Innate Pharma S.A. (IPH) Earnings Call Transcript & Summary

Ladies and gentlemen, thank you for standing by. And welcome to the Innate Pharma conference call. [Operator Instructions] I must advise you the call is recorded today on Wednesday, 24th of June 2020. And I would now like to hand over to your first speaker today, Mr. Mondher Mahjoubi, Chairman of Executive Board and Chief Executive Officer at Innate. Please go ahead, sir.

Thank you. Good morning, good afternoon, everyone. And thank you for joining our management call today. Before we start, I would like to remind you that we will make forward-looking statements regarding regulatory, product development and financial plans. These statements are subject to risk and uncertainties that may cause actual results to differ from those forecasted. As communicated earlier today, we are delighted to announce that the FDA has lifted the partial clinical hold on lacutamab clinical trial. As many of you are aware, the TELLOMAK Phase II trial is evaluating the efficacy and safety of lacutamab, an anti-KIR3DL2 antibody in patient with advanced T-cell lymphoma. On today's call, Pierre and I will take the opportunity to update you on what this means for the lacutamab program and specifically the TELLOMAK trial. For the Q&A, we'll also have Frédérique Brune join us. Frédérique is the Head of CMC and Supply Chain and is a member of the Executive Team. Can you please move to Slide #4? Lacutamab is our lead proprietary asset and the key value driver for the company. It has shown compelling activity as monotherapy in relapsed/refractory Sezary syndrome patients. And as you may remember, the TELLOMAK Sezary syndrome cohort has the potential to serve as a registration study, and lacutamab was granted fast-track designation earlier this year in this indication. If you move to Slide 5, and in the interest of time, I will not go into a great detail about the GMP issue we faced at the end of last year. Briefly, the situation was related to deficiencies with one of our manufacturing subcontractor that managed the fill and finish operation of lacutamab clinical trial -- clinical advise, sorry. The subcontractor revoked the certificate of conformity for the batch that was used in the TELLOMAK trial. And as a consequence, in the U.S., in Spain and Germany, the withdrawal of the certificate resulted in the recommendation that no new patient could enroll in the trial until the new GMP-certified batch was made available. However, already recruited patients could continue treatment in the trial due to the high unmet need in this indication, like MS and Sezary syndrome. In Italy, the trial was suspended, while the trial stayed open for recruitment in France and in the U.K. During this time, we have been working diligently to resolve the supply issue and mitigate the impact of recruitment, which has been compounded by the COVID pandemic, as you know. Can you move to Slide 6, please? And let me say that on the supply side first, I'm happy to say that we have resolved the GMP issue and have secured a new batch of products to be used in our clinical trial. This new batch was the basis of our IND amendment to the Food and Drug Administration which lifted the partial hold in the U.S. As additional contingency planning, we have made concerted effort to secure an additional batch from a separate manufacturer. This achievement is due to the great collaboration we have with our manufacturing partners as well as thanks to the efforts of Frédérique Brune and party. The company has already started to take the operational measures to reactivate the U.S. clinical trial sites and is taking all operational measures to start enrolling new patients as soon as possible. We are also consulting, as you can imagine, with regulatory authorities in Germany and Italy and Spain in order to resume the trial in this country. In addition, as you see on this slide, we have taken several actions to limit the impact of this partial hold in several countries and also to limit the impact of the COVID-19 pandemic on our recruitment. As a matter of fact, additional sites in the U.S. have been identified and are in the process of being activated. In particular, preference was given to clinical trial sites with a higher prevalence of patients with Sezary who have been previously treated with mogamulizumab, and this was based on dedicated feasibility studies that we have performed. If you now move to Slide 7, our figures that you are familiar with, the design of the TELLOMAK Phase II trial. I'm happy to report that the mycosis fungoides cohort, which are cohort #2 and cohort #3, had a minimal delay. We now expect full recruitment of Stage 1 study in early 2021 compared to second half of 2020 previously. And if the predefined number of responses were met in one or both MS cohorts, this would allow further expansion to Stage 2 of the study. And in fact, based on the kinetics of recruitment and the response assessment, the decision could be taken in the first half of next year, and we expect the first preliminary efficacy data starting in the course of 2021. Now on the Sezary cohort front, we expect preliminary efficacy data in the second half of 2022. PFS, duration of response, along with other key objectives, like quality of life, are absolutely critical in order to better understand the full magnitude of benefit of lacutamab in both Sezary syndrome patient as well as in MF. These data would be available at least 6 to 9 months after the recruitment of the last patient in their respective cohorts. Now can you move to Slide #8, please? We recently communicated that we took the decision to stop the PTCL cohort of TELLOMAK. In fact, enrollment of Sezary and MF continued due to the high unmet need, while PTCL patient had alternative therapies, in particular, combination partner, GemOx. We have also recently communicated that we are pursuing other opportunities to test lacutamab in PTCL. While we are fine-tuning our protocol, I would like to share with you today our vision and ambitions. So first, let me restate that PTCL is, with mycosis fungoides, a very important part of the life cycle management of lacutamab. That current treatments are available in PTCL space, but they are largely regarded by the medical community as unsatisfactory. In fact, in the first-line setting and despite a very high degree of response rate that sometimes is in the range of 80% to 85%, up to 70%, 7-0, 70% of the patients, depending on the subtype, of course, will relapse, highlighting the very ample room for improvement of the standard of care in this first-line setting. And for patients who do experience a relapse, there are, in fact, few options that are available. And actually, they are essentially available in the U.S. In general, these options are not considered very satisfactory due to the very short duration of response. And experts are recommending -- as a matter of fact, NCCN guidelines recommend considering clinical trials as a preferred option for such patient who relapsed after frontline treatment with PTCL. Hence, here again, a high medical need to develop agent that is supported by strong scientific rationale. In addition, close to half of the patients with PTCL express KIR3DL2, and we have generated preclinical data showing antitumor activity of lacutamab against primary PTCL. These data were shared by -- with the scientific community last year at the Lugano meeting. So based on our preliminary Phase I data, we started the classical development plan with TELLOMAK, starting in the [ route ] setting, the area of the highest unmet medical need. We have strong preclinical rationale for combination with chemotherapy agent, and we will continue to pursue that setting, which is the quickest path to market in PTCL, and the combination with chemotherapy partner is supported by preclinical data. So that's number one. We are pursuing the same setting that we have explored in TELLOMAK but in a different clinical trial. In parallel, we have been exploring how to bring lacutamab to more patient and expand on the exploration in PTCL. And the clinical plan we are working on today and will soon share with you consist of using lacutamab in the frontline setting in combination with the standard of care for the induction phase, but also in the maintenance phase, which is, of course, the most attractive setting. And from a medical need perspective, it's the most critical one as up to 70% of the patients, as I said, tend to relapse with frontline chemotherapy alone. Yet this development part is rather longer than that of the relapse setting, but also supported by strong preclinical rationale. So we will provide more information in the very near future on the clinical trial design that we are working on in collaboration with a notable academic group with a solid track record in lymphoma. Now I would like to invite Pierre Dodion, our Chief Medical Officer, to provide further granularity on our TELLOMAK clinical development plan. Pierre?

Thank you, Mondher, and good morning, good afternoon to everybody. I would like to start, and we are on Slide 10, to start by reminding several key features of the TELLOMAK study. TELLOMAK is an open-label, multi-core, multi-center international Phase II study that evaluates the efficacy and safety of lacutamab as monotherapy in patients with advanced cutaneous T-cell lymphoma. To further outline the clinical trial design, the trial has now 3 cohorts. One is assessing lacutamab as monotherapy in patient with Sezary syndrome. Patient will receive at least 2 prior lines of treatment, including mogamulizumab, and 2 others that are assessing lacutamab as monotherapy in patient with mycosis fungoides who have received at least 2 prior lines of treatment. The reason why we have 2 mycosis fungoides cohort is because we are stratifying the patients according to KIR3DL2 expression -- KIR3DL2 expressing versus non-expressing, and we'll get back to the definition of expression in a moment. As you know, Sezary syndrome is an indication for which we have demonstrated encouraging safety and efficacy data. We think that lacutamab has shown clear activity in these patients and that the drug has the potential for a fast-to-market approach. The Sezary syndrome cohort of the TELLOMAK study is designed and powered to potentially be a pivotal study. It does not have an interim readout. And as Mondher mentioned, we have FDA fast-track designation for lacutamab in Sezary syndrome, which allow us a more frequent and direct communication with the Food and Drug Administration. Also remind you that Sezary syndrome is an aggressive version of CTCL with poor prognosis, and that as many as 85% of the patient with Sezary syndrome do express KIR3DL2. If you look at the slides, the figure on the right side is showing the route of all plot that has been published earlier. Focusing now on the table on the left side, and first, on the left column, you can see that out of 35 patients with Sezary syndrome, lacutamab demonstrated a high response rate of 43%, but also very importantly, high durability of responses, long progression-free survival and a favorable safety profile. Additionally, lacutamab improved the quality of life of approximately 90% of the patient. This is an important observation as the disease is causing very painful skin irritation or pruritus, sores and pain. Moving a moment to the central column, it is also important to note that among those 35 patients, 28 had no evidence of large cell transformation, or LCT. LCT is a histopathologic feature that makes the disease harder to treat and more resistant to available therapy. And of note, patient with LCT are very often excluded from clinical trials, including the mogamulizumab pivotal trial, which I will get back in a second. Finally, focusing on the right column, 7 out of these 28 patients without LCT in our Phase I study were previously treated with mogamulizumab, which is now an approved treatment. Out of the 28 patients that I was mentioning, those patients without LCT, lacutamab showed even further encouraging results with an overall response rate of 53.6%, a duration of response of 13.8 months and a median duration of PFS of 12.8 months. These results compare very favorably actually to available treatment options in routine practice. And if we could move, please, to the next slide. First, let us remind everyone that there is no systemic therapy with a clear clinical benefit in patients who have received at least 2 lines of prior systemic therapy. In fact, vorinostat, which is an HDAC inhibitor, is the only agent that has been approved in that setting, and it has been approved only in the United States and not in Europe. In addition, the approval has been granted to patients with cutaneous manifestation of CTCL only, and that is, of course, not representative of the vast majority of patients with Sezary syndrome. Now if one looks at the data more carefully, the response rate in the short group of patients with Sezary syndrome was only 2% and the median progression-free survival was only 3.1%. That underlines the degree of the unmet medical need of such patients. So considering, all in all, the degree of unmet medical need and the very encouraging data observed in our Phase I study, we believe that lacutamab has an encouraging therapeutic benefit and superior safety profile. In addition, the same data, of course, provide the rationale to expand the exploration of lacutamab in other patient population expressing KIR3DL2 and thereby potentially broadening the scope of interest. So moving to Slide 12, we're going to discuss now in some more details mycosis fungoides. Mycosis fungoides is actually the most common CTCL subtype. It represents approximately 50% to 70% of all CTCL patients. And out of these, approximately 50% express KIR3DL2. There are approximately 6,000 new case of CTCL diagnosed per year in combined Europe and United States. Patients with mycosis fungoides who relapse after 2 prior systemic therapies have, again, very limited option. Brentuximab vedotin is approved, but this approval is restricted to patients who do express CD30. And in addition, that approval has been granted to patient who have received at least one prior systemic treatment. Mogamulizumab is also indicated for patients with MF after again one prior line of systemic therapy. Vorinostat is the only drug that is approved in the U.S. only, not in Europe, for patients after 2 prior lines of systemic therapy. And if you look at the table -- column on the right, you can see that the results achieved with vorinostat are not favorable with an overall response rate of about 7% and progression -- median progression-free survival of about 3 months. For the TELLOMAK study, we have adopted a biomarker stratified Simon 2 stage design that is evaluating the drug in 2 separate cohorts, one in patients expressing KIR3DL2 and the second one in non-expressers. And expression is defined at a level greater than 1%. That design is not only signal-seeking, but it also allows us to identify the likelihood or probability of therapeutic benefit from the treatment according to KIR3DL2 expression. And obviously, given the presumed mode of action of lacutamab, we are expecting to see higher activity in KIR3DL2-expressing patients. This approach, by the way, is totally aligned with regulatory requirement and has been endorsed by the Food and Drug Administration in response to our end of Phase I meeting, and this kind of design is intended to allow for an early call on the best development path. Finally, as Mondher mentioned, we expect to be able to communicate moving from stage 1 to stage 2 in the mycosis fungoides cohort in the first half of 2021 and to have preliminary efficacy data starting around year-end 2021. I'm now turning back to Mondher.

Thank you, Pierre. Before I open to questions. Let me take a moment to recap and, first of all, say how proud and happy we are with the FDA decision today. And we are taking, as I said, all operational measures to start enrolling new patients in the TELLOMAK trial in the United States. TELLOMAK trial, which is, as Pierre said, a central piece of our development strategy. Actually, our strategy remains the same. Our objective is to reach the market fast. And we choose to do it in Sezary syndrome, while we know this is a niche indication, but we know at the same time that it's a disease with a high unmet medical need. And the level of activity observed by lacutamab in the Phase I is a very powerful proof of principle of the mechanism of action of lacutamab. And this could be based on a single-arm cohort. This strategy is endorsed by the FDA, and it's based on the, as I said, the Phase I results. In parallel, we always said that we will expand lacutamab to closely rated but broader population starting with the mycosis fungoides, the cutaneous T-cell lymphoma. We elect to go after the third line, where there is no clinically active options and a very dismal prognosis. And the TELLOMAK data that we will present next year will, of course, inform the overall registration strategy in MF. We are also exploring the potential role of lacutamab in PTCL and all subtype of PTCL and all unmet need population, both in the front line and. As I said, it will be in combination with the standard of care, and we will be certainly testing the role of lacutamab in the maintenance setting, but we will also, as we started in the TELLOMAK trial, evaluate the role of lacutamab in the relapsed setting in combination with various chemotherapy partners. We are optimistic on our lacutamab clinical development strategy, and we will provide further information on our peripheral T-cell lymphoma strategy in the near future. At this time, we will now take questions, and I hand over to the operator.

[Operator Instructions] Your first question comes from the line of Yigal Nochomovitz from Citi Group.

Congratulations on the progress with TELLOMAK. So I just had a specific question with the TELLOMAK trial regarding the trigger for seeing the data in 2021 for MF and 2022 for Sezary. So if I understand correctly, it's a number of responses that you need to see in order to trigger the analysis or to show us the data. Can you just tell us, if you can, what -- how many responses you need to see in Sezary? And then for mycosis fungoides, how many responses do you need to see in cohort 2 and cohort 3? And is it a different number of responses?

Good. Thank you, Yigal. Pierre, would you like to take the question, please?

Yes, sir, certainly. Thank you for the question. These questions are described in very clear details in the study protocol and the statistical analysis plan and have been furthermore discussed with regulatory agencies, in particular, the Food and Drug Administration. It is even more important, quite obviously, for cohort #1, which is intended to be pivotal. The primary endpoint of the TELLOMAK study is indeed the response rate. We have not disclosed and will not disclose at the present time how many responses have to be seen in each cohort. To your point, yes, those numbers are different from one quarter to the next. I would like also to add that besides the response rate, quite clearly the longer-term outcome and, in particular, the response duration in our case is very, very crucial. Just to give you an example, good old chemotherapy can certainly induce a small number of responses in this patient with CTCL and Sezary syndrome, but they are extremely, extremely short. So it's not only a matter about the percentage of response but also the response duration.

Thank you, Pierre.

And then just one regarding Germany, Italy and Spain, can you provide any time lines as to what -- when those -- the regulatory clearance will happen in order to resume in those territories?

There are standard time lines. It's typically a 1-month review for regulatory agencies. So I think that we are talking about relatively short time lines considering the grand scheme. So it's not going to take a lot of time. But we have to follow the process, which includes the regulatory review and approval and then the IRB notification.

Okay. And have you provided any information on how many are enrolled so far in TELLOMAK? Or have you not disclosed that?

Pierre, the question is about how many patients are enrolled in the TELLOMAK trial. Did we provide any number?

Right. Yes. We have -- we are typically not disclosing rate of recruitment and the more specific numbers who have been recruited in the various cohorts. Because the shape of recruitment can vary so much from one trial to the next, what really matters is to get to the finish line as quickly as possible. But again, we have not disclosed recruitment numbers for the TELLOMAK study at this stage.

What I can say, Yigal, just to add on Pierre's response, actually, we were hit with the CMC issue and with the pandemic in the same time. And what we've done over the last 6 months is basically, we managed to minimize the impact of both. Expediting the CMC process to produce new batch, which we did in a record time, and minimizing to the extent possible the delay that may come from the pandemic by opening new sites in the U.S., so we can capture more patients who have been pretreated with mogamulizumab, okay? So that's our -- so we got some delay. We are very transparent about it. But overall, when you look at the pandemic on one side and the CMC issue, we managed to compensate that in -- actually in 6 months and restart recruiting as soon as possible.

Okay. And then just one more question. Should we expect to get an update when you do complete enrollment for Sezary and MF and TELLOMAK? Will you let the market know that the trial is fully enrolled?

So first of all, for the Sezary syndrome, as I said and Pierre reiterated this, we've had, thanks to the fast track designation, continuous dialogue with the FDA. So it's an open-label study, as you know, and we will certainly exchange with the health authority, with the regulatory first and, of course, if allowed to communicate, we will do it, certainly. And as you know, Yigal, the question for Sezary is not about the response rate. We know, based on the Phase-I data that this drug works. It's more about, as Pierre said, the quality of the responses and having more follow-up to, a, assess the progression-free survival but also to do all other assessment of the quality of life, in particular. So we will certainly announce the end of recruitment, but it's more important to announce the results. And the results, as Pierre said, may take between 6 to 9 months after the last patient is recruited. I think for the MF cohorts, as Pierre mentioned, Simon Phase I design, and there's a prespecified number of response that we are expecting. And when that number is met, we will certainly announce the milestone without necessarily presenting any specific data, but of course, we will inform the market about the move from stage 1 to stage 2 when that happens.

We have some questions submitted to us. Question 1, can you provide time lines on when we expect PTCL to start and when will this be a global study similar to TELLOMAK?

Excellent. Thank you. Pierre, would you provide a short answer because, again, I don't want to do the PTCL call before we do it in a couple of weeks. As I mentioned, we will have a dedicated call to present our PTCL development plan strategy and time line. But maybe, Pierre, you can provide a high-level answer.

Yes. Thank you, Mondher. Thank you for the question. Yes, we -- our work standard practice is to provide at least a general feature of all our clinical trials, and that includes also the critical time lines. As Mondher said during this call, we are working very actively on this. We are, I think, pretty close to the final decisions. And again, to reiterate what I said, those critical features will be announced.

And to complete the response, the answer to the question, yes, there will be company sponsored, i.e., global, and corporate-led trial as well, as we said earlier.

Okay. Your next question, can you comment on the PTCL patients that were enrolled in TELLOMAK? Will these patients be rolled over to the new trial?

Let me perhaps start to answer. This is a good question. The reality is that the number of patients with PTCL enrolled in the TELLOMAK study does not allow to have meaningful conclusions. So we'll have to wait for the new trial and new trial design. Considering your other question, one could certainly combine patients from the TELLOMAK PTCL cohort with the future trial. It will have to be restricted to, of course, the course with exactly the same design. The PTCL cohort of the TELLOMAK study was a combination of GemOx plus lacutamab in the so-called second-line setting. So any pooling effort would be limited to that type of patients. But I think that the key message that we want to convey here is that we are going to make a substantial effort to really broaden the scope of our PTCL program. We will retain, certainly, second-line GemOx combination approach but add other critical components to broaden the usage of the drug.

We now have questions on the telephone lines from Daina Graybosch.

I have 2 related. What I wonder, you mentioned that with the pandemic, you took the opportunity to open more sites so you can quickly recruit. Is there anything else you need to do for these particular patients? Any particular risks or settings that they're treated out to help run this trial through the continued pandemic? And the second question is you'll have -- I think, as many companies, you'll have patients recruited pre-pandemic and then during the pandemic. And I wonder if there's any risks in that and what you're doing in the trial design to help mitigate those risks, especially in cohort one.

Yes. Thank you. First, clearly, having a sufficient number of sites is a key ingredient for the success of any clinical trial. But I would add that it's not only a question of having a number of sites, it's also a question of having what I would characterize as good quality site, and in particular, referring again to cohort #1, because the target indication is 2 prior lines of systemic therapy plus -- or including prior exposure to mogamulizumab, we have really made a very strong effort to identify those sites who have sufficient recruitment of patients pre-exposed to mogamulizumab. So I think that this -- the combination of number of sites or the type of site is absolutely crucial for the success of the program. And I think that we -- this is exactly what we have been doing during the past few weeks, and we'll continue to do so when we activate the site in the coming -- in the near future. Concerning your other question, we have no substantial information that the quality of the trial could be impacted. The data monitoring visit to site first can be done to some extent remotely, and that has been a strategy used by the CRO that is helping us for the lacutamab study. In addition, data access, data control does not need to be performed immediately. It can be performed by a few days or a few weeks of delay. So for all those reasons, we don't think that the COVID pandemic will have any major impact on the data quality coming from the TELLOMAK trial.

Maybe a follow-up, how about differences in terms of if the patients get COVID, if these patients are particularly susceptible to side effects or at risk of death, I think more around the patient risk and less around the operational mitigation?

Again, we haven't really seen that. We are, of course, very well aware of the literature suggesting, for example, that the mortality due to COVID -- the mortality in cancer of patients could be increased due to the COVID pandemic. Again, that is not something that we have seen in the TELLOMAK trial. Now of course, all this is pretty recent. All this happened during the past 3 months. So we'll continue to pay a lot of attention to these questions. But again, at this stage, we have no evidence that anything like this is happening in the study.

We have no further questions from the telephone lines.

Okay. So if we have no more questions, I would like to thank you all for joining us today for this call. Again, I would like to thank my team and Frédérique Brune and her team who have done a terrific job to provide this batch on time. Again, we look forward to talking to you soon to update you on what's next with lacutamab in particular in the peripheral T-cell lymphoma setting. With that, I wish you all a wonderful day, and thank you very much for participating in this call. Bye-bye.

Thank you.

Thank you. Ladies and gentlemen, that does conclude your call for today. Thank you all for participating, and you may now disconnect.