Innate Pharma SA

PAR:IPH

Earnings Call Analysis

Earnings Call Transcript 2024-Q1

[Operator]

Thank you for standing by, and welcome to the Innate Pharma First Quarter 2024 Financial Results and Business Update Call. [Operator Instructions] I'd now like to turn the call over to Henry Wheeler, Vice President, Investor Relations and Communications. You may begin.

[Henry Wheeler, executive]

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 and 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 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 3, on today's call, we'll be joined by Herve Brailly, Interim Chief Executive Officer; then we have Sonia Quaratino, our Chief Medical Officer, who will cover updates on Lacutamab and IPH-6501. We will then hand the call to Yannis Morel, Chief Operating Officer, who will then discuss our ANKET and ADC platform updates. Arvind Sood, EVP, U.S. operations, will wrap and close. We also have Frederic Lombard on the call for Q&A. Herve, I now hand the call over to you.

[Hervé Brailly, executive]

Thank you, Henry. Turning to Slide 4. 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 and antibody-derived drug candidates. We look at 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 that 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 science, and of capital that we can reinvest to advance our proprietary products on 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 and our expertise in biology to develop innovative molecules for the 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 to -- from Phase I to Phase II. We are also pleased to see our lead proprietary ANKET IPH-6501 starting Phase I 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 further details in our ADC pipeline today presented by Yannis.

Finally, we are building a strong and sustainable foundation for our business with various partnerships across industry and academia, and, obviously, our AstraZeneca partnership is utmost importance with Monalizumab, continuing development in lung cancer. Next slide. The Slide 6 illustrates the variety of approaches that we have. I will now -- 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 like Lacutamab, ANKET and with the emerging assets ADC supported by partner products with AstraZeneca, Sanofi and Takeda, from late -- 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 a sustainable business.

Let's move to -- slide. In ASCO, we'll have -- in ASCO 2024, an important abstract's being published. This comprised the top line data from the Lacutamab/Telumab trial in Mycosis fungoides. IPH-6501 will be published with two posters, one in trial in progress on a preclinical assessment of IPH6501 and eventually two Monalizumab posters with updated Phase II COAST results in Stage III, unresectable in SLC on a Phase II 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 Lacutamab, on most advanced proprietary assets.

[Sonia Quaratino, executive]

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 II 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 II 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 proprietary asset, IPH-65, the Tetra-specific, antibody-based, NK-engager therapeutic or ANKET molecule, which is the first NK-engager to engage via a single molecule to activating receptor NKp46 and CD16. A tumor antigen, in this case, CD20 and an interleukin to receptor via an IL-2 variant, or IL 2B. The IL-2 variant is aimed to induce activation and proliferation of NK cells in the tumor microenvironment. IPH-65 is the first of the second-generation ANKET targeting CD20. We were pleased to announce earlier in the quarter that IPH-65 enter the clinic, and the first in human has started with the first patient dosed in March. The trial will enroll patients with relapsed refractory B-cell Non-Hodgkin's lymphoma, and the study will run in the U.S., Australia and France.

IPH-65 eliminates CD20-positive cancer cell via profound activation and proliferation of the NK cells. And by stimulating NK cells natural function by the variant IL-2, IPH-65 evokes a bystander effect and can also cause the elimination of CD20 negative tumor cells, overcoming tumor originating or loss of tumor antigen. The IPH format also addressed the common challenge associated with loss of CD16 by ensuring activation of intra-tumoral NK cells by the engagement of NKp46. The asset also differs from [ all generic ] NK cell therapy, including [indiscernible], 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 at ASCO annual meeting with the 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.

[Yannis Morel, executive]

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 [indiscernible] as 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 areas like autoimmunity 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 relapsed refractory AML 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 IPH-6501 entering the clinic with the first patient dosed in March. Next 6 months, two IPH-6501 poster will be presented at ASCO, one on the Phase I/II 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 fitting for antibodies or conjugate development than for ANKET. Our agreement with Takeda in the field provides a validation to its approach and highlights our capability to generate differentiated ADCs.

Now I will cover updates on our lead proprietary ADC program, IPH-45, 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 a proprietary antibody with a differentiated epitope, which is not overlapping with Enfortumab, the parental antibody of PADCEV. 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 Exatecan, a topoisomerase inhibitor with strong bystander effect, allowing to bypass MMAE related resistance mechanism and address tumors with low to heterogenous 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 MMA ADC, including in formula [indiscernible]. Slide 13 is a summary of some of the data presented at AACR. In a nutshell, we showed that IPH-45 has strong antitumor efficacy in a variety of preclinical models, including ones that are refractory to PADCEV because of high expression of the MDR1 Efflux transporter, a known mechanism of resistance to MMA. Also, we found very good efficacy in patient-derived PDX 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 provides the rationale to target, in addition to bladder, tumor type with medium- to low-expression of 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 favorable 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 an overview of the late-stage development of [ Tonalizumab ] in lung cancer. Based on the Phase II COAST data, AstraZeneca started in May 22, PACIFIC-9, a Phase III trial evaluating the addition of a [indiscernible] Monalizumab, or oleclumab, to durvalumab in unresectable stage III non-small-cell lung cancer patients who have not progressed after concurrent chemo addition therapy. The AZ sponsored NeoCOAST-2 Phase II study is also underway in an earlier lung cancer setting, namely in Stage IIa to IIIb, 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 Herve at the beginning, Monalizumab will have two poster presentations 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 will now hand over to Arvid.

[Arvind Sood, executive]

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 2 years for both our proprietary and partnered assets. Just a few weeks ago, we presented preclinical data on IPH-45, that Yannis has alluded to earlier, which, of course, is our Nectin tumor 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 TELLOMAK trial with our proprietary product, Lacutamab in MF or 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 are also making very good progress with our ANKET platform with some data coming at the upcoming ASCO conference. Two abstracts on IPH-65, our second-generation ANKET targeting CD20 for the treatment of relapsed refractory NHL or non-Hodgkin's lymphoma. Two abstracts will also be presented by our partner AstraZeneca on Monalizumab, Phase II clinical trials for the treatment of lung cancer. If we can then move to the last slide. So let me just conclude with the key -- 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 IPH-45 at AACR provides added clarity on our efforts there. Lastly, with about EUR 115 million in cash on our balance sheet as of the end of March of 2024, we are in a strong cash position for operations through the end of 2025. So Herve, with that, let me turn the call over to you, back to you, and then we can open it up for questions.

[Hervé Brailly, executive]

Yes. Thank you. We'll go straight to questions, please, operator.

[Operator]

We will now begin the question-and-answer session. [Operator Instructions] Your first question comes from the line of Daina Graybosch from Leerink Partners.

[Daina Graybosch, analyst]

But first on the MS data in the TELLAMEX study. If I remember correctly, part of doing that arm was to define a potential biomarker threshold by going broad and more narrow in Tier 2 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 IPH-6501. I wonder if you thought about potentially taking this engager forward in autoimmune diseases in addition to oncology?

[Sonia Quaratino, executive]

Thank you, Daina. 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. So we have made three different cohorts in TELLOMAK trial for the Mycosis fungoides, where we prospectively screen patients for the expression of the KIR3DL2, and we have a cohort of patients expressing 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 results in both KIR3 positive tumors, more than 1%, or KIR3 less than 1%. And there will be interesting data in both subsets. Now for the IPH-65, I will hand over to Yannis on this question because this is something that is very key to the business of Innate.

[Yannis Morel, executive]

Yes. Hi, Daina, yes, of course, it's something that we are following. As you know, there have been several attempts to use a T-cell engager, but also [ car ] NK to DP pathogenic B-cells. It's something that we could potentially contemplate at some point with IPH-6501. 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 to really characterize the pharmacodynamic effect of the drug in 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.

[Hervé Brailly, executive]

If I can complement here. We do believe that with the once platform, we have an interesting tool to address alternative therapeutic field beyond the tumor immunology, tumor treatment. Thanks to the very good safety profile that we see we don't get three on that we're going to document with ANKET-4 and is the report of 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.

[Operator]

Your next question comes from the line of Yigal Nochomovitz from Citigroup.

[Yigal Nochomovitz, analyst]

So with the MF data at ASCO, could you just talk about what you expect to discuss there? 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 time lines associated with the discussions with the FDA as well as like the time lines for filing the application?

[Sonia Quaratino, executive]

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 Lacutamab 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 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 [ hold ] our priority is really to progress the regulatory strategy with the FDA. Please let me know if I miss some point in your question.

[Yigal Nochomovitz, analyst]

The goal would be to file with the FDA. There wouldn't be any other studies, essentially. That would be the registrational study?

[Sonia Quaratino, executive]

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, in particular, the FDA expects from us, but we will discuss with the agency different options.

[Yigal Nochomovitz, analyst]

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

[Hervé Brailly, executive]

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 or potential other new agreements...

[Operator]

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

[Swayampakula Ramakanth, analyst]

So my question is on the collaboration 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, when -- what do you think your partner is planning to do once that -- after the data presentation at ASCO?

[Yannis Morel, executive]

Yes. Yannis speaking. I'm not sure to get your point on the Sanofi collaboration. Just to remind you that we are having two -- Sanofi's developing currently two ANKET molecule, which are the tri-specific ones, the third generation in the clinic, in [indiscernible] 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 2 programs this year. With regard to the early-stage ones, as you know, both of them are in solid tumors. One is targeting B7-H3 and the other one targeting another undisclosed solid tumor. We are progressing them at a preclinical 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 it's oncology pipeline. And clearly, the NK-cell engager that we are having with them are on the priority list from the -- on their oncology pipeline. And then on the mona, as you can see by the title and unfortunately, we cannot disclose more for the moment. The COAST presentation at ASCO will be a poster with updated results from the COAST. [indiscernible] has been published in JCO and presented at ESMO a couple of years ago. And now it's a more -- 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.

[Operator]

[Operator Instructions] Your next question comes from the line of Rajan Sharma from Goldman Sachs.

[Rajan Sharma, analyst]

So firstly, just on IPH 45, how should we think about the initial development plan there? Is it likely to be in PADCEV-resistant or PADCEV experienced patients in bladder cancer? And could you also just talk about your expectations longer term for the profile edge? 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 Lacutamab Sezary. You mentioned a potential exploring a fast-to-market strategy. Could you just kind of walk us through the potential patent market there? And is that predicated on MF?

[Sonia Quaratino, executive]

Rajan, thanks for the questions. Around IPH-45, of course, we have some ideas based on the preclinical data 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, {indiscernible] asset. May not only be in PADCEV 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?

[Rajan Sharma, analyst]

Yes, sure. So I think you talked about a fast-to-market strategy in Serzay 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?

[Sonia Quaratino, executive]

Right. Well, there are different options, of course. And as also thought previously, the option of asking for accelerated approval is -- 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 Sezary where we obtained FDA Fast Track designation. But of course, with the registrational trial would 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 it's very much on our radar.

[Operator]

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

[Jingming Chen, analyst]

This is Jiingming on for Lisa. So our question is for Lacutamab. So what was the good benchmark for PTCL data next year? What's your expectation for that readout?

[Sonia Quaratino, executive]

Is a very interesting question. Now PTCL, of course, is a very crowded space. It's a very crowded space. On the other hand, it remains quite unmet medical need for these patients. And Lacutamab has the advantage of having an extremely good safety profile as shown in the TELLOMAK study compare -- and that basically set it in front of many other therapies 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 drugs in the same space. It's a balance between efficacy and tolerability.

[Operator]

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