Innate Pharma - ADR Aktie

Hello, everyone. Welcome to the Innate Pharma first half 2026 business update and financial results. [Operator Instructions] I will now hand the conference over to Stephanie Cornen, Vice President, Investor Relations, Communication and Commercial. Stephanie, please go ahead.

Good morning and good afternoon, everyone. Thank you for joining us for Innate Pharma's first half 2026 business update and financial results conference call. The press release and today's presentation are both available on the IR section of our website. Before we begin, I would like to remind everyone that today's presentation includes forward-looking statements based on current expectations. These statements involve risks and uncertainties that could cause actual results to differ materially.

To briefly cover today's agenda, our CEO, Jonathan Dickinson, will begin with a strategic overview and outlook. Markus Jensen, our Chief Medical Officer, and Yannis Morel, our Chief Operating Officer, will then take us through updates on lacutamab, IPH4502, monalizumab, and our preclinical ADC pipeline. Frederic Lombard, our Chief Financial Officer, will then review our financial results. Jonathan will return for our upcoming catalysts and closing remarks before we open the call for Q&A.

With that, I will now hand it over to Jonathan.

Thank you, Stephanie. Good morning to those joining from the U.S. and good afternoon to our European participants. Turning to slide 5. The first half of 2026, together with developments since the end of the period, has been marked by important progress across our focus portfolio.

Starting with lacutamab, in August, we announced our strategic partnership with Sobi to advance the program in T-cell lymphoma. As announced yesterday, that partnership is now effective following the closing of the deal and the TELLOMAK-3, Phase III, has been initiated. We are targeting the first patient in the study in Q1 2027 as we work toward a filing for accelerated approval in Sézary syndrome in H2 2027.

For IPH4502, as announced in July, we completed Phase I dose escalation and cohort enrichment enrollment and have been seen preliminary anti-tumor activity, including objective responses in post-EV urothelial cancer, as well as in non-small cell lung cancer and head and neck cancer, with a sustainable safety profile observed to date. We will share initial Phase I dose escalation data at the EORTC-NCI-AACR meeting on November 18, 2026, in Barcelona.

Turning to monalizumab, enrollment in the PACIFIC-9 Phase III study has been completed, and we continue to expect the Phase III readout in the second half of 2026. Financially, our position has been strengthened by the $75 million Sobi upfront payment associated with the closing of the deal and the EUR 30 million equity financing. Together, these are expected to extend our projected cash runway through the end of the first quarter of 2028. Taken together, we believe these developments position Innate for several important catalysts in the second half of 2026.

Let me start with lacutamab. Lacutamab is our anti-KIR3DL2 antibody being developed in cutaneous T-cell lymphoma, or CTCL. Turning to slide 7, as I mentioned, in August, we announced a strategic partnership with Sobi to license lacutamab in T-cell lymphoma. The transaction has now closed. TELLOMAK-3, our confirmatory Phase III study in CTCL, has been initiated with the first patient expected in the first quarter of 2027. Innate will conduct the Phase III study, and we will file for accelerated approval in Sézary syndrome based on the existing Phase II TELLOMAK data.

Upon the potential accelerated approval, Sobi will receive exclusive global rights to commercialize lacutamab. Following positive Phase III results, Sobi will be eligible to obtain full global development rights. Under the terms of the agreement, the transaction includes a $75 million upfront payment, up to $40 million in near-term milestones connected to Sézary syndrome, and up to an additional $465 million related to Sobi's option to obtain full development rights and future regulatory and commercial milestones. The agreement also includes tiered double-digit royalties on future net sales.

I'll now hand it over to Markus to review the regulatory and development path forward. Markus.

Thank you, Jonathan. Lacutamab is now progressing towards Phase III TELLOMAK initiation and planned accelerated approval filing. So, from a regulatory and development perspective, the path forward is well-defined. We have FDA clearance to proceed with TELLOMAK-3, which now has been initiated with the first patient expected in the first quarter of 2027. The study includes a confirmatory cohort in Sézary syndrome and a registration cohort in mycosis fungoides. The existing Phase II TELLOMAK data are intended to support an accelerated approval filing in Sézary syndrome once TELLOMAK-3 is underway. With the filing currently planned for the second half of 2027.

As a reminder, lacutamab has received breakthrough therapy designation from the FDA for relapsed or refractory Sézary syndrome, as well as fast track designation from the FDA, PRIME designation from the EMA, and an orphan drug status in both United States and Europe. So, with the regulatory pathway established and the Sobi partnership now effective, our focus is on advancing TELLOMAK-3 towards first patient enrollment first quarter 2027.

Turning slide, please. I now move to IPH4502, our differentiated Nectin-4 exatecan ADC, which is in Phase I development -- clinical development for advanced solid tumors. IPH4502 was designed to address some of the key limitations of the first generation of Nectin-4 ADCs. The molecule combines an exatecan-topoisomerase-1 payload with our proprietary stable linker, and a high affinity Nectin-4 antibody that binds non-overlapping epitope compared with enfortumab vedotin. We believe these features provide an important point of differentiation as the Nectin-4 ADC landscape continues to evolve.

Importantly, we are now beginning to see that profile translate clinically and have observed preliminary anti-tumor activity with objective responses in heavily pretreated patients, including patients with urothelial cancer following prior enfortumab vedotin treatment, as well as in non-small cell lung cancer and head and neck cancer. The safety profile observed to date has been favorable with limited hematological toxicity. We completed dose escalation in July and are broadly tracking in line with our expectations across expansion cohorts with approximately 15 patients enrolled in both post-EV urothelial carcinoma and head and neck cancer, and somewhat lower enrollment in non-small cell lung cancer cohort. Data cleaning is ongoing, and we look forward to presenting the initial Phase I dose escalation data set at the EORTC-NCI-AACR Symposium on November 18, 2026.

Next slide, please. Our area of particular interest for IPH4502 is urothelial cancer following prior EV treatment. While EV plus pembrolizumab has significantly changed the treatment landscape, most patients progress within 2 years and there remains no established second-line standard treatment after progression of this regimen. Against that backdrop, the preliminary activity we have observed with IPH4502 in heavily pretreated post-EV patients, including objective responses, is encouraging. These remain early Phase I observations, and the upcoming data set will help us to determine how to best advance the program.

On slide 11, please, slide 12, please. I move forward to monalizumab, which is our NKG2A antibody being co-developed with AstraZeneca in non-small cell lung cancer. PACIFIC-9 is a randomized Phase III trial with unresectable stage III non-small cell lung cancer patients who have not progressed following a definitive platinum-based concurrent chemoradiotherapy. The study enrolled 1,051 patients in comparison to durvalumab plus oleclumab, durvalumab plus monalizumab and durvalumab plus placebo as a control, with progression-free survival as the primary endpoint. The program is supported by 3 earlier Phase II studies non-small cell lung cancer, including COAST, NeoCOAST and NeoCOAST-2. With enrollment complete, Phase III data remain expected in the second half of 2026.

I now hand over to Yannis to briefly review the economics of our partnership with AstraZeneca.

Thank you, Markus. As a reminder, under our monalizumab partnership with AstraZeneca, we have received up to date EUR 450 million. And the additional potential milestone in the agreement are up to EUR 825 million. Together with double-digit royalties outside Europe and 50% profit sharing in Europe.

Turning to slide 15, I'll move now to our next generation ADC pipeline. Beyond IPH4502, we are using our internal capabilities and technology to build a broad portfolio of differentiated ADC candidates. Turning to slide 16, leveraging our antibody discovery and engineering expertise, we have built a comprehensive ADC platform to develop a portfolio of next-generation ADCs designed to overcome the limitation of the current ones. Building on IPH4502 linker, which stability in patients is demonstrated by our emerging clinical data, we are developing a drug candidate portfolio around 3 approaches.

First, dual targeted bispecific ADCs to address tumor antigen heterogeneity and to expand addressable indication compared to single tumor antigen targeting. Second, bispecific ADCs with enhanced internalization to unlock the activity in antigen low expressing tumors. And finally, dual payload ADCs using complementary mechanism of action to overcome resistance.

I now hand over to Frederic for our financial results.

Thank you, Yannis. I'll now provide a brief overview of our financial position for the first half of 2026. Turning to slide 18. So, as of June 30, 2026, our cash, cash equivalents, and financial assets were amounting for EUR 21.4 million. That balance does not include the $75 million Sobi upfront payment, equivalent to EUR 65 million, nor the proceeds from the EUR 30 million equity offering.

The offering represents EUR 30 million on gross proceeds or approximately EUR 28 million in expected net proceeds. The primary use of proceeds is the continued clinical development of IPH4502, the advancements of our preclinical ADC portfolio, and as well as general corporate purposes. Together with the Sobi upfront payment, these proceeds are expected to extend our cash runway through the end of the first quarter of 2028.

I'll now hand over to Jonathan.

Thank you, Frederic. Moving to slide 20. And turning to our key catalysts for the remainder of 2026. For lacutamab, following closing of the strategic partnership with Sobi, TELLOMAK-3 has been initiated with the first patient planned for the first quarter of 2027, followed by a plan filing for accelerated approval in the second half of 2027.

For IPH4502, dose escalation enrollment is complete with preliminary anti-tumor activity and a favorable safety profile observed to date. We will report initial Phase I dose escalation data at the EORTC-NCI-AACR meeting on November 18, 2026. And for monalizumab, PACIFIC-9 enrollment is complete, with the Phase III readout expected in the second half of this year. So we have 3 important near-term catalysts across our focus portfolio, together with a strengthened financial position that supports our continued execution of these priorities.

With that, operator, we are ready to open the call for questions.

We will now begin the question and answer session. [Operator Instructions] Your first question comes from the line of Daina Graybosch with Leerink Partners.

Congrats on the updates. So just one for me. Bill on for Daina. So we've seen the prior exatecan-based ADC show some pretty good activity in the post-Padcev setting, but it did have some pretty high heme toxicities. Can you talk about IPH4502 stable linker design and sort of what gives you confidence you won't see the same sort of issues?

Maybe Yannis, you can take that one.

Yes, maybe I can start and let Markus comment. I mean, we have worked on the design of the linker and based on what we have seen at ASCO by others with their own linker, it seems that the stability of our linker that we have seen in preclinical models, including in non-human primates, seems to be translated into the human situation, leading to a very limited release of a free payload, which is one of the reasons of the systemic hematological toxicity of some ADCs.

Yes, what we can add is the Lilly data that have been released recently actually state that based on their own data that have seen in the trial. So the instable linker was used as an explanation for the hematologic toxicity in this data set.

Your next question comes from the line of Jeet Mukherjee with US Bancorp BTIG.

Pending an accelerated approval there, could you speak to the potential for frontline off-label use for lacutamab in Sézary syndrome, given that seems to be the case with mogamulizumab?

Yeah, maybe I will take that question, Jeet. So our expectation is that lacutamab will be listed in the NCCN guidelines, following the accelerated approval for both Sézary syndrome and for mycosis fungoides. I think with that listing, it seems to leave it open for physicians to be able to use the product across the different lines of therapy. So our expectation based on the safety profile of lacutamab, which is pretty benign, we expect that you will see some off-label usage in the first-line setting. And so, yes, I mean, I think there's an expectation you will see that.

And also, despite the fact that the accelerated approval will be in Sézary syndrome, there will also be an expectation based on the potential listing in the NCCN guidelines for mycosis fungoides that you will also see usage in MF. Hopefully, that answers your question.

Great. I appreciate that. Maybe just 2 other quick follow-ups. Just any initial thoughts on pricing? Do you think you could price at a premium to mogamulizumab? And then separately on PACIFIC-9, in terms of just the update format, anticipate perhaps a press release at minimum from AstraZeneca. But will Innate have their own press release and analyst call as well?

Yes. So in terms of pricing, we have completed pricing research in the U.S., which was conducted by ZS Associates. And what we were able to establish with U.S. payers was that we can price lacutamab between $500,000 and $625,000 per patient per annum. And that will be supported by our clinical data and the NCCN listing. So there is an expectation here that you will be able to achieve premium pricing, particularly in an indication like Sézary syndrome with a relatively low incidence, and then be able to carry that forward into the mycosis fungoides indication, which is a larger indication, but still an orphan disease. So that's pricing.

So -- and then with respect to PACIFIC-9, you're correct. The expectation is that there will be a press release from AstraZeneca when the results are available. And we would also look to press release that as well and potentially do some analyst calls following the availability of that primary endpoint data. Hopefully, that answers the question.

The next question will be read by Stephanie Cornen. Stephanie.

Yes, so we have a question from Clemence Thiers from Stifel. The first question is, as dose escalation and cohort expansion enrollment are now complete, should we expect the initial ENA dataset to be primarily a safety pharmacology update or mature enough to inform subsequent development decisions?

So Markus, maybe you can take that question.

Yeah, the question is almost the answer. So, this is out of 11 different indications and 76 patients. So we are expecting to see relevant and informative safety data. And we are also expecting response data from patients. And this will inform our next steps. We need to fully run the tables and we will review and disclose that as proposed on the ENA meeting.

And there is another question from Clemence. With the strengthened balance sheet following the recent financing, how far along the development path could you advance IPH4502 on your own?

So maybe that so -- I think you're all aware that we did a small equity raise of EUR 30 million a couple of weeks ago. The rationale behind that equity raise was to be able to progress seamlessly into the next steps for IPH4502. So we're well positioned now to be able to move into the next steps, whatever that will be, as the data will dictate what that is, whether it's dose optimization, and we're equipped to be able to do that.

If we would need to broaden the program, if the data supports going to potentially additional tumor types, then that would require additional funding to be able to conduct multiple dose optimizations across different tumor types. But at least for the initial steps, we're funded to be able to take those steps and take the product forward seamlessly into dose optimization. Hopefully, that answers the question again.

We have now reached the end of the Q&A session. I will turn the call back to Jonathan Dickinson, CEO, for closing remarks.

So thank you very much everybody for joining us today for our update and following our H1 results. We look forward to updating you as we progress through the important catalysts that we outlined today, which come across the remainder of the year. So thank you for your time and see you soon.

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

Hello, everyone. Thank you for joining us, and welcome to the Innate Pharma webcast call. [Operator Instructions] I will now hand the conference over to Stephanie Cornen, Vice President of Investor Relations and Communications at Innate Pharma. Please go ahead.

Good morning, and good afternoon, everyone. Thank you for joining us for the conference call. Before we begin, I would like to remind everyone that today's presentation includes forward-looking statements based on current expectations. These statements involve risks and uncertainties that could cause actual results to differ materially.

With that, I will now hand it over to Jonathan.

Thank you, Stephanie, and thank you, everybody, for joining us this morning in the U.S., this afternoon in Europe to discuss this morning's announcement of Innate Pharma's EUR 30 million equity raise. This week has been a very busy and important week for Innate Pharma, putting in place the critical elements, which allow continued advancement of the strategic agenda, which we announced in September last year.

As a reminder, this strategic agenda includes a number of items. First, advancing lacutamab into the confirmatory TELLOMAK-3 Phase III study in cutaneous T-cell lymphoma, which has already been greenlighted by the FDA. Study initiation allows advancement towards the BLA filing for Sézary syndrome under the FDA breakthrough therapy designation once patient recruitment is ongoing. The strategic partnership with Sobi, which was announced on Monday, allows initiation of the TELLOMAK-3 study. As a reminder, Innate will continue to run the study based on our extensive experience and expertise in CTCL.

At closing, which is subject to conditions, including antitrust clearance, Sobi will pay Innate a USD 75 million upfront as well as up to USD 40 million in near-term milestones associated with the Sézary syndrome accelerated approval. There is subsequently an additional USD 465 million of opt-in regulatory and commercial milestones as well as double-digit tiered royalties on future lacutamab sales. Sobi will take on the full global commercialization following the accelerated approval. The Sobi partnership now allows Innate to proceed at full speed with lacutamab using the proceeds of the agreement.

Second on the strategic agenda is the advancement of IPH4502, our second-generation differentiated Nectin-4 targeted ADC, which has shown preclinical activity in the PADCEV resistance setting as well as in tumor models of low Nectin-4 expression. We communicated on July 21 that we have completed enrollment in the dose escalation study with 76 patients. To date, we have seen preliminary clinical activity, including in the post-PADCEV urothelial cancer setting, where there is high unmet medical need and no standard of care as well as in non-small cell lung cancer and head and neck cancer. We also observed a favorable safety profile to date with limited hematological toxicity, supporting the hypothesis that our proprietary linker minimizes the release of payload into the circulation.

The dose escalation results will guide the next steps for development and the data will be presented at a medical conference before year-end. And the third part of our strategic agenda is the advancement of our ADC preclinical portfolio, building on the IPH4502 linker, which has shown stability in patients already. So -- with the ADC preclinical portfolio, we're following 3 approaches. The first is a dual targeted bispecifics approach to address tumor antigen heterogeneity and expand addressable indications compared to single tumor antigen targeting. The second part of the approach is bispecific ADCs with enhanced internalization to unlock activity in tumors with low antigen expression.

And the third part is using novel dual payload ADCs using complementary mechanisms of action to overcome resistance. The EUR 30 million equity raise, which was announced this morning, allows Innate to progress this strategic agenda, starting with seamless progression of IPH4502 into next development steps based on the data from the dose escalation Phase I and then progression of our next wave of preclinical ADCs towards candidate selection and IND-enabling studies. Also on our strategic agenda is next steps for monalizumab, our NKG2A targeted antibody, which is being developed with AstraZeneca in Stage III non-resectable non-small cell lung cancer. The primary completion date for the PACIFIC-9 study is the end of September with data for the primary endpoint expected by year-end. This is important for Innate and if positive, represents a significant future source of value for Innate with up to $825 million of potential milestones, a 50% profit share for Europe and double-digit royalties on sales outside of Europe, including the U.S. market. The EUR 30 million raise, together with the USD 75 million upfront payment payable upon closing of the strategic partnership with Sobi extends our projected cash runway through Q1 2028. The focus now is on execution and delivering against our highlighted strategic priorities. Thank you for your attention, and we can now open the line for questions.

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

I wonder for IPH4502, if you can give us any more guidance on how many patients in follow-up you'll have in the 3 highlighted indications, so the post-PADCEV, bladder, head and neck and lung. And then I have a follow-up after that.

So maybe I can take that one, Daina. So we've not given any guidance on the specific number of patients in each of the indications. What we've said is we expect to have 10 to 15 patients at the go-forward pharmacological doses in each of those indications. In terms of the amount of follow-up, as you can imagine, the last patients were recruited in the middle of July, and we will need to follow those patients and have the first scans, to be able to have efficacy data on all of the patients. So that leads us to a time point later in the year. And hence, the guidance that we will be presenting at a medical conference later in the year. I think most people have deduced that's not ESMO, so a subsequent medical conference.

Got it. And then we've had a lot of exatecan ADC readouts recently with, I'd say, wildly different therapeutic indices. You have the Tubulis one that was at ASCO. You have a Lilly one at ASCO. You have a Sutro one this week. I wonder if you could speak to more about why you think there's differentiation in the therapeutic index across these ADCs and what we should expect and why we should be excited about IPH4502?

Maybe I will let Yannis take that one. Do we have Yannis on the line? I don't think we do. So maybe I will give it my best shot and maybe Stephanie can jump in. So I think what we have communicated, Daina, is that what we've seen so far is that our linker, I think, benchmarks with the best linkers that we've seen out there. We've also been able to achieve doses which are in line with other Topo I and exatecan-based payloads. So we're at that point where with other targets at the particular dose we're at, we've basically seen efficacy with those other products. So I think that gives us a good sense of where we're at.

I think the other thing that we found very encouraging was the Lilly data set with their ADC with the [ camptothecin 98 ] payload at ASCO in terms of the fact that it validated the approach of coming with a TOPO1-based ADC targeting Nectin-4 post-PADCEV. So we took that as a validation, of course, with the caveats of the Lilly ADC and the payload being metabolized through 2D6 and having this genetic variation and potential liability associated with that. So if we pull that together, I think we're feeling quite confident that we have a window here from a dosing perspective where IPH4502 will be effective. And I think we've mentioned we have seen responses, including in the post-PADCEV setting. And basically, every one of our urothelial cancer patients that's been treated in our study has had PADCEV. And I think all but one has also received pembro.

So really, these patients have had the best standard of care. I think when you see any level of activity in this particular patient group, take into account where we've recruited these patients because the Phase I sites are open in -- with 5 sites in the U.S. and 2 sites in France. So all of these patients have had the best standard of care and are progressing on therapy when they enter the study. So when we see activity, we're genuinely seeing something real here. And we continue to be excited about that. Hopefully, that's answered part of your question. We have Yannis on the line now. So I don't know whether he wants to add anything to that. Yannis? You are on mute Yannis.

Okay. I'm sorry about that, Daina. It looks like Yannis is unable to speak. He's actually on vacation this week, somewhere where the Internet connection is not great, and he was dialing in at the last minute. So hopefully, I've addressed your question.

Maybe Yannis can follow up when he's back from his vacation.

Thank you. Thank you Daina. I think we can follow up offline maybe afterwards with Yannis.

Your next question comes from the line of Swayampakula Ramakanth with H.C. Wainwright.

Can you hear me?

Yes, we can hear you RK.

Okay. Just trying to understand the impetus behind the raise today. Is this EUR 30 million, is this going to -- is this to be thought of as a bridging funding between now and the close? Or is this so that you can hasten some of the work that you need to do on TELLOMAK-3 from here on?

So the rationale for the raise, RK, is basically to allow us to continue to move seamlessly into the next steps for IPH4502. What we didn't want to do is present the data later in the year and then have to go out and raise money to be able to go into the next steps. So having done this raise now, we can plan for the next steps for IPH4502 and dependent on what the data shows us, we can go seamlessly into those next steps. This is a competitive space. And I think based on where Lilly's recent presentation and some of the ambiguity around their program, we think now we're probably close to the front of the pack of at least Western-based Nectin-4 ADCs.

So we want to be able to continue the momentum and speed with 4502. And we also want to be able to take the next steps for our preclinical ADC portfolio. We have an exciting portfolio of preclinical ADCs, which we will reveal in due course at the appropriate time. Based on the fact that we have a linker that we believe is very effective now and has proven itself in the Phase I study, we're in a good place to be able to take advantage of our antibody engineering capabilities and produce bispecifics, but also to look at ways of improving internalization and also to look at novel dual payloads. And I don't mean combining MMAE and the TOPO I, I mean some genuinely innovative approaches from a payload perspective that will bring something different to the table. So the raise allows us to continue to move those programs forward now that we have the resourcing in place to be able to take TELLOMAK-3 into the next steps and to move forward. So this is really about making sure we can move fast on the rest of the portfolio.

A quick follow-up. So just following up on Daina's question. At what point, hopefully this year, that we would get a good picture of where 4502 is in the development pathway? And what are the different indications that you would certainly go into and also reveal some of the pipeline molecules that you're talking about. Is this going to be happening sometime within the rest of 2026? Or should we wait up to '27?

I think for the pipeline, it will be sometime in 2027. We would start to potentially communicate on those aspects. For 4502, we'll get a better sense of the data when it's presented at the medical conference later in the year. So I think that's basically the key piece here. And the next steps will obviously be based on the data. And we've not seen the full data set yet. So we need to see that data set. And that will dictate which tumor types we go into.

What we have said is that we've seen activity in urothelial cancer post-PADCEV. And we've also seen activity in head and neck cancer and non-small cell lung cancer. So I think they are likely candidates, but that, of course, has to be validated by the complete data set, which we will see later in the year.

Your next question comes from the line of Jeet Mukherjee with U.S. Bancorp BTIG.

Congrats on the financing. One question from me. Any additional thoughts around expansion opportunities for monalizumab outside of oncology, such as IPF or other fibrosis-related indications? I'm sure you saw the Science Translational Medicine article that came out a few months ago, highlighting monalizumab's potential in such indications. So I was curious regarding your thoughts around going in that direction.

Thanks, Jeet. We were, of course, very happy to see that publication. I think it's another potential avenue for monalizumab. What I would say at this moment in time, we're really focusing on the readout from PACIFIC-9. That's our critical gating criteria here. And I think if we see a positive study for -- with PACIFIC-9 in non-small cell lung cancer, then I think that's the time to really further evaluate other potential opportunities. And I think one thing just to remind of is that AZ have the license through the collaboration agreement for monalizumab for oncology and any additional indications. So the fibrosis indication would be a new indication that wouldn't fall under the collaboration agreement. So I think the bottom line is we'll wait and see what PACIFIC-9 delivers, and then I think we'll take some informed steps after that.

And if you don't mind, one additional follow-up. Could you just remind us what would be due upfront should PACIFIC-9 be positive?

We have not basically disclosed the schedule of the milestones. I think what we said is they're up to $400 million of development and regulatory milestones, and they follow the standard type of criteria that you would see for these sorts of deals. So I think you can probably work out what they are quite easily.

There are no further questions at this time. This concludes today's call. Thank you for attending. You may now disconnect.

Ladies and gentlemen, thank you for joining, and welcome to the Innate Pharma First Quarter 2026 Business Update and Financial Results. [Operator Instructions] I will now hand the conference over to Stephanie Cornen, Vice President of Investor Relations, Communications and Commercial Strategy at Innate Pharma. Please go ahead.

Good morning, and good afternoon, everyone. Thank you for joining us for Innate Pharma's Q1 2026 Business Update and Financial Results Conference Call. The press release and today's presentation are both available on the IR section of our website. Before we begin, I would like to remind everyone that today's presentation includes forward-looking statements based on current expectations. These statements involve risks and uncertainties that could cause actual results to differ materially.

To briefly cover today's agenda, our CEO, Jonathan Dickinson, will begin with a strategic overview and outlook. Sonia Quaratino, our Chief Medical Officer; and Yannis Morel, our Chief Operating Officer and I will then provide updates on lacutamab, IPH4502 and next-generation ADCs as well as AstraZeneca partner program, including monalizumab and IPH5201. Jonathan will then return with closing remarks. Frederic Lombard, our CFO, will join us for the Q&A. With that, I will now hand it over to Jonathan Dickinson.

Thank you, Stephanie. Good morning to those joining from the U.S., and good afternoon to our European participants.

Turning to Slide 5. We continue to execute against our strategy, which is focused on our 3 priority assets with discipline, and we're pleased with the strong progress we are seeing to date. Starting with lacutamab, our anti-CIR3DL2 monoclonal antibody, which is being developed in cutaneous T-cell lymphoma or CTCL. As you remember, we received the FDA clearance to proceed with the TELLOMAT-3 Phase III trial for lacutamab in CTCL, and we expect to be able to initiate the study in the second half of 2026. We have made progress in negotiating non-dilutive financing options for lacutamab, including potential pharma partnerships and royalty-based structures. From a commercial perspective, we believe that lacutamab represents a meaningful opportunity in CTCL in both the United States and Europe with additional life cycle expansion opportunities in peripheral T-cell lymphoma.

Moving to IPH4502, our differentiated Nectin-4 ADC, which is being evaluated in advanced solid tumors. The Phase I study is ongoing and approaching completion of enrollment in the dose escalation phase and backfill cohorts. As highlighted on the slide, we continue to observe preliminary antitumor activity in heavily pretreated patients, including in urothelial cancer patients previously treated with EV. We believe that IPH4502 may represent a differentiated opportunity, both in the post-PADCEV urothelial cancer setting and potentially across a broader range of solid tumors.

And finally, turning to monalizumab, our AstraZeneca partnered anti-NKG2A monoclonal antibody, which is being developed in non-small cell lung cancer. The ongoing PACIFIC-9 Phase III study remains on track for a planned readout in the second half of 2026. From a financial perspective, the partnership also continues to represent a potentially important source of future value for Innate, including potential milestones, profit sharing in Europe and royalties in the United States and the rest of world. Overall, we believe these 3 assets provide Innate with a focused portfolio of differentiated clinical stage opportunities spanning both proprietary and partnered programs. I'll now hand over to Sonia and Stephanie for a more detailed review of the lacutamab program.

Thank you, Jonathan. Turning to Slide 7. Lacutamab continues to progress towards initiation of the TELLOMAK-3 confirmatory Phase III trial and the potential accelerated approval pathway in Sezary syndrome. As a reminder, the Phase II TELLOMAK study has demonstrated clinical meaningful and durable activity in both mycosis fungoides and Sezary syndrome, including improvement in quality of life with a favorable safety and tolerability profile supporting potential for long-term treatment.

Based on this data, lacutamab has received breakthrough therapy designation from the FDA in relapsed or refractory Sezary syndrome. It has previously received Fast Track designation from the FDA, prime designation from EMA and orphan drug status in both United States and Europe. The Phase II data from the TELLOMAK trial also support the potential accelerated approval filing in Sézary syndrome once the confirmatory Phase III trial is underway.

In the next slide, the planned TELLOMAK-3 is an open-label multicenter randomized comparative study to demonstrate the efficacy and safety of lacutamab in 2 separate cohorts of patients with cutaneous T-cell lymphoma who have failed at least 1 prior systemic therapy. In Cohort 1, patients with any stage Sezary syndrome who have failed at least 1 prior line of systemic therapy, including mogamulizumab, will be randomized 1:1 to either lacutamab oleclumab.

In Cohort 2, patients with MS ranging from Stage Ib to 4 who have failed at least 1 prior line of systemic therapy will be randomized 1:1 to either lacutamab or mogamulizumab. Both cohorts will be randomized 1:1 and randomization will be stratified according to disease stage and region. The primary endpoint for both cohorts is progression-free survival assessed by blinded independent central review. The secondary endpoint for the secondary cohort is overall survival, while the key secondary endpoints for the MS cohort are quality of life and pruritus.

TELLOMAK-3 study is designed to serve as the confirmatory trial for Sezary syndrome while also supporting full approval in mycosis fungoides. And from a regulatory standpoint, we have received FDA clearance to proceed with this clinical trial protocol, and we continue towards Phase III initiation expected in the second half of 2026. Stephanie will now go through the commercial opportunity.

Thank you, Sonia. So we continue to believe lacutamab represents an attractive commercial opportunity supported by a focused and efficient commercial foot syndrome -- based on recent analysis, we estimate 30 Sézary syndrome in the U.S. with a prevalence of around 1,000 patients, the majority of whom are treated in a limited number of specialized academic centers. Mucositides larger 3,000 incident patients and the prevalence of around 12,000 patients in the U.S. from an analysis conducted by Associates are now available in the EHA 2026 online -- this is a highly concentrated treatment landscape with over 85% of patients managed in academic centers and a large proportion treated within approximately 50 key institution. This concentration enables a targeted commercial approach with limited infrastructure.

At the same time, Sézary syndrome and mycosis fungoides share the same prescriber base, which is a critical point from a commercial perspective. This means that an initial launch in Sézary syndrome is not a stand-alone opportunity, but a direct entry point into the broader CTC Importantly, when looking at the current market, moamizumab generated approximately $300 million in annual sales in 2025 as planned and is projected to reach $350 million in 2026 with strong adoption in Sézary syndrome and more limited penetration in mycosis fungoides. This provides a relevant benchmark for the market opportunity and highlights the potential for our therapy to capture share across both Sézary syndrome and mycosis fungoides.

From a value perspective, key drivers include treatment duration, which is supported by durability of responses, pricing and market share across a broader eligible patient population. Sézary syndrome, expanding to over $500 million across Sézary syndrome and mycodungoid in the second setting with additional upside as lacutamab moves into earlier lines of therapy and broader patient segments over time. I will now hand it over to Yannis to start the update on IPH4502.

Thank you, Stephanie. IH4502velntiated ADC, which is in Phase I. Slide 11, IH450 has been designed to overcome the limitation of the third-generation Nectin-4 ADCs and to deliver a more favorable therapeutic profile across multiple solid tumors. The drug candidate is based on a proprietary humanized antibody that binds to a distant nonoverlapping epitope on the Nectin-4 target. It is combined with a stable cleavable and heroinic linker, which supports high systemic exposure of the ADC while minimizing the release of freeexotican in circulation and therefore, reducing the risk of off-target toxicity. The payload is a potent topoisomerase 1 inhibitor with strong bystander activity enabling to target not only Nectin-4 expressing tumor cells but also neighboring cells with lower or heterogeneous expression. Moreover, it is not sensitive to the mechanism of drug resistance related to MMA, allowing to address patients who have been pre-exposed to PDC.

Next slide shows how IPH4502 is positioned within the evolving Nectin-4 ADC landscape. The first wave of Nectin-4 ADC largely relied on the MMAE payloads, including enfortumab vedotin. While EV has validated Nectin-4 as an important ADC target, other MMAE-based approach will most likely face similar limitation than EV, such as MDR1 resistance and peripheral neuropathy. IPH4502 is designed to address these limitations through payload and differentiated linker design -- we believe this creates a potential opportunity in bladder cancer, particularly in the post setting as well as across multiple tumor types with low or moderate Nectin-4 expression. Overall, we believe ITH4502 has a potential to be best-in-class TPO1ectin-4ADC driven by its differentiated design.

On the next slide, we show newly generated preclinical data that continue to reinforce the best-in-class potential of ITH4502 as a T1 Nectin-4 ADC. You can see that in both high and low Nectin-4 expressing models, ITH4502 demonstrates robust antitumor activity. However, the key differentiation versus other TO1ectin-4 clinical ADCs appears in model with low Nectin4 express H502 maintains meaningful antitumor efficacy, while the other clinical ADC show a clear loss of activity. This is really important as it highlights the unique ability of IPH2502 to remain active in tumors with lower target expression. Overall, across multiple in vivo models, we constantly observe better efficacy for IPH2502, supporting its best-in-class agent potential, particularly in low to moderate Nectin-4 expressing tumors. Now turning to Sonia for the clinical update.

Thanks, Yannis. Turning to Slide 14. We see the outline of the clinical design of the Phase I of IPH4502 study. We are currently evaluating this asset in a first-in-human Phase I open-label multicenter study in patients with advanced solid tumors known to express Nectin-4. We collect tumor biopsies at baseline from these patients and evaluated the Nectin-4 expression retrospectively. The study started in January 2025 and runs a specialized cancer sites in the U.S. and in France. This first-in-human study is guided by an adaptive Bing designed with backfill cohorts with the objective to assess safety, tolerability and preliminary antitumor activity. Cohorts are backfilled at lower doses during the dose-finding trial while prioritizing the dose escalation cohort to explore a higher dose. These backfills help to generate more data in terms of safety, PK, efficacy at a given dose level.

Enrollment in the dose escalation part of the study has progressed well and Phase I dose escalation and cohort enrichment are nearing to completion and the maximum tolerated dose has been reached. We have defined a clear therapeutic window with a favorable safety profile to date and see preliminary efficacy at different dose level within the defined therapeutic window in heavily pretreated patients with advanced solid tumor, including urothelial cancer patients who have progressed after mabenitin.

Turning to next slide. We see that we highlighted the growing therapeutic gap in bladder cancer after progression on EV plus pembro. Despite the advancement of unfortunate vedotin that has introduced in urothelial cancer patients, 2/3 of these patients still experience disease progression within 2 years and the management of patients who progress to this regimen has become a critical challenge. As of 2026, there is no single established gold standard for second-line therapy after EV pembro, but several strategies are utilized based on patient-specific factors.

For patients who received first-line EV plus pembro without prior platinum exposure, platinum-based chemotherapy, cisplatin or carboplatin with gemcitabine is the preferred subsequent option. Real-world data indicates modest efficacy with a median real-world time to next therapy of approximately 3 to 4.7 months. Due to the limited efficacy of current second-line options, enrollment in clinical trials is strongly prioritized in 2026 guidelines to investigate novel mechanism of action and combination therapies. This creates a significant unmet need in the post EV plus pro setting, and we believe IPH4502 is well positioned to potentially fill this therapeutic gap.

In the next slide, we'll see our development vision for IPH4502, which includes both bladder cancer and broader solid tumor opportunities. In bladder cancer, we see an opportunity to address the growing population of metastatic urothelial cancer patients who progress after EV-based therapy, where Nectin-4 expression appears to remain stable in tumor from patients who progress after EV. Over time, we also see potential to move to earlier lines, including in combination with anti-PD-1 therapy. Beyond bladder cancer, we believe IPH4502 may also have potential across multiple solid tumors with low to medium Nectin-4 expression, and we intend to consolidate the signals observed in the dose escalation study. Overall, our objective is to build a broad and modular clinical development strategy, starting with high unmet need populations and expanding into earlier lines of therapy and additional tumor types over time, depending on the emerging data.

Now before we move ahead with our partner program, this slide highlights how we have built a comprehensive ADC discovery platform to develop a portfolio of next-generation ADCs designed to overcome the limitation of the current ones. Building on the IPH4502 linker, which is -- which stability in patients is clearly demonstrated by our emerging clinical data, we are developing a drug candidate portfolio around three approaches. Dual targeted bispecific ADCs to address tumor antigen heterogeneity and to expand addressable indications compared to single tumor antigen targeting. Then bispecific ADC with enhanced internalization to unlock the activity in the low expressing tumors. And finally, dual payload ADCs using complementary mechanism of action to overcome resistance. Our next wave of ADC is currently progressing towards candidate selection and then IND-enabling studies. Now turning to Sonia.

Turning to Slide 19. We now provide an update on our AstraZeneca partnered programs, monalizumab and IPH5201 -- in the next slide, let's start with monalizumab. The PACIFIC-9 is a major Phase III randomized double-blind study to demonstrate that dual immunotherapy can significantly increase the survival rate of patients with unresectable Stage III non-small cell lung cancer who have not progressed following definitive concurrent chemo radiotherapy. The rationale for this trial is supported by 3 Phase II studies in early-stage non-small cell lung cancer, including COAST, NeoCOAST and NOCOST-2 studies. These studies reinforced the potential of targeting the NKG2A pathway to enhance the innate immune response alongside PD-L1 inhibition in early-stage lung cancer. And enrollment in PACIFIC-9 has been completed, and now we look forward to the data expected in the second half of 2026.

Now in the next slide, let's move to another asset this time in the adenosine pathway that is also codeveloped with AstraZeneca, IPH5201 that blocks CD39 an enzyme that converts ATP into adenosine, which suppress immune system. By preventing this conversion, the therapy is really driving the immune system within the tumor microenvironment. IPH5201 is currently evaluated in the MATIS Phase II trial in combination with durvalumab and neoadjuvant platinum-based chemotherapy in patients with resettable non-small cell lung cancer.

The recent preplanned interim data presented at the ACR Annual Meeting on April 21 during a clinical trial plenary session has significantly strengthened the case for this anti-CD39 antibody. The interim analysis of 40 patients demonstrated that the combination of IPH5201, durvalumab and chemotherapy is achieving pathological complete response rates that compare very favorably to the current benchmark. The primary endpoint of pathological complete response showed a strong correlation with PD-L1 expression level. Based on the robust 35.7% PCR rate in PD-L1 above 1% and 50% PCR rate in patients with tumor with PD-L1 expression of at least 50%. The study is now moving forward by focusing recruitment exclusively on patients with PD-L1 positive tumors.

No new or unexpected safety signals were identified. The combination was generally well tolerated with most adverse events being grade 1 or 2. CD3 cell density in tumors is warrant to be further investigated as an emerging biomarker for predicting pathological complete response in IH5201usurvalumab treatment. Overall, this encouraging early findings support continued investigation of IPH5201 in non-small cell lung cancer.

Coming to Slide 22. Slide 22 summarizes the financial highlights of our AstraZeneca partnerships. For monalizumab, the agreements amount up to $1.275 billion of milestones. We have already received $450 million and remain eligible to additional $825 million of potential payments AstraZeneca will book sales and Pharma will receive double-digit royalties on sales in the U.S. and rest of the world. In Europe, since Innate Pharma is contributing to 30% of the funding for the Phase III trial, we will get 50% of the profits and have the option to co-promote the drug ForX5201, the agreement is worth up to $85 million in milestones.

To date, we already received $60 million and remain eligible to $825 million. This agreement having a similar structure than the monalizumab Innate Pharma has also the option to Phase III trial in order to get 50% of the European profit and co-promotion rights. Otherwise, Innate Pharma will receive royalty in Europe like in the U.S. and rest of the Together, this partner program provides IM with meaningful potential nondilutive cash through future milestones, royalties and profit sharing economics. I will now hand over to Jonathan for closing remarks.

Thank you, Yannis, Sonia and Stephanie. So turning to our upcoming milestones. Over the coming quarters, we expect several important catalysts across our priority assets. For lacutamab, we remain focused on initiating the TELLOMAT-3 confirmatory Phase III study in the second half of 2026, subject to financing. For IPH-4502, the study is progressing very well, and we have observed preliminary antitumor activity with a favorable safety profile to date, including in patients with urothelial cancer relapsed or refractory to EV, which is a signal that we're starting to validate our preclinical hypothesis.

We look forward to continued maturation of the emerging clinical data set following completion of dose escalation and cohort enrichment. And for monalizumab, the PACIFIC -- the Phase III PACIFIC-9 trial in non-small cell lung cancer has completed enrollment with data expected for the primary endpoint in the second half of 2026. Taken together, these 3 programs provide a clear set of value-driving catalysts across our portfolio. With a cash position of EUR 25.4 million as of March 31, 2026, we remain disciplined in our execution and focused on advancing programs that we believe have the potential to deliver meaningful value for both patients and shareholders. With that, operator, we're now ready to open the call for questions.

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

I have a question on MATIS and CD39 since that was presented recently. The discussion at AACR pointed out that while the triplet compares quite favorably to prior outcomes with durvalumab plus chemotherapy, it looks pretty similar to prior outcomes with the PD-1 plus chemotherapy in the neoadjuvant setting. And I wonder what gives you confidence given that sort of range of broader benchmarks? And in the next part of the MATIS trial, is there a certain threshold of activity or biomarker finding that AZ and you are looking for to take it forward into Phase III?

I think Sonia between the two of you. I know you want to start and then Jan can fill in on the second.

Sure. Of course, you are right to say that this interim data show that the rate -- the PR rate that we observed at this interim analysis may be comparable to what has been seen in other trials using pembrolizumab. But when you are benchmarking, of course, with the same PD-L1 backbone that is durvalumab, you have to admit that there is a significant uplift this therapy as a single agent. And so in that respect, this has definitely produced an increase of pathological complete response. That is not matched by an increase of toxicities, which is remarkable. We've also seen that, for instance, in PCR high expression, this PCR rate goes even higher. Of course, we cannot predict where this trial might materialize in a Phase III. But so far, the data looks very promising.

Yes, like Sona said, I mean, this trial has basically is providing 2 level of information. So that when you add CD39 on top of an active PD-1 blocker, it's increasing the PCR rate. So for us, it's clearly if the signal is confirmed on the additional patients really validating the targeting of this checkpoint in the adenosine pathway plus targeting the, I would say, the efficacy of our drug candidate. Then whether will decide to take the license on this one and move it into Phase III, that's another question that is more actually for A. But from a perspective, it's very important to confirm and to establish that the blocking of CD39 can be effective in that perspective.

Your next question comes from the line of Christopher Liu with Lucid Capital Markets.

Maybe just two for me about 4502. So for the first question, are there any additional details you can give us on the profile of the drug at the go-forward dose? And for the second question, what do you see as the most compelling indications outside of bladder cancer for the asset considering market opportunity and potential competition?

Thanks for the question. At this moment, we can only say we have seen some efficacy readouts in a different dose level within the therapeutic window. And we will be a bit more specific around both dose levels as well as potential indications to bring forward at clinical conference this year.

Your next question comes from the line of Swayampakula Ramakan with H.C. Wainwright.

This is RK from H.C. Wainwright. Regarding the Nectin-4 ADC... You -- it's just Lilly's product, which are in Phase I and Bicycle recently deprioritized their product. So how do you see the competition going forward? And what sort of data would you be able to release in the next 6 months or so, so we have an understanding of how you are poised against the competition?

Well, thanks for the question. In fairness, we don't know much about Lilly so far. And we can only speculate that perhaps the asset was deprioritized because it doesn't look as good as the other Nectin-4 program that they also have in clinical development. We do not have the data because they have not been shared, and we can only see when the abstract will be available on the 21st of May. Yes. Sorry for not adding more color, but we don't have... details.

Yes. And then in terms of the data, I think Sonia mentioned earlier that we expect to present the data at a medical conference sometime Later in the second half of the year. And I think at that point, you will see go-forward indications and the data in urothelial cancer and yes, and next steps for the program.

Okay. And then on the collaboration with AstraZeneca, have you elected for the 30% funding on the PACIFIC-9? And what's -- is there any residual cash obligations between you and them?

I mean, between now and a positive readout... I just to qualify a couple of things. So the agreement that we have with AstraZeneca, it's capped at a certain level, and we are actually very close to the cap of the contribution. So there are actually minimal contributions required between now and the data readout.

Your next question comes from the line of Jeet Mukherjee with BTIG.

Two from our side. Just any further color or perspective on the status of the lacutamab partnership discussions? Do you anticipate or feel confident that a deal can be finalized before the third quarter of this year? And the second question, are we expecting any Phase II PTCL data from lacutamab this year as well?

So maybe on the partnerships, maybe I can start off and Yannis can fill in any gaps. So we are very confident that we will execute either a BD partnership or a royalty financing partnership for lacutamab. The discussions are quite advanced, and we would expect to be able to conclude one of those 2 types of partnerships moving forward in the relatively short term. And from our perspective, it doesn't really matter which way we go with either a BD partnership or a royalty financing partnership. We would be running the Phase III confirmatory study. So that will be in our control where we could utilize our expertise that we've developed in the CTCL area from the TELLOMAK-2 study. So we'll make that decision in the coming future, basically based on what's best for the company in terms of the NPVs of the 2 different approaches. So something coming in the future. Yannis, I don't know if you want to.

Short answer is yes, we are confident that we can execute something before Q3...

And just the second question around Phase II.

Yes. PTCL, as you know, is run by the LARC group, and we are towards the completion of this study, but I don't think that this data will materialize before the end of this year. Yes. And we have no further visibility on this study.

Yes. This is an IST, it's under the control of the LSA group. So this is not a place where -- it is independent where we can have control of the time lines. We know that the LSR group are quite excited about lacutamab in combination with the GEMOX chemo regimen, where they're studying this in late-stage patients. And we're optimistic that there will be data at some point in the future, but we can't put a very specific time line on that.

There are no further questions at this time. I will now turn the call back to Jonathan Dickinson, CEO, for closing remarks.

Okay. Thank you, everybody, for attending the earnings call today. We're at a point in time where I think we have some very exciting catalysts coming over the coming months. So just to remind you, on lacutamab, the initiation of the confirmatory Phase III program. For IPH4502, we're expecting to be releasing data on the first-in-human studies at a medical conference before the end of the year. And then on monalizumab, we have the results from the primary endpoint of the PACIFIC-9 study coming before the end of the year. So thank you, everybody, for attending, and we look forward to giving you some updates in the very near future. Thank you.

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

Ladies and gentlemen, thank you for joining us, and welcome to the Innate Pharma Full Year 2025 Earnings Call. [Operator Instructions]

I will now hand the conference over to Stephanie Cornen, Vice President of Investor Relations, Communications and Commercial Strategy at Innate Pharma. Please, Stephanie, go ahead.

Thank you. Good morning and good afternoon, everyone, and thank you for joining us for Innate Pharma's Full Year 2025 Business Update and Financial Results Conference Call. The press release and today's presentation are available on the Investor Relations section of our website.

Before we begin, I would like to remind everyone that today's presentation includes forward-looking statements based on current expectations. These statements involve risks and uncertainties that could cause actual results to differ materially. I will briefly cover today's agenda. Our CEO, Jonathan Dickinson, will begin with a strategic overview and outlook. We will then share updates on our 3 priority program, lacutamab, IPH4502 and monalizumab as well as IPH5201 in partnership with AstraZeneca. Speakers will be our CMO, Sonia Quaratino; our COO, Yannis Morel; and I. Frederic Lombard, CFO, will comment our financial results. Jonathan will return with upcoming catalysts and closing remarks before we open the call for Q&A.

With that, I'll now hand it over to Jonathan.

Thank you, Stephanie. Good morning to those joining from the U.S., and good afternoon to our European audience. Turning to Slide 5. Innate Pharma is a focused oncology company with a clear ambition to deliver high-value, differentiated therapies for patients with significant unmet medical need. Our strength lies in our deep expertise in antibody engineering and our ability to translate this into innovative therapeutic approaches, particularly in immuno-oncology and antibody drug conjugates. Over the years, we have built a pipeline of highly differentiated assets built on targets we believe have high potential to deliver meaningful clinical benefit. Today, we're focused on advancing these assets through late-stage development, combining smart, agile execution with a clear line of sight to key clinical and regulatory milestones.

Turning to Slide 6. Over the past year, we have taken important steps to deliver on our strategic priorities with an execution-driven organization. As we announced previously, we made the decision to prioritize investment on what we believe are our 3 highest value clinical assets, IPH4502, lacutamab and monalizumab. This strategic focus allows us to concentrate our resources where we see the greatest potential to generate clinical impact and long-term value. In parallel, we continue to leverage our internal expertise and platform capabilities to advance the next generation of ADCs. At the same time, we have streamlined the organization to ensure we are fit for purpose with a more agile structure that supports efficient decision-making and disciplined capital allocation. As previously communicated, we implemented a redundancy plan, which is expected to be completed by the end of April.

Turning to Slide 7. We continue to execute against our strategy with discipline across our core programs and are pleased with the strong progress we are seeing. First, as you remember, we received the FDA clearance to proceed with the TELLOMAK-3 Phase III trial with lacutamab in CTCL, and we expect to be able to initiate it in the second half of 2026. In parallel, we are actively advancing discussions with ongoing negotiations on several fronts, including potential pharma partnerships and royalty-based structures. We believe these approaches provide a disciplined path forward to support late-stage development while preserving shareholder value.

Second, we are advancing IPH4502, our novel Nectin-4 ADC, where we see the potential to deliver a differentiated profile and address significant unmet needs across multiple tumor types. IPH4502 is progressing rapidly with early signs of antitumor activity in heavily pretreated patients, including in urothelial cancer previously treated with EV and a favorable safety profile seen to date. We are starting to validate our preclinical hypothesis, which supports a differentiated profile versus MMAE-based approaches. We are currently enriching cohorts at pharmacologically active dose levels in urothelial cancer post EV, and selected additional tumor types and are excited by the progress we are seeing to date.

And third, monalizumab in partnership with AstraZeneca represents an important late-stage asset with the PACIFIC-9 Phase III trial data readout expected in the second half of 2026. Across these programs, we remain focused on driving value, prioritizing key milestones and ensuring that we are well positioned to deliver multiple catalysts over the near and medium term.

With that, I will now hand it over to Sonia.

Thank you, Jonathan. Now moving to Slide 9 and starting with lacutamab, our late-stage asset in cutaneous T-cell lymphoma. As a reminder, the Phase II TELLOMAK study has demonstrated a clinically meaningful and durable activity in both Mycosis Fungoides and Sezary Syndrome, including improvement in quality of life with a favorable safety and tolerability profile, supporting potential for long-term treatment. Building on this data, first, we have established a strong regulatory foundation obtaining Breakthrough Therapy Designation in relapsed or refractory Sezary syndrome as well as Fast Track, PRIME and Orphan Drug Designation.

Second, this data support a potential accelerated approval path in Sezary syndrome, the most aggressive CTCL subtype characterized by high unmet medical need and no standard of care after treatment with mogamulizumab. And lastly, we have received FDA clearance to proceed with the TELLOMAK-3 study, which intends to be a confirmatory study for Sezary Syndrome and the registrational study for Mycosis Fungoides. The initiation of TELLOMAK-3 is planned for the second half of 2026 as we evaluate financing options.

In Slide 10, I will now walk you through the Phase III trial design. The proposed Phase III study, TELLOMAK-3 is an open-label multicenter randomized comparative study to demonstrate the efficacy and safety of lacutamab in 2 separate cohorts of patients with cutaneous T-cell lymphoma who have failed at least 1 prior systemic therapy. In Cohort 1, there will be patients with any stage SS who have failed at least 1 prior line of systemic therapy, including mogamulizumab, and patients will be randomized 1:1 to either lacutamab or romidepsin.

In Cohort 2, patients with MF from Stage 1b to Stage 4 who have failed at least 1 prior line of systemic therapy will be randomized 1:1 to either lacutamab or mogamulizumab. Both cohorts will be randomized 1:1 and randomization will be stratified according to disease stage and region. The primary endpoint for both cohorts is PFS by blinded independent central review. The secondary key endpoint for the SS cohort is overall survival, whilst the key secondary endpoint for Mycosis Fungoides are quality of life and pruritus. As the Sezary Syndrome and Mycosis Fungoides study subpopulation are considered as independent cohorts, answering to distinct objectives, 2 sample sites are estimated to meet the primary endpoint in both SS and MF cohorts independently. As such, the study is powered to demonstrate superiority of lacutamab effect on PFS as compared to romidepsin in patients with SS who received at least 1 prior line of systemic therapy, including mogamolizumab, and that's compared to mogamolizumab in patients with MF who received at least 1 prior line of systemic therapy. From a regulatory standpoint, we have received FDA clearance to proceed with this clinical trial protocol, and we are now progressing towards Phase III initiation expected in the second half of 2026.

Slide 11 outlines the projected regulatory timelines for lacutamab in Sezary Syndrome and Mycosis Fungoides. As previously presented, the Phase II TELLOMAK data in Sezary syndrome are intended to support a potential accelerated approval once the confirmatory Phase III trial is underway. In this context, the TELLOMAK-3 study is designed to serve as a confirmatory trial for SS while also supporting full approval in Mycosis Fungoides. In the MF cohort, the primary endpoint of progression-free survival is expected to support full approval in both U.S. and Europe. Importantly, given the larger patient population in Mycosis Fungoides, we expect enrollment in this cohort to be faster, which may enable an earlier completion of the primary analysis in this indication. From a regulatory standpoint, this represents a stepwise development approach, starting with Sezary Syndrome with the highest medical need and then expanding into broader CTCL population.

From a commercial perspective, we see a focused and attractive opportunity for lacutamab in CTCL starting with Sezary Syndrome. Based on recent real-world data analysis, we estimate approximately 300 incident patients per year in Sezary Syndrome in the U.S. with a prevalence of around 1,000 patients, the majority of whom are treated in a limited number of specialized academic centers. Importantly, this is a highly concentrated treatment landscape with over 85% of patients managed in academic centers and large proportion treated within approximately 50 key institutions. This enables a targeted commercial approach with limited infrastructure. At the same time, Sezary Syndrome and Mycosis Fungoides share the same prescriber base, which is a critical point from a commercial perspective. This means that an initial launch in Sezary Syndrome is not a stand-alone opportunity, but a direct entry point into the broader CTCL market. Mycosis Fungoides represents a significantly larger opportunity with approximately 3,000 incident patients per year and the prevalence of around 12,000 patients in the U.S.

Importantly, when looking at the current market, mogalizumab generated approximately $300 million in annual sales in 2025 as planned and is projected to reach $350 million in 2026 with strong adoption in Sezary syndrome and more limited penetration in Mycosis Fungoides. This provides a relevant benchmark for the market opportunity and highlights the potential for a therapy able to capture share across both Sezary Syndrome and Mycosis Fungoides. From a value perspective, the key driver include treatment duration, supported by the durability of response, pricing and market share across a broader eligible patient population. Taken together, this supports a stepwise commercial strategy starting with an initial opportunity of up to $150 million in Sezary Syndrome expanding to over $500 million across Sezary and Mycosis Fungoides in the second line setting with additional upside as lacutamab moves into earlier line of therapy and broader patient segment over time.

And with that, Yannis and Sonia will now walk you through IPH4502.

Thank you, Stephanie. Turning to Slide 14. On this slide, I would like to highlight why we are particularly excited about our next-generation Nectin-4 ADC program called IPH4502. As mentioned earlier, IPH4502 is a differentiated ADC built to improve both safety and efficacy through a novel design. This molecule is based on a proprietary humanized antibody that binds on the Nectin-4 target to a distant and non-overlapping epitope versus enfortumab. It is combined with a stable, cleavable and hydrophilic linker, which supports high systemic exposure of the ADC while minimizing the release free exatecan in the circulation and therefore, reducing the risk of off-target toxicity.

The payload exatecan is a potent topoisomerase 1 inhibitor with strong bystander activity, enabling it to target not only Nectin-4 expressing tumor cells but also neighboring cells with lower or heterogeneous expression. Importantly, IPH4502 has demonstrated activity in models resistant to enfortumab vedotin, supporting its potential to address tumors that are either refractory to or progress after current standard therapies. Overall, the design of IPH4502 is intended to overcome key limitations of third-generation Nectin-4 ADCs and to deliver a more favorable therapeutic profile.

Slide 15. Here, we position IPH4502 within the current Nectin-4 ADC landscape and highlight its key differentiating feature. As you can see, the majority of Nectin-4 ADCs currently in clinical development, including approved and late-stage assets are based on MMAE payloads such as enfortumab vedotin or PADCEV. While these therapies have demonstrated clinical activity, they are also associated with certain limitations, particularly in terms of safety and resistance mechanism.

In contrast, IPH4502 is based on TOPO1 payload, exatecan, which we believe offers a differentiated mechanism of action. Importantly, this allows us to potentially overcome some of the limitations observed with MMAE-based conjugates, including activity in tumors that are resistant to or have progressed following enfortumab vedotin. Indeed, MMAE-based ADCs are largely developed in bladder first-line setting in direct competition with the approved standard of care when the trial of IPH4502 includes patients relapsing after enfortumab vedotin. In addition, as mentioned earlier, the strong bystander effect associated with exatecan may enable activity in tumors with low or heterogeneous Nectin-4 expression, thereby broadening the potential addressable patient population. Taken together, we believe that IPH4502 combines a differentiated design with a compelling mechanism, positioning it as a potential best-in-class TOPO1-based Nectin-4 ADCs.

Turning to Slide 16. Here, we present new preclinical data supporting the profile of IPH4502 as a potential best-in-class TOPO1 Nectin-4 ADC. Starting on the left-hand side of the slide, in a CDX model with high Nectin-4 expression, IPH4502 demonstrates strong antitumor activity as other TOPO1 ADC do. However, the key differentiation emerged in models with low Nectin-4 expression where IPH4502 maintains meaningful antitumor activity while other TOPO1 ADC in clinical development show a clear loss of efficacy. This is particularly important as it highlights the unique ability of IPH4502 to remain active in tumors with lower target expression. Overall, across multiple in vivo models, we consistently observed a differentiated antitumor profile for IPH4502, supporting its potential as best-in-class agents, particularly in low to moderate Nectin-4 expressing tumors. We believe this profile is driven by the combination of a high affinity antibody with a unique epitope, a stable and hydrophilic linker and a strong bystander effect of exatecan.

Now handing over to Sonia, who will present you the IPH4502 phase I trial.

Thank you. Now let's turn to Slide 17. IPH4502 is currently being evaluated in a first-in-human Phase I study in patients with selected advanced solid tumor known to express Nectin-4. The trial is guided by an adaptive BOIN designed with backfill cohorts with the objective to assess safety, tolerability and preliminary antitumor activity. The study runs at specialized cancer sites in the U.S. and in France. Enrollment in the dose escalation part of the study has progressed well. The maximum tolerated dose is currently explored, and we are enriching cohort at pharmacologically active dose levels, including patients with urothelial cancer relapsed or refractory to enfortumab vedotin, as well as selected additional tumor types. We've started to observe preliminary antitumor activity in this heavily pretreated patient population. Importantly, the safety profile to date remains favorable. As the next step, we will build the package necessary to support the rationale for the dose optimization and selection of the recommended Phase II dose.

Now turning to Slide 18. Based on the promising preclinical data we have generated, that suggests that IPH4502 has robust activity in UC models resistant to EV, and we are focusing on patients with UC who progressed after EV treatment. Despite the significant progress EV has delivered in treatment of urothelial cancer and most notably by nearly doubling survival rates when combined with pembrolizumab, challenges regarding resistance, side effect and long-term remission persist. In the first-line setting, the majority of patients progressed within 2 years with approximately 63% experiencing disease progression within 24 months.

On the right-hand side of the slide, we can see a fragmented treatment landscape and limited effective option for this patient and this treatment landscape is still dominated by platinum-based therapies. This real-world data show that the outcomes in this setting remain poor with time to next treatment of around 3 to 5 months and an overall survival in the range of 7 to 8 months with chemotherapy-based regimens. Taken together, this defines a clear therapeutic gap in the post-EV setting and IPH4502 is designed to address the significant unmet need in this patient population.

Turning to Slide 19. Based on the profile of IPH4502 and the data generated to date, we see a clear opportunity to develop the program across multiple solid tumors. In particular, in metastatic urothelial carcinoma, we are initially focusing on the post-EV setting, where, as shown on the previous slide, there remains a significant and growing unmet need. In this context, IPH4502 has the potential to provide a new treatment option for patients to progress after EV-based therapies. Beyond this initial setting, we also see the opportunity to move earlier in the treatment paradigm, including into first-line setting in combination with anti-PD-1 therapies. In parallel, we believe IPH4502 has the potential to be explored across multiple solid tumors beyond bladder cancer in tumor with low to moderate Nectin-4 expression. And overall, our objective is to build a broad and modular clinical development strategy, starting with high unmet need population and expanding into earlier lines of therapy and additional tumor types over time, depending on the emerging data.

Slide 20, I will now turn to monalizumab and IPH5201. Starting with monalizumab, the anti-NKG2A antibody co-developed with AstraZeneca. We remain focused on the progress of the Phase III PACIFIC-9 trial in non-small cell lung cancer, a trial led by AstraZeneca, which represent the next key step in the development of monalizumab.

In the next slide, we see that this double-blind Phase III PACIFIC-9 trial is designed to evaluate durvalumab in combination with either oleclumab, an anti-CD73 antibody or monalizumab, an anti-NKG2A compared to durvalumab alone in patients with resectable Stage III non-small cell lung cancer who have not progressed following platinum-based chemo radiotherapy. This study builds on a strong scientific rationale supported by controlled Phase II studies in early lung cancer, including COAST, NeoCOST and NeoCOST-2. PACIFIC-9 is a large global trial that has now completed enrollment with approximately 999 patients randomized in a 1:1:1 ratio across the 3 treatment arms. The primary endpoint is progression-free survival with efficacy comparisons of both combinations versus durvalumab monotherapy. We now look forward to the data expected in the second half of 2026.

Let's now briefly touch IPH5201 in the next slide. This is a first-in-class humanized blocking monoclonal antibody that targets CD39, an enzyme that plays a key role in suppressing the immune system within the tumor microenvironment. The ongoing MATISSE Phase II trial is a multicenter open-label single-arm study evaluating the combination of IPH5201 and durvalumab plus standard chemotherapy in patients with early-stage lung cancer. The study is conducted by Innate in collaboration with AstraZeneca. We are happy to share that the results of a preplanned interim analysis of this study have been selected for an oral presentation in a clinical trial plenary session at the AACR Annual Meeting in April in San Diego.

Turning to Slide 23. I would like to remind you the financial terms for both monalizumab and IPH5201 as our partnership with AstraZeneca represents an important upside for Innate. For monalizumab, the agreement amounts up to $1.275 billion of milestones. We already received $450 million and remain eligible to additional $825 million of potential payments. In case of monalizumab is approved, AstraZeneca will book sales and Innate Pharma will receive double-digit royalties on sales in U.S. and rest of the world. In Europe, as Innate Pharma is contributing to 30% of the funding for the Phase III trial, we will get 50% of the profit and have the option to co-promote the drug.

The agreement regarding IPH5201 is worth up to $885 million in milestones. To date, we already received $60 million and remain eligible to $825 million. This agreement having a similar structure than the monalizumab one, Innate has also the option to co-fund Phase III trials in order to get 50% of the profits in Europe and co-promotion rights. Otherwise, Innate Pharma will receive royalties in Europe like in the U.S. and rest of the world.

With that, I will now hand it over to Frederic to walk you through the financial results.

Thank you, Yannis. So now turning to Slide 25. I will walk you through our 2025 financial highlights. Revenue and other income amounted to EUR 9 million this year. It includes EUR 2.8 million from licensing and collaboration agreements, primarily related to recognition of proceeds from our partnerships with AstraZeneca and Sanofi. As well as EUR 6.2 million in governmental funding for research expenditures. Operating expenses were EUR 63 million, of which 73% were related to R&D. R&D expenses were EUR 43.6 million, decreasing by 16% year-over-year, reflecting the study's maturity as well as decrease in indirect R&D expenses, primarily due to lower staff costs and reduced scientific consulting and IP costs, partially offset by restructuring charges following the workforce restructuring plan execution.

G&A expenses were EUR 19.4 million, broadly stable year-on-year with a decrease in nonscientific consulting fees and reduced insurance expenses, partially offset by the workforce restructuring plan impact. Turning to our cash position. We ended the year with EUR 44.8 million in cash, cash equivalents and financial assets as of December 31, 2025. Based on our current operating plan, this provides funding visibility until the end of the third quarter of 2026.

With that, I will now hand it back to Jonathan for the closing remarks.

Thank you, Frederic, and turning to the next slide. As we close, I would like to highlight the strength of our focused portfolio built around 3 high-value assets, which are positioned to drive Innate value. Starting with IPH4502, we are making strong progress in Phase I. The study is progressing very well with high interest, and we are enriching cohorts at the pharmacologically active dose levels. We have observed preliminary antitumor activity with a favorable safety profile to date, including in patients with urothelial cancer, which are relapsed or refractory to EV, which is a signal that we're starting to validate the preclinical hypothesis. We believe IPH4502 has the potential to address the significant unmet need in the post-PADCEV setting, as well as the opportunity to expand beyond bladder cancer in low and moderate Nectin-4 expressing tumors, where IPH4502 could be best-in-class versus other TOPO1 Nectin-4 ADCs.

With lacutamab, we are preparing for confirmatory study initiation in the second half of 2026 based on non-dilutive financing options, which are currently under negotiation with pharma partners and royalty structures. And for monalizumab, the Phase III PACIFIC-9 trial in non-small cell lung cancer has completed enrollment with data expected for the primary endpoint in the second half of 2026. Taken together, these 3 programs provide a clear set of value-driving catalysts across our portfolio. Importantly, with a cash position of EUR 44.8 million at the end of 2025, we have funding visibility until the end of the third quarter of 2026, allowing us to continue executing on our key development priorities. Overall, we remain focused on advancing our pipeline and delivering on these upcoming milestones.

With that, we're happy now to open for questions.

[Operator Instructions] Your first question comes from the line of Swayampakula Ramakanth with H.C. Wainwright.

A couple of quick questions. Just to get started with IPH4502, you were reporting some preliminary antitumor activity in the ongoing trial. Can you provide us some additional specifics regarding the program? And also with changes going on within Nectin-4 ADCs among some of the competitors, how do you see your program in terms of strength and also how much outside interest is there for that specific program?

Yes. So maybe I can start off and address that, and maybe Sonia can hit some of the specifics, RK. So I mean, we continue to be very excited by the IPH4502 program. Clearly, the study is progressing very well, and there is a very significant amount of interest. We've been following the competitor activity here and what's been happening. If anything, we think that reinforces the competitive positioning of IPH4502. We're clearly focusing with the initial indication on the post-PADCEV setting. And as a TOPO1 ADC, we think we have a very good opportunity there, which was never open to MMAE-based ADCs. So we think some of the recent developments will actually potentially help us and really show the clear differentiation and positioning that we have with IPH4502.

And maybe, Sonia, you want to add something?

Sure. We have established the MTD, and this is going to be, let's say, at an expected level according to what we know for other exatecan-based assets. And it is very encouraging to see this preliminary activity at the therapeutic dose in different tumor types. And we are going to eventually explore even further this clinical activity.

Okay. And then on the MATISSE interim data presentation at AACR, I'm glad that you got an oral presentation slot at the conference. I'm not asking you to reveal the abstract or the details of the study. But in general, how should we think about the program itself? And what would we potentially be walking away from that oral presentation regarding that program?

You are taking it Yannis?

Yes. RK, Yannis speaking. So we are having this MATISSE clinical trial in collaboration with AstraZeneca, so Innate is running it. As you may remember, this program is under an option with AstraZeneca. So basically, with the AZ has an opt-in point before starting any Phase III. My -- I would say my expectation is that this Phase II is really dedicated to generate a sufficient data package to validate the target and to show if there is a path forward for the development in lung cancer.

And in terms of data, as you know, there is an embargo on the data until the meeting as it is a clinical abstract. The design of the trial has been shown at the trial in progress poster at ESMO in '23. And it was disclosed at that point in time that there will be some interim analysis for efficacy. And what will be presented at AACR is the interim on the first 40 patients, knowing that the trial is including up to 70 patients. And today, the trial is continuing.

Last question from me regarding the collaboration revenue from monalizumab program in the recent filing, it looks like that's dropped almost to 0 at this point, having met all the obligations. Do you foresee any additional milestones, especially with the upcoming second half PACIFIC-9 readout?

With regards to the revenue, you have to be careful because, in fact, it relates to the old agreement where we were co-developing the early stage of development. So this is the very leftover, and those projects are over. So now the project is completely in the end of AstraZeneca. So the accounting treatment is slightly different. It's not going through the revenue, it's through collaboration liabilities of the balance sheet. So you don't see it in revenue. It doesn't mean that we don't work actively together. And the future development of the program will depend also on the upcoming results expecting in the second half of the year.

Your next question comes from the line of Daina Graybosch with Leerink Partners.

Another one on MATISSE going into the AACR presentation. If I recall, the initial data that Astra generated was in relapsed/refractory lung cancer. I wonder if you could remind me of what you saw there with this program and why that gave Astra confidence to move this into the early-stage setting?

Daina, Yannis speaking. I think that's one of the key takeaway from the Phase I is that if you may remember, we presented that at a poster at ESMO IO a few years ago. Well, that we managed to identify a dose that was able to actually block the enzymatic activity in the patient of CD39. So as it was tested as a single agent and in combination with durvalumab in order to really define the dose to be explored in Phase II. But what was really the key learning was that at the dose that we are using, we are really able based on explant from patients to block the pathway in the patients.

So that's why then we are exploring this setting where there is also expression of CD39. It's something that, again, we have published in a previous poster in this early lung cancer. So it really gives us the opportunity to test the ability of -- by removing this adenosine pressure. We know that the antibody can do it. It's not the case of all the antibody that we have tested. We know that this one, 5201 can do it to test whether it will translate into an increase of activity of durvalumab in the setting where we know also based on the [indiscernible] trial that durvalumab is active in this setting.

And then maybe we haven't thought about CD39 in a while. Can you just remind us how that fits in relation to CD73, which Astra has with oleclumab as another substudy in PACIFIC-9. Just how they all fit together and whether CD39 alone is sufficient to block the adenosine inhibition?

Yes. So just to remind you, CD39 is the enzyme that is upstream in the pathway of degradation of ATP. So ATP is sequentially degraded into ADP and then finally into adenosine was, I would say, sequential degradation going through CD39 and then into CD73. So this is -- CD73 the downstream enzyme. So by blocking CD73, you potentially decrease the quantity of adenosine within the tumor microenvironment, but you do not prevent the degradation of ATP. Whereas by blocking CD39, and it's something that we have published also in cell reports a few years ago, when you block CD39 upstream, you not only limit the accumulation of adenosine, but you also induce the accumulation of ATP, which is known to be immune-stimulating through the P2X receptor.

And it's something that we have shown in preclinical model that it's of particular interest, especially when you combine with inducer of apoptosis like chemotherapy. And that is also the -- why it makes this agent like setting in the MATISSE trial so appealing because it's a combination of both with durvalumab, again, which is approved in this setting in this perioperative setting in operable lung cancer, but also there is chemo, which is an important inducer of ATP that can be blocked and accumulated by the blockade of CD39.

Your next question comes from the line of Jeet Mukherjee with BTIG.

Great. Maybe just starting with lacutamab. Just any color or updates you can share in terms of how those partnership discussions are going? And are there any particular deal structures or outcomes that you feel best aligns with Innate Pharma? And I have a follow-up question.

Yes. So I think if we're looking at lacutamab and how we're moving forward, and I think this is alluding to the financing question. I think the most important thing here is that we get lacutamab on the market for patients in the fastest way possible. And the timelines for approval from our perspective look similar for either a BD option or a royalty financing option. We also know that in either of those scenarios, we will be running the Phase III studies. So we will control the timelines and the regulatory interactions, and we'll be able to, I guess, to leverage our expertise and the networks that we've already established in CTCL.

So at the end of the day, our decision then is really based around what will bring the most value for shareholders in terms of the long-term value. And that's what we're currently evaluating and looking at both the potential of a BD partnership or a royalty financing structure. And watch this space, and we should hopefully make a decision in the not-too-distant future.

Great. And as my follow-up question, just coming back to 4502, in terms of the initial update that you'll disclose, is this one that will come as perhaps an investor webcast or perhaps at a medical conference? And are you able to say now if you've seen antitumor activity in other tumor types outside of urothelial carcinoma?

So maybe I can start off and then Sonia can give the details. I mean I think we're moving very well with this program. It's moving very fast. We have seen antitumor activity in both post-EV, but also in other tumor types. And maybe Sonia can fill in on the details.

Of course, this is a work in progress. And it is always very, very difficult to say, be more specific on an ongoing trial. But definitely, yes, we had also some durable clinical activity in some individuals heavily pretreated. As Jonathan said, we -- the data that we currently have show that our path forward in the EV, in the urothelial post-EV may be plausible and supported by data. And also, it was nice to see clinical activity in other indication. And forgive me for not being too specific on this. We are aiming, of course, to present at a medical conference as soon as the data get matured, then we are obtaining all the, let's say, data around of this Phase I trial.

Your next question comes from the line of Christopher Liu with Lucid Capital Markets. [Operator Instructions].

Apologies. I disconnected before, so I had to rejoin the call. So I apologize if I ask something that's already been asked. But I was wondering for the ADC, what can we expect to see from the upcoming data readouts? And then for lacutamab, what kind of sales infrastructure are you looking to build? And how much are you looking to spend on something like that?

Take the first question, Sonia?

In terms of study readout, what we are going to focus is to get the full safety profile. The PK that is also quite relevant in the ADCs and also show the level of free payload that may be of importance and influencing also the safety profile. And of course, all the efficacy readouts that we have from these patients, including the expression of Nectin-4 in their tumors because we collect tumor biopsies at screening to identify the expression of Nectin-4. This is done retrospectively and prospectively in the study. And so we already know that some of the subjects we have enrolled had a negligible level of Nectin-4. And this is done, of course, in batches. So this is what we aim to have out of this Phase I trial, and we intend to present to a medical conference.

And then addressing the second part of your question, Christopher, in terms of sales infrastructure. Just to reiterate that we've not made a decision yet whether we would do this ourselves or whether we would go through a potential BD partner. If we were to do this ourselves, what we have established is that CTCL, both Sezary and Mycosis Fungoides is treated in a relatively small number of centers in the U.S. It's predominantly treated in academic centers. The majority of the patients are treated in 50 centers in the U.S. and pretty much all of the patients within 100 centers.

So as you can imagine, you need a relatively small commercial infrastructure to be able to fully realize the associated commercial opportunity. So our estimate is a sales team probably of around 20 people, a medical affairs team to support that of probably 5 or 6 people and a handful of access people. So that's the sort of investment that you would actually be looking at if this was something that we ultimately decided to do ourselves.

There are no further questions at this time. I will now turn the call back to Jonathan Dickinson, CEO, for closing remarks.

Okay. So I'd like to thank everybody for attending the conference call today. And just to reiterate that it's an exciting year ahead for the company. We're very clearly on a path with lacutamab to initiating the Phase III confirmatory study and unlocking the potential for the accelerated approval and then a path to creating near-term revenue, which is important for Innate Pharma.

Then with IPH4502, we're progressing very nicely, and we're expecting to approach some catalysts as we go through this year as we develop the data set and develop a data set that is robust and meaningful to patients, to shareholders, to investors, potential investors. And obviously, that will generate some inflection points, which would allow us to look at in terms of how we could further fund that further development of IPH4502. And then, of course, finally, we have monalizumab, which is approaching a very important inflection point for the company.

So thank you for your time and attention, and we look forward to interacting with you over the coming weeks and months. Thank you.

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

Ladies and gentlemen, thank you for joining us, and welcome to the Innate Pharma Third Quarter 2025 Business Update and Financial Results. [Operator Instructions]

I will now hand the conference over to Stephanie Cornen, Vice President, Investor Relations, Communication, and Commercial Strategy at Innate Pharma. Please go ahead.

Good morning, and good afternoon, everyone. Thank you for joining us for Innate Pharma Q3 2025 Business Update and Financial Results Conference Call. The press release and today's presentation are both available on the IR section of our website.

Before we begin, I'd like to remind everyone that today's presentation includes forward-looking statements based on current expectations. These statements involve risks and uncertainties that could cause actual results to differ materially. To begin, I briefly cover today's agenda. Our CEO, Jonathan Dickinson, will discuss our strategic priorities and path forward. Then our CMO, Sonia Quaratino, will present clinical pipeline updates on IPH4502, monalizumab, and lacutamab. Afterwards, I will present the commercial opportunity for lacutamab before turning back to Jonathan with closing remarks, and we'll open the call for Q&A.

With that, I'll now hand it over to Jonathan.

Thank you, Stephanie. Good morning to those joining from the U.S., and good afternoon to our European audience. Turning to Slide 5. I would like to start with the strong momentum around lacutamab, supported by meaningful regulatory progress and new commercial opportunity insights. A few days ago, we received FDA clearance to initiate the TELLOMAK-3 Phase III trial in cutaneous T-cell lymphoma. This is a major milestone for the program, positioning lacutamab to advance towards potential accelerated approval in Sezary syndrome, supported by robust Phase II data. We expect the study to initiate in the first half of 2026, with filing anticipated following achievement of key enrollment milestones.

Our CMO, Sonia Quaratino, will provide additional color on the Phase III trial and the regulatory path. In parallel, we hosted a well-attended lacutamab KOL event in October, featuring leading experts in CTCL. The discussions highlighted the continued unmet medical need for new, effective, and well-tolerated therapies in this space and reinforced lacutamab's unique positioning. During the event, we also presented new real-world claims data underscoring the commercial opportunity in both CTCL, which we believe further strengthens the value proposition for this program. Stephanie Cornen, our Vice President of Investor Relations and Commercial Strategy, will review the real-world evidence-based commercial opportunities for lacutamab towards the end of our call today.

Moving to Slide 6. As you know, Innate Pharma's core strength lies in applying our deep scientific expertise to advance life-enhancing cancer therapies. Through our years of pioneering work in antibody engineering, we have built a differentiated high-value clinical pipeline supported by compelling data, positioning us to deliver treatments with truly transformative potential for patients and for all our stakeholders.

Moving to Slide 7. As we look ahead, our path forward is clear and focused. As you remember, at our half-year results, we announced the strategic decision to focus our investment on what we believe are our highest value clinical assets, including IPH4502, lacutamab, and monalizumab, to maximize impact and value creation. In parallel, we are advancing our next generation of ADC programs through research, building the foundation for future innovation. Finally, we are streamlining the organization to ensure we remain fit for purpose and aligned with our strategic objectives.

I'll now hand over to Sonia, who will take us through the clinical pipeline progress. Sonia?

Thank you, Jonathan. In this update, I would like to highlight the 3 clinical programs we believe hold the strongest potential to create significant value for Innate, IPH4502, monalizumab, and lacutamab. Starting with IPH4502, our differentiated ADC directed against Nectin-4. As a reminder, I would like to pinpoint the preclinical model where IPH4502 has demonstrated the 2 major feature of differentiation to an approved drug such as enfortumab vedotin. The first one is related to the payload of IPH4502, which is exatecan, a potent topoisomerase 1 inhibitor. Exatecan can induce a bystander effect, a phenomenon where it kills neighboring cancer cells in addition to the targeted cells. The exatecan is released from the antibody drug conjugate in the tumor and diffuses into nearby cells. This is beneficial for treating heterogeneous tumors where cancer cells may not all express the target antigens.

The second point of differentiation is that in preclinical models, we have demonstrated that IPH4502 can induce potent tumor regression in PADCEV MMAE-resistant models, allowing us to target tumors that are or have become resistant to PADCEV. We have, therefore, built the study design of the first-in-human trial on the basis of these preclinical findings. First, we look for signals in tumor types where Nectin-4 expression may be low or heterogeneous, opening to a very broad opportunity. Second, we enriched the study of urothelial cancer patients in the post-EV setting, where IPH4502 may overcome resistance to EV. This represents an area of high unmet need with no approved drugs and the potential to move rapidly into later-stage development.

With this hypothesis, the emerging clinical data will indicate the indication where IPH4502 can make the greatest impact. The first-in-human trial is guided by an adaptive design, and the main objective of this study are to assess the safety, tolerability, and preliminary efficacy of IPH4502 in patients with advanced solid tumors known to express Nectin-4. Enrollment in the dose escalation part of the study is progressing very well. We started the trial in January, and we have now reached already a pharmacologically active dose, and we have started to see early signs of clinical activity. We remain on track to complete the dose escalation by the first quarter of 2026. And after that, the dose optimization part of the study should commence.

Now let's turn to Slide 10 to provide an update on monalizumab, which continue to advance in collaboration with AstraZeneca. The double-blind PACIFIC-9 Phase III trial aims to demonstrate improved progression-free survival of durvalumab in combination with either oleclumab or monalizumab as compared to durvalumab with placebo in patients with unresectable Stage III non-small cell lung cancer who have not progressed after platinum-based chemo radiotherapy. The PACIFIC-9 study builds on very strong scientific rationale, supported by earlier studies such as COAST, NeoCOST and NeoCOST-2 trials.

This is a large global study that has fully completed enrollment with 999 patients randomized 1:1:1 across the 3 treatment arms. The primary endpoint is progression-free survival with efficacy comparisons for both combination arms versus durvalumab monotherapy. The study is fully recruited, and the independent data monitoring committee recently recommended continuation of the trial following a preplanned analysis, an important validation of the program progress. And we look forward to the data expected in the second half of 2026.

Now moving to Slide 11 and to lacutamab. As we highlighted during our KOL event last month, our development strategy is designed to enable a stepwise approach, beginning with Sézary syndrome, an indication with the highest unmet medical need, especially in patients who have progressed after mogamulizumab, then progressing with a larger opportunity in mycosis fungoides, and finally, expanding to peripheral T-cell lymphoma. We are preparing a confirmatory Phase III study in an FNSS, which, once underway, opens the door for our filing of the biologics license application for Sézary syndrome post mogamolizumab based on the existing Phase II TELLOMAK data. This represents a potential path to accelerated approval with a key milestone expected in 2027.

The confirmatory Phase III will also include patients with mucosis fungoidis, the largest CTCL subtype, where there remains a clear need for disease-modifying therapies. These results of the confirmatory Phase III trial will support a full approval in 2029 in NF and then full approval for Sézary and help establish lacutamab as a game changer in the therapeutic landscape across CTCL. Our goal is to position lacutamab within the NCCN guidelines as a preferred systemic therapy, not only for late-stage Sézary and mucosis fungoides, but ultimately for earlier-stage CTCL patients who continue to face limited treatment options.

Now beyond CTCL, we are also advancing development of lacutamab in peripheral T-cell lymphoma, a particularly aggressive lymphoma subtype with few effective treatment options, and an ongoing Phase II study will help defining lacutamab role in this patient population.

Turning to Slide 12. I would like to remind the data that will form the basis for the accelerated approval in Sézary post mogamulizumab. They are the long-term follow-up data from the TELLOMAK Phase II trial that was presented at ASCO 2025. Sézary is an aggressive subtype of CTCL. And post-mogamulizumab, there are no approved drugs that have demonstrated clinical efficacy. In heavily pretreated patients, all pretreated with mogamolizumab, lacutamab demonstrated an impressive global overall response rate of 42.9% with a median duration of response of 25.6 months. The median progression-free survival for the whole population was 8.3 months. Of note, lacutamab was very well tolerated with very favorable safety profile, underscoring lacutamab potential to deliver a meaningful clinical benefit in this aggressive and difficult-to-treat population.

Turning now to mycosis fungoides. Long-term follow-up data from the TELLOMAK Phase II trial showed that lacutamab achieved a global overall response rate of 19.6% with consistent activity observed regardless of KIR3DL2 expression level. The median duration of response was 13.8 months, and median progression-free survival was 10.2 months, again, with no difference between the 2 subgroups. Also in MF, lacutamab was very well tolerated with an excellent safety profile that supports its potential use for long-term systemic therapy at an early-stage disease.

Turning to the clinical development plan for the confirmatory trial. This is an open-label multicenter randomized comparative Phase III trial evaluating lacutamab in patients with cutaneous T-cell lymphoma who have failed at least one prior line of systemic therapy. In alignment with the FDA, the study includes 2 independent cohorts with distinct statistical analysis plans, one for Sézary syndrome and the other for mycosis fungoides. In the Sézary syndrome cohort, patients who have failed at least one prior systemic treatment, including mogamulizumab, will be randomized 1:1 to receive either lacutamab or Romidepsin, which is currently the only FDA-approved option for patients who progress after mogamulizumab. The primary endpoint is progression-free survival assessed by blinded independent central review, and the key secondary endpoint is overall survival.

In the mycosis fungoides cohort, patients with Stage Ib to Stage IV disease will also be randomized 1:1 between lacutamab and mogamulizumab, which represent the current standard of care for this population. Here again, the primary endpoint is PFS, weak pruritus, and quality of life as a secondary endpoint. As the Sézary syndrome and MF study subpopulations are considered as independent cohorts, answering to distinct objective sample sizes are estimated to meet the primary endpoint in both SS and MF cohorts independently. From a regulatory standpoint, we have received clearance from the FDA about this clinical trial protocol. And therefore, we are well placed to initiate the Phase III trial in the first half of 2026.

And with that, I will now hand over to Stephanie Cornen, who will walk us through the commercial opportunity for lacutamab and how we plan to unlock its full value across CTCL and beyond.

Thank you, Sonia.

Now looking at commercial opportunity an important parameter is about eligible population. CTCL is aware of this diseases and assessment incidence and prevalence remain a challenge, potentially underestimating its true burden. During the occurring event, associates presented the most up-to-date source based on U.S. TELLOMAK data Versus CTCL Patient population, which highlights the higher incidents and prevalence than previously described. So if we look into each of these opportunities, starting with Sézary syndrome, as discussed it should release near-term in U.S. based on the Phase II TELLOMAK data. Sézary syndrome may affect around 3x more patients than previously believed, with an annual incidence was around 300 patients, prevalence around 1000 overall Sézary patients. And according to U.S. TELLOMAK data, approximately 300 patients treated with mogamulizumab annually. Importantly, these opportunities clearly define and actual of approximately concentrating in special and referral centers which accessible with a focused commercial footprint. Our launch strategy will therefore target specialized centers already managing these patients, allowing for a near-term and derisk opportunity in the U.S.

Now moving to mycosis fungoides, which represents a larger opportunity. Here again, the TELLOMAK data shows a higher incidence than previous reported with approximately 3,000 U&M patients diagnosed each year in the U.S., and about one in four of these patients received systematic therapy. The goal of our Phase III, TELLOMAK-3, is to establish lacutamab as the new second standard of care, and our primary market research supports the view that physicians would adopt lacutamab as a second line of treatment base.

And again, importantly, Sézary syndrome enable a seamless expansion into mycosis fungoides since both indications are managed by sustainable network of prescribers. So in summary, we see Sézary syndrome as our first focused entry point into the CTCL market in the U.S., a manageable and concentrated launch opportunity that will also serve as the foundation for a broader commercial in MA.

Turning to Slide 17. This slide illustrates the market potential for lacutamab in CTCL and how we plan to expand over time through a stepwise strategy that Sonia previously described. We expect an initial opportunity of up to $150 million in the U.S. with accelerated approval in Sézary syndrome, where the patient population is small but highly concentrated and addressable through a focused commercial footprint.

As lacutamab moves into mycosis fungoides and secures full approval the opportunity could expand to around $500 million across the U.S. and Europe. And beyond that, we see additional upside as part of our life cycle management strategy. Lacutamab offers important standard care for early-stage patients, a segment where systemic treatments are less used today. And the unique profile of lacutamab that combines tumor targeting activity, improved quality of life, and a favorable safety profile makes it a compelling candidate to unlock earlier use of systemic therapy.

While the Phase III trial is designed to support registration across all stages of Innate in the second-line setting, we see a broader opportunity in addressing the Innate medical need of patients who are currently managed only with skin therapy and may benefit from lacutamab. In short, lacutamab offers a clear derisk path to commercialization starting with Sézary syndrome, expanded into larger CTCL segment over time, and then an even larger opportunity in PTCL.

And now I'll hand the mic to Jonathan for closing remarks.

Thank you, Stephanie. As part of our focused strategy, we are advancing 3 high-value clinical assets that form the core of Innate's portfolio. Starting with IPH4502, our novel and differentiated Nectin-4 ADC, we see a significant opportunity in bladder cancer, particularly in the post-PADCEV setting, as well as across other solid tumors with low to medium Nectin-4 expression. Enrollment in the ongoing Phase I trial is progressing well, with completion expected by late 2025 or early 2026. We've now reached a pharmacologically active dose level where we're beginning to see encouraging early signs of clinical activity.

Monalizumab, partnered with AstraZeneca, continues to advance in Phase III for unresectable non-small cell lung cancer, where enrollment in the PACIFIC-9 trial is now complete. Top-line data are expected in the second half of 2026, and this collaboration remains a key value driver with up to $825 million in total milestones and $450 million already received to date. And with lacutamab, our anti-KIR3DL2 antibody for cutaneous T-cell lymphoma, long-term follow-up from the TELLOMAK Phase II study has demonstrated meaningful and durable clinical benefit in both mycosis fungoides and Sézary syndrome, leading to breakthrough therapy designation in Sézary syndrome.

As you know, we've now received FDA clearance to proceed with the confirmatory Phase III TELLOMAK-3 trial, and we're on track to initiate in the first half of 2026, supporting the potential for accelerated approval in Sézary syndrome.

To wrap up today's call, I'll remind you that we have several value-driving catalysts ahead across Innate's portfolio. In the first half of 2026, we expect Phase I data from IPH4502, our Nectin-4 ADC program. This will be followed in the second half of 2026 by data from the PACIFIC-9 Phase III trial of monalizumab in collaboration with AstraZeneca. Looking beyond to 2027 and onward, we anticipate multiple milestones, including a potential accelerated approval for lacutamab in Sézary syndrome, the monalizumab BLA filing, and IPH4502 expansion phase data.

Finally, we ended the third quarter of 2025 with a cash position of EUR 56.4 million, providing runway through the end of Q3 2026 to deliver on these key milestones.

Operator, we can now open the Q&A session. Thank you.

[Operator Instructions] Your first question comes from the line of Christopher Liu with Lucid Capital Markets.

So I have 2. For the first one, what would you need to get done in the near term for the potential lacutamab commercial launch in Sézary syndrome? And for the second question, for IPH4502 and the upcoming data set, could you give us a little bit more color on what we can see at that readout?

Okay. Christopher, I can take that. So from a commercial perspective, I think one of the key things that we would need to get done prior to Sézary launch is the work to ensure that lacutamab will be included in the NCCN guidelines. So what we're aiming to be able to do, and we've already started the discussions on this with KOLs, is to ensure that when the BLA is approved for Sézary, that we basically already have lacutamab included in those NCCN guidelines for Sézary syndrome, but also for mycosis fungoides. So that will be one of the key pieces of work that we believe we will need to have in place prior to the BLA.

And then IPH4502, in terms of what we hope to have next year, I think we've communicated this on a number of occasions, but what we're aiming to have is a cohort of patients in the PADCEV resistant setting, probably 10-plus patients where we will hopefully see an interesting response rate and be able to show clinical activity as well as safety data. We also hope to have data in 1 or 2 other tumor types in a similar perspective. So 10-plus patients in 1 or 2 tumor types. What we're doing with the study, and I think Sonia mentioned this earlier, is we've set up the study in a way where we can basically chase signals. We can backfill cohorts. So when we see a signal in a particular tumor type, our objective is to backfill and to substantiate that signal. So hopefully, then in 1 or 2 other tumor types, you would have 10-plus patients. And again, hopefully, an interesting response rate that allows us to then move forward into the next stages for the development of the product. Thank you for the question, Christopher.

Your next question comes from the line of Justin Zelin with BTIG.

You've indicated that FDA views an accelerated approval pathway here for lacutamab as viable once the Phase III study is underway. Could you just expand whether FDA is looking for any additional supplementary analyses beyond the existing Phase II data set as part of that accelerated approval package? And then just second, based off of the feedback from the October KOL event. Do you have a sense of growing momentum from the KOLs for lacutamab to become the preferred second-line option here? And should we expect mogalizumab to naturally move later in the treatment paradigm?

Okay. So addressing the first part of your question, Justin. So from an FDA perspective, they have not given us an indication that we would require any further substantial analysis. So basically, the BLA approval will be based off the data we have in hand today from the TELLOMAK study and the results that we've already presented that led to the breakthrough therapy designation. So we see that as reasonably straightforward. The key thing to unlocking the BLA submission here is having the confirmatory study up and running and to have established an enrollment trajectory into that study that would satisfy FDA that this study will complete and will deliver the confirmation of the accelerated approval.

So that's something that we're obviously working very hard to be ready to do that ASOP because that counts down the -- it's the countdown to the submission of the BLA. We hope to be able to initiate the confirmatory Phase III study sometime around the middle of 2026. We would anticipate potentially a 6-month enrollment period to get the right trajectory to satisfy FDA requirements. And then that would allow us to submit the BLA sometime in early 2027, leading to FDA approval of the BLA, hopefully, sometime in the second half of 2027. So yes, so that hopefully answers the first part of your question.

Then in terms of KOL feedback, we do see very good KOL feedback on lacutamab, and we do sense a building momentum around that. I think if you were attending the KOL event, and I think the KOL used the word game changer, which was, I think, something that summarizes what lacutamab can potentially bring not only to Sezary syndrome, but also to mycosis fungoides. I think there's particular excitement around basically what can happen in MF.

If we look at the 5-year survival, of patients with MF, we do see a dramatic decrease in 5-year survival when patients progress from Stage 2a to Stage IIb, it drops from 78% to 47%. And we know that physicians want to be able to prevent that progression. And lacutamab, based on its tolerability profile and the excellent quality of life data for patients, is incredibly well placed to be able to slot into that area and be able to treat those patients at Stage b, Stage 2a, and hopefully prevent that progression of the patients to Stage Ib when you see the reduction in 5-year survival. So that's clearly, I think, factoring into the thinking of KOLs and how they will use this drug. So I think particularly in MF, we anticipate that lacutamab will be used ahead of Moga.

In Sezary, we're studying post-Moga. So our expectation is that the product will be used post-Moga. Based on the excellent safety profile, I think some physicians may choose to use it in the first-line setting off-label as well. But our main assessment and where we're targeting for positioning the product is post Moga and initially in the Sezary syndrome indication. Hopefully, I've answered your question.

If I could just fit in a quick question with a potential near-term approval here, could you just comment on your CMC readiness as far as commercial scale manufacturing, PPQ run stability work for lacutamab?

Yes, I can comment on that. I think the answer is we're in a good place. We're basically ready to go. That won't be on the critical path to submission of the BLA. So we've ticked that box, and we're ready to go from that perspective.

Your next question comes from the line of Swayampakula Ramakanth with H.C. Wainwright.

So I appreciate your comments on how you plan to file the accelerated approval application by the end of 2026. So what -- does this mean you're still hoping to get a partner on board? And in your previous conversations with potential partners, how much stress was there in terms of getting a clear signal from the FDA and a protocol blessed by the FDA?

Thank you for the question, RK. So in terms of partner discussions, having FDA acceptance of the protocol was an important consideration. It was potentially one of those boxes that we needed to tick for a number of them for us to be able to progress with those discussions. So yes, it was an important clearing event to be able to move forward with some of those partnering discussions. In terms of partnering, commenting on partnering, I think what the company is looking to do is basically to keep our options open.

We basically were continuously evaluating a variety of financial options to ensure we're appropriately positioned to support our growth initiatives and create long-term shareholder value. And we remain disciplined and opportunistic in our approach to capital management, and we'll pursue the opportunities that basically support where we're going here. So I think it's important that we keep the options open at this particular stage, particularly with the exciting news that we've seen more recently with lacutamab and the great path that we have forward.

Can I ask 2 quick follow-ups, one on 4502? What specific safety signals would you be looking out for, especially when you would like to see this differentiated against other TOPO1 inhibitor ADCs? And the second question is, so what's the thought process now for the ANKET platform, especially them taking a little bit of a backseat? What's the long-term plan for that platform?

So maybe I can take the first question, and then I will ask Sonia to take the question on the safety signals that we're looking out for. So -- on the ANKET platform, we are basically waiting -- we're actually finalizing the study for IPH6501. I think we mentioned previously that we've completed the dose escalation phase of the study, and we were basically exploring the MTD at this stage. We're still in the process of doing that. And we'll basically make any future decisions based on -- for IPH6501 based off clinical data. And that clinical data should come sometime in the first half of next year, and then we will be able to make the evaluations and the next steps.

In relation to IPH6101, we have now basically have most of the clinical data for the Phase I and Phase II returned to us from Sanofi. So we're now in the process of evaluating that data and trying to understand what next steps could be for the ANKET platform. What I would really like to clearly emphasize, though, is from a prioritization perspective, we're putting most of our time and effort behind IPH4502, behind lacutamab and behind monalizumab, and making sure that we advance those 3 assets as quickly as possible because we believe we have the highest chance to win for those 3 assets. Sonia, if you can take the question on the safety signals we're potentially looking out for?

Well, in terms of signal for IPH45, we try to establish a very well-tolerated and relatively safe drug. And in particular, we try to, of course, avoid all the MMA-specific adverse events like peripheral neuropathy, that is very often not reversible, and ocular toxicity. And so far, we did not see many adverse events or a specific trend in that respect. So the plan is to provide clinical efficacy in, let's say, unusual indication or indications where the Nectin-4 expression is not as high as urothelial cancer, with a very good benefit-to-risk ratio matched by a favorable safety profile. It's difficult to say a prior what you want to see, yes.

Your next question comes from the line of Diana Graybosch with Leerink Partners.

Yes, Bill on for Dana. I change it up a little bit, just asking about monalizumab. So I guess I'm just curious, can you just give us some, I guess, expectations for the readout in the second half of '26? Sort of what gives you the confidence that monalizumab, I guess, and durva can actually win out against durva?

Yes. So maybe I can take that question. So basically, we have good expectations for the PACIFIC-9 study. And what that is based on really is the COAST study, which was the Phase II study, a randomized Phase II study that was replicating the PACIFIC-9 setting. If you look at the results and the Kaplan-Meier curves from that study, they are very interesting. When you added monalizumab to durva, you basically added 12 months median PFS on top of durva. So if we retain a proportion of that effect size going into the PACIFIC-9 study, there's a very high chance that we will have a positive study. So that gives us a, I would say, a relative sense of confidence that this will be a positive study. Hopefully, that addresses your question.

There are no further questions at this time. I will now turn the call back to Jonathan Dickinson, CEO, for closing remarks.

Okay. I'd like to thank everybody for attending our quarterly earnings call. Thank you for your time and attention, and I wish you a great rest of the day. Thank you very much.

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

So 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 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.

So we will be making some forward-looking statements. So 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 Quaratino, 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. And 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. And 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. And as part of that, we have a plan to reduce our organization by 30%.

So that is the strategic update. Going into a few more details on those three priority assets. So 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. So the TELLOMAK was conducted in mycosis fungoides and in Sezary syndrome.

And in Sezary syndrome, we have basically an accelerated path to approval agreed with FDA. And 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. And that's what we will be hoping to be able to do in -- and to demonstrate that in the Phase III study. So that's lacutamab.

We then also have monalizumab. This is in collaboration with AstraZeneca. We have a partnership. This is well advanced. We are in a large randomized Phase III study, the PACIFIC-9, which has completed enrollment. And we passed the 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. So 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 Sezary 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 Sezary 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 Sezary syndrome indication, but it also will give us the Phase III randomized data for the mycosis fungoides indication. And with that confirmatory study, we expect to be able to have the full approval for MF and then the full approval for Sezary in 2029.

And then we have a life cycle 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 [ LISAC ] 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 release sometime in the second half of next year. And 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.

So it will 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 [ LISAC ]. They actually conducted the registration study that led to the approval of rituximab in aggressive non-Hodgkin's lymphoma. So that's the potential life cycle 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 you'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, Division Chief of Hematology and Bone Marrow Transplantation at the University of Kentucky, who will give us a good overview of the CTCL space as well as we'll discuss the data of lacutamab. Pierluigi is a very well-known world leader in CTCL, and it's a great pleasure that is willing to be with us today.

Thanks, 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 9 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. And 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 the -- 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 extranodal 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 make 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 2/3 of the cases of CTCL, Sezary syndrome is a small minority, about 5%; and the rest is kind of a hodgepodge of cutaneous T-cell lymphomas, primarily CD30 expressing anaplastic large cell lymphoma-related diseases.

Now when we look at the outcomes and the kind of the framework for czary, mycosis fungoides and PTCL, again, 2% to 5% of the CTCL patients are Sezary. Sezary really kind of is an advanced stage form of CTCL with heavy blood involvement is relatively rare, as the numbers show. But it's very aggressive. And the prognosis is poor. So on average, 1 out of 10 patients actually makes it alive at 10 years -- at 5 years.

Mycosis fungoides is, again, is a much more common subtype, is more indolent, particularly initially. It presents in the skin. And however, as I'm going to show, it transitions very, very often over time to kind of more advanced stage and at that point, really becomes a poor prognosis as well.

So 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. And they do have a poor prognosis, big unmet need there. As Jonathan was mentioning, kind of perhaps down the road, it 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 corporate group network in the U.K. And if you -- 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 pointer here? Yes, there we go. So the stages are down here, and this is a relative size of each population. So for about 30% here Stage IA, almost 40% Stage IB and so on. And here on the Y-axis is the 5-year survival. And as you can show, Stage IA to IIA, these are early-stage patients, and these are advanced-stage patients.

And the survival, as you can see here, there is a clear transition and demarcation of survival with the early stages -- sorry, the early stages having significantly better survival at 5 years and the more advanced stages having a very significantly inferior survival at 5 years.

Now -- so putting some sort of visualize what happens to patients with CTCL. Even at relatively early stage, I think it 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 patients 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. So this is superficial disease.

About 40% of the patients are diagnosed at Stage IB. Now they may actually potentially start to Stage IA, we just don't know. They present to the physicians and they present to the medical centers in Stage IB. And 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.

And 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 -- if you 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, and these are patients that we -- 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 late media, you will see that early stage is considered 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 IA to IB 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 a 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, it 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 IA to Stage IIB or higher. And 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 data sets. But this is one particular example, and it's particularly well spelled in terms of the transition to stage.

So first, right here on the left, as we mentioned, about 30% of the patients present with Stage IA. This is skin-only disease, less than 10% of the body surface area. If -- and this group of investigators follow 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.

And if you break it down according to which stage, 7% of the patients move on to stage -- from Stage IA to IB and sort of stay there as far as this particular data set is concerned. But then 10% and 8% of the patients not only advances to Stage IB to sort of greater involvement of the skin, but they go on to have tumor lesions and some of them actually go on to the blood, lymph node and visceral involvement. And 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.

And here's another example. If you just focus on now the patients who present with IB, Again, this makes about 40% of all cases. And here, you have about 30% of the patients who move on from Stage IB to IIB, 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 nodes and visceral.

Once you go -- 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 survival -- the disease-specific survival for patients with the so-called earlier stages IB or tumor stage is significantly impacted.

This is shown here. This is a different data set from the one showed 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. And 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. But right here on the left, this is the most common way of displaying stage. And this is progression. So risk of progression, of course, over a significant period of time, at 30 years. But you can see that even if you're diagnosed with the IA disease.

And if you go to the doctor and you have MF and you say that you have IA 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's not true for a significant fraction of these patients, as we will show you in the next slide.

So once you get to IB, and again, IB and IA is the same kind of skin lesions except to a greater extent. And the difference in extent is IA is less than 10%, IB is more than 10%, more or equal than 10%. It doesn't take much to actually to be in Stage IB.

Of course, then you have Stage IIB. So the progression here over a long period of time from -- for patients presented with IA is about 18%, 17%, 18%. For patient with IB, it's 40%. And these are the independent data compared to the slide I showed before. Once you get to IIB, the progression rate is very, very high.

So 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 match-related population over a period of 30 years.

Obviously, you would expect that the curve will go down with -- 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 IIB is really poor. And this is not even counting Sezary, it's not even counting Stage IV. 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 IIB.

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 data sets. 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 and MF, whether they are early stage or advanced stage, they all will need skin-directed topical therapy throughout the 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, we do chemotherapy for 6 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 a few effective and well-tolerated therapy. So therapies that actually not only are effective in terms of antitumor control, but also are well tolerated that can be extended so that the paradigm of continuous therapy is feasible. And so for these patients, 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. So this is a big, big challenge here.

Now the landscape of systemic therapies across available or recommended according to guidelines across the stages is shown here. This is fundamentally the NCCN guidelines. And 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 a 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, the 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 brentuximab, you have moga, you have Romidepsin and Vorinostat. Each one of these drugs, though, have significant drawbacks and concern.

Brentuximab, for example, there 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 brentuximab, but they go to the -- they push the neuropathy to the limit, but 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 a 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 then you look in diftitox, is 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, 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 brentuximab 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 Bexarotene, Romidepsin, Vorinostat; and all these drugs were approved based only on skin responses.

Now brentuximab and moga were approved in 2017, 2018 based on more complex response criteria called the Olsen 2011. And these response criteria require analysis -- independent analysis of compartment-based response. So you have to have a response in the skin, the lymph node in the blood. I'm going to show the slide next.

And so again, I want to emphasize that -- then you u look in diftitox, the target is CD25. The target had been studied and discovered all the way, even all the way here. So it's not a new target. And since brentuximab and moga, there have been really kind of no new target development for therapeutics in CTCL.

This -- it's kind of a snapshot here of the different compartments of response that are essential to assess global responses. So when you're talking about complete response, when we're talking about partial responses, we have to have responses across all these different comp.

The skin is the dominant compartment, of course, both in terms of symptoms as well as evaluation. But you have to have -- to have a PR, for example, you have to have responses in -- at least a PR in blood, viscera 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 -- it's a monoclonal antibody targeting KIR3DL2, which is expressed on a significant majority of the patients with CTCL, particularly all the patients -- with almost all the patients with Sezary, 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 and/or refractory Sezary syndrome requiring B2, so full blood involvement, or MF with at least 2 prior systemic therapies. The patients with Sezary syndrome had to have prior mogamulizumab. So all of them to be enrolled, they had to have mogamulizumab.

There are several different cohorts. One particular sort of important cohort with Sezary syndrome, 63 patients enrolled. To best of my knowledge, this is the largest cohort of patients with Sezary syndrome ever accrued on a clinical trial. And then there are several cohorts for MF.

The study endpoints, global overall response rate, again, important in looking at all the different compartments. According to [ us ] in 2011, a number of secondary endpoints.

The treatment, lacutamab is given intravenously once a week for 5 weeks, then every 2 weeks for 10 and then every month until disease progression or toxicity.

These are the data in Sezary syndrome post-moga. Again, all these patients had moga. And I would say that in Sezary 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, a 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 Sezary syndrome here with lacutamab.

Importantly, there's also a significant impact on quality of life, as shown here, both in terms of itch, right 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 response -- 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%. Fast 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 -- and the long 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, a very rapid responses as well here, not just for the complete response and 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 kind of a partial response already happened at week 5 and then achieved a complete response at week 37.

In terms of the blood compartment, the blood compartment, as shown by the subset in the cohort for Sézary syndrome, very fast responses and so clearance already at week 5. The lymph node, in this case, this patient did not have lymph node involvement. So the global response here, PR at week 5, CR at week 37. And 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 at -- on the left is the safety profile in Sézary syndrome. On the right, the safety profile in MF. In 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 are 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 in both in Sezary 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 based -- not just based on the data, but also based on the experience and treating patients with lacutamab, lacutamab is a drug that can be used for very prolonged periods of time in patients with both Sézary 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, 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 Ib, Ia or Ib, we know that they will progress over time. We know that they will need systemic therapy. And as of now, there is 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 compartment, 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 designation 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 a breakthrough therapy designation from the FDA. And 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 option, and this is only for very serious conditions. And for this reason, we have obtained the BTD for Sézary syndrome post mogamulizumab.

And I also want to stress, as Jonathan mentioned in his introduction, through different interaction 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. And this is what we are working on.

So in the perspective, we have completed a Phase I trial in Sézary syndrome. The Phase II TELLOMAK has been completed with -- in total, 170 patients. And now we are progressing towards the preparation of the Phase III trial. And 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 limitation 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 leader like Professor Porcu helping us in the development. And we are really at Innate, we have a first-class team of clinician, clinical operations, statistician cleanup that can really make this Phase III happening at fast pace. And 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 2 different cohorts with different statistical analytical plan, 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 1:1 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 patient at Stage Ib onwards and so Stage 1b to Stage 4. And these patients are randomized 1:1 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 certification factor 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 2 independent cohorts, they have 2 different sample size, and these sample size 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 time lines, 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 half of 2026. And according to these time lines, 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 1 year after the initiation of the Phase III, we may have -- 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 file the BLA based on the preliminary -- 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 3 different or some key milestones. One, in 2027 that is accelerated approval for Sézary syndrome. And 2029, 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 the treatment. They are categorized as non-MF, non-SS, but inevitably, they use the same drug that are used in MF and SS.

So you've seen -- this is 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 have 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 unmet 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 insights of the 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 Stephanie mentioned, we conducted a CTCL market analysis using the Komodo claims data set. We use the Komodo claims database because it has a 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 to 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're captured. So 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 and DOs. 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 3 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 1-year time span, keeping in mind was 20,000 patients. We looked at incidents where there were roughly 5,000 patients in 2023, 2,900 of these being MF, 316 being MF. And then in terms of the incidents over time, SS and MF remained 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, 3 years, 5 years and 7 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 is -- 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 a typical oncologic indication.

So looking at the top specialty. The specialties and the health care 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 Heme/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 an MF and undefined patient groups being lower at 20%.

All patients have relatively -- 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 health care 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 to 2025 on the graph on the left, 9% of patients within that time span received methotrexate at some point. Other commonly used agents are Bexarotene, BV and moga.

And 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. And we do see that there is less than 10% of patients who are prescribed by a dermatologist versus 80% and above that prescribe these 3 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. And just to kind of give some context here, the incidence has remained relatively steady in SS as well as in the general CTCL population and 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 database to gather CDCL epidemiology market landscape in 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 -- in all the individual 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 heme/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 Relations 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 real-world evidence from [PFS] state. The vision that we have at Innate for lacutamab is really to open doors positive CTCL patients. And so the key is really to bring to these patients therapy that provides durable disease control and also improve 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 had very good tolerability. We really want this drug to be a well -- if the patient join it as soon as possible, as early as possible. And this is really what we envisage here for lacutamab too and use true paradigm shift in 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 segment. First, you have Sézary syndrome indication and this is where the unmet medical need is the most urgent. There is no therapy approved once the patients have progressed after mogamulizumab in SS patients and the survival remains very poor. So this is -- that is the first segment for lacutamab.

Then the second segment in line with the Phase III design will be to establish lacutamab as the new second-line standard in MS patients. And then beyond as life cycle management opportunity there is the opportunity to expand use of lacutamab in early stage patient. And this would mean that it will create an expansion of the current CTCL market because currently, this patients are mostly treated with skin-directed therapy.

So this strategy became even more relevant when we received the insight 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 is in the U.S. and there is also a population in Europe of course.

So from this data we have seen that there is much higher incidence across CTCL segment and in effect it is about 3X 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 active 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 derisk 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 prevalence on 1,000 patients. And we have seen -- in the previous presentation that there are around 300 patients each year that are treated with moga, and so their population won't be editable for lacutamab therapy. These patients are treated mainly by the hemato-oncologists and they are managed within academic specialized centers. So overall, we see that this has 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 the 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 this research really supports the adoption of lacutamab as a second-line standard of care in 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 life cycle management box for lacutamab, but which is actually, as you understood, from the presentation from Pierluigi Porcu and Sonia, 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 this parameter of the drug may really enable this earlier adoption. And while we are running a Phase III that aim 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 need that has 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 are the duration of treatment that are aligned with the PFS. But also in the clinical studies, there are patients that have been on treatment for years, for 5 years, for 7 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 population 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 forecast. 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 life cycle management in this 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 it back to Jonathan.

So thank you, Pierluigi. Thank you, Sonia. Thank you, Chris, and thank you, Stephanie, 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 I'd just like 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 Stephanie in terms of the eligible patient population. So we feel like we have a really exciting opportunity in cutaneous T-cell lymphoma with both Sezary 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 PAC-9 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 Sezary 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 they are some of the key milestones.

And 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. Yes, we have Yannis Morel, our Chief Operating Officer, with us, who will also be able to support in some more of the more technical questions.

So let's go -- RK, I think you had your hand up first.

Thank you very much for doing this. My name is RK from HC 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 1b where most patients are still in tropicals, how easy is it to convince them to get into a systemic therapy?

Yes. So both great questions. Regarding the benefit, I think that the fact is that we -- in terms of overall survival at this point, we don't really know yet exactly how that will be impacted. But we know that Sezary is a very high-risk disease. The median survival is less than 2 years. As I said, about only 1 in 10 patients are alive at 5 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 lacutamab 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, they control the symptoms, it's already an immediate benefit. So to me, really, as others and Sonia has shown as well, I mean, in Sezary, 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 therapies.

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 kind of the historical flaw in terms of -- but the -- 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.

So then I think we had Justin, I think he had his hand up.

Justin Zelin from BTIG. 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.

Well, the protocol has already been submitted 1 month ago. And despite the FDA shutdown, we obtained feedback from the FDA and replied and address 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 Sezary and MF cohorts, what would you be looking for as far as the delta on PFS?

In which indication?

For both the Sezary and the half versus Romidepsin and Moga.

Well, we -- the intention is really to duplicate the numbers that we observed in TELLOMAK. When you look at Sezary, 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 a suboptimal comparator that is Romidepsin that is the only FDA-approved drug that is remaining in the armamentarium for this 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 Sezary and MF if the agent was available commercially?

Yes, definitely. I think that's really, I think, as a practitioner, as a physician treatment, that's, I think, really where the kind of besides Sezary, 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 time, patients try something and then they stop it. Either they stop it because they have some side effects or they stop because sometimes even a question of payers in terms of reimbursement. So there are a lot of issues, both medical and practical that really prevent patients from studying. 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.

This is Chris from Lucid 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/onc 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's the -- what are your thoughts on kind of the commercial strategy there?

I think from a -- maybe I'll take this one and maybe Stephanie wants to add something. I think this is -- for me, this is a 2-step approach. I think you start with basically with the hem/onc which is where the patients are being treated today. And then I think as a second step is what should be classified as sort of life cycle 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, but it will be in 2 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?

So I think that the breakdown in terms of the specialties that are seeing MF may be more nuanced that perhaps kind of the start differences that particularly the claim 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 in academic medical centers. At academic medical centers, very often, there is co-management of these patients. So dermatologists see it, medical oncologists. 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 oncology, the hematologists might be 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 some 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 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, there is true that there is a significant opportunity for more systemic therapy being prescribed, okay? And that I don't think has to necessarily to do 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 sort of they are 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. So I really feel that it's a very dynamic and the landscape is going to change, I feel, for sure, moving forward. And the strategy going back to what Jonathan said, 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 a little topical therapy. So I think there is a big opportunity for dermatologists to embrace systemic therapy, particularly if it is done in conjunction with hem/onc.

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 and investors should have confidence in Innate here when a partner hasn't stepped in.

Yes. 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, et cetera. 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 Sezary, 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?

Yes. I don't have so much to add, but it's -- I mean, very clear. We are having, I would say, for the last year some -- we have had further during the last year, some conversation with like midsized 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 derisked. 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 this 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 a very high level and you take the [ Sezary ] opportunity, which is in the range of 150, if you divide by 3, which was basically what was the starting point last year for a partner, it's not very attractive for the first indication. So -- but now with -- you have something that -- I mean, it's a bit like KIMMTRAK in the range of 150 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 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 to -- 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?

Yes. Yes.

Yes, I think we've got the confidence to move forward. And 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 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.

Yes. 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 would 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 1 because launching a product, starting a commercial team for $50 million. I mean, it's not profitable whether if you have already on heme franchise in place and you have like an add-on product on a full series of other product, it's an incremental game. But if you have to build everything, it's not worth the effort. So that's why we were at some point really faring 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 in CTCL?

Yes. So from a PTCL perspective, I mean, the -- 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 LYSA, 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 it's -- we don't have a specific plan yet. I don't know whether you want to say some more, Sonia?

Yes, in the sense, we have made some potential planning to move in first line in combination with CHOP -- and also the[ LYSAC ]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 subgroup 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 LYSA, 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 yes, 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 [ LYSAC ], they are a recruitment machine, and they do very well and they recruit studies very, 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.

And maybe one more question for me -- for Dr. Porcu and the broader team, what guidelines are most important in CTCL? And do you see an opportunity, like 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? And 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 sort of -- yes. I think 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 that is focused 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 ERTC may be ESMO as well. I do not 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 systemic -- safe systemic and effective systemic therapies become adopted -- approved and then adopted, the community oncologists 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.

Yes. And 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, and of course, we need to get the data published from 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.