatment characteristics, the tumor load of these patients. So this really tells us that these NK cells with the targeted approach can eradicate even at very small cell doses significant tumor masses.

Now what also has been shown is that these NK cells that we are using in our collaboration with MD Anderson produced by the specific activation protocol acquire some kind of memory like NK cell features, which allows them to persist for a prolonged period of time, and these are data that I just generated. So we do have some persistence, we probably also have some proliferation, definitely not to the degree that CAR-T cells have.

Another reason to go into higher doses, and that is also what Katy alluded to yesterday is to deepen the response, but also to increase the persistence of the NK cells beyond C1 or 2 infusions that we have given and to stabilize or to prolong these responses. And again, very small patient numbers, but what we have seen is with the very first patient at the higher cell dose of 1/10 to 10th to the 7. While this patient went into complete response already after the first cycle. So if you will, even more active, again, what was specifically encouraging is this is a patient that not only failed all of the classic pretreatment, including chemotherapy, PD-1 and Adcetris, but this patient, in fact, has a history of having received a CD30-targeted CAR-T product and has not responded to the CAR-T product. Again, telling you that the mechanisms of action and the capability of the innate immune system and the T cell system probably are different, and I think, are giving us very early, very encouraging data.

And then I believe you have an option to license the cord blood NK cell technology from MD Anderson. So how do you think about that as a strategy versus Artiva and does the company have the resources or interest to become a cell therapy company?

Yes, I'll hand that question back to Denise.

Sorry, can you hear me?

Yes.

Okay. Sorry, I had issue with the connection. Will you repeat the question?

Yes. It is -- I believe you have an option to license the cord blood technology from MD Anderson. And then you also have the Artiva collaboration. And so the question is really, going forward, does the company have the resources and/or interest to become a cell therapy company? Or would you continue collaborating with cell therapy experts?

Yes. Great question. So as far as MD Anderson goes, we've always had the option to take the license for the worldwide rights. And at the start of the clinical study, we felt that, that was the prudent time and we made the decision to take that option for the license. Such that the clinical data held and was very good that we could potentially move that forward and take that product ourselves. And so that's really providing optionality. We also really very much value our collaborations with NKMax and Artiva. And those are focused in similar but different areas and provide us with a multipronged approach to identify optimal ways to combine our engager with NK cell therapy. And at any point in time, we could have control of the -- obviously, the MD Anderson NK cell product or we could pursue a more strategic partnership with an NKMax or NKGen, actually, they just changed their name, or Artiva. So we're just going to let the data drive our decision moving forward. And I think it's still early days. It's a very, very promising. And we haven't made the strategic decision that we're 100% going to become an NK cell company, but the data is promising and would lead us to consider that at some point in the near -- in the future after more data is generated from all of these collaborations.

Your next question comes from the line of Yale Jen, Laidlaw & Co.

Thanks for taking up the follow-up questions and just some very brief ones. First one is that is there also an update on the ASCO for the CB-NK AFM13 combo in place?

Angus?

Go ahead, Denise.

I can take that. Yes, okay, Katy Rezvani had a session. Very similar to this session that she had at AACR, where it's focused on cellular therapeutics. We are not confirmed as to whether or not her panel discussion and presentation would include an update on the clinical trial that we're doing with her, but it certainly is an option, but we don't have confirmation of that just yet. It may be there, but we're not sure yet.

Okay. And maybe just a quick one that she mentioned yesterday that if the data is still very robust going forward for the Phase I study, it is possible to advance to Phase III. Any comments on your side?

No, we don't want to comment on this at this stage. I guess that for the time being, we want to finish the dose escalation, identify the optimal dose for the cells. And with that information, then decide on how to proceed.

Your next question comes from the line of Maury Raycroft from Jefferies.

Congrats on the progress. Just a quick one on AFM24. Just clarifying, you commented that at the initial doses so far, you're seeing a better safety profile than what you would expect with PKI or cetuximab. Just wondering if you can comment more on what differences you're referring to? And would you expect that to be independent of the PD biomarkers.

Andreas?

Yes. As we said, we would like to present all the data once we have established pharmacodynamic active dose. What you can see is that we have not seen some of the hallmark side effects, for example, skin toxicity or magnesium losses or so, which you would expect with this EGFR. But again, as we progress through, we will collect more data. But I think it's so far in line with our preclinical study, especially with cynomolgus monkeys. Remind there, even with the highest dose, we did not see any, for example, skin toxicities, which is in line with the completely different and innovative mechanism of action of this drug.

And the second question or the second part was, again, relating to PD. Can you repeat it?

Yes. Just wondering if the safety effects, I guess, do you view -- is that independent of the PD biomarker assays that you're doing? Or should they kind of go hand in hand?

Yes. I think we -- again, based on the mechanism of action and on the PD panel, we would not expect to see a direct correlation between any potential side effects. And PD markers, it's a new field. But again, the NK cell, as we have learned from AFM13, also from Katy's study, is pretty focused, I would say. And we have not seen in any of all our NK approaches, for example, a significant organ toxicities. And we expect that the same will be true for AFM24.

Got it. Okay. That's really helpful. And then one quick question on the AFM13 pivotal study in PTCL. Just wondering if -- at this point, if you guys could provide any more clarity on enrollment expectations and whether the final data could be second half of this year or first half of '22?

Andreas, do you want to take that?

Yes. Yes. What Adi mentioned already around cohort C is the TMF cohort. We are still in the middle of the pandemic situation. U.S. is getting a little bit better, but Europe is still heavily affected. So as we said already during the interim analysis around the interim analysis, currently, we do not feel comfortable to give a very concrete date in terms of enrollment.

Remember, protocol-mandated cohort B was on hold while we will be conducting the interim analysis. So cohort B has now been reopened. But I think it's too early to assess the full impact. And then make a concrete prediction of the time line. So I think if we have reopened cohort, be it for a little bit longer time and then we have a better grasp on the COVID situation, we should be in a position to give you a more granular answer than we can right now.

Thank you very much. And I guess there are no further questions, correct?

We have no further questions, so if you wish to continue.

Yes. Thanks very much. Just I want to thank all, everybody who was attending today for their listening in and questions and look forward to further updates in the next 6 to 9 months as we proceed. I wish you all have a nice day, and continue to have good meetings with us. Thank you. Bye-bye.

Thank you. That does conclude your call for today. Thank you all for participating, and you may now disconnect.