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spk05: At this time, I would like to welcome everyone to the innate. At this time, I would like to welcome everyone to the innate pharma full year 2023 financial results and business update call. Today's conference is being recorded and 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 that time, simply press the star key followed by the number one on your telephone keypad. If you would like to withdraw your question, press star one a second time. Thank you. And I will now turn the conference over to Henry Wheeler, Vice President of Investor Relations. Mr. Wheeler, you may begin.
spk04: Thank you. Good morning. Good afternoon and welcome, everyone. This morning, Innate issued a press release for our full year 2023 financial results and business updates. 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 IIS 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 Herve Braille, our Interim Chief Executive Officer. Then we will hand over to Sonia Quarantino, our Chief Medical Officer, who will cover updates on the Kutumab and IPH65. We will then hand to Yanis Morel, Chief Operating Officer, who will then discuss ANCET and ABC platform updates. Frederic Lombard, our CFO, will cover the financials. And we're very pleased to welcome Arvind Sood, EVP US Operations, who will wrap up and close. Herve, I now hand the call to you.
spk01: Thanks, Henry. Good morning and good afternoon, everyone. I would just like first to recall that innate trauma is a very important play on the field of NK cell pharmacology and innate immunity manipulation. We address that through different mechanisms of actions where we have corresponding products. It's first about engaging NK cells as cytotoxic effectors to tumor cells, and that's the approach that the we implement with the Enquete platform, but also with the essential toxic antibody, Lapetamab. We've also been pioneering the field of checkpoint inhibitors of NK cells with Monalizumab, which is a checkpoint which is shared, which is targeting a checkpoint which is shared by different classes of effector cells, both NK and T cells. and eventually through addressing suppression of the toxic immune response through IPH 62 and 63, which addresses the adenosine pathway. So that's it. What is the innate pharma strategy? Well, firstly, it's about creating near-term value, and that's what we want to achieve with our most advanced proprietary asset, Lactamab, which is in development in T-cell lymphoma. Actually, final CTCL on early PTCL data have been released by the end of 2023 at ASH. On here, we do look forward to the next step, which will be the data on mycosis fungoides, and that will inform the future of this program for the late stage development. Second, we continue to fuel our innovative portfolio with both Enquete and antibody drug conjugates. Enquete is really a core asset. It's a platform which generated several molecules, and as you know, The first molecule in clinic has been advanced by our partner Sanofi, who published in 2003 important first clinical data. We'll come back to that, of course, in greater detail for the SAR443579. But the Yonket portfolio is now expanding with a other assets that have been further licensed in by Sanofi, but also with a proprietary program that was recently announced is now, and this is a second generation of Enquete, which has now been brought to a clinic in phase one in lymphoma. On beyond Enquete, we also advance a second class of agents which are active as a single agent potentially in tumor with antibody drug conjugate, the first one being brought to... We work on bringing it to IND in 2024. Eventually, through partnership, we have Monalizumab door checkpoint inhibitor in phase three on AstraZeneca is pursuing this late stage asset, which will deliver in the next years very important data. So that translates into the portfolio, which is a combination of proprietary products on the partner asset. I will leave it to Sonia to detail the clinical stages on the clinical progress with those assets, especially, firstly, with Lepidamab. Sonia?
spk03: Thank you very much, Hervé. When we look at slide 7, I would like to summarize the progress we are making with Lepidamab. And here, in this space, we are pursuing a fast-to-market strategy for Lepidamab in the niche setting of Caesarean syndrome, where Lepidamab was granted the US Fast-Track designation and the EU Prime designation back in 2020. We have then expanded post-Caesarean syndrome to mycosis congoides, where we have seen encouraging preliminary data from the phase 2 telomath trial in patients that have a key 3DL2 expression level above as well as below the threshold of 1%. And we expect to present this data at one upcoming conference later this year. Now, the data in a method together with the data in ISS, will be shared with regulators to align on a path forward to maximize the value of lacutamab in CTCL, building on the existing fast-track and orphan designations. Now, if we move to the PPCL space, today we have announced that we are not going to reopen the recruitment of the phase one testing lacutamab in monotherapy in PPCL, as the number of observed objective responses did not meet the pre-specified threshold for activity with lacutamab as a single agent. However, based on the data presented at ASH last year, demonstrating the synergism between lacutamab and chemotherapy in preclinical models of PDCL, we remain committed to the development in PDCL and continue to enroll patients in the phase 2 combination trial with chemotherapy, gemcitabine and doxaliplatin, where we believe the combination can offer additional benefit to patients. On the next slide, slide eight, we have a summary on the final phase two data in cesarean that were presented at ASH last December in an oral presentation. This is a heavily pretreated post-mogamulizumab patient pool with at least five million prior systemic line of therapies, including MOGA, and the global overall response rate was an encouraging 37.5%. I would like to note the deepness of the partial responses as you can see on the waterfall plot on the slide. We have also reported in this patient population an overall response rate of 46.4% in the skin and 48.2% in the blood. and overall a clinical benefit rate of 87.5% and a medium PFS of 8 months with a durability of response of 12.3 months. A favorable safety profile was also observed, and we look forward to sharing this data set along with the final data in Mycosis Fungoides cohort with the regulator later on. Now on slide nine, we can switch gear to our most advanced proprietary ANCET, which includes a detuned variant IL-2 to include activation and proliferation of ANCI cells in the tumor microenvironment. We were pleased to announce earlier this month that IPH65, the first of this second generation ANCETs, which targets CD20, has entered the clinic, and the first in human has started with the first patient being those in March. The trial will enroll patients with relapsed refractory non-Hodgkin lymphoma, and we will run in the US, Australia, and France. In B-cell non-Hodgkin lymphoma compared to recent therapies, including CAR-T and T-cell engagers, IPH65 has a disruptive mechanism of action that eliminates cancer cell via profound activation and proliferation of the ANCI cells. And IPH65 differs from allogeneic ANCI therapies, including CAR-ANCI, as it is an off-the-shelf therapy that drives the proliferation of the patient's own anti-cells in non-hormonal lymphoma and does not require any lymphodepletion as for other cell therapies. Now the IPH65 format also addresses the common challenges associated with the loss of CD16 by ensuring the activation of intratumoral anti-cells via the activation of NKIP46. Finally, by stimulating the anti-cell natural function, IPH65 has bystander effect that can cause the elimination of CB20 negative tumor cells, overcoming tumor heterogeneity or loss of tumor antigen. Now I will turn to Yanis.
spk08: Thank you, Sonia. On slide 10, I wanted to highlight our proprietary first-in-class NK-cell engager platform that we call NKET. NKET is a versatile technology made of antibody-derived building blocks that is creating an entirely new class of multi-specific engagers to induce synthetic immunity against cancer. Level averaging our scientific expertise in the NK-cell space This platform is an engine for producing series of drug candidates addressing multiple tumor targets, both in heme and solid tumors. The activating NK cell receptor called NKP46 is the backbone of our technology, and since it has a stable expression at the NK cell surface, even in the tumor microenvironment, introduces an optimal activation of the NK effector functions. We have also developed a second generation version of the technology by incorporating a variant of interleukin-2 in order to induce NK cell proliferation. As you can see, our pipeline of NK molecule is significantly growing, with Sanofi having now licensed four molecules. Two are in the clinic in Kim, and two are at preclinical stage in solid tumor, including IPH67, which is the program for which Sanofi opted in December last year. We are also very pleased to see our proprietary portfolio of AMCAT progressing. The second-generation AMCAT, IPH6501, is now in the clinic, and we continue to fuel our pipeline with new preclinical programs against multiple targets. On slide 11, you can see an overview of the clinical data presented by Sanofi last year at ASH for the AMCAT IPH6101, also named SAR579. In this dose escalation, we were encouraged to see initial preliminary single-agent activity and safety for SAR579 in relapsed recurrent AML patients. At the one-week percube dose, five complete responses were observed out of 15 patients, with three responders remaining in remission at data cutoff at over 7, 12, and 14 months of treatment. SAR-579 was well-related up to 6 mcg per kg with no dose-limiting plasticity observed and two grade 1 CRS observed out of 43 patients. The FDA awarded Farsight-79 a fast-track designation in May, and we look forward to seeing further updates from Cyanophi in due course. On slide 12, you can see a summary of our Cyanophi alliance. In 2016, we signed an initial agreement for two ANCAT molecules worth up to €400 million in milestone plus royalty, among which we announced €16 million to date. Both programs, SAR-579 and SAR-14, have progressed into Phase I clinical trials. In December 2022, we signed a second agreement whereby Sanofi licensed the IPH-62 ANCAT program targeting B7H3, a solid tumor target and again option for two other targets. In December last year, they opted in for one of these programs called IPH67, targeting an undisclosed tumor target in solid tumors, triggering a 15 million euro milestone and making 40 million euro the total of payment received for this second agreement. Altogether, considering these two agreements, we are eligible for a total milestone package of up to 1.75 billion plus royalties. Slide 13 highlights our growing antibody drug conjugate pipeline. As we continue to develop next generation therapeutics, having single agent activity, utilizing our antibody engineering platform, we find that for some tumor targets, we can generate antibodies with good internalizing property that therefore are well suited for ADC development. Our agreement with Takeda in the field provides a validation to this research approach and highlights our capability to generate differentiated ADC candidates. I will now cover updates on our lead proprietary ADC program, IPH45, on the next slide. Slide 14 highlights IPH45 which is our proprietary Nectin-4-targeted ADC with a topo-1 inhibitor payload. We managed to create a differentiated product through multiple components. First, we generated a proprietary antibody with a differentiated epitope, not overlapping with Enfortumab, the antibody backbone of PADCEL. Then, we selected a validated cleavable linker designed to be hydrophilic in order to counterbalance the hydrophobicity of the payload and to allow for a high drug antibody ratio. Finally, we selected a well-validated topo-1 inhibitor with bystander effect, allowing to bypass MMAE-related resistance mechanism and to address tumors with heterogeneous Nectin-4 expression. Altogether, these elements result in a differentiating Nectin-4 ABC showing strong efficacy in preclinical models, including in PADCET refractory PDX, as well as encouraging PTA tox profile in the non-human primates. These preclinical data have been selected for presentation at an oral session at ACR in the coming couple of weeks. We are looking forward to presenting them and to filing the IND for this product this year. On slide 15, I would like to remind you of Monalizumab, the anti-NKJ2A checkpoint inhibitor that we have licensed to AstraZeneca for oncology. In this slide, you can see an overview of the late-stage development plan for monahizumab in lung cancer. MONA is currently being investigated in a phase 3 trial called Pacific 9. AstraZeneca started this phase 3, evaluating the combinations of either MONA or olecumab plus durvalumab in the unresectable stage 3 non-spousal lung cancer setting who have not progressed after concurrent chemo-radiotherapy based on the results of their phase 2 cost trial. Cause data were published in the Journal of Clinical Oncology in 2022, and after a median follow-up of 11.5 months, PFS data showed a hazard ratio of 0.42 in favor of MONA plus Durvalumab combination versus Durvalumab alone. The results also showed an increase in the primary endpoint of confirmed overall response for MONA plus Durva combination over Durva alone of 36% versus 18% respectively. The AstraZeneca-sponsored NEOCOS-2 study is also underway in an earlier setting of lung cancer, evaluating mona plus durvalumab with chemo in the neoadjuvant non-multicellular cancer patient, based on phase 2 data from the NEOCOS study, which show also superiority of the mona plus durvalumab combination over durvalumab in this neoadjuvant setting. I will now turn to Frédéric for the final shows.
spk09: Thank you, Yanis. On slide 16, the key elements of an innate financial position and financial results as of the year ended, 31st of December 23, is as follows. Cash, cash equivalent, short-term investment and financial assets amount to 102.3 million as of the end of last year, including financial instruments amounting to 9.8 million. This number does not include the 15 million payment received from Sanofi in January 24. Revenue and other income from continuing operations amounted to $61.6 million in 2023, which mainly comprises revenue from collaboration and licensing agreements received from the agreements with AstraZeneca, Sanofi and Takeda, and $9.7 million in resource tax credit. Operating expenses from continuing operations amounted to $74.3 million in 2023, with R&D now making up 75% of the OPEX. Research and development expenses from continuing activities amounted to 56 million in 2023, up 8.4% from prior year. The increase in R&D mainly results from an increase in direct research and development expenses, both clinical and non-clinical. General and administrative expenses amounted to 18.3 million down by 18.5% on prior year due to the decrease in personal expenses, non-scientific advisory fees and other expenses mainly resulting from efficiency measures applied by the company. The table in the press release summarized the IFRS consolidated financial assessments as of and for the year ended 31st of December 23, including 2022 comparative information. We now hand over to Anthony.
spk10: Thank you, Frederic. I won't go through all the catalysts that we have listed on slide 17, but I'll spend a few minutes on some of the key clinical catalysts that we have noted on this slide, and then we'll provide a summary before we turn to your questions. We are expecting the final data for a proprietary antibody lacutamate in mycosis fungoides imminently. and we look forward to presenting this data in detail at an upcoming medical meeting. Concurrent with that, we'll also commence interactions with the global regulatory agencies as we map out the next steps in its development. Our antibody therapeutic NK Cell Engager program that was earlier referred to as the ANCIP program, this continues to evolve. This program has received broad validation through the licensing of four programs to Sanofi. We have recently taken a proprietary program emanating from this hand-cut platform into the clinic ourselves by dosing the very first patient. This program, known as IPH6501, is targeting CD20 in B-cell non-Hodgkin's lymphoma. For monolizumab or antibody-targeting NKG2A, the Phase III trial called PACIFIC-9 is underway. This is a study looking at monolizumab plus dovalumab in non-small cell lung cancer. The thinking here is that the dual targeting of the PD-L1 and the MKG2A pathways through this combination will lead to enhanced antitumor activity versus single-agent therapy. We continue to advance other agents targeting the adenosine pathway in the clinic. An example is IPH5201, which is currently in phase 2. in combination with drivalumab and chemotherapy in treatment-naive patients with resectable early-stage non-small cell lung cancer. So just to conclude, over the years, we have established a strong expertise in immunopharmacology. With definitive Phase II data in hand, we are mapping out the regulatory next steps for lacutamab. Our proprietary NK cell engager platform, NKIT, has the potential of addressing both hematologic malignancies and solid tumors. We are pursuing ADCs with a focus on differentiation with IPH45. This is our ADC targeting Nectin-4, being a key example of our approach. And lastly, we continue to retain a strong cash position to fund our operations well through the end of 2025. We are excited about our prospects for the future. And before I close, I would also like to thank the many employees at Innate who work very hard in developing therapies for the potential benefit of patients. With that, we can open it up for questions.
spk05: Thank you. At this time, I would like to remind everyone in order to ask a question, press star and then the number one on your telephone keypad. And we will pause for just a moment to compile the Q&A roster. We will take our first question from Egal Nakamobitz with Citi. Your line is open.
spk06: This is Amin on for Egal. Thank you for taking our questions. We had a couple. First, on the PTCO program, that you are not planning to reopen the phase one monotherapy trial. Can you walk us through your thought process there and give us more grand details on that? And what was the internal bar for efficacy there? And then on the second, again on the CUCMAB, where are you standing within the process of finding a partner for the commercialization and development of the program? Are you expecting the upcoming data or MF to catalyze a partnership there?
spk03: Right. Let me say that in PTCL we have enrolled 20 patients and the data around safety from 10 patients were presented at ASH last year. But per protocol, we have included a formal, let's say, interim analysis where we defined a minimum number of objective responses that needed to be observed prior to continued recruitment. And despite we observed some objective responses in PTCL with lacutamab in monotherapy, this number of objective responses did not meet the minimum number preset by the protocol. As you understand, in PTCL there are many different therapeutic options. and many already provide a quite robust number of objective responses, and therefore our threshold was quite high, too much. We remain, however, committed to the PTCL through the phase two study in combination with chemotherapy, where we expect to see some synergism between lacudamab and chemotherapy, and therefore provide some meaningful clinical benefit to patients. The second question was around the partners. Is that correct? Is it?
spk06: The second question was on partnership, yes.
spk03: Partnership. And around the partnership for lacutamab, We are actively looking for different options to pursue the next stage with lacudamab in the CTCL, either via partnership or alternative options.
spk06: Okay, got it. That makes sense. And just one quick follow-up. Do you expect this discontinuation of monotherapy phase impact your plans on the partnership for this molecule?
spk03: Not really. I mean, the data on PTCL have no impact, neither on the phase two in PTCL in combination with chemo, but definitely not on the CTCL where we already have the data in-house.
spk06: Okay, got it. Great. Thank you very much for taking our questions.
spk05: And we will take our next question from Dana Graybosh with LeRink Partners. Your line is open.
spk02: Hi. I'm going to ask a follow-up on the one just asked on the single agent activity. It's hard because we can't see it. And so is this you had one response and you had a lot of shrinking staple disease or did you have three and it just didn't meet your bar. And so I wonder if you could give us any more specific details, particularly because I think we'd like to, what should make us confident clinically that this is going to prove out in GEMOX to be something more meaningful for patients and the unmet needs compared to the therapeutic options here?
spk11: And this is the operator, I apologize. Did our presenters go on mute? All right, and ladies and gentlemen, please stand by. We are experiencing technical difficulties.
spk05: And ladies and gentlemen, I will put music back on while we wait for our speakers to reconnect. Thank you.
spk11: Hello, Henry, this is Abby. Okay, perfect, give me just one moment. All right, and let me make a slide once again.
spk05: And ladies and gentlemen, thank you for your patience while we managed our technical difficulties. Ms. Graybosch, do you mind asking your question again, please?
spk02: that came from Citi, which is, I wonder if you could give us any more details on the specific responses or any correlation with CARE3DL2 activity. You know, what in the clinical data could we hang on to to be confident that we're going to see synergy in combination with chemotherapy next year? Mm-hmm.
spk03: I suspect you are talking about the PTCL rather than the mycosis fungoides. Yes. Oh, yes. Right. Okay. Basically, in this study, we have recruited patients who have an expression level of Kir3DL2 that is equal or above 1%. We did not, let's say, restrict to any subtype of PTCL. And we hope to present the data later on this year. Even if, you know, we are not going to reopen the study and the sample size is relatively small because it's around 20 patients.
spk02: So, then what gives you confidence in the gem mark and combo will prove successful?
spk03: This is an investigator-sponsored trial, and the date of completion is predicted to be towards the end of 2025.
spk02: And, yeah, but why do you think that this will be successful? Why continue with the IIT?
spk03: Because at ASH last year, we have presented some data that demonstrate some synergism in preclinical model with lacutamab and chemotherapy.
spk11: Okay. Thank you for that.
spk04: So, operator, I'll ask an offline question, and then maybe we can go back to the online questions. So, I have an offline question from Justine Tellez at Kepler-Chevreux. On lukutamab, regarding the potential progress made with the regulatory authorities in sensory syndrome, can you give us an update? And also, at what point are you regarding a desire to partner, which I think you covered already? So, regulatory interactions.
spk03: We are working, now that we have the data in MS and these data are, and these data are, these preliminary, these data are promising, we are working to, for a fast forward, I'm alongside SS and MS, and a plan to maximize the value of lacudamab is going to be discussed with the regulators.
spk11: Okay. I'll pass the next question to you.
spk05: All right. Thank you. Our next phone question comes from Arthur He with HC Wainwright. Your line is open.
spk07: Hey, good morning, everyone. This is Arthur for RK. Thanks for taking my question. So I just want to follow up on the question on the CUDA map. So are you guys to go to the agent with the data, both with the cesarean syndrome and the MF, or rather go for the cesarean syndrome data alone to talk to the agent to file the BLA? Just want to clarify that.
spk03: Sure. Sure. Originally, when we had the data of CSERI, there was the option of going to the regulators with the CSERI data alone, where we had fast track designation and prime. Now we can really plan to merge the data, as I said, to maximize the value of lacutamab, not only in cesarean, that is a small subgroup of the CTCL, but maximize the value of the drug in the whole of CTCL, together, of course, with mycosis fungoides. And of course, You know, the option of asking for accelerated approval still remains. And as you know, in order to get accelerated approval anyway, we need the 12 months durability of response that is needed for this. And of course, we need to align on what the registrational trial could look like.
spk07: Thanks for that. Really helpful. Just a quick on the NCATS program. It's great to see the progress along and the expanding of the portfolio. Specifically on the 6501, I'm just curious for the trial you got to evaluate initially, Is there a CD20 color for the patient inclusion? And how about the dosing strategy there, if you can give additional color? Appreciate it.
spk03: Sure. In the study are going to be recruited the CD20 positive non-Hodgkin lymphomas, again, in every subtype. And this is a classic first in human trial. And therefore, we are at the first cohort, as you can imagine, as the first patient was enrolled in March.
spk11: It's a dose escalation study with expansions.
spk07: Thanks. And how about the dosing-wise? What's the dosing interval and the strategy for the dosing escalation?
spk03: Well, the dose escalation is guided by the safety signals that we see and, of course, you know, by statistical consideration and appetite of the investigators, depending on the safety and the exposure that we observe at each cohort.
spk11: All right. Thanks. Thanks for the additional comment. Are there any more questions?
spk05: We have no further phone questions at this time. I would now like to turn the call back to Mr. Hervé Brailly for any closing remarks.
spk00: Thanks a lot for your questions. We're looking forward to the next meeting. The next important steps will be the presentation, the oral presentation at the ACR present the features for ADC, CD, the IPH45, and then, of course, the general meeting taking place on May 21st. So we're looking forward to reconnecting with you all on these two opportunities. And I wish you a very good day. Looking forward to the next steps. Great. Thank you, everybody.
spk05: And ladies and gentlemen, this concludes today's call and we thank you for your participation. You may now disconnect.
spk11: Looking forward to the next steps.
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