Good day, and welcome to Affimed Second Quarter 2020 Financial Results and Corporate Update Conference Call. At this time, all participants are in a listen-only mode. As a reminder, today's conference is being recorded. I will now introduce your host for today's conference, Alexander Fudukidis, Head of Investor Relations at Affimed. Please go ahead..

Thank you, [Shirley] [ph]. I would like to welcome and thank you all for joining us today for Affimed's second quarter 2020 financial results and operational progress conference call.

Before we begin, I would like to encourage everyone to go to the Investor Relations section of Affimed's Web site to find the earnings release and related financial tables. We also posted slides on our webcast, that's for our discussion today.

On the call today we are joined by doctors Adi Hoess, our Chief Executive Officer; Andreas Harstrick, Chief Medical Officer; Arndt Schottelius, Chief Scientific Officer; and Angus Smith, our new Chief Financial Officer, who joined us in July. We are also joining by Dr. Wolfgang Fischer, our Chief Operating Officer; and Ms.

Denise Mueller, Chief Business Officer. They will also 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 new information becomes available in the future.

These forward-looking statements are subject to risks and uncertainties, and actual results may differ materially from those expressed or implied in the 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 will turn the call over to Adi.

Adi?.

Thank you, Alex. Good morning, everyone, and thank you for joining us for our second quarter business update call. Today, we have some updates to share with you on our operational progress as well as on our financial results.

While we are still in the middle of a serious global health pandemic and a challenging economic downturn, at Affimed, we are quite confident that the steps we are taking in advancing our science and moving our pipeline forward are beginning to yield data that demonstrates the long-term potential of our innovative approaches and products.

COVID-19 continues to affect the scientists around the globe, and we hope that you and your families are well and safe. We are observing some impact of COVID-19 on the progress of our clinical studies. However, [since] [ph] last time, we are taking great efforts to minimize them.

As a result, we have been able to continue our progress on the clinical studies of AFM13 in the peripheral T-cell lymphoma and of AFM24 in EGFR-positive tumors, and which is very exciting to us, Genentech dose the first patient with an RO7297089, which as you remember is the BCMA/CD16A innate cell engager.

We are also making good progress on our preclinical pipeline. For our lead candidate, AFM13, our study in patients who have relapsed or refractory peripheral T-cell lymphoma in exhausted available standard of care treatment, are now being treated with AFM13 as a single agent.

We are executing according to our development timelines, and as previously stated, expect to complete the predetermined interim analysis in mid 2021. We are also looking at options to enhance AFM13's efficacy beyond monotherapy.

The first of these options is the combination with allogeneic NK cells in a study is conducted at the MD Anderson Cancer Institute under an IST. MD Anderson Web site now shows that the study is enrolling, but the initiation is impacted by the ongoing COVID-19 pandemic in Texas. First patient in the study is expected as soon as this situation improves.

For AFM24, we disclosed that we have completed the first cohort of our dose escalation study without any dose-limiting toxicity, and we are currently recruiting into the second dose cohort. We have all four plan sites active and recruiting.

Following the completion of the dose escalation phase of the study, we have the option to enroll patients into tumor-specific expansion cohorts, where we will look for single agent activity in a number of well-defined tumor types.

In addition, we are planning to initiate combination studies with checkpoint inhibitors, and we will be providing updates as the program continues to make progress. We are very pleased with the continued progress in our collaboration with Genentech.

Importantly, the Phase 1 clinical study with the BCMA/CD16A innate cell engager is now enrolling patients. This achievement represents the third innate cell engager to enter the clinic, and triggers a milestone payment to us during the third quarter in an amount that we are not able to disclose.

Last month, Angus Smith joined us as Chief Financial Officer. Angus will introduce himself later and discuss our financial position and the flexibility, provide us to continue to execute on our strategy and drive the future growth of our company.

During the Annual General Meeting of Shareholders, which was held in August 4, we're happy to report that all proposed agenda items were approved. This includes the addition of Dr. Annalisa Jenkins and Harry Welten to the supervisory board as new members.

Annalisa is a visionary leader who knows how to translate science from bench to bedside, and Harry is an accomplished financial executive who will help drive value-creating strategies for the company. These additions to the supervisory board further strengthen the company's industry know-how, experience and diversity.

As it has only been a month-and-a-half since we last spoke to you, we thought we would focus today's discussion on company achievements thus far and what gives us confidence in our signs, update you on our programs, and allow plenty of time for Q&A.

With that, I will now hand over the call to Andreas Harstrick, our Chief Medical Officer to give you a brief update on our clinical stage programs.

Andreas?.

Yes, thank you, Adi for the introduction and thank you all for joining us today, and I'm happy to give you an update on the progress in our clinical programs that we made over the last three months.

As you all are aware, COVID-19 pandemic is still present globally, and it continues to pose challenges for the conduct of clinical trials and the enrollment of patients.

The two guiding principles we are employing at Affimed is to ensure patient safety on the studies and to ensure trial data integrity, and this is in line, I think with our guidance given from all competent authorities.

Within this framework, however, the Affimed team is very proactively working with all of our participating sites to make sure that our innovative treatment is still available for patients in need of new therapeutics, and that we minimize the impact of COVID-19 to a minimum possible.

One important achievement in this regard is that we were able to secure drug supply for all of our ongoing studies, and can ensure uninterrupted treatment of all patients. To go into more detail, let's start with AFM13, our most advanced program first.

As you know, AFM13 is in registration directed of Phase 2 study AFM13-202 treating patients with relapsed and refractory peripheral T-cell lymphomas, who have exhausted all available standard of care options. The enrollment into the study is at a steady state.

We were able to activate 54 sites to our contributing patients in 10 countries around the globe. As you know, the study has Simon 2 Stage design with a pre-planned interim analysis after 40 patients in the pTCL cohorts, and as Adi said, we are confident that we will have the data from this interim analysis available by the mid of next year.

There was also a third cohort, or there is a third cohort in this study for patients with transformed mycosis fungoides, so a cutaneous form of T-cell lymphoma. This third cohort with mycosis fungoides was never part and never intended to be part of the registration program.

It was a proof-of-concept cohort only, and for COVID-19 related restrictions, the enrollment into this cohort is currently on hold.

As Adi also mentioned, we are continuing to make progress in our collaboration with MD Anderson Cancer Center, where we have an active IND for our first Phase 1 study of AFM13 in combination with allogeneic or natural killer cells.

As Adi said, the current status at the MD Anderson web page is recruiting, and we know that patients are currently screened and considered and we are expecting to the enrollment of the first patient as soon as COVID-19 related restrictions at MD Anderson lift up.

Now, let's move to our second program AFM24, as you know, by specific tetravalent molecule targeting both CD16A to activate natural killer cells and macrophages and the EGF receptor on solid tumors, as this compound is in a Phase 1, dose escalation part of the 101 study, and we are happy to report that we were able to activate all four pre-planned sites and all four pre-planned sites are contributing patients.

As we disclosed earlier, we have completed our Cohort One without observing dose limiting toxicities and are actively recruiting into dose cohorts to.

With this, I close the overview of clinical progress and I'm happy to hand over to my colleague, Arndt Schottelius, Chief Scientific Officer who will review with you some of our preclinical data that make us so excited about the opportunities that we can create for patients with ICEs and activating the innate immune system.

Arndt, please?.

Thank you, Andreas, and thank you all for joining. In the next few minutes, I would like to summarize, as Andreas mentioned, the preclinical and clinical data observed so far with our Innate Cell Engagers providing evidence that these molecules are potent and safe drug candidates.

I'll start by summarizing the data showing that our ICE is a potent molecule. As you see on slide five, if we take AFM13 as an example, AFM13 has been shown strong single agent anti tumor responses and T-cell lymphoma with an overall response rate of 50%.

The molecule has also shown promising signs of broad clinical development potential in augmenting other IO therapies such as PD-1 inhibitors. For example, in the Hodgkin lymphoma Phase 1b study, we've seen an impressive overall response rate of 88% with a complete response rate of 42% and 46% in the local and the central read respectively.

In the low part of the slide, we've also highlighted for you presentations of the studies past and in the future.

Additionally, our own experiments and the work with MD Anderson, we have seen promising preclinical data showing that the company With the adoptive transfer of NK cells enhanced the immune response of AFM13 leading to prolong survival in the respective mouse model, and as we mentioned the Phase 1b studied at MD Anderson is now in the last stages of preparation.

If we go to slide six, you see that in our preclinical studies with AFM24, we saw potent killing of EGFR positive tumor cell lines mediated by two distinctive mechanisms of action, potent ADCC or antibody dependent cellular cytotoxicity is seen irrespective of the mutational status of the tumor cells.

And we see potent killing mediated by ADCP or antibody-dependent cellular phagocytosis in tumor cells with high and low EGFR expression. Importantly in cells bearing the KRAS G13D mutation AFM24 shows preserved killing, potent killing, or ADCP or phagocytosis whereas disabilities lost for established treatments.

For the anti-BCMA, CD16 or RO729 formerly known as AFM26 molecule, we also saw very good potency in scinote monkeys, whereas a dose dependent killing of BCMA positive plasma cells, it was observed.

We believe that the observed improved potency is mediated by the dual mode of action of approach; the innate cell engagers are employing NK cells and macrophages to kill tumor cells and thus acquire a two-pronged mode of action of antibody dependent cellular cytotoxicity and antibody dependent phagocytosis to fight cancer.

Indeed this dual mode of action is differentiated from RNA cell targeted approaches, as these specifically activate NK cells only. RNA cell engages work and low expression levels.

The potency is thus, independent of the surface target expression, and you see this we continue in slide six with AFM13, we learnt that there was a broad range of cell lines that express different levels of tumor antigen, and we have not observed any dependency of target expression to the potency of the molecule.

The same holds true for AFM24 and the anti-BCMA engagers. Preclinically both molecules have shown high potency across a wide range of EGFR and BCMA surface expression, including at low target expression levels.

This implies that more patients could respond to treatment with RNA cell engager versus an antibody drug conjugate or ADC as the mechanism of ADCs have been shown only to rely on certain levels of target antigen, thereby missing those tumor cells with expression levels below the ability of the ADC to bind to target cells.

As we move on to slide seven and report on the safety front preclinically, our innate cell engagers demonstrate the low cytokine release. Some examples of this are the IND-enabling toxicology study in cynomolgus monkeys, which consistently showed no meaningful increases in serum cytokines.

For example, at the June, Virtual ACR Conference, a preclinical poster presentation on the RO729 molecule of Genentech short potent cell killing in tumor cell lines implying NK cells as effector cells with minimal increase in cytokines.

Also, a four-week safety study in cyno monkeys showed a favorable safety profile with no cytokine release or adverse findings FD15 one, five and 50, so five zero mixed per kick tested dose levels, and in the case of AFM24, only a transient increase in IL-6 was observed that was fully reversible within 24 hours of no signs of cytokine release was observed that would lead one to believe that there is risk of a cytokine storm in patients.

Important to note here is that none of the clinical studies of AFM13 have revealed any significant increases in serum cytokines. This data indicates that our ICEs have a tolerable and good safety profile.

Taken altogether, this data suggests that RNA Cell engagers are potents able to engage with low levels of antigen expression and has thus far demonstrated a good and tolerable safety profile.

Now in order to maximize the opportunity for molecules in addition to clinical development as monotherapies, we are also pursuing combinations with natural killer cells and other treatments such as checkpoint inhibitors such as PD-1 and PDL-1.

We go to slide eight, and first let me comment on our combination approach with NK cells, as you see on the slide there is evidence show that high NK cell numbers are associated with better outcomes. For example, patients with metastatic cutaneous melanoma have improved survival rates, if their tumors show evidence of NK cell infiltration.

We also know that patients with diffuse large B cell and follicular lymphomas treated with anti CD20 antibodies that have low peripheral NK counts tend to have poor survival. We are seeing that one of the limitations in treating patients is that they don't have the appropriate amount of NK cells.

So, we are working on supplementing NK cells through adoptive transfer and are currently assessing different approaches, as you can see on slide nine. As we go to slide 10, and as discussed earlier the improved tumor cell killing by loading NK cells with our ICEs.

As you see on the graph for in vitro data, on the right hand side of slide 10, it will be investigated in the MD Anderson Phase 1 study and CD30-positive recurrent or refractory Hodgkin non-Hodgkin lymphoma patients.

The preclinical data that we share here and I've shared before leads us to believe that we can expect to see an improvement in the efficacy of an innate cell engager AFM13 through the addition of NK cells. I am encouraged by the synergistic potential of combining our ICEs with NK cells and checkpoint inhibitors.

We're currently evaluating the opportunity on our developing clinical plans for these combinations with AFM24. Finally, let me just briefly summarize the recent posters presented in ASCR.

As a reminder, our AFM24 poster demonstrated its distinct mechanism of action different from other EGFR signaling inhibition approaches, potentially able to provide benefit to a broad range of cancer patients.

And in the case of the joint poster of Genentech, the pre-clinical pharmacology and safety of the BCMA/CD16A innate cell engager shows potent cell killing in tumor cell lines, employing NK cells as effector cells, minimal increase in cytokines, suggesting a low risk of cytokine release syndrome.

We hope this background was helpful for you, and I will now turn the call over to Angus to introduce himself and provide an update on the financials.

Angus?.

Thank you, Arndt. Before I discuss our financial highlights for the quarter, let me just say that I am thrilled to [technical difficulty] and I look forward to working with our talent [technical difficulty] exciting pipeline.

Turning to the results for the quarter, 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 will present in this call unless otherwise noted, will be in euros. We ended the second quarter with cash, cash equivalents and current financial assets of €92.6 million, compared to €104.1 million on December 31, 2019.

During the quarter, we received net proceeds of approximately €20.8 million under our aftermarket or ATM program. Based on our current operating plan and assumptions, we anticipate that our cash, cash equivalents and current financial assets will support operations into the first half of 2022.

Net cash used in operating activities for the quarter ended June 30, 2020 was €15 million compared to €5.6 million in the second quarter of 2019. The second quarter 2019 net cash used in operating activities included a milestone payment to the company from the Genentech collaboration.

Total revenue for the second quarter of 2022 was €2.9 million compared with €4 million in the second quarter of 2019. Revenue in 2020 and 2019 predominantly relates to the Genentech collaboration.

Revenue from the Genentech collaboration in the second quarter 2020 was comprised of revenue recognized for collaborative research services performed during the quarter. R&D expenses for the second quarter of 2020 were €11.7 million compared to €11.5 million in the second quarter of 2019.

Expenses in 2020 relate predominantly to our AFM13 and AFM 24 clinical programs as well as to our early stage development and discovery activities. G&A expenses for the second quarter of 2020 were €2.6 million, compared to €2.3 million in the second quarter of 2019.

The increase is primarily related to higher SOX compliance costs, legal, consulting and audit costs. Net loss for the second quarter of 2020 was €12.2 million, or €0.16 per common share, with net loss of €10.3 million or €0.17 per common share during the second quarter of 2019.

The weighted number of common shares outstanding for the quarter ended June 30, 2020 was 79.2 million. I will now turn the call back to Adi.

Adi?.

Thank you, Angus. As you can see from our presentation today, we're taking advantage of the knowledge that we've gained in the field of innate immunity and are applying it to our programs going forward.

This experience in working with innate immune system is something that we have uniquely established at Affimed and is helping us in guiding the design of unique therapies, which now have the potential to address very different kinds of cancers.

I just want to point out here that the EGFR is expressed in more than 10 tumors and that gives us a lot of optionality how to take this molecule forward. We're pleased with how things are moving forward for both our clinical and preclinical programs, especially in the current environment. Our preclinical programs are in track.

AFM13 and AFM24 are moving forward according to plan and Genentech is moving things forward with the anti-BCMA/CD16A innate cell engager. With our inflection points for the next 1.5 years were AFM13. We've mentioned that we want to present the interim data in peripheral T cell lymphoma around the middle of next year.

We've been successful in our collaboration with MD Anderson moving forward the combination of AFM13 and cord blood-derived natural killer cells. As we've said, we're ready to start our MD Anderson is ready to start and we hope to report first patient in and we will provide update as we move forward.

For AFM24, we're in the midst of dose escalation in order to generate safety and activity data. This is quite exciting for us because it's a drug with a very differentiated profile as compared to the other moieties currently used in targeting EGF receptor.

Now with the dose escalation and establishing the safety, we obviously will have the recommended Phase 2 dose coming up in order to then do dose cohort expansions, but as we've mentioned earlier as well we're also planning early on to move forward into combinations. We're very happy with the progress in the Genentech collaboration.

We've just provided the next update for the BCMA/CD16A engager with multiple other programs ongoing and things go well depending on program progression we can bring in additional milestone. And for our newest additions to the pipeline with AFM28 and AFM32, we're our starting the IND-enabling studies, so that we can have an IND filing first for AFM28.

Finally, before we open the session for Q&A, I would like to thank all our employees for their contribution and express our gratitude -- my gratitude in particular for our investigators and the clinical sites, the patients and all their families, and our investors, who are supporting us in our efforts to develop these innovative treatments for cancer patients.

It is through the combined efforts of all of you that keep us on the path of discovery and innovation. I'm now happy to close the presentation and we're open now for questions. Thank you..

Ladies and gentlemen, we'll now begin the question-and-answer session. [Operator Instructions] First question comes from the line of Maury Raycroft from Jefferies. Please go ahead. Your line is now open..

Hi, good morning, everyone. Congrats on the progress, and thanks for taking my questions.

To start off, just wondering for AFM24, I'm not sure how much you can say on this, but just wondering if both patients in cohort two have been dosed, and if you can talk more about the timing of dosing between patients? With the four sites activated, can you provide any more perspective about enrollment pace going forward?.

Andreas, can you take the question please?.

Yes. So, there were multiple parts of the questions. I hope I got them all. So the Phase 1 study of AFM24, as we said, we are recruiting into second cohort. We have not yet disclosed how many patients. It's a standard 3/3 design, which was a Bayesian dose modification, but that's basically what it is.

In terms of timing between the patients, there is a mandatory eight-day waiting period between patients. So, they cannot be treated all at the same time, but will be [staggered] [ph] with eight-day intervals, and there wasn't -- last part of the question around the four participating sites..

Right, yes, just wondering if you can provide any more perspective about enrollment pace going forward?.

Yes, currently the enrollment pace is as pre-specified by the protocol also. All sites are very active in screening patients, and as we said, all sites have already contributed patients..

Got it. Okay, great.

And then, also for AFM24, just checking if you can say more about the tumor types that you're screening for the study, and if you can also provide more perspective into the Checkpoint inhibitor and combo plans at this point?.

So, for the tumor types, in the dose escalation part, we are accepting all patients with -- or all histologies that are EGFR expressing, and where the patient has exhausted the respective standard of care treatments.

As Adi mentioned, this is a wide variety of potential tumors, probably the two most prevalent tumors would be colorectal cancer and non-small cell lung cancer, and these are the two histologies, where we would expect probably the majority of patients in the Phase 1.

Having said that, the dose escalation part would also be open for other EGFR expressing tumors, like for example, head and neck cancer, gastric cancer, or other solid tumors.

Now, once we have defined our dose-limiting toxicities, or if there are no dose-limiting toxicities, we have defined the recommended Phase 2 dose, we will enroll into tumor specific expansion cohorts, and these expansion cohorts are currently in the process of being defined.

Now, for our PD-1 combination plans, based on the interesting data, we have seen with PD-1 in combination with AFM13, which Arndt referred to, was a very encouraging complete response rate in excess of 40%.

We plan to have a combination with a PD-1 or PD-L1 inhibitor open rather soon probably in parallel to the last cohorts of the dose escalation of the single agent studies. So, it will be more or less a parallel development that we are anticipating right now..

Great. Okay, thanks for the additional perspective..

Any follow-up questions, Maury? Okay, we will now proceed with the next question. Next question comes from the line of Jim Birchenough from Wells Fargo. Please go ahead, Jim..

Hi, guys. Congrats on all the progress.

Maybe just a first quick question for Angus to start him off, collaborative research revenues, is that expected to be a stable number between $3 million to $4 million level, or is there any reason that might go off as programs progress, and as we think about the milestone that got paid in the third quarter, is it a simple matter to back out the assumptions around collaborative research revenues and that will give us some sense of the milestone, given that you can't say it exclusively?.

Yes, thanks, Jim, for the question.

So, our revenue numbers fluctuate from quarter-to-quarter based primarily on the number of hours that we're working on [through] [ph] various Genentech programs that are in progress, and you can see just looking back at the last several quarters, we've been fairly range-bound and call it $2 million to $5 million zone.

When you see increases it's typically a result of point-in-time milestone payments that we received.

So, this milestone payment that we discussed today that will hit in the third quarter will likely increase our revenues in the third quarter, and that would be sort of an add-on to the range that you've seen over the last several quarters of -- again kind of to the $5 million -- €2 million to €5 million rather..

Got it. Okay, that's helpful.

And then maybe just on cohort one for AFM24 and what we might learn from that cohort? Can you remind us if you're doing pre and post-biopsies and what kind of translational work you might be doing, and how that might inform the ability to recruit innate cells to the tumor site?.

Yes. So, in the dose escalation part, we do a pre-treatment biopsy post or on-treatment biopsies are optional. We do have a significant correlative science program looking at peripheral activation markers of NK cells as well as on cytokine profiles. Once we are in the expansion phase, so we are recruiting into tumor specific cohorts.

I think this is the part where we will get most of the correlative science as we have more homogeneous patient population. We maintain our requirement for a pre-treatment biopsy and we'll have posts or on-treatment biopsies in selected cohorts..

And then just given the comments on the variability and peripheral NK cell populations, is there any sense in screening patients for their NK cell levels given that patients who screen low may not have adequate NK cells or macrophages to recruit or you feel like within the variability of innate cell in the blood that that you'll be able to have an effective treatment and it's not worth screening for that variable..

I think currently it would be premature to -- depends on what you mean with screening. So, we are definitely determining the levels of circulating NK cells and also looking at some of their characteristics [technical difficulty].

I think we currently do not have enough data to define a cutoff or a threshold and this may very well vary between tumor histologies and also be dependent on the infiltration of NK cells in the tumor microenvironment variable which we have seen in our AFM Columbia study to have some impact on the likelihood to respond to the patients.

So, I think in the beginning of the program, we will be opened for all comers. We will assess all of these important biomarkers and then based on the activity data and the readouts that we are seeing we may modify as the program defining certain thresholds, but currently I think it would be premature to do that..

And maybe just a final question, just the MD Anderson collaboration is focused on cord blood-derived NK cells.

Is there any thought through other NK cell sources including potentially iPSC derived NK cells?.

Adi, you want to take this question or should I take it?.

No, well, Andreas, why don't you go ahead?.

Okay.

Yes, you're right when cord blood derived NK cells is one source of NK cells, and if you watch the field of NK cell based approaches, especially as the fields around companies, and institutes providing different sources of NK cells, there is definitely speed picking up and there is a variety of options to look at, and this is what we do not only from our side, but we have also received proactive inquiries of potential working models together.

So, we are looking at the entire NK cell field and then evaluate various options there..

Great, thanks for taking the question guys..

Maybe as a great comment, so we see this cord blood-derived NK cells already quite advanced in clinical development. So they have already been many patients treated while with the iPSC is currently, there is still a safety to be determined and obviously in combination we learn more on functionalities.

So this is somewhat to us on how functional and iPSC-derived versus a peripheral in case are less, and it's good to see the first candidate and so we are quite not only happy, but we've checked so many different options at the moment for NK cells and we are indeed very convinced about the activity of the core blood derived cells from MD Anderson..

Thanks, Adi..

Thank you. Our next question comes from the line of Ike Oji from BMO Capital. You line is now open. Please go ahead..

Hi, good morning, gentlemen. Thanks for taking my question. This is Ike on for Do Kim.

Just a couple regarding that BCMA innate engager, I understand that you've got limited visibility on the entirety of their clinical developed pathway, but if you can provide any type of insight in terms of what Genentech kind of has planned made in terms of could it potentially pursue an accelerated pathway for the asset? And secondly, again you don't provide complete details on deck milestone payments, but if you can provide some additional perspective on what the future milestones, but asset might hold in terms of Phase 2, Phase 3 things of that sort.

Should we expect increasing size of value for each milestone payments, that'd be helpful for us? Thanks..

Adi.

Maybe I take the question on the pathway and then hand over to you with the milestones?.

Yes. Please go ahead, Arndt..

So thanks for the question. I mean, as you already correctly say we cannot really speak in detail for Genentech, but we can share with you I think your awareness.

Of course, licensing this molecule was a big part of the deal we did with Genentech, they're obviously excited about the strong differentiation potential of the molecules were demonstrated at ACR at the poster just to review again. The very strong preclinical cell killing selective no cytokine release.

Very good safety profile and good pharmacodynamic marker specific BCMA plasma cell killing in the cyno monkey. So, despite the also recent approvals of the income, first incomers in the space, I would say that kinetic shares are excitement with a differentiation potential, and a way for a potentially best-in-class molecule. Maybe I'll leave it there.

I think, it's a clearly strongly, clinically-validated space, and I think this molecule will enable Genentech and we as their partner to have a strong position in the space..

Yes, regarding the financial. So, I just want to recall the deal, when it was signed. So we received $96 million in upfront cash.

And as a total of more than $5 billion in milestones that are in different categories, so there are a pre-tentative milestone payment that are indeed multiple clinical milestone payments regulatory and sales milestones and on top, we can receive royalties, which as we described are on the higher end of what you would expect for the early nature of the license agreement.

Beyond that, we're able to disclose any further details. Unless Genentech would allow us or the rush would allow us to do so, usually and that's just the general statement is that the payments will increase the further the program progresses..

Okay. Thank you for that. And just one more quick question, I think I might have misheard it, and this is in regards to AFM24, I believe you mentioned that there was a patient that had increased IL-6 cytokine levels that was resolved over 24 hours.

Just curious, was that self-resolving, or that patient received IL-6 inhibitor?.

Yes, Ike, thanks for brining that up, and the clarification. So, the transient IL-6 [00:00:07] was reported in the IND-enabling cyno tox study what you referred to the AACR poster. Indeed, we saw with the dosing a kind of moderate peak that quickly went down, was completely resolved without any treatment.

Obviously, one doesn't do that in the -- because this is cyno tox study, and again, when we see this in the context because it was transient and fully reversed leads us to the conclusion which of course will be looked at carefully in patients that we should not expect any kind of cytokine release syndrome..

All right, thanks for that clarification..

Sure..

And your next question comes from the line of Yale Jen from Laidlaw & Company. Please go ahead. Your line is now open..

Hello..

Yes, hello. Yes, hi, can hear you..

Hi. Sorry, that my headsets fell off. Thanks for taking the questions. My first question is that for the AFM13 for the registration study that it's a Simon 2 set-up.

So, what might be the threshold of ORR in the 40 patients and so the internal result before you can move forward? So just curious what -- any information you can reveal on that front?.

I am afraid we cannot give a concrete response rate. It's based also on the Bayesian design, so there's some interdependence of response rates, but we usually do not disclose threshold, but it's a classical Simon two-stage design..

Okay, no problem.

And also just curious in terms of AFM24 that you are dose escalating, but at least based on the animal data, is any thought when you might start to see the potential effective dose to start?.

I think currently it's not possible to predict when we will have the optimal biologically active dose as there are number of covariants like finding sites for CD16, finding sites for EGFR, and then distribution, and as you know, the animal model especially in terms of pharmacokinetics and pharmacodynamics are very difficult to translate the relevant tox species, and you have to add that's only tox species is the cynomolgus monkey.

However, we do not have any cynomolgus monkey tumor models available. So, we cannot really bridge between what we see as a toxicology studies and then what we would see in terms of efficacy for tumors. So, it will be something that we will have to define in our clinical program..

Okay, great.

Maybe let's take in one last question here that in terms of adoptive NK cell from cord blood driven NK cells, first of all could that be potentially used in solid tumor, and any comments in terms of regarding that possibility?.

This is as Adi said something that we are actively looking into, well starting out with lymphomas obviously with AFM13 targeting CD30, but our vision is that also for AFM24, we will develop certain development options in combination with NK cells. Could be cord blood derived NK cells, could be NK cells from another source.

That is something that we will define, but the intention is also to have a program where AFM24 would be partnered with exogenous NK cells..

Okay, great. Thanks. Appreciate it and congrats for the all the progress this far..

Have no further questions at this time. For any closing remarks, please go ahead speakers..

Yes, thank you again for listening in and following our updates. The progress is coming smoothly along despite that we are affected by COVID. We have friends in the team significantly in order to address any issues that may relate to the conducting of these clinical trials, or to the interactions with the specific sites.

So, we are very happy to be able to -- have been able to address any of the issues that have been arising, and I indeed want to thank again the entire team here at Affimed for managing all that through this difficult times.

We are quite excited that we can move forward these programs, either it's monotherapies, and now looking at different options of combination. If you've heard, we are focused on natural killer cells and checkpoint inhibitors, in particular, PD-1s or PDL-1s.

So, we feel that we have with the multiple programs addressing different targets we can provide a cadence of data over in the next quarters and years, and very happy to report any additional updates as we move along. Thanks a lot again for listening in, and all the best. Goodbye..

Thank you. And that does conclude our conference for today. Thank you all for participating. You may all disconnect. Stay safe everyone..

Thank you. Bye-bye..