Affimed Q3 2021 Earnings Call Transcript

Quartr
Provided by Quartr
November 10, 2021

Key Takeaways

  • The registration-directed AFM13 monotherapy study in relapsed/refractory peripheral T-cell lymphoma remains on track for full enrollment in H1 2022, and an expanded MD Anderson trial (including Hodgkin and CD30+ non-Hodgkin patients) will report updated safety and efficacy data at a mid-December event.
  • AFM24 has been assigned a 480 mg recommended Phase II dose based on safety, PK/PD and target-saturation data, with monotherapy expansion cohorts opening by year-end and combination studies with atezolizumab and autologous NK cells expected to complete first dose escalation in H1 2022.
  • AFM28, a first-in-class CD123-targeting innate cell engager for AML, is gearing up for an IND submission in H1 2022 and the initiation of a Phase I clinical trial in H2 2022.
  • As of September 30, cash and equivalents stood at €198.7 million, after a Q3 net loss of €17.1 million, providing runway into the second half of 2023 under current operating plans.
  • Affimed’s three-pronged development strategy—monotherapy, NK cell combinations and checkpoint inhibitor combinations—is designed to deliver a continuous flow of clinical data across multiple programs through 2022 and beyond.
AI Generated. May Contain Errors.
Earnings Conference Call
Affimed Q3 2021
00:00 / 00:00

There are 10 speakers on the call.

Operator

Thank you, Jonathan, and thank you all for joining us today for our Q3 2021 results and operational update call. Before we begin, I'd like to remind everyone that we issued the relevant press release earlier today and that it can be found on the Investor Relations section of website. On the call today, we have the following members of our management team: Doctors Adi Hurst, our Chief Executive Officer Andreas Arstrik, our Chief Medical Officer Arndt Sutilius, our Chief Scientific Officer Wolfgang Fischer, our Chief Operating Officer Ms. Denise Miller, our Chief Business Officer and Angus Smith, our Chief Financial Officer. The whole team will be available for the Q and A session.

Operator

Update. Before we start, I will quickly go through the Safe Harbor statement. Today's discussion contains projections and forward looking statements regarding future events. Update. These statements represent our beliefs and assumptions only as of the date of this call.

Operator

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 risks and uncertainties, and actual results may differ materially from those expressed or implied in these statements due to various factors, including, but not limited to, those identified under the section entitled Risk Factors in our filings with the SEC and those identified under the section entitled Forward Looking Statements and the press release that we issued today and filed with the SEC. With that, I'll turn the over to Adi. Adi?

Speaker 1

Yes. Thank you, Alex, and good morning, everyone. Thanks indeed for joining our Q3 update call, and I'm very pleased with the continued progress towards our goal acquisitions as for several potential value creating milestones through the end of 2022. Today, in addition to providing an update efforts. On our leading programs, we will spend a little bit of time to introduce you to AFM28, our most advanced pre clinic in Edseling danger, which is expected to enter the clinic in 2022.

Speaker 1

Update. On Slide 3 of the presentation that we made available to accompany our call today, we summarized Affimed's strategy for developing our innate selling actions. We introduced our 3 pronged development strategy to you about a year ago. Update. As we said to you, then we believe this strategy allows us to explore different development approaches, thereby increasing the probability of access for each of our molecules.

Speaker 1

What we have learned to date about the safety of our molecules appeals is indeed supporting not just monotherapy, but also combination approaches. The first approach efforts. Where the patient's own innate immune system is still functional indeed involves developing our innate cell engager molecules as monotherapy. Update. Our combination therapy approach involves pursuing novel therapeutic combination, including combinations with NK cell therapy outcomes.

Speaker 1

The combined cells create CAR like NK Therapeutics that seek out and destroy tumors. An example of update is our investigator sponsored clinical trial at MD Anderson Cancer Center. On Slide 4, we are showing update, where we are with our leading innate cell engagers, AFM13 and AFM24 and the recently added AFM28 in a nutshell. Outlook. All three of these innate cell engagers bind to CD16A on natural killer cells and macrophages with high affinity update and also find on specific targets on cancer cells to bring the innate immune system to fight against outcomes.

Speaker 1

This slide shows our AFM13 innate cell engager target CD30 positive lymphoma, AFM24, positive AML indications. We are embarking on a broad development strategy for each outcomes, which we believe will be the basis for continuous data flow from our pipeline over the next several quarters. Since we introduced you to our 3 pronged strategy, we've also made a lot of progress efforts to support our claim. We have published clinically and preclinical data that make us more confident about the path that we have set for our outcome. Our goal in all of these efforts at Affimed is to bring innovative therapies to cancer other patients who are often out of these options when it comes to managing their disease.

Speaker 1

These are very sick patients who frequently see their disease return after multiple lines of treatment. Very proud to have been able to offer these undeserved and frequently without hope patients another opportunity to fight their disease. And as we have shown, for example, with AFM13 and in particular in combination with natural outlook. With that introduction, let me give you a quick update on our program. Jumping now to slide 6.

Speaker 1

This shows a snapshot of where we are with AFM13. Our registration directed study of 13 monotherapy in relapsedrefractoryperipheral T cell lymphoma is on track to complete enrollment in the first half of 2022, and we expect to provide guidance about timing for data as we get closer to the completion of enrollment. We also are very pleased update to share with you that the investigator sponsored clinical trial at MD Anderson Cancer Center evaluating cold blood derived natural killer cells pre complex with AFM13. It's going very well. As of October outlook.

Speaker 1

A total of 18 patients have now been enrolled in the study, including 12 patients at the highest dose, continue to gather robust data on safety and efficacy. And according to the MDMD Anderson have submitted a protocol amendment to allow for expansion of the study to treat up to 40 patients at the highest dose, now including Hodgkin lymphoma patients and CD30 positive non vascular lymphoma patients. Finally, we plan to present updated data from the study at a company event in mid December and expect to provide additional details on the date and time for this event in the coming We're also very excited about our progress with AFM24, where we believe the execution of our 3 over the next several quarters. Andreas, our Chief Medical Officer, will now tell you more about where we are with uptrends. Andreas?

Speaker 2

Yes. Thank you, Adi, and good morning, good afternoon to all of update. It's my pleasure and my privilege to give you an overview of our development program with AFM24 effort and to review some of the recent progresses that we have made in this program. If we move to Slide 8, this slide gives you an outline of the development strategy for AFM24. And as you see, it is a very comprehensive, very broad development approach.

Speaker 2

We expect to investigate AFM24 as a monotherapy and in combinations with either PD L1 inhibitor, atezolizumab, or with autologous NK cells in a total of 7 different integrations across 9 expansion cohorts. This broad approach is intended to deliver the highest probability of success update, the process that we used to select indications and to maximize a probability of success. Estimates. The selection of the indications for each study was based on a very thorough and very comprehensive analysis that use the data of more than 10,000 patients across 144 tumor subtypes. And these were initially ranked based on 20 criteria that included, but are not limited update to factors like EGF receptor expression, involvement and function of estimate, but also looking at unmet medical need and potential passes to market.

Speaker 2

If we can move to Slide 10, we show you the general concept that applies to all of our studies. All studies are based, as I said, on a selection of indications that in the individual situation we believe have the best chance of therapeutic success. The individual cohorts In each of these studies follow an optimized SIMON2 stage design. This design provides us with an opportunity to make gated investment decisions. In the first step, each cohort will recruit 12 to 18 patients after we which have a preplanned interim analysis.

Speaker 2

This interim analysis is associated with predefined success thresholds. In the case that individual success thresholds are met, we will recruit up to 40 patients in each cohort, ups. Furthermore, since these are open label studies, we will have the opportunity for interim data readouts. Update. With that said, let me update you on the development of AFM24 in our monotherapy study, which is shown on Slide 11.

Speaker 2

As you are all aware, the initial part is a dose escalation part in order to define the recommended Phase II dose. It is important to reiterate that the goal of the dose escalation part was to identify the pharmacologically active and safe dose of AFM24 for as fast as possible. Therefore, in the dose escalation part, there was no selection of patients with tumors estimates that are more likely to respond to single agent as defined by our indication selection process. Efforts. Slide 12 shows you the recruitment status so far.

Speaker 2

Up to now, we have attributed to 29 patients across 6 dose cohorts. As you can see, the study population outcomes, with colorectal cancer harboring either RAS or RAS mutations being the most frequent tumor type. Also important to note that all these patients were heavily pretreated all available treatment options for their given tumors. On Slide 13, we provide a summary of the actions that were treated at the 480 milligram cohort. Of note, 4 out of 6 patients are still receiving therapy with AFM24 as they are deriving clinical benefit update according to the assessment of the treating physicians.

Speaker 2

2 patients have shown stable disease beyond 3 months and continue treatment. Of specific note, patient 5, while classified with progressive disease, has experienced a meaningful clinical benefit and also continues on treatment. Update? We plan to submit detailed data from the dose escalation for a presentation at a medical conference actions in the first half of twenty twenty two. Moving on, we are pleased to announce that we have determined that 4 80 milligrams is a safe and pharmacodynamically active dose and will be our recommended Phase team.

Speaker 2

This decision is based on a comprehensive review of safety, pharmacokinetic exposure and pharmacodynamic data, including CD16A receptor occupancy on peripheral NK cells. Actions. As supportive pharmacodynamic data, we have also measured the activation, which exhibit continuous activation of NK cells at doses of greater than 160 milligrams. From a safety perspective, no dose limiting toxicities were observed at either 320 or 4 up to 80 milligrams. In the next two slides, we share the data on the pharmacokinetics antireceptor occupancy that has reported as a recommended Phase II dose decision.

Speaker 2

On Slide 15, efficacy of dose and exposure at doses of 320 milligrams 480 milligrams, efforts, which indicates that we achieved saturation of target mediated elimination by EGFR, meaning that EGFR receptors at these doses are likely saturated. In the graph of the right side, you also see that the trough levels that we are reaching with 320 and 480 milligrams shown in green and blue dots are comparable to the cetuximab updraft levels at the marketed cetuximab dose indicated as a gray sated area. If we move to Slide 16. We review here the data that we have obtained with CD16 receptor occupancy, Afifi, and I will take a minute to walk you through the slide. On the left graph, you see the measured CD16A receptor occupancy on circulating NK cells.

Speaker 2

As you can see that we initially see an increase in CD16A occupancy with increasing doses, which plateaus at 480 milligrams, indicating a saturation of CD16A in the periphery. Now the important question is how does this translate into the tumor and how is this correlated to activity. On the right, you see 2 curves from our in vitro studies. The blue curve is tumor cell killing by NK cells in the presence of IFM24. The red curve is CD16A receptor occupation.

Speaker 2

As you can see, maximum tumor cell killing is achieved as dose ranges that are associated with relatively modest occupancy. It is important to note though that when we speak about relative receptor binding, let's say, of 10%, this does not mean that we have only activated 10% of NK cells. Every NK cell has found AFM24, but on the individual cell level, there is a 10% occupation of available receptors, which already translates into maximum cytotoxicity. Now the vertical line here indicates outlook of AFM24, we expect in the tumor at a dose of 4 80 milligrams. For this calculation, we have taken a very conservative assumption, which is that AFM24 concentrations in tumor tissue actions will be 200 fold lower than in circulating blood.

Speaker 2

But as you can see that even under these very conservative assumptions, 480 milligrams results in the CD16A occupancy in the tumor that is sufficient update. Our decision for 400 milligram as a recommended Phase II dose is based on the good safety profile and the PK and PD data that I just showed. As next steps, we plan to open the expansion cohorts at 4 80 milligrams plan to continue dose escalation of AFM24 to 7 20 milligram. The cohort is currently open for patient enrollment. Together additional safety data and provides the basis for alternative scheduling like a once every 2 zero one Phase III application of AFM24.

Speaker 2

If we now turn to the 2 combination studies, efforts, namely the combination with NK ZENS autologous NK cell AFM24103 and the combination study with atezolizumab AFM24102. Actions. For both of these trials, the starting dose of ASM24 will be 160 milligrams, followed by dose escalation steps approval through which we will assess safety and identify a recommended Phase II dose for the combination. These recommended Phase II doses will then be used in the dose expansion phases, which as I described will follow assignment 2 stage design in 5 of the 6 cohorts with interim analysis after 12 to 18 patients and the ability to enroll up to 40 patients. Actions.

Speaker 2

On Slide 18, you see the design of the C102 study where we combine AFM24 IV with atezolizumab. In this trial, we will focus on non small cell lung cancer, gastric cancer and hepatobiliary pancreatic cancer, all areas of very significant outlook. The cohorts in non small cell lung cancer and gastric cancer follow the described assignment 2 stage design. The 3rd cohort that can include hepatocellular cancer, biliary tract cancer and pancreatic cancer Is it designed as a signal identifying basket cohort with descriptive statistics? Here we show the design of our study 24,103, combination of AFM24 colorectal cancer and head and neck cancer.

Speaker 2

We believe that this innovative approach actions. In these indications where patient's endogenous NK cell numbers are dysfunctional or only exist in sufficient numbers where we also evaluate CRC, but require previous treatment with EGFR antibodies and thus will most likely exclusively recruit CRC patients with KRAS wild type. The CRC cohort in 103 will focus mainly on patients with KRAS mutations. Finally, on AFM24, you may have seen the presentation at the most Ashland triple meeting, where we showed that AFM24 enhances cytotoxicity against EGFR positive tumor cells when combined with of SNK-one hundred and one, the autologous NK cell product. The addition of AFM24 to autologous SNK-one hundred and one cells improved cell killing when compared to NK cells alone in EGFR positive tumor cell lives regardless of EGFR mutational efforts.

Speaker 2

To summarize on Slide 19, the status of the AFM24 outcomes. We are very excited that we can now embark on a broad development program in several indications with significant unmet medical needs. These studies, as shown, will generate a continuous flow of data in 2022 and beyond. With that, I will turn hand the call over to my colleague, Arnd Soteljos, who will present our novel fully owned ICE AFM 28. Outlook.

Speaker 2

Arndt, please?

Speaker 3

Thank you, Andreas. And also from me, good morning, good day, everybody. Warm welcome to the call. I'm really excited to introduce AFM 28 to all of you, which is our newest addition outlook for our portfolio. As shown on Slide 21, we recently announced our newest targets in myeloid malignancies.

Speaker 3

We chose CD123 as it is almost universally expressed on leukemic blasts and leukemic stem cells in patients with AML, both at diagnosis and at relapse and independently of cytogenetic risk. AFM28 is being developed for the treatment of patients With acute myeloid leukemia, we believe that AFM28 could be the key to novel treatment approaches efforts that can fulfill several unmet needs. I would like to spend a few minutes to explain this and lay out why we are so excited about adding AFM28 to the arsenal against leukemia. AML is After most common form of adult acute leukemia, more than 40,000 patients are outcomes with this disease every year in the 7 major markets. The outcomes have remained very poor and treatment options are generally limited, particularly for relapsed or refractory disease.

Speaker 3

Apps within 1 year. Only 1 of 3 patients is alive after 1 year once they become ataxo refractory. And after 5 years, it is only 1 out of 10 patients. It is obvious analysis by inducing deeper responses and by eradicating measurable residual disease or MRD. Efforts.

Speaker 3

In addition, for patients who have relapsed or are refractory to standard treatment, alternative options achieved for patient population that is elderly. Note that over 80% of patients are over 60 years old and can often not tolerate treatments associated with toxicity. So efforts. These new approaches not only need to be more effective, they also need to be safer. Recent data have demonstrated that natural killer cell based innate immunotherapy is emerging as a promising treatment option in AML actions based on the demonstrated susceptibility of leukemic blasts for NK cell killing and clinical activity of allogeneic NK therapy and relapsedrefractory disease.

Speaker 3

Also, these treatments are remarkably well tolerated. Estimates. Yet these approaches rely on the cell's natural ability to recognize leukemic cells. So these cells are not specifically escape of leukemic stem cells and AML has been described. So to effectively deplete leukemic cells, access.

Speaker 3

Including leukemic stem cells, a targeted approach, in addition to natural cytotoxicity, has the potential to induce more frequent and deeper responses. We believe these statements are also supported by the data that we have generated estimates with AFM13 in combination with NK cells. We designed AFM20 updates to be differentiated versus available therapy and to bring a truly novel approach to the treatment of AML. Update. As we show on Slide 23, AFM28 binds with high affinity to both CD123 and and no such molecule currently exists to our knowledge.

Speaker 3

It thereby strongly activates NK cells, inducing ADCC and through binding to CD123 causes depletion of leukemic blasts and leukemic stem cells. We will be presenting preclinical data for AFM28 at ASH and plan to submit an IND application in the first half of twenty twenty two and to start a clinical study in the second half of twenty twenty two. With that, I'll hand the call over to Angus to review the financials. Angus?

Speaker 4

Thank you, Arndt. Aptomed's consolidated financial statements have been prepared in accordance with IFRS as issued by accounting standard for or IASB. The consolidated financial statements are presented in euros, which is the company's functional and presentation currency. Therefore, actions. All financial numbers that I will present in this call, unless otherwise noted, will be in euros.

Speaker 4

We ended the Q3 of 2021 with cash and cash outlook of €198,700,000 compared to €146,900,000 on December 31, update. Based on our current operating plan and assumptions, we anticipate that our cash and cash equivalents will support operations into the second half of twenty twenty three. Net cash used in operating activities for the quarter ended September 30, outlook. With €25,600,000 compared to €3,600,000 in the Q3 of 2020. Total revenue for the Q3 ended September outlook.

Speaker 4

Revenue for the Q3 of 2021 mainly comprised of collaboration revenue from Genentech and update. Research and development expenses for the Q3 of 2021 was €20,600,000 compared to €10,100,000 for Q3 of 2020. The increase in R and D expenses compared to the same period last year were driven primarily by increased expenses for AFM24, and an increase in share based payment expense. General and administrative expenses for the Q3 of 2021 were euros 6,800,000 compared to €3,500,000 in the quarter ended September 30, 2020. Share based payments.

Speaker 4

Net finance income for the quarter ended September 30, 2021 was €1,500,000 compared to finance loss of €3,100,000 in the quarter ended September 30, 2020. Net finance income loss is largely due to foreign exchange gains losses related to assets denominated in U. S. Dollars as a result of currency fluctuations between the U. S.

Speaker 4

Dollar and the outlook. Net loss for the quarter ended September 30, 2021 was €17,100,000 or €0.14 per common share compared with a net loss of €6,000,000 or €0.07 per common share for the quarter ended September 30, 2020. Update. The weighted number of common shares outstanding for the quarter ended September 30, 2021 was 119,800,000. With that, I'll turn the call go back to Adi for closing remarks.

Speaker 4

Adi?

Speaker 1

Thank you, Angus. As you've heard now, we have made continuous progress with our 2 lead programs, AFM13 and 24. And soon, we plan to have a 3rd innate cell engager items that aren't presented called AFM 28 in the clinic. As we now look ahead, as shown on Slide 24, outcomes from which we expect to report data. Our expected key milestones are as follows.

Speaker 1

For AFM13, we will host an investor event update in December, where we plan to provide a data update on our ongoing trial in combination with natural epithelial cells. In addition for AECOM30 monotherapy in peripheral T cell lymphoma, we expect to complete enrollment in our registration directed study in the first half of next year. We've broadly explained gravistand with AFM24. And for monotherapy, we are now planning to open the expansion cohort before the end of this year. We submit an abstract with data from the dose escalation for presentation at a Medic Medical Conference in the first half of twenty twenty two.

Speaker 1

Studies for Efem24 in combinations either with natural killer cells or with anti PD L1 atezolizumab. We are expecting to complete the 1st dose escalation cohort in each study during the first half of twenty twenty update. To start with the dose cohort expansion, the safety is favorable and thereby also be able to provide update as we progress. For AFM 28, a very new candidate that we carefully IND submissions in the first half of twenty twenty two and subsequently the initiation of clinical studies. We're planning again, outlook.

Speaker 1

We are preparing the company to meet these opportunities and look forward to bringing innovative medicines to patients that need them. Efforts. Now on behalf of the entire team, I would like to once again express my gratitude to everybody who is contributing to release efforts. We're now ready to take any questions that you may have. Operator?

Speaker 5

Our first question comes from the line of Dana Greifel from SVB Leerink. Your question please.

Speaker 6

Hi. Thank you for the questions. Estimates. Just looking at the data that you presented on AFM24, maybe a 2 part question. Can you remind us why you think These three planned expansion cohorts will be most amenable to single agent activity.

Speaker 6

So the CRC KRAS wild type, the EGFR lung and RCC. And then it is, I guess, those tumor types where you did see the stable disease or that patient progressive disease that continues on treatment. Can you share anything more about those patients? Did they have high eGFR expression? Were they refractory to other EGFR targeted therapies?

Speaker 6

Thank you.

Speaker 1

Thanks, Dana. I'll hand this over to Andreas, please.

Speaker 2

Yes. Hi, Dana. So let's start with probably Second question second part first. So the patients that we have treated on 4 80 milligrams, we have these 2 patients with EGFR mutant, our non small cell lung cancer and our colorectal cancer patients. Outlook.

Speaker 2

Important to note, we fixed or we decided which combination or which Tumor types will go into which of the studies prior to seeing the data. And as I said, This decision was really driven on this comprehensive analysis that we showed, where we looked data for more than 10,000 patients and then really looking at biology of the innate immune system activating and inhibiting factors in k cell biology. So what we see now here on Slide 6, again, very small and on the cohort 6, very small patient numbers. It's a little bit maybe an early confirmation of our selection process. If you look at the colorectal cancer patients, wild type patient number 1, this would be a patient who would have qualified for the expansion cohort.

Speaker 2

Patient number 3, EGFR mutant non small cell, another patient that would have qualified. And patient 5, Again, EGF Newton would be in the patient that would have qualified. The other 2 patients, 24, where we have follow-up data, patient 6 is very early in his treatment would have not qualified for the expansion cohort as monotherapy. So again, the sequence was different. So we looked at the biology first and then decided which are the most likely cohorts or most likely tumor types that can respond.

Speaker 2

Again, with this very small data set, there seems to be a trend that exactly these tumors really do quite well on AFM24 monotherapy. IP? Now we have measured eGFR across our cohorts. Most patients have moderate to high expression. I do not have individual patient numbers or data, but I would expect us to EGFR mutant or small cell lung cancer patients have rather high expression of EGFR receptor.

Speaker 2

As a requirement, I needed to exhaust all previous lines of therapy. So all of these patients have been pretreated and have become resistant to EGFR targeting therapies, whether it's TTIs for antibodies.

Speaker 6

Our

Speaker 5

next question comes lines of Maury Raycroft from Jefferies. Your question please.

Speaker 7

Hi, good morning. Good day everyone and congrats on the updates update. Thanks for taking my questions. I had a question on AFM-two forty two. For that one, you showed a lot of helpful PK and PD data.

Speaker 7

I'm wondering if you can tie it together with what you're seeing in the 6 patients at 4 80 mgs, particularly in respect to antitumor activity as you approach steady state? And if you can talk more about what you're seeing on cytokines and NK cell activation markers as exposure increases?

Speaker 2

Actions? I can take the first part and then I hand over to Arnd regarding cytokines. So yes, as you see, these patients are treated at the 4 80 milligrams. So this is the dose level where we achieve dose proportionality. So we have basically saturated eGFR binding.

Speaker 2

As we showed, we also CD16A receptor occupancy and correlating figures in the tumor that according our experiments are sufficient to maximum activation of the tumor residing NK cells. We have not broken down these data on an individual patient level yet, but this is something that we will have to do in the future.

Speaker 3

And maybe And maybe Mark

Speaker 2

can talk on the NK cell, yes.

Speaker 3

Yes, sure. Happy to do So you noted, Maury, we didn't share that data because we want to disclose that as discussed at an upcoming conference in 'twenty 2, what we see, what I can share with you in terms of the cytokines, to give you an example, in front of gamma, TNF alpha important for NK activation. The dose is at or above 160 when we look at the steady state levels. We see a steady increase. Assets?

Speaker 3

We didn't see a real difference between $320,000,000 $480,000,000 but we see that it clearly was rising above F-one hundred and sixty, making the point again that this is clearly pharmacologically active. In terms of the activation markers, similarly, we want to share that data when is also a little bit more matured. But the same trends that we see at doses above 160, We saw an increase of those activation markers, again showing that we have consistent NK cell activation. Hopefully that helps with your question.

Speaker 7

Yes, that's very helpful. And maybe one other question on the AFM13 plus on cord blood NK cell combo study. Just wondering if you can talk more about expectations on durability, for this upcoming update. And also just checking if you have plans to move this study over to sponsorship at Affimed at some point?

Speaker 1

Andreas, can you take the question please?

Speaker 2

Yes. So what you see or what you realize is When you compare to the status that we have basically by the middle of the year, June or so, we have added a very significant number of patients over the last couple of months. So I would say that For the highest dose cohort, time to progression or duration of response data will be are quite immature in December as many of these patients have recently started treatment within the last 3, 4 months. So of course, on the lower doses, we have a longer follow-up. But again, this will not be the therapeutic doses set that we will move outlook into our expansion cohort and will use subsequently.

Speaker 2

Now in terms of sponsorship, we have not have decided. So as we always said, we are working on with several CDMOs to transfer. The production process, we are in the process of doing that and we'll provide updates as we have more concrete data to

Speaker 5

update. Our next

Speaker 6

progress. I have a follow-up question on the AFM13, the cord blood NK cell combo. Can you talk a little bit about the decision to Expand into both HL and NHL patients, what should we Expect the split to be should this are you looking to enroll more NHL patients? And maybe talk a little bit about how update. If at all this changes your strategy in what to focus on, whether it's HL or

Speaker 2

Yes. So as you know, CD30 is a target that is expressed on Hodgkin's, but also on non Hodgkin's lymphoma like T cell lymphoma, a subset of CD30 positive B cell lymphomas. So currently, we are following, if you will, a 2 pronged approach. So clearly, our main indication or First indication, I would say, will be Hodgkin's lymphoma where we have the wealth of data and where we have seen these very impressive responses assessment already in the first four patients. So this is the study is now designed that it will recruit 30 Hodgkin patients at the recommended Phase II dose, which we believe gives us good data set to move on with Hodgkin's on the registration path.

Speaker 2

Efforts? Now the second part is a little bit opportunistic. Again, there's also very significant medical need in impaired T cell lymphomas and in diffuse large B cell lymphomas. So we thought that we at least should explore NK cell based AFM13 based combinations in these diseases that could potentially result in a second or a second and a third development pathway. So this is really broadening the indications.

Speaker 2

But for now, Hodgkin will be our lead indication where we will try to move ahead with full steam.

Speaker 6

Update. Great. Thank you. And just a follow-up question on the ASM24, the data that you presented. You've been dose escalating outlook.

Speaker 6

But have you seen any indication, especially with the lower doses where patients have been treated for a longer period of time, The deepening of responses?

Speaker 2

We have yes, yes. We have occasionally seen some disease stabilization at the lower doses. But again, According to our data, the maximum pharmacokinetic pharmacodynamic active or activity was set in around 160 to 320 with 480 being our selected dose right now. So these are really anecdotal anecdotal observations. As we said, out of our 4 80 milligram cohort, ups?

Speaker 2

4 of 6 patients are still on treatment. So I think this will be interesting to cohort to watch whether we do see deepening of advances.

Speaker 6

Great. Thank you very much.

Speaker 5

Thank you. Our next question comes from the line outlook. Your question please.

Speaker 8

Good morning. Thanks for taking our questions and thank you for all the detail efforts. Can you speak to why CD133 in the context of the CD33 ENGAGEMENT you built for Aflina, compare CD123 to CD33 and innate cells to T cells in application in AML? Thanks.

Speaker 1

Yes. I'm happy to take this question, Arndt.

Speaker 3

Yes. Happy to do that. Nick, yes, I think we already also provided some background information. As you rightly, Sanfomena has this CDF33, I think a very valid target, of course, in combination with a CD3, the T cell engager. Why are we why have we I elected maybe let me speak about or reiterate CD123.

Speaker 3

1 is it is very broadly expressed on the leukemic blasts. Assets. It's also expressed equally leukemic stem cells and importantly non NOS unhealthy stem cells. So we have a very high selectivity. We've also followed our approach in selecting this when we look at in a way The programs that have been out there like an FC enhanced CD123 target antibody that was outcomes comes from kind of Johnson and Johnson a while ago, talacotuzumab that was not continued because as an Fc enhanced antibody without the additional mechanisms of actions that we believe We add in terms of also the efficacy, in terms of the, let's say, tuning engineering with the molecule, we see a great potential to address that medical need.

Speaker 3

Indeed, also with those approaches, Specifically excited is in the prospect, of course, testing monotherapy, but then very quickly combining AFM28 update with allogeneic NK cells. Why? Because we know in AML, of course, a myeloid disease, NK cells and macrophages actions will not be fully, at least fully functional or not functional. So adding in a way, you could say, the payload of meclizorab action with allogeneic NK cell transfer, we see a very high probability of success to getting to those deep responses that we're looking at, which is this very high medical need to really get to also minimal residual disease negative patients. Hopefully, that kind of addresses your question, Nick.

Speaker 8

Yes. And I think I guess the point of NK T cells emphasizes the safety advantage you feel there is with an NK cell versus a T cell engager?

Speaker 3

Yes, absolutely. That is an important point. We have now seen consistently across our innate cell engagers, excellent safety profile. I mean, some of the early IRRs that we have seen very well manageable schedule pretreatments. So NK cells are just by the nature of their biology, very effective but much safer than T cells.

Speaker 3

Again, I think we know the principle by now. It's not only the cytokine storm, but it's also really the, In a way autoimmune effects that we see where T cells once unleashed are just not selective in kind of targeting or attack in the tumor versus healthy tumors. Various NK cells very well distinguish Klitties, thus a very much better safety profile. And As I laid out, I think when you look at the very elderly patient population that we have frail patients that will not tolerate some of them, high dose chemotherapy. We see this as a very differentiated good profile with an NK cell engagement.

Speaker 8

Terrific. And then maybe just last one for me. In solid tumors, obviously with FM24, you described very elegantly the 3 pronged strategy, you've already elucidated to an NK cell combo. So for FM 28, at least 2 pronged. Is there a 3 pronged Strategy do you think that's applicable for AFM28 myeloid disease?

Speaker 3

Assets? That's a really good question. Happy also for Adi or Andreas to jump in. We have currently also publicly said we want to make the combination with allogeneic and K cells a priority because of the reasons I've been giving. There may be update cases for also the kind of 3rd pillar, that's not something that we have fully thought through and would update update accordingly as we move on with our plans.

Speaker 5

Efforts. Thank you. Our next question comes from the line of Brad Cagnino from Stifel. Your question please.

Speaker 9

Thank you and appreciate the updates today. Just quickly on the protocol amendment for AFM13NK, was that driven by MD Anderson or by your team? And if you could talk more about the reason behind that. And then I'm also interested in the breakdown of the 6 AFM24 patients you had at 480 mg cohort. You highlighted how 3 of these would have been eligible for the monotherapy expansion cohort, But they had 4 to 7 prior lines of therapy, it looks like.

Speaker 9

In the expansion cohort, should we expect This number of prior lines of therapy or will you be looking for patients that maybe earlier at 1 or 2 prior lines? Thank you.

Speaker 1

I guess Andreas, both questions are up to you.

Speaker 2

Yes. So let's start with the amendment of the protocol. I think Important to reiterate, we have a very good, very close working relationship with MD Anderson. So I would say it was basically a joint effort, joint decision. Efforts?

Speaker 2

Initially, the protocol was only designed to evaluate safety. So it was a acute Phase 1 safety protocol. But then I would say even for us a little bit unexpectedly, we saw this Really significant antitumor activity already at the lower dose levels. And so we immediately developed the desire to gather more efficacy data and to basically put this compound on a development path. So we use the existing protocol to allow for more patients at the recommended Phase II, which will give us sufficient number of patients to really have a good solid estimation of efficacy in Hodgkin's lymphoma.

Speaker 2

And as we always said, we'll provide us the basis to engage With health care, with regulators for the most appropriate and the fastest path towards approval. So this was a joint decision and it was really driven by our enthusiasm, both MD Anderson and our enthusiasm about the data we were seeing. Now in terms of the expansion cohorts in study 101, yes, you are right. These patients are heavily pretreated. And I think Taking this into account, seeing this degree of activity in late line, at least for us, is really very encouraging.

Speaker 2

Whether there will be less pretreated patients in the expansion cohort is a little bit hard to say. The expansion cohort still requires that patients have exhausted all available treatment options for their respective diseases. So I would say we will see a majority of patients with 3 to 4 lines of previous therapy. Again, we are acting here in an area of a very significant unmet medical need, which It's a scene for a potential accelerated approval process if you can show a robust and reproducible activity In patients that have no treatment alternatives left.

Speaker 8

Thank you.

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