Affimed NV (AFMD) 2024 Q1 法說會逐字稿

Good day, everyone, and welcome to Affimed's first quarter 2024 earnings and corporate update call. (Operator instructions) As reminder, today's conference call is being recorded.

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

Thank you, Michelle, and thank you all for joining us today for our first quarter 2024 update call. Before we begin, I'd like to remind everyone that we issued the relevant press release and presentation on our website today, which you can find under the in the Investor Relations section.

On the call today, we have members of our management team, including Andreas Harstrick, our Chief Medical Officer and acting Chief Executive Officer; Wolfgang Fischer, our Chief Operating Officer; Denise Mueller, our Chief Business Officer; and Harry Welten, our Consulting Chief Financial Officer.

Our financials today will be presented by our Vice President of Finance, Michael Wolf. The team will be available for Q&A after the prepared remarks. Before we start, I would like to remind you that today's presentation contains projections and forward-looking statements regarding future events.

These statements represent our beliefs and assumptions only as of the date of this call. Except as required by law, we assume no obligation to update these forward-looking statements publicly or to update the reasons why actual results could differ materially from those anticipated in the future the forward-looking statements, even if new information becomes available in the future.

These forward-looking statements are subject to risks and uncertainties and actual results may differ materially from those expressed or implied in these statements due to various factors, including but not limited to, those identified under the section entitled Risk Factors in our filings with the SEC, and those identified under the section entitled Forward-Looking Statements in the press release that we issued today and filed with the SEC.

With that, I'll turn the call over to Andreas. Andreas?

Yes. Thank you, Alex, and good day everyone and thank you for joining us today for our first quarter 2024 earnings call. I'm excited to share with you today clinical data on all three of our clinical programs that, as we believe, are validating our approach of using the innate immune system as an additional tool to fight cancer.

When we announced the strategic reorganization of Affimed and our focus on the advancement of our clinical assets in January, we guided that our goal would be to generate meaningful data for all three programs in the first half of the year. I'm proud to say and thankful to all of my coworkers in Affimed and to all our clinical investigators that today we can deliver on this guidance.

As shown on slide 3, we now have clinical validation for all three assets for AFM24. We are advancing the combination study with atezolizumab in treatment refractory patients with non-small cell lung cancer, both in the EGFR wild-type and in the EGFR mutant subgroups.

Data that we shared at ASCO demonstrate durable responses in patients with EGFR wild type tumors with three or four responses ongoing now for over seven months, we also see meaningful and confirmed tumor responses in the EGFR mutant subgroup tumor type that is generally considered unresponsive to immunotherapy.

We can also share exciting data for our clinical LuminICE trial of Acimtamig in combination with AlloNK cells in patients with refractory Hodgkin's Lymphoma. Seven patients have had their CT scans, meanwhile, assessed by blinded independent REIT which will be as the primary end point of the study as agreed upon with FDA.

In these patients, we see objective responses in six out of seven patients for an overall response rate of 85.7%. Importantly, this includes four patients with a complete remission.

Finally, AFM28, our CD123, targeting ICE for the treatment of refractory AML has shown remarkable clinical activity at dose level 5 of our single-agent dose escalation study. We have observed one complete response and five patients with stable disease at dose level 6, we see two patients with a complete response in the CRI respectively, and three patients with stable disease.

Importantly, the complete response from dose level 5 is now ongoing and stable for more than five months and five of the six patients at dose level 6 are continuing on treatment with a possibility for further deepening of responses. Also importantly, no dose-limiting toxicities were observed in dose level 5 and 6, thereby establishing a safe and effective regimen for further development.

Let us look at the US data in some more detail. Today, I will start with Acimtamig. As a reminder on slide 5, you'll see the trial design as agreed upon with FDA. We now have completed enrollments in two cohorts one and two and are actively recruiting cohorts three and four.

We admit that there are still a slight delay in recruitment compared to our initial expectations. As discussed on our last earnings call. This is mainly due to a higher rate of patient dropout during the screening period. However, with additional sites now active and more experience with the protocol at the site level, we expect to see a further improvement in patient recruitment and a reduction in the dropout rate.

In terms of safety shown on slide 6, the adverse event profile is in line with our previous experience with Acimtamig and the combination of Acimtamig and AlloNK cells, respectively. It is important to note that in the LuminICE-203 study, we did not use steroids as part of the premedication for a Acimtamig and therefore, we were expecting a slightly higher rate of infusion-related reactions compared to some studies with Acimtamig, which steroid premedication was routinely used.

Four of seven patients developed Grade one or two infusion-related reaction/CRS event. One of these four patients had a short lasting Grade 3, CRS as assessed by the investigator, which manifested mainly by high fever and a decrease in blood pressure.

However, the patient responded readily to standard of care treatment, importantly, in this patient shortly after this event. And there was also an acute CMV infection diagnosed and thus the relative contribution of infusion of Acimtamig versus acute CMV infection to the overall symptoms is not clear. Importantly, there were no treatment discontinuations due to side effects of Acimtamig or AlloNK.

Also, there were no instances of bleeding. I can't or graft versus host disease. As the clinical activity of the combination is, I think, remarkable as shown on slide 7, six of seven patients showed an objective response by independent read including four patients was a complete remission.

So these data are directly comparable with the data that were reported by MD Anderson Cancer Center for the symptomatic in combination with fresh pre complexed NK cells and does indicate that co-administration of ICE with allogeneic. NK cells is active fit. No pre complexing is needed, and the cryopreserved NK cells seem to be comparable to fresh NK cells in terms of antitumor activity.

Also, these results demonstrate set data from a single site study at MD Anderson are reproducible in a multicenter setting of these seven patients were enrolled by four different institutions.

Slide 8 shows the patient's characteristics underscoring that these patients are heavily pretreated with a median of four lines of previous therapy. All patients had failed combination chemotherapy, PD-1 targeting therapy and brentuximab. In addition, five of seven patients had also failed after autologous stem cell transplant.

On slide 9, you'll see an example of a patient with multiple manifestations of this refractory Hodgkin's lymphoma, including axillary lymph nodes, supra classical area, lymph nodes, spleen and Ingrid lymph nodes. The patient had failed all standard of care options, including stem cell transplant and presented was B symptoms, which clinically is a very unfavorable prognostic factor. As you can see, all tumor manifestations resolved after only one cycle of therapy.

Let's move on to AFM24. Since we presented the data in detail during our ASCO presentation, I will be brief here has flown on shown on slide 11. So combination of AFM24 and atezolizumab has meaningful activity in patients with heavily pretreated EGFR wild type non-small cell lung cancer.

In 15 evaluable patients, there were four objective responses at eight patients with stable disease. Of note, all patients had failed combination chemotherapy and PD-1 targeting therapy or responders were documented progressive on previous anti-PD-1 treatments.

Importantly, responses and tumor control induced by AFM24 atezolizumab appear to be durable, as shown on slide 12, where you see the long-term follow-up data, the progression-free survival for the whole study population is 5.9 months, which compares favorably to the 4.5 months, which is usually achieved in these patients with standard of care treatment.

Even more encouraging is the fact that streamer of the four emissions are still ongoing now at more than seven more than eight and more than nine months, respectively. It appears very unlikely that this data can be explained by tislelizumab activity alone.

Even though there are occasional responses to PD-1 rechallenge after intervening chemotherapy, PFS data in these patients has been very short, even in PD-1 non pretreated patients in platinum refractory non-small cell lung cancer. Atezolizumab has shown a progression-free survival interval of only 2.8 months.

Our recent results in patients with heavily pretreated EGFR mutant non-small cell lung cancer, as shown on slide 13, supports the activity of the AFM24 atezolizumab combination in 13 patients at our response evaluable for responses and six patients with stable disease were achieved.

Compared to the data that were reported at ASCO, meanwhile, all objective responses have been confirmed by follow-up scans and all responses are ongoing. This is remarkable as EGFR mutant non-small cell lung cancer is in general regarded as unresponsive to immunotherapy.

Slide 14 shows the market opportunity for drugs that are targeting refractory non-small cell lung cancer in the seven major markets. There are 175,000 patients with EGFR wild-type non-small cell lung cancer and roughly 35,000 patients with EGFR mutant non-small cell lung cancer annually who fail standard of care therapy and will need additional treatment options.

Current treatment options for these patients are unsatisfactory with PFS durations around 4 to 4.5 months. Also many salvage regimens include chemotherapy that is often difficult to tolerate for this heavily pretreated patients. The combination of AFM24 plus PD-1 could provide a chemotherapy-free alternative was meaningful activity and significantly better tolerability for these patients.

Finally, let's review the most recent data of AFM28, our CD123, targeting ICE for the treatment of acute myeloid leukemia. As shown on slide 16, here, we have escalated the dose through six cohorts up to 300 milligrams weekly. I think this study is also a good example of the ability of our organization to execute clinical studies.

The first patient in this program was treated in March 2023 and the whole dose escalation trial over six cohorts was executed in only 15 months. The safety profile, as shown on slide 16, four, dose levels, five and six. We did not see any dose-limiting toxicities. The most frequent side effects were infusion-related reactions mainly of low grade.

Only three patients had a Grade 2 infusion-related reaction responding in all cases to symptomatic treatment. And there were no grade three or higher IRRs, one patient experiences for limiting for blasting cells, limiting CRS of Grade 1.

Infections or characteristic manifestations of acute leukemia and was seen in half of the patients. However, none of the infections was considered treatment related by the investigator. In addition, we observed meaningful target interaction at doses of 200 milligrams and above was near a complete saturation of CD123 binding sites on the tumors and occupation levels of CD16A on NK cells that include preclinical experiments result in potent NK-cell activation.

The clinical activity as displayed on slide 17, in dose level 5, we saw one complete response and five patients with stable disease. All patients were heavily pretreated of notes, the complete remission is still ongoing after more than five months Dose Level 6, we saw two patients with a complete response in the CRI respectively, and three patients with stable disease.

Five patients from dose level 6 remain on treatment with additional cycles and thus with the option to deepen their responses. I think since these results are remarkable, most of these patients with advanced AML have very low numbers of own NK cells when they start treatment.

So it appears that AML could be very sensitive to NK-cell mediated killing if already low numbers of endogenous NK cells when directed to the leukemia cells by AFM28 can produce complete responses.

These data taken together was impressive activities that we have seen was a combination of Acimtamig and allogeneic NK cells in Hodgkin lymphoma support our strategic intent to pursue further development of AFM28 in association with a cryopreserved allogeneic NK cell product.

With this, we would I can address an area of significant unmet medical need in the seven major markets. We see over 14,000 patients per year who failed at least two lines of standard therapy and require a new treatment option. Many of these patients are elderly and show frequent co-morbidities, thus limiting the use of aggressive chemotherapy. Immunotherapy has not been successful so far in AML.

The treatment approach based on the activation of innate immune system, could therefore be an important additional strategy for the treatment of these patients. With this, I will close the overview of our clinical programs and hand over to Michael Wolf for a review of our financial data. Michael, please.

Thank you, Andreas. Balance sheet and income statement highlights are shown on slide 20 and 21 of the presentation. A quick reminder that Affimed's consolidated financial statements, it has been prepared in accordance with IFRS as issued by the International Accounting Standards Board for IASB.

The consolidated financial statements are prepared in euros since our financials are described in detail in the press release we issued this morning. I will only provide highlights on this call. We ended the first quarter with cash, cash equivalents and investments of EUR48.5 million compared to EUR72 million on December 31, 2023.

Based on our current operating and financing plan, we anticipate that our liquidity will support operations for the second half of 2025. Net cash used in operating activities for the quarter ended March 31, 2024 was EUR23.8 million compared to EUR33.2 million for the quarter ended March 31, 2023.

Total revenue for the quarter ended March 31, 2024 was EUR0.2 million compared with EUR4.5 million for the quarter ended March 31, 2023. Net loss for the quarter ended March 31, 2024 was EUR19.2 million compared with a net loss of EUR32 million for the quarter ended March 31, 2023.

Now I turn the call back to Andreas for final remarks. Andreas?

Yes, thank you, Michael, for concluding remarks. Let's go to slide 22. I think this has been a very exciting and very successful quarter for Affimed in which we were able to help change clinical validation of all three of our programs. I think the strongest conclusions that we draw from this data to date is consistency.

When you see a single dataset in one study in one particular disease setting of course, you may always think could this be a chance finding. But what we are demonstrating today is consistent activity signals across three different programs that are all designed to leverage the power of the innate immune system to fight cancer.

We see this in four different indications and with two different combinations. Initial results from our Acimtamig and AlloNK program show remarkable activity, which seem to be on par with the data reported by MD Anderson. The difference is that we were able to generate this data with co-administration of ICE and the NK cell and was cryopreserved off-the-shelf NK cells.

Both factors set enables the use of this approach in a real-world multicenter setting for AML, we see that AFM28 can use and can induce responses even in a setting where only very few NK cells are available to fight leukemia. I think it is very reasonable to expect the boost in activity of sufficient amounts of active allogeneic NK cells are added as we have shown in our LuminICE study.

Therefore, we are actively exploring ways to continue there AFM28 program in combination with off-the-shelf allogeneic NK cells. And last but not least, we see consistent activity for the combination of AFM24 and atezolizumab. The strategy that utilizes the crosstalk between the adaptive and innate immune system.

When we started this program, since there were a lot of doubts whether innate immune system could even attack solid tumors, given the largely immunosuppressive environment that has felt in many solid tumors.

Meanwhile, we have demonstrated our objective and durable responses in heavily pretreated EGFR wild type non-small cell lung cancer patients with the longest response now ongoing for 10 months in patients with prior documented progression on PD-1 targeting therapy.

This data is supported by the observation of objective and confirmed responses in patients with heavily pretreated EGFR mutant non-small cell lung cancer, a disease that historically has not been sensitive to immune mediated treatments. Of note, we see these results with a regimen that does not include any chemotherapy and thus may be better tolerated in this heavily pretreated patient population.

I think the totality of the data reported today support our strong belief that the innate immune system can be utilized to fight multiple types of hematological and solid tumors, and -- Affimed's propriety ICE molecules can provide the necessary targeting and activation as guided, we will have additional important data readouts in the course of the year.

Affimed with its portfolio of several potent NK cell engagers and was its experienced and highly motivated clinical development organization. It's well-suited to advance the use of the innate immune system has an initial additional treatment option for patients in need. We will continue our path to advance these exciting programs and thereby bring value to our organization, our patients and our shareholders.

With this, I thank you all for your attention, and I'm happy to take questions. Operator, please.

(Operator instructions) Kripa Devarakonda, Truist Securities.

Hey, guys. Thank you so much for taking my questions and congrats on all the progress on across the three three assets you have. So I have a question about luminaires. You talked you mentioned that Cohort one and two were enrolled and our assumption is that well, patients we saw data from seven patients today.

I know you said you were going to see updates later. Just wanted to get clarification on the remaining five patients. Had they not reached the first scan, which if I remember correctly seven. And when we see the next update, you know, will we get durability data or have a sense of the longest duration of follow-up? Thank you.

Yes. Thank you, Kripa, for your question. So first, your conclusion is right. We have included 12 patients in cohorts one and two. So they are filled. We are actively recruiting cohorts three and four Now the reason why we have not shown the data of the remaining five patients simply as we mentioned, that we initially had a certain delay in the recruitment of these patients are in the middle of they are treatments that first cycle, as you rightfully say, we have our first assessment on roughly week seven and week eight.

Now what you also reported today is that we want all our PET CT scans to be evaluated by blinded independent wheat, which is the FDA prescribed our final endpoints. So we want to make sure that data will really be consistent with the data sets that may go to FDA since may add another two to three weeks before you have your independent final readout data.

So we will have the data of these 12 patients are definitely in Q3. The question of follow up, of course, is always when are the first patients treated. Again, we will have a full update, of course, of these 12 patients, but realizing that and some of these patients have recently been entered, the first follow-up will probably be like three, four, five months follow-up they're not due to the fact that we expect a lot of relapses, but simply patients have not been on treatment for longer.

So if you want to have a real long-term follow-up where patients have the chance to be a year or so on this protocol since probably will more be towards the end of the year.

Thank you so much.

Daina Graybosch, Leerink Partners.

Yes. A question for me to on LuminICE-203. Andreas. I wonder if you could talk about what was driving the screen failures of dropout. I just wonder if there's any implications of that for the type of patients that could be treated by this going forward. And yes, let's take that.

Yes. That's a great question. And we spent quite some time investigating what happened. I think there's still some training on the sites because physicians may have been over eager to enroll patients. So we had a couple of patients and third arm initially looked like they would fulfill all inclusion criteria, then after review, we found out that, for example, one patient had no previous or it is a little brentuximab treatment, one patient did not have a PD-1 treatment.

One patient had a documented or allergic reaction to CD3 targeting treatments are than we have seen a couple of patients. Again, these are very sick patients. We acquired viral infections and they deliver to patients was an intervening COVID infection that made them drop out.

And in fact, we had one or two patients who withdraw informed consent when they considered are significant commuting distances. Again, we only have like 10 sites opened, so for some patients in the US. There is still a very significant commuting involved to participate in this trial.

With more training on the trial side, I think at least we will see a reduction in patients who are not fulfilling all inclusion criteria with more sites actors, we can reduce the commuting issues. I think the third issue patients with Hodgkin's Lymphoma was four or five previous treatments are more prone to virus infections.

So we may still see some patients who acquire intermittent mode. Co-morbidities are intermittent diseases while in the screening period.

Perfect. That's very helpful. Thank you.

Maury Raycroft, Jefferies.

Hi, congrats on the progress and thanks for taking my question. Tom, just based on your insights into enrollment and guidance for having another data update on the first two cohorts in Q3. At this point, can you project when you think you'll complete the run-in phase and start the randomization phase. I guess, is there anything more on time lines that you're able to say about the study at this point?

And then can you remind me if you need to go back to FDA to get feedback before you can start the randomized part of the study?

Yes. So let's take the first the last question first. So we do not need to go back to FDA or FDA have approved the whole sequence of study. So it's completely in our decision on up to our decision to progress into the Stage one stage two. Also, I would point to open the cohort for peripheral T-cell lymphomas. In terms of guidance, again, we have fully enrolled cohorts one and two.

And as I said, we expect to have the data of the additional five from patients in terms of responses in Q3, and then we will give updates on occur at our earnings calls. We also intend to submit these data to the scientific conference. For cohort three and four, and we will do a projection once we are through this staggered period again, cohort three and four have, the first three patients per cohort staggered.

This has been a little bit of an uncertainty in cohorts one and two. So I think we do have better guidance once we have completed the first six patients in cohorts three and four.

Okay, understood. And I'm just wondering if you can clarify if the if the data are a mix of cohorts one and two and at this point, do you have any any view on how the two different dose cohorts are comparing as far as the dosing strategies?

Again, it's a limited number of patients. We have a equal representation of cohorts one and two, I think we have four patients and one in three patients in two of up to this point, we did not see any differences. Both cohorts have contributed our responses and complete responses.

Interestingly, we also have not seen any differences in side effects. So the 200 milligrams or 300 milligram Acimtamig dose are absolutely similar into in terms of their side effect profile.

Okay, thanks for taking my questions. Are back in the queue.

Li Watsek, Cantor Fitzgerald.

Hey, good morning and thanks for taking my questions. I'm wondering if you can just comment on, you know, the number of site cause that these certifications being created and I know the protocol allows up to three cycles. So just wondering if you can give some information there.

And we are currently we basically have everything. So we have a couple of patients in the second cycle. We have operations are now going into Cyprus. We are we have a patient who is now going to stem cell transplant are incomplete response. So it's yes, it's a mixture of cycles of importantly, as a treatment has been very well tolerated.

So we have not seen any treatment discontinuations due to side effects and all patients basically go as plants without sequence of cycles.

Okay. And then maybe a follow-up question for the patient baseline characteristics enrolled in this study versus at the MD Anderson, one of four study. Can you maybe just, comment on prior lines of treatment and are there any response to most recent treatment for these patients.

And I remember, I think in 104 study, we're looking at maybe seven prior lines of treatment versus here for and maybe just talk a little bit about how should we think about patient patient patients enrolled?

Yes. So here we pass are technically a somewhat shorter number of lower number of previous treatment lines. Which I think is already reflecting what we expect to see also in the marketplace when patients are before we published the MD Anderson data. They simply did not have any any alternative.

So physicians were trying quite exotic things which amounted to this high number of previous lines of therapy. Now with this very active treatment available to our physicians start to refer earlier patients thought to this treatment option because they also feel that this is by far the best chance of patients who have failed chemotherapy, etceteras and PD-1.

So it's a good development, I think because our patients get to a potentially life-saving treatment earlier, it is good also in terms of market protection, if we can establish this regimen in earlier lines of treatment.

Importantly, the FDA was very clear on what defines a patient with unmet medical need, and that is our failure of combination chemotherapy, failure to PD-1 and failure to et cetera. And all these patients fulfills the FDA required criteria for unmet medical needs.

Okay, great. Thank you.

Yale Jen, Laidlaw & Company.

Good morning and thanks for taking the questions. And congrats on the progress. Just two quick ones here. First one is for AFM28, you have got you guys are talking about seeking having NK cells to that study, what's the current progress and what was the option being considered at this moment?

Yes, we are in active in an active process to identify an allogeneic and cryopreserved NK cell products. These are discussions that are ongoing. So I cannot say a lot of details here, but I think we are on a very good way.

Okay, great. And maybe one housekeeping question is we just noticed that the for the last quarter, is it [$23 million] of cash used that you guided that thought in terms of runway to the second half of next year, shall we for modeling purposes. Should we consider that the expense going forward for the next few quarters will be reduced more and that will be the projection, would that be the project? Thanks.

I think that's a question I would hand over to Harry or Michael.

No, I'm happy to answer these questions. So the cash guidance into H2 2025 is based on operational financial plans. So one element contributing to that is a significantly lower spend as a matter of fact, we spend in Q1 2023, 10 million more then in Q1 this year.

So we do have reduced spend based on the fact that we only have half the personnel, we significantly reduced costs, regard lease expense, et cetera. So that's one contribution.

The other one, it includes certain amounts more of payments to be made be it with business development, albeit with other financing transactions. And we continue tightly monitor our spending. And so that's how this guidance came along.

Okay, great. That's very helpful. And thanks for taking the question.

Brad Canino, Stifel.

Thank you.

Just to double-click on the drop-outs question following Dana's question, I think the question when there are so many dropouts is always the potential for the results to have some form of bias from a selection of a narrow patient population and maybe those that are fit enough to wait as the enrollment process is being streamlined, it would be good to hear your view on whether or not this has occurred.

And second, could you talk about your ongoing relationship with Artiva and both companies' commitment to the study as the program continues to advance now? Thank you.

Yes. So for the dropouts from as I said, we have not seen any pattern. And importantly, I do not see any indication of a selection bias against. It's a very mixed mixed bag of reasons. Some are logistic my belief is that that will be solved if we have a even broader product geographic spread of participating sites.

Some is that people were, I think, very enthusiastic, and we see this enthusiasm on our investigator sites to enroll a patient and some patients did not really fulfill all criteria for unmet medical need home. As I said, we had patients who had not been pretreated with, ADCETRIS.

These patients are receiving a surface treatment now they will have the option if they should fail, ADCETRIS. Just to go back into the study, we have a very clear defined are population of patients, again, failing chemotherapies, failing PD-1, failing, ADCETRIS.

And if they're transplant eligible, they should also have received a transplant before. And so this is something that FDA agreed upon is an area of complete unmet medical need, and we will stick very closely to this FDA guidance, but I do not see any selection bias or any enrichment of certain patients.

In terms of our relationship with Artiva, they are as enthusiastic about the data as we are. We have a good relationship we have strong support from the Artiva side to continue on this study on this program. And so there's nothing else to report other than real working relationship.

Great to hear the color. Thanks, Andreas.

Thank you. (Operator Instructions) There are no further questions. This does conclude the Q&A session. You may now disconnect. Everyone, have a great day.

Thank you. Bye-bye.

You are welcome.