Good afternoon, and thanks for joining us to have a conversation with Jonathan Dickinson, CEO of Innate Pharma, and Stéphanie Cornen, VP Investor Relations. Innate Pharma is a global clinical stage biotech company developing immunotherapies for cancer patients, leveraging its expertise in antibody engineering and innovative target identification. Innate's proprietary pipeline is now centered on antibody drug conjugates led by IPH4502, a differentiated Nectin-4 exatecan ADC, currently in phase I in solid tumors and where dose escalation enrollment has been completed in July, and preliminary data from the 76 patients are expected by the year-end. In parallel, Innate is also advancing two partner late-stage assets, lacutamab, recently licensed to Sobi for T-cell lymphoma, and with Innate running the TELLOMAK-3 confirmatory phase III in support of a planned accelerated approval filing for Sézary syndrome. The last but not least, monalizumab, which has been partnered with AstraZeneca. AstraZeneca is currently running a PACIFIC-9 clinical trial with primary endpoint expected in unresectable non-small cell lung cancer expected by year-end. To discuss all these assets, I welcome Jonathan and Stéphanie to this fireside chat. Jonathan, briefly, for folks who are new to Innate, how would you frame the company's strategies today now that some of the proprietary pipeline is quite centered in the ADC space, and with the other two assets partnered away? Yeah. I think our strategy doesn't really change versus where we were I guess roughly a year ago. About a year ago, we changed our strategy, and we really focused on our three core assets. We actually have eight assets in the clinic, but we really wanted to focus on the three assets that we believe have the best chance to win. It doesn't mean that the other assets are not moving forward. They're in academic collaborations or they're moving forward in a, I would say, a low expenditure sort of mode. So we're putting all of our time and attention into those three core assets, and we've had a number of strategic priorities for those assets. The first was around lacutamab, which was basically moving forward and taking it into a confirmatory phase III study under the Breakthrough Therapy designation from FDA and the accelerated approval pathway that we'd established. But we needed to raise capital to be able to do that, and we were looking at a number of ways of actually doing that. We finally concluded that the best way forward was with a partnership, and we managed to sign a partnership with Sobi in early August. What I really want to emphasize is that doesn't mean we're handing the product completely over to Sobi. Yeah. As part of the partnership, we continue to execute the phase III program, the TELLOMAK-3 program, and we will take forward the accelerated approval, so we will be filing the BLA. So really, lacutamab is still a very core part of what we are doing moving forward, and taking it through to the next steps, which are obviously really important. Then we continue to focus on IPH4502, our Nectin-4 ADC. We have a pivotal data readout coming later this year. So that remains the key focus for the company. Then we have the partnership with AstraZeneca for monalizumab, which is targeting NKG2A in combination with durvalumab. The primary completion date for the phase III pivotal study is actually September, so end of September, so just in a couple of weeks' time. We expect the data readout from the primary endpoint before the end of the year. It is a really busy period of time over the next few months as we continue to execute against those three priority programs that we established. At the same time we established that strategy, we also communicated that we would focus our preclinical activities on coming up with the next wave of ADCs. So we are making good progress along that line, and we are really focusing on some, I would say, interesting and novel aspects to make sure that we bring some potentially best and first in class ADCs to the table out of our preclinical organization. Fantastic. So Stéphanie, you spent quite a bit of this year talking to Investors, obviously with some of the fundraising conversations that you have had. So in general, what do you think people are not still valuing in the story, and where do you think people should start paying attention now that at least the funding part of it is not a question anymore? Yeah. Thank you, Ramakanth. So indeed I think that some parts of the Innate story are still underappreciated. One good example of this was lacutamab. We have spent the past 12 months with Jonathan and Yannis trying to raise awareness about what is the CTCL market, and I think that with the Sobi partnership and the economic of the deal, we have now a tangible external validation of the potential of lacutamab, which is great. Now I think that eyes are focused on Mona, of course, but also IPH4502. The question we receive the most is about the positioning of this asset in the current Nectin-4 ADC landscape, and more broadly in the increasingly competitive ADC landscape. What we refer to is about the evidence that we already have. We know that PADCEV has validated Nectin-4 as a target in urothelial cancer, but there remain a high unmet medical need in the post-EV setting. Lilly has presented two clinical dataset in the post-EV setting, validating in a way the potential of a Topo 1 Nectin-4 ADC in this setting. However, this also reminded us that something that we all know, that in ADC design matters. Because one of the asset from Lilly has been discontinued because of tolerability challenge, and the other one required some pharmacogenomic testing. I think that now the question is really not about is Nectin-4 Topo 1 ADC a valid approach, but is there a Nectin-4 Topo 1 ADC out there that can meet the expectation of a manageable safety profile and a meaningful clinical activity? This is exactly what we are trying to achieve with IPH4502. Very good. Let's start off with the recent news, which is a Sobi partnership. Right. As you stated, you're not really given the development part of the lacutamab. You're still running the clinical trial. Can you speak a little bit more about that arrangement into why you feel lacutamab is better to be developed in your hands, and do you think you would have gotten a better in terms of economics if you had an outright sale of the asset itself? Yeah, it's an interesting question. We spent a lot of time really evaluating which direction to go in. Is this something we should try and do ourselves? Is this something we should partner? I think it really all depended on the deal that was on the table, and I think we'd always communicated this. If we got the right deal, then partnering will clearly be the preferential way forward. In the absence of the right deal, we were prepared to try and take this forward ourselves, and we thought it would be viable to be able to commercialize lacutamab ourselves. It's a relatively small number of customers that you would need to hit in the U.S. Probably 50 centers you would get to the majority of the patients. So it was definitely something that was viable to take forward as a small biotech company. But at the end of the day, we got a really great deal on the table with Sobi, which had really good deal economics associated with it. It provided the capital up front for us to be able to move forward with the phase III program and really start the clock on moving towards the accelerated approval. I think if we look at the partner we have, it's a really great partner for lacutamab. The initial indication is Sézary syndrome. It's an ultra-rare indication. Then coming with mycosis fungoides, which is also a rare indication. So Sobi has a real specialty in rare diseases and in particular in oncology. I think what we're able to do here is combine the synergies of both companies. We have expertise in CTCL and allowing us to continue to take the phase III program, that sort of builds on our skillset. And then we have Sobi who will come in. They have the infrastructure there to be able to commercialize lacutamab in the most effective way, the most quickly. We will be able to provide lacutamab, I would say, to patients probably more quickly and more effectively with Sobi taking that role than if we were building an organization ourselves. That is good for patients, but it is probably good for Innate at the end of the day in terms of the royalties that we will achieve on sales and the milestones that we will hit under the collaboration agreement. I think in the end, it was a pretty easy, straightforward decision to actually go with the partnership. The accelerated approval filing that we are talking about still rests on the phase II TELLOMAK data in the Sézary post-mogamulizumab with 43% global ORR and 25.6-month median duration of response. What have your FDA interactions told you that needs to be in place to do that filing, and where should TELLOMAK- 3 enrollment be at that point? The discussions we had with FDA under the Breakthrough Therapy designation, which is really important because it gave us really good access to FDA, and we had a number of backward and forward interactions. But basically, the guidance we got from FDA was that we need to have the confirmatory study up and running. It needs to be recruiting patients, and we need to have established a recruitment trajectory that gives them confidence that we will go on to fully recruit the study. We believe that that means we need to have recruited some patients. We need to have a good number of the sites open. Basically demonstrating that the company is committed to moving this forward. And at that point, we will have a pre-submission meeting with FDA and file the accelerated approval BLA off the back of that. In terms of timelines, we expect to have the TELLOMAK 3 study initiated in the coming weeks. We expect to be able to have the first patient included in the beginning of 2027. And then we expect to submit the BLA in the second half of 2027, which with a six-month clock will read to an accelerated approval in the first half of 2028. Can we just discuss a little bit on the highlights of the TELLOMAK-3 study itself as it is set right now, and then in terms of enrollment that we are talking about, that you have to show a certain trajectory. Is there anything hard in terms of sales with the FDA, or is it a trajectory which they decide whether it's the right one? No, just addressing that question, I think the conversation we had with FDA is that they want to see the study up and running. I think that's the most important thing is that the study is up and running, particularly in a rare disease like- Correct Sézary, where there's a very small number of patients. We've seen recently, I think with some FDA precedents, that they're being quite lenient on this in rare diseases. Yeah. They're giving quite a lot of leeway. Our expectation is you have the study up and running, you've recruited a handful of patients, you have the right number of centers open that shows that you're really committed to getting the patients, and it should be a relatively straightforward path at that point. In terms of the study itself, we plan to go to nearly double the number of centers that we went to in TELLOMAK. Okay. We have a lot of experience in this market, having recruited the TELLOMAK study. We know where the patients are, we know the centers that we need to go to, and we're increasing our footprint. It will be a global study. That gives us a lot of confidence that we'll be able to recruit the patients in a very timely way, and we'll fulfill the requirements that the FDA need to see that this study is going to deliver. Okay. Getting into IPH4502, the Nectin-4 exatecan ADC. How differentiated is this molecule versus other Nectin-4 ADCs that are out there in the clinic? We specifically designed this molecule to be differentiated, and we did that in a number of ways. The first is the epitope that we hit. We hit a non-overlapping epitope versus any of the other Nectin-4 ADCs out there. What we've been able to demonstrate pre-clinically is that that means that we combine not only the high Nectin-4 expressing tumors, but also the low and the moderate Nectin-4 expressing tumors. That's one level of differentiation. We think we have a better antibody, basically from a binding perspective for Nectin-4. Then with the payload, we've switched the payload out. We have a very well-validated payload in exatecan. I think that's important, because we're not encountering some of the issues like with the Lilly Nectin-4- ADC. They had this issue with metabolism through CYP2D6 where there is genetic variation with their camptothecin payload. That led to some severe toxicity in the low metabolizers. That creates issues for their program. You need to be aware of drug-drug interactions. You have to exclude the low metabolizers. Then if you think from a commercialization perspective, that is difficult. That is important. We have exatecan, it is a very well-known payload. That overcomes the drug resistance issue associated with MMAE as a payload. That has been validated by the Lilly approach actually, so that is great. Then we combine that with our proprietary linker, and we know we very tightly bind the payload. That is important because if there is less recirculating payload, we see less toxicity. We see that coming through in our phase I dose-finding study, where we have low levels of recirculating payload. We have seen minimal hematological toxicity, which would be an off-target tox. Yep. Our DLT was actually an on-target tox. I think it is validating our linker approach and pulling all those three levels of differentiation together. I think we have an opportunity to thread the needle here and really come up with something that can show efficacy, but can have a really good level of safety, and not have some of the liabilities of some of the other Nectin-4 ADCs which are out there today. Okay. At the year-end data update that we are expecting from this molecule, what sort of data will make you comfortable that you are on the right pathway? I think the key thing is the safety. Obviously, the primary endpoint of this phase I dose-finding study is safety. If we see good safety combined with some level of activity, I think that will give us confidence that we have a pathway to move forward with this particular product. We'll look forward to presenting the complete data set. I think the importance will be the totality of the data set. Our phase I dose-finding study, it's a basket study in a range of different tumor types. We've tried to over recruit in certain tumor types, so that we will be able to see some sort of trends in that. It will be the totality of the data which will count particularly from an efficacy perspective, and then from a safety perspective across the board. In terms of the ADC portfolio that you're talking about, you have previously talked about looking into bispecific formats, better internalization, and also novel dual payloads. Of all these things that you're talking about, which ones do you think are close to be unveiled maybe in 2027? Are you still playing with these different formats to figure out which one gets closer to pre-IND stage? I think what we're doing, we're really focusing now on trying to bring something to the table that's going to be truly innovative. There's a lot of work ongoing in the ADC space, a lot of potential molecules out there. I think the key thing here is to come with something that's going to be truly differentiated. We're actually following three approaches at the moment from an ADC perspective. We're looking at bispecifics to start off with, and we have, I would say, a world-class expertise in antibody engineering. This is something that we do a really good job of. What we're trying to do is then to combine that with a couple of things. We're trying to look at very tumor-specific antigens that are maybe expressed at very low levels. It's difficult then to get enough payload into the tumor cells. What we're aiming to do is to combine those very tumor-specific antigen antibodies with professional internalizing molecules, so that we're able to ensure that with this very specific approach to a tumor, we're able to get enough of the payload into the tumor cell and to have the cell killing that's required to have an effective product. That's one approach that we're really looking at. The other is dual payloads combined with the bispecifics and the other approach. When I say dual payloads, it's not a question of combining a Topo 1 and a tubulin inhibitor. It's really coming up with novel payloads that will bring something truly differentiated to the table. We're really working really hard in our preclinical organization now to bring the right target products through into the next steps to then be able to go into the IND-enabling stage. We're a little bit away from being able to do that. That's not something you should expect in the next couple of months. But it's something we've got some very interesting concepts that we're working on, and we're very confident that we're going to have some approaches that we'll be able to take forward next year, and then potentially from that into IND-enabling studies. One quick question on monalizumab. You were talking about how the study could end in September, but the primary endpoint data is expected hopefully by the year-end. What sort of data are you looking that it'll get disclosed? And how should investors view that data in relationship to the totality of that program? For monalizumab. I think for mona, it's a PFS endpoint. I think providing we're hitting a reasonable hazard ratio with a good PFS number, I think there'll be a path forward. If we see a positive study here, this should move forward, and it should move forward into commercialization. And I think it's in AstraZeneca's interest to take forward the product. They need to protect the durvalumab franchise. This would be one way to do that, and they have a substantial amount of sales at stake here in the Stage 3 non-resectable, non-small cell lung cancer setting. Mona will play a very important role here if the study is positive. Based on the COAST data, which was a randomized phase II with the regimen that's being used in the PACIFIC-9 study, it led to a 12-month median PFS advantage in the mona arm versus durvalumab. So we have a reasonable level of confidence that if we can come close to replicating that level of efficacy, that you're going to see a positive study. And I think that obviously will be transformational for the company because there's some excellent deal economics associated with a positive study. Under the original collaboration agreement, there was up to EUR 825 million, on top of the EUR 450 that we've already received. There's a mixture of development, regulatory milestones, and commercial milestones. And obviously, that will be transformational for the company. It will be a fantastic source of non-dilutive funding for some of the other programs we want to take forward, like our ADCs and potentially IPH4502. It's a really important catalyst for the company. Just a last question and to close the conversation. AstraZeneca's license on monalizumab is only for oncology indications. Do you see that drug in other indications potentially outside of oncology? If yes, do you see yourselves partnering it out or looking for another way of non-dilutive funding? Yeah. I think you're referring to some very interesting data presented earlier in the year in fibrosis. Yes There was a very strong preclinical hypothesis for taking the product into fibrosis. I think for us, the PACIFIC-9 study is gating. If that study is positive, then I think fibrosis is something that we should definitely be looking at, and looking at how we take that forward. As you stated, the AstraZeneca license is just for oncology, so the fibrosis indication would be proprietary for Innate Pharma. I think we will be open to different approaches here if we've got a good source of non-dilutive funding coming in from mona through the AZ collaboration. That would afford us the opportunity to potentially do this ourselves. My guess is that if PACIFIC-9 is positive and mona is moving forward, that AstraZeneca would be very interested to control the entire rights— Rights. Yeah. for monalizumab. I think they could potentially be a partner that we would certainly be having discussions with. I think because fibrosis is such a big unmet medical need, if there really is a good approach here, there could potentially be other companies. I think it could get competitive. We should be able to find a partner or take it forward ourselves. I think that's all a next step after a positive PACIFIC-9 study. Fantastic. Yeah. Great. Thank you very much, Jonathan. Thanks for taking time. Thank you, and thanks for inviting us.