Innate Pharma S.A. (IPHA) Q1 2025 Earnings Report, Transcript and Summary

Hello, and thank you for standing by. My name is Lacey, and I will be your conference operator today. At this time, I would like to welcome everyone to the Innate Pharma First Quarter 2025 Financial Results and Business Update Conference Call. [Operator Instructions]. Thank you. I would now like to turn the call over to Henry Wheeler, Vice President of Investor Relations. You may go ahead.

Thank you. Good morning, good afternoon, and welcome everyone. This morning, Innate issued a press release for our Q1 2025 Business Update and Financial Results. We look forward to highlighting the progress made during the year-to-date, as well as addressing future goals and milestones. The press release and today's presentation are both available on the IR section of our website. On Slide two, before we start, I'd like to remind you that we'll be making forward-looking statements regarding the financial outlook in addition to regulatory and product plan development. These statements are subject to risks and uncertainties that may cause actual results to differ from those forecasted. On Slide three, to cover today's agenda, after an introduction from Jonathan, our CEO, Yanis Morel, Chief Operating Officer, will discuss the preclinical ANKET platform and ADC updates. Sonia Quaratino, our Chief Medical Officer, will cover the clinical updates on the lacutamab 6501 and 4502, who will then hand the call to Jonathan to wrap and close. We also have Frederic, our CFO, on the line for Q&A. Jonathan, over to you.

Thank you, Henry, and good morning to our U.S. participants and good afternoon to everybody in Europe. I'm happy to have the opportunity today to update you on the latest developments at Innate Pharma. Starting with Slide five, which illustrates our revised strategy, as you remember, we updated our strategic focus for 2025, which we shared during our presentation at the JPMorgan Healthcare Conference in January. As a reminder, this is illustrated on Slide five. This strategy is focused on three key growth pillars that we believe will drive long-term value for Innate Pharma, our shareholders, and most importantly, for patients. The first pillar is our NK-Cell Engagers, the ANKET platform which continues to be a critical component of our strategy. We are advancing three key programs from this platform, IPH65, our CD20 targeted ANKET, is currently in phase one. We're excited about IPH65's potential to address hematological malignancies and potentially autoimmune diseases. IPH61 rights will be returned to Innate as of July 1st, and it is progressing in Phase 2 and with Phase 1 data already presented. It was also awarded fast track designation for the treatment of acute AML. We believe that this asset has potential to significantly impact patients' lives. IPH64, our BCMA target ANKET, is in Phase 1 in myeloma in partnership with Sanofi and will be transitioned into autoimmune disease. These three assets continue to drive our leadership in NK-Cell Engager therapies. The second strategic pillar is our antibody drug conjugates. We're particularly enthusiastic about IPH45, our Nectin-4 targeted ADC. The IND cleared last year, and the first patients were dosed in January 2025. This differentiated Topo-1 ADC targets high, moderate, and low Nectin-4-expressing tumors. With Nectin-4 being expressed at varying levels in a range of large tumors, IPH45's ability to bind low, moderate, and high-expressing tumors preclinically significantly expands the potential product opportunity. We also have IPH43, our MICA/B targeted ADC program, which is in research, further advancing our capabilities in ADC. The third pillar is our current late-stage assets. We're committed to advancing our late-stage programs, particularly lacutamab. Following positive Phase 2 data, FDA feedback on next steps, and the U.S. FDA breakthrough therapy designation, we're actively progressing partnership discussions. We are particularly pleased with the lacutamab BTD designation, which underscores its potential to treat Sezary syndrome patients with high unmet medical need. Additionally, monalizumab continues to progress well with AstraZeneca in the PACIFIC-9 Phase 3 trial, and we remain optimistic about [Technical Difficulty]. Turning to Slide six, which highlights our impressive pipeline. As you can see, we're advancing a robust pipeline with eight innovative assets currently in the clinic. The highlights include our proprietary asset, IPH65 for B-cell lymphomas, and our soon-to-be proprietary asset, IPH6101 for AML. Our Sanofi partner's asset, IPH6401, which is now being developed in autoimmune disease, and our proprietary ADC, IPH45, targeting Nectin-4 expressing solid tumors. In Phase 2, we have proprietary KIR3DL2-targeted antibody lacutamab for CTCL and PTCL. And finally, we have our AZ partnered asset, monalizumab, which is being studied for neoadjuvant non-small cell lung cancer, and is in a Phase 3 study for unresectable stage three non-small cell lung cancer. These assets showcase the productivity of our R&D organization and our commitment to delivering breakthrough treatments across a range of cancers and autoimmune diseases. Turning to slide seven, this summarizes the recent transaction with Sanofi. We're very pleased that Sanofi chose to make a €50 million strategic equity investment into Innate Pharma, which reflects their excitement and confidence in the ANKET and our ADC platforms, and the products which are in development. We're pleased to have Sanofi as a significant company shareholder with a 9% holding in our stock. As part of the agreement, Sanofi will return the rights to the CD123 targeting ANKET, IPH6101, which they were pursuing in AML. This will occur on July 1st. As part of their broader strategic reprioritization, this is why the asset was returned. We will evaluate the data for IPH6101 once received and determine the next steps for this program. As a reminder, Sanofi had progressed IPH6101 into Phase 2 in treatment refractory AML patients and initiated a first-line AML Phase 1 study in combination with venetoclax and azacytidin. The other aspects of the agreement with Sanofi remain unchanged. They announced that they pivoted the BCMA targeted ANKET IPH6401 from myeloma into autoimmune indications. They've also have IPH6201, the B7H3 targeted ANKET, and an undisclosed target as part of the agreement. The total potential milestones due on these assets is over 1 billion under our existing 2016 and 2022 agreements. Turning to Slide eight, this highlights our upcoming ASCO presentations. We are very pleased that the long-term follow-up data for lacutamab has been accepted for presentation at ASCO, and we will have updates of both the Sezary syndrome data and the mycosis fungoides data, which was used to support the FDA breakthrough designation. And we're excited that this data, which will be shared at ASCO, continues to mature and improve with time. We also have a trial-in-progress presentation for our differentiated Nectin-4 targeted ADC, IPH4502, and AstraZeneca will present updates for monalizumab from the NeoCOAST-2 trial ahead of the upcoming Phase 3 readout for PACIFIC-9 next year. I'll now hand over to Yannis Morel, our COO, who will present the preclinical data for IPH4502 and IPH6501, and in particular, new data, which was recently presented at AACR in Chicago, and which further differentiates IPH4502. Yannis?

Thank you, Jonathan. I will now highlight the science behind our two strategic pillars that are the NK Cell Engager, ANKET, and the Antibody Drug Conjugate. ANKET is our proprietary first-in-class NK Cell Engager platform. It is a multi-specific plug-and-play technology aiming at engaging NK Cells to our tumor cells by triggering the most stable activating receptor expressed on NK Cell called NKp46. The interesting feature of this platform is that by swapping the tumor binding portion, it can produce multiple drug candidates addressing a variety of targets in oncology, but also in other diseases like autoimmune and inflammatory disease. The recent transition into inflammation of SAR'514, also called IPH6401, our BTMA ANKET developed by Sanofi is illustrating that potential. On the next slide, Slide nine, I'd like to highlight the structure of IPH6501, our lead proprietary ANKET, which is now in the clinic. It's a second-generation NK Cell Engager targeting CD20 that's specifically designed to eliminate B-cells and to induce expansion of patients' own NK Cells. The unique design of IPH6501 involves several key components. First, there is an FAB targeting the tumor-associated antigen, here CD20, in a monovalent way. Second, like in a regular antibody, there is an FT portion that activates the NK Cell receptor CD16. Then the third and key component of the molecule is the NKp46 binder. It targets the NKp46 activating receptor, which is the most specific marker of human NK Cells and which expression is stable on NK Cells in tissues and especially in the tumor-infiltrating ones. Finally, the IL-2 variant portion provides the proliferation signal that is redirected towards NK Cells, helping them to increase their antitumor activity. On the next slide, Slide 10, I like to highlight some of the key differentiating properties of IPH6501 over an approved CD20 T-cell Engager. These data were published last year in Science Immunology. First, on the left, in in-vitro assay, IPH6501 can deplete autologous CD20-positive B-cells with greater efficacy than the T-cell Engager. Also, on the right, you can see that IPH6501 induce significantly less pro-inflammatory cytokines than its T-cell Engager counterpart in non-human primates, thus limiting the risk of cytokine release syndrome in patients. On Slide 11, I will now highlight IPH4502, our lead proprietary ADC. We are very excited by this novel and differentiated Nectin-4 topo-1 exatecan ADC that is currently in Phase 1. This asset is built with a proprietary humanized anti-Nectin-4 antibody, which binds with high affinity to a unique epitope of Nectin-4. With an active FC, it's inducing as well ADCC and CDC, enhancing its immune response potential. The linker used is hydrophilic, stable and cleavable, ensuring high ADC exposure and low release of free exatecan, which minimize potential side effects. The payload exatecan is a potent topoisomerase-1 inhibitor. It has demonstrated bystander activity, as well as strong activity in model resistance to MMAE, which is a payload used in PADCEV, but also in several second generation Nectin-4 targeting agents. These properties allow IPH4502 to potentially target patients with low or heterogeneous Nectin-4 expression due to the bystander effects, as well as patients pre-exposed to MMAE ADC, either because they do not tolerate MMAE or because they are refractory or became resistant to it. I will now highlight some of the recent data that we have presented at ACR in Chicago a couple weeks ago. Next slide. On Slide 12, it is shown that IPH4502 can induce strong anti-tumor efficacy in a Bladder PDX model that became resistant to enfortumab vedotin. Indeed, starting from a Bladder PDX model, which is sensitive to EV on the left, repeated injection of EV induced resistance over time, and this resistance is related to the upregulation of the efflux form MDR-1 without loss of Nectin-4. Interestingly, as the expression of Nectin-4 is maintained, like it's observed in patients treated with PADCEV, and as exatecan is not sensitive to MDR-1, a single injection of IPH4502 can overcome this resistance and induce complete tumor regression. On the next slide, Slide 10, then we have shown that IPH4502 has strong anti-tumor activity in multiple non-bladder Nectin-4-expressing PDX tumor models, including here ADNOC, TNVC, and esophageal cancer. Interestingly, in these two last models, TNVC and esophageal, where Nectin-4 expression is low or heterogeneous, PADCEV didn't show efficacy, highlighting the potential of IPH4502 to address tumor types where PADCEV is not approved. Finally, on the next slide, in this last slide from our ACR poster, I like to highlight very interesting data benchmarking IPH4502 to PADCEV and to a homemade version of the Nectin-4 topo-ADC from Eli Lilly, which is in Phase 1 as well. As you can see in the upper row, when Nectin-4 expression is high, the three ADCs have similar efficacy. However, in the lung cancer model with low Nectin-4 expression, IPH4502 is the only one to show good efficacy. It's notable also that the biosimilar version of the Lilly candidate has no activity at all. And this is explained and actually shown in the poster by a poor internalization and a weaker bystander effect compared to IPH4502. I will now hand over to Sonia to highlight the clinical progress of our proprietary program.

Thank you very much, Yannis. And in Slide 16, I will now cover the proprietary clinical programs, IPH6501, our CD20 targeting and case elongation. IPH4502, the Nectin-4 ADC, and then lacutamab, the anti-KIR3DL2 antibody developed in CTCL. In Slide 16, you will find a high-level overview of timelines for IPH6501. This first in human trial is recruiting well and throughout this year, we plan to complete the dose escalation and we'll look for initial safety data, PK and pharmacodynamic readouts, as well as any preliminary efficacy signals. As a next step, we'll open the dose optimization part of the study to select the optimal dose for subsequent studies and then open expansion cohort in non-Hodgkin lymphoma subtypes. The emerging safety profile and the therapeutic window from the dose escalation will also indicate if this asset may be positioned in B-cell mediated autoimmune diseases where rituximab is often used as a standard of care. In the next slide, we can move to the next program, IPH4502, our lead targeting Nectin-4 and following the IND clearance at the end of September 2024, the first patient was dosed earlier in January this year and the first dose cohort was dosed within a week. We have recently received health authority authorization in France and the French sites are also now operational alongside the U.S. sites. The study is recruiting very well. We are actively working to progress the dose escalation as quickly as possible and we can foresee to be in the pharmacologically active range in the second half of the year. We are therefore looking to generate preliminary Phase 1 safety data by the end of 2025 and then to establish activity in Nectin-4 expressing tumor types that express different level of Nectin-4 from low to moderate and high. As a reminder, the rationale and design of this study will be presented as a trial in progress at the ASCO annual meeting in a couple of weeks. Now in the next slide, I'm excited to share the progress with lacutamab, our first in class anti- KIR3DL2 antibody. This is an antibody that depletes the tumor cells that express KIR3DL2 and is currently under development for the treatment of cutaneous T-cell lymphoma and peripheral T-cell lymphoma, both of which are cancers with high unmet needs. Our Phase 2 data in Sezary syndrome and Mycosis fungoides were presented at ASH 2023 and ASCO 2024 and there were highly encouraging showing that lacutamab have the potential to make a significant impact on these patients. We are thrilled to have received FDA breakthrough therapy designation in addition to the previous FDA fast track and EMA prime designation for SS patients who have failed at least two prior systemic therapies. This designation paved the way for a faster path to approval and are also a testament to the strength of the data. Additionally, Lacutamab has also been granted orphan drug designation for CTCL in the U.S., further emphasizing the critical role it could play in treating rare and challenging cancers. We are very excited about the ongoing development of Lacutamab and its potential to provide a significant benefit to patient when its difficult to treat cancers and we are actively preparing the regulatory package to the FDA and for the EMA to receive authorization to proceed with the Phase 3 trial. We continue to remain engaged with the FDA to finalize the Phase 3 protocol and discussion are progressing according to internal plans. In the next slide, we also look forward to the ASCO presentation on the long-term follow-up for Lacutamab in mycosis fungoides and Sezary syndrome and the compelling data that supported the breakthrough therapy designation. Now, with the strong MF and SS data that we previously presented at ASH 2023 and ASCO 2024, the breakthrough therapy designation and the supporting long-term follow-up data that we are going to present at ASCO this year, there is an increased confidence in the potential of Lacutamab. Our aim is to ensure that Lacutamab gets to patients who need it as quickly as possible and to maximize the value by an accelerated approval. We look forward to update you with the PTCL trial that is performed by the Lysa group and the trial is currently progressing well. I will now hand over back to Jonathan to close this meeting.

Thank you, Sonia, for the update. As you've heard, we have several upcoming R&D catalysts that can be meaningful to our long-term growth. We have several programs coming out of our ANKET platform like our proprietary Tetra-specific ANKET IPH6501, which is progressing well in Phase 1. We also look forward to the first data from IPH4502, our ADC targeting Nectin-4, which is also progressing well in Phase 1. Near term, we're looking forward to the next steps for lacutamab, including finalizing the Phase 3 confirmatory study with FDA following the BTD designation, while advancing partnering discussions, which are well underway. Turning to Slide 22, I'd like to conclude our prepared comments with a few thoughts outlined on the slide. We have a differentiated pipeline with several first-in-class opportunities. We now have eight products in clinical development with four that are currently proprietary and four that are partnered. Our cash position of €72.5 million as of the end of March, excluding the 15 million received from Sanofi's equity investment, will enable Innate to fund our operations through to mid-2026. I would now like to open the call for Q&A.

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

Okay. This is a question, sorry about my voice. I wonder if you could talk about as you look at the IPH6101, CD123 and CAT, as you look through the data coming from your former partner and how ongoing, what's your bar there that it would be worth further investments internally from Innate, specifically on efficacy and safety? Thank you.

Thank you. Yannis, do you want to take that one?

Yes. I think, hi Daina, Yannis is speaking. Yes, thank you for your question. I think it's a bit too early. We actually just signed the restructuring of this agreement. We didn't get the entire package of the data. We will start transitioning the asset back to Innate with an effective transition, completed with a due date for the completion of the transition by July 1. So it's currently a process that is ongoing.

I understand the process. And I understand you haven't seen the data yet, but do you not have any strategic guiding principles before you see the data about what your bar would be before looking at it?

Maybe I can come in here, Daina. I think it depends on the setting we look to take it into. And I think that depends on seeing the data. We need to see whether this is a product for the refractory setting, or whether it's a product for the first line AML setting, or is this a product that should be used for maintenance? And to be able to make those decisions, we need to see the data and understand where that can take us. And I think there would obviously be different bars for each of those different settings. And it would lead to a potentially different decision. So it's a little early to answer your question, but yes, watch this space. I mean, I think hopefully in the next few weeks, we will get at least the first cut of data back from Sanofi. So we'll be able to understand a little better what's been happening in those studies. And then I think that can guide us. And then hopefully by the time of the full transition at the end of July, we'll be in a position to make some firmer statements about what we plan to do with the product.

Your next question comes from the line of Swayampakula Ramakanth with HCW.

So Jonathan, just at the high level, with 87 and change in million in the bank, you have three assets that you're kind of working on with the Sanofi product coming back and also the 6501 and 4502. So what's the high level strategy here in terms of making sure that you can take this product forward? It looks like the industry is having a tough time with financing right now. So how are you thinking through in terms of utilizing your resources in the right way?

Yes. I mean, first of all, we were very happy to receive the strategic investment from Sanofi, which I think as you just pointed out, brings our cash to almost 90 million. That gives us some options in terms of what we do next. Built into our plans, we basically have the ability to take 6501 and 4502 through to the next decision points, which are clearly high in our strategic thinking. There are key priorities in terms of making sure that we get through to those points, which will hopefully generate data, which will allow us to potentially secure further funding via partnerships or via an investment raise. So that basically is the strategies around getting through to those next inflection points, particularly for 4502 and 6501. And that's where we're putting our focus and our effort. And then of course, making sure that we establish hopefully a partnership for lacutamab, which will fund the future development of lacutamab and the confirmatory study that will be required to take advantage of the accelerated approval opportunity in the U.S. for Sezary syndrome. And so they're really, from our perspective, where we're putting our time and attention and making sure that we're adequately funding those programs to make sure that we can go as fast as possible. And I think we've demonstrated that we're going fast. I think 4502 is a good example of that, where we went from IND to first patients recruited at the end of January this year in a very quick period of time. I think it's probably as good as it gets in our industry. We're seeing that program continue to move very quickly in terms of recruitment, which will hopefully put us in a place to be able to share data later in the year. So that's really the strategic focus from the company at this perspective. Now, we have to take IPH6101 on top of that and really identify what we wanna do with this asset. Do we want to partner it out again? That's also a potential opportunity. Do we want to find a way to be able to take this forward ourselves? And again, as I mentioned in the previous question, we need to understand the data a little better to understand which setting is the right one to take the product into to understand what it would take to do that in terms of funding. So that's where we're at today. But I think the key message is our focus is around 4502 and 6501.

Thanks for all that color. On the lacutamab, the long-term follow-ups data that you're gonna put out in a couple of weeks here, how much of that data is being sought after in your conversations with potential suitors?

Yes, that's data that is in the data room that we provide to the companies that are basically under CDA. And that is an important part of the consideration of partner companies because as I alluded to earlier, and as Sonia alluded to, the data with time continues to get better and significantly better. And that makes the argument or the case around the lacutamab even stronger, which is why FDA gave a BTD designation for the product a couple of months ago. So yes, it's important data.

Your next question comes from the line of Rajan Sharma with Goldman Sachs.

So I had one on the B7H3 ANKET. I think it's IPH62, which is partnered with Sanofi. It seems like the B7H3 development landscape is becoming quite crowded. So it'd be helpful just to get your perspectives on the rationale for the target. And also if you could just discuss why this may be a better target for the ANKET platform rather than an ADC, which seems to be the modality that most companies are using to target it. Thank you.

Thank you, Rajan. I think Yannis can take this one.

Yes. Hi, Rajan. So this program is actually the basis of our collaboration expansion with Sanofi in '22. It's a target on which we were working for quite some time at the research level and for which we had a very good and impressive efficacy data in preclinical models. So that's why Sanofi decided to take a license on this one. And then I would say for the mid to long-term development strategy, it's more a question for Sanofi. I agree with you that the target is getting more and more attention, especially through the ADC, but having this alternative orthogonal mechanism, which is an immune mechanism with NK cells could be also a very interesting way to target the B7H3.

Thank you, Rajan. Operator, could you come for further questions? And then I have another question offline.

[Operator Instructions]

Okay, thank you. So a question I received offline from [Osema Dengir at ODO [ph]. On financial visibility, does the current financial visibility include the phase three for lacutamab? Are you considering financing options? And if yes, what options would be favored in that case?

So maybe I can take this one. So in our current cash runway, it does not include the Phase 3 confirmatory study for lacutamab. In terms of how we're looking to move forward, our preferred option, I think, as we mentioned, is to establish a partnership where the partner would basically pick up the cost of the confirmatory Phase 3 study. Having said that, what I think we've said many times is, we won't do a bad deal for lacutamab and we won't give this product away because we believe that this has a significant potential in excess of 500 million. It's hitting a very high unmet medical need for patients. It has a very good reputation as a product amongst the clinical investigators. So we're clearly not going to give this away. So we are exploring alternative options and you can imagine all of the various alternatives that will be possible. We're looking at those options and our objective is to have basically a range of options to choose from at the point when we need to initiate the Phase 3 study, either with a partner or finding a way to fund this ourselves if we need to. And that's basically where we're at today. Okay, I think that was it. I think that was the one. There are no more questions. So I'd like to thank you for your attention and we'll close the call. I wish you all a great day.

Ladies and gentlemen, that concludes today's call. Thank you all for joining. You may now disconnect.