Earnings Call Transcript - IPHA Q1 2021

Operator, Operator

Good day, and thank you for being here for the Innate Pharma 2021 First Quarter Business Update Conference Call. This call is being recorded today, Tuesday the 11th of May, 2021. I will now turn the call over to your first speaker today, Dr. Mondher Mahjoubi. Please go ahead.

Mondher Mahjoubi, CEO

Thank you. Good morning, good afternoon, and welcome, everyone. This morning, Innate issued a press release providing a business update for the first quarter 2021. I look forward to explaining the progress made during the quarter, as well as addressing future goals and milestones. The press release and today's presentation are both available on the IR section of our website. Please move to Slide number 2. And before we start, I would like to remind you that we will make forward-looking statements regarding the 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. Please move to Slide number 3. On today's call, I'm delighted to be joined by Dr. Joyson Karakunnel, EVP and Chief Medical Officer. I would also like to take this opportunity to welcome our new CFO, Frederic Lombard, who officially started at the company in April and will join the Q&A section of this webcast, which will follow the prepared remarks by myself and Joyson. As you may have noticed, in the past, we have only held conference calls marking our half-year and annual results. However, in order to provide more regular updates on our business progress, we have decided to hold conference calls on a quarterly basis. It's important to note, though, that as we do not publish full quarterly financials, there will be no formal remarks about our financials during this call or the third quarter call. On Slide number 4, you have the classic intro slide of Innate Pharma. We are pioneers in the field of innate immunity, as you know, and NK cells. And we follow the science to develop innovative therapeutics for patients, leveraging our know-how and antibody generation platform. We are using this expertise and know-how to develop a robust pipeline of novel medicines for cancers, but also for other life-threatening diseases with high unmet medical need. Slide number 5 actually depicts our reserve strategy. And I'm very pleased to see the growing momentum in understanding the important role NK cells play in developing therapeutics to treat cancer. We are the leader in the field of using natural killer cells to activate innate immunity, and this scientific foundation is at our core. As you know, early approaches to immunotherapy were T cell centric and many focused on enhancing T cell responses by targeting inhibitory pathways with immune checkpoint inhibitors, for example. These therapies have led to unprecedented successes and transformed the natural history of many cancers. However, the unmet medical need is still high as only a small fraction of patients respond to T cell therapy, and there remains significant relapse among those who do. Broadly speaking, T cells are not autonomous in their effector function and need help from cells of innate immunity, which we believe will present the second wave or the next generation of immunotherapy. And to us, choosing the right targets to direct the body's immune response is paramount. We do this by utilizing our fundamental understanding of NK cell biology, tumor microenvironment, and tumor antigen. Please move to Slide #6. Our pipeline shows how we have translated this into a robust portfolio of proprietary and partnered assets. It also illustrates how we are executing against our strategy with our lead asset, lacutamab, supported by partner and earlier-stage products. Additionally, we have a rich pool of preclinical projects, which we will carefully select and bring forward and fuel our clinical pipeline. Let me remind you of our strategy on Slide #7. Our strategy centers around three core priorities. First, create a near-term value driven by our lead proprietary product candidate, lacutamab, which is in development for T cell lymphoma. Second, fuel our pipeline and create longer-term value by leveraging our antibody engineering capabilities to develop innovative molecules with a primary focus on our multi-specific NK cell engager, delivered from our proprietary platform. And third, we are building a strong and sustainable foundation for our business, leveraging the various partnerships across industry and academia, which further validate our science and offer capital that we reinvest to advance our portfolio. During the first quarter of 2021, we have worked diligently to execute against these three core priorities. Number one, we have continued to advance lacutamab as we pursue a broad development strategy across T cell lymphoma. Earlier this year in February, we held a virtual IR meeting where we highlighted the advancement of the mycosis fungoides arm of our Phase II TELLOMAK study into stage 2, which occurred earlier than anticipated. In addition, we announced our step-wise approach in developing lacutamab in peripheral T-cell lymphoma with two clinical studies for KIR3DL2-expressing patients with relapsed PTCL, including a randomized controlled trial in collaboration with our partner at the Lymphoma Study Association, or LYSA. We have also worked hard to advance our R&D efforts with our early-stage program moving forward. At the start of the year, we were pleased to announce that Sanofi made the decision to progress IPH6101, our lead NK cell engager, into IND-enabling studies. IPH6101 is now SAR44357. This is the first candidate to emerge from our multi-specific NK cell engager platform, and we are excited by the prospect of this technology, which we believe will fuel our pipeline well into the future. We look forward to telling you more about our progress here later in this call and in the near future. I would now like to pass the call over to Joyson who will review the progress made with our portfolio.

Joyson Karakunnel, Chief Medical Officer

Thank you, Mondher. On Slide 8, let me start with lacutamab, our first-in-class humanized monoclonal antibody that targets the immune receptor KIR3DL2. As you may remember, KIR3DL2 is an inhibitory receptor found in approximately 65% of patients across all cutaneous T-cell lymphomas and even more in certain aggressive subtypes, but with limited expression in healthy tissue. To date, data from lacutamab have shown promise, demonstrating compelling single agent activity and offering immense potential in lymphomas historically associated with a poor prognosis for which there are few therapeutic options at the advanced stages. On Slide 9, as Mondher mentioned, this past quarter we hosted a virtual investor event featuring key opinion leaders in cutaneous and peripheral T-cell lymphomas. During this event, we highlighted both the unmet need in these populations as well as the therapeutic rationale for our TELLOMAK study, evaluating lacutamab in subsets of CTCL. Additionally, we introduced a broad development strategy to advance this program initially for Sezary syndrome, a niche CTCL indication with high unmet need, into other forms of T-cell lymphomas, notably mycosis fungoides and the broader PTCL population. On Slide 10, let me first highlight the progress in our ongoing Phase II TELLOMAK study for Sezary syndrome and mycosis fungoides. We were pleased to share that we had moved the KIR3DL2-expressing mycosis fungoides cohort from stage 1 to stage 2, clearing a predetermined threshold before 50% of the cohort was enrolled. This was very encouraging. And I'm pleased to announce that the preliminary data from the stage 1 of this cohort will be presented by Dr. Martine Bagot in an oral session on the 22nd of June at the 16th International Conference on Malignant Lymphoma, ICML, Lugano. And this year, it is being held virtually. For the Sezary syndrome cohort, enrollment is on track, and we expect to be able to report top line data in 2022. Sezary syndrome offers us a potential fast-to-market opportunity as we received fast-track designation in the U.S. and PRIME designation in the EU last year. On Slide 11, simultaneously, we are working to advance our recently announced clinical development plan for peripheral T-cell lymphoma, which will focus initially on the relapse setting where the unmet medical need is most significant in patients expressing the target KIR3DL2. We expect to initiate our Phase Ib trial evaluating lacutamab as a monotherapy by midyear. The study will enroll approximately 20 patients and will evaluate safety and characterize clinical outcomes. First data are expected in 2022. Separately, our partner, LYSA, will initiate an investigator-sponsored Phase II study to evaluate lacutamab in combination with chemotherapy GEMOX versus GEMOX alone. This study will be a multicenter, randomized study with approximately 60 relapsed/refractory patients outside the U.S. and is expected to be initiated in the second half of 2021. We believe that this step-wise approach will prove efficient in identifying the optimal regimen for lacutamab in the relapsed PTCL setting. Depending upon the data generated in these initial studies, we will consider initiating a separate trial in combination with other standard of care treatments, and eventually we would look to move lacutamab into earlier lines of treatment, including as a potential combination in the CHOP regimen in frontline PTCL or as a consolidation therapy following standard first-line treatment. On Slide 12, now turning to our R&D efforts. We continue to advance multiple programs forward based on our proprietary multi-specific NK cell engager platform, which we believe will be the key to unlocking next-generation clinical molecules in immunotherapy. At the start of the year, we announced that Sanofi had taken the decision to progress IPH6101, or SAR443579, into IND-enabling studies. As you may remember, IPH6101 is an NKp46-based NK cell engager using our proprietary multi-specific antibody format. IPH6101 is a part of our ongoing research collaboration with Sanofi to evaluate up to two NK cell engagers and its advancement into the IND-enabling studies that triggered a EUR 7 million milestone payment to Innate. Sanofi is now responsible for all future development, manufacturing, and commercialization of IPH6101, and we remain eligible for future development and commercial milestones. On Slide 13, as you know, our NK cell engager platform is at the heart of our research and is a major component of our long-term development strategy. To date, we have developed a robust portfolio of product candidates using our trifunctional NK cell engagers, or NKCE-3, which has demonstrated potent NK cell activation, cytotoxicity, and efficient control of tumor growth. Our innovative approach means that we are continually working with our NKCE platform to further develop and expand its capability, including the development of a next-generation tetrafunctional NKCE or NKCE-4. Our Chief Science Officer, Eric Vivier, will speak more about these latest innovations in our platform during his plenary talk at the annual meeting of the Federation of Clinical Immunology Societies, also known as FOCIS, on the 10th of June. Additionally, we will hold an investor and analyst event midyear where we will cover both the next-generation NKCE platform and present the lacutamab mycosis fungoides data that are being presented next month at the ICML Lugano conference. In addition to our progress with lacutamab and our next-generation NKCE antibody, we have also made progress with IPH5301, our CD73 blocking antibody, and the Phase I trial is expected to begin later this year. IPH5301 targets the adenosine immunosuppressive pathway and has the potential to promote antitumor immune responses across a wide range of tumors. Now I would like to turn the call back over to Mondher for concluding remarks.

Mondher Mahjoubi, CEO

Thank you, Joyson. As you can see, we are working diligently to execute across all our strategic pillars and believe that we are laying the groundwork to drive near and long-term value for patients and shareholders. Looking at our clinical program, we expect to achieve a number of milestones over the next 18 to 24 months. As you've heard from Joyson, our Phase II TELLOMAK study for lacutamab continues to progress, and we expect to share preliminary data from stage 1 of the KIR3DL2-expressing MF cohort at the Lugano meeting in June as well as expecting to report potentially pivotal data in Sezary syndrome in 2022. In addition, we anticipate moving our monotherapy PTCL program into the clinic by midyear with initial data expected in 2022, with the combination studies sponsored by LYSA expected also to start in the second half of this year. In parallel, we continue to develop our NKCE technology platform, and we are very encouraged by the preclinical results for our next-generation NK cell engagers. We believe that this represents a natural evolution of our platform, illustrating the potential of natural killer cells to be a potent cellular player for the next generation of off-the-shelf cancer immunotherapies. We look forward to Eric sharing more details on the innovation we have made at the FOCIS meeting next month. Highlights, as you heard from Joyson of the next-generation NKCE platform, together with the lacutamab MF data presented at Lugano, will also be presented at an online IR event to be held on June 23. Details for accessing the event will be posted on our website in due course and publicized via our usual channels closer to the date of the event. Lastly, we are also very pleased to have such productive collaboration with industry and academic partners to advance monalizumab and avdoralimab alongside early-stage programs such as IPH6101. In addition, as you have seen, we are well-capitalized to deliver on our ambitious development goals and look forward to keeping you updated on our progress throughout 2021 and beyond. That concludes our prepared remarks. We will now open the call to questions. Operators, please can you start with the first question?

Operator, Operator

Our first question comes from Yigal Nochomovitz from Citigroup.

Yigal Nochomovitz, Analyst

I had a question about the positive early signal that you've seen in the KIR3DL2-expressing MF cohort. My question is, can you speak to the durability of these responses that you've seen so far? And was there any correlation between the degree of expression of the target KIR3DL2 and the responses?

Mondher Mahjoubi, CEO

Very important question, indeed, about the quality of the response we achieved with lacutamab. Before I hand over to Joyson to give you more details, as you may remember from the Phase I study published about now two years ago in Lancet Oncology, the duration of responses and even disease control, including progression-free survival in the Phase I was quite impressive in the range of 11 to 12 months. So not only could lacutamab have generated a significant tumor shrinkage in the range of 45%, but with durable responses in Phase I. Of course, we look forward to sharing with you these data soon in the next couple of months. But keep in mind that stage 1 was essentially about the tumor shrinkage. That's what basically triggers the move from stage 1 to stage 2. Now I'll leave it to Joyson to provide more color about this question.

Joyson Karakunnel, Chief Medical Officer

Thank you, Mondher, and thanks for the question. So I think when we look at this, I would look at it similar to what Mondher was just mentioning. In the Phase I study, we talked about the duration of response with the Sezary syndrome, and that, as Mondher was mentioning, was longer than the benchmarks at that time. I think when we look at the mycosis fungoides stage 1 cohort, the key things to remember here is that the stage 1 to stage 2 was dependent upon response, and due to that, we would be showing early data. What we are trying to also do is show you the totality of the data. So I think during Lugano, what you will be able to see is both the KIR3DL2-positive as well as the KIR3DL2-negative cohort totality. This will be early data, so clearly, we may not have as much follow-up as we would like. But that's what we're hoping to present at Lugano.

Yigal Nochomovitz, Analyst

Okay. So based on the data at Lugano, we will have some sense as to how well the response correlates with the expression of KIR3DL2?

Joyson Karakunnel, Chief Medical Officer

Yes, I think it will be – so it will be very early data, but yes, I think you will get a sense of that.

Mondher Mahjoubi, CEO

Yes. So Yigal, let me maybe rephrase your question to make sure we understand it. There are two cohorts in this MF trial: the KIR3DL2-positive expression and KIR3DL2-negative. The stage 1 to stage 2 translation we talked about is in the KIR3DL2. So in the patient population that express the tumor antigen. The level of activity that we will be presenting is in the KIR3DL2-positives. So we won't be showing data in the KIR3DL2-negatives so far because we are still – it's still ongoing.

Operator, Operator

Our next question comes from the line of Daina Graybosch from SVB Leerink.

Daina Graybosch, Analyst

Two for me. First, do you have any data, any updates on when we could see monalizumab data, in particular, anything from the ongoing lung cancer trial? And the second question is whether you guys see a role for NK adoptive cell therapy to be combined with your NK cell engager program, and if you know whether Sanofi has any plans to look at the combination, given their recent acquisition of an NK cell therapy company, Kiadis.

Mondher Mahjoubi, CEO

Thank you, Daina. Great questions, particularly the second one. The first one, I'm sorry to disappoint you. But as you know, this trial in particular, the COAST and NeoCOAST trials are sponsored by AstraZeneca, and I do not have more information than what they disclosed publicly, which is that they plan to present this data in the second half of 2021. So we are really looking forward to seeing this data in the second half of 2021. For the second question, I'll start, and please, Joyson, chime in. I think what we have seen at the last AACR and what was published already by the MD Anderson team last year is very encouraging and makes a lot of sense to somehow boost the NK cell engager platform or NK cell engager antibodies with fresh cells that you infuse at the same time. It makes a lot of sense. Of course, we cannot speak or speculate on what Sanofi's strategy is in this field. I think the obvious next step is, of course, to move IPH6101 into the clinic and start the Phase I. But I can tell you that we are looking at this field very carefully and are very excited about the prospect of having this combination that seems at least in hematologic malignancies to produce quite spectacular tumor shrinkage and clinical benefit. Joyson, would you like to complete or add anything on this question, as well as on to monalizumab, if you know more?

Joyson Karakunnel, Chief Medical Officer

No. I have to say, monalizumab, I think you summed it up very well. And also on the second question, I think that was a great summary, and I have nothing more to add.

Daina Graybosch, Analyst

Thank you for that. You know I have to ask about those lung trials every time.

Mondher Mahjoubi, CEO

You have to. I mean, Daina, if you don't ask it, I would be surprised. Thank you.

Joyson Karakunnel, Chief Medical Officer

We'll just predict the question from now on, Daina.

Operator, Operator

Our next question comes from the line of Swayampakula Ramakanth from H.C.W.

Swayampakula Ramakanth, Analyst

This is RK from H.C. Wainwright. In terms of the NK cell engager program with Sanofi, so we know that the first one is getting into the pre-IND studies. On the second molecule that potentially Sanofi can take into development, would that also be against the same target, in the sense, NKp46? Or could it be against other targets that not only you but other folks are also looking at?

Mondher Mahjoubi, CEO

I think – I believe you know that NKp46 is an activator receptor expressed on NK cells, and it's one of the most specific and stable activator receptors for NK cells. Unlike many others, I know to mention NKG2D or CD16, we know that those receptors may eventually get downregulated when the NK cells are traveling to the tumor microenvironment. Here we are talking about really a very specific and very stable. I think it's important for us to highlight the fact that our platform is basically versatile by the fact that you can change tumor antigen, but we are extremely delighted actually with the proprietary platform we developed around NKp46. So the various partnerships that we will be developing, including the second program that we have with Sanofi, is still using NKp46 as an activator receptor, but a different tumor antigen that Sanofi did not want to disclose at this point in time. So it's the same technology as for the first one, 6101, but with a different tumor antigen. Beyond Sanofi, again, we are developing both proprietary but also a partnered multi-specific, keeping NKp46 and changing the tumor antigen depending on, of course, the collaboration and the partner that we are working with. In addition, as you've seen in Joyson's last slide, what Eric Vivier will be presenting next month at the FOCIS is basically even the next-generation of multi-specific NKCE, what we call NKCE-4, where we are still leveraging the NKp46 platform, but trying to ensure that we have an even more potent and efficient antibody targeting different tumor antigens. I hope I answered your question.

Swayampakula Ramakanth, Analyst

Yes, you did. Regarding the clinical programs, particularly the one with lacutamab in PTCL, you mentioned that you're starting the monotherapy and the GEMOX combination is being initiated by the LYSA group. For the combination with CHOP, do you need to wait for the data from your monotherapy study before proceeding with the CHOP combination? Or are you staggered in these studies and not required to wait for all the monotherapy data?

Mondher Mahjoubi, CEO

Yes. Again, a very, very important question that will give Joyson the opportunity maybe to remind you a little bit about the strategy behind the selection of the monotherapy approach, our strategy in relapsed PTCL. Joyson, would you like to take the question?

Joyson Karakunnel, Chief Medical Officer

Sure. When we consider the strategy for PTCL, our initial focus is on KIR3DL2-positive patients, informed by early data from the mycosis fungoides cohort. Looking ahead, we have two potential approaches for monotherapy, particularly in earlier treatment settings with a CHOP combination. One approach would be to wait for all the monotherapy data before starting the first-line setting. Alternatively, if the initial monotherapy data is promising, we could begin the earlier treatment setting sooner. Both options are under consideration as we advance these trials and evaluate the data.

Operator, Operator

Our last telephone question comes from the line of Liisa Bayko from Evercore.

Liisa Bayko, Analyst

Just a couple of questions for me. First of all, for the PTCL study, do you envision that sort of following the general design of TELLOMAK, or can you maybe speak to how you're thinking about the design of that study?

Mondher Mahjoubi, CEO

Joyson? Okay. Go ahead.

Joyson Karakunnel, Chief Medical Officer

We are currently exploring all possible approaches. As we gather more data on mycosis fungoides, we are focusing on KIR3DL2-positive patients. However, as we observe longer-term data, particularly for mycosis fungoides, we may reassess our strategy, especially if it aligns more with TELLOMAK, which includes both expressers and non-expressers. Although it is still early, we are taking all these strategies into consideration. First, we are looking at monotherapy specifically for KIR3DL2-positive patients. Second, we will continue to examine mycosis fungoides data from the TELLOMAK study, especially the long-term results, and we are considering including a non-expressing cohort in the PTCL study. Additionally, while LYSA is pursuing a chemotherapy combination, we will also evaluate other available standard care options in the U.S. based on the PTCL data. I hope this clarifies your question.

Liisa Bayko, Analyst

Yes. And can you maybe describe a little bit more on kind of the non-expressers, what would be the rationale for activity there?

Mondher Mahjoubi, CEO

Go ahead, Joyson.

Joyson Karakunnel, Chief Medical Officer

When we examine the non-expressers, I believe you're asking why one might anticipate seeing expression among them, especially in light of lacutamab's mechanism of action. I would say this relates to what we observe with many biomarker subsets, primarily tumor heterogeneity. Additionally, sampling error plays a role. Both factors can contribute to the sensitivity of the test. While we are confident in the test's ability to detect expression, the crucial question is whether our sampling is representative or if it's heterogeneous, which could explain why we aren't detecting it.

Liisa Bayko, Analyst

Okay. Understood. For 6101, can you discuss the IND-enabling work you are doing and when we can expect that to enter the clinic? We're excited to learn more about the NK engager platform.

Mondher Mahjoubi, CEO

So Liisa, as you know, the 6101 program is fully under the responsibility of Sanofi. They are conducting the classic IND-enabling studies with the ambition and goal to start the clinic as soon as possible. So we do not have any data or comments to disclose at this point in time about what Sanofi's doing to move this drug into the clinic.

Liisa Bayko, Analyst

It's really up to them regarding their plans to disclose the preclinical information, which they typically do not share. Do you have any idea when they might begin clinical development?

Mondher Mahjoubi, CEO

The announcement early this year is, I would say, a testimony for their interest to move this to the clinic as quickly as possible. And you know the usual process and what type of IND-enabled study. So the plan is to go as fast as possible, but they did not disclose specific dates.

Liisa Bayko, Analyst

Okay. Fine. Thanks a lot.

Operator, Operator

I'd now like to hand the call back to you, sir, for your webcast questions.

Mondher Mahjoubi, CEO

Yes. Thank you. Actually, I have one question from the webcast. It's an update on the FORCE timeline. FORCE is the randomized Phase II study that is testing the potential role of avdoralimab in the treatment of COVID-19-driven pneumonia. As you know, this is an investigator-sponsored trial, and it's currently ongoing. I cannot give timelines or further details about the progress on this study as Innate is not responsible for the running. I can only say that the trial has completed enrollment and is ongoing for patient follow-up and data analysis, and we'll share with you this data as soon as they become available. That's what I see on the webcast so far. Okay. If there are no more questions, I would like to thank you all for joining this call. I look forward to our next investor relation event in June to update you on the progress of our portfolio, especially on the NK cell engager platform as well as the lacutamab data in mycosis fungoides patients that will be presented at the Lugano meeting. With that, I close the call and thank you very much. Have a good day.

Operator, Operator

Thank you. That does conclude today's conference. Thank you to everyone who's participated in today's call. You may now all disconnect.