My name is Krista, and I will be your conference operator today. At this time, I would like to welcome everyone to the Innate Pharma Virtual KOL Event. All lines have been placed on mute to prevent any background noise. After the speaker's remarks, there will be a question and answer session. If you would like to ask a question during that time, simply press star followed by the number one on your telephone keypad. If you would like to withdraw that question, again, press star one. If you would like to ask a web question, please type your web question in the question box on the right-hand corner of your screen. 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 and Hematopoietic Stem Cell Transplantation at the Sidney 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 we'll discuss the result of the phase II TELLOMAK study, and then I will wrap up for a summary before initiating the Q&A. Thank you, Matilda. Just to summarize, we have presented the data of lacutamab at ASCO last week, and after the data at ASCO that 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 two 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 SAR579, a first-generation ANKET to phase II in refractory AML. 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 slides, just to remind you, our pipeline of proprietary and partnered asset. 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 3 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 two ANKETs 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 abstracts. Of course, very important, the result in MF for lacutamab that we are discussing in a minute. Two posters for IPH65. One was a trial in progress, and another poster around the preclinical, or the scientific rationale for the second generation ANKET, and two posters around monalizumab. Lacutamab, that specifically kills cells expressing the KIR3DL2, is a tumor-associated antigen expressed at a high level in all Sézary patients, at moderate expression level in 50% of patients with mycosis fungoides, and patients with peripheral T-cell lymphoma.
The TELLOMAK trial is a phase II focused on CTCL, and at ASH 2023, we reported the data in assessable 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 two 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 GEM-OX alone, and results are expected at the end of 2025. Now, for the result 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, not just with you, Sonia, and the Innate team, but also with Susan Thornton, the CEO of the Cutaneous Lymphoma Foundation, and to sort of discuss in the Q&A you know, 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 relapse 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%-60% of all the CTCLs, 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 2B to 4B stage. And the survival, five-year survival for this, for this group is only 15%-25%. So this is an aggressive malignancy, in advanced stage. mogamulizumab was approved in 2018 for adult patients with at least one prior systemic therapy.
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 cohort of 6.7 months. Now, of note, most patients who received moga on this trial relapsed and progressed. And in terms of safety, grade three and four AEs were observed in 41% of the patients, and nearly 20% of the patients discontinued moga for safety reasons. Therefore, this really remains kind of a high medical need population. And if you look at the chart, 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 patient with CTCL. Then there is a whole series of additional types, 30%, which will not be discussed today. Next slide, please. In terms of target, as Sonia mentioned, KIR3DL2 is expressed in more than 90% of the patient 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, and 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 two prior systemic therapies. Next slide, please. Sonia mentioned, you know, 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 1B to 4 mycosis fungoides after at least two prior systemic therapies.
Patients were enrolled based on KIR3DL2 expression, defined as a greater or equal than 1% or less than 1%. This was based on central review by two pathology experts with a consensus scoring decision tree. I will show an example of KIR3DL2 stains in one of the next slides, towards the end. Patients with large cell transformations, 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 five weeks, then every two weeks for 10 doses, and then every four 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 a third had advanced skin stage, so-called stage 2, and the rest had stage 3 and stage 4. Patients were heavily pretreated and with a median of 4 prior lines of systemic therapy.
Now, while prior mogamulizumab was not required for eligibility in cohort 2 and 3, unlike cohort 1, which is the Sézary patients, about a third of the patients with MF here, in fact, did receive a 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 at the... I'm sorry. At the time of data cutoff, which is, as mentioned, October 13, 2023, 100 patients received treatment. The slide focuses on the primary endpoint for the study, which, as I mentioned, is global overall response rate. Now, this requires scoring on all four 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 at the top row there. And the global overall response rate for the two cohorts, greater or more, 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%. 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 Olsen 2022 criteria.
This is something that we did, specifically in the Sézary cohort, and we presented at Lugano, in 2023, and which also, we examined response according to the new Olsen 2022 criteria. And the, 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, you know, may have been palpable or, abnormal, or in any way of concern, but they were not proven to be, pathologically involved and, 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 the neoplastic lymph node activity, were not considered involved. And this is important because, you know, the- according to the Olsen 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 would 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, you know, all the different, you know, the whole cohort and to the two different cohorts will be 22.4%, 29.2%, and 16.9%. Next slide, please.
So this is the waterfall plots for best overall response by mSWAT. So again, I wanna emphasize that, kind of, the best overall response here is the response in the skin, which is measured by mSWAT for each cohort. 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 overall 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 are Cohort 3 patients with less than 1% KIR3DL2. And also here, responses were observed, deep responses.
Eight 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 two prior systemic therapies, and for mogamulizumab was one prior systemic therapy.
Next slide. Thank you. So this slide and the next one just illustrate two clinical cases from patients enrolled on study just to provide the audience with kind of a flavor of what, you know, 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 10%, between 10% and 80%, skin involvement with patch of plaque disease. And that's why there is a substantial amount of skin involvement in this patient.
The patient with B1, which means, you know, 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 compartments, the blood was already a complete response by week 5, as often seen, in a B1 disease with lacutamab. The lymph nodes were not involved. 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, you know, clinical manifestation of the skin lesions here. This is 74- years- old male, initially diagnosed in 2020. Two prior lines of systemic therapy. This patient also had T2, so between 10% and 80% skin involvement with patch and plaque disease, and was also B1 at baseline. And this patient also was N2 by lymph node assessment. In terms of response, PR from week 5, once again, very rapidly. Blood PR starting from week 13. A lymph node, you know, the patient had stable disease with an N2 at baseline.
I'd like to point out that this patient, with the revised Olsen criteria, would have been potentially a partial response because N two would not be considered involvement of the lymph node. 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 and lacutamab-related adverse events observed in at least 5%. I think that the take-home message here is that, you know, based on the already encouraging results from the phase I, TELLOMAK really confirms that the overall safety of lacutamab is excellent in this heavily pretreated population. Once again, with 30% of them having received prior mogamulizumab.
There was no unexpected toxicity. There was no sign of, you know, autoimmune manifestations. And so the safety signal was very strongly confirmed. Next slide, please. This is just a sort of a kind of an additional view at the safety in terms of the most common related adverse events. Once again, some, you know, general toxicities common with any form of immunotherapy, fatigue, nausea, asthenia, arthralgias, some diarrhea, but nothing significant in this cohort, phase II cohort confirmed. Next slide, please. So here, I want to spend a minute just showing the audience here, the stains for KIR3DL2. Once again, the stains were interpreted by two expert pathologists.
And the point of this slide is to show that there is some intrapatient variability observed between biopsies, because if you look at patient A, which is the top two panels, and patient B, which is the bottom two panels, you know, 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 one showed an estimate of 1.3% KIR3DL2 positive in mononucleated cells, and biopsy two showed 60%. So there's significant variability here from site to site. And this patient, of course, was enrolled in cohort two, so they're equal or greater than 1%. Now, patient B had an initial biopsy was scored as 0.8% KIR3DL2 positive.
In a second biopsy, there was scored as 26% KIR3DL2 . And so the patient B ended up as well in cohort 2 with more than, you know, equal or more than 1%. Again, this was based on the consensus review and the discussion between the two pathologists. Next slide, please. So in conclusion, TELLOMAK, a phase II study of lacutamab monotherapy in CTCL. The study enrolled MF patients with at least two 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 delayed 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, 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 to for your attention for this presentation. Sonia, back to you. I'm happy to answer any question the Q&A later on. Thank you.
Thank you, Professor Porcu, for this very comprehensive presentation. 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 had failed at least one systemic therapy, whereas in TELLOMAK, patients failed at least two systemic therapies. This is a big difference in this setting. As you mentioned, also, 34% of patients had received prior moga. That is an equivalent of one third of the ITT population.
Now, when we look at the overall response rate, the efficacy of mogamulizumab, and we can see that it very well compare with what we observe in the TELLOMAK study, as in the MF population, we observed a 21% response. That well 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, well, that is the primary endpoint of the phase III. What we observed in lacutamab is almost double than what observed in the MAVORIC trial in the mycosis fungoides population, 10.2 months versus 5.4.
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 a high unmet medical need. In the next slide, thank you. Now, strong of this, TELLOMAK data, 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 a Sézary syndrome and perhaps maximum of 50% of the mycosis fungoides patients after two previous lines 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 where very low levels of KIR3DL2 were detected.
In terms of business case, we can see this increase from the original 1,500 available patients per year to potentially 3,500. Also, it is not unreasonable to think for a line extension and a move 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 continued to be a very busy year for Innate Pharma. We have seen the results for lacutamab. We will end the phase I of IPH-53, the anti-CD73. We have seen the initiation of IPH-65, 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 three 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.
Thank you. We will now begin the question-and-answer session. If you would like to ask a question, please press star one on your telephone keypad to raise your hand and join the queue. If you would like to withdraw that question, again, press star one. And if you would like to ask a question over the web, please type your question in the question box on the bottom right-hand corner of your screen. Your first question comes from the line of Yigal Nochomovitz with Citigroup. Please go ahead.
Hi, guys. This is Ashiq Mubarack on for Yigal. Thanks for taking my questions, and very much appreciate the detailed schedule of that today. Just one on maybe cross-trial comparisons with MAVORIC . I think you guys showed a lot of data from both yourself and from that study. You know, you made the point about levels of pretreatment being different, but I'm also wondering about what other, you know, 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 3, stage 4 type patients, and we're curious about how that might affect any cross-trial comparisons, especially on PFS. Thanks.
Sonia, do you want me to take that question, or you want to take it?
If you like. Yes, yes, please. I think that your answer will be much appreciated.
Okay. Thank you, Sonia. So I would say this: I think that, you know, when it comes down to sort of the population for a trial in this phase, I think that one of the most important things in addition to stage—I mean, stage is important, is relevant, but I think one of the most important things is the number and type of prior therapies that people received. 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, you know, and that is reached in almost every single patient with mycosis fungoides at some point.
Then, you know, essentially, the clock, so to speak, starts ticking in terms of the progression on therapies. And therefore, when I look at the composition of a patient trial, to me, in terms of the challenge and the value of the therapy that is being delivered, it really is driven primarily by the prior therapy. So in this sense, I would say that the major differentiator between TELLOMAK and moga and MAVORIC , the phase III, is that the lines of therapy were fewer in MAVORIC . And as we mentioned a few times, you know, about a third of the patients in TELLOMAK, of the MF patients, had a prior moga.
So it's really sort of, to me, that's what, you know, what drives the comparison and what drives the value. Obviously, MAVORIC was kind of a larger trial. It was a randomized trial. The other thing is, you know, in terms of the assessment of the patient, say, for example, nodal disease. The assessment of nodal disease in TELLOMAK has been much more rigorous than the assessment of nodal disease in MAVORIC , just because of historical reasons. I mean, we know a whole lot more now about how exactly to approach, you know, the different compartments than we did when MAVORIC was initially designed. I hope this answered your question.
Yep, that's, that's a very helpful color. And maybe, 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? Thank you.
Hi, there. I believe that we've lost Sonia. Sonia, are you back online? Sonia, are you back online now? Yep.
Yeah, apologies for that. Maybe 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-
Hello, Henry?
Oh, hello, Sonia. Go ahead. We just had a question in about the regulatory next steps for lacutamab, if you'd like to answer.
We cannot hear.
Apologies for the technical difficulties, everyone. Yeah, as I was stating, as we stated in the Q1 earnings call, we're approaching the FDA next steps, regulatory next steps for lacutamab. So we'll update you on that one.
Hello, Henry?
Sonia, we can hear you.
Henry? Hello.
Yeah, Sonia, we can hear you. Operator, can we take the next question, please?
Absolutely. Your next question comes from Daina Graybosch with Leerink Partners. Please go ahead.
Hi. I have three questions for Doctor Professor Porcu, and maybe I'll take them one at a time.
Okay.
The first one is, you know, with all these different ways of assessing response, I wonder if you could talk about how you reassess progression, specifically when you decide to switch a patient's treatment.
Mm-hmm.
Secondarily, do you have the duration of treatment, maybe the duration of treatment for these MF patients in TELLOMAK?
I hear two questions. I could be wrong, but I mean, I think your first question is, I mean-
Yes.
How do we assess response with all these different compartments? And, and perhaps kind of a secondary question from that is, so how you know 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 that 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 important point, which is the issue of the measurement, the scoring of disease progression, and how to assess response. The first thing I would say, of course, you know, global response is a complex endpoint. That's part of the challenge of drug development in CTCL, specifically in mycosis fungoides. And that is because you have these multi-compartment sort of assessments, which are required for scoring a global response.
It is sort of, you know, often it is sufficient that one particular compartment does not achieve, you know, 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, you know. So however, having said that, now both in terms, 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 endpoints. As I mentioned before, there has been a learning curve over time.
So that, for example, kind of the so the structure for endpoint assessment in the initial trial, in MAVORIC , for example, was of a certain degree, you know, good, but perhaps not perfect. And now, moving forward, TELLOMAK has a much more rigorous approach. I think this is my opinion, and, you know, it is, I think it's the opinion of all the investigators. So, you know, first of all, the skin, it's important to note that the skin drives response, global response. And this is true, by the way, it's true also, regardless of whether you're dealing with Olsen 2011 or Olsen 2022, the skin continues to drive global response. Radiographic progression is a really touchy sort of point, because it...
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 leave, you know, the definition of progression to, say, the treating investigator or, you know, well, let's say the treating investigator, the decision of switching to a different type of therapy can is really kind of multifactorial, and it is influenced to a very significant degree from 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, you know, progression really had to be centrally reviewed and approved, to jump on the other cohort, I think that there are still some questions, you know, you know, how really sort of stringent some of those were. So it is a big deal when you have progression-free survival as your primary endpoint. So that kind of addresses the, I think, the progression question. And regarding the duration of treatment, most trials, including TELLOMAK, really have continuous treatment until disease progression or, you know, safety issue or toxicity. And that is why, you know, 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, you know, the drug is well-tolerated or the investigator feels the drug is well-tolerated. I think you said you have a follow-up on these two things.
Oh, I have a different follow-up, and I have a follow-up on your answer. So I guess when we compare cross 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 of treatment was for MF in this study?
A different duration of treatment between TELLOMAK. To be honest, I don't think I have that information. So on average... perhaps Sonia may have this. On average, how long, you know, how long people stayed on treatment, you know, between TELLOMAK and MAVORIC ? I apologize, but I don't think I have that. I don't want to misquote anything. Regarding the progression, I mean, I think that, you know, progression is defined. I don't want to give the impression that progression is vague, is vague. Progression is defined by the response criteria. And therefore, you know, as long... You know, I think that if, if, you know, if you have experienced investigators, you have to sort of take the the scoring of progression, you know, for what it is, according to the criteria.
It has to be, obviously, you know, all the data have to be reviewed, just like in TELLOMAK. In MAVORIC , the progression was required to move to the investigational arm. In TELLOMAK, it's just a secondary, by the way, a secondary endpoint. The primary endpoint is a global responder. I don't know, Sonia, you want to add anything to that in terms of the primary endpoint for TELLOMAK versus MAVORIC ? That-
So what 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 the PFS as a primary endpoint. But as you mentioned, PG, the, let's say it was essential in MAVORIC to have the central review because, you know, it is clear that patient would not like to have the vorinostat and would like to cross over as quickly as possible to the investigational arm, which was the mogamulizumab. Here we have a single arm study, and therefore, there is no incentive, so to speak-
Yeah.
for patient to abandon the study. You know, 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.
Thank you.
And then, one more question, one more question from me. I wonder, let's say lacutamab is approved with 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? Thank you.
This is a very interesting question that would require a crystal ball. I'm afraid, you know, 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, then.
Yeah, I mean, I think that... So I agree with Sonia. You know, and I think that, I guess what she's referring to specifically, is kind of a formal, official guidelines, right? You know, so, say, for example, the NCCN guidelines, which, you know, most people follow, certainly here in the U.S., but also abroad. And, you know, and I'm not part of the committee in the NCCN, so I'm not speaking officially on anybody's behalf, this is just as a practitioner. So, I mean, I think that the just like Sonia mentioned, the NCCN guidelines will have to examine the specific sort of, you know, approval of the drug.
As you know, typically the NCCN, you know, 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 gonna be discussed. Practically speaking, which I think is what you're referring to, I mean, I think that having another, you know, an active drug, you know, a quite active drug in Sézary, I mean, there's a huge unmet need in Sézary patients.
And so I think that there would be broad, a very rapid adoption of the drug, particularly when you look, you know, at the safety of the drug, which is, again, this is. There's no phase III comparison at this point, you know, 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, you know, that's what is gonna drive the adoption of lacutamab, not just in Sézary, but also in MF, particularly because it is effective.
And it is effective, you know, regardless of whether you have more than 1% or less than 1% KIR3DL2 expression. So I see this as, you know, I see the adoption of lacutamab as a kind of a very, you know, kind of easy path, so to speak, once the drug is approved. Susan, I don't know if you wanna say anything as a patient, you know, about that. I think it would be good to hear your thoughts.
Sure. Oh, there we go. Great. Thanks. Yeah, you know, as I'm listening and I'm thinking, sitting in my shoes, as a patient, who didn't have a lot of options as an MF patient back in the mid-nineties, 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, you know, 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.
Having another option, most of these folks, as you've mentioned, have gone through probably every therapy we have available and combinations and over the course of many years. 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 in public because of the way their disease looks, is, I think, you know, it kinda goes beyond the pictures, and the data don't show the day-to-day lived experience, particularly of this patient population, where you know, the psychosocial, the physical impacts are huge. That's my two cents for what it's worth.
Thank you.
Your next question comes from Liisa Bayko with Evercore ISI. Please go ahead.
Hi, this is streaming in for Liisa. Thanks for taking our questions. I have a follow-up to one of the prior questions for Dr. Porcu. Is there any correlation of clinical stage and the treatment effect, PFS in particular? And I have another question for the management. How much confidence do you have that lacutamab will be competitive in the second-line setting for Sézary syndrome? And do you require a partner to bring lacutamab forward? Thank you.
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, you know, it's, I think it has more to do with the prior therapies. Now, granted, I think that for patients with very advanced CTCL, say, a patient with stage 4, you know, A or B, you know, it, it's with very bulky disease or very heavy peripheral blood involvement, and those patients are very high risk, and I think there may be. But this is not, you know, 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 other patients, you know, the difference between, you know, 1 B, for example, and 2 B or 3. In my experience and in my recollection of the data overall, I don't think there is a strong correlation. And then regarding the, I wanna make sure. What, again, is the question about how confident I am in lacutamab being second line?
Yes, that there-
Can you rephrase that question a little bit? Yeah.
Yeah, I'm just curious, like, for you know, Dr. Porcu or for the company, so how much confidence do you have that lacutamab will be, you know, competitive in the second-line setting for Sézary syndrome? Because we know for the, you know, Sézary syndrome cohort, all patients actually had to have, you know, moga as a prior line of treatment.
Yeah.
Thanks.
Maybe I'm gonna let Sonia take that first, and then I give you my physician's perspective on that.
Right. Yes. Of course, you know, 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 patient 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, you know, we can really explore the possibility or open the possibility that this drug can have a successful future also in a second-line setting.
You know, 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, you know, this is something completely new, and I would like to have PG's perspective from, the investigator point of view.
Mm-hmm. I mean, I think that what really kinda drives the adoption of therapy in the real world is driven by two things, obviously. You know, one is a general sense of a knowledge of the efficacy, particularly for, you know, a disease like Sézary syndrome, which is aggressive, and therefore efficacy is really kind of a very important component. And the second is safety, you know, especially long-term safety. And that's where I think, based on all the information that we have so far, you know, there is the signal here is that the safety of lacutamab I would say has an edge compared to moga.
Think about, you know, moga, as you all know, is, is a drug that has, is associated with a significant percentage of moga-associated rash, that often requires, you know, 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 there's a lot of effort in understanding how that, you know, how those two things can be distinguished. But, you know, and then sometimes you have to stop moga, and then when you restart it, you know, the rash recurs. So there are a certain, you know, 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 you know, the practitioners are gonna have to decide, is gonna be you know, about really kind of long-term safety if the efficacy is more or less equivalent. Another matter, of course, which, for which I cannot comment at all, obviously, is you know, is the cost, approval, in you know, insurance approval, logistics. You know, all you know, in the real world, those things, at the end of the day, matter you know, in our ability as you know, patient treating cancer doctors to select one treatment or another. So those are the considerations.
I'm confident that, you know, it has a space in second line, and you know, I think it will be successful in second line.
Great.
So also ask about the next-
Sorry, Sonia, you were saying?
I thought that the question also had something around partnership or-
Oh, the combinations.
Yeah, yeah.
So-
Partnership.
Yeah, I forgot about that.
Well, I mean, I think that combinations, you know, obviously, you know, at this point are purely kind of hypotheticals, but, I guess, you know, the one thing you want in any partner for, you know, combinatorial therapy is, you know, 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, you know, additional therapies in this space.
Got it. Got it. Okay, thanks.
Thank you.
We have no further questions in our queue. So with that, we will... Oh, 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.