Good morning to everybody here in New York, and good morning to our participants online, and good afternoon to everybody in Europe. We're very excited to be here this morning. We have, from an Innate Pharma perspective, our lacutamab KOL event, where we'll be reviewing the clinical perspectives and the commercial outlook for lacutamab. I'm very excited that we have over 100 people joining us this morning online and here in the room in New York City. We will be making some forward-looking statements. We have our standard disclosure statement here. What we're going to be looking to cover as we go through the next couple of hours. I'll start off with an introduction and a few background details.
Then we'll get into the real nitty-gritty and get into the medical perspective, where we have Pierluigi Porcu and Sonia Quarantino, our CMO, who will be taking us through that, looking at the landscape and the perspectives for lacutamab, and then how we're going to be taking forward lacutamab through the next steps. Then we'll get into the commercial perspective, and Stéphanie Cornen from Innate and Chris Stuessy-Vidas from ZS Associates will take us through the commercial opportunity. And we have some exciting, from our perspective, exciting new claims data on the market, which make it significantly more interesting than it was in the past. And then we'll have some closing remarks from myself again, and then we'll go into a Q&A session, and hopefully we can answer all of your questions. So, just a little bit of background on Innate Pharma for those who maybe don't know us.
So, we're a company that's been around for around 26 years. We have, I would say, a world-class expertise in monoclonal antibody engineering. And as a result of those capabilities, we've developed a clinical pipeline of products that address high unmet medical need. And that's a series of products that are first and best in class. And then, I think coming closer towards commercialization, we have a couple of assets that are really near-term with a clear path to market, to commercialization, and to generating revenue. So, more recently, we had a refresh of the strategy for the company, which we put out with our half-year results in September this year. And what we decided is really to focus our time and our attention on three of our assets that we believe have the best chance of being successful.
Those three assets are IPH4502, it's lacutamab, and it's monalizumab. We also have focused our R&D activities on generating our next ADCs and putting our R&D efforts behind that. At the same time, we decided to streamline our organization and really make it fit for purpose versus the strategy that we have just announced. As part of that, we have a plan to reduce our organization by 30%. That is the strategic update. Going into a few more details on those three priority assets. Starting off with lacutamab. lacutamab is our anti-KIR3DL2 antibody, which is targeting cutaneous T-cell lymphoma. This is a first-in-class antibody. It has a Breakthrough Therapy Designation from FDA. That is based on the TELLOMAK Phase II data, which is completed. The TELLOMAK was conducted in mycosis fungoides and in Sézary syndrome.
In Sézary syndrome, we have basically an accelerated path to approval agreed with FDA. To take advantage of that accelerated path to approval, we need to initiate a confirmatory Phase III study. We believe that this product really has the potential to change or to transform the treatment of CTCL patients by treating them earlier in their disease so that we can hopefully prevent them from progressing and impact their survival. That's what we will be hoping to be able to do and to demonstrate that in the Phase III study. That's lacutamab. We then also have monalizumab. This is in collaboration with AstraZeneca. We have a partnership. This is well advanced. We're in a large randomized Phase III study, the PACIFIC-9, which has completed enrollment. We passed a futility analysis.
We expect the primary completion date of the PACIFIC-9 study to be June next year, and we expect to have data in the second half of 2026. Obviously, that's really important from an Innate Pharma perspective. If we have a positive study, we have milestones of up to $825 million due to the company as a mixture of development, regulatory, and commercial milestones. We also have a 50% profit share for Europe and double-digit royalties on sales outside of Europe, so including the U.S., that's monalizumab, and then finally, we have IPH4502, which is our Nectin-4 targeted ADC. This is a product that we're very excited about. We basically have a novel antibody. It hits a novel epitope from a binding site perspective.
And what this means is that it can basically bind not only high-expressing Nectin-4 tumors, but also the low- and moderate Nectin-4-expressing tumors. And we have a different payload with the product. So, we have an Exatecan payload rather than MMAE. And what we have as a consequence of that is an opportunity in the post-Padcev setting and also in solid tumors that express low and moderate levels of Nectin-4. We have a Phase I study ongoing. And that study is moving very quickly. We expect to have data, early data, efficacy and safety data towards the end of this year or early next year. And what I can say is that we're now at the pharmacologically active dose, and we have already demonstrated clinical activity.
We're not going to share the details of that, but that will be something that we will share in the longer term. So, moving back to lacutamab and the potential path forward for lacutamab. It starts in Sézary syndrome. And this is where we have the BTD from FDA. To take advantage of that BTD, we need to have the Phase III confirmatory study up and running. We expect then to be able to submit the BLA based on the existing TELLOMAK data that we have in our hands today in Sézary syndrome. That's in patients post-mogamulizumab. And we expect that accelerated approval to come to fruition with an approval in 2027. The confirmatory study validates the Sézary syndrome indication, but it also will give us the Phase III randomized data for the mycosis fungoides indication.
With that confirmatory study, we expect to be able to have the full approval for MF and then the full approval for Sézary's in 2029. We have a lifecycle management opportunity in peripheral T-cell lymphoma. We have single-agent activity in peripheral T-cell lymphoma with lacutamab. We are currently conducting an investigator-initiated study with the LYSARC group in France. This is in later-stage peripheral T-cell lymphoma patients, and it's in combination with GemOx chemotherapy. We're excited, quite excited about the potential next step. The data from that study should be available mid-next year and released sometime in the second half of next year. We're already working on a plan to then go into the first-line setting for peripheral T-cell lymphoma in combination with CHOP chemotherapy. It'll be a little bit L-CHOP regimen, a little bit like the R-CHOP regimen that was developed in aggressive non-Hodgkin's lymphoma.
Actually, by the LYSARC's, they actually conducted the registration study that led to the approval of Rituximab in aggressive non-Hodgkin's lymphoma. So, that's the potential lifecycle of lacutamab. So, if we sum that up where we are today, we have strong data already from the TELLOMAK study. This is allowing us to take the next steps. We're building regulatory momentum. We have submitted a final protocol to FDA for that confirmatory study. We expect to be able to initiate it sometime during the first half of 2026. And I think probably what is the most exciting development in the last couple of months is our better understanding of the U.S. market based on claims data, which we'll hear about later today, which makes it a significantly greater commercial opportunity than we had previously thought. So, that concludes my introduction.
What I'd like to do now is to hand over to Sonia, who's going to lead us through the medical part and introduce our KOL, Pierluigi Porcu.
Thank you very much, Jonathan. And before we start with the medical part, it's my great pleasure to introduce our guest today. That is Professor Pierluigi Porcu, the Division Chief of hH ematology and Bone Marrow Transplantation at the University of Kentucky, who will give us a good overview of the CTCL space, as well as will discuss the data of lacutamab. Pierluigi Porcu is a very well-known world leader in CTCL, and it's a great pleasure that he's willing to be with us today.
Thank you, Sonia.
All right. Okay, good morning, everyone, and both here as well as online, and as Sonia mentioned, I am a Medical oncologist, and I've been treating cutaneous T-cell lymphomas for more than 30 years now, so I have kind of a long view on the natural history of this disease as well as the development of new therapies for it. I was at Ohio State for many years. I moved to Thomas Jefferson University in Philadelphia for about nine years, and I very recently moved to the University of Kentucky in Lexington, and one of my goals today is to offer you kind of an outline of the unmet needs as well as the opportunity that we have in CTCL in terms of the open space and what the clinical needs are.
I will do that, I hope, by offering you kind of a view of the longitudinal natural history of this disease. So, first, just a few words about T-cell lymphomas in general. This is a space that I know very well, not just in terms of CTCL, but also in terms of PTCL. And these are kind of a relative frequency of both PTCL and CTCL across essentially worldwide, the U.S., Europe, and Asia. As you can see there, the majority of the case of T-cell lymphomas are peripheral T-cell lymphoma. These are nodal and extracorporeal disease, not just limited to the skin. And about 30%, 29%-30% of the other T-cell lymphomas are cutaneous T-cell lymphomas. Now, when you look at this is sort of the breakdown.
If you look at the number of patients and the overall prevalence of these diseases, CTCL actually makes a significant majority of those because patients with CTCL actually live much longer than patients with peripheral T-cell lymphomas. And when you look at the breakdown of the CTCL, as you can see, mycosis fungoides makes about two-thirds of the cases of CTCL. Sézary syndrome is a small minority, about 5%. And the rest is kind of a hodgepodge of cutaneous T-cell lymphomas, primarily CD3 expressing anaplastic lymphoma and related diseases. Now, when we look at the outcomes and the kind of the framework for Sézary mycosis fungoides and PTCL, again, 2%-5% of the CTCL patients are Sézary. Sézary really kind of is an advanced stage form of CTCL where it's heavy blood involvement. It's relatively rare, as the numbers show, but it's very aggressive. And the prognosis is poor.
On average, one out of 10 patients actually makes it alive at 10 years, at five years. Mycosis fungoides is, again, a much more common subtype. It is more indolent, particularly initially. It presents in the skin. However, as I'm going to show, it transitions very, very often over time to kind of more advanced stage. At that point, it really becomes a poor prognosis as well. For the peripheral T-cell lymphomas, we're not going to spend much time at all here discussing it, but briefly, these are kind of very aggressive diseases. I think the important thing about lacutamab is that there is a significant fraction of those diseases that express KIR3DL2. They do have a poor prognosis, big unmet need there, as Jonathan was mentioning, kind of perhaps down the road would be good to see the opportunity for lacutamab in PTCL.
Now, what this slide shows is a snapshot essentially of the distribution of stages across a fairly large series of patients with CTCL that were sort of published from a cooperative group, a network in the U.K., and I'm going to walk you through this slide because I want to make sure the numbers, there's no confusion about the numbers, what the circles show is the size of the population according to each particular stage. Is that a pointer here? Yeah, there we go, so the stages are down here, and this is a relative size of each population, so for example, about 30% here is stage 1A, almost 40% stage 1B, and so on, and here on the Y-axis is the five-year survival, and as you can show, stage 1A to 2A, these are early-stage patients, and these are advanced-stage patients.
And the survival, as you can see here, there's a clear transition in demarcation of survival with the early stages, sorry, the early stages having significantly better survival at five years, and the more advanced stages having a very significantly inferior survival at five years. Now, so putting some sort of visualize what happens to patients with CTCL, even at relatively early stage, I think is really important for this audience to really kind of grasp and understand. And so, as I mentioned, and this is based on other series that show fairly consistent distribution of stage. About 30% of the patients are diagnosed with the earliest possible stage of CTCL. This is the patient shown right here in the top panel. So, these patients have less than 10% typically of the body surface area involved with CTCL, mostly in the form of what we call patch and plaque disease.
This is superficial disease. About 40% of the patients are diagnosed at stage 1B. Now, they may actually potentially start at stage 1A. We just don't know. They present to the physicians and they present to the medical centers in stage 1B. They have more than 10% body surface area as well with flat patch and plaque disease. The disease remains indolent, but at this point, it really starts to be progressive. I'm going to show a visual of that in the next couple of slides. As you can see, just from the cosmetic standpoint, these patients may itch, so they may have symptoms. But also from the cosmetic standpoint, there's a significant involvement of the skin.
If you sort of have to go to work and the disease affects your face or exposed areas of the body, then it really presents a significant impairment in terms of your ability to socialize and to work, let alone the symptoms of itching and burning of the skin that patients have, and again, these are patients that have early-stage disease, so if you typically look at some of the descriptions of CTCL in the literature or in some kind of lay media, you will see that early stages consider really sort of almost a benign disease or is considered something that perhaps does not represent a significant unmet need. In reality, there is a significant unmet need even in the patient with early stage, who, by the way, they make the majority of the patients diagnosed with CTCL.
Once the disease progresses to more advanced stage, and typically there's a transition from 1A to 1B and then to higher stages, at this point, this is what happens to the patient. This is kind of an ulcerated tumor. There are patients who have tumors like this and ulcerations like this to more than 50%-60% of the body surface. This becomes a devastating disease, not just from the standpoint from the cosmetic and symptomatic standpoint, but also in terms of survival, and if you look at, for example, the mutation burden, the biology of the tumor cells in patients with this stage of disease really has no particular difference compared to, say, peripheral T-cell lymphoma. The mutations are similar, in fact, and the survival is significantly impaired, and so, I want you to remember how you can actually go from stage 1A to stage 2B or higher.
This happens in a very significant fraction of the patients. This is actually more of a visual cartoon of how that transition occurs. This is based on a very large study that was published in Italy. And then there are actually survival and transition data that also have been confirmed in several other datasets. But this is one particular example, and it's particularly well spelled in terms of the transition to stage. First, right here on the left, as we mentioned, about 30% of the patients present with stage 1A. This is skin-only disease, less than 10% of the body surface area. And this group of investigators followed these patients for 35 years. Okay? And so, if you look at the transition here, you will see that even in the earliest stage, about 25% of the patients move on during their lifespan to a greater stage.
If you break it down according to which stage, 7% of the patients move on from stage 1A to 1B and sort of stay there as far as this particular dataset is concerned. But then 10% and 8% of the patients not only advance to stage 1B, to sort of greater involvement of the skin, but they go on to have tumor lesions, and some of them actually go on to develop blood, lymph node, and visceral involvement. So, altogether, 25%. You have to understand that once you get to this point, these are patients whose survival is impacted. These are patients who will need systemic therapy, and they will need it for most of their lives. Here's another example. If you just focus on now the patients who present with 1B. Again, this makes about 40% of all cases.
And then here you have about 30% of the patients who move on from stage 1B to 2B, so tumor stages, or to kind of systemic disseminated disease. And then, of course, you have the patients who do present with tumor stage at the beginning, and about half of these patients progress to blood, lymph node, and visceral. Once you arrive to this, the disease-related mortality for these patients is very high. I mean, we're talking about 80%. Okay? And even the disease-specific survival for patients with the so-called earlier stages, 1B or tumor stage, is significantly impacted. This is shown here. This is a different dataset from the one shown in the previous slide. And I'm just focusing here on kind of the early stage or the tumor stage. So, I'm not focusing on kind of the visceral blood involvement, the highest stages.
This is the disease progression according to clinical stage. I'm going to ask you to just stay focused here. This is just a different way of displaying the stage. Right here on the left, this is the most common way of displaying stage. This is progression, so risk of progression, of course, over a significant period of time, at 30 years. You can see that even if you're diagnosed with the 1A disease, and if you go to the doctor and you have MF and you say that you have 1A disease, most of the doctors are going to tell you that, "Don't worry about it. You're going to be just fine.
You're going to die of something else," and that is true for many of these patients, but it is not true for a significant fraction of these patients, as we will show you in the next slide, so once you get to 1B, and again, 1A is the same kind of skin lesions, except to a greater extent, and the difference in extent is 1A is less than 10%. 1B is more than 10%, more equal than 10%. It doesn't take much to actually be in stage 1B. Of course, then you have stage 2B, so the progression here over a long period of time for patients present with 1A is about 18%, 17%-18%. For patients with 1B, it's 40%, and these are the independent data compared to the slide I showed before. Once you get to 2B, the progression rate is very, very high.
Why is this important to know the progression rate? It's important because progression affects survival. And again, if you look at survival here over time, the IA is pretty good. Nobody has really ever done a formal study looking at the overall survival of the patient with IA compared to, say, age- and gender-matched populations over a period of 30 years. Obviously, you would expect that the curve will go down as people age. But based on the experience that investigators have, there is a feeling that actually having IA does impact survival, particularly over a long period of time in the population of patients who progress. Now, once you start getting to IB, again, this is still considered early stage. It's only 10% or more of body surface involvement. But then the survival really at 10 years is significantly impacted.
And then the survival at 10 years for 2B is really poor. And this is not even counting Sézary. It's not even counting stage 4. These are sort of the transition from the earliest possible stage to more extensive involvement in the skin to a less favorable early stage and then to 2B. So, what is the landscape as far as treatment that physicians deal with and patients deal with? Now, historically, the conventional wisdom has always been that patients with early stage really only need skin-directed therapy or topical therapy. I think that now we know that that is not true based on a lot of these large datasets.
And this is also recognized by the NCCN, as shown in one of the next slides, that essentially supports the introduction of systemic therapy for patients pretty much at all stages, with just a difference in terms of the type of systemic therapies that are being recommended, as I will show. Now, patients with CTCL, NMF, whether they are early stage or advanced stage, they all will need skin-directed topical therapy throughout their lifespan. So, even when they're getting systemic therapy, they will continue to need skin-directed topical therapy for symptom control primarily. And this is true throughout their lifespan. Now, there are a significant number of challenges and unmet needs in therapy, particularly for systemic therapy. First, we know that there are really no durable responses. Even with the more recently approved therapeutics, we don't really see durable responses.
The idea of sort of going through a set of therapeutic interventions, just like for aggressive lymphomas, for example, you do chemotherapy for six months and then stop. This paradigm does not work for patients with CTCL. These patients need to have continuous therapy, very few treatment-free intervals, and most of the time, the intervals are really due to interruption because of toxicity or because of symptoms management, not necessarily because there is no need to control the disease. Another big issue is that there are very few complete responses. This means that patients will have persistent symptoms throughout the therapy. They will have a poor quality of life, and then primarily, kind of we are unable to prevent disease progression because without having really kind of deep, complete responses, there's no way to prevent disease progression, and then the third is that there are few effective and well-tolerated therapies.
Therapies that actually not only are effective in terms of anti-tumor control, but also are well-tolerated, they can be extended so that this paradigm of continuous therapy is feasible. For these patients, obviously, this leads to frequent treatment interruptions, changes of therapy, a lot of conversations about patients sort of needing therapy, but they don't want to do it because they have side effects. This is a big, big challenge here. Now, the landscape of systemic therapies available or recommended according to guidelines across the stages is shown here. This is fundamentally the NCCN guidelines. I guess the take-home message here is the fact that, as I mentioned, systemic therapy is recognized as an important intervention across all the different stages.
In terms of what the NCCN is recommending for systemic therapy, if you look at the guidelines, in earlier stages, very often, these are the drugs that are recommended to start, primarily because we have a lot of longitudinal safety data on these drugs. And so, based on that, striking the balance between therapy and efficacy and safety, these drugs are well-known. Now, when we start moving to more advanced stages or second line, perhaps after this, then you have rituximab, you have moga, you have romidepsin, and vorinostat. Each one of these drugs, though, has significant drawbacks and concerns. Rituximab, for example, is clearly kind of a lifetime dose-limiting sensory neuropathy beyond which you just cannot go.
And we see patients who are desperate to actually have disease control that would like to continue with Rituximab, but they push the neuropathy to the limit, but it really becomes debilitating in these patients. At some point, you have to stop. moga, another drug that was introduced more recently, it's a good drug. It was an excellent introduction to the therapeutic landscape. However, now we know that there are significant frequency of autoimmune phenomena and a fairly severe moga-associated rash as well. romidepsin is infusional, long infusion, weekly, has severe fatigue and GI toxicity. It's not an easy drug to take for a very long time. And then Vorinostat, the primary issue with Vorinostat is just very limited efficacy. Now, Denileukin diftitox, it's a drug that was recently reapproved. And it's an effective drug, but it has vascular leak syndrome concerns, eye toxicity, and infusion reactions.
And then gemcitabine, liposomal doxorubicin, and pralatrexate. These are chemotherapeutic agents, classical cytotoxic chemotherapy that we try to avoid, if at all possible, in patients with CTCL. I think that the take-home message here is that if you look at novel targets for therapy, there really haven't been any novel targets of therapy since the development of these drugs, of rituximab and moga here, which is now approaching 10 years. And so, in terms of the regulatory development and the approval for these drugs, again, we go back to the early days, essentially, with denileukin diftitox, romidepsin, vorinostat. And all these drugs were approved based only on skin responses. Now, rituximab and moga were approved in 2017, 2018, based on more complex response criteria called the Olsen 2011. And these response criteria require independent analysis of compartment-based response.
You have to have a response in the skin, in the lymph node, and in the blood. I'm going to show this slide next. And so, again, I want to emphasize that denileukin diftitox, the target is CD25. The target had been studied and discovered all the way here. It's not a new target. And since Rituximab and moga, there have been really kind of no new target development for therapeutics in CTCL. This is kind of a snapshot here of the different compartments of response that are essential to assess global responses. When we are talking about complete responses, when we're talking about partial responses, we have to have responses across all these different compartments. The skin is the dominant compartment, of course, both in terms of symptoms as well as evaluation.
But you have to have a PR, for example. You have to have responses in at least a PR in blood, visceral, and lymph nodes as well. And you may have also very good responses in these compartments, but if you don't have at least a PR in the skin, you cannot call it a complete response. So, in terms of unmet need, to kind of summarize here, specificity, we want a target that is specific for the malignant cells, but not the healthy cells. And certainly, KIR3DL2 is a good target for that. We need to have kind of profound responses for the best clinical benefit. We want to have long duration of responses, improving PFS and overall survival. The drug has to be tolerable, well-safe, and improve the patient quality of life.
This leads me to kind of the data from TELLOMAK, which Jonathan has mentioned briefly in his introduction. I'm not going to repeat about the target of lacutamab. It's kind of a monoclonal antibody targeting KIR3DL2, which is expressed on a significant majority of the patients with CTCL, particularly all the patients, almost all the patients with Sézary syndrome, about half of the patients with MF, and a significant fraction of the PTCL as well. TELLOMAK was a Phase II enrollment completed at this point. The eligibility criteria were relapsed/refractory Sézary syndrome requiring B2, so full blood involvement, or MF with at least two prior systemic therapies. The patient with Sézary syndrome had to have prior mogamulizumab. So, all of them to be enrolled, they had to have mogamulizumab. There were several different cohorts. One particular sort of important cohort with Sézary syndrome, 63 patients enrolled.
To the best of my knowledge, this is the largest cohort of patients with Sézary syndrome ever accrued on a clinical trial, and then there were several cohorts for MF. The study endpoints. Global overall response rate, again, importantly looking at all the different compartments, according to Olsen 2011. A number of secondary endpoints. The treatment, lacutamab, is given intravenously once a week for five weeks, then every two weeks for 10, and then every month until disease progression or toxicity. These are the data in Sézary syndrome. Post-moga, again, all these patients had moga, and I would say that in Sézary syndrome, certainly lacutamab is a game changer, for sure. You look at the very fast median time to global response of 2.8 months, excellent progression-free survival of 8.3 months, and median duration of response, long median duration of response.
You look at the depth of the responses here in the waterfall plot. So, fantastic results for Sézary syndrome here with lacutamab. Importantly, there's also a significant impact on quality of life, as shown here, both in terms of itch, right here on the left by visual analog scale, as well as in the multi-domain Skindex-29 quality of life score. Again, important here to see that the improvement is fast at early weeks. It also happens in patients who do not necessarily fit the response criteria for PR or CR. Even patients with stable disease actually have an important improvement in quality of life. In terms of mycosis fungoides, here shows on the right and on the left and on the right, the two different subgroups of patients according to KIR3DL2 expression, more than 1% or less than 1%.
I think the take-home message here is there's no significant difference in terms of the overall responses in these 107 patients according to KIR3DL2. And when we look at the global benefit ratio here, 86%, including the stable diseases, we have a 29% response in terms of skin responses. The global overall response, again, accounting for all the different compartments, is about 20%. Faster responses as well here, 2.8 months, which is important in mycosis fungoides as well, because the symptoms from itching and burning of the skin are very debilitating. And the median duration of response is robust, with almost 14 months of median duration of response here, which is better than the median duration of response with mogamulizumab in MAVORIC, significantly better.
And so, same for the quality of life in terms of the endpoint and long-term progression-free survival here on the left, looking at 12 months and at 24 months, very similar according to KIR3DL2 expression. And in terms of the pruritus measurement by visual analog scale, very rapid responses as well here, not just for the complete response or partial response, which happens quickly, but if you wait long enough, even in the patient with stable disease, you see that eventually quality of life improves. This is just an example of a patient with MF on trial, multiple prior lines of therapy. This is a stage at baseline. And essentially, starting looking at week 57, the skin had a kind of a partial response. It already happened at week five and then achieved a complete response at week 37.
In terms of the blood compartment, as shown by subsetting the cohort for Sézary syndrome, very fast responses. Clearance already at week 5. The lymph node, in this case, this patient did not have lymph node involvement. The global response here, PR at week 5, CR at week 37. This patient was still ongoing as of January of this year in global complete response. Now, what about safety? That's why I think one of the, in addition to the efficacy, the impact on the quality of life, I think that the safety of lacutamab is particularly remarkable. If you look, on the left is the safety profile in Sézary syndrome. On the right, the safety profile in MF. MF is broken down again by KIR3DL2 expression.
But overall, I think that the take-home message here is that the serious treatment emergent adverse events, relatively low percentage, particularly treatment emergent adverse events that led to treatment discontinuation. As I mentioned, treatment discontinuation is one of the key challenges in therapy for CTCL over time with any agent. And so, here is very low, the treatment discontinuation, both in Sézary syndrome as well as in MF. Here are the data for MF. These are the serious treatment emergent adverse events, particularly grade 3 or related grade 3, very small percentage. And then discontinuation only in a small number of patients. So, not just based on the data, but also based on experience in treating patients with lacutamab. lacutamab is a drug that can be used for very prolonged periods of time in patients with both Sézary syndrome and MF. So, where is then the opportunity here?
We feel that lacutamab really kind of has the opportunity to impact disease, both in terms of the advanced stage patients. If you think about Sézary syndrome, clearly a very important impact there. But even more so, I believe that where the opportunity really is in the 70% of the patients who present with stage 1A or 1B, we know that they will progress over time. We know that they will need systemic therapy. And as of now, there's no systemic therapy that really has been able to show control and prevention of the stage transition from early stage to advanced stage. So, I believe that that's where the major opportunity is, being a safe drug and effective, I think, introducing it early on. That's sort of where I see it applied in practice. Thank you very much for your attention. We can have questions later, right?
Okay. Okay. Great. Thank you.
Thank you, PG, for this excellent overview. We couldn't have a better person to really outline the CTCL space and the need that we need in CTCL. Now, we've seen this slide before in terms of what is the quest in CTCL. And I would say that lacutamab, from what we've heard from Professor Porcu, can really tick the many boxes that are needed. Meaning, lacutamab is a first-in-class antibody against KIR3DL2, which is a tumor-associated antigen that is not expressed on healthy cells, with the exception of a small fraction of NK cells. But that means that there is no collateral damage. And this is an aspect that is very much reflected in the good tolerability of this drug and the favorable safety profile.
We've seen that there is no difference for patients that express KIR3DL2 or, let's say, higher level of KIR3DL2 or lower level of KIR3DL2, because this is a very powerful drug. And most of the time, we are even below in our detection to the sensitivity of the target. Now, in terms of efficacy, we've seen durable responses in all compartments: skin, lymph nodes, blood, and a long PFS, both in Sézary syndrome, post-mogamulizumab. And I want to stress the fact that there are really no approved drugs, with the exception of romidepsin and Vorinostat, with the limited clinical efficacy that they had, that are approved post-mogamulizumab. And we really have this long progression-free survival in both MF and Sézary. Now, where are we in terms of regulatory path with this drug?
At Innate Pharma, we have worked with lacutamab, and we have completed Phase I and Phase II. And during the course of these studies, we secured some of the regulatory designations that are related to the indication, to the orphan disease indication. And that really brings some advantages in terms of market exclusivity. We also had the fast track. But I want to stress that the most important designations that we have obtained are the one based on review of the early data. And these are the data that Professor Porcu has shown in SS, in particular. And we had the PRIME designation given from the EU. And only 26% of the applications actually received this designation. It's very hard to receive designation. And more recently, we also received the Breakthrough Therapy Designation from the FDA.
This is a program that the FDA established to accelerate the development and the review of a program for which there are no or very limited therapeutic options. This is only for very serious conditions. For this reason, we have obtained the BTD for Sézary syndrome post-mogamulizumab. I also want to stress, as Jonathan mentioned in his introduction, through different interactions with the FDA, a Type C meeting, an end-of-Phase II meeting, and then the breakthrough therapy designation, we have, let's say, the endorsement of the FDA that we can really that the data that we obtain from the TELLOMAK study are good enough for an accelerated approval. This is what we are working on. In perspective, we have completed a phase I trial in Sézary syndrome. The Phase II TELLOMAK has been completed with, in total, 170 patients.
Now we are progressing towards the preparation of the Phase III trial. As Jonathan mentioned, the protocol has already been submitted to the FDA. Over the years, we have really gained a lot of experience in understanding the disease, in understanding what are the potential issues and limitations of a clinical trial in CTCL. We have established a long-term collaboration with all the sites in Europe, in the U.S. We have key opinion leaders like Professor Porcu helping us in the development. We are really, at Innate, we have a first-class team of clinicians, clinical operations, statisticians, clinops that can really make this Phase III happening at fast pace. This is why we are really now so keen to move forward with this Phase III. Now, what is the design that we have submitted to the FDA?
Now, this is an open-label, multicenter, randomized comparative Phase III study of lacutamab in patients with cutaneous T-cell lymphoma that have received at least one prior systemic therapy, and the study, upon request of the FDA, has two different cohorts with different statistical analytical plans, one for Sézary syndrome and the other for MF, and that basically means that patients with Sézary syndrome that have received at least one prior systemic line, including mogamulizumab, are going to be randomized one-to-one against lacutamab or romidepsin, which is the only drug that is available to patients who failed on moga. The primary endpoint of the study is progression-free survival as assessed by blind independent central review, and the key secondary endpoint is overall survival. The patients in the MF cohort are patients at stage 1B onwards, and so stage 1B to stage IV.
And these patients are randomized one-to-one against lacutamab or mogamulizumab, that is a very good standard of care for patients in this condition. And again, the primary endpoint is progression-free survival by blind independent central review. And the key secondary endpoint are quality of life and pruritus. Now, the stratification factors for the randomization are in both subgroups: the disease stage, early disease versus late disease, and region, U.S. versus Europe versus rest of the world. Now, because these are two independent cohorts, they have two different sample sizes. And these sample sizes have been estimated by considering the number of patients that are needed in each cohort to meet the primary endpoint of progression-free survival for Sézary against romidepsin and for MF against mogamulizumab.
In terms of regulatory timelines, we are in the process of selecting the CRO that should help to initiate the study, opening the sites. And our intention is to start the Phase III at the beginning or by the first half of 2026. And according to these timelines, since we know from the FDA feedback that we need the Phase III underway to file for the BLA for the accelerated approval, we have predicted that around one year after the initiation of the Phase III, we may show the FDA the right trajectory of recruitment to satisfy this condition of the Phase III underway and file the BLA for accelerated approval in Sézary syndrome, third line post-mogamulizumab.
Immediately afterwards, because the MF recruitment is going faster than the recruitment of SS, which is a much rarer disease, we will have by 2028 finished the enrollment and filed the BLA based on the primary analysis for progression-free survival in MF. And this is a BLA that we will file in 2029. And to follow is the BLA for the regular approval of Sézary at the end of 2029, along with the submission to the European authorities for both MF and SS. So, in summary, we are going to have three different or some key milestones. One, in 2027, that is accelerated approval for Sézary syndrome. And 2029, a full approval for Mycosis fungoides and Sézary in second line plus. And so we are moving one line earlier compared to where we are with the accelerated approval.
And then, from 2029, we can really expand in earlier stage and other CTCL patients. Those patients that still need treatment, they are categorized as non-MF, non-SS, but inevitably, they use the same drug that is used in MF and SS. So, you've seen this slide before in the NCCN guidelines. In reality, we have very few drugs that are specifically approved in the CTCL space. And here are outlined in blue the very old drug, mainly based on safety, like bexarotene, interferon alpha. Methotrexate has never been really studied specifically in CTCL. It comes with an old approval in the lymphoma bucket: brentuximab vedotin, mogamulizumab, romidepsin. And Professor Porcu has beautifully outlined the limitation and the toxicities related to this drug. And then we have some off-label use, because there is really nothing that the investigators can offer this patient outside of these drugs.
And so they can off-label use drugs like gemcitabine, doxorubicin, pralatrexate, never really studied specifically in CTCL And it is our intention, really, to place lacutamab on the NCCN guidelines, to have it as a preferred systemic treatment, not only for the late-stage disease, but really bridging the need, the high-end medical need for those patients that may have an early disease. We don't want them to progress, and they need efficacious and well-tolerated drugs. And this is the end of my presentation. And now we can move to the commercial part with Stéphanie. Thank you.
Thank you, Sonia. So now we are going to enter the second part of the presentation with the commercial opportunity of lacutamab. And we'll start with the presentation from Chris Stuessy-Vidas from ZS Associates. So ZS Associates has conducted a study of the CTCL population based on real-world claims data. And Chris is going to share some of the key insights of this study.
Hello, everyone. My name is Chris Stuessy-Vidas. I'm with ZS Associates in the San Francisco office. ZS is a consulting firm that is very much in the life sciences space and helps with commercial strategy. We service a wide range of clients, from large pharma to small biotech. My role specifically within ZS is to do opportunity assessments on novel assets, as well as forecasting. I am a pharmacist by background. I did my undergrad and my PharmD at the Ohio State University, and as Stéphanie mentioned, we conducted a CTCL market analysis using the Komodo Claims data set. We use the Komodo Claims database because it has wide coverage of medical claims as well as pharmaceutical claims, and a few things to note about the methodology and the data here. The primary time frame for this analysis is 2018- 2023.
The primary therapeutic frame is the NCCN listed agents, as well as some targeted additions based on physician utilization. And then we want to read this as utilization patterns and channel mixes. Specifically, we're trying to understand the prevalence and incidence of CTCL, as well as the treatments used in the disease. A few notes here. So the counts are based on provider-coded patients, and they don't reflect misdiagnosed or undiagnosed patients. The 2024 and 2025 data is incomplete given data lag. This is consistent with all claims data sources. There are a few analyses that do have more recent data, but absolute counts will not include anything from 2024 and 2025. Komodo captures 95% of U.S. patients, meaning that a patient is, if they have one claim associated with them, they are captured.
Komodo has a very wide range in the number of lives in the U.S. that are covered. However, ultra-rare diseases like SS can be affected by the absence of a single data point, given the small patient numbers. And then the specialty analysis that I will go over in a little bit is dependent on certification status specific to MD/MDOs. So if there is a nurse practitioner who is a hematology oncologist that's working under a physician, they won't be included in that analysis. Finally, this information is really useful, but any kind of claims data needs to be triangulated with secondary research and primary research in order to really understand the data, and especially the patient journey with something like CTCL. A little bit more about the methodology here before I actually get started into the data.
I just want to call out that these groups are used to look at different subtypes of CTCL. We are limited by the ICD-10 codes that are part of the ICD-10 lexicon. So these are kind of the breakdown. The first three on the left are relatively straightforward. So we have all CTCL patients, which includes all the codes beneath C84.0, which is MF, C84.1, which is SS, and C84.A, which is CTCL unspecified. Then we have specific subgroups for only MF, C84.0, and only SS, C84.1.
And then for the undefined patients, since providers can code multiple ICD-10 codes on a claim, and there are sometimes miscoding, as well as potentially a provider not having a strong diagnosis and putting an unspecified code, we wanted to remove patients if they ever had an MF code or an SS code to actually get to truly different subtypes in MF and SS that was spoken to a little bit earlier, so looking at this actual data, starting with the left-hand side, we have the CTCL subtype distribution, and as mentioned earlier, this is very consistent with literature, so 64% of patients fall within the MF codes, 5% fall within the SS, and 31% fall within the undefined. We also looked at prevalence. In 2023, the prevalence of just a one-year time span, keeping in mind, was 20,000 patients.
We looked at incidence, where there were roughly 5,000 patients in 2023, 2,900 of these being MF, 316 being SS. And then in terms of the incidence over time, SS and MF remain relatively consistent at about 300 patients and 3,000 patients, respectively. Just a little bit further on the subtype breakdown, we wanted to make sure that there were no major shifts in subtype mix over time. So we looked at the time frame a few different ways: three years, five years, and seven years, and relatively very consistent with 65% versus 5% in MF and SS, respectively. One of the things that we wanted to look at specifically was MF by treatment modality. MF is a little bit unique in the oncology space in that there are a lot of patients that necessarily aren't treated systemically.
So we wanted to test that hypothesis, and we looked at the MF patients by treatment modality. So we found that 80%, roughly, were treated, 73% with topical therapy, 25% with systemic, specifically pharmacotherapy, 17% with phototherapy, and 3% with ECP. So we do see that there is a significantly lower proportion of patients being treated systemically than in typical oncologic indication. So looking at the top specialties and the healthcare organizations here, so the graph on the left is broken out by dermatology and hematology/oncology. And what we see is that in SS specifically, there is a much higher percentage of patients being seen by a hem/onc. So this is between the time span of 2022 to year-to-date of 2025. And we see that 63% of patients saw a hematologist/oncologist in SS, compared to in MF and undefined patient groups being lower at 20%.
All patient groups relatively see a dermatologist at some point in time, with 69%, 75%, and 60% in SS, MF, and undefined, respectively. We also looked at the top healthcare organizations, and this is defined as having greater than 71 CTCL patients. Again, this is in the time frame of 2022 to 2025, and what we see is that in these high-volume institutions, the majority are in the academic setting, with 87%, 86%, and 81% in SS, MF, and undefined, respectively, so looking at the actual therapies, the actual pharmacotherapy used for these patients, the most frequently used systemic therapies are the FDA-approved ones. Specifically, within the time frame of 2023- 2025, on the graph on the left, 9% of patients within that time span receive methotrexate at some point. Other commonly used agents are Bexarotene, BV, and moga.
One of the things that we were really interested in seeing is the specialty breakdown by the intravenously given products, just to see if that would be less in the dermatologist setting. We do see that there is less than 10% of patients who are prescribed by a dermatologist versus 80% and above that prescribe these three specific IV infusions. Finally, we saw strong use of mogamulizumab in SS patients. Since its launch in 2018, it has steadily climbed to around 300 patients in 2023. Just to kind of give some context here, the incidence has remained relatively steady in SS as well as in the general CTCL population. The prevalence has steadily increased over time as well. Finally, just to recap the key points here.
Again, we looked at the U.S. claims data from Komodo Health to gather CTCL epidemiology, market landscape, and HCP and HCO insights. With respect to epidemiology, we saw that the prevalence was around 20,000 patients in 2023. The incidence was relatively stable at 5,000 patients a year, with 2,900 of these roughly being MF and 300 being SS. We saw that the subtype mix was consistent with literature, around 64% MF and 5% SS. In terms of the market landscape for MF specifically, we saw that 79% were treated, 25% received systemic pharmacotherapy. The FDA-approved drugs are the most frequently used systemic therapies, and mogamulizumab has had steady growth and strong use in SS. Finally, with respect to prescriber dynamics, CTCL is like all the subtypes treated by dermatologists 71%.
However, 20% do see a hematologist/oncologist, and the concentration is mainly in academic centers for high-volume institutions. The SS subtype, however, has much higher hem/onc involvement at 63% of patients seeing a hematologist/oncologist and 79% of patients being prescribed mogamulizumab by a hematologist/oncologist.
Thank you.
Thank you very much, Chris. So now we are going to enter the last section about the commercial opportunity for lacutamab. So at Innate, I am in charge of the investor relation and the commercial strategy. And so now I will focus on the commercial strategy for lacutamab. So given all the insights that we have received today with the CTCL landscape, the TELLOMAK Phase II data, and the real-world evidence from ZS Associates, the vision that we have at Innate for lacutamab is really to open doors for the CTCL patients. And the objective is really to bring to these patients therapies that provide durable disease control and also improve their symptoms, which are the itching, the skin lesions, the fatigue. And this is what really truly matters for these patients.
So if you have a drug that is able to specifically target the malignant T cells and improve the control of the tumor, improve the quality of life of these patients, and have very good tolerability, you really want this drug to be available in the patient journey as soon as possible, as early as possible. And this is really what we envisage here for lacutamab to induce a true paradigm shift in the CTCL landscape. So concretely, if we look at the strategy that Sonia has presented a little bit earlier, it is actually, we think, a very logical and stepwise approach that is designed to unlock the value across CTCL segments. First, you have the Sézary syndrome indication, and this is where the unmet medical need is the most urgent.
There is no therapy approved once the patient has progressed after mogamulizumab in SS patients, and the survival remains very poor, so this is the very first segment for lacutamab, then the second segment, in line with the Phase III design, would be to establish lacutamab as the new second-line standard in MF patients, and then beyond, as a lifecycle management opportunity, there is really the opportunity to expand use of lacutamab in these early-stage patients, and this would mean that it would create an expansion of the current CTCL market because currently these patients are mostly treated with the skin-directed therapy, so this strategy became even more relevant when we received the insights from this real-world claims evidence, so CTCL remains a rare disease, and like for every rare disease, the assessment of the incidence and the prevalence remains a challenge.
And here, what Chris from ZS Associates presented today is the most up-to-date view of the CTCL population in the U.S. And we have a reminder here that all the figures that we are presenting are in the U.S., and there is also a population in Europe, of course. So from this data, we have seen that there is a much higher incidence across CTCL segments. And in SS, it is about three times the incidence. In MF, it is about 50% higher. And this really has changed our view of this opportunity because now we see that already the first segment, the Sézary syndrome indication, with this number of patients, is already a commercially attractive opportunity at launch.
So now if we look a little bit into details in each of these segments, so first, the Sézary syndrome indication, as Sonia presented, this is what we consider the near-term de-risk opportunity because the plan is really to submit the BLA for the accelerated approval once the Phase III is underway based on the data from the TELLOMAK Phase II, so we are not waiting for any additional clinical data to submit for this BLA. The incidence is around 300 new patients with a prevalence around 1,000 patients, and we've seen in the previous presentations that there are around 300 patients each year that are treated with moga, and so the population will be eligible for a lacutamab therapy. These patients are treated mainly by the hematologist/oncologist, and they are managed within academic specialized centers.
So overall, we see this as a really focused and accessible commercial footprint because there is a very limited number of centers and physicians. And additionally, we already have this good network established where we know many of them. The second indication, the mycosis fungoides, here the objective from the Phase III is to establish lacutamab as a new second-line standard for the MF patients. With regard to the incidence, the same. It is higher than previously anticipated. And we have seen that from the data, around 25% of the MF population are already receiving a systemic therapy. So there is already a tangible opportunity within this pool of patients. And we have run market research, interviewing physicians, testing the target profile of lacutamab for the Phase III based on the Phase II data.
And the outcome of these researches really supports the adoption of lacutamab as a second-line standard of care in the MF. And importantly, the expansion into MF will be a very efficient expansion because the centers and the physicians that treat SS and MF for systemic therapy are the same. So the planned infrastructure that will be in place with the SS launch will be the same for MF. So this is where we anticipate really a fast approach at the time of the launch in MF as well.
And the last bucket, which is more the lifecycle management box for lacutamab, but which is actually, as you understood from the presentation from Pierluigi Porcu and Sonia Quaratino, a very important one for the program, is about the ambition to become the standard of care for these early-stage patients that as of today do not have many options as a systemic therapy approach. There is really this unique profile of lacutamab with the improvement of the quality of life, durable PFS, the favorable safety, and all of these parameters of the drug may really enable this earlier adoption. And while we are running a Phase III that aims to support approval in MF across stages, but as a second-line systemic therapy, we believe that there is an even broader opportunity to move earlier and to really unlock the access of these patients that currently receive only the skin-directed therapy.
So if we look at the revenues that are generated by the drugs that are currently approved in CTCL, a very good example is mogamulizumab because mogamulizumab is approved in MF and SS after one prior line of systemic therapy. And so the revenues that are reported by the company essentially reflect the CTCL market potential. So they have seen their revenue increasing steadily over time. And when you see that the plan in 2025 is to reach around $300 million of revenue and that it is for a drug that has a strong market share in SS, which is the less frequent indication, and probably a limited share in the MF population, you can only imagine what is the potential for a drug that will take share in the SS and will take even more share in the MF population.
And given the disease burden and unmet medical needs that have been described today, we really believe that this is a market that is just waiting to grow and to have the right therapy to do it. And of course, this is the potential that we have with lacutamab. So for lacutamab, the value driver is the duration of treatment that is aligned with the PFS, but also in the clinical studies, there are patients that have been on treatment for years, for five years, for seven years. And this is not something that you see with the current systemic options that are available. So this is truly remarkable for a systemic therapy in CTCL. Second value driver, the pricing. And third value driver, as we have extensively discussed today, the market share and the eligible populations that we intend to grow.
So altogether, this is the final slide of this commercial opportunity section. What you will find here are the real-world evidence-based forecasts. We envisage an opportunity up to $150 million in the Sézary syndrome indication, which will be the first indication launched. And there will be a potential up to $500 million combining the SS and MF as second-line option. And then there is opportunity to go beyond this by expanding the use as lifecycle management in these early-stage patients, with really this opportunity to create a market for lacutamab and for patients. So thank you for your attention. And now I'm handing back to Jonathan.
So thank you, Pierluigi Porcu. Thank you, Sonia. Thank you, Chris, and thank you, Stéphanie, for your interesting presentations. What I'd just like to do is to quickly wrap it up. So this is a slide that I showed at the beginning. So just to remind you, we have the data, the strong data available today from the TELLOMAK study. That's leading us to build regulatory momentum. We've submitted the final protocol to FDA. We're expecting to be able to initiate that Phase III study imminently. And we've got a broad emerging opportunity, which I think Chris nicely demonstrated and Stéphanie in terms of the eligible patient population. So we feel like we have a really exciting opportunity in cutaneous T-cell lymphoma with both Sézary and MF and an opportunity to really revolutionize, I think, the care for patients, particularly for the early-stage patients, and hopefully be able to prevent them progressing to stage IIB and beyond, where we see the significant impact on their survival. So very exciting times and a very clear path forward for lacutamab.
I'd just like to remind you of a couple of things in terms of key catalysts for our portfolio for Innate Pharma. So the first is around Nectin-4, our IPH4502. We're expecting to have the phase I data around the end of this year, beginning of next year, preliminary efficacy and safety data. So watch that space. We have monalizumab with the readout of the PAC9 study and the top-line data expected during the second half of next year. Going out into 2027, we have the lacutamab accelerated approval in Sézary syndrome. We'll have a BLA submission for monalizumab providing a positive study. And we'll also have further data on IPH4502 from the Phase I/Phase II expansion cohorts. So there are some of the key milestones. And then with that, I'll conclude the presentations from today, and we can open up for a Q&A.
Maybe we'll start in the room first, and then we can go online. So if the speakers would like to come and sit up front, maybe Yannis, you want to join us as well. Yep, we have Yannis Morel, Chief Operating Officer with us, who will also be able to support in some of the more technical questions. So let's go. RK, I think you have your hand up first.
Good morning, and thank you very much for doing this. My name is RK from H.C. Wainwright. Dr. Pierluigi, based on your presentation and also looking at 25.5 months of duration of response in the post-moga population, how does that translate into a tangible benefit for patients? And second question is, when you start thinking about treating patients in early stage, especially in stage IB, where most patients are still in topicals, how easy is it to convince them to get into a systemic therapy? Thank you.
Yeah, so both great questions. Regarding the benefit, I think that the fact is that in terms of overall survival at this point, we don't really know yet exactly how that would be impacted. But we know that Sézary syndrome is a very high-risk disease. The median survival is less than two years. As I said, about only one in ten patients are alive at five years. And we think that that is really because the disease is not well controlled. And so I would imagine that with better disease control, rapid, as Dr. Porcu did in TELLOMAK, we will see kind of an improvement in overall survival.
In terms of benefit beyond overall survival earlier on, anything that we can do for these patients to actually control the disease in the blood, control the symptoms, it's already an immediate benefit. So to me, really, as others and Sonia has shown as well, I mean, in Sézary, it's a game changer. In terms of the early-stage patients, that's also a very good question. I think that one of the reasons why we see that continuous disease stage progression is because the systemic therapies are really not very effective. It's true, and that may be behind also some of the numbers that Chris showed about how many patients actually are getting systemic therapy. I think that the issue is that patients have this mindset that once they start using systemic therapy, the disease is more advanced or they are sort of in bad shape.
And that is based on the kind of historical data looking at the only thing that the doctors had available before was chemotherapy. And so there is a kind of a historical flaw in terms of, but I think that as long as the therapy is safe and we can show it, then I think that there will be adoption of systemic therapy. And that's sort of what we really like to see moving forward if we want to change that natural history. So far, nothing has really been able to change that.
Thank you.
So then I think we had Justin. I think he had his hand up.
Hi, Justin Zelin from BTIG. Thanks for putting this on. So maybe a question for the company. I know you submitted the protocol for the Phase III to the FDA. When do you expect to have alignment feedback from FDA? And I have some follow-ups.
Okay. Well, the protocol has already been submitted one month ago. And despite the FDA shutdown, we obtained feedback from the FDA and replied and addressed their comments. And so we may expect a green light any time.
Great. And as far as what you'd be looking for for success in the Sézary and MF cohorts, what would you be looking for as far as a delta on PFS? In which indication? For both the Sézary and the MF versus romidepsin and moga.
Well, the intention is really to duplicate the numbers that we observed in TELLOMAK. When you look at Sézary, the PFS that we have shown is comparable. It's really numerically comparable to what mogamulizumab obtained in an earlier line. And I remind again, in the trial, we are post-moga. And of course, we cannot use mogamulizumab as a comparator arm because we are post. And so we use, let's say, a kind of suboptimal comparator that is romidepsin. That is the only FDA-approved drug that is remaining in the armamentarium as a comparator drug.
And so that I think I already addressed the question for SS. And for MF, in the TELLOMAK study, we have shown a progression-free survival in excess of 10 months for the MF population. And mogamulizumab in the MAVORIC trial had a progression-free survival of 5.4 months. And when you also look at the confidence interval, the numbers are not overlapping at any stage. And so that is also reflected in the estimation of the sample size that you have seen projected in the study design.
Great. And maybe a question for Pierluigi. Just given the safety profile of lacutamab that we've seen so far, and you mentioned that safety is a priority in this indication, and also the breadth of activity you see across the expression levels, would you consider using lacutamab in earlier lines for patients and, let's say, broader in the CTCL landscape beyond Sézary and MF if the agent was available commercially?
Yeah, definitely. I think that's really, I think, as a practitioner, as a physician treating patients, that's, I think, really where the kind of besides Sézary, which is really kind of the top, I think that that's the second biggest unmet need. I think that one of the issues in early-stage patients is that really, because of the safety of the drugs that are being used, a lot of times patients try something and then they stop it.
Either they stop it because they have some side effects, or they stop it because sometimes even questionable payers in terms of reimbursement. So there are a lot of issues, both medical and practical, that really prevent patients from starting. I think if certainly physicians and patients who know their disease have the option of having a safe therapy that they can start early to try to prevent that progression, I think it would be really embraced at all levels.
Great. Thanks for taking the questions.
Hey, this is Chris from LifeSci Capital Markets. Thanks for the R&D day today. Maybe first one for the company. Based on the claims data for MF, it seems like there's an imbalance for who's prescribing in terms of the hem/oncs and the derms. Is there a commercial strategy in mind for potentially how to tap into the Derms who aren't prescribing systemic therapies as much? What are your thoughts on kind of the commercial strategy there?
I think from a, maybe I'll take this one, and maybe Stéphanie wants to add something. I think this is a, for me, this is a two-step approach. I think you start with basically the hem/onc, which is where the patients are being treated today. And then I think as a second step is what we classify as sort of lifecycle management. Then I think you broaden out, and you do go to Derms, and you try and get the patients treated earlier. And I think that's basically the approach that we were looking b ut it will be in two steps.
Got it. And then maybe one more for Dr. Porcu. In terms of what we see with the prescribing today, like I mentioned, it doesn't seem very high in MF. Why do you think that is currently? And do you believe, based on the data we've seen with lacutamab today, that can potentially change?
I think that the breakdown in terms of the specialties that are seeing MF may be more nuanced than perhaps kind of the stark differences that particularly the claims data seem to have shown. I mean, if we look at, for example, the one thing we know is that a lot of these patients are seen at academic medical centers. At academic medical centers, very often, there's co-management of these patients. So dermatologists see it, medical oncologists see it.
It may not be, for example, if it is early stage, then the dermatologist will see them most of the times, but they always go and see perhaps the medical oncologist or the hematologist maybe once. Or at any point in time in transition during the care of the patient where there is a question whether the treatment should be changed or certain new additional sort of therapeutic intervention need to be initiated. So it's really a co-management. And if you look at the percentage that Chris showed, I mean, 85% of the patients are seen in academic medical centers. To me, this is my extrapolation. I mean, to me, that means that 85% are seen by both Derm and medical oncology.
It's true that the decision-making about prescriptions, what therapy is prescribed, depending on which stage they're in, is probably being driven by more Derm in the early stages and Hem/Onc in the advanced stages, but I think that there is much more transition and discussion in terms of which therapy. At the end of the day, certainly, it's true that there is a significant opportunity for more systemic therapy being prescribed. Okay, and that I don't think has to do necessarily specifically with Derm or Hem/Onc. I mean, it has to do with the fact that some of these patients are, in fact, concerned about starting systemic therapy. Maybe they're sort of reluctant to do it.
And they do that because they heard kind of horror stories from either online, on Facebook, or on other sort of places on the internet where you have to hear these different stories about systemic therapy. So I really feel that it's very dynamic, and the landscape is going to change, I feel, for sure, moving forward. And the strategy, going back to what John was saying, I mean. Dermatologists, there are a number of systemic therapies that now dermatologists are using for all kinds of indications, right? So for psoriasis, atopic dermatitis. So the world is changing, and it's not just applying little topical therapies. So I think there is a big opportunity for dermatologists to embrace systemic therapy, particularly if it is done in conjunction with a Hem/Onc.
Yeah. Great. Thank you guys so much.
Daina.
Hi. Daina Graybosch from Leerink Partners. You've had success with lacutamab for a number of years, and you've also been working to seek partners for a number of years. And now you've made the decision to go alone. And I wonder if you could talk about those partnership discussions, why you think that didn't materialize, and why we should have confidence, an investor should have confidence in Innate here when a partner hasn't stepped in.
Yeah. Maybe I can start with that, and maybe Yannis can add something to it. So if I look at the partnership discussions we've had, they've been very good discussions. We've had complete alignment generally on the development path and where we're going and the data and the chances of success, etc. Where we had issues with partners was on the size of the marketplace. And that was, I would say, the rate-limiting step.
And I think if you look at the old numbers that we were looking at, and particularly for Sézary, which will be the first indication with the accelerated approval, it was relatively small. And I think what's led to the change in our thinking is the new data, the claims data that we have, which shows us that the initial commercial opportunity is significantly larger than we previously anticipated. That makes the first launch on its own commercially viable for either Innate or for a partner. And that gives us a renewed sense of confidence in terms of where we can go. And I think we have a team that's showing that they can demonstrate, they can deliver from an operational effectiveness perspective.
If you look at what we're doing with IPH4502 today and the speed with which we're moving forward and showing positive results, I think you see the strength that we have from a clinical operations perspective and Sonia's team, which is particularly strong, so we're very confident that we can deliver for investors and we can get lacutamab over the line very quickly. Yannis, I don't know if you want to add anything.
Yeah. No, I don't have so much to add, but it's, I mean, the latency is very clear, and we have had, I would say, during the last year some conversation with mid-size pharma who can be very interested by the lacutamab. I mean, there is no point on the clinical data. Everybody agreed that we have a very, very strong clinical data package, that the path forward is also very clear and very de-risked. And what was really challenging so far are the discussion around the commercial opportunity. And note that we have had this new analysis based on the real-world data only very recently during the summer.
With regard to potential deal, I mean, without disclosing too much, I mean, what was also aligned with what Jonathan said, that potential deal structure that we at some point contemplated was where Innate were actually performing the Phase III for the partner. That was something that we had in mind, and we were discussing and are discussing with some partner. But again, this new data basically changed.
I mean, if you take at the very high level and you take the Sézary opportunity, which is in the range of $150 million, if you divide by three, which was basically what was the starting point last year for a partner, it's not very attractive for the first indication, but now you have something that, I mean, it's a bit like Kimmtrak in the range of $150 million for the very first indication with the opportunity to grow to the MF, even, I mean, after full approval, but potentially before if we have the NCCN guidelines, so even during the Phase III, so it totally changed the attractiveness of the first indication and also the dynamics of the uptake.
So that makes our own, I would say, interpretation on the opportunity, but our board also more desirable development by our own and try to finance it, to do it ourselves and to maintain more value for the company and for the shareholder.
Is it fair, listening to you, to say that now that you see more commercial opportunity, you might be more attractive to partners, but that also gave you confidence to go alone? You mentioned Kimmtrak. I guess that's a company that's gone alone. So is that fair?
Yeah.
Yes.
Yeah.
Yeah. I think we've got the confidence to move forward. We know we have the capabilities internally to deliver the Phase III study. It's roughly double the size of the TELLOMAK study. This is well within our wheelhouse and capabilities. We know the investigators. We know the sites. We know where we're going to recruit patients.
So this is something we can very effectively do ourselves. And then I think we keep our options open. If a good partnership deal comes along, we'll clearly look at it and evaluate it in a very open way. But we also keep open the opportunity to do this ourselves if that good opportunity or good partnership doesn't come along. Just maybe also to give you a bit more background on our thinking and how it evolved during the last year, that again, if you take the simple math of like a $50 million opportunity, that was also the reason why we were thinking it would be good to have a commercial partner from day one because launching a product, starting a commercial team for $50 million, I mean, it's not profitable.
If you have already a heme franchise in place and you have like an add-on product or a full series of other products, it's an incremental gain. But if you have to build everything, it's not worth the effort. So that's why we were at some point really fearing the partnership. I know with this first indication, which is more attractive, it completely changed our perception.
Let me ask about PTCL. So do you also think you have the organization and capabilities to run the frontline L-CHOP trial? And can you help us understand sort of the relative investment if you would move to Phase III in that trial and then the Phase III confirmation trial and CTCL?
Yeah. So from a PTCL perspective, I mean, do we have the organization to deliver that? Yes, I think we do. Again, we've been working. There's a big overlap between the physicians who are treating PTCL and CTCL, so again, we know the sites. We know the centers. We're working very well with LYSARC, who are doing basically the investigator-initiated study, which is due to deliver middle of next year, so I'm confident that we have the ability to do that. In terms of sizing of the study, Sonia, and what that would look like for PTCL, I mean, I think we have maybe some high-level thoughts on it, but we don't have a specific plan yet. I don't know if you want to say some more, Sonia.
Yes, in the sense we have made some potential planning to move in the first line in combination with CHOP, and also the LYSARC is extremely keen to continue this collaboration, and that would be ideal for us because also PTCL is extremely complex. There is a variety of little subgroups that encompass the PTCL, let's say, space, and they are probably best placed to dissect this, and so I think that this collaboration would be extremely useful in terms of study design, comparator arms. We have made some prediction, and we can elaborate. So you're talking like a cooperative group registration trial?
I think potentially it could be if you look at the LYSARC, they actually did the Phase III registration trial for Rituximab back in the early 2000s. It's a long time ago. I was at Roche at the time, and I was actually leading that program at that point in time. So I had first-hand experience of working with it was called the GELA Group at that point, so yeah, but it could be a combination of several collaborative trial groups coming together to speed the recruitment.
I think we need to work through the final logistics of what it could look like, but I think speed is important, so if you were just restricting yourself just to the LYSARC, they are a recruitment machine, and they do very well, and they recruit studies very rapidly, but I think if you can involve a couple of groups, you can go even quicker, and ideally, you would want to spread it across multiple geographies, not just Europe.
Maybe one more question for me. For Dr. Porcu and the broader team, what guidelines are most important in CTCL? Do you see an opportunity? What's the path for those guidelines, let's say, with lacutamab approval to also give some sort of evidence for potential treatment in MF? Do you see uptake there, not just in academic centers, but more broadly? And then to the team, how you're planning on engaging those appropriate guideline groups?
So I mean, you mean clinical practice guidelines? Yeah. I think that the clinical practice guidelines that are most used here in the U.S. are the NCCN. There is a very good dedicated specific subcommittee of the NHL, the lymphoma committee within NCCN that specifically is focused on cutaneous lymphomas, not just T, but also B cell-based focus on cutaneous lymphomas. Then they actually release a subset of the guidelines specifically for cutaneous lymphomas. So certainly, academic dermatologists, not just academic oncologists, they look at the NCCN guidelines. Those are the guidelines that the trainees are being taught to look at. In Europe, I think that the guidelines, the most common guidelines are the EORTC, maybe ESMO as well.
I don't have direct knowledge of the market share of those guidelines in Europe specifically, how often they're used, but in the U.S. is NCCN, and then I would guess at this point that as safe and effective systemic therapies become adopted, approved, and then adopted, the community oncologist will be certainly eager to sort of use and treat some of these patients in their offices following the guidelines. At the moment, they don't do that because not just these patients are relatively uncommon, but because they're not familiar with some of the drugs that currently are being used.
A nd then from a company perspective, clearly we intend to engage with NCCN very early. Our objective is to have both SS and MF included in those guidelines at approval to allow physicians the flexibility in terms of how they would use lacutamab moving forward, so yes. Yeah. And of course, we need to get the data published in the TELLOMAK study to do that. So that's one of our key next objectives is to make sure that the TELLOMAK data, which is excellent, is published in a high-quality journal to facilitate moving forward then with NCCN and ESMO in Europe.
More questions in the room? Maybe we have some questions online.
Only in French. I'll let you handle those offline.
Okay. You mean you don't read French? Okay. All right. Well, then if we don't have any further questions, I'd like to thank all of you for your participation. I believe we had over 100 people attending today, which is great to see the interest in cutaneous T-cell lymphoma and lacutamab and Innate Pharma. So thank you for your time and attention, and we look forward to interacting with you over the coming weeks and months. Thank you.