Innate Pharma S.A.

Hello, and thank you for standing by. My name is Regina, and I will be your conference operator today. At this time, I would like to welcome everyone to the Innate Pharma third quarter 2024 business update and financial results conference call. All lines have been placed on mute to prevent any background noise. After the speaker's remarks, there will be a question and answer session. If you would like to ask a question during this time, simply press star, then the number one on your telephone keypad. To withdraw your question, press star one again. I would now like to turn the conference over to Henry Wheeler, Vice President, Investor Relations. Please go ahead.

Thank you. Good morning, good afternoon, and welcome, everyone. This morning, Innate issued a press release for our Q3 2024 business updates 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 risk and uncertainties that may cause actual results to differ from those forecasted. Slide three, on today's call, we are very pleased to be joined by Jonathan Dickinson, our new Chief Executive Officer. Jonathan is a seasoned healthcare professional and joins from Insights. He has a strong background in oncology and previous roles include Ariad, BMS, Roche, and Novartis. On the next slide, to cover today's agenda, after an introduction from Jonathan, Sonia Quarantino, our Chief Medical Officer, will cover updates on Nucutimab, IPH6501, and 4502. We will then hand to Yanis Moral, Chief Operating Officer, who will then discuss our ANCET platform, ADC-CITC, and MonolizMAP updates. Arvind Sood, EVP, US Operations, will wrap and close, and we'll also have Frederick Lombard, our CFO, on the line for questions. Jonathan, I now hand the call over to you.

Thank you, Henry. Good morning and good afternoon to everybody on the call. I'm very excited to join Innate Pharma, a company which is at the forefront of cutting edge science in oncology. The innovative work being done at Innate is truly inspiring and world class, and I'm looking forward to using my extensive oncology experience to shape the Innate portfolio to maximize the future commercial potential and drive the next chapter of Innate's exciting journey. I look forward to meeting with as many of you as possible in the coming weeks. Turning to slide six, I would like to remind you of our strategy. As a company with proprietary assets in early clinical stages and partnered assets in early to later stages, Our strategy involves leveraging our world-class expertise to develop first and best in class antibody-based therapies for cancer. Our current business model centers around the three priorities highlighted in slide six, where we look to drive value from our proprietary R&D efforts through our well-established late stage partnerships. Our ambition is to take our proprietary assets further along the clinical development pathway, and thereby transform cancer care through a strong pipeline of novel, differentiated antibodies. The first of these priorities is our lead proprietary asset, leucutamab, where we look to create near-term value. Leucutamab is in development for T-cell lymphoma, with the top-line phase II CTCL data already presented. Based on this data, we have had recent interactions with FDA. Sonia will cover this feedback later in today's presentation, and we're now assessing the best path forward to maximize the potential of Leucutamab, including a potential partnership. Second, we continue to fuel our pipeline and create longer-term value by leveraging our antibody engineering capabilities to develop innovative molecules with a primary focus on our multi-specific NK cell engager proprietary platform called Anket. We're pleased to see continued progress with Sanofi presenting various updates for the lead Anket program, IPH61-SAR579. We're pleased to see our lead proprietary Anket, IP65, continue to progress in phase one. As we develop antibody targets for our ANCHAIR platform, we recognize that some of these targets may be better suited to an ADC approach. We will illustrate further details of our ADC pipeline today, where our lead asset, IPH45, has now received IND clearance from FDA and will start phase one trials by Q1 next year. Finally, we're building strong and sustainable foundations for our business by developing value creating partnerships across industry and academia monolizumab which is partnered with az is a good example of these partnerships and the product as part of this collaboration is advancing well in phase three trials in lancaster turning to slide seven this shows a summary of our pipeline which highlights how we continue translate our science into a robust portfolio of proprietary and partnered assets. When the IPH45 Phase 1 study starts by Q1 next year, we will have eight clinical assets. The slide also illustrates how we are executing against our strategy with our lead proprietary assets, the Kutumet, Hankhet, and emerging ADCs, and which is supported by partner products from late to early stage with AstraZeneca and Sanofi. We anticipate a series of potential clinical data readouts and catalysts in the short to mid-term as we leverage our R&D engine and scientific know-how to create a sustainable business. Moving to slide eight, which highlights our Q4 conference activity at CIDC and ASH. At the CIDC meeting last week, we presented further clinical data on our next generation CD20 targeting Yanket IPH65, as well as preclinical data on our Nectin-4 targeting ADC IPH45, which will be covered by Yanis later in today's presentation. At ASH, we were pleased to see, or we're pleased to see, that the Kutumat data was accepted for an oral presentation, highlighting follow-up on the telemark trial in relapsed recurrent spontaneous T-cell lymphoma, as well as a poster on translational analysis. I would like to now pass the call over to Sonia, who will review the progress made with our clinical portfolio. Sonia.

Thank you, Jonathan. I will now cover the key proprietary clinical programs in the next slide. Lacutamab, IPH 6501, our CD20 targeting NCI engager, and now also IPH4502, the Nectin-4 ADC that is fast approaching the clinic. Can you move to the next slide, please? Thank you. On this slide, I will briefly recapitulate where we are with lakutamab before moving to the feedback from our recent interaction with the FDA. We have already presented the primary result of the TELOMAC trial, a phase two single arm study that includes both cesarean and mycosis fungoides patients. The data in cesarean syndrome were presented at ASH last year and the results in mycosis fungoides at ASCO this year. Also this year, we will have a relevant presence at ASH with an oral presentation on the health-related quality of life in cesarean and translational results from Telomac. The TELEMACH study is continuing and we collect more follow-up data from these patients. And similarly, in peripheral T cell lymphoma, we continue to enroll patients in the KILP trial, a randomized phase two where lacutamab is administered in combination with gemcitabine and oxaliplatin versus gemcitabine and oxaliplatin alone. And we believe that this combination may offer additional benefit to patients with PTCL. As a reminder, lacudamab is a monoclonal antibody that targets Kir3DL2 and was shown to deplete the cells that express the receptor, which is expressed in more than 90% of cesarean syndrome patients and approximately in 50% of patients with mycosis fungoides or PTCL. The FDA granted an orphan drug designation for lacudamab for the treatment of CTCL and fast track designation for the treatment of adult patients with refractory relapsed cesarean syndrome who have received at least two prior lines of systemic therapies. We submitted the results from the Telomac trial and the proposed regulatory pathway to market approval, including the possibility for an accelerated approval for cesarean syndrome to the FDA and received an encouraging feedback. And the company will continue to align with the FDA around the necessary confirmatory phase three trial. We are currently evaluating the next step for the program, including potential licensing with a partner to deliver the confirmatory phase three trial in CTCL. Now, where do we stand in terms of business case? On this slide, the data generated from the TELOMAC trial confirmed clinical benefit, not only in SS, but also in mycosis fungoides. regardless of the expression of the target Kir3DL2, highlighting an opportunity for the CTCL space without a companion diagnostic. Therefore, the number of CTCL patients that could potentially benefit from lacutamab expands from 1,500 to 3,500 in the 2-plus line of therapy, and to 5,000 patients should we move to an earlier line setting. With the strong cesarean syndrome and mycosis fungoides data we presented at ASH last year and ASCO this year, there is increased confidence in the potential of lacutamab. And our aim is to ensure that lacutamab gets to patients who need it as quickly as possible and to maximize the value via an accelerated approval. On slide 13, we now switch gear to our most advanced proprietary anchored asset, IPH65. a tetraspecific antibody-based NK cell engager therapeutic, or NKET in short, which is a first-in-class NK engager that engages the tumour via a tumour-associated antigen, in this case CD20, and the NK cells via two activating receptors, NKP46 and CD16, as well as the interleukin-2 receptor via an IL-2 variant or IL-2V. The IL-2 variant is the characteristic of this second-generation tetraspecific ANCET aimed to induce activation and proliferation of endogenous NK cells in the tumor microenvironment. We were pleased to announce earlier this year that IPH65 entered the clinic and the first in human as started with the first patient being dosed in March. The trial is currently recruiting patients with relapsed refractory B-cell non-Hodgkin lymphoma. We presented preclinical data at ASCO meeting this year showing that IPH6501 effectively and preferentially stimulated ankyl cell proliferation from PBMC of NHL patients and depleted autologous CD20 positive B cells from healthy donors with greater efficacy than a CD20 T cell engager and inducing lower level of pro-inflammatory cytokines, which is often a limiting use of T cell engagers. The current Phase I-II study has been presented as trial in progress at ASCO this year and the European Haematology Association Congress, and more recently at the SIDC Annual Meeting, which Yanis will cover shortly. In the next slide, I'll give you an overview of timeline for IPH 6501 And throughout the year, we plan, and next year, we plan to complete the dose escalation and look forward for initial safety data, PK and pharmacodynamic readouts, as well as preliminary efficacy signals. Throughout 2025 and beyond, we will open the dose optimization part of the study to select the optimal dose for subsequent studies and then open expansion cohorts in non-Hodgkin lymphoma subtypes. On slide 15, I will summarize the next step of our lead ADC, IPH 4502, following the IND clearance at the end of September. We are actively working to progress towards phase one, and we are looking forward to generating preliminary phase one safety data in 2025, and then establishing anti-tumor activity in tumor types with both low and high expression of Nectin-4. IPH4502 is a top-of-one ADC targeting N4, and the proclinical characterization was presented at ACR and CITC this year, highlighting the key differentiation features of this product. And based on this data, we feel that we have a novel and differentiated ADC to target N4 in the broad panel of tumor indications beyond blood cancer by overcoming the challenges associated with Nectin for MMAE-based ADCs, including mFortumab-Vedotin. I will now hand over to Yanis to cover the earlier pipeline of ANCET and ADCs, as well as partnered asset, Monalizumab.

Thank you, Sonia. I will now highlight the two classes of exciting next-generation antibody therapeutics on which we are focusing all our research activities, the NKSL Engagers, Enquete, and the LDCs. On slide 17, I draw your attention to our portfolio of Enquete. Enquete is our proprietary first-in-class NKSL 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 of the NK molecule, it can produce multiple drug candidates, addressing a variety of targets in oncology. but it can also potentially harness MCAT cells to eliminate pathogenic cells in other diseases, like in autoimmune disease. Earlier this year, Sanofi progressed the most advanced MCAT, SAR579 to Phase 2, on the back of initial efficacy data showing single agent activity with durable complete responses in relapsed factory IML patients, and started also a new Phase 1 to trial in frontline IML in combination with venetoflax and azacitinib. As mentioned by Sonia, our lead proprietary on-camp, IPH65, is now in the clinic. It is a second generation molecule which incorporates a variant of IL-2 to induce expansion of patients' own NK cells. The first patient was in March, and we recently presented new supporting preclinical data at the CCC conference. I will now cover the key updates we presented at 6C for both IPH65 on-camp program and the NECIN4 ADC IPH45. The IPH65 poster presented at the conference summarized the rationale to target the various subtypes of relapsed or refractory BNHL patients. First of all, on the left, you can see what we think is the key advantage for ANKET over existing C20 targeting antibodies like rituximab. Whereas CD16, the receptor for the FC portion of antibodies to mediate ADC is strongly down-modulated on NK cells in the NIF node of patients, NKP46 expression is maintained, providing a stable anchor for the ANKET. By assessing the function of NK cells for multiple patients, We have shown also that IPH65 was able to induce efficient killing by diseased NK cells across B-NHL subtypes, including diffuse large B-cell lymphoma, follicular lymphoma, or mantle cell lymphoma. Finally, we made the interesting observation that post-CAR-T patients had an increased NK-T cell ratio, and as shown here on the right, an increased NKP46 expression level further supporting the rationale to evaluate IPH65 in this patient. On the next slide, the IPH45 poster summarized the key differentiating features of our drug candidates. As shown earlier in the year at ACR, IPH4502 is a novel DAR8 exaticant-based nectin for ADC, that had the ability to target Nectin-4 low-expressing tumors where PatSafe does not work. In the CITC poster, we further demonstrated that IPH45 has also the ability to target tumors having an heterogeneous expression of the Nectin-4. Indeed, by mixing at a one-to-one ratio, Nectin-4 expressing cell line with the same cell line crispered out for Nectin-4 in order to mimic an heterogeneous tumor, showing only 50% of positivity, IPH45 induces complete tumor regression of the mix. This effect is completely Nectin-4 dependent and is not related to a non-toxic effect since IPH45 had no effect in the Nectin-4 non-expressor model. We also generated a PDX model of PAD-SAVE-dequired resistance. We obtained it by making 5 injections of PAD-SAVE. resulting in a PDX model that is eventually relapsing under PADSET, but is completely sensitive to IPH45, highlighting the ability of IPH45 to address patients pre-exposed to PADSET. These two posters are available on our website. On slide 20, I would like to remind you of Monalizumab, the anti-NKG2A that we have licensed to AstraZeneca for oncology. On this slide, you can see an overview of the late-stage development of monolizumab in lung cancer. Based on the Phase II cost data, AstraZeneca started in May 2022 the Phase III trial called Pacific9, evaluating the addition of either monolizumab or olecumab to durovalumab in unresectable Stage III non-prostate lung cancer patients who have not progressed after concurrent chemoradiation therapy. We were encouraged that over the summer, the Independent Data Monitoring Committee recommended the continuation of the Phase 3 Pacific 9 trial based on a pre-planned analysis. Together with the COST and the NEOCOST data, the NEOCOST 2 data presented at the World Lung Congress in September provided a third proof point in a controlled Phase 2 study that monelizumab provides additional anti-tumor activity on top of durvalumab in early lung. I will now hand over to Ari.

Thank you, Yanis. Good morning, good afternoon, everybody. So we have several upcoming R&D catalysts that can be meaningful to our long-term growth. I would draw your attention particularly, this I believe is slide 23, I would draw your attention particularly to the ones that are bolded on this slide. Near term, we are looking forward to the next steps for lacutamab now that we have the positive FDA feedback. Programs coming out of our ANCET platform continue to advance as IPH6101, targeting CD123 and hematologic malignancies, and partnered with Sanofi, progressed to phase two earlier this year. Our proprietary tetraspecific ANCET that goes by IPH6501 is now in clinical development. And our ADC-targeting Nectin-4 has cleared IND and is due to start phase one soon. I would like to conclude our prepared comments with a few thoughts outlined on slide 24. We have a differentiated pipeline with several first-in-class opportunities. We now have seven products in clinical development, with three that are proprietary and four that are partnered. Our cash position of around 96.4 million euros through the end of September will enable us to fund operations through the end of 2025. So with that, I would like to open the call for Q&A. Regina, perhaps you can review the process for asking questions for our listeners.

At this time, I'd like to remind everyone in order to ask a question, simply press star followed by the number one on your telephone keypad. Our first question will come from the line of Lisa Baker with Evercore ISI. Please go ahead.

Hi, this is streaming on for Lisa. Thanks for taking our questions. So I'm just wondering, could you please provide some color on lacudimab to be presented, lacudimab data to be presented at ASH, especially what does the translational data entail? Also, it would be nice if you could, you know, give some color regarding the regulatory path for lacudimab. Is FDA supportive of styling with current data in celery syndrome for accelerator approval? or is the filing predicated on finding a partnership? Thank you.

Thank you for the question. Sonia, could you take that one, please?

Absolutely. Just unmuted. Regarding the data that are going to be presented at ASH, I'm afraid I cannot add any color. There are some embargoes that need to be respected. And so I'm afraid you have to wait until December for that. I can provide a bit more, perhaps, color on the FDA interaction that we had. We have received this encouraging initial feedback and the FDA endorsed our proposed regulatory pathway, you know, in general lines. The FDA acknowledged that the currently available data from the phase one and the phase two telomax studies may be sufficient to support the BLA submission, paving the path for an accelerated approval for cesarean syndrome, and the company will then align with the FDA around the confirmatory phase three trial to support such, let's say, accelerated approval. And we are working towards this to make it happen.

Got it. If I may follow up really quick, could you provide some color on timing for the next step? Or when should we expect to hear about details for or alignment with FDA for the phase three confirmatory trial. Thank you.

Well, around the timing for the FDA will also depends on our, let's say, business case in the sense that, as you know, we are also looking for partners that can potentially carry out such a phase three trial. We will pave the way by producing a regulatory strategy, which eventually may also need to be discussed with the potential partner. Got it. Thank you.

Our next question comes from the line of Dana Graboche with Learing Partners. Please go ahead.

Hi. Thanks for the question. I think I understand from the previous one I'll just follow up on that you really need to find a partner to do a confirmation study, and that will gate reviewing that with FDA and having a more concrete path to accelerated filing. Can you confirm that and then talk to us about what you're doing to find that partner and how those conversations have been going?

Sonia, do you want to take the first part of that question and then we'll come back to Yanis and myself?

Certainly. As I just briefly mentioned, we are working towards this confirmatory phase three study for the CTCL indication in more general terms. And And of course, this would be nice to be, let's say, aligned with a potential partner before going for another, let's say, type C meeting with the FDA to discuss the, let's say, the goal life of such a study. And we are looking for partners or many other, let's say, options to make this happen.

Thank you, Sonia. So, I mean, I can add something to what Sonia has just said. So, I guess we're keeping our options open at this stage. We are very actively seeking a partner, but we're also exploring other ways that we might be able to take forward a Lakota Market History study that would meet the FDA requirements here. So, I think it's difficult to say any more on that. We're in discussions at this point in time, and I think when we have some information that we can provide that we will share that moving forward.

Can you provide maybe your guiding principles for why you would go with a partner versus these other ways so we can better understand that process?

Yanis, do you want to take a stab at that one? Yeah. Hi, Dana. So like Jonathan said, we are entertaining several options in parallel. I would say classical partnering is one option. And what will guide us is the way to maximize the return for innate. So we really want to, we think that here we have potentially a drug that is really active in CTCL and we really want to execute swiftly the registrational part of the development and anything that will maximize the return for the company and the shareholder will be prioritized.

Our next question will come from the line of Rajen Sharma with Goldman Sachs. Please go ahead.

Hi, thank you for taking my question. Sorry, just another one on Lakita Mab and partnering strategy. I was just wondering, do you kind of have an internal deadline or sort of line in the sand in mind for finding a partner and executing on a potential deal there versus, you know, will there be some point in time when you decide that that's not going to happen and you'll start to take this forward alone? And then maybe related to that, it's just one on cash. So your runway is to the end of 25. So you're sort of into the last 12 months. I guess, is that something that you're comfortable with? And what are the options to extend the runway here? And then I've got a follow up on next in four, which I'll come back to.

So thank you, Arjun. Maybe Yanis, you can take the first part and then we can go to Frederick for the cash runway.

Yeah. Hi, Rajat. Yeah, obviously, it will be busy during the next few months. Obviously, the FDA feedback was an important milestone to actually resume discussion with several partners, but also for the other type of option we are looking at. So it's clearly something that we can get during the next several months, hopefully, yeah.

Okay, thank you guys. Frederic? Yeah. On the cash runaway, just one thing first is that when we communicate on this cash runaway, there is no options that is not fully guaranteed, so we are comfortable with the cash runaway that we are publishing first. And second, we are, as usual, constantly monitoring financing needs, including dilutive and non-dilutive options that we are currently working on. and we would provide them with dates when needed and when finalized.

Any other question on the next one?

Yeah, so just on that one, and, you know, obviously clear on the slides that you see the potential for the asset in kind of PADSEV or EV refractory patients. But just thinking about kind of differentiation beyond that, do you think there's an opportunity to differentiate on on tolerability or safety, and are there any key adverse events, for example, that you might call out as a differentiation?

So, Yanis, do you want to take that one?

Yeah, we think that there are several lines of differentiation, like what we have shown here at CITSI, that IPH45 is working in preclinical models that are resistant to PADCEL, either through a primary resistance or a quiet resistance, like I've just shown today. We have also And it's in the poster that you can find on the website showing that it can target Nectin-4 low-expressor tumor model. And we are now accumulating data in other tumor types, like breast cancer. And this is really a differentiating factor compared to PADSEV, which is really working well in bladder, where the expression of Nectin-4 is high and homogeneous. In terms of tolerability, as we are using Exatican, we do not expect the same kind of toxicity as with MMA. And yeah, that's basically the different possibilities that make the potential business case for this Nectin-4 exatic and IPH-45 broader than PAD-CEP because they are, and it's also in our poster, there are many, many solid tumors that do express Nectin-4, if not at the same level of bladder, but that could be a within the reach of 45, but not that safe.

And as a reminder, to ask a question, simply press star 1 on your telephone keypad.

I'll take a question received online from Eric Leberigo at Stifel. On the Kutz map, Is the understanding correct from your initial interactions with the FDA that the agency would not be against the filing with the drug for cesarean syndrome and maybe even CTCL with potential in the second case to get a conditional approval based on a confirmatory phase three trial? If this understanding is correct, is it what a partner was waiting for to move on and sign up for a collaboration with you on the asset? Or is it more the PTCL data dependant? I'll stop there. Sonia, probably a question for you.

Henry, I'm not sure I understood the first part of the question. Would you mind to repeat that?

Is the understanding correct from the initial interactions with the FDA that the agency would not be against a filing with the drug for cesarean syndrome and maybe even CTCL with the potential in the second case to get a conditional approval based on confirmatory phase three trial?

Correct. Right. Yes. Sorry. It was the negative that skipped my understanding before. Yes. Basically, the data in Cesare, where we would be looking for the accelerated approval, because, of course, accelerated approval can only be given to indication with a high unmet medical need and says that he would qualify for such an indication, you know, would be given based on the phase two and phase one data but of course any accelerated approval can only be obtained when the confirmatory trial is up and running and depending on the recruitment rate is must be quite advanced on on that and you know this approval is completely independent from the ptcl which is a very different indication in that respect

Yannis, do you want to take that? Yeah, and with regard to the question on the partnership, I would not say that the FDA feedback was a way to sign a deal, but it was more an important milestone to progress discussions, and that's where we are today.

And then the second part of Eric's question, what would you consider as the most likely next step for LakutaMap, a formal filing with the FDA or a partnership with a third party, and what are the reasonable timelines for this to happen?

Maybe Sonia.

Okay. The most likely timelines is really to go ahead and prepare a phase three that can be then taken up by a partner and or eventually finding either option to fund the study and make it in a different ways.

Okay. Thank you. Another offline question from Jingming at Evercore ISI. Could you please remind us why Sanofi decided to return IP67 and KET? Is it due to activity signals, safety, or other reasons, e.g. strategic prioritization?

Yes.

Yeah. Hi, Jingming. Sanofi did not provide any specific reason for the termination. I just remind you that IP67 was a very early stage research program. So not even at the candidate selection, it was even years away from candidate selection. So there is no specific technical or scientific reason behind that decision. It's really up to Sanofi to comment on that. And I also remind you that the rest of the agreement isn't touched. We are having the CD123 and the BCMA in phase two and phase one, and having the B7H3-NCAD program progressing well in the preclinical development.

Operator, next question please.

We'll take our next question from the line of Arthur He with HCW. Please go ahead.

Hi, good morning. This is Arthur for RK. Thanks for taking my question. So I have two questions on the NCAD. So one is for the 5201, your own 6501. Sorry. You said you are currently already in the clinical trial. So could you give us some guidance on the timing for the data update from your own program?

Sonia, can you take that one, please?

Of course. I think you are referring to IPH6501, which is the second generation anchored in the B-cell non-Hodgkin lymphoma. We open the phase one, the dose escalation that goes according to the usual times of a dose escalation with, you know, DLT windows, et cetera. And we believe that we will complete the dose escalation by 2025 and then open a dose optimization. And so we will have by 2025 data around safety pharmacokinetics, pharmacodynamic and early clinical antitumor efficacy, even though the number of patients tested in each dose level are very limited, classic of any dose escalation. But this is what we expect by, let's say, 2025 and in 2026, let's say more clinical efficacy data, of course.

Thanks, Sonia. And so another question is just want to follow up on the IPH 67.

Are you able to disclose which target they are, these assets are targeted for or it's still kind of this death mode?

I can answer that one. That's a target that we're not currently disclosing at this point in time.

Okay, no problem. Thanks. Thanks for taking that question.

Again, for any questions, simply press star 1 on your telephone keypad. That's star 1 for any questions. We have no further questions at this time. Ladies and gentlemen, that will conclude today's meeting. Thank you all for joining. You may now disconnect.