Innate Pharma S.A. (IPHA) Q1 2024 Earnings Report, Transcript and Summary

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. [Operator Instructions] I'd now like to turn the call over to Henry Wheeler, Vice President, Investor Relations and Communications. You may begin.

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 year-to-date, during the quarter-to-date, as well as addressing future goals and milestones. The press release in today's presentation are both available on the IR section of the website. On Slide 2, before we start, I'd like to remind you that we'll be making 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 3, on today's call, we will be joined by Herve Brailly, our Interim Chief Executive Officer. Then we have Sonia Quaratino, our Chief Medical Officer, who will cover updates on the lacutamab and IPH65 alone. We will then hand to Yannis Morel, Chief Operating Officer, who will then discuss our ANKET and ADC platform updates; Arvind Sood, EVP, U.S. Operations, who will wrap up and close. We also have Frederic Lombard on the call for Q&A. Herve, I'll now hand the call over to you.

Thank you, Henry. Turning to Slide 4. I'd like to remind you for strategy. Our ambition is to develop innovative drug candidates that contribute to transform concept care for a strong pipeline of differentiated antibody on 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. All 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 is in development for T cell lymphoma, and with top line MF data are 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 signs on our capsule that we can reinvest to advance our proprietary 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 lacutamab. Second, we continue to fuel our pipeline and create longer term value by leveraging our antibody engineering capabilities on our expertise in biology to develop innovative molecules with a primary focus on our multi specific NK cell engager, that's the platform called ANKET. We are pleased to see continuous progress with our partner Sanofi, presenting various updates for the lead ANKET candidate, which has recently been transitioned from Phase 1 to Phase 2. We are also pleased to see our lead proprietary ANKET IPH6501 starting Phase 1 trials. As we develop antibody targets for our ANKET platform, we recognize some of these targets might be more applicable for ADC technology. And we have a further details in our ADC pipeline today presented by Yannis. Finally, we're building a strong and sustainable foundation for our business with various partnerships across industry and academia on obviously our AstraZeneca partnership is of utmost importance with monalizumab continuing development in lung cancer. Next slide. The Slide 6 illustrate the variety of approaches that we have. I will now move to Slide 6 to the portfolio, sorry. On Slide 6 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 lacutamab ANKET, 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 the R&D engine looks to leverage our scientific knowhow to create a sustainable business. Let's move to Slide. In ASCO will have in ASCO 2024 an important abstracts being published. This comprise the top line data from the lacutamab, TELLOMAK trial in mycosis fungoides. IPH6501 will be published with two posters, one in trial in progress on a preclinical assessment of IPH6501. On eventually, two monalizumab posters with updated Phase 2 COAST results in Stage III unresectable NSCLC on the Phase 2 in extensive stage SCLC trial. I would like now to pass the call over to Sonia, who’ll review the progress made with the portfolio, starting with lacutamab almost advent proprietary asset.

Thank you, Herve. On Slide 7, let me summarize the progress we are making with lacutamab. Lacutamab has been developed in cutaneous T cell lymphoma as the target KIR3DL2 is expressed in more than 90% of patients affected by Sezary syndrome and approximately in 50% of patients with mycosis fungoides. The TELLOMAK trial is a Phase 2 single arm study, including both Sezary and mycosis fungoides. And last year, we presented the top line result in Sezary syndrome at ASH. We have now analyzed the top line results of the mycosis fungoides cohorts. While we have seen encouraging preliminary data in patients with KIR3DL2 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 Sezary syndrome, where lacutamab was granted the U.S. 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 2 combination trial with chemotherapy GEMOX, where we believe the combination will offer additional benefit to patients. On Slide 9, we now switch gear to our most advanced property asset IPH65. The tetra specific antibody-based NK engager therapeutic or ANKET molecule, which is the first ANKET engager to engage via a single molecule two activating receptor and KP46 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 NK cells in the tumor microenvironment. IPH65 is the first of the second generation ANKET targeting CD20. We were pleased to announce earlier in the quarter that IPH65 enter the clinic, and the first inhuman has started with the first patient dose in March, the trial will enroll patient with relapsed refractory B-cell non-Hodgkin's lymphoma, and the study will run in the U.S., Australia, and France. IPH65 eliminates CD20 positive cancer cell 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 address the common challenge associated with loss of CD16 by ensuring activation of intratumoral NK cells wide engagement of NKp46. 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 own NK cells in B cell neurological lymphoma, and does not require lympho depletion, as for cell therapy. IPH 65 is going to be present ASCO annual meeting with two poster, one as trial in progress and the other outlining the preclinical disruptive mechanism of action. I will now hand over to Yannis to cover the early pipeline.

Thank you, Sonia. On Slide 10, I wanted to draw your attention to our portfolio of ANKET drug candidates, which has made significant progress during the last quarter. As you remember, ANKET molecules are produced through our proprietary first-in-class and 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 ANKET 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 area like autoimmunity and inflammation. Last quarter, Sanofi Advanced SAR’579 to Phase 2 on the back of initial efficacy data showing single agent activity with durable complete responses in relapse 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 ANKET IPH6501 entering the clinic with the first patient dosed in March. Next month, two IPH6501 poster will be presented at ASCO, one on the Phase 1/2 trial design and the other one on the 6501 technical 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 ANKET. Our agreement with Takeda in the field provides the 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 Nectin-4 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 proprietary antibody with a differentiated epitope, which is non-overlapping with enfortumab the parental antibody of Padcev. Then we selected a validated [Chemo] and hydrophilic linker that counterbalance the hydro obesity of the payload and allows the use of high drug antibody ratio of eight. Finally, we selected [indiscernible] Topo 1 inhibitor with strong bystander effect, allowing to bypass MMAE related resistance mechanism and address tumors with low -- and 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 Enfortumab Vedotin. Slide 13 is a summary of some of the data presented at ACR. In a nutshell, we showed that IPH45 has strong anti-tumor efficacy in a variety of preclinical models, including ones that are refractory to Padcev because of high expression of the MDA1 [indiscernible] transporter, the known mechanism of resistance to MMAE. Also, we found very good efficacy in patient derived Padcev models with low expression of Nectin-4 as shown on the graph in the center of the slide, where Padcev does not work either. This data provide a 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 Padcev is so far limited. With a favourable developability profile including high yield productivity, drug stability, and encouraging PK tox data in animal studies. We are looking forward to filing the IND this year. On Slide 14, 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 overview of the late stage development of monalizumab in lung cancer. Based on the Phase 2 COAST data, AstraZeneca started in May ‘22, PACIFIC-9, a Phase 3 trial evaluating the addition of monalizumab or oleclumab to durvalumab in unresectable Stage III non-small cell lung cancer patients who have not progressed after concurrent chemoradiation therapy. The AZ sponsored NeoCOAST-2 Phase 2 study is also underway in an earlier lung cancer setting, namely in stage IIA-IIIB non-small cell lung cancer patient and is evaluating the addition of monalizumab to durvalumab and chemo in the perioperative agent like setting. As mentioned by earlier at the beginning, monalizumab will have two poster presentation at ASCO, one being an update of the COAST 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'll now hand over to Herve.

Yannis, 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 Yannis alluded to earlier, which of course is our Nectin-4 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 telematics trial with our proprietary product lacutamab in MF for mycosis fungoides. This combined with data and Sezary 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're also making very good progress with our ANKET platform with some data at the upcoming ASCO conference. Two abstracts on IPH65, our second generation ANKET targeting CD20 for the treatment of relapse refractory NHL or non-Hodgkin's lymphoma. Two abstracts will also be presented by your partner AstraZeneca, monalizumab, Phase 2 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 ANKET 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 EUR115 million in cash on our balance sheet as of the end of March of 2024, we are in a strong cash position operations to the end of 2025. So, Arvind with that, let me turn the call over to you, back to you and then we can open it up for questions.

Yes, thank you. We'll, we'll go straight to questions. Please operator.

[Operator Instructions] Your first question comes from the line of Daina Graybosch from Leerink Partners.

The first on the MF data in the TELLOMAK study. If I remember correctly, part of doing that -- was to define a potential biomarker threshold by going broad and more narrow and KIR3DL3 expression. I wonder if you could talk about if that's still the intent and the 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.

These are both great questions. Let's start with lacutamab. Since the expression level of KIR3DL2 in mycosis fungoides is relatively modest compared to Sezary and it is also expressed in roughly 50% of patients. We have made three different cohorts in TELLOMAK trial for the mycosis fungoides where we prospectively screen patient for the expression of the KIR3DL2. And we have a cohort of patient express 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 KIR3 positive tumors more than 1% or KIR3 less than 1%. And there will be interesting data in both subset. Now for the IPH65, I'll hand over to Yannis on this question because this is something that is very key to the business of Innate.

Of course, it's something that we are following. As you know, there have been several attempts to use T cell lung engager, but also CAR-NK to deplete pathogenic T 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 T cell depletion before considering e expansion to other therapeutic areas, but in theory, something that we could contemplate on the meat to long term.

If I can complement here, we do believe that with the ANKET 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 ANKET 3 on that we are going to document with ANKET 4 on with the report the 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.

Next question comes from the line of Yigal Nochomovitz from Citigroup.

So with the MF data at ASCO, can 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? You're going to be speaking with the FDA, well, based on that data that you've recently seen, are you going to 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 application?

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 are asking around -- your question is around the regulatory path forward for lacutamab after the presentation of the MF data at ASCO. And our aim here is to ensure that lacutamab gets to patients who needs this drug as quickly as possible. And our aim is really to maximize the value of the drug, not only in Sezary, 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, we are all -- our priority is really to progress the regulatory strategy with the FDA. Please let me know if I miss some point in the question.

But the goal would be to file with the FDA. There wouldn't be any other study essentially that would the registrational study.

Well, it is now mandatory to have a registrational trial. Also, monalizumab as open the field by having a randomized control 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.

And then regarding the health of the financial situation, you have runway till the end of 2025. Are there milestones from Sanofi or AstraZeneca that you're expecting between now and the end of 2025 that would spend the cash?

The cash position and the projection of cash until end of ‘25 does not include and does not take into account any potential milestone from existing agreements nor potential other new agreements.

Your next question comes from the line of Swayampakula Ramakanth from HCW.

My question on 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 monalizumab, what do you think your partner is planning to do once that after the data presentation at ASCO?

Yannis is 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 ANKET molecule, which are the tri-specific ones, the third generation in the clinic, in -- with the CD1, 2, 3 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 program this year. With regard 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 and this close solid tumor, we are progressing them at the technical stage, but we can unfortunately not comment on the timing when this molecule will reach the clinic. What I can say that the collaboration with Sanofi is very active. You may have seen also during the last month that Sanofi also refocused is oncology pipeline. And clearly the NK cell engager that we're having with them are on the priority list on their oncology pipeline. On the mona, as you can see by the title, and fortunately we cannot disclose more for the moment, the COAST presentation at ASCO will be a poster with updated results from the COAST. It has been published in GCO and presented at a small couple years ago. And now it's a more a longer term and updated data, but we cannot 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.

Your next question comes from a line of Rajan Sharma from Goldman Sachs.

Firstly, just on IPH45, how should we think about the initial development plan now? Is it likely to be in Padcev resistant or Padcev experienced patients in bladder cancer? Could you also just talk about your expectations longer term for the profile there? 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 lacutamab on Sezary, you mentioned a potential exploring of faster market strategy. Could you just kind of walk us through the potential passing market there and is that predicated on MF?

Rajan, thanks for the questions. Around IPH45, of course, we have some ideas based on the preclinical data on out to better position this asset. Of course, the initial trial will be a dose escalation study to assess the safety tolerability and signs of antitumor 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 may not only be in parts of refractory patients, but for instance, there is a possibility strong of the preclinical data that we recently published at AACR also in all those tumors that express a low level of Nectin-4 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, lacutamab, do you mind repeating your question?

Yes, sure. So I think you talked about a fast to market strategy in Sezary syndrome. Could you just maybe walk us through how you're thinking about that and what the potential options could be? And then just from a commercialization perspective, is that predicated on also getting an approval in MF.

Right. Well, there are different option of course, and as also thought previously the option of asking for accelerated approval is remains open. And as we need the 12 months durability of response and a registrational trial ongoing in order to obtain accelerated approval in the niche indication of Sezary where we obtain FDA fast track designation. But of course, with the registrational trial, we'd also, aim to bring lacutamab on the market for the MF 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.

Your next question comes from the line of Liisa Bayko from Evercore ISI.

This is Jingming on 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?

Hi Lisa. Very interesting question. Now, PTCL, of course, it's a very crowded space, apologies, it's a very crowded space. On the other hand, it remains a quite unmet medical need for this patients. And lacutamab has the advantage of having an extremely good safety profile as shown in the TELLOMAK’s study compare. And that basically, set it in front of many other therapists that have a 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 what other competitors are with other drug in the same space. It's a balance between efficacy and tolerability.

And this concludes our question-and-answer session, and does conclude today's conference call. Thank you for your participation. You may now disconnect.