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

My name is Krista, and I will be your conference operator today. At this time, I would like to welcome everyone to Innate Pharma Virtual KOL event. [Operator Instructions]. Thank you. I will now turn the conference over to Dr. Sonia Quaratino, Chief Medical Officer of Innate Pharma. Sonia, you may begin your conference.

Thank you very much. It is a great pleasure to hold this meeting today to present the data in mycosis fungoides. We have recently presented at ASCO with lacutamab. It is a great pleasure to have with us today, Professor Porcu, that is the principal investigator of the TELLOMAK study is Director of the Division of hematologic malignancies hemopoietic stem cell transplantation at the Kimmel Cancer Center, Jefferson Health, Philadelphia. And we also have with us today, Susan Thornton, the CEO of the Cutaneous Lymphoma Foundation that will only participate in the Q&A session, should any of you would like to have the view from the patient perspective. Now I will start with a very brief introduction before introducing Professor Porcu that will discuss the results of the Phase II TELLOMAK study, and then I will wrap up for a summary before initiating the Q&A. Now just to -- thank you, Matilda. Just to summarize. We have presented the data of lacutamab at ASCO last week. And after the data in [ ASCO ], we presented at ASH last year, with this data, we continue to pursue a fast-to-market strategy with lacutamab, which is our lead proprietary asset. Within this proprietary portfolio, we are also very pleased to present 2 posters at ASCO with IPH65, the second-generation ANKET and one oral presentation that was delivered at the last AACR with the Nectin-4 ADC IPH45. Within the partnered portfolio, we are also very pleased with the news that Sanofi progressed IPH65 or SAR’579, first generation ANKET to Phase II in refractory AML. And of course, we remain tuned to Monalizumab, which is in Phase III and the Phase III is currently underway. Now on the top of the slide, just to remind you our pipeline of proprietary and partnered assets at the top of the slide, you will find the proprietary pipeline that is very well balanced among proprietary antibodies like lacutamab and IPH53, an antibody against CD73 our ANKET and now the new entry, the antibody drug conjugate. In the partnered asset, Mona is in Phase III in unresectable Stage III non-small cell lung cancer in combination with durva and explored in Phase II in neoadjuvant setting alongside the CD39. Sanofi also is continuing the development of 2 angles in the heme space with IPH65 that has currently in Phase II in AML. And the anti-BCMA IPH64 in Phase I in multiple myeloma. As I mentioned previously, last week at ASCO, we had 5 abstract. Of course, very important, the result in MF for lacutamab that we are discussing in a minute, 2 poster for IPH65. One was a trial in progress and another poster around clinical -- the scientific rationale for the second-generation ANKET and 2 poster around Monalizumab. Lacutamab that specifically kills cells expressing the KIR3DL2 is a tumor-associated antigen expressed at a high level in all Sézary patients a moderate expression level in 50% of patients with mycosis fungoides and patients with peripheral T-cell lymphoma. The TELLOMAK trial is a Phase II focus on CTCL and at ASH 2023, we reported the data in a SS in a heavily pretreated patient population including moga, which is considered the top standard of care in this setting. We will now present the TELLOMAK data in mycosis fungoides, where 100 patients who received at least 2 prior systemic therapies were allocated to different cohorts depending on the KIR3DL2 expression level higher or lower than 1%. In the ongoing KILT study, a randomized controlled study in PTCL, lacutamab is tested in combination with gemcitabine and oxaliplatin versus GemOx alone. And results are expected at the end of 2025. Now for the results of the Phase II TELLOMAK study. It's a pleasure to introduce Dr. Porcu.

Thank you, Sonia, to everyone. It's a great pleasure to be on this call this morning together just with you, Sonia, and Innate, but also with Susan Thornton CEO of the Cutaneous Lymphoma Foundation and to discuss in the Q&A, a very important part of all of this, which is the reason why we're doing this trial, which is patients. So as Sonia mentioned just a week ago on behalf of the TELLOMAK investigators, I had the distinct pleasure of presenting the results of the TELLOMAK Phase II trial. Which investigates lacutamab in patients with CTCL. Specifically, we presented the results for the relapsed/refractory mycosis fungoides cohort with a data cutoff of October 13, 2023. Next slide, please. So just to provide a brief background and some clinical context for the development of lacutamab. Mycosis fungoides is a mature T-cell lymphoma that is affecting primarily the skin at least a presentation that comprises about 50% to 60% of all the CTCL, as shown in the pie chart on the right. Now about 25% of the patients present with advanced stage, which is defined as the composite IIb-IVB stage and the survival for this group is only 15% to 25%. So this is an aggressive malignancy in advanced stage. Mogamulizumab was approved in 2018 for adult patients with at least 1 prior systemic therapy. And as shown in this slide, the efficacy benchmarks for this population, which included Sézary patients are an objective response rate of 28% in the entire cohort, and specifically 21% in the mycosis fungoides patients. A median progression-free survival for the whole quarter of 6.7 months. Now of note, most patients who receive moga on this trial relapsed and progressed. And in terms of safety, grade 3 and 4 AEs, we're observing 41% of the patients and nearly 20% of patients discontinued moga for safety reasons. Therefore, this really remains kind of a high medical need population. And if you look at the chart, at the pie chart on the right, again, In more detail, you will see that once again, MF is the most common CTCL. Sézary is just a very small fraction, but a very high unmet need because there are no effective therapies. Now large cell transformation, which was an exclusion for TELLOMAK only affects about 5% of the patients with CTCL. And then there is a whole series of additional types of 30%, which will not be discussed today. Next slide, please. In terms of target, as Sonia mentioned, KIR3DL2 is expressed on more than 90% of the patients with Sézary syndrome at high density and in about 50% of the patients with mycosis fungoides. Lacutamab is a first-in-class humanized anti-KIR3DL2 cytotoxicity, as shown on the right, in phagocytosis inducing antibody under development in T-cell lymphomas, including CTCL, but also peripheral T-cell lymphoma, again, it will not be discussed today. Because of a high unmet need and very encouraging safety and efficacy data in the Phase I, Lacutamab was granted orphan drug designation in CTCL by both the EMA and the FDA and was granted prime by the EMA and fast track by the FDA designation for Sézary syndrome after at least 2 prior systemic therapies. Next slide, please. As Sonia mentioned, TELLOMAK is a Phase II multi-cohort study evaluating monotherapy lacutamab in both mycosis fungoides and Sézary syndrome. The Sézary syndrome data have been presented already at ASH last year and also Lugano last year. And today, we present data in all mycosis fungoides patients. The eligibility including relapsed/refractory Stage IB-IVB mycosis fungoides after at least 2 prior systemic therapies. Patients were enrolled based on KIR3DL2 expression defined as greater or equal than 1% or less than 1%. And this was based on central review by 2 pathology experts with a consensus scoring decision 3. I will show an example of KIR3DL2 stains in one of the next slides towards the end. Patients with large cell transformation, as I mentioned, were excluded. The primary endpoint was global, overall response rate with multiple secondary endpoints listed here. In terms of dosing and drug administration, lacutamab is an intravenous infusion is given weekly for 5 weeks then every 2 weeks for 10 doses and then every 4 weeks until progression or unacceptable toxicity. Next slide, please. So this table shows the demographics for all 107 patients enrolled and then in the main column to the left and then separately for Cohort 2 and Cohort 3 towards the right. The median age for the entire cohort was 62 years. As expected in this disease, there was a slight predominance of males. Importantly, less than half of the patients had early stage and the majority of the patients had advanced stage. This meant about 1/3 had advanced skin stage, so called Stage II and IIB, and the rest had Stage III and Stage IV. Patients were heavily pretreated and with a median of 4 prior lines of systemic therapy. Now while prior moga was not required for eligibility in Cohort 2 and 3, unlike cohort 1, which is the Sézary patients, about 1/3 of the patients with MF here, in fact, did receive mogamulizumab as one of the prior therapies. I think this is important to keep in mind. The median follow-up for the cohort was 11.8 months. Next slide, please. So the data of -- I'm sorry, at the time of data cutoff, which is, as mentioned, is October 13, 2023, 100 patients received treatment. The slight focus is on the primary endpoint for the study, which, as I mentioned, is a global overall response rate. Now this requires scoring on all 4 disease compartments in mycosis fungoides, which are skin, lymph nodes, viscera and blood. The global overall response rate for all patients regardless of KIR3DL2 expression was 16.8% as shown on the top row there. And the global overall response rate for the other -- for the 2 cohorts, greater or more than 1% was 20.8% and 13.6%, respectively. The time to global response was quite short with a median of about 1 month. And if we look at just responses in the skin, which is the second to last row, there, it was 29%. And very respectable and encouraging response rate in the skin. Now the last row describes what the response rate -- the global response rate would be if we adopted the also in 2022 criteria, this is something that we did specifically in the Sézary Cohort, and we presented at Lugano in 2023. Which also -- we examine response according to the new [indiscernible] 2022 criteria. And the major difference between the 2011 and the 2022 criteria, primarily involves the assessment of lymph nodes. And it requires that nodal involvement to be pathologically proven, which in the lingo of the staging criteria is called N3. Therefore, lymph nodes that may have been palpable or abnormal or in any way of concern, but they were not proven to be pathologically involved and because no biopsy was done, and they are called NX. Or lymph nodes that were, in fact, pathologically assessed and they were N1 or N2, which is their mythopalic lymphadenopathy were not considered involved. And this is important because according to the -- [ also ] in 2011, those lymph nodes, if still detected, would make for a stable disease. And instead for the 2022 criteria, it would make for a response, and therefore, we make the difference between a stable disease and partial response. So if we look at that in terms of the last row, you will see that responses -- global responses across all the different -- the whole Cohort and the 2 different Cohorts will be 22.4%, 29.2% and 16.9%. Next slide, please. So this is the waterfall plot for best overall response by mSWAT. So again, I want to emphasize that kind of the best overall response here is the response in the skin, which is measured by mSWAT for each cohort on the -- First of all, early and deep responses were observed in both cohorts as the individual patient data here show -- on the left, we display cohort 2 patients with greater or equal than 1% KIR3DL2 expression. As you can see, 10 patients achieved global ORR response, including 2 complete responses and deep responses in the skin were observed, including several patients who did not quite achieve global response but were very close. On the right, our Cohort 3 patients with less than 1% KIR3DL2 and also here, response were observed. Deep responses, 8 patients achieved a global overall response and several deep cutaneous responses also were observed here. Next slide, please. This is the progression-free survival for both cohorts. Cohort 2 is in blue, Cohort 3 in green. The median progression-free survival for the entire cohort is 10.2 months. And for Cohort 2 and 3, the progression-free survival, respectively, is 12 and 8.5 months. I think the important message here is that both curves look quite competitive compared to the progression-free survival for mycosis fungoides in MAVORIC, which was only about 5 months -- 5.6 months. And considering that 30% of these patients in the TELLOMAK had actually received prior mogamulizumab. And again, the entry criteria, the eligibility for TELLOMAK was at least 2 prior systemic therapies. And for moga was one prior systemic therapy. Next slide. Thank you. So this slide and the next one, just illustrate 2 clinical cases from patients enrolled on study just to provide the audience with kind of a flavor of what the manifestations of the clinical response is this, in particular, is a 68-year-old woman who was diagnosed in 2016, multiple prior lines of therapy. This patient had stage T2, which is essentially more than 80% -- I'm sorry, more than 10%, between 10% and 80% skin involvement with [ patch and black ] disease. And that's why there is a substantial amount of skin involvement in this patient. And the patient was B1, which means blood involvement, not reaching the criteria for a Sézary syndrome, which would have been an exclusion. In this patient, there was a PR in the skin at week 5, so very rapidly. And then there was a CR at week 37. In terms of the other components, the blood was already a complete response by week 5 as often seen in B1 disease with Lacutamab. The Lymph nodes were not involved. And the -- in terms of global response, it was a PR from week 5 and then a CR starting from week 37. Which is still durable with the last evaluation at week 153 in January of this year. So these are very long durable responses. Next slide, please. This is another patient with a slightly different clinical manifestation of the skin lesions here with a 74 years old male. Initially diagnosed in 2020. 2 prior lines of systemic therapy. This patient also had T2, so between 10% and 80% of skin environment with [ patch and black ] disease. Was also on B1 baseline, this patient also was 2 by lymph node assessment. In terms of response, PR from week 5, once again better rapidly, blood PR starting from week 13, lymph node the patient had stable disease with an end to a baseline. I'd like to point out that this patient with the revised [indiscernible] criteria would have been potentially a partial response because N2 would not be considering involvement of the lymph nodes. And in terms of global response this was a PR from week 13, once again, very durable with ongoing response at week 69. Next slide, please. These are the treatment emergent in lacutamab related adverse events observed in at least 5% I think that the take-home message here is that based on the already encouraging results from the Phase I, TELLOMAK really confirms that the overall safety of lacutamab is excellent, in this highly pretreated population. Once again, were 30% of them having received prior Mogamulizumab. There was no unexpected toxicity. There was no sign of autoimmune manifestations. And so the safety single was very strongly confirmed. Next slide, please. This is just a sort of a kind of an additional view of the safety in terms of the most common related adverse events. Once again, some general toxicities common with any form of immunotherapy, fatigue, nausea, asthenia, [ Arthrologist ], some diarrhea, but nothing significant in this court Phase II cohort confirmed. Next slide, please. So here, I want to spend a minute just showing the audience here the stains for Q3. Once again, the stains were interpreted by 2 expert pathologists. And the point of this slide is to show that there is some intra-patient variability observed between biopsies because if you look at patient A, which is the top 2 panels and patient B, which is the bottom 2 panels, each one of these patients had two biopsies and they were done at the same time, just from different locations. And for patient A biopsy 1 showed an estimate of 1.3% KIR3DL2 positive in mononuclear cells and biopsy 2 shows 60%. So there is significant variability here from site to site. And this patient, of course, was enrolled in Cohort 2 so they're equal greater than 1%. Now patient B had -- an initial biopsy was scored a 0.8% KIR3DL2 positive. In the second biopsy, there was score that's 26% KIR3DL2. And so the patient B ended up as well in Cohort 2 with more than equal more than 1%. Again, this was based on the consensus review and the discussion between the 2 pathologists. Next slide, please. So in conclusion, TELLOMAK Phase II study of Lacutamab monotherapy in CTCL. The study enrolled MF patients with equal -- at least 2 prior systemic therapies. In the MF population, there were early responses in heavily pretreated patients with MF. Antitumor activity was observed in patients with both equal or greater than 1% and also less than 1% KIR3DL2 expression at baseline. Median progression-free survival is quite good with 10.2 months on the whole MF population, considering the number of prior systemic therapies and the lack of available drug for this patient population. Once again, no safety concerns or delay toxicities even long-term follow-up. Identified in this cohort. And the excellent tolerability of lacutamab provides a strong rationale for further investigation of lacutamab in combination with other anti-lymphoma agents and the further development of lacutamab to bring better treatment for patients with relapsed/refractory CTCL both Sézary and MF, which -- who badly need additional treatment options. Next slide, please. So enrollment for lacutamab is now complete. The data are maturing, and we are looking forward to continue follow-up on the data. TELLOMAK was a remarkable clinical trial that really was possible due to the international collaboration from multiple active sites partnership with patient advocacy organizations like the Cutaneous Lymphoma Foundation, ensuring accrual for this very rare malignancy that continues to represent a high unmet need and needs additional therapies. Thank you, therefore, to all the investigators, the experts, the staff, patients and families, and thank you for your attention for this presentation. Sonia, back to you. I'm happy to answer any questions. the Q&A later on.

Thank you, Professor for this very comprehensive presentation. And in the next slide, I really would like to put some of the data you just eloquently presented in the context of the treatment landscape. And in particular, of course, against Mogamulizumab that tops the standard of care in CTCL space. Now we need to remind that in MAVORIC the MF patients that fail at least 1 systemic therapy, whereas in TELLOMAK patients failed at least 2 systemic therapies. And this is a big difference in this -- in this setting. As you mentioned, all -- 34% of patients had received prior Moga, that is an equivalent of 1/3 of the ITT population. Now when we look at the overall response rate and the efficacy of a Moga, we can see that it's very well compared with what we observed in the TELLOMAK trial study as in the MF population, we've observed a 21% response that when compared to the 16.8% that we observed in the overall mycosis fungoides population. And when we look at the PFS, the progression-free survival, that is the primary endpoint of the Phase III, the -- what we observed in lacutamab is almost double than what was observed in the MAVORIC trial in the mycosis fungoides population. 10.2 months versus 5.4 months. And it is exactly for this reason that we consider this result today very encouraging. And we consider also lacutamab as a promising new therapy for patients with high unmet medical need. In the next slide, thank you. Now strong this TELLOMAK. Today, we have confidence in lacutamab potential in the CTCL space. Now we started the trial with an expectation for a small niche consisting of Sézary syndrome. And perhaps maximum of 50% of the mycosis fungoides patients after 2 previous line of treatment. But now we know that this population could be revised to include a greater proportion of the MF population as we have clinically meaningful results also in the subgroup of patients were very low level of KIR3DL2 were detected. And in terms of business case, we can see this increase from the original 1,500 [ available ] patients per year to potentially 3,500. And also, it is not unreasonable to think for a line extension and moves to an earlier line, further increasing the population to around 5,000 per year. Now in the next slide, I really would like to conclude that 2024 continue to be a very busy year for Innate Pharma. We have seen the results for lacutamab, we will end the Phase I of IPH53, the anti-CD73. We have seen the initiation of IPH65, the second-generation ANKET for CD20-positive B-cell lymphoma. We have seen also the progression of our ADC IPH45, targeting Nectin-4 which will go through an IND. And of course, we are happy to see the progression of IPH65 to Phase II and IPH64, the anti-BCMA to Phase I with Sanofi. And in the next slide, to conclude, we continue our mission to create value in our 3 pillars through lacutamab, the ANKETS and more recently, the delivery of differentiated ADCs. And we remain with a strong cash position to the end of 2025. We now can open the Q&A. Thank you very much for your attendance.

[Operator Instructions]. Your first question comes from the line of Yigal Nochomovitz with Group.

This is Ashiq Mubarack on for Yigal. Just one on maybe cross-trial comparisons with MAVORIC. I think you guys showed a lot of data from both yourself from that study. You made the point about the levels of pretreatment being different, but I'm also wondering what other differences in the patient population might affect that cross-trial comparison. I think one thing we've noticed is that maybe MAVORIC enrolled more Stage III, Stage IV type patients. We're curious about how that might affect any cross trial comparisons, especially on PFS.

Sonia, would you want me to take that question? Or you want to take it?

If you'd like -- Yes, please. I think that your answer will be much appreciated.

Okay. Thank you, Sonia. So I would say this. I think that the -- when it comes down to sort of the population for a trial in this space, I think that one of the most important things in addition to stage -- I mean, stage is important and is relevant. But I think one of the most important things is that the number and type of prior therapies that people receive. I mean the natural history of mycosis fungoides in particular, is one of continuous sequencing of systemic therapies. Once the need for systemic therapy is reached. And that is reached in almost every single patient with mycosis fungoides at some point. Then essentially, the clock, so to speak, starts taking in terms of the progression on therapies. And therefore, if I -- when I look at the composition of a [indiscernible] patients in a clinical trial, the -- to me, in terms of the challenge in the value of the therapy that is being delivered and really has to -- is driven primarily by the prior therapy. So in this sense, I would say that the major differentiator between TELLOMAK and Moga in MAVORIC, the Phase III, is that the lines of therapy were fewer in MAVORIC. And as we mentioned a few times, about 1/3 of the patients in TELLOMAK of the MF patients had a prior Moga. So it's really sort of -- to me, that's what drives the comparison and what drives the value. The -- obviously, MAVORIC was kind of a larger trial. It was a randomized trial. The other thing is the -- in terms of the assessment of the patient -- for example, nodal disease, the assessment of nodal disease in TELLOMAK has been much more rigorous than the assessment of novel disease in MAVORIC for -- just because of historical reasons. I mean we know a whole lot more now about how to exactly to approach the different components than we did when MAVORIC was initially designed I hope this answers your question.

Yes. That's a very helpful color. And maybe one more quick question for the company. What's the sort of development path and regulatory path from here? Do you need to have discussions with regulators on additional studies? Or how are you thinking about it at this point?

I believe that we've lost Sonia. Sonia, are you back online now? Yes. Apologies for that. We can come back to Sonia when she reconnects. Just as a reminder for the regulatory next steps as stated in the previous earnings call [indiscernible]

Hello, Henry?

Hello Sonia, go ahead. We just had a question about the regulatory next steps for lacutamab, if you'd like to answer. Apologies for the technical difficulties, everyone. Yes, as I was stating -- as we stated in the Q1 earnings call, we are -- we're approaching the FDA next steps -- regulatory next steps for lacutamab. So we'll update you in that -- and.

Hello, Henry?

Yes, Sonia, we can hear you. Operator, can we take the next question, please?

Absolutely. Your next question comes from Daina Graybosch with Leerink partners.

I have a question for Dr -- Professor Porcu, and maybe I'll take them one at a time. The first one is, with all these different ways of assessing response, I wonder if you could talk about how you assess progression, specifically when you decide to switch a patient treatment? And secondarily, do you have the duration of treatment, maybe the duration of treatment for these patients in TELLOMAK.

So I hear 2 questions. I could be wrong. But I mean, I think the first -- your first question is, I mean, how do we assess response with all these different components. And perhaps kind of a secondary question for that is, so how do we actually define progression, which is quite challenging. And then the other is the last question was about the duration of response. Do I have the right?

Well, no, actually. So I want to know how -- I think we understand how you define response, specifically how do you define progression and decide to switch to systemic therapy? And then what was the duration of treatment for lacutamab in this study? And then I have a follow-up after that.

Got it. Okay. All right. Sounds good. So I think that you are touching on a very, very important point, which is the issue of the measurement, the scoring of disease progression and [indiscernible] response. The first thing I would say, of course, global responses are complex end point. That's part of the challenge of drug development in CTCL, specifically mycosis fungoides. And that is because you have this multi-component sort of assessments, which are required for scoring a global response. And it is sort of -- often, it is sufficient that 1 particular component does not achieve a response, a stable disease, for example, to really kind of put a big dent on the overall global response. I think that the first. So However, having said that, now both -- especially at the level of the investigators conducting clinical trials in CTCL; and as well as the companies that are kind of learning how to sort of deal with these complex end points. And as I mentioned before, there has been a learning curve over time. So they are, for example, kind of the -- so the structure endpoint assessment in the initial trial in MAVORIC, for example, was of a certain degree good, but perhaps not perfect. And now moving forward, TELLOMAK has a much more rigorous approach. I think this is my opinion, and it is -- I think it's the opinion of all the investigators. So -- first of all, the skin, it's important to know that the skin drive response, global response. And this is true, by the way, it's true also regardless of whether you're dealing with -- [ also ] in 2011 or [ also ] in 2022, the skin continues to drive global response. Ratio progression is a really a touchy sort of point because, I would say this, the first -- the most important thing is that progression be defined with a centralized review of the data. Because if you -- often you leave the definition of progression to say, the treating investigator or -- well, let's say, the treating investigator the decision of switching to a different type of therapy is really kind of multifactorial. And it is influenced to a very significant degree on what the patients really experience. And in fact, that was one of the major challenges in MAVORIC, which actually had a crossover design from the Vorinostat to Mogamulizumab. And I would say that despite the fact that progression really had to be centrally reviewed and approved, to jump on the other cohort. I think that there are still some questions how really sort of stringent some of those aware. And so it is a big deal when you have progression-free survival as your primary endpoint. And so that kind of addressed, I think, the progression question. And regarding the duration of treatment, most trials, including TELLOMAK, really have continuous treatment until disease progression or safety issue of toxicity. And that is why safety is so important in any drug development for MF because at the end of the day, most patients stay on treatment for a very long period of time if they respond, and then after a while, the driver of continuation on therapy and on trial for trials is whether the patient feels that the drug is well tolerated or the investigator field the drug is well tolerated. I think you said you have a follow-up on these 2 things.

I have a different follow-up and then I have a follow-up on your answer. So I guess when we compare across study, the PFS results how much subjective judgment is there? Could there be simply a difference in progression-free survival because that central review judged differently between TELLOMAK and MAVORIC. And then back to the duration of treatment, do we have a specific number from TELLOMAK of what the duration treatment was for MF in this study?

Different duration of treatment within TELLOMAK. To be honest, I don't think I have that information. So on average, perhaps Sonia may have this. On average, how long -- how long people stay on treatment between TELLOMAK and MAVORIC. I apologize. I don't think I have that. I don't want to misquote anything. Regarding the progression, I mean I think that progression is defined. I don't want to give the impression that progression is vague. Progression is defined by the response criteria. And therefore, as long I think that if you have experienced investigators, you have to sort of take the scoring of progression for what it is according to the criteria. It has to be, obviously, all the data have to be reviewed just like in TELLOMAK. In MAVORIC, the progression was required again, to move to the investigational arm. In TELLOMAK just a secondary, by the way, a secondary endpoint. The primary endpoint is a global response. I don't know, Sonia, do you want to add anything to that in terms of the primary endpoint for TELLOMAK versus MAVORIC that...

So while we are, I think, comparing a Phase II that is TELLOMAK with an overall response rate as a primary endpoint to the MAVORIC that has a PFS as a primary endpoint. But as you mentioned, Pierluigi, the -- let's say, it was essential in MAVORIC to have the central review because it is clear that patients would not like to have the [ vorinostat ] and would like to cross over as quickly as possible to the investigational arm, which was Mogamulizumab. Here, we have a single ARM study. And therefore, there is no incentive, so to speak, for patients to abandon the study. They really stay until true progression, I would say. Nevertheless, we will do the central review of the data as part of our conduct for the study.

Right. And then one more question. One more question for me. I wonder, let's say, lacutamab is approved with the accelerated approval on Sézary syndrome. How do you think the CTCL guideline community will reflect their recommendation for MF. Do you think it's available for SS that there might be a guideline recommendation to use an MF ahead of an official regulatory label update?

This is a very interesting question that would require a crystal ball. I'm afraid, I really cannot comment on this. Of course, we are working to get -- to maximize the value of lacutamab not only for Sézary but also for the larger population of Mycosis fungoides. And we will go in an interaction with the FDA to define the path forward, but I cannot really comment on what is coming next and what is coming first.

I wonder if Dr. Porcu could comment on that.

Yes. I mean I think that -- so I agree with Sonia. And I think that -- I guess what she's referring to specifically is kind of formal official guidelines, right? I'd say, for example, the NCCN guideline, which most people follow, certainly here in the U.S. but also abroad. And I'm not part of the committee in the NCCN. So I'm not speaking officially on anybody's behalf. Obviously, just as a practitioner. So I mean, I think that just like Sonia mentioned, the NCCN guidelines will have to examine the specific sort of approval of the drug. As you know, typically, the NCCN receive kind of an application from the company once the drug either is approved or is about to be approved. And then they discuss how to sort of integrate that in the guidelines. And I don't think there's anything we can say, I can say, specifically about how that's going to be discussed. Practically speaking, which I think is what you're referring to, I mean, I think that having another -- an active drug, quite active drug in Sézary, I mean there's a huge unmet need in Sézary patients. And so I think there would be broad -- a very rapid adoption of the drug, particularly when you look at the safety of the drug, which is -- again, there's no Phase III comparison at this point. So -- but just historically looking at the MAVORIC and also post-marketing data with Moga and looking at the safety as available so far in the clinical trial with lacutamab, lacutamab seems to be a safer drug. I think I can say that. And so that's what is going to drive the adoption of lacutamab, not just in Sézary, but also in MF, particularly because it is effective. And it is effective regardless of whether you have more than 1% or less than 1% KIR3DL2 expression. So I see this as -- I see the adoption of lacutamab as kind of a very kind of easy path, so to speak, once the drug is approved. Susan, I don't know if you want to say anything as a patient about that. I think it would be good to hear your thoughts.

Sure. There we go. Great. Thanks. Yes, as I'm listening and I'm thinking, sitting in my shoes, A, as a patient who didn't have a lot of options as an MF patient back in the mid-90s. And what we have today, which still is not enough and talking to patients around the world who are really grappling and struggling with the disease and having new options would be incredibly beneficial. Most folks that are living with particularly MF and Sézary, of course, are also grappling with severe quality of life challenges the skin issues, the itch, the flaking, the visibility of it, the impact of that on someone's day-to-day life is huge. And having another option, most of these folks, as you've mentioned, have gone through probably every therapy we have available in combinations and over the course of many years. And having something else to put in the toolbox that could potentially give a longer duration of response even at stable disease where the skin is in a much better place where people can sleep, people can wear clothing, people can not feel like they can't go outside and public because of the way their disease looks is -- I think it kind of goes beyond the pictures and the data don't show the day-to-day lived experience, particularly of this patient population where the psychosocial, the physical impacts are huge. So that's my $0.02 for what it's worth.

Thank you.

Your next question comes from Lisa Bayko with Evercore ISI.

This is Jingming on for Lisa. So I have a follow-up to one of the prior questions for Dr. Porcu. So is there any correlation of clinical stage and the treatment effect PFS in particular? And I have another question for the management. So how much confidence do you have that lacutamab would be competitive in the second-line setting for Sézary syndrome. And do you require a partner to bring lacutamab forward?

So regarding the correlation between stage and progression-free survival, I don't have -- I cannot think of data kind of showing a correlation, either positive or negative. I mean it's I think it has more to do with the prior therapies. Now, granted, I think that for patients with very advanced CTCL patients with stage IV, A, or B, will be with very bulky disease or very heavy peripheral blood environment, and those patients are very high risk. And I think there may be. But this is not -- this is really not kind of the majority of the population either in TELLOMAK or in the MAVORIC. That's really a very, very, very small fraction of patients. In most of the patients, the difference between IB, for example, and IIB or IIIB, in my experience and in my recollection of the data overall, I don't think there is a strong correlation. And then regarding the -- what again is the question about how confident I am in lacutamab being second line? Can you rephrase that question a little bit, yes?

Yes, I'm just curious, like for Dr. Porcu the company. So how much confidence do you have that lacutamab would be competitive in the second-line setting for Sézary syndrome. Because we know for the Sézary syndrome cohort, all patients actually had to have Moga as a prior line of treatment?

So maybe I'm going to let Sonia take that first, and then I'll give you my physician's perspective on it.

Right. Yes. Of course, in the Sézary syndrome, all patients were pretreated with Moga. And this is, let's say, a space with high unmet medical need because once patients fail on Moga, there is very little that the investigators can really offer to patients. And so there is certainly a space as a third-line therapy. On the other hand, I think that by looking at the response rate that also we had in mycosis fungoides between patients who were pretreated with Moga or non-pretreated with Moga we can really explore the possibility open the possibility that this drug can have a successful future also in a second-line setting. And for the same token, considering also the an extremely well-tolerated profile and the unremarkable safety profile that is showing, there is also a possibility in the future that lacutamab could also be dosed in combination with other drugs, even with chemotherapy, for instance. And here, actually, this is something completely new, and I would like to have PG's perspective from the investigator point of view.

I mean I think that the -- what kind of drives the adoption of therapy in the real world is driven by 2 things, obviously. One is a general sense of a knowledge of the efficacy particularly for a disease like Sézary syndrome, which is aggressive, and therefore, efficacy is really kind of a very important component. And the second is safety, especially long-term safety. And that's where I think, based on all the information that we have so far, there is the signal here is that the safety of lacutamab, I would say, has an edge compared to Moga. I think Moga, as you all know, is a drug that has -- is associated with a significant percentage of Moga associated rash. That often requires the initiation of systemic steroids let alone the challenge of having to figure out whether the patient is having progression of disease as opposed to a Moga-associated rash, which is -- there's a lot of effort in understanding how that -- how those 2 things can be -- distinguished. But -- and then sometimes you have to stop Moga. And then when you restarted the rash recurs. So there are a certain series of practical challenges in managing. Now Moga is a great drug. Just to be very clear, and it was great that it was approved. But again, as Susan mentioned, we need more options. And I think at the end of the day, when the practitioners are going to have to decide is going to be about really kind of long-term safety if the efficacy is more or less equivalent. Another matter, of course, for which I cannot comment at all, obviously, is the cost approval, insurance approval, logistics. In the real world, those things, at the end of the day, matter in our ability as a patient treating cancer doctors to select one treatment or another. So those are the considerations. I'm confident that it has a space in second line. And I think it will be successful in second line. [indiscernible] Sorry, Sonia, you were saying?

[indiscernible]

I thought that the question also had something around partnership or..

The combination. Yes, yes.

[indiscernible]

I forgot that. Well, I mean, I think that combinations, obviously, at this point, are purely kind of hypotheticals. But I guess the one thing you want in any partner for combinatorial therapy is non overlapping toxicity and a good safety profile. So I think that with that, lacutamab to me, sounds like a good partner for any number of potential additional therapies in this space.

And we have no further questions in our queue. So with that, we will -- my apologies. That does conclude today's conference call. Thank you for your participation, and you may now disconnect.

Okay.

Thank you PG and Susan. Much appreciated.