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spk04: Thank you for standing by and welcome to the Innate Pharma third quarter 2023 financial results and business update. I would now like to welcome Henry Wheeler, VP Investor Relations and Communications to begin the call. Henry, over to you.
spk00: Thank you very much. Good morning, good afternoon and welcome everyone. This morning, Innate issued a press release for our Q3 financial results and business update.
spk04: Thank you for standing by and welcome to the Innate Pharma third quarter 2023 financial results and business update. I would now like to welcome Henry Wheeler, VP Investor Relations and Communications to begin the call. Henry, over to you.
spk00: Thank you very much. Good morning, good afternoon and welcome everyone. This morning, Innate issued a press release for our Q3 financial results and business update. 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. On slide three, on today's call, we will be joined by Monda Manjubi, our Chief Executive Officer. Then we are pleased to welcome Sonia Carantino, our new Chief Medical Officer, who will cover updates on acutumab and monolizumab. We'll then hand the call over to Yanis Morel, EVP of BD and Product Portfolio Strategy, who will then discuss our ANCET and ADC platform updates. We also have Frederic Lombard, our CFO on the line, for Q&A. Monda, I now hand the call over to you.
spk07: Thank you, Henry. Good morning, good afternoon, everyone, and thank you for joining us on this call. Please move to slide four. Slide four is a reminder of our strategy. As an early clinical stage company, our business model centers around three key priorities where we look to drive value from our early R&D efforts through later stage partnerships where it makes sense to do so. Our ambition is to develop innovative drug candidates that contribute to transform cancer care through a strong pipeline of differentiated antibodies. Firstly, we look to create near-term value driven by our lead proprietary drug candidate, Lakutamab, which is in clinical development for T-cell lymphoma, with updates coming at this ASH meeting, including final CTCL and early PTCL data. 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 early R&D engine. We want to make sure that if we can gain valuable competencies via a partner agreement for Equitamab, we will consider that in our development plans for the product as we look to later stage trials, as we have done in the past for other companies. partnered assets. 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 NCAT, our multi-specific NKCL Engager proprietary platform. And we are pleased to see continued progress with Sanofi presenting various updates for the lead ANCET program SAR443579 this year at ASCO, at ESMO, and also upcoming at ASH. We also look to move our lead proprietary ANCET, APS6501, toward phase one trial this year. Moreover, as we develop antibody targets for our NCAT platform, we recognize that some of these binders may be more suitable for antibody drug conjugate therapeutics, and we announce some further updates in our ADC pipeline today. Last but not least, we are building a strong and sustainable foundation for our business with various partnerships across industry and academia. And here, our AstraZeneca partnership with Mona Lisa is progressing well in Lancaster. Before I hand over to Sonia, on slide five, you have a summary of our pipeline, which shows how we continue to translate our science into a robust portfolio of proprietary and partnered assets. But it also illustrates how we are executing against our strategy with our lead proprietary assets, LakutaMap, Enquete, and Emergent ADCs, supported by partnered products with AstraZeneca, Sanofi, and Takeda from China. late to early stage development. We anticipate a series of potential clinical data readouts and catalysts in the upcoming couple of years as our R&D engine looks to leverage our scientific know-how to create sustainable business. I would like now to pass the call over to Sonia, who will review the progress made with our portfolio, starting with Lekutamab, our most advanced proprietary asset. Sonia?
spk08: Thank you, Wunder. On slide six, let me summarize the progress we are making with lacutamab, our antique year 3D L2 antibody. In T-cell lymphoma, we are pursuing a fast-to-market strategy for lacutamab in the niche indication of cesarean syndrome, where lacutamab was granted US fast-track designation and EU prime designation in 2020. We have expanded past cesarean syndrome to mycosis fungoides, and we have seen encouraging preliminary data from our phase two trial in both diseases. For the cesarean syndrome, we announced early this month that final data is due at ASH next month, and we expect to have final data announced for the mycosis fungoides later this year. Finally, we continue to enroll patients with refractory relapse peripheral disalymphoma in phase 1b with lacutamab monotherapy and in a randomized phase 2 with lacutamab in combination with chemo and some update will also be presented at ASH. We announced earlier this month that the U.S. FDA placed lacutamab trial on a partial clinical hold due to one case of haemophagocytic lymphocytosis in the Telomac trial. We are currently undertaking efforts to address the FDA request and carried out an in-depth analysis of the HLH case together with the steering committee with independent experts, which point to the fact that the case is related to the aggressive disease progression. On slide seven, we have the final efficacy data in cesarean syndrome that have been accepted for oral presentation at ASH. The abstract details that in this heavily pretreated post-mogalizumab patient pool with a medium number of six prior therapies, the global overall response rate was an encouraging 37.5%, as can be seen on the waterfall plot on the slide, and an overall response of 46.4% in skin, and 48.2% in blood. We also observed a clinical benefit rate of 87.5% and the median progression-free survival of eight months. It was very encouraging to see efficacy confirmed in the larger phase two trial in these late-line patients together with a favorable safety profile. We look forward to sharing the full presentation at the ASH annual meeting in San Diego and sharing the data with the regulatory authorities. Next, I would like to update you on Monalizumab, an asset we have licensed to AstraZeneca. To remind you, Monalizumab is an anti-NKG2A which acts upon the checkpoint pathway to potentiate NK cells and activate tumor-infiltrating CD8 T-cells. On this slide, you can see an overview of the late-stage development plan for monolizumab in lung cancer. Building upon the data of the Phase II COAST trial, AstraZeneca commenced Pacific 9, a Phase III trial of durvalumab alone or combined with monolizumab, or olecumab, an anti-CD73 antibody, as consolidation therapy for patients with unresectable stage 3 non-small cell lung cancer who have not progressed after concurrent chemoradiation. The phase 2 cost study had a similar study design to the Pacific 9. The result of an interim analysis after a median follow-up of 11.5 months was were published in Journal of Clinical Oncology in 2022. The results showed that the primary endpoint of confirmed overall response rate by investigator assessment was 35.5% with dervalumab plus monelizumab versus 17.9% with dervalumab alone. PFS was prolonged for Durvalumab plus Monalizumab versus Durvalumab alone with a hazard ratio of 0.42. And the 12-month PFS rate was 72.7 with Durvalumab plus Monalizumab versus 33.9 with Durvalumab alone. The AstraZeneca-sponsored NEOCOST2 study is also underway in an earlier stage in lung cancer, evaluating monolizumab and durvalumab with chemo in the neoadjuvant setting. I will now hand over to Yanis to cover our ANCET and ADC platform.
spk06: Thank you, Sonia. On slide 9, I wanted to highlight our proprietary NK cell engager platform that we call NKET. NKET standing for antibody-based NK cell engager therapeutics. NKET is a versatile fit-for-purpose technology made of antibody building blocks that is creating a new class of multi-specific engager to induce synthetic immunity against cancer. This technology platform, which is leveraging our scientific expertise in the NK cell space, is an engine for us to create a series of drug candidates addressing multiple tumor targets. The backbone of the ENCAT platform consists in the unique engagement of the activating NK cell receptors, NKP46 and CD16 on the NK cells, which allows for optimal harnessing of the NK cell functions. In addition, this mechanism can be further increased by the addition of the IL-2 variants in order to induce NK cell proliferation. On slide 10, I wanted to share our enthusiasm for this platform. As you can see, our pipeline of ANCAT molecule is significantly growing, with Sanofi having now licensed three molecules, with two of them in the clinic, and having an option on two other undisclosed targets. Also, our most advanced proprietary ANCAT, IPH65, which is targeting CD20 and is armed with an IL-2 variant, has cleared IND and is currently starting Phase 1. In addition, we have several proprietary preclinical programs against multiple targets. On the right panel, you can see the detailed mechanism of action of the ANCET molecules, which we have published in a couple of articles in high-impact journals. Our Nature Biotechnology paper, published in January this year, describes the joint work with Sanofi on the CD123 and KSL Engager IPH6101 or SAR579. SAR579 is a co-engaging NKP46 and CD16 on NK cells, and therefore triggers potent antigen-dependent killing of IML tumors, as well as production of key cytokines for the anti-tumor immune response, but without inducing the systemic cytokine release, which is a dose-limiting feature of the T cell engagers. Moreover, we have shown in our cell report medicine paper that the incorporation of an IL-2 variant into an N-CAT induce a preferential NK cell proliferation within the tumor microenvironment, increasing therefore the number of anti-tumor effector NK cells. On slide 11... You can see an overview of the clinical data presented this year at ASCO and ESMO, and also the abstract that has been accepted for presentation at this year's ASH meeting for the CD123 Enquete Program, also named SAR443579. In the ASH abstract, we were encouraged to see further single-agent activity and safety for the SAR579 in relapsed refractory AML patients. Additional complete responses were observed, with now 5 complete responses out of 15 patients treated at the 1 mg per kg dose levels. SAR579 was well tolerated at dose up to 6 mg per kg, with no dose-limiting toxicity observed, and only 2 grade 1 CRS observed out of 43 patients. We look forward to the full presentation at ASHE. In the ESMO update, two of the complete responders previously reported at ASCO remain in remission after 8.8 and 12.2 months after treatment, highlighting the durability of these responses. The FDA awarded SAR 579 fast-track designation in May, and Sanofi plans to evaluate further those levels. We look forward to further updates from Sanofi in due course. On slide 12, you can see a summary of our Sinophia Alliance. In 2016, we signed an initial agreement for two ANCAT molecules worth up to 400 million euros in milestones, among which we announced 16 million to date. Both programs have progressed, with SAR579 and SAR514 now in Phase 1 clinical trials. In December last year, we signed a further agreement whereby Sanofi licensed the IPH62 Enquete program targeting B7H3, a solid tumor target with an option on two other undisclosed targets. Sanofi paid 25 million euros upfront with a 1.35 billion in total milestone plus royalties. This now takes the total milestone package of our collaboration up to 1.75 billion plus royalties. We look forward to working with Sanofi as we bring this new ANCET to the clinic. Slide 13 highlights our growing ADC pipeline. As we continue to develop next-generation therapeutics utilizing our antibody engineering platform, we find that for some tumor targets, we can generate antibodies more suited for ADC than for ANCET, especially when they show good internalizing properties. Our agreement with Takeda in the field is providing a validation to this research approach and highlights our capability to generate differentiated ADC candidates. On slide 14, I wanted to give you some more details on our Nectin-4 targeted ADC, IPH45, as we prepare the IND. We have selected an antibody targeting a unique epitope, which is not competing with the one of Amfortumab-Vedotin or PADSEV, And we are using a topo1 payload with a stable and hydrophilic linker. These key scientific attributes for IPH45 translate into features that have the potential to maximize the Nectin-4 opportunity across various solid tumors. First, in preclinical models, IPH45 has demonstrated a larger therapeutic index and a longer PK compared to Enfortumab B.1. which could improve the dosing regimen and aim at a better safety profile in patients. Second, as shown on the graph on the right, IPH45 shows strong antitumor efficacy in preclinical in vivo model resistant to Enfortumab B.1, suggesting that IPH45 could be active in patient refractory or relapsing after EV or other MMAE-based therapeutics. Last, the bystander effect of the topo1 payload selected together with the increased therapeutic index suggests that IPH45 could address multiple tumor types across various NECTIN4 expression levels. Altogether, IPH45 has a unique profile with promising preclinical data that could translate into better patient outcomes across indications and lines of treatment. I will now turn to Mander for a summary.
spk07: Thanks, Yanis. Please move to slide 15, where we highlight the updates we are looking forward to at ASH in a few weeks' time in San Diego, where we will share the LACUTA map updates and Sanofi will present SAR 579 anchor updates. We also plan to host a KOL call on-site during the conference, and we look forward to further discussing the LACUTA map data with you. So let me summarize now, and maybe if we move to slide 16, you are maybe familiar with this slide. We continue to work diligently to execute across all our strategic pillars, and we believe that we are laying the foundation to drive near and long-term value. Looking at our clinical program, we expect to achieve a number of milestones over the next two years. As you've heard from Sonia, Lacutamab phase 2 Telomac final cesarean syndrome and MF data is due at the end of this year, in addition to initial PDCL data. In parallel, we continue to develop our NCAT platform, further reinforced by our partnership with Sanofi, and we are very encouraged by the initial clinical data presented at Congresses this year, and the IND clearance for our proprietary NCAT which is progressing toward the clinic. We believe that these represent a natural evolution of our platform. Last but not least, for monolezumab, the lung cancer trials are underway, and we continue to advance the adenosine pathway agents in the clinic where the phase 2 for APH5201 in early lung cancer is underway. Let's move to the conclusion slide, please. As you can tell, we continue our exciting journey at Innate. We look to build our business to create value for patients and stakeholders. In summary, we have positioned Innate Pharma for the future with our strategy and made meaningful progress across all three strategic pillars. With our R&D engine and antibody engineering expertise, our science is producing more candidates to progress to the clinic. So we are developing alone, some we are developing alone, and some partnered. We have a focus on our NKCell Engager platform, NKET, as well as antibody drug conjugates. But in parallel, our late-stage portfolio continues to advance as we look to maximize the late-stage portfolio assets of both lacutamab and monolizumab. Second, our partnership strategy continues to evolve. with the Takeda deal adding to those of AstraZeneca and Sanofi. Finally, we continue to carefully manage our resources so we can continue our sustainable business and invest in progress in our pipeline. I'm very pleased that we continue to have a strong cash position with a runway into the second half of 2025. So collectively, We are driving value across our business and finally advancing our goal to deliver innovative medicine to patients. We look forward to keeping you updated on our progress. That concludes our prepared remarks. We will now open the call to questions.
spk04: At this time, I'd like to remind everyone, in order to ask a question, press star then the number one on your telephone keypad. We'll pause for just a moment to compile any questions. Again, if you'd like to ask a question, please press star one on your telephone keypad now.
spk00: Operator, can we take the first question, please?
spk04: Our first question comes from the line of Dana Graybosh with LeeRink Partners. Please go ahead.
spk05: Hi, this is Rabib on for Dana. What is your view of SAR443579 or IPH61 dosing profile to date? And how do you think that reads through to the ANCET platform more broadly? Thank you.
spk07: Thank you. Probably Yanis is the best person here to answer the question about the dosing profile for 61 and beyond that, of course, the rest of our NCAT drug candidates.
spk06: Yeah, the data that have been presented by Sanofi up to date on the ASCO, but also more recently at the ESMO show that the clinical responses were observed at the cohorts where the maximum dose was one mcg per kg. The ASH abstract also reports additional response at 1 mcg per kick, but not at higher doses. This suggests a potential bale-shaped effect on the drug, and like you can see in the abstract, more details on that should be presented at the ASH meeting. But if you look back at the ESMO presentation, there were blast reduction at all doses tested. What it tells us is that we may for, I mean, on a target per target basis, you know, because a multispecific engager is binding on one side to the tumor, but on the other side on the NK cells. you may adapt the dose in the phase one from one target to the other. But, you know, it's not something that is unusual. There has been also some example recently, for example, with the Tarlatamab from Amgen, where the 10 mg flat dose showed better results than the 100 mg flat dose in small cell lung cancer. Thank you, Ernest.
spk04: Our next question comes from the line of Yigal Yashimovitz with Citi. Please go ahead.
spk02: Hi, team. This is Carly. I'm for Yigal. Thanks for taking our questions. For lacudimab, we wanted to get your latest thinking on the next steps for CTCL. I think in the past you've talked about the potential for the CSRI cohort to support an accelerated approval pathway. So just curious if that's still part of the plan, and then what different scenarios could look like for mycosis and goitis as well in terms of future studies. Thank you.
spk07: Yeah, I'm going to take the question. So as you know, our aim is to pursue the development of lacrytumab Beyond the cesarean syndrome, the mycosis fungoides cohort in the TELEMEC trial is a signal detection study because we didn't generate previously data. Outside cesarean syndrome. So this is, you know, the first prospective controlled phase two study to generate additional data outside cesarean. And of course, our main goal is to make sure that lacrytamab gets to the patient who needs it. as quickly as possible. It's clear that in the cesarean syndrome, given the orphan drug designation, or of course, the FAST-HAC designation, as well as the PRIME designation in Europe, there is a significant unmet medical need, especially in those patients who are progressing after two prior line of therapy, especially after mogamolizumab. And clearly, the immersion data that we are generated and about to present to ASH will be discussed with the FDA in terms of potential suitability for accelerated approval and also the confirmatory phase three strategy building, as I said, on the existing first track and offer designation. As you know, our business model, of course, is clear. Further development and registration of this asset is something we intend to progress via partnership. leveraging the capabilities and expertise of a partner in an area that we do not have existing capability of expertise. This will allow us to focus on our proprietary and innovative portfolio, and we will provide you updates as and when we can, and trust that you understand the sensitivity of any potential partnership prior to formal announcement. I also know that in our discussion with the FDA, we will certainly discuss about the confirmatory phase three trial, which, of course, will be including not only cesarean, but clearly other form of CCL, in particular, mycosis fungoides.
spk02: Okay. I hope that was helpful. Okay. Yes, yes, perfect. Thank you. And then just a follow-up question, maybe on the Nectin for ADC program. Seems like you think there's potentially an opportunity in the post-PADSEV setting here. I'm just wondering if you could talk a little bit more about early thoughts on the development strategy and then just timelines for bringing that into the clinic. Thank you.
spk06: Yes, indeed, by actually switching the class of payload and going after a topo1 inhibitor, we are seeing some pretty good efficacy in preclinical models after PADSEV and in models that are resistant to PADSEV. And what is also encouraging for this approach is that there are some reports in the literature showing that patients who are relapsing to PADSEV are not losing the expression of the antigen. So the antigen is still there, but it's more a mechanism of resistance against the payload that is developing within these patients. So this is clearly one path that we at some point would like to explore. to explore in our clinical development plan, but it's not only the only one, as the non-nectin-4 can be also expressed in several other solid tumors that are so far showing pretty limited activity with the PAD-SEV, and this leveraging the wider and larger therapeutic index of our compounds. And in terms of timing, we are actively working to file an IND next year with this one.
spk02: Okay, thank you for taking the questions.
spk04: Again, as a reminder, the floor is now open for your questions. To ask a question at this time, please press star 1 on your telephone keypad. Our next question comes from Arthur He with HC Wainwright. Please go ahead.
spk03: Hey, everyone. This is Arthur for RK. Thanks for taking my questions. So, I just wonder for the 579 data at the ASH, could you give us more color on the safety side, especially for that grade 4 case, grade 4 neutropenia? Could you give us more color on that?
spk07: So, I'm not sure. I'm getting the question right. So far, actually, based on the abstract, the safety profile of 579 or APH 6101 was reported as favorable. There were one... Grade 4 neutropenia, but we don't have details more than what is in the abstract, so clearly something to ask when the data will be presented at ASH in a couple of days. But a reminder, those are heavily pretreated patients, median number of prior line of therapy. Most of the patients received venetoclax. A significant number went through stem cell transplantation. And this is, of course, interesting to better understand the reason of this great for neutropenia, whether it is disease-related or drug-related.
spk03: Thanks for that. My second question is... I'm just curious, when you are evaluating different binders, which is super for the NCAT or versus the ADC platform, what kind of criteria or selection preference for each side? Just curious from your perspective. Thanks.
spk07: I'm going to hand over to Yanis to give you a more detailed answer. But as we explained in the past, of course, some of the binders are more suitable for ANCAT. The ones that internalize actually are by design favorable candidates for the ADC. But Yanis can give you more color on our thinking on how we select those binders.
spk06: Yes, but it's obviously a target by target discussion because you know that some targets do have this property to internalize and some do not. And depending on this property of the target, the structure and the ability to generate binders that are hitting the target at different epitopes, we can generate binders that are rather staying at the cell surface and are pretty good candidates for an ENCAT molecule and others that do internalize. And this, we are screening that in vitro. with pretty classical methods that are widely used by people developing ADCs. And we are checking the ability to induce the direct killing based on the expression level of the target. So there are also many more parameters that we are taking into account, like the medical need, the development path, and the potential opportunity for this molecule. But in terms of antibody characteristics, this is really one of the
spk04: we are we are using in one of our early filters oh thanks thanks for taking all my questions our next question comes from the line of lisa baiko with evercore isi please go ahead hi um this is jamie alfred lisa thanks for taking our questions
spk01: So I have two questions. So one is, maybe I've missed it in the prepared remarks, but can you give us an update on your clinical hold for lacudimab? And then my second question is for your PTCO update at ASH. What will be an appropriate benchmark for this data? Thank you.
spk07: Okay. The first question. is about Lactamab clinical hold, you said, I think, and probably it's time and opportunity for Sonia to provide an update on the partial clinical hold for Lactamab, and then I'll take the question on PDCL.
spk08: Certainly. As mentioned before, the FDA placed the partial clinical hold due to one case of HLH that was reported in one subject. We, of course, intend to lift the partial hold as soon as possible once the FDA requests have all been satisfied. However, this clinical hold or partial hold does not impact the Telomac timelines because the recruitment in both mycosis fungoides and cesare have been completed and the final data are imminent. And for the PTCL, we have also recruited the, let's say, first cohort of patients and we are making an interim analysis of the data. And I have to remind that this HLH case that has been highlighted in the Telomat trial is indeed related to transformation of the cesarean into a large-stranded lymphoma. And as you probably know, HLH is commonly reported as a complication of cutaneous fissile lymphoma.
spk07: Thank you, Sonia. So for the second question, so let me first maybe go back a few years ago when we finished phase one. At that time, we didn't have data outside cesarean syndrome. Most, if not all, the patients included in the phase one program had cesarean syndrome. And of course, the obvious question, we are excited and we are still excited by the signal we've seen in cesarean patients, but the main question was to see whether there is activity outside cesarean. And the logic next step was to go in cutaneous T-cell lymphoma outside cesarean and test for the drug in mycosis fungoides. That was the priority number two, and that's what we will be communicating at the end of the year. As we said, we are on track to have the final data in-house in mycosis fungoides, but from the data published, the interim data published last year and updated even recently this year, we are confident that the signal is present actually when Q3DL2 is expressed. Hence, the potential for lacutamab to be used in the treatment of peripheral T cell lymphoma. I remind you that almost half of the patients with PTCL do express K3DL2. We are running two trials in the difficult-to-treat relapsed refractory setting. One is a company-sponsored trial. It's mainly a safety phase 1B trial. that we are conducting and for which we will present an update in a couple of weeks at ASH. And the second trial is a an investigator-sponsored trial performed in collaboration with the LISA group, and it's a combination trial. And I think the combination strategy in particular in the relapse refractory is something very important. We are, of course, excited by the preclinical data that we have generated and that we will be published at ASH, as I said, in a couple of weeks. We remain optimistic about the potential to run combination trials in the relapse refractory setting, but also in first line. And the plan, of course, is to expand the development of laquitamab in peripheral T cell lymphoma beyond the difficult to treat relapse refractory, but that's the first step.
spk01: Got it. Thank you.
spk04: There are no further questions at this time. I would now like to turn the call over to Monder Majubi for closing remarks.
spk07: Thank you. As a concluding remark, I would say. A, we are very encouraged by the robust outcomes of leucoderma in heavily pretreated patients with cesarean syndrome. Discussions with the FDA will enable us to evaluate the potential for accelerated approval and to firm up phase three plans. We are, of course, in ongoing dialogue with potential partners that can realize the full potential of the drug for patients with T cell lymphoma, both cutaneous and peripheral T cell lymphoma. Second message, we are making great progress with our early stage pipeline. Pleased to see the progress of APH61 or SAR579 in AML. with an update at the upcoming ASH. Pleased to announce that we have cleared the IND for APS65, and we are waiting for the start of the phase one this year. And finally, as you've heard from Yanis, excited by our differentiated anti-NICTIN4 ADC with the top one payload, which is moving toward IND next year. Last but not least, sufficient cash to fund operation into H2 next year with, as of end of September, 122 million euros. 25, sorry, yeah, fund cash in H2 2025. Thank you very much.
spk04: I would like to thank our speakers for today's presentation and thank you all for joining us. This now concludes today's call and you may now disconnect.
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