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

Hello, and welcome to the Innate Pharma lacutamab KOL event. [Operator Instructions]. I'll now turn the conference over to Henry Wheeler, VP of Investor Relations and Communications. Please go ahead.

Thank you. Good morning, good afternoon, and welcome, everyone. Thank you for joining today's Innate KOL call on lacutamab where we look forward to sharing updates from data presented at ASH here in San Diego over the weekend. Today's presentation is available on the IR section of the website. On Slide 2, before we start, I would like to remind you that we'll be making forward-looking statements regarding the financial outlook in addition to product development. These statements are subject to risks and uncertainties that may cause actual results to differ from those forecasted. On Slide 3, on today's call, we will be joined by Dr. Sonia Quaratino, our Chief Medical Officer. And we'd also like to thank Dr. Porcu, Director, Division of Hematological Malignancies and hemopoietic stem cell transplantation, Sydney Kimmel Cancer Center, Jefferson Health, Philadelphia as our KOL on the call today. Slide 4, just quickly to cover the agenda. Firstly, we'll hand over to Sonia for an introduction. Dr. Porcu will then go through the results presented here at ASH from the Phase II TELLOMAK study before handing back to Sonia for a close, and we'll then open the lines for Q&A. Sonia, I'll now hand over to you.

Thank you, Henry. Good morning, good afternoon to everyone, and thank you for joining us on this call. Slide 5 is a reminder of our strategy. As an early clinical stage company, our business model centers around 3 key priorities where we look to drive value from our early R&D efforts through later-stage partnership where and when it makes sense to do so. Our ambition is to develop innovative drug candidates that contribute to transform cancer care through a strong pipeline of differentiated antibodies. Firstly, we look to create a near-value driven by our lead proprietary product candidate, lacutamab, which is in development for T-cell lymphoma with updates at ASH, including the final Sezary syndrome and early PTCL data. As a reminder, our focus remains to leverage the value of our products as much as possible, which will further validate our science and offer capital that we can reinvest to advance our early R&D engine. We are actively looking to advance the future development, registration and launch of the asset via partnership as we have done in the past for other partner assets. Second, we continue to fill our pipeline and create longer-term value by leveraging our antibody engineering capabilities to develop innovative molecules with the primary focus on ANKET, our multi-specific NK-cell engager proprietary platform, and we are pleased to see continued progress with Sanofi presenting various updates for the lead ANKET program, SAR443579 this year at ASCO, ESMO and also this week at the ASH meeting. We also look to move our lead property ANKET IPH6501 towards Phase I trial. As we develop antibody targets for our ANKET platform, we recognize some of these binders may be more suitable for ADC therapeutics. And we have announced some further updates in our ADC pipeline last quarter. Last but not least, we are building a strong and sustainable foundation for our business with various partnerships across the industry and academia. And here, our AstraZeneca partnership with monalizumab is progressing in lung cancer. On Slide 6 is a summary of our pipeline, which shows how we continue to translate our science into a robust portfolio of proprietary and partnered assets. It also illustrates how we are executing against our strategy with our lead proprietary assets, lacutamab, ANKET and emerging ADC, supported by partner products with AstraZeneca, Sanofi, Takeda, from late to early stage development. We anticipate a series of potential clinical data readouts and catalysts in that coming couple of years as our R&D engine looks to leverage our scientific know-how to create a sustainable business. On Slide 7, we would like to highlight the presence we have at this year's ASH Annual Meeting as well as TELLOMAK Phase II data, which was presented as an oral presentation on Saturday, which Dr. Porcu is about to cover. We also will update you on some initial Phase Ib PTCL, preclinical combination and clinical safety data, which was presented on Sunday as a poster presentation. We were also pleased to see our partner Sanofi, presenting an update on our lead ANKET program, SIR443579, a CD123 target, NK-cell engager on Sunday. In the presentation, we were encouraged to see further single agent activity and safety for the program in relapsed/refractory AML patients. Additional CR, complete response, were observed with now 5 CR out of 15 patients treated at 1 milligram per kilogram dose level. SIR-443579 was well tolerated at doses up to 6 milligram per kilogram with no dose-limiting toxicities and only 2 Grade 1 CRs observed out of 43 patients. The FDA awarded the program Fast Track designation for the treatment of acute myeloid leukemia in May, and we look forward to further updates from Sanofi in due course. On Slide 8, let me summarize the progress we are making with lacutamab, an anti-KIR3DL2 antibody. In T-cell lymphoma, we continue to pursue a fast-to-market strategy in the niche indication in Sezary syndrome, while lacutamab was granted U.S. Fast Track Designation and the new prime designation in 2020. We have expanded past Sezary syndrome to mycosis fungoides, and we have seen encouraging preliminary data from our Phase II trial in both diseases. Dr. Porcu will cover the data on Sezary syndrome shortly. On the mycosis fungoides cohorts also included in TELLOMAK, we are eagerly anticipating final data due in-house by the end of the year, and we aim to share the data in the near future. Finally, we continue to follow patients with refractory relapsed peripheral T cell lymphoma in the Phase Ib with lacutamab monotherapy. Enrollment continue in the study in the randomized Phase II with lacutamab in combination with chemo sponsored by [indiscernible]. We announced earlier in the year that the US FDA placed lacutamab IND on a partial clinical hold due to one case of hemophagocytic lymphohistiocytosis in the TELLOMAK trial. We have responded fully to the FDA request, which including corporation of risk mitigation and management strategy for HLH in ongoing lacutamab studies. And we've carried out an in-depth analysis of the case, together with the steering committee with independent experts, which point to the fact that the fatality is related to the aggressive disease progression and lacutamab unrelated. We await the resolution of the hold as we continue to cooperate with the FDA on this matter. On Slide 9, I will now hand over the call over to Dr. Porcu, who will update us on the TELLOMAK trial. Over to you.

Thank you very much. Thank you, Sonia, for the introduction. And everyone, welcome, and I'm very happy to present the data on lacutamab in patients with relapsed/refractory Sezary syndromes, final results of the TELLOMAK Phase II study. This presentation was given on Saturday, as Sonia mentioned, to a packed room with a lot of lymphoma investigators from all over the world. So next slide, please. And these are the investigators on the TELLOMAK trial. Next slide, please. So lacutamab as shown in the cartoon on the right is a first-in-class humanized anti-KIR3DL2 cytotoxicity-inducing antibody that is in development for the treatment of patients with cutaneous T-cell lymphoma, particularly mycosis fungoides and Sezary syndrome as well as Sonia mentioned, peripheral T-cell lymphoma. Now Sezary syndrome is a rare aggressive T-cell malignancy with a very poor outcome in a high unmet need and at the moment, there is no approved therapy for patients who fail or have received mogamulizumab. A Phase I trial with Sezary syndrome patients who have received at least 2 prior systemic therapies show that global overall response rate of almost 33% and the median duration of response of 13.8 months with a median progression-free survival approaching 1 year. Based on these data, the drug received orphan drug designation from the treatment of CTCL and then received PRIME and Fast Track designation for Sezary syndrome, patients treated with at least 2 prior systemic therapies. Next slide, please. TELLOMAK is an international multi-cohort Phase II trial of a single-agent lacutamab in 2 CTCL subtypes shown here. And the drug is given intravenously weekly for 5 weeks, then every 2 weeks for 10 doses and then every 4 weeks until disease progression or unacceptable toxicity. Cohort 1 enrolled patients with Sezary syndrome with at least 2 price systemic therapies, one of which had to be mogamulizumab. Eligibility criteria are listed in this slide, essentially relapsed/refractory advanced stage CTCL, B2 blood stage involvement. And patients had to have no evidence of large cell transformation based on central histological review. The study, the primary study endpoint is global overall response rate, and there were a number of secondary endpoints listed in this slide. Next slide, please. This shows the patient characteristics at baseline with a total number of patients enrolled 56 and the median age was 69. The follow-up -- the median follow-up was 14.4 months. The distribution between males and females reflect the distribution of -- the general distribution of this disease in the real world. All patients had advanced stage. All patients had the B2 blood involvement and approximately 70% of the patients had lymphonodal involvement. The median number of prior therapies was 5. And once again, all the patients enrolled had to have prior mogamulizumab. Next slide, please. This slide summarizes the efficacy results based on global response and then compartment response. And I want to start with the best global response on the left column here, that's showing an overall response rate of 37.5%. And then moving on to compartment responses, which are very important in treatments in development for CTCL. The best response in the skin overall response rate was 46.4%. And the best response in blood was 48.2%. I'd like to point out the depth of responses in blood with 15 patients, 26.8% achieving a CR. There were also quite encouraging responses in the lymph node compartment, which is notoriously difficult in this disease with approximately 20% of our response rate, including 3 complete responses. Next slide, please. Now focusing now on global overall response on waterfall plot here looking individual patients, remarkable once again, the fact that there were deep responses with 2 CRs and 19 PRs. And the high global overall response rate really reflects multi-compartment efficacy here. It's notable that many of the PRs were very deep and they -- many of them were almost complete responses. The median time to global response was 2.8 months. Next slide, please. Response is also durable. And this slide shows that the median duration of response for the responders was 12.3 months. And looking at patients still in response at 6 and 12 months, the percentage was, respectively, 74.1% and 61.7%, again, emphasizing that responses in these patients were durable. Next slide, please. Now this slide focuses on in-depth on the blood responses. On the left is the waterfall plot for showing individual changes in blood tumor burden in patients, once again displaying the significant depth of responses with 27 patients, about 48.2%, achieving a blood response, again, 15 patients achieving a complete response with a very rapid median time to blood response of 1 month. We also like to point out that there was one patient who had an unconfirmed CR, who then went on to achieve a confirmed CR after the data cutoff. The panel on the right, and I apologize, can you move to the next slide? Sorry, Sonia. Thank you. This is a slide I'm talking about. My apologies. This is the blood response. So once again, on the left is a waterfall plot according to changes in response -- in blood response. The -- on the panel on the right, it shows the responses according to KIR3DL2 status and with the best blood response and best global response. And I think what's notable here is first, that KIR3DL2 expression on circulating tumor cells was found in all patients to a degree. And in the vast majority of the patients, 92.3%, the median frequency of KIR3DL2 expression was very high. So looking at the expression of KIR3DL2 and response, there was a greater number of responses -- most of the responses occurred in patients who had a high level of KIR3DL2 expression, although there were patients who also had responses even with a low level of expression on KIR3DL2. Now moving on, I guess, back, Sonia, thank you on the responses by compartment in the skin. Again, on the left is a waterfall plot showing that the 46.4% of the patients achieved the skin response. Responses also in the skin were deep, not as deep as in the blood, but quite deep nonetheless, with 5 CRs, 21 PRs. Again, many of the PRs were very, very deep. The median time to skin response was 2.8 months. The panel on the right, it emphasizes the fact that when we look at the subset of patients who had high level of expression of KIR3DL2 in skin, first, we see that 87.5% of the patients had greater -- equal or greater than 1% expression of KIR3DL2. And if we look at this group and we compare the pattern and the breakdown of responses between the group and the entire study population, the pattern response is very similar. There's no significant differences. Only 7 patients after this whole cohort had less than 1% expression of KIR3DL2. And if we go back now to the left, looking at the patients noted with a blue asterisk, you can see that even in those patients with less than 1% expression, there were responses including very good responses. Next slide, please. Next slide. Thank you. So now on to the progression-free survival, which is shown in this slide, it's with a fairly mature follow-up, once again, 14.4 months of median follow-up on this cohort. The progression-free survival was 8 months. And looking at different benchmarks here on the curve, there were patients at 12 months and 18 months that were still alive without progression with 43.3% at 12 months and 38.9% at 18 months, which is quite a respectable progression-free survival for this disease, including the fact that all these patients had received prior mogamulizumab. Next slide, please. Now this slide summarizes the safety data from the TELLOMAK. And I like to point out that about 60% -- 57% of the patients experience any lacutamab-related adverse event with the 4 listed here general disorders of administration site conditions, skin, GI and laboratory investigations representing the most common lacutamab-related adverse events. The one thing I'd like to point out here is that the frequency of skin and cutaneous reactions in this population with lacutamab was low, which is important in the context of the existing standards of care. In terms of serious adverse events, there were a few serious lacutamab-related adverse events, three led to a discontinuation of lacutamab with the causes listed in the notes. And there were 3 deaths due to -- I mean, 3 deaths related to adverse events, but none of them was lacutamab related. Next slide, please. This slide provides a summary information on 2 of the patients enrolled on the TELLOMAK primarily to give an idea of the patterns of responses, including nodal responses, which once again are particularly challenging in this disease. So the first case on the left is 58 years old woman with 10 prior lines of therapy who was advanced stage, of course, and also had a biopsy-proven lymph node involvement defined as N3. This patient is currently ongoing on therapy with a sustained global CR at week 117. What's remarkable about this patient is the fact that she achieved a rapid complete response in blood at week 5. And then an initial partial response in both lymph nodes and skin evolved gradually, but reasonably rapidly as well to a complete response in the lymph nodes at week 13 and in the skin at week 45. The patient on the right is a 51-year-old woman with prior -- 6 prior lines of therapy, also advanced stage, also biopsy-proven lymph node involvement. And she is in a sustained global CR at week 29. What's remarkable about this patient is the fact that in addition to a very rapid response in blood, complete response in blood, this patient was shown by the PET scan images there also had a complete response in the lymph nodes at week 5. And the skin response also evolved. Again, fairly rapidly from a partial response at week 5 to a complete response at week 13. Next slide please. So in conclusion, TELLOMAK is a Phase II study evaluating monotherapy with anti-KIR3DL2 antibody lacutamab in CTCL. Cohort 1 enrolls patients with Sezary syndrome with at least 2 prior lines of therapy, one of which had to be mogamulizumab, which is their high unmet need patient population with no approved therapy post Moga. If we look at the 56 patients enrolled and the analysis of data cutoff, there is evidence of very good clinical activity with a favorable safety profile, safety in particular, confirming the initial data from the Phase I in patients where these patients were heavily pretreated with a median prior therapies of 5. As shown in the slides, responses were as noted across all compartments, which is extremely important, including CRs in all components. And then in patients who achieved the global response, responses were rapidly, not just in the blood but also in the skin and the median duration of response was 12.3 months. The enrollment, as we announced in the summer in Lugano, the enrollment to TELLOMAK is now completed. The patients are being followed, of course, and as they do and accrual of additional data will lead to more mature assessment of this key study endpoints. Next slide, please. So TELLOMAK was a remarkable international collaboration that really supported -- is supporting the development of new drugs, new investigational therapies in a very rare malignancy, hematologic malignancy for which there are no good standards of care at the moment after mogamulizumab. So obviously, it's remarkable. And this has been only possible thanks to collaboration of multiple sites, both across Europe and the U.S. and the sites are listed here. We also want to thank all the patients and their families, all the investigators and the site staff. This study is sponsored by Innate Pharma. Thank you very much. I'm happy to take any questions with Sonia here on this call.

[Operator Instructions]. One moment please for your first question.

Thank you, Dr. Porcu for the excellent presentation. I will now continue by providing a summary and then we can take questions. Now as you can see on Slide 26, we continue to work diligently to execute across all our strategic pillars and believe that we are laying the foundation to drive near- and long-term value. And looking at our clinical stage programs, we expect to achieve a number of milestones over the next 2 years. We have covered the lacutamab Phase II TELLOMAK in Sezary and anticipated mycosis fungoides data, which is imminent. In parallel, we continue to develop our ANKET platform, further reinforced by our partner, Sanofi, and we are very encouraged by the initial clinical data presented at Congress this year and the IND clearance for our proprietary ANKET and progress in the clinic. For monalizumab, the lung cancer trials are proceeding well, and we continue to advance the adenosine pathway agents in the clinic where the Phase II for IPH5201 in early lung is underway. And now let's move to the conclusion slide. On the final summary slide, as you can tell, we continue our exciting journey at Innate. We look to build our business to create value for patients and stakeholders. In summary, we have positioned Innate Pharma for the future with our strategy and made meaningful progress across all strategic pillars. With our R&D engine and antibody engineering expertise, our science is producing more candidates to progress to the clinic. Some, we are developing alone and some partnered. We have a focus on NK cell-engager platform, the ANKET as well as ADC. And in parallel, our late-stage portfolio continues to advance as we look to maximize our late-stage assets lacutamab and monalizumab. Our partnership strategy continues to evolve with Takeda deal adding to those already existing with AstraZeneca and Sanofi. We have carefully managed our resources so we can continue a sustainable business to invest in progressing our pipeline. And I'm very pleased that we continue to have a strong cash position with a runway into the second half of 2025. Collectively, we are driving value across our business and ultimately advancing our goal to deliver innovative medicine to patients. We look forward to keeping you updated on our progress and now I will hand over to questions. Thank you.

[Operator Instructions]. Your first question comes from the line of Daina Graybosch of Leerink Partners.

Yes. I have a couple of questions for the doctor. Dr. Porcu. I wonder as you look forward and think about the next trials you might do of lacutamab in T-cell lymphoma as the company will have to do one for confirmation of regulatory approval. I wonder what kind of designs would be top of the list for you?

Yes. Thank you. That's a great question. And I think that it's a complex conversation that will have to include both considerations about science and data and also considerations about the regulatory path that the FDA may sort of lay down for us. Obviously, I'm not in a position to discuss that particular component for innate. I can say now it is fluid and unclear. One thing that we all know is that the FDA historically recently has been focused on emphasizing the importance of randomized trials with a comparator. I think that the complexity here is going to be that the selection of a competitor that I think is going to be meaningful in a patient population, for example, like in this case, with Sezary syndrome that had received already the comparator. And as an investigator looking forward to see the development and the accelerated development of drugs for this patient population, I think that the design of TELLOMAK by requiring the presence was having been exposed to mogamulizumab in before. To me, that is a very strong -- it's a very strong feature of the trial because it really kind of offers a very strong value in terms of the response efficacy both in terms of response, duration as well as progression-free survival. So looking at what the next study may -- the next best study may be, I don't think I'm in a position right now to say because we're going to have to see, first of all, the continue of the final efficacy on TELLOMAK as more follow-up accrues and then see what the FDA is going to sort of analyze in terms of proposition for the confirmatory study. So it's a very, very dynamic and exciting moment right now to look at the final development of lacutamab.

And then maybe -- thank you. One more follow-up for me is there's been a lot of changes in endpoints in this indication over time. And there's yet another one, which hasn't been used in this trial because this trial started before that. As you look across all these end points, what's endpoint for you in your clinical practice, do you look to that you think best exemplifies the clinical benefit that you see in patients in front of you?

Yes. That's another great question really. So I agree that there has been a lot of shift and changes in the primary endpoints of the studies, for example, the CR overall response 4 like for the Alcanza trial, progression-free survival for Maverick, a global overall response rate here for TELLOMAK. I would say that the most clinically relevant endpoint, the changes depending on the disease. So if you look at CTCL overall, certainly, the durability of the response or potentially progression-free survival is an important endpoint. As complex as it is because for CTCL, progression-free survival can be fairly challenging to define. Now for Sezary, though, which is the data that I presented today and we presented on Saturday, I think that the depth of the responses are really, in my view, the most important endpoints because we know that it's been very difficult to achieve deep global responses where the drug is affecting all compartments of the disease. And without -- in the absence of those deep global responses, we know that the meaningfulness of the responses and the clinical benefit is not great. So to some degree, it depends on the specific subset that we're looking at, and that adds complexity to a global assessment from your standpoint, for example, of what's the value of all these different drugs is.

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

For Dr. Porcu. You mentioned that there were some responders in the patients that had very low KIR3DL2 in the assay. Can you just comment on the explanation for how those would respond? Or may it have been something with the assay that didn't completely reflect the expression because they just did a bad sampling and actually, they did have higher KIR3DL2 than the assay would suggest?

Right. Yes, that's also a good question. That's something that Innate is obviously looking at very carefully internally. Just as an investigator, not being part of the team that is actually doing these assays. I can say that, number one, just for like any biomarker, if you look at any biomarker for targeted therapy in development or recently developed, there are always -- there's always a spectrum of expression of the biomarker. And typically, you will see responses also low levels. The best example perhaps is CD30. That's number one. Number two, here [Technical Difficulty] biomarker in different compartments because one thing is skin, another one is blood. The assays are different, obviously, in blood and skin and the antibodies used are also different in blood and skin. And these are snapshots of course, of expression at one time point. And then because CTCL in general, including Sezary, is really a multi-compartment [Technical Difficulty].

Apologies. We seem to have lost Dr. Porcu. Bear with us while we just try and reconnect him. In the meantime, Yigal, do you have any further questions for Sonia or we can wait until he returns.

Sure. I just wanted to check on the -- kind of on the comments before around the filing strategy. Is the plan to speak to the FDA once you have the final MF data about accelerated approval? Is the expectation that's a likely outcome? Or you don't know yet, and you need to talk to them?

Absolutely. The plan is to have the MF data that are going to be -- the top line results are going to be in-house by the end of this year and then approach the FDA and also, as Dr. Porcu outlined with the previous question, any accelerated approval must present a confirmatory trial, and we will discuss with the FDA around the study design, the patient population that is going to be part of the study design, whether it's Sezary plus mucositis fungoides or Sezary alone and the comparator arm. And so this is something that we will be able to define only after we had this interaction next year.

And then one other one Sonia, just with this study, what was the requirement in terms of the Moga washout time? I am just curious if there was -- with the half-life of Moga is in it, if there is any thoughts...

Now all patients -- yes, all patients received mogamulizumab as part of the inclusion criteria. However, there was a 5-week washout period prior to entering the study. Now going back to your question, unfortunately, we have lost Dr. Porcu that he was addressing the question of the KIR3DL2 expression in different compartment. And of course, the stages are also different. Sometimes what you see and what was presented in the slides is the expression level at baseline. Now we know that on therapies lacutamab can upregulate the expression of KIR3DL2. And so it is not uncommon and also, this is a target that can be upregulated on tumor cells. And therefore, it's not uncommon to see movement let's say, either up regulation or down regulation, depending on the different stages of disease. It seems we have back Dr. Porcu?

Yes. Sonia. Sorry everyone. For some reason my connection got lost. But I'm on with my phone. If you can hear me okay. I am happy to be part of the conversation.

Yes. We can hear loud and clear.

I mean, I think you answered all the questions Sonia that I think...

Yes. Pierluigi, I don't know if you wanted to conclude on the KIR3DL2 expression because we lost you at that time. You were talking about a KIR3 expression in the different compartments, skin and blood. I don't know if you wanted to add on that because we lost you at that point.

Yes. Thank you. No, sorry. So I think that's a key thing really that it's -- when we look at the expression, at entry, it's looking at any one compartment, the expression can be slightly different. So I'm not either surprised or sort of concerned that this -- the fact that we are seeing a few response, the majority in the blood, the majority of the responses that we're seeing in patients who had a high level of expression and the vast majority of them did. So I think this is just normal, I would say, I would call it background noise for kind of biomarkers. And regarding the fact that, Sonia, that you mentioned that it is possible even that the expression of KIR3DL2 in one or more component may actually change as treatment goes on. And therefore, that could also affect the response. I think at this point, we don't know for sure. I mean, I think that's a good, I think, hypothesis based on some data that I understand are available. And therefore, that would be definitely worthwhile exploring further because if it is, that actually will be quite a remarkable additional angle in terms of lacutamab for this patient population.

Your next question comes from the line of Liisa Bayko of Evercore ISI.

For PTCL, can you give us a sense of when we're going to have data there that sort of gives us an indication of efficacy.

Sonia, you will take and do this?

Sure, sure. For PTCL, we have a study, an IST study with a cooperative group and the study will provide some data in 2025. This is a PTCL in combination with GemOx.

Okay. Great. And then for the MF study, what are your expectations? And what would be you your interpretation of the differences between cohort 2 and cohort 3? And sort of responding in one of these populations that is either positive or negative for the biomarker. Do you -- again, just talking about noise, and you mentioned in your prior comment, would you see that more as kind of noise based on maybe some similar consideration to Sezary or compartment related? Or how are you thinking about sort of interpretation and implications for [indiscernible]for example?

This is a great question. And in one way -- Dr. Porcu would you like to take the question or...

As you wish. I'm happy -- as you wish, Sonia. I'm happy to take a stab at it, and then you can sort of pitch in. I -- at least I can give you my perspective on this, and then Sonia can give her perspective. I mean I would say, as an investigator, I would say this; one, that the -- I think the analysis of the expression of KIR3DL2 in the skin or any other biomarker, it's a little more complex than the expression in blood because in blood by flow, it's fairly easy to look at the population that you're looking at in terms of -- both you can do, both by gating as well as by additional antibody markers. So it's much more clean in the blood by flow cytometry. In the skin, you have to look at -- it's a complex environment, macro environment there, a lot of different cells. Sometimes identifying the tumor cells may not be immediately obvious or easy. And therefore, when we look at the expression of any biomarker in the skin, I would say, we always have to be a little cautious particularly in terms of interpreting differences between levels of expression and then correlating those differences to outcomes. So to kind of then to go to your question, I would say that it's pretty obvious that the expression of KIR3DL2 in MF is positive. And I believe -- Sonia, correct me if I'm wrong, but I think it's about 50% of the MF patients express KIR3DL2. And this is as opposed to Sezary where the expression is much higher. In fact, all patients expressed some KIR3DL2, and the vast majority of them expressed a very high level of KIR3DL2. So with that in mind, I think that we will see what the response is -- the final responses to lacutamab in MF are, I think, that Innate has this cohort, the all-comers cohort that the purpose of the cohort is exactly to see -- to have a whole spectrum of expression on KIR3DL2 and see how the response is going to be that in that cohort. So I'm waiting -- as an investigator and clinician, I'm waiting to see the final results of the MF cohort. I don't necessarily hang my head on the fact that patients have to be strongly KIR3DL2 positive to respond and whether there is a cutoff or a threshold at this point, I don't have any data to really to support. If that's the case, we're just going to have to be driven by what the data show. Sonia, do you want to add something?

Thank you Pierluigi. It was brilliant. I don't have anything to add.

Your next question comes from the line of Swayampakula Ramakanth of HCW.

Most of my questions have been answered, but I have one question to Dr. Porcu. As an investigator, when you're looking at all the data that you have at hand from the study in Sezary syndrome, and when you compare it against what you have seen so far, is there any piece of data that you feel you still need to get your hands on to kind of internally, just for yourself to make a decision on how you would want to use this in your clinic.

Yes. That's also a great question. Well, I mean -- so when we are treating patients in the clinic, we always -- the calculation always is a balance between efficacy and safety. So I would say the efficacy/safety equation in balance, at the end of the day, that's really kind of the most important decision that -- or item that we have to look at. So with that in mind, I feel already pretty good about lacutamab in patients with Sezary syndrome specifically, which I think that's your question, but in general, also for MF. And so the safety of lacutamab as based on the Phase I that was already published and then now the Phase II, I think it's very good. I would go as far to say that it is competitively good in respect to the existing standard of care because there -- and -- well, to be explicit, mogamulizumab, which is an approved drug, so we can talk about it. Moga has a number of adverse events that are -- can be concerning. We know one is the MAR, the Moga-associated rash, which may not be severe from a medical standpoint necessarily, although sometimes it can be, but it's quite a handful because patients that require often steroids, they cannot resume therapy. So it kind of is really a significant sort of burden. And in addition to that, there are also less common but still observed immune-mediated effects from Moga. And so based on all the data that we have so far, we don't see those with lacutamab. I mean, obviously, it's still early. The drug is not in the market yet and a lot of things can happen after the drugs can get used in the market. So -- but for now, I think that is an important part of the calculation. Efficacy-wise, as I mentioned, to us, as clinicians, we really need to see responses across all compartments. And one of the strength of TELLOMAK is that the quality of the data on nodal responses in particular, is significantly better than the quality of the data that we had with all prior therapies. And so based on that, I don't feel that I have to kind of -- I'm waiting for anything major at this point. And except for the data in mycosis fungoides, this still have to mature and nothing we want to know. Does this address your question?

Yes.

Again, we've just got a couple of questions online as well. So maybe for Sonia, I'll bundle them together just on the regulatory strategy. So do you anticipate to file in the U.S. and the EU? And also thinking about the TELLOMAK trial was in heavily pretreated patients. Given the results, do you think it's possible to go in an earlier line setting against Moga or a disease?

Well, I think in a way, all these questions have been kind of addressed by some of the questions before. Of course, they are important questions. But as Pierluigi just mentioned, the favorable safety profile of lacutamab together with efficacy that, that of the response that we have seen from the Phase I, together with Phase II can really point to define that lacutamab can be used also in earlier line. Of course, this needs to be discussed with the regulators. And depending on what the control arm could be, it's not impossible to see also a registrational trial in an earlier setting. And we will go for FDA discussion in early 2024.

Okay. Thank you very much. I don't see any further questions on the line or on the phones. Sorry, one further question has actually just come in. So Eric Le Berrigaud at Stifel. Two questions for Dr. Porcu. Number one, by TELLOMAK design, patients had to be post Moga and therefore, second line plus but the reality is that patients had received 4 line plus on average. Can you let us know how and when you're using Moga in your daily practice, which patients, what stage? And the second part is, considering the risk-benefit balance seen in TELLOMAK, would you say it may be a loss of chance for patients not to be used earlier than fifth line when available. So Dr. Porcu?

Yes. Thank you. Great question. So the -- in terms of now the real-world use of mogamulizumab in patients with CTCL definitely is being used earlier on, particularly in patients who have blood involvement, which is defined as not necessarily B2, but also B1. And it's something that now practitioners across the world are assessing more and more in patients with CTCL. And there are data now that are proving and being presented looking at how Moga is being used in the real world. And it's true that it's being used earlier on. So based on that, certainly, I would say that the same pattern could easily be projected for lacutamab. And I would imagine that we would not -- for patients, particularly for patients who have blood involvement, again, pending the final data for MF, which at this point, I don't think we can kind of make any meaningful comment on. But for Sezary, patients who have blood involvement, I think that if lacutamab were available, people would use it much earlier. The median number of response for prior therapy was 5 actually in the Sezary cohorts. So Yes, we definitely would use it earlier, and this is going to be a pattern, I think, for most active drugs moving forward with -- in this space.

Now I don't see any further questions on the line or on the chat. So Dr. Porcu, thank you very much. Thank you very much everyone for joining today. Dr. Quaratino thank you. And have a good rest of your day. Thank you.

Okay. Thank you, everyone. Okay.

This concludes today's conference call. You may now disconnect.