Innate Pharma SA (IPHA) 2024 Q4 法說會逐字稿

Hello, and welcome to the Innate Pharma full-year 2024 financial results and business update. (Operator Instructions)

I would now like to turn the conference over to Henry Wheeler, Vice President, Investor Relations and Communications.

Thank you. Good morning, good afternoon, and welcome, everyone. This morning, Innate issued a press release for our full-year 2024 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 2, before we start, I would like to remind you that we will be making forward-looking statements regarding the financial outlook in addition to the 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 3, to quickly cover today's agenda, after an introduction from Jonathan Dickinson, CEO; Yannis Morel, COO, will then discuss our pre-clinical and platform and ADC updates. He'll then hand over to Sonia Quaratino, our Chief Medical Officer, to cover the clinical updates on the lacutamab, IPH6501, and IPH4502. He will then hand to Frederic to cover the financials, our CFO, who will then hand to Jonathan, who will then wrap and close.

Thank you, Jonathan, over to you.

Thank you, Henry, and good morning to our US participants, and good afternoon in Europe. I'm happy to have the opportunity today to update you all on the latest developments at Innate Pharma.

Turning to slide 5, which illustrates our significant achievements, as we look back at 2024 and what we have achieved so far in 2025, I'm excited to share the progress made in advancing our innovative therapies and the key milestones we're expecting. IPH65 remains a key focus for Innate, and we're pleased that the first patients were recruited into the Phase 1 dose finding trial in the first half of 2024.

This represented a critical step in the product's clinical development, and we are now focusing on progressing the trial rapidly through the next dosing cohorts so that we're able to share data towards the end of this year or early next year. We are highly committed to this program and optimistic about its potential to address unmet needs in oncology and potentially autoimmune diseases.

We are thrilled with the progress of our Nectin-4 targeted ADC, IPH45, with the first patients dosed in January 2025, following the IND clearance in September 2024. This is an exciting milestone, and we are confident that this therapy will make a meaningful impact for patients. Our team is dedicated to moving this program forward rapidly and delivering the next generation of treatment for patients in need.

Finally, we turn to lacutamab, which has made good progress recently on the path to commercialization. We are incredibly excited about the breakthrough therapy designation granted to lacutamab by the FDA. This brings lacutamab one step closer to a potential accelerated approval following the productive feedback received from FDA last year.

This achievement is based on the strong data we have seen to date and reinforces the potential lacutamab has to significantly help patients in need. As we continue our interactions with the FDA to finalize the confirmatory Phase 3 in the coming months, we also look forward to sharing updated long-term follow-up data via publications at key scientific meetings. We also continue to look for the best path forward for lacutamab with partnership discussions advancing well.

We also continue to advance our early pipeline with the expectation to discover new ANKETs and ADCs. As we look ahead to 2025, we are confident that we are building momentum across our pipeline with significant achievements in IPH65, IPH45, and lacutamab. We remain dedicated to delivering breakthrough therapies to patients in need and are excited about the opportunities the next years will bring.

As we reflect on our strategic focus for 2025, I want to take a moment to remind you of the updated strategic focus we shared during our presentation at the JPMorgan Healthcare Conference in January, which is illustrated on slide 6. Our strategy is focused on three key growth pillars that we believe will drive long-term value for Innate Pharma, our shareholders, and importantly for patients.

The first pillar is our NK cell engagers. The ANKET platform continues to be a critical component of our strategy. We're advancing three key programs. IPH65, our CD20 ANKET, is currently in phase one. We're excited about IPH65's potential to address hematological malignancies and potentially autoimmune diseases.

IPH61, our CD123 targeted ANKET, is progressing in Phase 2, with Phase 1 data already presented by our partner Sanofi. Fast track designation was awarded for the treatment of acute myeloid leukemia. We believe that this asset has the potential to significantly impact patients' lives.

IPH64, our BCMA ANKET, is in a Phase 1 trial in myeloma in partnership with Sanofi and will be transitioned into autoimmune diseases. These three assets continue to bolster our leadership in NK cell engager therapies.

The second strategic pillar is our antibody drug conjugates. We are 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 over expressing Nectin-4 tumors. With Nectin-4 being overexpressed at varying levels in a range of large tumor types, IPH45's ability to bind low, moderate, and high expressing tumors pre-clinically significantly expands the potential product opportunity.

We also have IPH43, our MICA/B targeted ADC program in research, further advancing our capabilities in ADCs. The third pillar is our current late-stage assets. We're committed to advancing our late-stage programs, particularly lacutamab, with positive Phase 2 data and the FDA feedback on next steps. We are actively progressing partnership discussions.

Lacutamab has also been awarded US FDA breakthrough therapy designation, which underscores its potential in treating Sézary syndrome patients with high unmet medical need. Additionally, monalizumab continues to progress well with AstraZeneca in the PACIFIC-9 Phase 3 trial, and we're optimistic about its future potential.

Slide 7 highlights our impressive pipeline. We are advancing a robust pipeline with eight innovative assets currently in the clinic. The highlights include our proprietary asset IPH65 for B cell lymphomas; our Sanofi-partnered assets, IPH6101 for AML and IPH6401 now for autoimmune diseases; and our proprietary ADC IPH45 targeting Nectin-4 expressing tumors.

In Phase 2, we have our proprietary KIR3DL2 targeted antibodies lacutamab for CTCL and PTCL. And finally, we have our A partner acid monalizumab, which is being studied for new adjuvant non-small cell lung cancer and in a Phase 3 study for unresectable Stage 3 non-small cell lung cancer. These assets demonstrate the productivity of our R&D organization and our commitment to delivering breakthrough treatments across a range of cancers.

Slide 8 illustrates our Q4 conference activity at SITC and ASH last year. At the SITC meeting, we presented further pre-clinical data on our next generation CD20 targeting ANKET IPH65, as well as extensive pre-clinical data on our Nectin-4 targeted ADC, IPH45.

At ASH last year we were pleased to present lacutamab quality of life and pruritus data in an oral presentation. This oral presentation showcased the consistency between the clinical and quality of life data and the important impact of lacutamab on patient wellbeing. There was also a poster presentation of translational data from the TELLOMAK trail.

I would like to now pass the call to Yannis who will review the pre-clinical rationale of our key strategic pillars in ANKETs and ADCs. Yannis?

Thank you, Jonathan. I will now highlight the two exciting next-generation antibody therapeutic classes on which we are focusing the NK cell engagers, ANKETs, and antibodies drug conjugates.

On slide 10, I draw your attention to our portfolio of ANKET. 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 towards tumor cells by triggering the most stable activating receptor expressed on NK cells 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 it can also potentially harness NK cells to eliminate pathogenic cells in other diseases like in autoimmune disease.

In '24, Sanofi progressed the most advanced ANKET SAR'579, to Phase 2 on the back of initial efficacy data showing single agent activity with durable complete responses in relapsed refractory AML patients and started also a new Phase 1/2 trial in frontline AML in combination with venetoclax and azacytidin.

For the BCMA targeting ANKET IPH6401, the Phase 1/2 study led by Sanofi for the treatment of patients with relapsed or refractory multiple myeloma will be stopped early, and the product will now be pursued in autoimmune indication.

As will be covered by Sonia, our lead proprietary ANKET IPH65, is now in the clinic. It's a second-generation molecule which incorporates a variant of IL-2 to induce the expansion of patients' own NK cells, and for which we presented new supporting technical data at the CITI conference at the end of last year.

On slide 11, I'd like to highlight the structure of IPH6501, which is our lead proprietary ANKET. It's a novel CD20 targeted tetra-specific NK cell engager that's specifically designed to target B cells. The unique design of IPH6501 involves several key components, each of which enhance its therapeutic potential.

First, we have a MICA/B targeting the tumor associated antigen here CD20 in a monovalent way. Second, like in a regular antibody, we have an Fc portion that activates the NK cell receptor CD16. Then the third and key component of the molecule is the NKp46 binder. It targets this NKp46 activating receptor, which is the most specific marker of human NK cells, and which expression is stable on tumor infiltrating NK cells.

Finally, the IL-2 variant portion provides the proliferation signal that is directed towards NK cells, helping to boost their activity and enhancing their immune response against cancer cells. IPH6501 represents a significant innovation in our NK cell engager platform, and we are excited about the potential it holds for patients with B cell malignancies.

As we continue to advance these assets, we believe it could pave the way for a new class of immunotherapies targeting solid and hematologic tumors and potentially autoimmune disease. On slide 12, I will highlight IPH4502, our lead proprietary ADC. We are very excited by this novel and differentiated Nectin-1 topo-1 exatecan ADC that is currently in phase one of development.

This asset is built with a proprietary humanized anti-Nectin-4 antibody which binds with high affinity to Nectin-4. With an active Fs, 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 and that demonstrates bystander activity as well as strong activity in MMA resistance model, allowing it to target tumors that may be resistant to previous ADC therapies.

Slide 13, as presented at AACR and SITC last year, IPH4502 has demonstrated superior efficacy to enfortumab vedotin in bladder cancer pre-clinical model, especially in tumors with low Nectin-4 expression or in model resistance to EV. Its unique design translates into high internalization and strong bystander effect, making it effective even in Nectin-4 low tumors.

This could position IPH4502 as a potentially valuable therapy for a broad range of solid tumors, including breast cancer or lung cancer, but also with strong combination potential with PD1 targeting agents. As we continue advancing IPH4502 through clinical development, we are excited by its broad therapeutic potential and look forward to the data we'll generate in the coming months.

I would like now to hand over to Sonia who will cover the progress of our clinical programs.

Thank you very much, Yannis. I will now cover the proprietary clinical programs IPH65, the second-generation NK cell engager targeting CD20 positive B cell lymphoma, IPH45, the Nectin-4 ADC to be developed in solid tumor, and lacutamab developed in CTCL and PTCL.

Now in slide 16, we present an overview of timelines for IPH6501. If we continue with the current fast-paced recruitment, we plan to complete the dose escalation by the end of this year, and we may have initial safety data, PK, and pharmacodynamic readouts, as well as any preliminary efficacy signals.

As a next step, we will 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 therapeutic window from Phase 1 will also indicate if this asset may also be safely and effectively positioned in the autoimmune field, in particular in B cell-mediated autoimmune diseases where rituximab is used as a standard of care.

Moving to the next program in slide 17, we summarize the next steps of our highly differentiated ADC IPH4502 targeting Nectin-4. Following the IND clearance at the end of September, the first patient was dosed in January in the US and the first cohort was dosed within a week.

We are swiftly proceeding with the dose escalation in this trial, and we may have also -- and we have already received health authority authorization in France, and the first site in France will be opened soon. We are actively working to progress this dose escalation as fast as possible, and we are looking forward to generating preliminary Phase 1 safety data by the end of the year, and then to establish activity in tumors expressing different levels of Nectin-4 from low to moderate and high. The study will be presented at ASCO this year.

Finally, in slide 18, I'm excited to share the progress of lacutamab, our first-in-class anti-KIR3DL2 antibody that kills those tumor cells expressing this tumor associated antigen. This asset is under development for the treatment of cutaneous T cell lymphoma, an indication with high unmet medical need, and via an investigator-sponsored trial in peripheral T cell lymphoma, PTCL.

The results from the Phase 2 in CTCL in Sézary syndrome and mycosis fungoides were presented at ASH 2023 and ASCO 2024, and they've been highly encouraging, showing that lacutamab has the potential to make a significant impact on this patient population.

Based on these results, we are thrilled to have received FDI breakthrough therapy designation for Sézary syndrome in addition to the previous regulatory milestones such as FDA fast track, EMA prime designation for SS patients who have failed at least two prior systemic therapies. These designations paved the way for a faster path to approval and also are a testament to the strength of the data.

Additionally, lacutamab has been granted orphan drug designation for CTCL in the US, further emphasizing the critical role it could play in treating rare and challenging cancers. We are incredibly excited about the ongoing development of lacutamab and its potential to provide significant benefit to patients with these difficult-to-treat cancers, and we are actively preparing the regulatory packages for the FDA and for EMA to receive authorization to proceed with the Phase 3 trial.

In slide 19, I would like to discuss, the path forward, where do we stand in terms of business case. And the data generated from the TELLOMAK trial confirmed clinical benefit not only in Sézary but also in MF regardless of the expression of the target KIR3DL2, highlighting the opportunity for the CTCL space without a companion diagnostic.

Therefore, the number of CTCL patients that could potentially benefit from lacutamab expands to 3,500 in the second prior line of therapy and to 5,000 should we move in an earlier line setting as discussed with the FDA. With the strong MF data presented at ASCO and the data in Sézary at ASH 2023, the BTD and the supporting long term follow-up data that we will 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 needs as quickly as possible and to maximize the value via an accelerated approval. And I will hand over to Frederic.

Good morning. The key elements of Innate financial position and financial results as of and for the year ended December 31, 2024, are as follows. Revenue and other income from continuing operations amounted to EUR20.1 million in '24. It mainly comprises revenue from collaboration licensing agreements at EUR12.6 million and a resource tax credit for EUR7.5 million.

Revenue from collaboration and licensing agreements mainly resulted from the partial or entire recognition of the proceeds received pursuing the agreements with AstraZeneca and Sanofi. Operating expenses from continuing operations amounted to EUR71.7 million in 2024 with 73% of expenses related to R&D.

General and administrative expenses from continuing activities amounted to EUR19.7 million in 2024, showing an increase of EUR1.4 million versus prior year. This variation results cumulative -- results cumulatively from a reduction in personal expenses, a one-off increase of non-scientific fees, and an increase in other expenses mostly driven by R&D tax credit financing costs.

R&D expenses from continuing activities amounted to EUR52 million in 2024 and a reduction of EUR4 million versus prior year. Half of this decrease was due to a decrease in direct research and development expenses in line with the maturity of clinical development programs. The other half of the decrease was due to depreciation and amortization.

Cash, cash equivalent, short-term investments, and financial assets amounting to EUR91.1 million as of December 31, 2024. Financial liability amount to EUR31 million down from EUR39.9 million from the end of 2023. This change is mainly due to the loan repayments. So based on that and based on our calculations, this gives us sufficient cash to fund operation through the mid-2026. So I now hand over to Jonathan.

Thank you, Frederic. We have several upcoming R&D catalysts that can be meaningful to our long-term growth. I would draw your attention, particularly to the ones that are bolded in this slide. Programs coming out of our ANKET platform continue to advance as IPH6101 targeting CD123 and hematological malignancies and partnered with Sanofi progressed to Phase 2 last year.

Our proprietary tetraspecific ANKET that goes by IPH65 is now in clinical development. We're also looking forward to the first data from our ADC targeting Nectin-4 in Phase 1. Near term, we're looking forward to the next steps for lacutamab now that we have positive FDA feedback and BTD designation and, of course, partnering discussions underway.

Turning to slide 25, so that's the conclusion, and I would like to hand over to the operator for Q&A.

(Operator Instructions) Daina Graybosch, Leerink Partners.

Hi, guys, thank you for the question. I want to ask one about NHL and your expectations for IPH6501. I think that some of the recent therapies, the CD19-targeted therapies, for instance, have underperformed some of the Street's expectations and I wonder if you have a hypothesis on why and what gives you confidence there's a market for IPH6501? And then do you have confidence as a single agent or do you think that we'll need to get to combinations?

Thank you, Daina, for the question. As you know, the non-Hodgkin lymphoma space, it's a highly crowded, space, and we acknowledge that, of course. On the other hand, we expect to see some efficacy based on the data that we obtained from pre-clinical model. Especially as the CD20 is a target that is not down regulated in the disease, similarly to the CD19, for instance.

And in particular, the safety profile that we expect to see, and it's so far confirmed is very benign. And that could also be a differentiating factor for other ongoing therapies that are in the space, considering that patients in this trial are particularly frail, and they've pre-treated with already an extensive number of drugs.

For the time being, we focus on the monotherapy. We cannot exclude that this could also be used in combination with the standard of care. Of course, yeah, and only emerging data will confirm.

There are no further questions at this time.

Hi, I've got some offline submitted questions. So first question from Eric Le Berrigaud, Stifel. On IPH6401, is the understanding correct that Sanofi is not adding autoimmune diseases as a new space where to investigate the candidates but is switching focus from MM, where development is terminated into auto autoimmune disease?

At first glance, it looks disappointing, not only because BCMA is well established in multiple myeloma and Sanofi is a player in this space, but also because BCMA looks much more speculative and uncertain in autoimmune disease. It looks highly exploratory. Any chance you can share what type of autoimmune diseases would be prioritized and if any evidence has emerged associating BCMA with any?

Yes. Yannis speaking. Yes, Eric, your understanding is correct. The IPH6401, so the BCMA targeted NK cell engager will now be refocused from multiple myeloma towards autoimmune disease. We see that -- rather as given the strategic focus and the very strong capabilities of our partner Sanofi in I&I, we see that as a positive signal. We didn't see any data for the moment from the ongoing Phase 1, but we assume that the data are supporting this transition, and we really look forward to seeing which indication Sanofi will progress this asset in I&I.

Swayampakula Ramakanth, H.C. Wainwright.

Thank you. Quick question on the partnering discussions, ongoing partnering discussions regarding lacutamab. I apologize, I was not on the call as this kind of dots between earnings calls, so at least if you can highlight what, what's going on in that realm?

Hi, RK. Yannis speaking. We are having like several parallel discussions with potential partners that are progressing well. We have a data room open, and people are looking into it. And so far, I cannot really tell you more about it, but just that it's progressing well.

Okay, thank you. And then on the ANKET programs, in both with the 6101 and 6401, do you see any one of them moving into the next stage of development, either in late '25, early '26? Or what do you think is -- or how do you think those two programs are progressing in Sanofi's hands, and what sort of indications would they be going after in the next -- in the late stage of development?

For the IPH61, so the SAR'579, actually Sanofi already transitioned from Phase 1 to Phase 2 last year. We get a milestone for that and now they are really in this confirmation phase in relapsed/refractory IML setting, so they need to first complete that before transitioning to a later stage of development.

For IPH6401, as I just said, the development is now repurposed into I&I. We don't know yet in which indication will be targeted. We will know more when Sanofi will start the clinical development of it. But you can guess that it will be in B cell-mediated disease because the target is BCMA.

So the purpose is to deplete cells that are producing antibodies because they are expressing BCMA. But for the moment we still need to have more information from Sanofi to really understand in which indication it will be developed.

Okay, thanks for taking the questions.

Daina Graybosch, Leerink Partners.

I wonder if you could update us on potential confirmatory trial strategies or plans that you're considering going to with FDA that could support the accelerated approval of lacutamab?

Hi, Daina. We are, let's say currently working to align with both the FDA and EMA around the confirmatory trial. And this is going to be in the CTCL space so SS as well as MS. This is going to be, let's say a global trial, and it needs to be really finalized the details with the health authorities.

And you can't give us any details on various design elements that you're considering different options for?

Well, this is going to be a randomized control study, and we need really to have an agreement with the FDA before we can really discuss more details. You can imagine that the primary endpoint might be PFS. And in terms of the comparator to be used for this study, this is something that we really need to align and have the buy in from the health authorities before we can discuss it on this forum.

All right, thank you.

All right. So another question received offline from Eric Le Berrigaud, Stifel. I'm unclear whether you've made a decision to move forward with lacutamab in Sézary syndrome to regulators or if it is yet dependent on Phase 3 formal start in CTCL and/or upon finding of a partner more globally for the drug across all indications? Thanks for clarifying.

I presume that this question refers to the accelerated approval that we have discussed with the FDA in our type C meeting at the end of last year. And if so, the accelerated approval can only be obtained when the Phase 3 is up and running and recruiting.

So in that respect, going back to the question that Daina made before, our plan is to have a Phase 3 in MS and in SS and only then we can go back to the FDA with the pre-BLA meeting and submit the package to obtain an accelerated approval, while the Phase 3 is up and running. I hope that I've addressed the question.

Maybe I can add something. It's Jonathan here. We are very actively working at this point in time to finalize that phase 3 program, clinical trial confirmatory study. So we're working on the premise that, we're moving forward, with that Phase 3 confirmatory study.

And in due course, once that study is up and running, and the recruitment is well underway and there's a good cadence of recruitment in the study will be the time point at which we can then go back to FDA and potentially have a discussion about when exactly the BLA could be filed. But the company is working on the premise that this will be moving forward, ideally with a partner, which I think was part of the question.

But if we can't find a partner with a good deal, which I think is important from our perspective, it has to be a good deal that makes sense, from an Innate perspective, then we are working on a plan B to be able to take this forward ourselves.

Thank you. Another question offline again from Eric Le Berrigaud, Stifel. Lastly, considering that EUR91 million of available cash provides runaway into mid-'26, is it fair to expect cash burn to be circa EUR60 million to EUR70 million per year? Or are you including in the calculation any cash inflow over the period that goes beyond tax credits?

Thanks for the question. So as usual, we do not plan in the cash burn anything which is not under our control. So any potential proceeds from potential coming partnership or equity is not included because it's -- the probability is until it's signed, it's 50-50, let's say.

So it's not included, and we have a small cash inbound of EUR6 million which is a financing which is absolutely under our control with more than 95% and which is very limited. So as usual, no major inflow which is not already public, and the cost is as expected based on the strategy.

Thank you, Frederic. Another question received offline, from Oussema Denguir, ODDO. A quick question on working capital variation maybe I've missed something in the release. Can we have more color on the trade receivables variation?

So this one, it's a particular year for sure. We've communicated on that last year. We did enjoy the repayment of 2019 and 2020 research tax credit in 2024 for about EUR30 million, so it has provided an inflow in cash of EUR30 million but the corresponding trade receivable decrease. And also, as I explained before, we have decided to finance the cash, the resource tax credit of 2023 instead of waiting for 2027 to have the cash in.

So it's also generated EUR8.5 million of credit receivable, this decrease in the year. So in this year you had more than in a range of nearly EUR40 million of credit receivables decrease, which is one off related to the to the resource tax credit repayment.

Thanks, operator. No further questions offline unless there are any more on the call.

There are no questions at this time.

Okay, thank you very much.

This will conclude today's conference call. Thank you for joining. You may now disconnect.