Earnings Call Transcript - IPHA Q1 2024

Operator, Operator

Thank you for joining us for the Innate Pharma First Quarter 2024 Financial Results and Business Update Call. To minimize background noise, all lines have been muted. There will be a question-and-answer session after the speaker's remarks. Now, I would like to hand the call over to Henry Wheeler, Vice President of Investor Relations and Communications. You may begin.

Henry Wheeler, Vice President, 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 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.

Herve Brailly, Interim Chief Executive Officer

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. 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 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 findings on our capabilities 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 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. We have 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. Our AstraZeneca partnership is of utmost importance, with monalizumab continuing development in lung cancer. Next slide. Slide 6 illustrates the variety of approaches that we have. I will now move to Slide 6 to discuss the portfolio. 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 catalysts in the upcoming couple of years as the R&D engine looks to leverage our scientific know-how to create a sustainable business. Let's move to ASCO 2024, where we will have an important abstract published. This comprises 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. Eventually, two monalizumab posters will present updated Phase 2 COAST results in Stage III unresectable NSCLC and the Phase 2 extensive stage SCLC trial. I would like now to pass the call over to Sonia, who will review the progress made with the portfolio, starting with lacutamab, our almost advanced proprietary asset.

Sonia Quaratino, Chief Medical Officer

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 Sézary syndrome and approximately in 50% of patients with mycosis fungoides. The TELLOMAK trial is a Phase 2 single-arm study, including both Sézary and mycosis fungoides. 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. 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 sharing the data with you then. We are pursuing a fast-to-market strategy for lacutamab in Sézary syndrome, where lacutamab was granted the U.S. fast track designation and EU PRIME designation in 2020. We look forward to discussing the data with the FDA to define the next steps. In PTCL, we continue to enroll patients in a Phase 2 combination trial with chemotherapy GEMOX, where we believe the combination will offer additional benefit to patients. On Slide 9, we now switch gears to our most advanced proprietary 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 receptors, NKp46 and CD16, a tumor antigen in this case CD20, and an interleukin-2 receptor via an IL-2 variant, 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 entered the clinic, and the first in human has started with the first patient dose 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. IPH65 eliminates CD20 positive cancer cells via profound activation and proliferation of the NK cells. 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 addresses the common challenge associated with loss of CD16 by ensuring activation of intratumoral NK cells via wide engagement of NKp46. The asset will be presented at the ASCO annual meeting with two posters, one as a 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, Chief Operating Officer

Thank you, Sonia. On Slide 10, I want to highlight our portfolio of ANKET drug candidates, which has shown significant progress in the past quarter. As you recall, ANKET molecules are developed using our proprietary first-in-class NK cell engager platform. This technology is multi-specific and modular, built from antibody-derived components, designed to engage NK cells with tumor cells by activating the NK cell surface receptor NKp46. An interesting aspect of this platform is that by altering the tumor-targeting part of the ANKET molecule, we can create multiple drug candidates targeting various oncology indications, and it may also enable NK cells to eliminate pathogenic cells in other disease areas such as autoimmunity and inflammation. Last quarter, Sanofi advanced SAR'579 to Phase 2 based on initial efficacy data demonstrating single-agent activity with durable complete responses in patients with relapsed refractory IML. We look forward to further updates from Sanofi. Additionally, as Sonia mentioned, we are excited to report that our second-generation ANKET, IPH6501, has entered clinical trials, with the first patient dosed in March. Next month, we will present two posters on IPH6501 at ASCO, one detailing the Phase 1/2 trial design and the other focusing on its technical characterization. We are also actively working to broaden this portfolio to include additional tumor targets, particularly in solid tumors. Slide 11 shows our expanding portfolio of ADC drug candidates. As we develop next-generation antibody therapies, we have found that for certain tumor targets, we can produce antibodies with strong internalizing properties, making them more suitable for ADC development compared to ANKET. Our collaboration with Takeda in this area validates our approach and showcases our ability to create differentiated ADCs. I will now provide updates on our lead proprietary ADC program, IPH45, which targets Nectin-4 and was recently presented at an oral session at ACR in San Diego. Slide 12 outlines IPH45's overall structure. It consists of a proprietary antibody with a unique epitope that does not overlap with enfortumab, the parent antibody of Padcev. We have chosen a validated chemotherapy along with a hydrophilic linker that balances the payload's hydrophobicity, allowing for a high drug-antibody ratio of eight. We also selected a Topo 1 inhibitor with a strong bystander effect to overcome MMAE-related resistance mechanisms and target tumors with low and varied Nectin-4 expression. Collectively, these factors create a novel and differentiated ADC aimed at Nectin-4 across a wide range of tumor types, in addition to bladder cancer, by addressing the challenges faced by Nectin-4 MMAE ADCs, including enfortumab vedotin. Slide 13 summarizes some data presented at ACR, indicating that IPH45 demonstrates strong anti-tumor efficacy across various preclinical models, including those resistant to Padcev due to high expression of the MDA1 transporter, a known resistance mechanism to MMAE. We also observed significant efficacy in patient-derived Padcev models exhibiting low Nectin-4 expression, as illustrated in the graph in the center of the slide, where Padcev is ineffective. This data supports targeting not only bladder tumors but also other types with medium to low or heterogeneous Nectin-4 expression, such as breast, lung, prostate, head and neck, and pancreatic cancers. Efficacy reported with Padcev thus far has been limited. Given our strong developability profile, including high yield productivity, stability, and promising PK and toxicity data from animal studies, we aim to file the IND this year. On Slide 14, I want to highlight monalizumab, the anti-NKG2A we licensed to AstraZeneca for oncology. This slide provides an overview of the late-stage development of monalizumab in lung cancer. Based on Phase 2 COAST data, AstraZeneca initiated PACIFIC-9, a Phase 3 trial in May 2022, assessing the addition of monalizumab or oleclumab to durvalumab for patients with unresectable Stage III non-small cell lung cancer who have not progressed after concurrent chemoradiation. The AZ-sponsored NeoCOAST-2 Phase 2 study is also in progress in an earlier stage of lung cancer, specifically in stage IIA-IIIB patients, evaluating the combination of monalizumab with durvalumab and chemotherapy in a perioperative setting. As mentioned earlier, there will be two poster presentations at ASCO for monalizumab: one updating the COAST results and the other presenting the investigator-sponsored MOZART trial for first-line treatment of extensive-stage small cell lung cancer. I will now hand it over to Herve.

Herve Brailly, Interim Chief Executive Officer

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 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 TELLOMAK trial with our proprietary product lacutamab in MF for mycosis fungoides. This combined with data in Sézary syndrome that Sonia alluded to, which has been previously communicated, will form the basis of our interactions with regulatory bodies as we map out the 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 relapsed refractory NHL or non-Hodgkin's lymphoma. Two abstracts will also be presented by our partner AstraZeneca on monalizumab and 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 strong affirmation. Our pursuit of ADCs is based on developing differentiated, potentially best-in-class assets. 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 2024, we are in a strong cash position to operate until 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.

Arvind Sood, EVP, U.S. Operations

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

Operator, Operator

Your first question comes from the line of Daina Graybosch from Leerink Partners.

Daina Graybosch, Analyst

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 then narrowing in on KIR3DL3 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.

Sonia Quaratino, Chief Medical Officer

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 the TELLOMAK 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. At the ASCO annual meeting, you will see the result in both KIR3 positive tumors more than 1% and KIR3 less than 1%. There will be interesting data in both subsets. Now for the IPH6501, I'll hand over to Yannis on this question because this is something that is very key to the business of Innate.

Yannis Morel, Chief Operating Officer

Of course, it's something that we are following. As you know, there have been several attempts to use T cell lung engagers, 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 T cell depletion before considering expansion to other therapeutic areas, but in theory, something that we could contemplate in the medium to long term.

Herve Brailly, Interim Chief Executive Officer

If I can complement here, we do believe that with the ANKET platform, we have an interesting tool to address alternative therapeutic fields beyond tumor immunology and tumor treatment. Thanks to the very good safety profile that we see with ANKET 3, and that we are going to document with ANKET 4, 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.

Operator, Operator

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

Yigal Nochomovitz, Analyst

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?

Sonia Quaratino, Chief Medical Officer

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 goal is really to maximize the value of the drug, not only in Sézary but also in the larger population of mycosis fungoides. Capturing the whole CTCL space, and after the data is 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.

Yigal Nochomovitz, Analyst

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

Sonia Quaratino, Chief Medical Officer

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

Yigal Nochomovitz, Analyst

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 expand the cash?

Frederic Lombard, Participant

The cash position and the projection of cash until end of 2025 do not include and do not take into account any potential milestone from existing agreements or potential other new agreements.

Operator, Operator

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

Swayampakula Ramakanth, Analyst

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 after the data presentation at ASCO?

Yannis Morel, Chief Operating Officer

Yannis is speaking. Not sure to get your point on the Sanofi collaboration. Just to remind you that we are having Sanofi develop currently two ANKET molecules, which are the tri-specific ones, the third generation in the clinic, 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. We are really looking forward to potentially see updates on these two programs this year. Regarding 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 close solid tumor. We are progressing them at the technical stage, but we unfortunately cannot comment on the timing when these molecules 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 month that Sanofi also refocused its oncology pipeline. The NK cell engagers that we are having with them are on the priority list of their oncology pipeline. Regarding the monalizumab, as you can see by the title, unfortunately, 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 of years ago. Now it's a longer-term and updated data, but we cannot comment on what AZ will do after this data disclosure. So far, the PACIFIC-9 trial is ongoing, and that's the only thing that we can say.

Operator, Operator

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

Rajan Sharma, Analyst

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? If so, on safety, how do you think that may work mechanistically? And then just secondly on lacutamab on Sézary, you mentioned a potential exploration of a faster market strategy. Could you just kind of walk us through the potential passing market there, and is that predicated on MF?

Sonia Quaratino, Chief Medical Officer

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. 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 the clinical development plan for this asset, but it may not only be in parts of refractory patients, but for instance, there is a strong possibility based on the preclinical data that we recently published at AACR to also target tumors that express a low level of Nectin-4 that at present are not captured by other Nectin-4 ADCs. 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 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, Chief Medical Officer

Right. Well, there are different options, of course, and as also mentioned previously, the option of asking for accelerated approval remains open. We need the 12 months durability of response and a registrational trial ongoing to obtain accelerated approval in the niche indication of Sézary, where we obtained FDA fast track designation. However, with the registrational trial, we also aim to bring lacutamab to the market for the MF patients as well. 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 ongoing and is very much on our radar.

Operator, Operator

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

Jingming Chen, Analyst

This is Jingming on for Lisa. So our question is for lacutamab. What would be a good benchmark for PTCL data next year? What's your expectation for that readout?

Sonia Quaratino, Chief Medical Officer

Hi Lisa. Very interesting question. Now, PTCL, of course, it's a very crowded space. On the other hand, it remains quite an unmet medical need for these patients. Lacutamab has the advantage of having an extremely good safety profile as shown in the TELLOMAK study compared to other therapies. This could also give it 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 to what other competitors are doing with other drugs in the same space. It's a balance between efficacy and tolerability.

Operator, 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.