Affimed NV (AFMD) 2018 Q1 法說會逐字稿

Good day, and welcome to the Affimed First Quarter 2018 Financial Results and Corporate Update Conference Call. Today's conference is being recorded. At this time, I would like to turn the conference over to Anca Alexandru. Please go ahead.

Thank you. I'd like to welcome you to our Investor and Analyst call on the results for the first quarter of 2018. On the call with me today are Adi Hoess, CEO of Affimed, who will present a corporate update and Florian Fischer, Affimed's CFO, who will walk you through the financials. Also on the call is Leila Alland, Affimed's CMO, who will be available for questions in the Q&A session.

Before we start, please note that this call and the Q&A session contain forward-looking statements, including statements regarding our future financial condition, business strategy and our plans and objectives for future operations. These statements represent our beliefs and assumptions only as of the date of this discussion.

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 forward-looking 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 Cautionary Statement Regarding Forward-Looking Statement in our Form 6-K filed with the SEC earlier today.

Thank you for your understanding. I will now hand the call over to our CEO, Adi Hoess, who will provide a corporate update.

Thanks a lot, Anca. Affimed has multiple ongoing clinical stage programs built on our antibody platform that are advancing in Phase I and Phase IIa studies. The NK-cell engager AFM13 is being developed to treat CD30-positive malignancies and has shown a favorable safety profile as monotherapy and in combination with pembrolizumab as well as emerging efficacy data. The T-cell engager AFM11 is being developed to treat CD19-positive B-cell malignancies, and we are evaluating safety and preliminary efficacy in 2 Phase I studies in NHL and ALL.

Furthermore, a second T-cell engager based on our platform is being developed by Amphivena to treat CD33-positive malignancies such as AML in a Phase I dose escalation study. We recently introduced our Redirected Optimized Cell Killing platform, ROCK in short. This is a highly customizable NK and T-cell engager platform and 2 preclinical stage programs have led to candidate entering IND-enabling study. Furthermore to accelerate our pipeline development, we have formed partnerships with industry, academia and advocacy groups such as Merck, the MD Anderson Cancer Center, Columbia University, Leukemia & Lymphoma Society, just to mention a few of our collaborators.

Slide 4 shows our unencumbered clinical and preclinical pipeline. All of our NK-cell engagers bind to CD69 on NK-cells, while for T-cell targeting, the engagers bind to CD3 on T-cells. Our lead product candidate AFM13 has shown positive efficacy data as monotherapy in Hodgkin lymphoma and also in CD30-positive lymphoma, which we believe represents a novel opportunity with limited competition, for example, in anaplastic large cell lymphoma or peripheral T-cell lymphoma.

We have also reported encouraging efficacy of AFM13 in combination with a checkpoint inhibitor, Keytruda. I will provide more detail on the clinical data for AFM13 in this call.

Our EGFR-targeting NK-cell engager, AFM24, has the potential to widen the therapeutic window and address the patient population resistant to standard of care. We are developing AFM24 as a first-in-class NK-cell engager in solid tumors and believe that AFM24 also has the opportunity to improve efficacy of checkpoint inhibitors.

AFM26 is a BCMA-specific NK-cell engager that we're developing in multiple myeloma. In particular, we aim to leverage BCMA as a target in autologous stem cell transplant eligible patients, a setting where we believe NK-cell engagers represent a well-differentiated opportunity. Our T-cell engager AFM11 confers a well-differentiated approach for CD19-positive malignancies, in particular, for the treatment of diffuse large T-cell lymphoma and mantle cell lymphoma. We believe that AFM11 represents a great opportunity for Affimed with the potential to pave the path for fast market approval.

A second T-cell engager program based on our platform called AMV564 is being clinically developed by Amphivena, a company of which we own about 18.5% fully diluted.

Slide 6. To the updates. As announced in March, Dr. Leila Alland joined us as Chief Medical Officer. Her broad expertise in immuno-oncology and oncology will be instrumental to advance our product candidates through the clinic and for developing our future clinical development strategy. We're happy to have Leila with us on the call today, and she will be available to answer your questions during the Q&A session.

Our long-standing supervisory board member, Rick Stead, has decided to step down from Affimed's Supervisory Board effective June 19, 2018. We're very grateful to Rick for his valuable contributions during his 11-year tenure. Our Supervisory Board intends to nominate Dr. Mathieu Simon, a seasoned immuno-oncology expert, as a new supervisory board member succeeding Rick. As you know from our fourth quarter 2017 update, in February 2018, we completed an underwritten public offering on the Nasdaq Global Market, raising a total of approximately $24.5 million in net proceeds.

In terms of platform updates, we're very excited to have officially launched our ROCK platform. ROCK stands for Redirected Optimized Cell Killing. We officially introduced ROCK to the scientific community in 2 well-received presentations at the PEGS, Protein Engineering Summit, in Boston in early May 2018.

I will talk more about ROCK later.

Throughout the first quarter, we have continued to progress our NK-cell engagers through clinical and preclinical development as shown on Slide 7. In February 2018, we reported very encouraging data from studies of our lead candidate, AFM13. We intend to present our next set of data from the AFM13 combination study with Keytruda at the 23rd Annual Congress of European Hematology Association called EHA in Stockholm in mid-June 2018. At the AACR 2018 Annual Meeting in Chicago, we presented data highlighting our progress toward novel EGF -- EGFR-targeting therapy. We showed data on 2 development candidates from our AFM24 program, which are based on our ROCK platform. We anticipate completely -- completing IND-enabling studies for one of the candidates by mid-year 2019. We continue to advance our AFM26 lead candidate through preclinical development. This BCMA-targeting NK-cell engager is designed to address the medical need of eliminating minimal residual disease in patients with multiple myeloma. Again leveraging our ROCK platform, we're developing several different antibody formats for AFM26.

Slide 8. Regarding our T-cell engager programs, we see a great opportunity with our differentiated proprietary formats, which are highly specific, have unique PK/PD profiles, and do not confer nonspecific activation of T-cells in absence of target cells. While to date, several competitive programs presented with low objective response rates are (inaudible) , our 2 Phase I escalation trials of AFM11 are progressing well. Both our trials in patients suffering from NHL and from ALL respectively are actively recruiting patients as dose escalation continues.

Further clinical validation could come from Amphivena's AMV564, a CD33/CD3-specific T-cell engager based on our technology platform. The other Phase I study is ongoing and recruiting in AML. Amphivena is also planning to initiate a study in myelodysplastic syndrome and is exploring the potential to address myeloid-derived suppressor cells in solid tumors.

Slide 9. We believe that the ability to utilize different antibody formats to activate innate and adaptive immune cells is a prerequisite to developing effective therapies for different cancers and other life-threatening diseases. Our versatile ROCK platform meets this need and enables us to develop differentiated therapies aimed at improving efficacy and safety. We're very proud of our fantastic team, who have employed the extensive drug development expertise to create ROCK. Its unique modularity is built on a proprietary toolbox and long-standing engineering know-how. Specifically, the ROCK platform allows the generation of antibodies that target different tumor-associated antigens, use the avidity effect, possess long cell retention time, recruit NK cell through our anti-CD16A-specific and T-cells through our anti-CD3-specific epitopes, offer different PK profiles and show excellent stability and manufacturing features.

Importantly, the ROCK platform can suitably be applied for development of NK and T-cell recruiting antibodies.

Slide 10 shows in detail how our ROCK platform is built up and designed to reduce the complexity of antibody engineering. ROCK employs a toolbox of scaffolds, linkers and antibody binding domains and from these building blocks, we can create very distinct antibody formats either solidly comprising antibody variable domains or full-length IgG scaffolds. The antitumor antigen binding domain can then simply be plugged into the antibody format. Based on ROCK's modular nature and versatility, we can engineer and assess different formats in parallel.

Slide 11. Our approach to high-affinity CD16A targeting on NK cell is unique in the industry and allows us to address the need of targeting malignant cells that escape elimination by current therapeutics. As we know, NK-cells are crucial in the body's defense against pathogens and malignantly transformed cells. While in the past, most immune-oncology approaches have focused on T-cells as effector cells. NK-cell-based approaches are being -- becoming more and more widely investigated with a variety of different technologies emerging from both at academic institutions and within the industry. We believe that the overall progress in the field is very encouraging.

A recent data publication shows signs of efficacy of adoptive transfer or CAR-NK treatment as presented, for example, at the recent Innate Killer Summit. To our knowledge, CD16A is the only receptor-triggering ADCC and does not require additional co-stimulatory signals. Importantly, CD16A is constitutively expressed on about 95% of NK-cells. Our approach is unique as our antibodies target a specific epitope on CD16A. We've optimized such CD16A binding to maximize NK-cell-mediated killing with more than a thousandfold greater affinity to CD16A as compared to monoclonal antibodies.

In addition, binding to CD16A is largely unaffected by plasma IgG. A major hurdle for NK-cell activation by IgG-based therapeutic antibody. This is particularly important as in the ground state CD16 on innate immune cells is occupied by polyclonal plasma IgG. This creates a significant threshold for IgG-based therapeutic antibodies as there is a huge excess of plasma IgG versus therapeutic antibody, however, not for Affimed CD16A targeting antibodies. The unique epitope recognized by our NK-cell engagers results in them being virtually unaffected by plasma IgG. Furthermore, CD16A binding is independent of the valine/phenylalanine polymorphism and finally our highly specific NK-cell engagers do not bind to CD16b or neutrophils avoiding a sync effect. We believe that these features are highly important in targeting malignant cells, which escape elimination by current therapies, for example, cells with low target expression.

Slide 12. A virtual lack of affection by IgG competition on cytotoxicity is shown here on the right side. While Affimed CD16A ROCK molecules are virtually not affected, IgG-based monoclonal antibodies show a very potent competition of cytotoxicity by polyclonal IgG, thereby preventing NK-cell killing. Our approach is introducing a potent novel mechanism of action that we're using for a variety of antigens as I'll describe later.

On the left side, you can see that our proprietary NK-cell engages are designed for efficient T-cell killing even at low target BCMA expression of a few hundred receptors per cell. All of these features result in overall increased potency and efficacy.

Slide 13. We believe that optimal I/O approaches build on both innate and adaptive immunity. Tumor immune evasion impairs both NK and T-cell function and, therefore, optimal I/O approaches should build on both immune systems. NK and T-cells are very different in how they recognize a tumor. While an NK cell shows nonspecific recognition, T-cells are only active once they can specifically recognize a tumor. Hence, the mechanisms by which a tumor can prevent destruction are very different. While for NK-cells, the inability to recognize tumor cells may be the key mechanism, for T-cells it is the inhibition of their activation, for example, through checkpoint inhibitors. In this context, we have generated data in Hodgkin lymphoma, both in vivo and in patient combining treatments targeting innate and adaptive immunity. As mentioned earlier, we are generating clinical proof-of-concept for our NK-cell engager approach by developing our lead candidate, AFM13, as mono and combination therapy. In the past, we have reported data showing that we have observed clinical efficacy in both mono and combination therapeutic setting. AFM13 has already demonstrated evidence of safety and clinical efficacy in heavily pretreated Hodgkin lymphoma patients in a Phase I study, and 3 clinical studies for AFM13 are currently ongoing. In Phase IIa in relapsed/refractory Hodgkin lymphoma led by the German Hodgkin Study Group, the favorable safety profile was confirmed and single-agent activity was demonstrated in patients failing standard treatment, including Adcetris. In February, we reported data from a Phase Ib/IIa IST in relapsed/refractory CD30-positive lymphoma led by Columbia University. Here single-agent activity was demonstrated, including one complete response, one partial response and one stable disease in the first cohort comprising 3 patients. These results are very encouraging as they provide further evidence that NK-cell engagers as monotherapy are able to induce tumor regression in this indication.

In general, diffuse CD30-positive lymphoma has an attractive indication that may broaden the potential for -- of AFM13. Both ISTs are open and actively recruiting patients currently. We're also conducting a Phase Ib study of AFM13 in combination with Merck's Keytruda in relapsed/refractory Hodgkin lymphoma. As previously reported, the combination was well tolerated with most of the adverse events observed mild to moderate in nature and manageable with standard of care. To date, we have reported best response preliminary data for 9 patients showing objective response rate and CRs, which compare favorably to historical data of anti-PD1 monotherapy alone in a similar patient population. We observed an ORR of 89% and a CR rate of 44%. In this study, recruitment has been completed and we intend to present the next dataset at EHA in mid-June.

Slide 15. We believe that our AFM24 program promises to be a well-differentiated I/O therapy to current standard of care treatment such as cetuximab. Through our molecule binding modality and the resulting immune effector cell activation, our molecules are differentiated from cetuximab by their immunotherapeutic mechanism of action.

In these molecules, the EGFR-binding domain was selected to minimize inhibition of EGF receptor-mediated signal transduction with the aim of achieving therapeutic efficacy, while lowering the risk of side effects such as skin toxicity that are associated with anti-EGFR monoclonal antibodies. The approach of NK-cell-mediated targeting of EGFR-expressing human cancers introduces a novel, highly potent effector function to address the needs of patients who may not benefit from anti-EGFR monoclonal antibodies. At AACR, we presented in vitro and in vivo data for 2 ROCK-based AFM24 candidates, showing the first evidence supporting this new mechanism of action. We anticipate completing IND-enabling studies for one of the candidate by mid-year 2019.

Slide 16 shows data from the 2 candidates. They're called AFM24 (sic) [AFM24_I] and AFM24_T. Both candidates bind with high affinity to primary human NK-cells in the presence and absence of polyclonal IgG, which is shown on the top right. On the bottom right, AFM24_I demonstrates potent tumor growth inhibition at different concentrations.

Slide 17 summarizes our work for AFM26, which we are developing as an NK-cell engaging bispecific antibody targeting B-cell maturation antigen. And we are addressing the medical need in multiple myeloma. Preclinical development for our candidates based on the ROCK platform is ongoing.

Slide 18. As mentioned earlier, our tetravalent multispecific antibody platform has several differentiating features and offers the potential to overcome the challenge to find the optimal therapeutic window with a T-cell engager. Differentiating features include no nonspecific activation of T-cells in absence of target cells, targeting tumor cells with very low target expression, lysis of tumor cells independent of number of T-cells as well as significantly improved PK versus the BiTE. Our lead candidate AFM11 is in clinical development, and we are in the process of determining the recommended Phase II dose. Two Phase I dose escalation trials are ongoing and actively recruiting patients with relapsed/refractory ALL and NHL, respectively. With our T-cell engagers, we have the potential to pave a path to fast market approval in indications such as diffuse large B cell lymphoma and mantle cell lymphoma. As mentioned earlier, we have a second program that's developed by Amphivena called AMV564, which is a CD33/CD3-specific antibody, which is based on our technology platform. Amphivena continues to recruit patients into its first in-human Phase I dose escalation study with relapsed/refractory AML.

I will now hand the call over to our CFO, Florian Fischer, who will provide further details on the financial figures.

Thank you, Adi. Affimed's consolidated financial statements have been prepared in accordance with IFRS as issued by the International Accounting Standard Board or IASB. The consolidated financial statements are presented in euros, which is the company's functional and presentation currency. Therefore, all financial numbers that I will present here in this call, unless otherwise noted, will be in euros. Any numbers referring to Q1 2017 and Q1 2018 are unaudited.

Cash and cash equivalent totaled EUR 55.3 million as of March 31, 2018, compared to EUR 39.8 million as of December 31, 2017. The increase was primarily attributable to the net proceeds of EUR 19.7 million from public offering, partially offset by Affimed's operational expense.

Net cash used in operating activities was EUR 6.9 million for the first quarter 2018, compared to EUR 7.2 million for the first quarter of 2017. Cash flow from financing activities amounted to EUR 22.6 million for the first quarter of 2018, compared to EUR 16.4 million for the first quarter of 2009 -- 2017. Affimed expects to have cash to fund its operations at least until the fourth quarter of 2019. This provides run rate for the planned development of our clinical programs as well as for further discovery and early development activities.

Revenue for the first quarter of 2018 was EUR 500,000 compared to EUR 400,000 for the first quarter of 2017. Revenue in both periods was derived from Affimed's collaboration with LLS and the AbCheck service revenue. R&D expenses for the first quarter of 2018 were EUR 6.4 million compared to EUR 5.4 million for the first quarter of 2017. The increase was primarily related to higher expenses for AFM11 preclinical programs and infrastructure. G&A expenses for the first quarter of 2018 were slightly lower with EUR 2 million compared to EUR 2.2 million for the first quarter of 2017.

Loss for the first quarter of 2018 was EUR 8.2 million or EUR 0.15 per common share compared to a loss of EUR 7.8 million or EUR 0.19 cents per common share for the first quarter of 2017. The increase in loss was primarily related to higher spending on R&D for AFM11 preclinical programs and infrastructure.

I will now turn the call back over to Adi for a summary of our 2 clinical programs and our pipeline. Adi?

Thanks a lot, Florian. Our strategy is to maximize the value in our unencumbered clinical and preclinical pipeline of NK and T-cell engagers as well as from our platform. We are expanding our leadership in NK-cell-mediated tumor cell killing by leveraging our lead product AFM13 as monotherapy in CD30-positive lymphoma and in combination with Keytruda. Based on the encouraging clinical data, we are currently planning follow-on clinical studies. The clinical data for AFM13 are further stimulating the generation of an NK-cell engager pipeline into our advancing further preclinical candidate such as AFM24 and AFM26. Another focus of our activities is the exploration of NK-cell engagers in combination with adoptive NK-cells or immune-activating agent such as IL-2 and IL-15 as we have previously mentioned. We're also advancing T-cell engagers and our lead molecule, AFM11, is being investigated in the studies that I mentioned before with the goal to identify the MTD and achieve proof-of-concept. Indeed, we're also planning follow-on clinical studies for AFM11. With Amphivena's AMV564 additional (inaudible) is possible in AML. Having developed our ROCK platform, we can now continue to broaden our engager pipeline and we'll leverage our pipeline and technology to create value through next-generation product and partnership opportunity.

On Slide 21, you can see an overview of our executive team, which we have strengthened considerably over the last year. We are a joint European and U.S. team, combining deep pharma and biotech expertise as well as program planning and execution of immuno-oncology clinical development and importantly all the commercial strategy and business development expertise.

Thank you very much for interest and the call is now open for questions.

(Operator Instructions) Our first question today comes from Do Kim of BMO Capital Markets.

On the AFM13 update that you're expecting at EHA, could you tell us what we should expect in terms of data? Will you have results for all 24 patients?

Leila, are you going to jump in here, please?

Yes. I'll jump in that. So as Adi said, we'll be providing an update at the EHA meeting in mid-June, and we will have data on approximately 18 patients at that meeting. This will include data, which includes at least 3 months data from all 18 patients. It will be the most up-to-date data that we have. We're currently compiling that data and we'll be ready to present that in mid-June.

Great. And I wanted to ask about the ROCK platform. Are your plans to use that exclusively for internal drug development? Or is there a strategy to potentially find partners for drug discovery to license externally?

Yes. It's a -- thanks for this question. It's a very good question. And indeed, one of our strategies has been with learning of how our molecules worked in the clinic is then to specifically design molecules that may have different features. So that work has been ongoing since a while and resulted now in this -- in the ROCK platform. And we primarily, obviously, did that for our own benefit because the AFM24 and AFM26 are based on that platform, and we've carefully designed these molecules to address specific settings. So that was the first intention that the result of the platform was always aimed to be a platform used for product development, indeed for Affimed target. Obviously, there are more opportunities out, and we are now sharing the data with the broader industry, that's why we gave a -- 2 presentations at the PEGS meeting, and we are currently collecting feedback on that. But again, we may do certain collaborations with third parties, but we're not a service company that now broadly gives success to multiple targets. So we will do this in a very detailed manner where a party may have an interest to do a significant collaboration with Affimed. That's our strategy currently that we will pursue.

We will now take a question from Maury Raycroft of Jefferies.

I'm excited to see the additional data at EHA. I guess, maybe just a few points of clarification on the EHA data for the AFM13 combo for some of the patients, will we see 6-month follow-up?

Again, Leila?

Yes, sure. So with any clinical study patients have been involved for a range of time is depending on when treatment began. So what we'll be presenting at EHA is patients who've been on study for a minimum of 3 months and some of whom will have been on study for longer.

Okay. Okay. Great. And as far as the 6 additional patients, who I believe have been enrolled, so if those patients have been treated, would you potentially top line all 24 patients around the EHA update? So maybe you have the 18 in the EHA presentation, but then have all 24 included in some sort of press release outside of that conference. Is that possible?

No. We have guided to anticipating full 3 months' data by mid-year and full 6 months' data by the end of the year. We'll be presenting the most up-to-date data at EHA, which will include the data on approximately 18 patients.

Got it. Okay. Okay. And then for next steps with -- meeting with the regulators, I guess, what will be the expectations going into that meeting? And what will you be trying to accomplish with that?

Is your question in relation to AFM13?

Yes. Yes, for the combo. I think there was -- at some point, there was some guidance around that, that there would potentially be a meeting with regulators following the AFM13 combo data. So I'm just wondering if there is any additional clarity on what -- if that would happen and if there is some sort of expectations for what the meeting would be?

Okay. Thank you. We are in the process of establishing our clinical development strategy moving forward. And this includes interactions with regulatory authorities as well as with all of our stakeholders, including our investigators and our KOLs and, of course, our collaboration partner, Merck, our collaborator for the combination study. So we will update you in due course when these plans have been solidified.

Okay. Sounds good. And as far as, I don't know if you can comment on this or not, but for the EHA data for the combo study, is that going to be an oral presentation or a poster? Can you disclose that?

We will notify that. It has been accepted for poster presentation.

Got it. And last question is based on the T-cell lymphoma trial. Is it possible that we could see data from that at EHA as well?

As you know, this is an investigator-sponsored study, and we've been working closely with the sponsor of the study to provide regular update of the data. We will not have additional data to be presented at EHA.

We will now take a question from Yale Jen of Laidlaw & Company.

Just in terms of the ROCK platform you recently developed, could you give us some sense, maybe quantitatively, to compare with the earlier version, I mean, or the original version of the NK engagers, so we may see some sort of quantitative differences or any specific attributes that was the improvement? In other words, a little bit more color on this platform?

Yes. So thanks Yale for this question. Indeed we are -- how does the platform work now? So what -- as I've indicated, there is a toolbox of scaffold, linkers, antibody domain, and what we've been doing over the past years, we've generated a very significant amount of very different molecules, some are IgG based, some are just based off Fc-binding domain -- sorry, just off antibody-binding domain. And what our goal was that we can identify a minimum number of scaffolds that are very different and, I guess, they're shown in the presentation how they differentiate. So some have full-length IgGs, others incorporate diabody motif, others just have a tetravalent structure. And what we are doing is that we can use a very small number of these kind of validated formats, plug-in antibody binding domains and then have a set of, let's say, 5, 10, 15, very different molecules and not just the TandAbs as we have had previously available. Then we'll take these molecules forward of which we already know that they are stable, that they are well manufactured and then we profile them in a variety of assays. So in the beginning, you will not have to make a choice either to go for whatever I call it form, A, B, C or D, you will just take, as I say, the small number of antibodies that all are EG -- directed against the tumor antigen, compare them in a variety of assays and then at the end, you can decide which one you're going to take forward. How are they differentiating? They're differentiating by affinities. They're differentiating by their BiTE distribution. They're differentiating by their PK. So they all have features that can influence uptake into the tumor that can also influence dosing regimen. So this would be the versatility that we have available, and we can take a conscious decision on which is the best candidate after we've generated data. I hope this helps on how we are employing it and that we do not have to pick a particular antibody format in the first place.

So it potentially give you a broader variety of sort of end product prospects to be choose from -- or screening it from as well as it is a platform that maybe technically easier to assemble a large number of a variety things instead of a more specific sort of process that has been used -- will narrow the process being used before. Was that a fair way to think about that?

Yes, exactly. It gives us a much broader footing in terms of how these molecules now are comprised of. So they -- as I said, they all have different features. We're exploring them in parallel. And as I said, the TandAbs are part of ROCK as much as IgG structures are or what we call (inaudible). So there is an enormous versatility in this platform, and the eventual candidate is being picked based on a target product profile, but many of -- as I say, all of these candidates would already qualify in principle to be within the target product profile, but only the final molecules that we have available then can be tested.

And maybe just one follow-up in here, which I believe you mentioned that 24 is selected or processed from the ROCK process, and is that 26 also is the same way? And the follow-up question really on that is that going forward, would you going to sort of revamp some of these, for instance, existing 11, 13 to a more, more better -- greater sort of versatility type of screening process for -- going forward?

So it's a very good question. So indeed, the first half of your question is on 24 and 26. Yes, they are indeed based on the ROCK platform. But each of the respective programs always comprise an antibody that's based on a IgG domain, but it's also just solidly based on antibody-binding domain. So we have still the full breadth of different kind of antibody modalities available both for AFM24 and for AFM26. Another good question is how would we go back to AFM13 and AFM11. Let me give you an answer specifically for AFM11. From what we've learned in the field is that we have currently seen efficacy of T-cell engagers based on a BiTE. So this is (inaudible). And there is some sort of proof-of-concept also available from a DART. These are based -- these are both fairly short-lived molecules that are given by continuous infusion because their half-life is in the range of just a few hours. There have been platforms developed that have longer half-lives, so they are based on IgG formats, but as the companies have reported, either ORRs were not high enough or some of the programs even have to be stopped. So for T-cells, such as T-cell engagers such as AFM11 or even AMV564, the structure we have available currently may already be a quite good one. And that's why we are progressing AFM11, and we're not thinking in that direction that we need to have a replacement for AFM11 based on another ROCK molecule. So T-cell engagers, NK-cell engagers, as I say, they've gone -- they go through a very thorough process. Then we check the TPP and the candidates we have available and those that are generated new in our minds fulfill the TPPs so that we eventually can bring this product if they're potent enough and safe enough to the market.

We will now take a question from Jim Birchenough of Wells Fargo.

Question on AFM11. Can you remind us where we're at in the dose escalation? And if we're at a dose that one would expect efficacy and then ultimately, when you think about the dose range that's being explored here, at what point do you think we'll be able to benchmark against (inaudible) or even against the CD19 CAR-T?

Leila, do you want to jump in here or shall I go?

Yes, sure. I'd be happy to. Thank you for the question. Both studies are actively recruiting patients and dose escalation continues for both studies. We are currently in dose level 4 for the NHL study and in dose level 5 for the ALL study. We plan to complete dose escalation and once we have completed this, we will be able to provide a more meaningful update, including our -- the comparison of our data compared to what would be expected with (inaudible). I believe we've mentioned in the past that with some preclinical data -- that based on preclinical data, we could reach potentially active doses somewhere between dose levels 5 to 7, but of course, it's difficult to predict from preclinical such clinical data. We've not guided to a specific time point at which we will be presenting data. But dose escalation continues, as I said, for both studies and we're -- we'll have a lot more data available as the year progresses.

And, Leila, just on AFM13, we've got the 3-month update for 24 patients by mid-year and 6 months by year-end. Do you need that 6-month update to advance discussions on a Phase II? Or is the 3-month data sufficient to have those discussions with FDA and initiate a Phase II?

We are actively having those discussions currently internally and with our stakeholders. I think we have ongoing discussions with regulators, so I don't think we're looking for a specific dataset, I mean, to trigger those activities now.

And then maybe, Adi, just on the ROCK platform. Can you say whether that platform may -- might accelerate the process of -- from discovery to IND filing? What's that current time line? And could ROCK -- with this modular platform accelerate that, do you think?

Yes, thanks a lot. That's a very good question and indeed it does. So this modularity and versatility allows us to generate lead candidates indeed very quickly. So if we have an antibody-binding domain available, we can just plug that in, then profile the -- these candidates next to each other and then initiate research cell and generation. I mean, there is always an optimal scenario and when I had mentioned time lines, always my researches are jumping on my throat, indeed. But it's indeed a very straightforward process. So you can imagine engineering new antibodies by plugging in antibody-binding domains, you can do it in a few months. And then when these candidates are really stable and effective, then you can just go ahead with initiating IND-enabling studies. So exact time lines is always hard to predict because this also relates to the specific target the other assays available that are required, but it's at least as fast as generating monoclonal antibodies.

And I was going to ask you about time lines, and I will. I understand you might not be able to answer, but for AFM24 and AFM26, do you have a target timeframe for IND-enabling studies for each of those?

Yes, we do. We have announced it for indeed AFM24. So that we will -- we're planning to have the IND by mid-year 2019. For 26, we haven't yet announced, but for AFM24, we did.

We will now take a question from Peter Lawson of SunTrust Robinson Humphrey.

Adi, just on AFM11. Just -- do you think you can get data from NHL patients first or ALL? And any color around the line of patients you're seeing in the dose escalation for both of these?

Leila?

Yes. So I'm pleased to say that we have 2 studies that are dose escalating in parallel, one with NHL patients and the other with ALL patients. So it's a little bit difficult to predict which one will show activity first. But fortunately, we've not taken a sequential approach, but we've taken a parallel approach and so we're gathering data for both patient population.

Sorry, (inaudible) this is something new -- you may recall that in the past studies, we're not progressing as fast. There were different reasons associated with that. We have addressed all these in the meantime and the progress is indeed very good, but what we're asking you is a little bit more patience before we are -- as I say, before we are coming to more solid data in the dose escalations as they are ongoing and then we can inform you. So we keep you updated on that as we progress.

But we shouldn't think about those

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it's more of a 2019 event do you think?

In terms of timing, again, I -- we're not at the moment committing to any time lines, in essence. As Leila has said, we are approaching active dose levels from our preclinical experiments, dose levels 5, 6, 7, you can see that as Leila just said, we are approaching or we are in the midst of these dose levels. So it is a T-cell engager, in essence, meaning that these are molecules that are very potent. And things are progressing well in our end. So in terms of being more precise, it's very challenging to be so. But on the other side, it's progressing well. So we're accumulating data on our end.

Got you. And then I guess, in AFM13 for Hodgkin's lymphoma, how do you see the kind of commercialization path in diseases relatively well controlled (inaudible) against ADC kind of I/O option? Where do you see AFM13 kind of fit in into that paradigm?

So there are a -- still a significant number of patients that are not cured, especially patients that relapsed/refractory to stem cell transplants or any third, fourth, fifth line patient even if other therapies are available, these patients indeed go on these therapies, but eventually they relapse. So the market opportunity remains. And here it's rather dependent on how your efficacy is perceived and how the durability of responses is perceived and that's what you are currently generating. So we are not concerned about the market opportunity at that stage. We are seeing a good data on AFM13 relating to safety and efficacy. When I mean good, it's very encouraging what we have reported. And if -- so basically that gives us a lot of energy in order to bring these molecules forward. So overall, both in the setting of T-cell lymphoma and Hodgkin lymphoma, there is a very reasonable market opportunity in the relapsed/refractory setting.

And then, I apologize if I missed it, but the CD30-positive lymphoma, any color around the enrollment there. We had some nice initial data in February -- very nice initial data in February. Just when can we get the next update and any color around the CD13 how that's panning out?

Yes. We have said in the past our (inaudible) IST second, we're only recruiting patients that have cutaneous lesions. So there is a very specific subset of patients that we allow to enter the study for the reason that we are taking serial biopsies. And we've originally mentioned that we're working with investigator to present these data and our original plan was to have funding available in the second half of 2018.

Got you. Is there a particular venue or is it going to be a kind of top line thing?

As of now, that's too premature on how we want to do that. But the one thing we can tell you is that there is a significant excitement by being investigators on the conduct of the trials. So we'll just choose it as soon as all data are available.

Got you. Is there any way you can disclose how many patients you're going to looking up there?

Well, originally, we've said that we are treating a minimum of 9 patients, but there may -- it's always an option that we can expand that. As you may recall, in the beginning of the year, we have raised cash that gives -- will give us the opportunity to expand, especially the CD30-positive lymphoma indication. So those are the things that are currently ongoing. And just forgive us if we can't be precise enough because these are all ongoing discussions and we're just, as Leila has mentioned, bringing all these things together and then we can lay out these plans in much more detail. But as I said on my -- one of my last slides, we are planning ahead now for both AFM13 and AFM11, the next set of clinical studies.

We will now take a question from [Peter Overkamp] of [Peter] GmbH.

I have one short question about the ROCK platform. Do you have any suggestions what is with MHC peptide molecule that is not on your pipeline anymore?

Yes. We have a variety of earlier-stage program, amongst that is the MHC targeting peptide. So we have worked on that in order to show that we can make antibodies against very challenging targets. We've then converted these antibodies to both NK-cell and T-cell engagers and could, again, demonstrate that we have the opportunity to eliminate cells with low target expression, but obviously, our resources have to be focused. We see in the meantime much more activities for AFM13. We've just described the encouraging opportunities in -- with our combo study also with the T-cell lymphoma study. So that's where we're focusing. AFM11 is progressing very nicely. So again, that's where our commitment has been given to and on top of that, we have moved along 24 and 26 now to a substantial maturity on the preclinical side. So we are focusing on those programs for the time being as lead candidate, but obviously, there are earlier-stage molecules that we're not sharing with public domain at that stage, but obviously, we're discussing that with potential industry partners.

Suppose your ROCK platform does not inhibit these molecules, but would enable them as well?

Yes. The ROCK platform is just broadening the opportunity of selecting very different molecules. So this is rather making it more likely to identify developing candidates against specific targets. But what we have been doing is we have identified certain indications, I will call it, tumor indications that the need is to eliminate cells with very low target expression. Some reasons for the resistant is not that you have cells reoccurring that are target negative, but it's just very low. We're seeing this with BCMA over and over again that there are patients that represent with cancer cells that just have 100 copies. And we know that conventional technologies, IgG based, regular monoclonal antibodies or antibody drug conjugates would not really be suitable to eliminate such cells. So this is where our focus has been and the ROCK platform has been optimized towards such applications.

Ladies and gentlemen, as there are no further question in the queue, I would like to turn the call back to Mr. Adi Hoess for any additional or closing remarks.

Yes. Thanks to all of you for listening in on our Q1 financial earnings call. I appreciate all your questions. And as we said, we are very happy to have made significant progress with our programs, both clinically and preclinically and also have presented this new platform. And you could see the lively discussion that there is quite excitement. Thanks a lot.

Ladies and gentlemen, that will conclude today's conference call. Thank you for your participation. You may now disconnect.