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spk07: Thank you for standing by and welcome to the Innate Pharma first quarter 2024 financial results and business update 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 followed by the number one on your telephone keypad. If you would like to withdraw your question again, press the star one. Thank you. I'd now like to turn the call over to Henry Wheeler, Vice President, Investor Relations and Communications. You may begin.
spk01: Thank you. Good morning, good afternoon, and welcome, everyone. This morning, Innate issued a press release for our Q1 2024 business update and financial results. We look forward to highlighting the progress made during the quarter 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 the website. On slide two, before we start, I'd like to remind you that we'll make forward-looking statements regarding our 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, on today's call, we'll be joined by Hervé Braille, interim chief executive officer. Then we have Sonia Carantino, chief medical officer, who will cover updates on the Kutumab and IPH 6501. We'll then hand the call to Yanis Morel, Chief Operating Officer, who will then discuss our ANCET and ADC platform updates. Arvind Sood, EVP US Operations, will wrap and close. We also have Frederick Lombard on the call for Q&A. Hervé, I now hand the call over to you.
spk00: Thank you, Henry. Turning to slide four, I'd like to remind you of our strategy. Our ambition is to develop innovative drug candidates that contribute to transform cancer care through a strong pipeline of differentiated antibody-derived drug candidates. We look to drive value from our early R&D efforts through later stage partnerships where and when it makes sense to do so. Our business model is centered around three key priorities. Firstly, we look to create near-term value driven by our lead proprietary product candidate, Lacutamab, which, as you know, is in development for T-cell lymphoma, and with top-line MF data coming at ASCO this year. As a reminder, our focus remains to leverage the value of our products as much as possible, which will further validate our science and offer capital that we can reinvest to advance our proprietary products. products and R&D engine. With the latest data in hand, we will assess the best path forward to maximize the potential of this asset Lakota map. We continue to fuel our pipeline and create longer-term value by leveraging our antibody engineering capabilities and our expertise in biology to develop innovative molecules with a primary focus on our multi-specific NK-cell engager. That's the platform called Enquete. We are pleased to see continuous progress with our partner Sanofi presenting various updates for the lead Enquete candidates which has recently been transitioned from phase one to phase two. We are also pleased to see our lead proprietary on-ket IPH6501 starting phase one trials. As we develop antibody targets for our on-ket platform, we recognize some of these targets might be more applicable for ADC technology, and we have further details in our ADC pipeline today presented by Yanis. Finally, we are building a strong and sustainable foundation for our business with various partnerships across industry and academia. Obviously, our AstraZeneca partnership is of utmost importance with Mona Lisa continuing development in lung cancer. Next slide. The slide six illustrates the variety of approaches that we have. I will now move to slide six to the portfolio. Slide six is a summary of our pipeline, which shows how we continue to translate our science into a robust portfolio of proprietary and partnered assets. It also illustrates how we are executing against our strategy with our lead proprietary assets like LakutaMap, Onket, and with the emerging assets ADC supported by partner products with AstraZeneca, Sanofi, and Takeda from late to early stage development. We anticipate a series of potential clinical data readouts on Catalyst in the upcoming couple of years as our R&D engine looks to leverage our scientific know-how to create a sustainable business. Let's move to the next slide. In ASCO, we'll have, in ASCO 2024, an important abstract being published. This comprises the top-line data from the LACUTAMAB telomac trial in mycosis fungoides. IPH6501 will be published with two posters, one in trial and progress on a preclinical assessment of IPH6501. on eventually two Monalizumab posters with updated phase two cost results in stage three, unresectable in SLC, on the phase two in extensive stage SCLC trial. I would like now to pass the call over to Sonia, who will review the progress made with our portfolio, starting with Leketamab, our most advanced proprietary asset.
spk04: Thank you, Harvey. On slide seven, let me summarize the progress we are making with lacutamab. Lacutamab has been developed in cutaneous tisal lymphoma as the target KIRT3DL2 is expressed in more than 90% of patients affected by cesarean syndrome and approximately in 50% of patients with mycosis fungoides. The TELOMAC trial is a phase two single arm study including both cesarean and mycosis fungoides. And last year, we presented the top-line result in cesarean syndrome at ASH. We have now analyzed the top-line results of the mycosis fungoides cohorts, where we have seen encouraging preliminary data in patients with Keir 3DL2 expression levels above and below 1%. The top-line results in mycosis fungoides were accepted for a poster presentation at the ASCO annual meeting, and we look forward to share the data with you then. We are pursuing a fast-to-market strategy for lacutamab in cesarean syndrome, where lacutamab was granted the US Fast-Track designation and EU Prime designation in 2020. And we look forward to discuss the data with the FDA to define the next steps. In PTCL, we continue to enroll patients in phase two combination trial with chemotherapy, GEMOX, where we believe the combination will offer additional benefit to patients. On slide nine, we now switch gear to our most advanced proprietary asset, IPH65, the tetraspecific antibody-based NK-engager therapeutic or NKET molecule, which is the first NK-engager to engage by a single molecule two activating receptor NKP46 and CD16, a tumor antigen, in this case CD20, and an interleukin-2 receptor via an IL-2 variant or IL-2V. The IL-2 variant is aimed to induce activation and proliferation of ANCI cells in the tumor microenvironment. IPH65 is the first of the second generation ANCET targeting CD20. We were pleased to announce earlier in the quarter that IPH65 entered the clinic and the first in human has started with the first patient dose in March. The trial will enroll patients with relapsed refractory B-cell non-automatic lymphoma and the study will run in the US, Australia and France. IPH65 eliminates CD20-positive cancer cells via profound activation and proliferation of the NK cells. And by stimulating NK cells' natural function via the variant IL-2, IPH65 evokes a bystander effect and can also cause the elimination of CD20 negative tumor cells, overcoming tumor heterogeneity or loss of tumor antigen. The IPH format also addressed the common challenge associated with loss of CD16 by ensuring activation of intratumoral NK cells by the engagement of NKIP46. The asset also differs from allogeneic NK cell therapy, including CAR-NK, as it is an off-the-shelf therapy that drives the proliferation of the patient-owned NK cells in B-cell non-Hodgkin lymphoma and does not require lymphodepletion as forced cell therapy. IPH65 is going to be present at ASCO annual meeting with Propostera. one as trial in progress and the other outlining the preclinical disrupted mechanism of action. I will now hand over to Yanis to cover the early pipeline.
spk03: Thank you, Sonia. On slide 10, I wanted to draw your attention to our portfolio of Enquête drug candidates, which has made significant progress during the last quarter. As you remember, NK molecules are produced through our proprietary first-in-class NK cell engager platform. It is a multi-specific plug-and-play technology made of antibody-derived building blocks aiming at engaging NK cells towards tumor cells by triggering the most stable activating NK cell surface receptor called NKP46. The interesting feature of this platform is that by swapping the tumor-binding portion of the ANCET molecule, it can produce multiple drug candidates addressing a variety of targets in oncology, but also it can potentially harness NK cells to kill pathogenic cells in other disease areas like autoimmunity and inflammation. Last quarter, Sanofi advanced SAR579 to phase 2 on the back of initial efficacy data showing single agent activity with durable complete responses in relapsed refractory IML patients. We are looking forward to seeing further updates by Sanofi. Also, as just mentioned by Sonia, we are very pleased to see our proprietary second generation Enquete IPL6501 entering the clinic with the first patient dosed in March. Next month, two APH 6501 posters will be presented at ASCO. One on the phase one to trial design and the other one on the 6501 preclinical characterization. Last but not least, we are putting a lot of efforts to further expand this portfolio to additional tumor targets, including in solid tumors. Slide 11. highlights our growing portfolio of ADC drug candidates. As we continue to develop next-generation antibody therapeutics, we find that for some tumor targets, we can generate antibodies with good internalizing properties and therefore more suited for antibody drug conjugate development than for on-cats. Our agreement with Takeda in the field provides a validation to this approach and highlights our capability to generate differentiated ADCs. Now, I will cover updates on our lead proprietary ADC program, IPH45, which is targeting NECMIN4 and which has been presented at an oral session at ACR in San Diego last month. Slide 12 highlights IPH45's overall structure. First, it is composed of a proprietary antibody with a differentiated epitope, which is non-overlapping with Enfortumab, the parental antibody of PADSEV. Then, we selected a validated cleavable and hydrophilic linker that counterbalance the hydrophobicity of the payload and allows the use of a high drug-antibody ratio of 8. Finally, we selected Exatican, a topoisomerase 1 inhibitor with strong bystander effect, allowing to bypass MMAE-related resistance mechanism and address tumors with low to heterogeneous Nectin-4 expression. Altogether, these elements create a novel and differentiated ADC to target Nectin-4 in a broad panel of tumor indication on top of bladder cancer by overcoming the challenges associated with Nectin-4-MMAE-ADC, including Enfortumar-Bedotin. Slide 13 is a summary of some of the data presented at AACR. In a nutshell, we showed that IPH45 has strong antitumor efficacy in a variety of preclinical models, including ones that are refractory to PADSEV because of high expression of the MDR1 influx transporter, a known mechanism of resistance to MMAE. Also, we found very good efficacy in patient-derived PDX models with low expression of NECTIN4, as shown on the graph in the center of the slide, where PADSEV does not work either. These data provide the rationale to target, in addition to bladder, tumor type with medium to low expression or heterogeneous expression of nectin 4, like breast, lung, prostate, head and neck, and pancreas, where efficacy reported with PAD-SEV is so far limited. With a favorable developability profile, including high yield productivity, drug stability, and encouraging PK tox data in animal studies, who are looking forward to filing the IND this year. On slide 14, I would like to remind you of Monalizumab, the anti-NKJ2A that we have licensed to AstraZeneca for oncology. On this slide, you can see an overview of the late stage development of Monalizumab in lung cancer. Based on the phase two cause data, AstraZeneca started in May 22, Pacific 9, a phase three trial evaluating the addition of either monolizumab or olecumab to durvalumab in unresectable stage 3 non-small cell lung cancer patients who have not progressed after concurrent chemoradiation therapy. The AZ-sponsored NEOCOST2 phase 2 study is also underway in an earlier lung cancer setting, namely in stage 2a to 3b non-small cell lung cancer patients and is evaluating the addition of Monalizumab to Durvalumab and chemo in the perioperative agent-like setting. As mentioned by Hervé at the beginning, Monalizumab will have two poster presentations at ASCO, one being an update of the cost results, and the other one, a presentation of the investigator-sponsored Mozart trial in the first-line treatment of extensive-stage small cell lung cancer. I will now hand over to Arvind.
spk06: Yanis, thank you. So just a few comments as we close out our prepared comments. Let me just highlight a few of the milestones that are expected over the next couple of years. We expect to achieve a number of milestones over the next two years for both our proprietary and partnered assets. Just a few weeks ago, we presented preclinical data on IPH45 that Yanis alluded to earlier, which of course is our necton targeting ADC at the recently held AACR. We also expect the upcoming ASCO to be a busy one for us, as we expect to present the final data from the TELEMEC trial. with our proprietary product, lacutamab, in MF for mycosis fungoides. This, combined with data in cesarean syndrome that Sonia alluded to, that has been previously communicated, will form the basis of our interactions with regulatory bodies as we map out next steps. We are also making very good progress with our ANCET platform with some data at the upcoming ASCO conference. Two abstracts on IPH65, our second-generation ANCET-targeting CD20 for the treatment of relapsed refractory NHL, or non-Hodgkin's lymphoma. Two abstracts will also be presented by our partner, AstraZeneca and molalizumab. phase two clinical trials for the treatment of lung cancer. If we can then move to the last slide. So let me just conclude with a few key takeaways. We'll continue to leverage our expertise in immunopharmacology, and I hope with the examples that we have just provided of upcoming catalysts with lacutamab and the ANCET platform, it provides a strong affirmation. Our pursuit of ADCs is based on developing differentiated, potentially best-in-class assets, and I hope the presentation of our data with IPH45 at AACR provides added clarity on our efforts there. Lastly, with about 115 million euros in cash on our balance sheet as of the end of March of 2024, we are in a strong cash position in operations to the end of 2025. So, Orvi, with that, let me turn the call over to you, back to you, and then we can open it up for questions.
spk01: Yeah, thank you. We'll go straight to questions. Please operate up.
spk07: Thank you. We will now begin the question and answer session. If you would like to ask a question, press star 1 on your telephone to raise your hand and join the queue. If you would like to withdraw your question, again, press star 1. Your first question comes from the line of Dana Graybosh from Learing Partners. Your line is open.
spk05: Hi, thank you for the questions and the update. The first on the MS data in the TELEMEC study, if I remember correctly, part of doing that arm was to define a potential biomarker threshold by going broad and more narrow and here to DL3 expression. I wonder if you could talk about if that's still the intent and how you're going to go about picking a potential threshold for a biomarker going forward. And then the second question is on IPH6501. I wonder if you thought about potentially taking this engager forward in autoimmune diseases in addition to oncology. Thank you.
spk04: Thank you, Diana. These are both great questions. Let's start with Lakutama. Since the expression level of Kir3DL2 in mycosis fungoida is relatively low, modest compared to cesarean, and it is also expressed in roughly 50% of patients. We have made three different cohorts in telomac trial for the mycosis fungoides, where we prospectively screen patient for the expression of the Kir3DL2, and we have a cohort of patients expressing in more than 1%, less than 1%, and all comers. And we have been working alongside the trial on a companion diagnostic. But at the ASCO annual meeting, you will see the result in both tier 3 positive tumors more than 1% or Kir3 less than 1%, and there will be interesting data in both subsets. Now, for the IPH65, I will hand over to Yanis on this question, because this is something that is very key to the business of Innate.
spk03: Yeah. Hi, Dana. Yeah, of course, it's something that we are following. As you know, there have been several attempts to use T cell engager, but also CAR-NK to deplete pathogenic B cells. It's something that we could potentially contemplate at some point with IPH6501, but for the moment, it's a bit early. Like Sonia mentioned, we just started the dose escalation. We really need to... First, establish the safety and the dose and to really characterize the pharmacodynamic effect of the drug in the B-cell depletion before considering expansion to other therapeutic areas. But in theory, it's something that we could contemplate on the mid to long term.
spk00: Yeah, if I can complement here, we do believe that with the Enquete platform, we have an interesting tool to address alternative therapeutic fields beyond the tumor immunology, tumor treatment. Thanks to the very good safety profile that we see with Enquete 3, on that we're going to document with Enquete 4, and with the reported efficacy data that we have in various preclinical models. So it's a bit early to anticipate there and make any strong statement on the future direction. But we strongly believe that we have a platform of very high value to address a number of pathologic conditions beyond cancer.
spk05: Great, thanks.
spk07: Okay, our next question comes from the line of Yigal Nachumetvich from Citigroup. Your line is open.
spk10: Yeah, hi, thanks. So with the MS data at ASCO, could you just talk about what you expect to discuss there, and how will that impact the filing strategy? Is it pretty much consistent with what you've already outlined that you're going to be speaking with the FDA? Well, based on that data that we've recently seen, are you going to, you know, make any changes to the way you're thinking about crafting a label for the drug? And then what are the timelines associated with the discussions with the FDA as well as likely timelines for filing the applications?
spk04: I think I can take the question. I'm very sorry if I'm missing something from your question because the line was not ideal and correct me if I'm wrong. You're asking around, your question is around the regulatory path forward for Lakota map after the presentation of the MF data at ASCO. And our aim here is to ensure that lacutamab gets to patients who need this drug as quickly as possible. And our aim is really to maximize the value of the drug, not only in cesarean, but also in the larger population of mycosis fungoides, and so capturing the whole CTCL space. And after the data will be presented at ASCO, our priority is really to progress the regulatory strategy with the FDA. Please let me know if I missed some point in the question.
spk10: The goal would be to file with the FDA. There wouldn't be any other studies, essentially. That would be the registrational study.
spk04: Well, it is now mandatory to have a registrational trial. Also, Mogamulizumab has opened the field by having a randomized controlled study in CTCL. And this is very likely what the regulators, and in particular the FDA, expect from us. But we will discuss with the agency different options.
spk10: Okay. And then regarding the health of the financial situation, you have runway till the end of 2025. Are there milestones from Genovi or AstraZeneca that you're expecting between now and the end of 2025 that would extend the cash?
spk03: The cash position and the projection of cash until end of 2025, does not include and does not take into account any potential milestone from existing agreements nor potential other new agreements.
spk10: Okay. Thank you.
spk07: Your next question comes from the line of Swamp Akula Ramakha from HCW. Your line is open.
spk02: Thank you. My question is on the collaborations that's been going on with Sanofi on some of your earlier stage molecules. I want to see what commentary you have on that. And then in terms of monolizumab, what do you think your partner is planning to do once after the data presentation at ASCO?
spk03: Yeah, so hi, RK Yanis speaking. Not sure to get your point on the Sanofi collaboration. Just to remind you that we are having two, Sanofi is developing currently two Oncate molecules, which are the tri-specific ones, the third generation in the clinic, in HIM, with the CD123 that has been presented last year at ASCO and ASH. and the BCMA, which has entered the clinic also last year. And we are really looking forward to potentially see updates on these two programs this year. With regard to the early stage ones, as you know, both of them are in solid tumors. One is targeting B7H3, and the other one is targeting another undisclosed solid tumor. We are progressing them at the preclinical stage, but we can unfortunately not comment on the timing when this molecule will reach the clinic. What I can say is that the collaboration with Sanofi is very active. You may have seen also during the last month that Sanofi also refocused its oncology pipeline, and clearly the NK cell engager that we are having with them are on the priority list on their oncology pipeline. Yeah, so... Thank you for that, and thanks. Yeah, and then on the MONA, as you can see by the title, and fortunately we cannot disclose more for the moment, the cost presentation at ASCO will be a poster with updated results from the cost. You know, it has been published in GCO and presented at ESMO a couple of years ago, and now it's a more longer term and updated data, but we cannot disclose comment on what AZ will do after this data disclosure, but so far the Pacific 9 trial is ongoing, and that's the only thing that we can say.
spk02: Thank you. Thanks for taking my question.
spk07: Again, if you would like to ask a question, press star 1 on your telephone keypad. Your next question comes from a line of Rajan Sharma from Goldman Sachs. Your line is open. Hi, thanks for taking my question.
spk08: So, firstly, just on IPH45, how should we think about the initial development plan now? Is it likely to be in PADSF resistant or PADSF experienced patients in bladder cancer? And could you also just talk about your expectations longer term for the profile? Do you think there's an opportunity to differentiate both on efficacy and on safety? And if so, on safety, how do you think that may work mechanistically? And then just secondly, on the Kutumab on Cesare, you mentioned a potential exploring a faster market strategy. Could you just kind of walk us through the potential passive market there? And is that predicated on MS? Thank you.
spk04: Rajan, thanks for the questions. Around IPH45, of course, we have some ideas based on the preclinical data on how to better position this asset. Of course, the initial trial will be a dose escalation study to determine to assess the safety, tolerability and signs of anti-tumor activity of this asset. And based on the characteristics shown in the trial, we will refine, of course, the clinical development plan for this asset. It may not only be in parts of refractory patients, but for instance, there is a possibility that strong of the preclinical data that we recently published at AACR. Also in all those tumors that express a low level of Nectin-4s that at present are not captured by other Nectin-4 ADC. And so, of course, all this is purely speculative at the moment and only the data will confirm. Now, regarding Lakutamab, do you mind repeating your question?
spk08: Yeah, sure. So I think you talked about a fast-to-market strategy in SIDARI syndrome. Could you just maybe walk us through how you're thinking about that and what the potential is? options could be? And then just from a commercialization perspective, is that predicated on also getting an approval in MS?
spk04: Right. Well, there are different options, of course. And as also thought previously, the option of asking for accelerated approval remains open. And as you know, we need the 12 months durability of response and a registrational trial ongoing in order to obtain accelerated approval in the niche indication of Cesare, where we obtained the FDA fast track designation. But of course, with the registrational trial, we'd also aim to bring lacutamab on the market for the NF patients as well. And let's not forget that we remain committed also to PTCL. It's still behind in terms of development, but this is also an indication that is still ongoing and is very much on our radar.
spk07: Thank you. Your next question comes from a line of Lisa Baco from Evercore ISI. Your line is open.
spk09: Hi, thanks for taking our questions. This is Jamming Elm for Lisa. So our question is for Lacutamab. So what would be a good benchmark for PTCL data next year? What's your expectation for that readout? Thank you.
spk04: That's a very interesting question. Now, PTCL, of course, is a very crowded space. Apologies. It's a very crowded space. On the other hand, remains a quite unmet medical need for these patients. And lacutamab has the advantage of having an extremely good safety profile, as shown in the TELOMAC study. Compare and that basically set it in front of many other therapists that have less tolerable profile. And this could also be an advantage for the patient population that has quite different comorbidities and cannot accept harsher therapy. The combination with the chemotherapy should bring the efficacy, of course, to patients. to what other competitors are with other drug in the same space. It's a balance between efficacy and tolerability.
spk09: Got it. Thank you.
spk07: And this concludes our question and answer session and does conclude today's conference call. Thank you for your participation. You may now disconnect.
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