Innate Pharma - Q1 2024

Transcript

Operator (participant)

Thank you for standing by, and welcome to the Innate Pharma first quarter 2024 financial results and business update call. All lines have been placed on mute to prevent any background noise. After the speaker's remarks, there will be a question-and-answer session. If you would like to ask a question during this time, simply press star followed by the number one on your telephone keypad. If you would like to withdraw your question, again press the star one. Thank you. I'd now like to turn the call over to Henry Wheeler, Vice President Investor Relations and Communications. You may begin.

Henry Wheeler (VP of Investor Relations and Communications)

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 two, before we start, I'd like to remind you that we'll make forward-looking statements regarding our financial outlook, in addition to regulatory and product plan development. These statements are subject to risks and uncertainties that may cause actual results to differ from those forecasted. On slide three, on today's call, we'll be joined by Hervé Brailly, Interim Chief Executive Officer. Then we have Sonia Quaratino, Chief Medical Officer, who will cover updates on lacutamab and IPH6501.

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 US Operations, will wrap and close. We also have Frédéric Lombard on the call for Q&A. Hervé, I now hand the call over to you.

Hervé Brailly (Interim CEO)

Thank you, Henry. Turning to slide four, I'd like to remind you of our strategy. Our ambition is to develop innovative drug candidates that contribute to transforming cancer care through a strong pipeline of differentiated antibody-derived drug candidates. We look to drive value from our early R&D efforts through later-stage partnerships where and when it makes sense to do so. Our business model is centered around three key priorities. Firstly, we look to create near-term value driven by our lead proprietary product candidate, lacutamab, which, as you know, is in development for T-cell lymphoma, and with top-line MF data coming at ASCO this year. As a reminder, our focus remains to leverage the value of our products as much as possible, which will further validate our science and offer capital that we can reinvest to advance our proprietary products 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 and our expertise in biology to develop innovative molecules with a primary focus on our Multispecific 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 I to phase II. We are also pleased to see our lead proprietary ANKET, IPH6501, 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. Obviously, our AstraZeneca partnership is of utmost importance, with monalizumab continuing development in lung cancer. Next slide. The slide six illustrates the variety of approaches that we have. I will now move to slide six, to the portfolio, sorry. On slide six is a summary of our pipeline, which shows how we continue to translate our science into a robust portfolio of proprietary and partnered assets. It also illustrates how we are executing against our strategy with our lead proprietary assets like lacutamab, ANKET, and with the emerging assets ADC supported by partnered products with AstraZeneca, Sanofi, and Takeda from 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 a sustainable business. Let's move to slide. In ASCO, we'll have in ASCO 2024, an important abstract being published. This comprises the top-line data from the lacutamab Telomac trial in mycosis fungoides. IPH6501 will be published with two posters, one in trial in progress on a preclinical assessment of IPH6501, and eventually two monalizumab posters with updated phase II combo results in stage 3 unresectable NSCLC, and 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, our most advanced proprietary asset.

Sonia Quaratino (CMO)

Thank you, Hervé. On slide seven, 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 Sézary syndrome and approximately 50% of patients with mycosis fungoides. The Telomac trial is a phase II single-arm study including both Sézary and mycosis fungoides, and last year we presented the top-line result in Sézary syndrome at ASH. We have now analyzed the top-line results of the mycosis fungoides cohorts, where we have seen encouraging preliminary data in patients with 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 sharing the data with you then.

We are pursuing a fast-to-market strategy for lacutamab in Sézary syndrome, where lacutamab was granted the US Fast Track designation and EU Prime designation in 2020, and we look forward to discussing 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 nine, we now switch gear to our most advanced proprietary asset, IPH6501, 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-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.

IPH6501 is the first of the second-generation ANKET, targeting CD20. We were pleased to announce earlier in the quarter that IPH6501 entered 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 lymphoma, and the study will run in the U.S., Australia, and France. IPH6501 eliminates CD20-positive cancer cells via profound activation and proliferation of the NK cells, and by stimulating NK cells' natural function via the variant IL-2, IPH6501 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 addresses the common challenge associated with loss of CD16 by ensuring activation of intratumoral NK cells via the 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's own NK cells in B-cell non-Hodgkin lymphoma and does not require lymphodepletion as for cell therapy. IPH6501 is going to be present at ASCO annual meeting with two posters, 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 (COO)

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 NK cell engager platform. It is a multispecific 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 areas like autoimmunity and inflammation.

Last quarter, Sanofi advanced SAR'579 to phase II 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 were very pleased to see our proprietary second-generation ANKET, IPH6501, entering the clinic with the first patient dosed in March. Next month, two IPH6501 posters will be presented at ASCO, one on the phase I/II trial design and the other one on the 6501 preclinical characterization. Last but not least, we are putting a lot of efforts to further expand this portfolio to additional tumor targets, including in solid tumors. Slide 11 highlights our growing portfolio of ADC drug candidates.

As we continue to develop next-generation antibody therapeutics, we find that for some tumor targets, we can generate antibodies with good internalizing properties and therefore more suited for antibody-drug conjugate development than for 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 AACR in San Diego last month. Slide 12 highlights IPH45's overall structure. First, it is composed of a proprietary antibody with a differentiated epitope, which is non-overlapping with M42 mAb, the parental antibody of Padsev. Then, we selected a validated cleavable and hydrophilic linker that counterbalances the hydrophobicity of the payload and allows the use of a high drug-antibody ratio of eight.

Finally, we selected exatecan, a topoisomerase I inhibitor with strong bystander effect, allowing to bypass MMAE-related resistance mechanisms and address tumors with low to heterogeneous Nectin-4 expression. Altogether, these elements create a novel and differentiated ADC to target Nectin-4 in a broad panel of tumor indication on top of bladder cancer by overcoming the challenges associated with Nectin-4 MMAE ADC, including MDR1/ABCB1 gene. Slide 13 is a summary of some of the data presented at AACR. In a nutshell, we showed that IPH45 has strong antitumor efficacy in a variety of preclinical models, including ones that are refractory to Padsev because of high expression of the MDR1 efflux transporter, a known mechanism of resistance to MMAE.

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 Padsev does not work either. These data provide a rationale to target, in addition to bladder, tumor types with medium to low expression or heterogeneous expression of Nectin-4, like breast, lung, prostate, head and neck, and pancreas, where efficacy reported with Padsev 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 monalizumab in lung cancer.

Based on the phase II COAST data, AstraZeneca started in May 2022, PACIFIC-9, a phase III trial evaluating the addition of either monalizumab or oleclumab to durvalumab in unresectable stage 3 non-small cell lung cancer patients who have not progressed after concurrent chemoradiation therapy. The AZ-sponsored NeoCOAST-2 phase II study is also underway in an earlier lung cancer setting, namely in stage 2a to 3b non-small cell lung cancer patients, and is evaluating the addition of monalizumab to durvalumab and chemo in the perioperative adjuvant-like setting. As mentioned by Hervé 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 Arvind.

Arvind Sood (EVP of US Operations)

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 Telomac trial with our proprietary product lacutamab in MF for mycosis fungoides. This, combined with data in Sézary 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 at the upcoming ASCO conference. Two abstracts on IPH6501, 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 and 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 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 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 Hervé, with that, let me turn the call over to you, back to you, and then we can open it up for questions.

Hervé Brailly (Interim CEO)

Yeah, thank you. We'll go straight to questions, please, operator.

Operator (participant)

Thank you. We will now begin the question-and-answer session. If you would like to ask a question, press star one on your telephone to raise your hand and join the queue. If you would like to withdraw your question, again, press star one. Your first question comes from the line of Daina Graybosch from Leerink Partners. Your line is open.

Ramakanth Swayampakula (Managing Director and Senior Equity Analyst)

Hi. Thank you for the question and the update. The first on the MF data in the Telomac 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 DLL3 expression. I wonder if you could talk about if that's still the intent and how you're going to go about picking a potential threshold for a biomarker going forward. And then the second question is on IPH6501. I wonder if you thought about potentially taking this engager forward in autoimmune diseases in addition to oncology. Thank you.

Sonia Quaratino (CMO)

Thank you, Diana. These are both great questions. Let's start with lacutamab. Since the expression level of KIR3DL2 in mycosis fungoides is relatively modest compared to Sézary, and it is also expressed in roughly 50% of patients, we have made three different cohorts in Telomac trial for the mycosis fungoides, where we prospectively screen patients for the expression of the KIR3DL2. We have a cohort of patients expressing more than 1%, less than 1%, and all-comers. We have been working alongside the trial on a companion diagnostic. But at the ASCO annual meeting, you will see the result in both KIR3DL2 positive tumors, more than 1%, or KIR3DL2, less than 1%. There will be interesting data in both subsets.

Now, for the IPH6501, I will hand over to Yannis on this question because this is something that is very key to the business of Innate.

Yannis Morel (COO)

Yeah. Hi, Diana. Yeah, of course, it's something that we are following. As you know, there have been several attempts to use T-cell engager, but also CAR-NK to deplete pathogenic B-cells. It's something that we could potentially contemplate at some point with IPH6501, but for the moment, it's a bit early. Like Sonia mentioned, we just started the dose escalation. We really need to first establish the safety and the dose and to really characterize the pharmacodynamic effect of the drug in the B-cell depletion before considering expansion to other therapeutic areas. But in theory, it's something that we could contemplate on the mid to long term.

Hervé Brailly (Interim CEO)

Yeah. If I can comment 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're going to document with ANKET 4 and with the reported efficacy data that we have in various preclinical models. So it's a bit early to anticipate there and make any strong statement on the future direction. But we strongly believe that we have a platform of very high value to address a number of pathologic conditions beyond cancer.

Ramakanth Swayampakula (Managing Director and Senior Equity Analyst)

Great. Thank you.

Operator (participant)

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

Ramakanth Swayampakula (Managing Director and Senior Equity Analyst)

Yeah. Hi. Thanks. So with the MF data at ASCO, could you just talk about what you expect to discuss there and how will that impact the filing strategy? Is it pretty much consistent with what you've already outlined? Are you 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?

Sonia Quaratino (CMO)

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. Correct me if I'm wrong. Your question is around the regulatory path forward for lacutamab after the presentation of the MF data at ASCO. Our aim here is to ensure that lacutamab gets to patients who need this drug as quickly as possible. Our aim is really to maximize the value of the drug not only in Sézary but also in the larger population of mycosis fungoides, and so capturing the whole CTCL space. After the data will be presented at ASCO, our priority is really to progress the regulatory strategy with the FDA. Please let me know if I missed some point in the question.

Ramakanth Swayampakula (Managing Director and Senior Equity Analyst)

But 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 (CMO)

Well, it is now mandatory to have a registrational trial. Also, mogamulizumab has opened the field by having a randomized control study in CTCL. And this is very likely what the regulators, in particular the FDA, expect from us. But we will discuss with the agency different options.

Ramakanth Swayampakula (Managing Director and Senior Equity Analyst)

Okay. And then regarding the health of the financial situation, we 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 send the cash?

Yannis Morel (COO)

The cash position and the projection of cash until end of 2025 does not include and does not take into account any potential milestone from existing agreements nor potential other new agreements.

Ramakanth Swayampakula (Managing Director and Senior Equity Analyst)

Okay. Thank you.

Operator (participant)

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

Ramakanth Swayampakula (Managing Director and Senior Equity Analyst)

Thank you. So my question is on the collaborations that's been going on with Sanofi on some of your earlier stage molecules. I want to see what commentary you have on that. And then in terms of monalizumab, what do you think your partner is planning to do after the data presentation at ASCO?

Yannis Morel (COO)

Yeah. So hi, okay. Yannis speaking. I'm not sure I get your point on the Sanofi collaboration. Just to remind you that we have two; Sanofi is developing currently two ANKET molecules, which are the trispecific ones, the third generation in the clinic, in hem, with the CD123 that has been presented last year at ASCO and ASH, and the BCMA, which has entered the clinic also last year. And we are really looking forward to potentially see updates on these two programs this year. With regard to the early stage ones, as you know, both of them are in solid tumors. One is targeting B7-H3, and the other one is targeting another undisclosed solid tumor. We are progressing them at the preclinical stage, but we can, unfortunately, not comment on the timing when this molecule will reach the clinic.

What I can say is that the collaboration with Sanofi is very active. You may have seen also during the last months that Sanofi also refocused its oncology pipeline. Clearly, the NK cell engager that we are having with them are on the priority list on their oncology pipeline. Yeah. So on.

Ramakanth Swayampakula (Managing Director and Senior Equity Analyst)

Thanks for that. Then.

Yannis Morel (COO)

Yeah. And then 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 JCO and presented at ESMO a couple of years ago. And now it's 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.

Ramakanth Swayampakula (Managing Director and Senior Equity Analyst)

Thank you. Thanks for taking my question.

Operator (participant)

Again, if you would like to ask a question, press star one on your telephone keypad. Your next question comes from a line of Rajan Sharma from Goldman Sachs. Your line is open.

Ramakanth Swayampakula (Managing Director and Senior Equity Analyst)

Hi. Thanks for taking my question. So firstly, just on IPH45, how should we think about the initial development plan now? Is it likely to be in Padsev-resistant or Padsev-experienced patients in bladder cancer? And 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 Sézary, you mentioned a potential exploring a faster market strategy. Could you just kind of walk us through the potential passive market there, and is that predicated on MF? Thank you.

Sonia Quaratino (CMO)

Rajan, thanks for the questions. Around IPH45, of course, we have some ideas based on the preclinical data on how to better position this asset. Of course, the initial trial will be a dose escalation study to assess the safety, tolerability, and signs of antitumor activity of this asset. Based on the characteristics shown in the trial, we will refine, of course, the clinical development plan for this asset. It may not only be in Padsev refractory patients, but for instance, there is a strong possibility 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. 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?

Ramakanth Swayampakula (Managing Director and Senior Equity Analyst)

Yeah. Sure. So I think you talked about a faster market strategy in Sézary 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 (CMO)

Right. Well, there are different options, of course. And as also thought previously, the option of asking for accelerated approval remains open. And as you know, we need the 12-month durability of response and a registrational trial ongoing in order to obtain accelerated approval in the niche indication of Sézary where we obtained 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.

Ramakanth Swayampakula (Managing Director and Senior Equity Analyst)

Thank you.

Operator (participant)

Your next question comes from a line of Lisa Bayko from Evercore ISI. Your line is open.

Lisa Bayko (Managing Director)

Hi. Thanks for taking our questions. This is Jamie Ilm for Lisa. So our question is for lacutamab. So what would be a good benchmark for PTCL data next year? What's your expectation for that readout? Thank you.

Sonia Quaratino (CMO)

Hi, Lisa. Very interesting question. Now, PTCL, of course, is a very crowded space. Apologies. It's a very crowded space. On the other hand, it remains quite a medical need for these patients. Lacutamab has the advantage of having an extremely good safety profile as shown in the Telomac study. That basically set it in front of many other therapies that have a less tolerable profile. 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. But it's a balance between efficacy and tolerability.

Lisa Bayko (Managing Director)

Got it. Thank you.

Operator (participant)

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