Innate Pharma S.A. (IPH) Earnings Call Transcript & Summary

Good day, and thank you for standing by, and welcome to the Innate Pharma IR Event. [Operator Instructions] Please be advised the conference today is being recorded. I would now like to hand the conference over to your speaker today, Henry Wheeler. Please go ahead, sir.

Thank you very much, and welcome all to our investor event update on lacutamab and our ANKET NK cell engager platform. My name is Henry Wheeler, and I'm pleased to be with you today, having recently joined the company to lead our Investor Relations efforts. I'm very much looking forward to working with many of you to further discuss the exciting sites pipeline that Innate has to offer. With that, I will hand over to our CEO and Chairman of the Executive Board, Mondher Mahjoubi. Mondher, please go ahead.

Thank you, Henry. We are very pleased to have you on board. Thank you all for joining us today. As Henry said, I'm Mondher Mahjoubi, CEO of Innate Pharma, and I'm very pleased to welcome you to today's virtual investor event during which we will highlight recently presented data from our ongoing Phase II TELLOMAK study for lacutamab as well as preclinical data from our next-generation NK cell engager platform. Next slide, please. First, I would like to remind you that we will make forward-looking statements regarding the financial outlook in addition to regulatory and product development plans. These statements are subject to risks and uncertainties that may cause actual results to differ from those forecasted. Next slide, please. On today's call, I'm joined by Dr. Joyson Karakunnel, our Chief Medical Officer; and Dr. Eric Vivier, our Chief Scientific Officer. In addition, we are very pleased to be joined by Dr. Martine Bagot, Professor and Head of the Dermatology Department at the Saint Louis Hospital, University of Paris. Dr. Bagot is a leading expert in the treatment of cutaneous T-cell lymphoma, the primary investigator of our Phase I study with lacutamab and TELLOMAK study investigator. Next slide, please. So following my brief introduction, Joyson will provide you an overview on lacutamab as well as high-level summary of our recent development with this program. Following that, our future KOL, Dr. Bagot will provide an in-depth review of the TELLOMAK mycosis fungoides data, which were recently presented at the 16th International Conference on Malignant Lymphoma, Lugano. After that, we will pause to take your question on the lacutamab data. Then Eric Vivier will present the preclinical data of the ANKET, which was presented at the Federation of Clinical Immunology Society Virtual Annual Meeting early this month. Finally, I will close out the event with some concluding remarks, and then we will open up the call for question with all of our speakers. Next slide, please. Today's call focuses on 2 key advancements in our portfolio that not only set the stage for near-term value, but also highlight the strength and the depth of our core platform which will help to drive our growth well into the future. First, data from Stage 1 of the KIR3DL2-expressing MF cohort of our ongoing Phase II TELLOMAK study, which were presented yesterday provides very encouraging validation for lacutamab. This signal has allowed us to move into Stage 2 of the study much earlier than expected and support our broader T-cell lymphoma strategy with lacutamab. Next to that, recent advancements in our antibody-based NK cell engager therapeutics, or ANKET platform, represents a new evolution enhancing our existing trispecific NK cell engagement technology to support tetra-specific format. As you may remember, NK cells play a critical role in the cancer innate immunity cycle. And engaging them has the potential to improve the therapeutic window for cancer treatment compared to T-cell engagers. ANKET is a versatile fit-for-purpose technology that has created an entirely new class of molecules to induce synthetic immunity against cancer. Together, these updates reinforce our strategy and development capability, and we are very excited to share them with you today. Next slide, please. And before we move on to the main event, I'd like to spend a few minutes providing a brief overview of the company and highlighting recent execution against our corporate strategy. We at Innate Pharma are committed to building a robust pipeline of novel antibody therapeutics that leverage the body's own innate immunity target in area of high unmet medical need. Our core strategy and focus for '21 and beyond, which we introduced earlier this year are as follows. First, we are working diligently to drive near-term value with lacutamab, our lead proprietary asset. Secondly, we are working to leverage our antibody engineering capabilities to continue to develop innovative molecules with a primary focus on NK cell engagers. And lastly, we are also building a very sustainable business by creating a robust pipeline of differentiated assets in order to support our goal of delivering much-needed product to patients. As you have seen with our approach with monalizumab, we are committed to creating a strong foundation by creating products and bringing them through the early-stage clinical development, then leveraging partnership in order to secure nondilutive revenue streams for the business. This strategy both validates our scientific approach in technology as well as ensuring we can continue to invest in our science and pipeline. Next slide, please. Enabling this effort is our scientific know-how in the field of innate immunity. First, we are very pleased to see the growing momentum in understanding the important role NK cells play in developing therapeutics to treat cancer. These early approaches to immunotherapy were T cell-centric and have focused on enhancing T cell responses by targeting inhibitory pathways with immune checkpoint inhibitors. These treatments have led to unprecedented successes and have transformed the natural history of many cancers. Yet, the unmet medical need is still high as only a small fraction of patients respond to T cell therapy, and there remains significant relapse among those who do. Broadly speaking, T cells are not autonomous in their effector function and need help from cells of innate immunity. Broadly speaking, as I said, which we believe represent the second wave or next generation of immunotherapy. To us, choosing the right targets to direct the body's immune response is paramount. And we do this by utilizing our fundamental understanding of NK cell biology, tumor microenvironment and tumor antigen. In essence, we are using the expertise we developed at Innate over the last 20-plus years to harness the antitumor activity of NK cells and engage the right target to leverage the body's immune response. Next slide, please. Over the past 6 months, we have worked diligently to execute against all 3 pillars of our strategy, and today's call exemplifies just that. Number one, we are driving near-term value in lacutamab and are pleased to be able to share data from Stage I cohort 2 of our TELLOMAK study. In addition, we are working diligently to initiate our peripheral T cell lymphoma clinical program, which includes both a monotherapy trial in addition to combination trials with our partner [ LYSA ] to start later this year. Second, we continued to advance our innovative R&D pipeline with very encouraging preclinical data from the ANKET platform, demonstrating the power and opportunity behind this next-generation NK cell engagers. And we also announced earlier this year that Sanofi made the decision to progress IPH6101, our lead ANKET asset into IND-enabling study. Finally, AstraZeneca continues to advance monalizumab, which is currently in Phase III in head and neck cancer. Next slide, please. Before I hand the call over to Joyson to dive into our main event today, I want to highlight our pipeline, which demonstrates how our scientific expertise translates into a robust portfolio. First, lacutamab, our lead proprietary asset, and we are exploring its potential across T cell lymphoma, but we have also balanced our pipeline with partnered asset, which provide us with nondilutive revenue streams. For example, monalizumab and IPH6101. And finally, we are advancing a healthy preclinical pipeline, which will help to fuel our future clinical portfolio, driven by our NK cell engager platform or ANKET. With that, I'll turn over to Dr. Joyson Karakunnel, our Chief Medical Officer, who will provide more detail on lacutamab. Joyson, over to you.

Thank you, Mondher. Slide #11. We are very excited to share new data from our TELLOMAK study today, data that was presented recently at the 16th International Conference on Malignant Lymphoma. By way of a refresher before we dive into the data, lacutamab was designed to bind to KIR3DL2 on tumor cells and recruit immune effector cells to deplete the tumor. Fc receptors on NK and myeloid cells are activated, including CD16 and CD64, inducing antitumor cytotoxicity. The Phase I data from this program in Sézary syndrome, a rare subtype of CTCL, were very encouraging and published in the Lancet Oncology, providing the evidence for us to move forward with our Phase II study, TELLOMAK. Based on these data, we have been granted FDA Fast Track designation, EMA prime designation in Sézary syndrome as well as orphan drug designation in the EU and U.S. for CTCL more broadly. Slide 12. As KIR3DL2 is expressed across subtypes of T-cell lymphoma, but not on healthy tissues, we are pursuing a broad and stepwise development strategy for lacutamab. Sézary syndrome represents a niche indication with an unmet need. From there, we can expand into other forms of T-cell lymphomas, such as mycosis fungoides. And finally, we are working to initiate our 2-probe -- 2-pronged PTCL program this year. Slide 13. Here, you can see a breakdown of KIR3DL2 expression across subtypes of T-cell lymphomas, specifically including Sézary syndrome, mycosis fungoides and peripheral T-cell lymphoma, which makes this an important biomarker expressed in more than 50% of patients in mycosis fungoides and peripheral T-cell lymphomas and more than 90% of patients in Sézary syndrome. Our understanding of the target in the disease area has informed our development strategy around these disease areas. Slide 14. Our TELLOMAK Phase II study is currently ongoing. We are evaluating lacutamab in 2 CTCL subtypes, Sézary syndrome and mycosis fungoides. Again, given the rare indication and high unmet need in Sézary syndrome, Cohort 1 of this trial offers potential to serve as a pivotal trial. In the mycosis fungoides population, we split the study into 2 cohorts based on greater than 1% KIR3DL2 expression in our in-house assay to more directly measure its relevance as a target. As we announced in February, this study has advanced to Stage 2 based on the positive early signal we saw in Stage 1, which was notably achieved before 50% of the planned patients were recruited into this cohort. We are very pleased to have Dr. Bagot on the call today who will elaborate momentarily on the data from Stage 1 of this cohort that was presented at ICML 16, Lugano. Across all arms of the study, we recruited relapsed/refractory patients who had received greater than 2 therapies prior to enrollment. In the mycosis fungoides cohort of this study, the patients were heavily pretreated with a median of 4 lines of prior treatment. Slide 15. In addition to our TELLOMAK study, we have initiated our clinical development program of lacutamab in relapsed PTCL, where there remains a significant unmet medical need. In this setting, we are deploying a 2-pronged approach by advancing 2 parallel clinical trials to evaluate lacutamab as monotherapy in combination with the standard of care in relapsed/refractory PTCL expressing KIR3DL2. We will run a multicenter Phase Ib monotherapy trial, which will enroll approximately 20 relapsed patients to evaluate safety and characterize clinical outcomes for lacutamab in the relapsed/refractory PTCL setting. In addition, dependent on the data, we will also consider starting a separate trial in combination with other standard of care. Our partners at LYSA will run an investigator-sponsored Phase II study, KILT, which will evaluate lacutamab in combination with chemotherapy, GEMOX versus GEMOX alone. This will be a multicenter, randomized study and recruit approximately 60 relapsed/refractory patients outside the U.S. Overall, we believe this is an efficient data-driven strategy to identify the optimal regimen for lacutamab in the relapsed setting and eventually support advancing lacutamab as an earlier line treatment including combinations with CHOP in the frontline PTCL setting or as a consolidation therapy following standard first-line treatment. With that said, I'm very excited to hand the call over to Dr. Martine Bagot, who will walk us through the recently presented Stage 2 Cohort 1 data from our TELLOMAK study in mycosis fungoides.

Hi. Good morning, everybody. Can you hear me well? Can you hear me?

Yes.

Okay. So -- well, I present to you the results presented at ICML on the results of lacutamab in patients with mycosis fungoides according to KIR3DL2 expression. And these are early results from the TELLOMAK Phase II trial already presented. I'm sorry, I do not have the numbers of the slides, but I'm on the slide with my conflict of interest. So next slide is background, Slide 18. Next slide. You know that lacutamab is an antibody directed against KIR3DL2. And you know that KIR3DL2 expression is very high in Sézary syndrome patients, more than 90%. And approximately half of mycosis fungoides patients express also KIR3DL2 expression. Next slide. We presented previously the results of this first-in-human Phase I study. These results have been published in 2019 in Lancet Oncology. In this study, most of the patients presented Sézary syndrome. Out of 44 patients, 35 with Sézary syndrome. And these Sézary syndrome patients had failed 2 prior systemic therapies. This study showed no dose-limiting toxicity. Maximum tolerated dose was not reached. And the global response was very interesting since 42% -- 42.9% of the patients achieved a global response with the mean duration of response of 13.8 months. Next slide, please. Now we see the -- present now the new study in patients and methods. But the TELLOMAK study present today is a multi-cohort international open-label Phase II trial. And in this study, the patient received lacutamab monotherapy weekly for 5 weeks, every 2 weeks for the next 10 weeks. And then every 4 weeks until progression or unacceptable toxicity. I will not speak about the Cohort 1 that is concerning Sézary syndrome patients. I will speak about Cohort 2 and 3, that is mycosis fungoides, who have failed at least 2 prior systemic therapies, and these patients who present an important medical need, and it highlights that this population does not have lots of treatment options. And there are 2 cohorts. Cohort 1 is the patients expressing more than 1% of KIR3DL2 and Cohort 3, patients with negative KIR3DL2 staining. For the Cohort 2, all these studies are in 2 stages. For Cohort 2, Stage 1 will be performed on 21 patients. And if at least 3 responses are observed, the study will go on for Stage 2 for 9 additional, 29 patients. And concerning Cohort 3, negative patient, Stage 1 comprises 18 patients. And if at least 3 responses are observed, that we go on with Stage 2, 20 patients. Next slide, Slide 24. The primary endpoint of the study will be overall response rate according to the already published international consensus criteria. And the disease has to be evaluated in different compartments, in the skin, the blood and the lymph node. On the skin, the mSWAT, is international criteria. The blood is evaluated by central flow cytometry. And lymph node and viscera are evaluated by CT or PET/CT. And the evaluation are performed at week 5, and then every 8 weeks during 1 year followed by every 12 weeks thereafter. And there were other key secondary endpoints such as toxicity, duration of response, progression-free survival, overall survival at 1 and 2 years, quality of life, PK and immunogenicity. Slide 25. What are the key eligibility criteria. The patients that will be included in the study are mycosis fungoides at any stage, except, of course, patients with Sézary syndrome. They must have an ECOG performance less than or equal to 2. There are 2 cohorts according to the expression of KIR3DL2 and the positive patient should be positive in at least 1 skin lesion based on central evaluation. Patient should not have evidence of large cell transformation, also based on central histologic evaluation. They should have received at least 2 prior systemic therapy and they will have a minimum washout period of 3 weeks. And of course, this should have the feasibility of at least 1 skin biopsy at screening. And so this population is a population who does not have a lot of treatment options. It's a population with a high unmet medical need. Slide 26. What are the preliminary results from the Stage 1. Slide 27. You see that in those groups of 2 and 3, the age is approximately 60. There are more male than female. And it's important to note that the screening with KIR3DL2 is associated to a more advanced stage population. You see that in the KILT Cohort 2, the number of patients in stage 3 or 4 is higher than in the Cohort 3. And also the blood involvement at baseline, B1 because B2 patients were excluded. But you see then there's more patients with B1 enrollment are observed in Cohort 2 than in Cohort 3. You also can note that these patients were heavily pretreated since they had -- the patient had a median of 4 prior therapies. Slide 28. So this is the result of preliminary results of Cohort 2. You see that the median follow-up is still short, 4.8 months. But it is important to consider that there are quite a lot of confirmed responses. Now at the time the results were presented in Lugano, there were 4 confirmed, 1 CR, 3 PR responses and 2 not yet confirmed responses. Now these unconfirmed has been confirmed. So the number of confirmed responses is now 6. And you see that some patients have quite a long duration of follow-up in this Cohort 2. And so these results show that these preliminary data suggest that some responders may have quite long duration of response. Slide -- I do not have in my slide Cohort 3. Do you have Cohort 3 on your slide?

No.

No? Okay. So I speak only of Cohort 2. And now the response by compartment. If you look at the response by compartment, you see that the responses are -- in the skin are quite high because say about 17 patients at the beginning and who observed 1 CR, 8 PR and 2 at time of the presentation unconfirmed PR that are now confirmed. In the blood, very interesting, you can see that there are 7 patients with blood involvement. And among these 7 patients, 4 complete response. And among lymph node, 8 patients, 1 partial response. So it's interesting. These skin results are extremely interesting because skin is very important for quality of life of the patient. And so it is very interesting to see that the majority of patients had represented a very good complete or partial response in the skin. Here you can see the results of Cohort 3. The results are less prominent on the 19 patients involving the skin. We had only 2 partial responses. However, you can see that there are a number of patients who presented a response less than the 50%, that is stabilization of the disease. And the stabilization of the disease can anyhow be interesting for the patient. Slide 31, presents you the treatment-related adverse events. And you see that the any grades are quite a low number of adverse events, mainly Grade 1 or 2, asthenia, nausea, arthralgia, diarrhea, fatigue, but not severe adverse events. And there was only 1 patient presenting with an adverse event leading to treatment discontinuation with serious adverse events. And this patient had cough before beginning of the treatment. And finally, he was -- the cough increased. He was tested, was COVID negative and finally turned out that this patient had interstitial lung disease, but -- so the suitability of the drug, of course, is not proven since he had a very few infusion and the symptoms began before the infusion of lacutamab. And so the conclusion of the study is that in mycosis fungoides patients, expression of KIR3DL2 greater than 1% is associated with advanced stage disease, mainly in the blood of lymph node in comparison to [indiscernible] expression. Interestingly, in Cohort 2, lacutamab showed high level of clinical response in mycosis fungoides patients and the expansion to Stage 2 is already underway. In mycosis fungoides patients with no KIR3DL2 expression, expansion with Stage 2 will be triggered if additional confirmed responses are observed during follow-up. But on the whole, lacutamab showed a very favorable safety profile in mycosis fungoides. What is very interesting is that there is no skin toxicities that confirms the very well -- good tolerance observed during the first already published study. And this absence of skin toxicity is extremely interesting for patients with skin tumors, with skin lymphoma because without the drugs, as you know, there is a high percentage of skin exanthema, skin eruption, and it's very difficult to note if the patient has a drug reaction or progression of the disease. And what's very interesting with lacutamab is that we have no skin toxicity. Of course, long-term follow-up would be required to provide more major conclusions and duration of response and progression-free survival, but these preliminary results are already extremely encouraging. Thank you for your attention.

Thank you very much, Martine. Great presentation, and I understand it's a little bit challenging not to see the slide while you are talking, but I think everyone could follow your clear presentation of those preliminary data. We have planned to pause here and maybe have a first set of questions on the data themselves. So we really dig more deep into the clinical data you just presented yesterday in the Lugano meeting, and then we'll take back the rest of the presentation. So I hand over to the operator. And the plan is that I take the question and then I hand over to you, and if there is a need, of course, Joyson is in the backup for addressing any technical questions you need him to intervene. That's okay?

Okay.

Thank you very much. Operator?

[Operator Instructions] And your first question comes from the line from Yigal Nochomovitz from Citigroup.

I had one question for Dr. Bagot. You've seen the 6 out of 17 overall response rate in the mycosis fungoides trial. I'm just curious to know how does this level of efficacy compare to current best available therapy in mycosis fungoides?

You mean compared to already available other monoclonal antibody?

Yes. Yes.

Yes? Well, I think it's -- in the skin, it might even be better because you know that, for example, mogamulizumab is extremely efficient in the blood, not so efficient in the skin. It may be efficient in the skin. It's not always -- in many patients, we have a very brilliant response in the blood, not so much in the skin. So I would say that lacutamab -- results with lacutamab are extremely encouraging in the skin or in patients with only skin involvement and no blood involvement. We have very interesting results in the skin.

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

I have 2 questions. The first is, I'm wondering if you can talk about why you did this interesting dose ramp with weekly, then every 2 weeks and then every 4 weeks? And the second question is in the low expression patient population, do you have any idea or hypotheses on maybe what was driving the small response rate? Is there another marker or patient characteristic that was common over the patients that had a greater benefit? And I think you need one more response to progress to Stage 3. And I guess this is the third question. Is it possible that some of these patients would continue to deepen? Is that common with this therapy in what you've seen so far for these patients to deepen over time?

Okay. I'm sorry I didn't hear so much, but I understand the first question was the frequency of infusion. It's very classical in these patients with infusion every week and during 1 month in order to increase the link of the antibody to the [indiscernible] that it related to pharmacokinetic studies, and you know that you need to have infusion every week during the first month. And for example, with other antibodies, for example, mogamulizumab, the infusions at the moment are every 2 weeks. So it's interesting that with lacutamab, we do have 2 weeks during 4 months. And then at least in the first trial because in this trial, we don't have -- we have only a 4-month follow-up experience, but we know that the previous study with Sézary patients, it was possible to maintain the response by infusion every 4 weeks. So that's very interesting for the patients to come to the hospital only for 4 weeks and not every 2 weeks. And confirming your second question, I'm not sure I get everything. I think it was related to the patients with KIR3 negative staining. It might have been that -- it could have been possible that the threshold detection of KIR3DL2 is not optimal. So we wanted to test whether there was a difference between the patients with KIR3 positive expression or KIR3 negative expression. And it turns out that the patients with KIR3 positive expression has better results. Anyhow, the patient with KIR3 negative presents some responses. So it's really difficult to say what is the explanation of that, but we could say that it might be logical, patient that expressed a higher expression has better responses. But at the moment, it is not possible to say that the KIR3 negative patients do not respond at all. And as you know, it will be possible that the Stage 2 is achieved also in the Cohort 3. But we have seen less brilliance in the patient of Cohort 2 now, especially in the skin.

And the last question, Martine, is about would you expect that some of the patients who are in stable disease may deepen their response and have additional response in this cohort. We have only 2 so far.

Yes, of course, it's possible that we have more. And concern -- that means that in this disease, if the patient is in complete response or partial response, we need to confirm the response after 4 weeks. That's why some patients were unconfirmed and became confirmed after 4 additional weeks. But of course, it is possible. We have several patients still pending, and we hope that some patients will become responder while not considered a responder just now.

Can I ask one more follow-up? I wonder, you said that the skin resolution is really important to quality of life for these patients and you need an actual partial response to advance to Stage 2. Is the skin resolution in these negative expressers meaningful enough quality of life that you may even consider using it for patients, if these results continued to have challenging skin problems?

I'm sorry, could you -- I didn't hear very well. Mondher, could you please repeat the question?

The question, we have shown the skin response in Cohort 2 and Cohort 3. So first of all, in Cohort 1 -- in Cohort 2, the skin response is quite outstanding actually, really, you have almost 11 out of 17 patients who respond. In Cohort 3, you asked patients who have skin responses, in your answer about the skin response earlier, Martine, you talked about quality of life. And if we take the global response rate aside and think only about skin responses, would that be meaningful enough even though the level of response in the skin is lower in Cohort 3, would you consider that as meaningful enough in the non-expression?

Okay. Okay. I understand. So the international criteria is decreased by more than 50% of the skin lesions. But as I told you, if a patient has a decrease by 25%, it's already a very interesting result. It is considered stabilization disease, not partial response, but for the patient, the patient has a very pruritic, pruriginous skin lesions. And if he or she has a decrease of 30%, of course, it is an interesting result. It may be worthful of course, but you have to distinguish criteria, international criteria, and the quality or life of the patient. For the quality of life of the patient, stabilization of disease is already a very interesting achieved goal.

Yes. Thank you, Martine. Let me maybe add further clarification with regard to the staining and the level of expression. First of all, the trial was designed with 1% KIR3DL2 expression rate as a cutoff for Cohort 3. While this reflects, of course, nonexpressed patient, it also means that some could have varying level of expression. And in this patient, it's not surprising to see potential responses. It is also possible and here maybe speculating that the expression of KIR3DL2 is heterogeneous in a given patient. And as patients with cutaneous T-cell lymphoma often have several skin lesions, a biopsy could be taken from a lesion that does not express KIR3DL2, while other lesions in the same patient that were not biopsied might do. So the phenomena of interpatient tumor heterogeneity is widely described across different tumor types and might be applicable also in this disease. So I think it's important that we put those preliminary data into context and have more follow-up to better assess whether we hit the criteria to move to Stage 2 or not. So back to the question. Thank you, Daina, for very important and, I think, a clarifying question.

So I have another question that comes from the line of Jingming Chen from Evercore.

Can you hear me?

Yes, we hear you.

Okay. Actually, I don't know why it came in as Jingming Chen. This is Liisa Bayko.

But we are actually not surprised.

Evercore. Sorry, I don't know, there's some mix up. I think you might have this line designated to Jingming. But Jingming and I work together. So you're on the right track. In any case, can you talk about sort of the differential response across skin and the other compartments and sort of why that is mechanistically? And then in the kind of global score, can you talk about the relevant -- relative importance of those different compartments to the scoring system?

Can I repeat the question? Did you get the question, Martine?

Yes, yes, yes. So the difference between the different compartment. Well, in this disease, it is very important to evaluate the compartment differentially. In the presented disease, actually, we have very low data on the other compartments. We have, for the moment, a few data on the blood and on the nodes. The skin is easier to evaluate because you see the patient. I can tell you that the skin, of course, is extremely important for the patient, for the quality of life and also for reduction of pruritus. But of course, it will be also important to evaluate to see what will be the effect on the other 2 compartments. But I think maybe you can tell me further. I don't have the preliminary data. I think we do not have this data now. We will get them in the future of the study.

And then can you just talk about the global score and sort of how it's weighted between those different compartments?

Yes. No, the global score is a combination of the skin, nodes, blood and visceral involvement if it exists. It's not so frequent, visceral involvement. Until there is a score -- combination score between there is a stage, a lymph node stage, and you combine the skin evaluation, the blood evaluation and the node evaluation, and this gives a global score. And also, there are also a criteria for responses. Also you evaluate the response in different compartments, and you have to combine all of these evaluations to have the global evaluation.

Okay. And are they equally weighted? Or is like one compartment worth more?

All compartments are important, but the rate is different for the skin. It is surface and the depth of the lesion for the skin. For the blood, it's number of the tumor cells in the blood. For the nodes, it's a measure of the nodes on CT scan. So -- and for all these compartments, you have internationally recognized evaluation of the -- at the beginning and also of the response. And you have to combine all these 4 evaluations to have a global score.

Okay. I get that. And do you weight them equally? In other words, is the skin worth as much as the node and is that worth as much as the blood?

Many patients do not have -- some patients do not have nodes. Actually, early -- mycosis fungoides usually have only skin involvement. And some of them have blood involvement, not B2 because there should be Sézary, but some of them, for example, you see they have B1. And sometimes, the nodes are not involved nodes, sometimes they have inflammatory nodes related to the skin lesions. So when we follow, of course, we follow the skin, we evaluate the skin, we evaluate the blood, and we are doing CT scan only for patients who have the node involvement. If the patient has no node involvement at screening, we are not evaluating CT scan, of course, every 3 or 4 months. We are doing scans for the nodes only in patients who had the node involvement at the beginning of the screening.

Okay, yes. What I'm trying to ask about is just the relative importance of those different components.

So Liisa, this is Joyson. Maybe I can add to what Dr. Bagot is saying. So as she was mentioning, this is all based on the EORTC criteria for lymphoma -- cutaneous lymphomas. And that's the group she was just talking about. When you look at the global response, what you do is you kind of -- it's -- think of it more of sequential. You'd look at the skin first. Depending upon the skin, if it's a CR, PR or SD, then you evaluate the node criteria in blood. So I wouldn't think of it as where you say skin has 3 points, nodes have 2 points and blood have 1 point. It's more of saying, here's skin, what is the skin response and then to meet the global response do the other compartments fit into those criteria. Does that help clarify it?

Okay. So it seems like you have to have a skin response and other -- in order to meet, right, to look at the rest?

Yes. Correct. So you'd have to have a skin response to be able to have a global response of CR or PR. So to have a CR -- yes?

If you do not have skin response in all compartment, you do not have a CR, of course. To have CR, you have to have CR in all compartments. And sometimes you have CR in one compartment and PR in other compartments. And usually, that means PR, global PR.

I see. Okay. And so I guess we'll have then as you get the data from the nodes and from the blood and kind of the initial responses we've seen so far will the global responses, that will change and evolve. Is that fair to say?

So maybe -- this is Joyson again. So maybe I can respond to it and then Dr. Bagot, please feel free to add. So each of these are assessed at a given time point. So each assessment is independent of -- so an assessment number 1 is independent of the assessment number 2. So your global response is based on -- at assessment 1, I'm looking at skin, node, blood. And then I get a certain response. Then I go on to assessment number 2, and I get a certain response. So I can't change the responses that are already here, that we're showing on the screen, those won't change because those are best global responses. So these patients have all had responses as their best response. So even if it's not as though the skin compartment, if it becomes PD, all of a sudden the response changes for the patient, the previous response has changed for the patient.

Okay. Okay. I was under the impression you hadn't yet gotten all the data for skin and blood yet for some of those earlier.

Yes. So I would think of it as maybe I can go back to [indiscernible] when we do scans at week 8, for solid tumors, we do scans at sort of, let's say, 2 months, right? So if that patient gets a response, no matter what they get down the road, this is going to be their best response. So in a similar format, this is more of just all 3 of these compartments make up that assessment. So we've already assessed for assessment 1, as an example, skin, node and blood. So now we move on to assessment 2, and then we look at skin, node, and blood. It just kind of goes down.

Thank you. We've got one more question on the line, and then maybe we'll start with the next session. So from H.C. Wainwright, what biomarkers are being looked at to ensure the mechanism of action of lacutamab in the study? And what percentage of MF patients have skin involvement? And do patients with skin involvement progress to systemic disease?

Patients with skin involvement may or may not progress. Some patients with early-stage patients always stay -- remain with only skin involvement, and some of them progress to blood involvement or node involvement or even viscera involvement, but not all. Some of them will remain what -- with only involvement of the skin. But as you can see, expression of KIR3DL2 is related to patients with a more advanced stage with patients who have a more higher tendency to develop extra skin involvement. It's very striking that the percentage of patients expressing KIR3DL2 is higher than the group of patients with low blood involvement quoted as B1. And this group of patients has a higher KIR3DL2 expression than the patients that presents only -- who present only with skin involvement.

Thank you, Martine. Really very, very interesting session, and I hope we'll have time at the end of the presentation to come back to lacutamab, TELLOMAK data, but also other question about the overall clinical development plan and strategy. It's my pleasure now to introduce Eric Vivier, our Chief Scientific Officer, who will present, as I said, the preclinical data from the ANKET platform. He presented earlier this month whose data at the Annual Meeting of the Federation of Clinical Immunology Society. Eric, over to you?

Yes. Thanks, Mondher. So we are at Slide 34. And I should say that it's really a thrill to share with you today our latest innovation to our proprietary multi-specific NK7 engager platform that we call ANKET. Can we go to Slide 35 now? So ANKET stands for antibody-based NK-cell engager therapeutics. And these multi-specific molecules are made of various building blocks, as illustrated here, and then we'll update you today on our recent generation of tetra-specific ANKET, which is made of an antibody fragment here in yellow that recognize the tumor antigen, antibody fragment here in green that recognize NKp46, and Fc portion of a human gamma 1, human IgG1 antibody that is called Fc here in red that will interact with CD16, and then a variant of the interleukin 2, IL-2v, and I will describe you one. Next slide. So the reason why we are so excited about the ANKET is because we are announcing 2 breakthroughs. First, a technological breakthrough and second, an efficacy breakthrough. So on the technological breakthrough, as you can see on the left-hand side of this slide, ANKET is a versatile fit-for-purpose technology that is creating an entirely new class of tri- and tetra-specific molecule to induce strategic immunity against cancer. On the efficacy breakthrough, and this is the right side of the slide, this unique NK cell engager engages for the first time to activating NK cell receptors, namely NKp46 and CD16, but also the combination of receptors for IL-2 -- IL-2R beta and IL-2R gamma with this IL-2 variant and the tumor antigen in a single tetra-specific molecule. And this is leading to the harnessing of NK cell effector function against cancer. This also provides proliferation, as I will show you in the next slide. And overall, it demonstrates a better antitumor efficacy than approved -- clinically approved antibodies within the limit of the preclinical model that I will review for you today. Coming now to Slide 37. Because in that slide, I would like to start to show you why it's so important to harness NK cell in cancer therapy. So we all know that T cells are key to the control of cancer and they really can do that. But we also know from decades of immunology that T cells are not autonomous in what they do. They need cells around them, cells of innate immune system to become real effective cells. And natural killer cells belong to this group of cells of the innate immune system. Natural killer cells are known since inception for their capacity to induce the killing of tumor cells and they certainly do that, but they do something more. They are also able to secrete an array of cytokines and chemokines, which are extremely important for the onset, the maintenance and the shaping of the adaptive immune response. This is expected here when NK cells secrete XCL1, for example, of CCL5 on Flt3 ligand, which are cytokines and chemokines which are so important for the activation of a specific subset of dendritic cells called cDC1, which are, by themselves, extremely important for the activation of tumor antigen-specific T cells. In parallel, NK cells are able to secrete gamma interferon, which is promoting both the innate and the adaptive part of the immune response. Next slide. So the reason why we choose NKp46 or antibody fragments against NKp46, I should say, to build our ANKET is meaningful. And I will start by this slide that really show you a very important point. When you look at NK cells infiltrating the tumor, and you focus on activity NK cell receptors, and we have looked at NKp46, CD16 and NKp30. And if you concentrate on the blue curve, it's obvious to appreciate that the expression of NKp46 is stable as the tumor bed, which is not the case for CD16 and not the case for NKp30 either. Next slide. Also, in terms of the transduction pathways, which are linked to the engagement of this activating receptor, it is very important to show that different NK cell receptors have different signaling pathways and outcome. And what is really important for NKp46 as well as CD16 is that both of these cell surface receptors, as you can see here in green and red, they are noncovalently coupled as the cell membrane with ITAM polypeptides which are here in purple, which are very important to initiate a full-blown activation of NK cells through protein tyrosine kinase pathway and also PI3 kinase pathway. This is not the case for all NK cell receptors. You can see that for NKG2D for example, which is in human only coupled to DAP10 which is coupled to the PI3 kinase pathway, but not to the ZAP-70 or Syk protein tyrosine kinase pathway. And at the same time, as I told you by constructing our new generation of tetra-specific ANKET, we are also inducing a crosstalk of this ITAM signaling pathway with the IL-2 receptor pathway. And this is seen in the next slide, when you have this tetra-specific ANKET, which engage NKp46, CD16 and IL-2 receptor in a single molecule. Next slide. And as you can see, now we are inducing the coligation, the crosstalk between these pathways. The importance is obvious. By engaging NKp46 and CD16 at the same time, as we show already some time ago, we induced a very nice activation of NK cell effective function. But now that for thinking the IL-2 receptor pathway, we add the proliferation and other activation as we should. So next slide. So in order to do that, we generated a variant of the interleukin 2, that we call IL-2v. And as you can see, looking at the vector, this IL-2 variant, IL-2v doesn't bind to the alpha chain of the IL-2 receptor, but does bind very well to the beta chain of the IL-2 receptor. Why did we do that? Next slide. Well, it's because the alpha chain of the IL-2 receptor, CD25, is highly expressed on subpopulation of T cells, in particular, the T regulatory cells, Tregs, and one doesn't want to activate this Tregs for obvious reasons. So as you can appreciate here, when we have generated this variant of IL-2 here in orange, we nicely activate NK cells, but we lose efficacy and activity in Tregs, which is exactly what we are looking for as compared to wild type IL-2, which is in black. And the same is true for other subsets of T cells. So that's the first point. The IL-2 variant is promoting IL-2 receptor activation in NK cells and [ need ] regulatory T cell activation. Next slide. But we do more than that. Because now we compare this IL-2 variant to the tetra-specific ANKET and look at the results. This is in green. Now we are improving the activity of this IL-2 variant on NK cells. And while we are not impacting on the low activity of this IL-2 variant on Tregs as you can appreciate. So this is working exactly as expected. What are the functional consequences of the treatment of NK cells using this tetra-specific ANKET. So we started by looking at the activation of primary human NK cells in vitro. Next slide. And as you can see and as expected, this tetra-specific ANKET induces a very nice NK cell proliferation. This is in light green or bright green and you could compare with the orange, we see actually the IL-2 by itself. And here, you can understand how readdressing the redirection, so to speak, of the IL-2 towards NK cells is so efficient in terms of proliferation. Next slide. So we've been already -- we are at Slide 46, just to make sure. So now we've looked at cytokine secretion and chemokine secretion. Here, we just focused on interferon on the left-hand side and midpoint data on the right-hand side. And we are comparing different variants of this ANKET molecule. The tetra-specific ANKET is in green with closed circle and the other variants are according to the legend. So first of all, yes, the tetra-specific ANKET induces very nice cytokine and chemokine secretion. What is really important is to compare this closed circle green with open circle green because what we have done here is actually to release the capacity to the ANKET -- of the ANKET to recognize the tumor antigen. It's an antitumor antigen less ANKET, if you will. And then you can appreciate that in the absence of this tumor antigen recognition, there is no secretion of cytokine or chemokine within the limit of this dose, which is extremely important because it tells us there is no off-target effect in terms of cytokine secretion and chemokine secretion by the tetra-specific ANKET. Next slide. So obviously, we've been looking at cytotoxicity. And when you talk about NK cells, this is a big thing to do. So we've done it. And as you can appreciate, exactly the same results as for the cytokine and chemokine secretion. Very nice induction of cytotoxicity and no induction at all when you lose the tumor antigen binding capacity. Now very importantly, also, when you mutate the other part of the tetra-specific ANKET, for example, you delete the capacity to interact with CD16, you delete the capacity to interact with NKp46, you lose activity. And you will see that, in particular, by deleting the capacity to bind NKp46, you actually mimic what others have done using antibody or targeting CD16 and you can appreciate that you lose much of the activity. Next slide. So once we have done that, it was obviously very important to challenge the activity of this tetra-specific ANKET in vivo. So this is what we have done. And frankly, when I saw this result for the first time, I was breathless. I've been working on NK cells since 25-plus years. I started to work on NK cells in Harvard. And I was wishing since then to see this kind of efficacy in preclinical models, and I have never seen something like that. Most of the time, you can see a delay in the growth of the tumors, but this is not what we are seeing here. What we are seeing here when we inject in immunodeficient mouse, is very important, so we are only addressing NK cells. We have no T cells, no B cells. So they are by themselves. We inject them with human tumor cell that express CD20. We have generated here tetra-specific ANKET that recognize CD20, and we don't see any tumors no more. So this is really I think a tremendous activity that -- which is unprecedented at least. Next slide. So we have Slide 49 now. What I would like you to do here is to concentrate on the green curve versus the blue curve because what we're comparing here is a tetra-specific ANKET that engages NKp46, CD16, the IL-2 receptor, this is on the NK cell side and the tumor antigen on the tumor side, this is in green, versus in blue, an antibody that [indiscernible] tumor antigen that will also bring IL-2, but will only -- will rely on CD16. So not engaging NKp46 at all, but you can appreciate the difference. It's obvious. Adding an NKp46 anchoring eventuality lead to the tremendous efficacy of this tetra-specific ANKET. So obviously, as we are scientists, then Slide 50, we are really interested, I dissected at the molecular level, what are the molecular mechanisms underlying this activity. So in a nutshell, we could show using different kind of technology. So on the left-hand side, immunohistology; on the right-hand side tpCR of the tumor bed. And you can appreciate that what we can see is a huge infiltration of the tumor bed with NK cells, the NKp46 plus, but they're also expressing [indiscernible] So they are not only NK cells, they are activated NK cells, which is absolutely key and they also producing gamma as you can on the right-hand side. Now I would like to switch to Slide #51, which I think addresses a very important point. What if we try to activate NK cells using tetra-specific ANKET on one side, this is a green curve in the middle or the same component, but not in the same molecule, namely here in this vector a trispecific ANKET with an antitumor antigen, an anti-NKp46 and CD16 binding element in one molecule. And separately, IL-2 variant. And the result again is black and white, I should say, red and green. In green, you have this tremendous activity of this tetra-specific ANKET, and in red, but you have some activity when you compare the black on with red, there is some control. But this kind of usual control that we see in papers and papers, but not the tremendous activity that we see with the tetra-specific ANKET. Next slide is Slide 52. So obviously, these experiments were made in an immunodeficient mouse. So it was very important to work in a syngeneic mouse model with the full competent immune system, so we turned into a regular black-6 mouse that we challenged using the B16-F10 melanoma, which is injected IV. And so this is a model of disseminated tumor or metastatic melanoma, if you will. But the point here is to compare the activity in the syngeneic model, full immune response present of a tetra-specific ANKET with obinutuzumab because here again, we have transfected CD20, human CD20 at the surface of the B16 melanoma to be able to compare what is comparable with obinutuzumab. And you can see, we see tremendous activity of the tetra-specific ANKET. It's like the tumor was not even injected into the mice. I can reassure you the mice was injected with the tumor. But we see a total control of the tumor model, which is not the case for obinutuzumab. Next slide. So in Slide 53, we were interested to challenge this even further. What about in nonhuman primate? And could we actually measure pharmacokinetics, pharmacodynamics and obviously, very importantly, the safety of this tetra-specific ANKET. And we've been doing this. This is represented here, in a dose-response manner, you can see that, yes, the tetra-specific ANKET targeting the monkey CD20 is able to induce the [ application ] of monkey B cells, which is expected. The PK, which is not represented here is quite nice. It's equivalent to human gamma 1, which is extremely nice again. And very importantly, no sign of toxicity. So this tetra-specific ANKET is very well tolerated in nonhuman primate. So to wrap this up and see my last slide, Slide 54, I would like to say in conclusion that ANKET is a versatile platform and several combinations of NK and tumor binders are really exciting to test. Importantly, our new tetra-specific platform creates a synergy. I hope that demonstrate that. And this synergy is not observed by the separate combination of each element, which is very nice. So with this, I will leave the floor to Mondher for the concluding remarks.

Thank you, Eric, for this, not only very interesting update on ANKET, but very energizing and passionate presentation. And I would also like to thank Dr. Bagot for her excellent review of the Stage 1 Cohort 2 data for mycosis fungoides, which continues to highlight our belief in this program. Before we open the call to questions, I would like to briefly summarize today's deck and reiterate upcoming milestones across our programs. Please move to Slide #56. As you can see, we have streamlined development strategy to position lacutamab as the new standard of care across KIR3DL2 expressing T cell lymphoma. The data presented today reinforce its approach, demonstrate lacutamab's potential in T-cell lymphoma more broadly. This is no longer a Sézary syndrome drug. We continue also to pursue this step-wise strategy and look forward to updating you on the progress of the TELLOMAK study, which Cohort number 1 in Sézary syndrome, I remind you, has the potential to serve as a pivotal study, but also by initiating our 2-pronged peripheral T cell lymphoma program, including a monotherapy study, which we sponsor and the combination study run by our partner, LYSA, which will evaluate lacutamab in combination with GEMOX and standard of care, both are expected to start this year. On Slide 57, you just see in the presentation and the update from Eric. Our proprietary multi-specific ANKET platform remains very exciting for us. Overall natural killer cells present many advantages for us, including the ability to kill tumor cells and activate other parts of the immune system. IPH6101, our lead trispecific candidate has shown positive manufacture ability properties leading to its selection as a drug candidate for development by Sanofi and it is as we speak, in IND-enabled studies. Our new tetra-specific format is the first NK cell engager technology to engage activated receptor, NKp46 and CD16, a tumor antigen and the cytokine IL-2 variant in a single molecule. And we believe that tetra-specific format which leverages the advantage of harnessing NK cell receptor function against cancer, but also targeted NK cells with proliferation and activation signal could represent the next generation of immuno-oncology drug, and we look forward to advancing this new pipeline candidate from this platform in the future. Slide 58. Yes, Slide 58. The next 18 to 24 months will be very exciting for us, as we continue to execute across all 3 strategic pillars and create value for patients and stakeholders. A, we will continue to drive value with lacutamab and our next key data readout for Sézary syndrome and mycosis fungoides are expected next year. Secondly, we will continue to leverage our proprietary NK cell targeted platform, ANKET to advance our natural killer cell engager portfolio. And lastly, we are committed to winning a sustainable business by leveraging partnerships, including our work with Sanofi and AstraZeneca, which both validate our scientific technology and provide revenue streams to reinvest in our R&D efforts. Thank you for your attention on today's call, and we look forward to highlighting our continued progress throughout the remainder of the year. We will open now to your questions. Operator, first question?

[Operator Instructions] And the next question comes from the line of Daina Graybosch from SVB Leerink.

A couple of questions for you. One, just a clarifying and then 2 on the biology. So before you showed us the syngeneic mouse model, you showed us a bunch of mouse data. Can you clarify specifically what that murine data was in? And then my second question is, have you looked at the sort of direct and indirect contribution of antigen-specific CD8 T cells in the system? I guess I'm trying to get at how conditional 2 NK cells do you make the IL-2 stimulation by having the Fc and NKp46? Are you still seeing some activation of T cells directly? Or is this mostly an indirect NK cell effect on T cells and can you tease that out?

Yes. Thanks, Daina, those are excellent questions. I will start by the second question. This is exactly what we are doing right now. I don't have any definitive answer. We are absolutely now looking, as you can imagine, in the syngeneic model that we have, the one that I described, but others as well, what is the contribution of the different cell types. The hypothesis that we are testing, and this is supported by recent data from other groups, as you probably know, is that, in fact, NK cells can directly recognize tumor cells. They provide cell debris, which can be actually cross primed to present the antigen to T cells, but they also secrete this array of cytokines and chemokines and then T cells come into the game. And this is what we are testing again. We don't have any definitive answer. It's also possible and you looked carefully at our data. So thanks for that. But indeed, the IL-2 variant, despite it's a variant can also activate T cells, although at a very different dosage, as you can appreciate. So this is what we are dissecting. And so we don't have any definitive answer for that. We hope that our hypothesis is true, that NK cells not only contribute to develop the tumor, but also to initiate a T cell response. The only data that I can share with you is the fact that as a tumor bed, when we have this high efficacy of the tetra-specific ANKET in the syngeneic model as well as skin model, we do see secretion of Flt3 ligand, CCL5 and XCL1 by NK cells, which is obviously a good sign of the propensity of this ANKET activity with NK cells to activate dendritic cells and T cells, but that remains to be dissected. Does this answer your questions?

Yes, it does.

And your next question comes from the line of Liisa from Evercore.

Can you maybe further explain the difference between IL-2 versus the IL-2 variant that you're using as part of your [indiscernible]

Yes, absolutely. Sorry, it was not clear enough. So as you probably know, IL-2 is recognized by a receptor made of 3 different chains, the alpha chain, CD25, IL-2R alpha, the beta chain, CD122, IL-2R beta and IL-2R gamma. It turns out that there are -- the IL-2 variant that we have generated is so-called alpha less IL-2. It doesn't bind IL-2R alpha, as I could show you in [indiscernible] slide, that is Slide 42, but maybe I was too fast on that. So this IL-2 this is CD25. By doing so, we do not activate Tregs because Tregs express high level of CD25, and this is how that can detect IL-2. So we concentrate the IL-2 to cells that [ continuously ] express the beta and the gamma chain of the IL-2 receptor, namely in particular, I should say, NK cells. Other cells can also [ constitute ] beta and gamma, but NK cells do. And then we readdress this IL-2 by incorporating it into a tetra-specific ANKET that makes it even more available to NK cells and less available to the other cells.

Okay. Got it. Is it difficult to manufacture or pretty straightforward?

Well, so far, so good, frankly. I mean we all know that [ CNC ] is an issue for everybody, including us. But so far, so good, really we cross fingers. You probably are aware that for the trispecific ANKET, we have derisked this part because Sanofi is progressing with our trispecific ANKET. So we have the good manufacturability of this trispecific form. And we've been generating the tetra-specific form based on this high specific format and so far so good.

And just to be complete on this, Liisa, we also have one fully proprietary tetra-specific ANKET. We have recently selected the candidate, and we are now moving actively towards the IND based on the experience of the trispecific that we have in collaboration with Sanofi. Okay?

Great. And that's a perfect segue to my next question. As you think about ANKET in the clinical environment, what tumor types are going to test first, where do you think you might see the best responses? I know it's early, but I'm just curious on how you're thinking about development.

Well, maybe I'll start with some answers, and I'm sure that my colleagues either Joyson or Mondher will complete. Being an NK cell maniac since years, I have the tendency to believe that NK cells can help in the elimination of many different tumor types. But starting by the hematologic disease for obvious reason, which is to increase the likelihood of encountering between the tumor cells and the NK cells, which are circulating as you know. So this is what we are exploring right now in preclinical models. But we are very excited about all the combinations that we could do because it's a versatile platform. So as long as you have a tumor antigen and as long as you have freedom to operate or other means to have access to an antibody that recognizes the tumor antigen, then we can [indiscernible] and test it.

And maybe to be complete on this, I would say we start with validated tumor antigen, i.e., tumor antigens against which therapeutic monoclonal antibody has proven efficacy and manageable toxicity. So we don't go fishing. We go after tumor antigens that are quite well validated. And also, to be complete, we know that the name of the game when it comes to immuno-oncology is most likely the combination therapy. And of course, we are exploring in particular at the research technical level, the combination with [indiscernible]

And your next question comes from the line of Yigal Nochomovitz from Citigroup.

If I could just go back to the TELLOMAK Sézary pivotal trial. As you showed in Phase I, about a 43% ORR 14-month duration of response and about 12-month PFS. So I'm just wondering if these numbers are a good benchmark for what you need to show in the pivotal Phase II trial? Or do you believe you need to do better to have a competitive drug profile? And what factors do you think could drive a higher response in the pivotal trial for Sézary?

Very important question. I'll ask Joyson to provide you the overall strategy we are pursuing when it comes to MF and the benchmark. But keep in mind, first of all, that Sézary disease is quite different from the MF and not only by the level of expression of the target, but also by the phenotype of the disease itself. The data from the Phase I quite unique in the sense that this was very heavily pretreated patient population. And so far, actually, the level of activity observed in the Phase I stands out as really quite impressive. I think for MF, Dr. Bagot reminded us at the beginning, the patient characteristics, the median number of prior line of systemic therapy was 4. So we are basically in a heavily pretreated patient population. And the benchmark that is in our hands, in our heads, of course, about MAVORIC is essentially in second line. But let me hand over to Joyson to give you a little bit more detail on the level of activity that we expect to see in MF to consider this as a win.

Yes. So just to add to what Mondher said, I think when we look at the TELLOMAK study and the data that was presented by Dr. Bagot, this is, as Mondher mentioned, is a heavily pretreated population. It's a patient who -- it's a patient population who median lines of therapy were 4. And especially in the cohort where we saw responses and advanced population. So in this therapeutic area, mogamulizumab is the only approved antibody in greater than one line of therapy or second line. And so we -- looking at the data that we have on hand, I think that would be in comparison to mogamulizumab is where we'd be looking at our benchmarks. And so it is very early data. And to answer your question, I think we'll have to await the results of the TELLOMAK trial, especially Stage 2 to further get an inclination about how we would position our Phase III trial.

And maybe to complete, Yigal, you know that the MAVORIC trial enrolled patients who had one or essentially prior line of therapy, and the response rate in MF was 21%.

Okay. And do you have any thoughts on the benchmark for Sézary?

37%. Sorry, go ahead.

No, no, no, I was going to say 37%.

There are no further questions. Please continue.

No further questions on the -- okay. So with that, we come to the end of this investor call. I first of all give my thanks to the speakers. Thank you, Dr. Bagot for your leadership in driving the TELLOMAK trial. I mean your contribution to share those preliminary data on lacutamab, which, of course, are very important to us. As I said, validate our initial hypothesis and of course, we look forward to updating you on additional data from the TELLOMAK study next year. I would like also to thank my colleagues Joyson and Eric for their presentation. And I would like to also thank the people who asked the question, the analysts, who provided us with a very thoughtful question today that, of course, will help us continue to improve on our plan, and I look forward to our next meeting with you. Thank you very much. Have a great day.

This concludes today's conference call. Thank you for participating. You may now disconnect.