Good day, and thank you for standing by, and welcome to the Innate Pharma 2021 first quarter business update conference call. At this time, all participants are in a listen-only mode. After the speaker presentation, there'll be a question and answer session. To ask a question during the session, you will need to press star one on your telephone. I must advise you that this call is being recorded today, Tuesday, the 11th of May 2021. If you require any further assistance, please press star zero. I would now like to hand the call over to your first speaker today, Dr. Mondher Mahjoubi. Please go ahead, sir.
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 two, 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 three. 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 It's important to note, though, that as we do not publish full quarterly financials, there will be no formal remarks about our financials during this call or the third quarter call.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 four, you have the classic intro slide of Innate Pharma.
We are a pioneer 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 five actually depicts our research strategy. 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 a 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 have mainly 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 represents the second wave or the next generation of immunotherapy. To us, choosing the right targets to direct the body's immune response is of paramount. We do this by utilizing our fundamental understanding of NK cell biology, tumor microenvironment, and tumor antigen. Please move to slide number six. 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 partnered and earlier stage products. We have a rich pool of technical projects, which we will carefully select and bring forward to fuel our clinical pipeline. Let me remind you our strategy on slide number seven. Our strategy is centered around three core priorities. First, creating near-term value driven by our lead proprietary product candidate, lacutamab, which is in development for T-cell lymphoma. Second, fueling our pipeline and creating 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. 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 II, which occurred earlier than anticipated. In addition, we announced our stepwise approach in developing lacutamab in peripheral T-cell lymphoma with two clinical studies for KIR3DL2 expressed in patient with relapsed PTCL, including a randomized control 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 R&D enabling studies. IPH6101 now is SAR443579. This is the first candidate to emerge from our multi-specific NK-cell engagement platform. 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 like now to pass the call over to Joyson, who will review the progress made with our portfolio. Joyson?
Thank you, Mondher. On slide eight, 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 advanced stages. On slide nine, 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 Sézary 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 Sézary syndrome and mycosis fungoides. We were pleased to share that we had moved the KIR3DL2-expressing mycosis fungoides cohort from stage one to stage two, clearing a predetermined threshold before 50% of the cohort was enrolled. This was very encouraging, I'm pleased to announce that the preliminary data from the stage one 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. This year it is being held virtually.
For the Sézary syndrome cohort, enrollment is on track. We expect to be able to report top-line data in 2022. Sézary 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 I-B trial evaluating lacutamab as monotherapy by mid-year. The study will enroll approximately 20 patients and will evaluate safety and characterize clinical outcome. 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 multi-center 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 stepwise 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 care treatments, eventually, we would look to move lacutamab into earlier lines of treatment, including as potential combination in the CHOP regimen in frontline PTCL, or as a consolidation therapy following standard first-line treatment. On slide 12. Turning now 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 tri-functional NK cell engagers, or NKCE3, 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 tetra-functional NKCE or NKCE4. Our Chief Scientific 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 mid-year where we will cover both the next generation NKCE platform and present the lacutamab and 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.
Thank you, Joyson. As you can see, we are working diligently to execute across all our strategic pillar and believe that we are laying the groundwork to drive near and long-term value for patient and shareholders. Looking at our clinical program, we expect to achieve a number of milestones over the next 18-24 months. As you heard from Joyson, our phase II TELLOMAK study for lacutamab continues to progress, and we expect to share preliminary data from stage one of the CTCL to express MF cohort at the Lugano meeting in June, as well as expecting to report potentially pivotal data in Sézary syndrome in 2022. In addition, we anticipate moving our monotherapy PTCL program into the clinic by mid-year, with initial data expected in 2022, with the combination study 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 an important cellular player for the next generation 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 23rd.
Details for accessing the event will be posted onto our website in due course and publicized via our usual channels in closer to the date of the event. 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. 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 question. Operators, please can you start with the first question?
Thank you. Once again, if you have a question for today's call, please press star one on your telephone and wait for your name to be announced. That's star one if you have a question. Our first question comes from the line of Yigal Nochomovitz from Citigroup.
Hi. Thank you very much for taking the questions. 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? Was there any correlation between the degree of expression of the target KIR3DL2 and the responses?
Thank you, Yigal. Very important question indeed about the quality of the response we achieve with the 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 The Lancet Oncology, the duration of responses and even disease control, including progression-free survival into phase I, was quite impressive in the range of 11-12 months. Not only lacutamab could 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 this data soon in the next couple of months. Keep in mind that the stage one was essentially about the tumor shrinkage. That's what basically triggered the move from stage one to stage two. Now I leave it to Joyson to provide more color about this question.
Thank you, Mondher, and thanks for the question. 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 Sézary 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 one cohort, the key things to remember here is that the stage one to stage two was dependent upon response, and due to that, we would be showing early data.
I think what we're also trying to do is show you the totality of the data. I think during Lugano, what you will be able to see is both the KIR3DL2 positive as well as the non-expressing KIR3DL2 cohort totality. This will be early data, so clearly we may not have as much follow-up as we would like. That's what we'd be presenting at Lugano.
Okay, thank you. Based on the data at Lugano, we will have some sense as to how well the spread, the response correlates with the expression of KIR3DL2?
Yeah, I think it will be. It will be very early data, but yes, I think you will get a sense of that.
Yeah. Yigal, let me maybe rephrase your question to make sure we understand it. There are two cohorts in this MF trial, the KIR3DL2 positive or expression, and the KIR3DL2 negative. The stage one to stage two translation we talked about is in the KIR3DL2, in the patient population that express the tumor antigen. The level of activity that we will be presenting is in the KIR3DL2 positive. We won't be showing data in the KIR3DL2 negative so far because it's still ongoing.
Okay, I understand. Thank you.
Thanks.
Thank you. Our next question comes from the line of Daina Graybosch from SVB Leerink. Your line is open. Please ask your question.
Thanks for the questions. Two from 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? The second question is, whether you guys see a role for NK adoptive cell therapy to be combined with your NK cell engager program. If you know whether Sanofi has any plans to look at the combination given the recent acquisition of an NK cell therapy company, Kiadis.
Thank you, Daina. Great questions, in particular the second one. The first one, I'm sorry to disappoint you, as you know, this trial, in particular, the COAST and NeoCOAST trial, are trials sponsored by us, AstraZeneca, 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. 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 also 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 in 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. I can tell you that we are looking at this field very carefully and very excited about the prospect of having this combination that seems at least in heme malignancy to produce a quite spectacular tumor shrinkage and clinical benefit. Joyson, would you like to complete or add anything on this question as well as on the monalizumab, if you know more?
No, I have to say, the Monalizumab, I think you summed it up very well. Also on the second question, I think that was a great summary, and I have nothing more to add.
Thank you for that. You know I have to ask about those phase I trials every time.
Yeah. I mean, you have to. I mean, Daina, if you don't ask, I would be surprised. Thank you.
We'll just predict the question from now on and say, Daina, it's those trials. Thank you.
Thank you. Our next question comes from the line of Ramakanth Swayampakula from H.C. Wainwright. Your line is open. Please ask your question.
Thank you. This is RK from HCW. Good afternoon, Mondher, and good morning, Joyson. 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 it could be against the other targets that not only you but other folks are also looking at?
Thank you, RK. Thank you for your question. Great to talk to you as well. I believe you know that NKp46 is an activator receptor expressed on NK cells. It's one of the most specific and stable activator receptor for NK cells. Unlike many others, I don't know to mention NKG2D or CD16, we know that those receptors eventually may 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 the monta gent. We are extremely delighted, actually, with the proprietary platform we developed around NKp46.
The various partnership that we would 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. 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. Again, keeping the 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 NKCE4, where we are still leveraging the NKp46 platform, but trying to ensure that we have even a more potent and efficient antibody targeting a different tumor antigen. I hope I answered your question.
Yes, you did. Thank you for that. Going into the clinical programs, especially the one with lacutamab in PTCL, as you stated, you're initiating the monotherapy and the GEMOX combination is being started by Liisa Bayko. However, for the combination with the CHOP, do you need to see the data from your monotherapy study before you embark onto the CHOP combination? Or you're basically staggering these studies and don't have to wait for all of the data from the monotherapy to come out?
Very important question that will give Joyson the opportunity maybe to remind you a little bit the strategy behind the selection of the monotherapy approach or strategy in relapsed PTCL. Joyson, would you like to take the question?
Sure. Thanks, Mondher, and thanks for the question. When we look at the strategy for PTCL, we are targeting, first of all, KIR3DL2-positive patients. That's going in with the at least early data that we've seen in the mycosis fungoides cohort based on that hypothesis. When we look forward in time, what we would see is that the monotherapy there's two approaches that we could take. One is sort of, and I'm specifically talking about an earlier line setting, which would be a CHOP combination. For that, what we'd like to do is, one, we would be waiting for the totality of the monotherapy data before beginning the first-line setting.
To your point, we could stagger it to where what we would do is basically, as we start to see the data from the monotherapy single-arm study, we would begin to, if the data is very encouraging, start the earlier line setting at that point. There's definitely those two approaches that are possible, and we're considering both of those as we start these trials and start looking at the data.
Thank you. Thank you both, and talk to you guys soon. Thanks. Thanks, RK.
Thank you. Our last telephone question comes from the line of Liisa Bayko from Evercore. Your line is open. Please ask your question.
Hi, Bayko.
Hi there. Just a couple of questions from me. First of all, for the PTCL study, do you envision that sort of following the general design of TELLOMAK? Can you maybe speak to how you're thinking about the design of that study?
Thank you, Liisa. Joyson? Okay, go ahead.
Thank you, Mondher Mahjoubi. Thanks for the question. We're considering all approaches at this point in time, but at this point, at least as the data in the mycosis fungoides starts to evolve, as well as we're placing our bets on the KIR3DL2 positive. That's not saying, of course, as we start to see longer-term data, especially in the mycosis fungoides, where we may reevaluate our strategy, and it starts to look more of like the TELLOMAK where we have an expressers as well as non-expressers. I think it's very early, but we are definitely keeping all those approaches in mind. One, to look at the monotherapy in the KIR3DL2 positives and only look at that subset.
Two, continuing to evaluate the mycosis fungoides in the TELLOMAK study, especially the longer-term data, and considering putting in a non-expressing cohort into PTCL. As also the combination. Not only is LYSA running a chemotherapy combination, but we would also be looking at other standard of cares that are available in the U.S. in combination, depending upon the PTCL data. I hope that answered the question.
Yeah. Can you maybe describe a little bit more on kind of the non-expressers? What would be the rationale for activity there?
Go ahead, Joyson.
I think when we look at the non-expressers, I think if I understand the question correctly, you're asking if you were to see expression, why would you expect to see expression in the non-expressers considering the mechanism of action of lacutamab? What I would say is, I think it goes to what we see with a lot of biomarker subsets, and that is tumor heterogeneity, that's number one, and then number two is sampling error. I think both of these c an lead to sort of the, I guess you could say the sensitivity, not only the sensitivity of the test being able to pick up, which we're confident about that, but more importantly is that are we sampling or is it heterogeneous, and that's why we're not picking it up.
Okay. Understood. 6101, can you maybe talk about what kind of IND-enabling work you're doing and when we can expect that to enter the clinic? We're excited to see more about the NK Engager platform.
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. We do not have any data or comments to disclose at this point in time about what Sanofi is doing to move this drug into clinic.
Well, it's kind of really, it's on their hands.
Yeah.
They're pretty upfront and disclose that much preclinical stuff. They don't generally do that. Okay. Do you have any sense of when that will start clinical development?
I mean the announcement early this year is, I would say, a testimony for their interest to move this to the clinic as quickly as possible. You know the usual FOCIS o f IND-enabling study. The plan is to go as fast as possible. They did not disclose specific dates.
Okay, fine. Thanks a lot.
I'd like to hand the call back to you, sir, for your webcast-
Yeah.
Questions.
Thank you. Actually, I have one question from the webcast. It's 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 question, I would like to thank you all for joining this call, and 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.
Thank you. That does conclude today's conference. Thank you to everyone who's participated in today's call. You may now all disconnect.