Innate Pharma S.A. (IPHA) Q3 2024 Earnings Report, Transcript and Summary

Hello and thank you for standing by. My name is Regina and will be your conference operator today. At this time, I would like to welcome everyone to the Innate Pharma’s Third Quarter 2024 Business Update and Financial Results Conference Call. All lines have been placed on mute to prevent any background noise. After the speakers’ remarks, there will be a question-and-answer session. [Operator Instructions] 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 2, before we start, I would like to remind you that we'll be making forward-looking statements regarding the financial outlook in addition to regulatory and product plan developments. These statements are subject to risks and uncertainties that may cause actual results to differ from those forecasted. Slide 3, 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 Incyte. He has a strong background in oncology and previous roles include ARIAD, BMS, Roche and Novartis. On the next slide, today’s agenda, after an instruction from Jonathan, Sonia Quaratino, our Chief Medical Officer, who will cover updates on the lacutamab and IPH6501 and 4502. We will then hand to Yannis Morel, Chief Operating Officer, who will discuss ANKET platform ADC SITC and monalizumab updates; Arvind Sood, EVP, US Operations will wrap up and close and we’ll also have Frederic 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 am very excited to join in a pharma, a company, which is at the forefront of cutting-edge science in oncology. The unit of innovative work being done at Innate is truly inspiring 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 the Innate's exciting journey. I look forward to meeting with as many of you as possible in the coming weeks. Turning to Slide 6, I would like to remind you of our strategy. As a company with proprietary assets in early critical 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 to cancer. Our current business model centers around the three priorities highlighted in Slide 6 where we look to drive value from our proprietary R&D efforts through our well-established late-stage partnership. 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 assets lacutamab, where we look to create near-term value. Lacutamab is in development for T cell lymphoma with the top-line Phase 2 CTCL data already presented. Based on this data, we've 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 lacutamab including a potential partnership. Second, we continued to fill 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 are pleased to see continued progress with Sanofi presenting various updates to the lead ANKET program IPH61/SAR’579. We're pleased to see our lead proprietary ANKET IP65 continue to progress in Phase 1. As we develop antibody targets for our ANKET platform, we recognize that some of these targets may be better suited to an ADC approach. We will illustrate further details on our ADC pipeline today, where our lead asset IPH45 has now received IND clearance from FDA and will start Phase 1 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. Monalizumab which had partnered with AZ is a good example of the partnership and the product as part of this collaboration is advancing well in Phase 3 trials in lung cancer. Turning to Slide 7. This shows a summary of our pipeline, which highlights how we continue to translate our savings 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. This slide also illustrates how we are executing against our strategy with our lead proprietary assets, lacutamab, ANKET, and emerging ADC. And which is supported by partnered 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 8, which highlights our Q4 conference activity at SITC and ASH. At the SITC Meeting last week, we presented further clinical data on our next-generation CD20 targeting ANKET IPH65, as well as pre-clinical data on our Nectin-4 targeting ADC, IPH45, which will be covered by Yannis later in today's presentation. At Ash, we were pleased to see - we're pleased to see that lacutamab data was accepted for an oral presentation highlighting follow-up on the TELLOMAK trial in relapsed recurrent cutaneous 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 property clinical programs in the next slide, lacutamab, Iph6501, our CD20 targeting NK-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 lacutamab before moving to the feedback from our recent interaction with the FDA. We have already presented the primary result of the TELLOMAK trial, a Phase 2 single alarm study that includes both Sezary and mycosis fungoides patients. The data in Sezary 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 Sezary and translational results from TELLOMAK. The TELLOMAK 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 acute trial, randomized Phase 2 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, lacutamab 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 Sezary syndrome patients and approximately in 50% of patients with mycosis fungoides or PTCL. The FDA granted an orphan drug designation for lacutamab for the treatment of CTCL and fast track designation for the treatment of adult patients with refractory relapsed Sezary syndrome who have received at least two prior lines of systemic therapies. We submitted the results from the TELLOMAK trial and the proposed regulatory pathway to market approval including the possibility for an accelerated approval for Sezary syndrome to the FDA and received an encouraging feedback and the company will continue to align with the FDA around the necessary confirmatory Phase 3 trial. We are currently evaluating the next step for the program, including potential licensing with the partner to deliver the confirmatory Phase 3 trial in CTCL. Now where do we stand in terms of business case? On this slide, the data generated from the TELLOMAK trial confirmed clinical, benefit not only in assess, 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 two plus line of therapy and to 5,000 patients should we move to an earlier line setting. With the strong Sezary 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 July 13th, we now switch gear to our most advanced proprietary ANKET asset IPH65, A tetraspecific antibody base NK cell engager therapeutic or ANKET in short, which is a first-in-class NK engager that engaged the tumor via a tumor associated antigen in this case CD20, and the NK cells via two activating receptor NKp46 and CD16, as well as the interleukin-2 receptor via an IL-2 variant or IL-2 V. The IL-2 variant is the characteristic of this second-generation tetraspecific ANKET, aimed to induce activation and proliferation of endogenous NK cells in the tumor micro environment. We were pleased to announce earlier this year, that IPH65 entered the clinic and the first-in-human has started with the first patient been 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 IPH 6501 effectively, and preferentially stimulated NK 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 ending using lower level of pro-inflammatory cytokines, which is an often a limiting use of T-cell engagers. The current Phase 1/2 study has been presented as trial in progress at ASCO this year and the European Hematology Association Congress and more recently, at the SIDC Annual Meeting, which Yannis will cover shortly. In the next Slide, I’ll give you an overview of timeline for IPH6501 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 IPH4502, following the IND clearance at the end of September, We are actively working to progress towards Phase 1 and we are looking forward to generating preliminary Phase 1 safety data in 2025 and then establishing anti-tumor activity in tumor types with both low and high expression of Nectin-4. IPH4502 is the total 1 ADC targeting Nectin-4 and the pre-clinical 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 Nectin-4 in a broad panel of tumor indications beyond blood cancer by overcoming the challenges associated with Nectin-4 MMAE based ADCs, including Enfortumab Vedotin. I will now hand over to Yannis to cover the earlier pipeline of ANKET and ADCs, as well as partnered asset monalizumab.

Thank you, Sonia. I will now highlight the two class of exciting next-generation antibody therapeutics, on which we are focusing all our research activities, the NK cell engager, ANKET and ADC. On slide 17, I draw your attention to our portfolio of ANKET. ANKET is our proprietary first-in-class NK cell engager platform, which is multi-specific plug-and-play technology, aiming at engaging NK cells towards tumor cells by clearing the most stable activating a set of NK cells called NKp46. The interesting feature of this platform is that by swapping the tumor-binding portion of the ANKET molecule, 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. Earlier this year, Sanofi summarized 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 a new Phase 1/2 trial in frontline AML in combination with venetoclax and azacitidine. As mentioned by Sonia, our lead proprietary ANKET IPH65 is now in the clinic. It is a second-generation molecule, which incorporate a variant of IL-2 to induce expansion of patients’ own NK cells. The first patient was dosed in March and we recently presented new supporting preclinical data at the SITC Conference. I will now cover the key updates we presented at SITC for both IPH65 ANKET hold on and the Nectin-4 ADC IPH45. The IPH65 poster presented at the conference summarize the rationale to target the various subtypes of relapsed or refractory B-NHL patients. First of all, on the left, you can see what we think is a key advantage for ANKET over existing CD20 targeting antibodies like rituximab. Whereas, CD16, the receptor for the FC portion of antibodies to mediate ADC – modulated on NK cells in the lymph node of patients NKp46’s 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 disease NK cell across T-cell and the 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 increase NKp cell ratio and as shown here on the right, an increase in NKp46’s expression mirrored for those supporting the rationale to evaluate IPH65 in these patients. On the next slide, the IPH45 poster summarize the key scientific features of our first candidates. As shown earlier at the - in the year at ACR, IPH4502 is a novel exatecan-based Nectin-4 ADC, that had the ability to target Nectin-4 for low expressing tumors where [Indiscernible] does not work. In the SITC poster, we further demonstrated that IPH45 has also the ability to target tumors having a heterogeneous expression of the Nectin-4. Indeed, by mixing at a 1 to 1 ratio, Nectin-4 expressing cell line, with the same cell line this part out for Nectin-4 in order to mimic a heterogeneous tumor showing only 50% of positivity, IPH45 induced complete tumor regression of the mix. This effect is completely a Nectin-4 dependent and it's not related to a non-toxic effect since IPH45 and no effect in the Nectin-4 non-expression. We also denied the PDX model of bedside acquired resistance. We obtain it by making five injection of bedside resulting in a PDX model that is eventually elapsing on the bedside that is completely sensitive to IPH45 highlighting the ability of IPH45 to address patients could expose to bedside. 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 another view of the late-stage development of Monalizumab in lung cancer. Based on the Phase 2 COAST data AstraZeneca started in May ‘22 the Phase 3 trial called PACIFIC9 evaluating the addition of either Monalizumab or oleclumab to durvalumab in unresectable Stage 3 non-small cell lung cancer patients who have not progressed after concurrence chemoradiotherapy. We were encouraged that over the summer, the Independent Data Monitoring Committee recommended the continuation of the Phase 3 PACIFIC9 trial based on the pre-planned analysis. Together with the COAST and the new COAST data, the new COAST 2 data presented at the World Lung Congress in September provided the thorough proof points in the control Phase 2 study that Monalizumab provides additional antitumor activity on top of durvalumab in earlier. I will now hand over to Arvind.

Thank you, Yannis. 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 a positive FDA feedback. Programs coming out of our ANKET platform continue to advance as IPH6101 targeting CD123 in hematologic malignancies and partnered with Sanofi progressed to Phase 2 earlier this year. Our proprietary tetraspecific ANKET that goes by IPH6501 is now in clinical development. And our ADC targeting Nectin-4 has tiered IND and is due to start Phase 1 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, excuse me. We now have 7 products in clinical development with 3 that are proprietary and 4 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 by asking questions for our listeners.

[Operator Instructions] Our first question will come from the line of Lisa Baker with Evercore ISI. Please go ahead.

Hi. This is [Indiscernible] on for Lisa. Thanks for taking our questions. So I'm just wondering, could you please provide some color on lacutamab to be presented – lacutamab data to be presented at Ash? Especially what does the translational data Intel? Also be nice if you could give some color regarding the regulatory path for lacutamab, is FDA supportive of filing with current data in Sezary syndrome for accelerated approval? Or, and then is the filing predicated 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 in general lines. The FDA acknowledged that the currently available data from the Phase 1 and the Phase 2 Tellomak studies may be sufficient to support the BLA submission paving the path for an accelerated approval for Sezary syndrome. And the company will then align with the FDA around the confirmatory. Phase 3 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 like when should we expect to hear about details for or alignment with the FDA for the Phase 3 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 we are also looking for partners that can potentially carried out such Phase 3 trial. We will pave the path - the way by producing the 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 Daina Graybosch with Leerink 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 more concrete path to accelerated filing. Could 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 Yannis and myself.

Certainly. As I just briefly mentioned, we are working towards this confirmatory Phase 3 study for the CTCL indication in more general terms. 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 Go Live of this such 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 just said. So, I - what we 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 lacutamab free study, that would meet the FDA requirements here. So, I mean, 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 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?

Yannis, do you want to take a stab at that?

Yeah hi, Daina. So like Jonathan said we are on top of several options in parallel. I would say practical 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 activity in CTCL. And we really want to execute with - the registrational part of the development and anything that you maximize the return for the company and the shareholder will be prioritized.

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

Hi. Thank you for taking my question. Sorry, just another one on lacutamab and partnering strategy. I am just wondering do you kind of have an internal deadline or for line in mind for finding a partner and executing on a potential deal versus what will 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 born on cash. So your runrate to the end of 2025 so you are sort of into the last 12 months. I guess, is that’s something that you are comfortable with and what are the options to extend the runrate here? And then I have a follow-up on Nectin-4 which I will come back to you.

Thanks, Rajan. Maybe Yannis, you can take the first part and then we can go to Fredric for the cash runway.

Yeah, hi, Rajan. Yeah, obviously it will be a - it will be busy during the next few months. Obviously, the FDA feedback was an important milestone to actually resumed discussion with several partners, but also for the other type of options we are looking at. So it's clearly something that that we can get during the next several months.

Okay, thank you, Yannis. Fredric?

Yeah, on the cash runway, just one thing. First is that, when we communicated on this cash runway, there is no options that is not fully guaranteed. So we are comfortable with the cash runway that we are publishing first. And the second one that we are as usual constantly monitoring financing needs including dilutive and non-dilutive options that we are currently working on. And we will provide an update when needed, when finalized.

Any other questions and that’s important?

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

Yannis, do you want to take out?

Yeah, we think that there are several lines of differentiation, like what we have shown here at SITC, that we, IPH45 is working preclinical models that are EV resistance like said through a primary resistance or quite resistance, like I just shown today. We have also, and it's in the poster that you can find in the website shown that it can target Nectin-4 low expression tumor model. And we are now accumulating data in other tumor types like breast cancer. And this is really - different checking factor compared to bedside which is really working well rather where the expression of the Nectin-4 is high and homogeneous. In terms of reliability as we are using as exact we can. We do not expect the same kind of toxicity as with MMAE. And yeah, that's basically the difference possibility that make the potential business case for all these Nectin-4 exactly can IPH45 model than bedside, because there are, and it's also in our poster. There are many, many solid tumors that do expect Nectin-4 is not at the same level of data. But that would be - within the reach of 45, but not that said.

[Operator Instructions]

We’ll take a question received online from Eric Le Berrigaud with Stifel. On the lacutamab, is the understanding correct for your initial interactions with the FDA that the agency will not be against the filing with the drug for Sezary syndrome or maybe even CTCL with potential in the second case to get a conditional approval based on a confirmatory Phase 3 trial. If this understanding is correct is what a partner is waiting for to move on and sign up for a collaboration with you on the asset? Or is it more of the PTCL data-dependent? Well, 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. The agency would not be against a filing with the drug for Sezary syndrome and maybe even CTCL with the potential in the second case to get conditional approval based on confirmatory Phase 3 trial.

Correct, right? Yes, sorry. I was the negative that skip my understanding before. Yes. Basically, the data in in Sezary 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 Sezary would qualify for such an indication. Would be given based on the Phase 2 and Phase 1 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 must be quite advanced on that. And this approval is completely independent from the PTCL, which is a very different indication in that respect.

Yannis? Do you want to take the…

Yeah, and with the other – the question on the partnership, I would not say that the FDA feedback was awaited to sign a deal that it's - it was more an important milestone to progress discussions. And that's where we are today.

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

Maybe Sonia.

Okay. The most likely timelines is really to go ahead and prepare a Phase 3 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 way.

Okay. Thank you. Another offline question from Jingming at Evercore ISI. Could you please remind us what Sanofi decided to return like IPH67 ANKET? Is it due to activity signal safety or other reasons EG strategic prioritization?

Yeah. Hi Jingming. Sanofi did not provide any specific reason for the termination. I just remind you that. IPH67 was a very early-stage research program. So not even at the candidate selection point even, The other way from candidate selection. So there is no specific technical or scientific reasons behind that decision. It's really up to Sanofi to comment on that. And I also remind you that the rest of the agreement is in touch. We are having the CD123 and the BCMA in Phase 2 and Phase 1. And having the B7H3 ANKET program progressing well in the preclinical developments.

Okay. Operator. Next question please.

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

Hi, good morning. I am Arthur on for RK. Thanks for taking my question. So, I have two questions on the ANKET. So one is, for the [Indiscernible] I mean, 6201 - 52501 Sorry. You said you are currently in the - already in a clinical trial. So, could you give us some guidance on the timing for the date update from this your own program?

Sonia. Can you take that one please?

Of course. I think you are referring to IPH6501, which is the second-generation ANKET in the B cell non-Hodgkin lymphoma. We opened the Phase 1 the dose escalation that goes according to the usual kinds of a dose escalation with, BLT Windows et cetera. And we believe that we will complete that 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, anti-tumor 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 IPH67. Are you able to disclose which target they are - this asset target for or it’s still kind of discussions?

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

Okay. That’s all. Thanks for taking my question.

[Operator Instructions] 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. We're all clear.

Great. Thank you, Regina