Innate Pharma SA (IPHA) 2021 Q4 法說會逐字稿

Good afternoon, ladies and gentlemen, and welcome to the Innate Pharma Full Year 2021 Results Conference Call. (Operator Instructions) As a reminder, this conference call is being recorded.

I will now hand over to Mr. Henry Wheeler, Head of Investor Relations of Innate Pharma, to begin. Sir, please go ahead.

Thank you. Good morning, good afternoon, and welcome, everyone.

This morning, Innate issued a press release providing a business update for the 2021 full year results. We look forward to presenting the progress made during the year to date as well as addressing future goals and (inaudible) .

The press release and today's presentation are both available on the IR section of the website.

On Slide 2, 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.

On Slide 3, on today's call, we will be joined by Mondher Mahjoubi, our Chief Executive Officer, who will then hand over to Dr. Joyson Karakunnel, our EDP management (inaudible)

(technical difficulty)

Mondher, I'll now hand over to you.

Thank you, Henry. Can you hear me well?

I can hear you well now.

Perfect. Thank you. So let me first start by reminding you our strategy. Please move to Slide 4. As you know, our strategy centers around 3 key priorities: where we look to drive value from our early R&D efforts through later-stage partnerships, where it makes sense to do so.

Firstly, we look to create near-term value driven by our lead proprietary product candidate, lacutamab, which is in development for T-cell lymphoma.

Second, we continue to fuel our pipeline and create longer-term value by leveraging our antibody engineering capabilities to develop innovative molecules with the primary focus on our multi-specific NK cell engager platform called ANKET.

Last but not least, we are building a strong and sustainable foundation for our business, leveraging various partnerships across industry and academia.

Our goal is to leverage the value of our product as much as possible. We want to make sure that if we can gain valuable competencies, we have a partner agreement, we will consider that in our development plan for the product. This will further validate our time and offer capital that you can reinvest to advance our early portfolio.

Let me now turn to the next slide where I will cover the highlights for 2021. 2021 was a very busy year for Innate where we continued to deliver on our strategic objectives, and we have demonstrated steady progress across all key strategic pillars, as can be seen on this busy slide.

Starting with lacutamab first, we presented exciting mycosis fungoides data earlier in the year at the ICML meeting in Lugano and announced the advancement to the next stage of the Phase II trial, TELLOMAK. We also initiated last year 2 trials in the larger indication of peripheral T-cell lymphoma.

In the R&D pipeline, we were very pleased to see the lead tri-specific ANKET compound selected by Sanofi entered into the clinic. The data on the CD123 targeted agent in AML preclinical model were also presented at SITC last year. So we continue to progress our proprietary tetra-specific ANKET towards IND-enabling studies with (inaudible) preclinical data presented throughout the year.

On the adenosine pathway front, we have initiated our Phase I trial with our anti-CD73 IPH5301 in partnership with the IPC Cancer Center here in Marseille, and we look to further discussions with AstraZeneca on the next steps for our anti-CD39 IPH5201.

Finally, as we turn to monalizumab, we were very pleased to see our partner AstraZeneca comment in other Phase III registration and trial, PACIFIC-9, in Stage 3 unresectable lung cancer and also start with [further] on device Phase II study called NeoCOAST-2 in the neoadjuvant setting for resectable lung cancer patient.

At ESMO last year, we saw data presentation from the Phase II randomized COAST trial, and we expect to see more in the earlier length [sitting] from the NeoCOAST-2 trial in a few weeks at the AACR meeting.

Finally, as you may remember, at the end of the year, we also presented data from the triplet combination of monalizumab, durvalumab and cetuximab in frontline head and neck cancer at the ESMO-IO.

Please move to the next slide. Before I hand over to Joyson, here's an overview of the pipeline, which shows how we have translated 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 asset, lacutamab, supported by partner and early-stage products, in particular, (inaudible) NK cell engager platform.

We are also pleased to see the progress throughout the portfolio with multiple assets in the clinical stage now progressing from Phase I to registrational Phase III, and we look forward to the sales of potential clinical data readouts and catalysts in the upcoming couple of years as our R&D engine looks to leverage our scientific know-how to create a sustainable business.

I would like now to pass the call over to Joyson, who will review the progress made with our portfolio starting with lacutamab, our most advanced proprietary asset. Joyson, please?

Thank you, Mondher.

On Slide 7, let me start with our first-in-class humanized monoclonal antibody that targets the immune receptor, KIR3DL2. As you may remember, KIR3DL2 is an inhibitory receptor bound at approximately 65% of patients across all cutaneous T-cell lymphoma 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 T-cell lymphomas historically associated with the poor prognosis for which there are few therapeutic options at an advanced stage.

Let me highlight the progress we have made this year in our ongoing Phase II TELLOMAK study for Sézary syndrome and mycosis fungoides. In mycosis fungoides, the KIR3DL2 expressing cohort moved from Stage 1 to Stage 2, clearing a predetermined threshold before 50% of the cohort was enrolled.

The KIR3DL2 mycosis fungoides data was also presented in 2021 at Lugano, and the next mycosis fungoides data will be in 2022.

Today, we are also announcing the opening of an all-comers cohort in the mycosis fungoides setting to further evaluate our FFPE companion diagnostic being considered for late-stage trials. As expected, our scientific hypothesis was confirmed by the data in the non-expressing cohort, as the number of responses to move to Stage 2 was not reached as per the Simon 2 stage design, and recruitment into this cohort was stopped.

For the Sézary syndrome cohort enrollment is on track, and we expect to be able to report preliminary data in 2022.

On Slide 8, we have a summary of the Cohort 2 mycosis fungoides data in KIR3DL2 expressors And Cohort 3 non-expressors. In the preliminary results of Cohort 2, we showed an overall response rate of 35% in late-line patients with limited treatment portion.

As the median follow-up is only 4.8 months, we anticipate presenting longer-term follow-up on the duration of response at the next update. Even with the short followup, there have been 6 out of 17 confirmed responses.

In the skin compartment, we have 11 out of 17 confirmed responses. Of the 3 compartments, the skin compartment is important because of its association with quality of life for patients.

As you look to the right of the slide, you can see the Cohort 3 non-expressors data. As I explained earlier, as anticipated in this non-expressing cohort, the 3 required events per the Simon 2 stage design was not reached for the trial in -- to progress from Stage 1 to Stage 2. And due to this, recruitment was stopped. We are encouraged by the data and look forward to further proof points in 2022.

On Slide 9, let me summarize the progress we are making with lacutamab. We are pursuing a fast-to-market strategy for lacutamab in T-cell lymphomas, with a potentially pivotal trial underway in the initial setting of Sezary syndrome where lacutamab was granted U.S. Fast Track designation and EU PRIME designation last year.

We have expanded past Sezary syndrome to mycosis fungoides, where we have seen encouraging preliminary data from our Phase II trial.

For the Sezary syndrome cohort, enrollment is on track, and we still expect to be able to report top line preliminary data in the second half of 2022.

In mycosis fungoides, we moved the KIR3DL2 expressing cohort from Stage 1 to Stage 2 earlier than anticipated. And as expected, due to the number of events not having been reached, the non-expressing Cohort 3 was close to enrollment. The next preliminary mycosis fungoides data is due in the second half of 2022.

Finally, we are advancing into peripheral T-cell lymphoma and have started 2 clinical trials in the relapse setting.

On Slide 10, I would like to update you on our monalizumab efforts. To remind you, monalizumab is an anti-NKG2A, which acts upon the checkpoint pathway to potential NK cell activation that we have out-licensed to AstraZeneca. There are currently 2 ongoing Phase III trials with monalizumab, 1 in combination of cetuximab in head and neck cancer and 1 in combination with the anti-PD-L1 durvalumab in lung cancer.

On this slide, I wanted to recap the results for the randomized Phase II COAST study that AstraZeneca conducted in unresectable Stage 3 non-small cell lung cancer presented at ESMO in September 2021 and the first-line head and neck data we presented at ESMO-IO in December 2021. For the COAST study, the 3 arms evaluated the combination of durvalumab plus monalizumab and durvalumab plus oleclumab, AstraZeneca's anti-CD73. For the results shown here, both arms performed well versus the standard of care on durvalumab.

After a median follow-up of 11.5 months, the results of an interim analysis showed a 10-month PFS rate of 72.7% for durvalumab post monalizumab versus 39.2% with durvalumab alone. The results also showed an increase in the primary endpoint of confirmed overall response rate for durvalumab plus monalizumab over durvalumab alone of 36% versus 18%, respectively.

On the right side of the slide, Cohort 3 evaluated the triple combination of monalizumab, durvalumab and cetuximab in front-line head and neck cancer. The data demonstrated antitumor activity in the first study to evaluate this chemo-free triplet combination in the first-line recurrent or metastatic head and neck cancer setting.

As a reminder, the standard of care is based off the KEYNOTE-048 trial. The approval is for pembrolizumab monotherapy in CPS greater than or equal to 1 and pembro plus chemo in all-comer patients. We continue to collaborate with our partner AstraZeneca on potential next steps for this program.

Finally, in lung cancer, we are pleased to see that NeoCOAST study has been accepted for an oral presentation on April 11, 2022, at the American Association for Cancer Research Annual Meeting this year.

On Slide 11, you can see an overview of the late-stage development for monalizumab in lung cancer. As mentioned, based on the Phase II COAST data, AstraZeneca has commenced PACIFIC-9, a Phase III trial evaluating the combination of either monalizumab and oleclumab plus durvalumab in the unresectable Stage III non-small cell lung cancer setting, who have not progressed after concurrent chemoradiation therapy.

Separately, AstraZeneca also announced that it is starting a Phase II clinical trial, NeoCOAST-2, in Stages IIA to IIIA non-small cell lung cancer that includes a treatment arm with monalizumab in combination with durvalumab and chemotherapy. We look forward to seeing the data from Phase II NeoCOAST at AACR as mentioned.

On Slide 12, moving to head and neck cancer. As mentioned, we presented data from Cohort 3 of the Phase II trial at ESMO-IO for the triplet of monalizumab plus durvalumab plus cetuximab in the first-line head and neck cancer. Additionally, the Phase III INTERLINK-1 trial of monalizumab plus cetuximab in IO-pretreated head and neck cancer is ongoing, with final data expected in 2024.

We look to further work with our partners, AstraZeneca, on this potential (inaudible).

On Slide 13, we are pleased to have presented our latest innovation to our proprietary multi-specific NK cell engager platform that we call ANKET, which Eric Vivier has presented at several meetings last year, including ESMO and SITC. ANKET stands for antibody-based NK cell engager therapeutics. These multi-specific molecules are made up of various building blocks as illustrated here. ANKET is a versatile fit-for-purpose technology that is creating an entirely new class of tri- and tetra-specific molecule to induce strategic immunity against cancer.

This technology platform will be an engine for our pipeline, creating value by a multiple target candidate and further reinforces our scientific expertise in the NK cell space. Our excitement for the NK platform is brought on because of the preclinical data we have to date.

First, the ANKET platform allows for the harnessing of NK cell effector function and NK cell proliferation in preclinical models against cancer.

Second, the preclinical efficacy is due to the unique NK cell engagement of the activating NK cell receptors, NKp46 and CD16, but also the IL-2 variant, which targets receptors for the IL-2R beta and IL-2R gamma complex, which is unique to the tetra-specific molecule and includes a specific tumor antigen.

Overall, it demonstrates a better preclinical antitumor efficacy than we have seen preclinically with clinically approved antibody.

On Slide 14 is a summary of the data presented at SITC 2021 on our lead trispecific ANKET asset selected by Sanofi. This is the first NKp46/CD16 based NK cell engager to enter the clinic. On the left side of this slide, you can see the preclinical data showing that CD123 targeted IPH6101 tri-specific ANKET demonstrated potent antitumor activity against all AML cell lines, including primary AML, which were resistant to ADCC by a competitor anti-CD123 antibody.

On the right of the slide, we demonstrate that in nonhuman primate, there is sustained pharmacodynamic effect, combining efficient depletion of CD123 expressing cells with minor cytokine release and a favorable safety profile in comparison to T cell engagers. We are pleased to see the Phase I trial underway by Sanofi.

On Slide 15, we wanted to highlight the data on our recent generation of tetra-specific ANKET, which is made up of 4 components: in yellow, an antibody fragment that recognizes the tumor antigen; in green, an antibody fragment that recognizes NKp46; in red, an FC portion that will interact with CD16; and then in a blue -- in blue, a variant of the interleukin 2.

On the left, we show you the contribution of the tetra-specific ANKET with the non-alpha-IL-2 variant. The black graph on the far left is the vehicle. The green graph is the tetra-specific ANKET, and the red graph on the right is a tri-specific ANKET with a systemic IL-2 variant.

You can see the benefit with the green graph, including the tetra-specific ANKET with the IL-2 variant. On the right, you can see the benefit of the tetra-specific versus the vehicle as well as obinutuzumab in lung [mouse] models. On top, you have the vehicle. In the middle, tetra-specific ANKET, and on the bottom, the CD20 obinutuzumab.

Activity is seen with the tetra-specific model that is not seen with obinutuzumab. We look forward to further updates on ANKET throughout the year as we progress toward IND-enabling study.

I will turn to Frederic for an update on the financials.

Thank you, Joyson, and good day, everyone.

So moving to the finance, Slide 16. I will start with one of our key metrics, as usual, our cash position. Our cash and cash equivalents amounted to EUR 159.7 million as of December 31, 2021. This includes the state guaranteed loan of EUR 28.7 million we received in December 2021.

In addition, as you can see, we are efficiently managing our resources, so that we can best capitalize on our progress and data read out to explore development pathways in debt identifications. We believe this approach ensures that we remain in position to strategically invest in our vision for Innate.

Now going into the P&L, I will only comment on the main and most significant lines, and you have a very detailed comment in the appendix of the press release that you can refer to for information. Note that as compared to our previous filing, Lumoxiti activity has been classified as discontinued operations in the separate lines of the P&L for all relating Lumoxiti income expenses.

I'll start with our revenue and other income, which amounted to EUR 24.7 million this year. It mainly resulted from revenues from collaboration and licensing agreements and governmental funding. The revenue line is characterized by the spreading of the upfront and opt-in payments received from AstraZeneca for monalizumab, which I'll remind is recognized on the basis of percentage of completion of the work performed by the company. I also remind you that it has no impact on cash flow.

Operating expenses amounted to EUR 72.5 million, showing an increase by 5% compared to 2020. R&D expenses were at EUR 47 million, decreasing by 5% compared to the last year, but increase was mainly due to the decrease in depreciation and amortization of intangible assets acquired by the company, mostly IPH5201 fully amortized at the end of 2020 and monalizumab, partly offset by an increase in direct research and development expenses, clinical and nonclinical.

Also the company has paid EUR 11.4 million to AstraZeneca related to the co-funding of the monalizumab programs in 2021 compared to EUR 1.8 million in 2020.

Turning to G&A expenses. They were EUR 25.5 million for the year. The increase here was mainly due to an increase in restructuring costs relating to the evolving U.S. business, excluding Lumoxiti and to an increase of [nonscientific] [ancillary] fees.

G&A expenses related to Lumoxiti discontinued operations amounted to EUR 8.5 million in 2021 compared to EUR 12.3 million in 2020, respectively. In 2021, these expenses are mainly composed of the settlement amount of USD 6.2 million equivalent to EUR 5.4 million to be paid in April this year to AstraZeneca as part of the termination and transition agreement.

As a reminder, the company has communicated in its 2020 consolidated financial statements on a contingent liability estimated to a maximum of EUR 12.8 million related to the sharing of certain manufacturing costs. These are the last Lumoxiti-related expenses we are expecting this year. Total G&A costs, including Lumoxiti discontinued operation increased actually by 9% year-on-year.

To recap, we have a strong cash and cash equivalent position with is EUR 159.7 million at the end of 2021. We estimate that we have enough cash to fund planned operation to at least 2023.

With that, I'm turning back to Mondher.

Thank you, Frederic.

Please move to Slide #17. Frederic If you can put your cell phone on mute, please. Okay, so as you can see on Slide 17, we are working diligently to execute across all our strategic pillars, and we believe that we are laying the foundation to drive near and long-term value.

Looking at our clinical program, we expect to achieve a number of milestones over the next 2 years. As you've heard from Joyson, our Phase II TELLOMAK study for lacutamab continues to progress. We continue to expect to report preliminary data from the potentially total [child] and Sezary syndrome as well as data in mycosis fungoides in the second half of this year.

In addition, as you've heard, we are moving our peripheral T-cell lymphoma program into the clinic with initial data expected next year.

For monalizumab, we look forward to further clinical development in early lung cancer, with the head and neck cancer trial underway. We continue to advance the adenosine pathway agents in the clinic where we look forward to data from the anti-CD39 IPH5201 in 2023.

In parallel, we continue to develop our ANKET technology platform, and we are very encouraged by the preclinical results from our next-generation NK cell engager. We believe that this represents a natural evolution of our platform, with data presented at conferences last year. We are very excited to see the lead tri-specific ANKET in the clinic with Sanofi and look forward with updates on our proprietary, ANKET throughout 2022.

Let's move to the conclusion slide #18. As you can tell, we continue our exciting journey at Innate. We look to build our business to create value for patients and stakeholders. And in summary, we have positioned the company for the future with our strategy and made meaningful progress throughout 2021 across all 3 strategic pillars.

We have carefully managed our resources, so we can continue to invest and progress in our pipeline, and I'm very pleased that we continue to have a very strong cash position with nearly EUR 160 million as of 31st of December 2021, which provides us a runway into the 2023.

Collectively, we are driving value across our business and ultimately advancing our goal to deliver innovative [medicines] to cancer patients. We look forward to keeping you updated on our projects throughout the year.

That concludes our prepared remarks. We will now open the call to questions.

(Operator Instructions) And our first question today comes from Daina Graybosch of SVB Leerink.

Maybe 3 for me, 2 on lacutamab, 1 on monalizumab. On lacutamab, can you confirm and help me understand the new all-comers cohort in mycosis fungoides in the context of not moving forward in the KIR3DL2 negative into the next stage? So what's the purpose of the all-comers when you're not moving the other cohort forward?

And then the second question on lacutamab is for mycosis fungoides, after this next stage of TELLOMAK, do you expect ultimately to be able to get a single-arm approval in MF? Or would you expect the need to move into a randomized study for approval on MF?

And then finally on monalizumab, can you confirm that we're still on track to have the interim fertility analysis in the INTERLINK study that's connected to a milestone payment to Innate Pharma from AstraZeneca this year?

Thank you, Daina. I'll answer all 3 questions. But I quickly answer the third one, the Interlink interim analysis is still on track, and we are expecting this to happen in 2022, most likely in the second half of 2020. No change to the time line. The date that you have seen on the slide presented by Joyson is for the final analysis, but the interim is still scheduled throughout the end of this year.

Now for your 2 questions on the lacutamab, I'm going to ask Joyson to maybe provide a little bit more details on the why we are doing this cohort and eventually what the impact that could have. And of course, as you've heard, this is a -- we have a continuous dialogue with the FDA, so we can give a little bit more color on our MF registration strategy.

Joyson, please.

Thank you, Mondher, and thank you, Daina. So I'm going to kind of combine these questions into 2, so please feel free to let me know if I cannot answer those questions.

So just as a reminder, for Cohort 2 and Cohort 3, when we were selecting those patients of expressors versus non-expressors, this was based on frozen biopsy samples. So the IHC assay was based on frozen samples, and that's what we used as a tool for selection.

Now going forward, the all-comer cohort, to answer your first question, the all-comer cohort will be evaluating an FFPE companion diagnostic approach. We don't anticipate that this is going to lead to any type of delay in development since we have seamlessly integrated this into the TELLOMAK study, and it comprises of patients that are similar to Cohort 2 and Cohort 3.

That connects with our registrational approach, as you mentioned. So I think when we look at this overall, a single-arm approach is always possible and always dependent upon the data. But at this time, we are planning for a Phase III would be required for registration. And as such, we would look to use the optimal assay in this registrational trial, which we believe will be the FFPE. And so we're continuing with these Phase III discussions with health authorities, and we hope to disclose more soon, especially as the data readouts come along. I hope that answers the question.

So just to confirm potentially what is -- yes, just to confirm potentially after this new cohort, the percentage of patients that are positive may change slightly because it could be optimized in this work to really understand the best cutoff for further enrichment. .

Yes. So to -- the total percentage of patients could change. I think what we know is it is around 50%, so we wouldn't anticipate a huge variation there in comparison between the pathway.

Yigal Nochomovitz from Citi.

This is Carly on for Yigal. Our first question is on the CD73 program. Can you talk a bit more about the rationale for focusing on HER2-positive cancers? Is there evidence that CD73 plays a larger role in immunosuppression and HER2-positive cancers versus other tumor types?

I guess, just interested in your thoughts there because I don't believe we've seen others in the CD73 space focused on the HER2 segment specifically.

Thank you. Before I hand over to Joyson, again, I wanted to just put this into the context of trying to differentiate our anti-CD73 from the rest of the crowd. We are not the first. We are indeed the latest to get into the clinic. And that, of course, we used to totally learn from what other company has delivered and because trial was extremely useful to help us actually better understand potential synergy with ideation therapy as a potential position and be early to (inaudible) cancer.

But at the same time, we have looked at the preclinical models and what we have in-house to try to differentiate our development when we came up with this strategy, which is not in play for now because we started the classic dose escalation.

But I'm going to hand over to Joyson probably to give you a little bit more background why we're going up for this indication on this combination with trastuzumab. Joyson?

So thanks, Mondher, and thank you for the questions. So to begin, it goes back to what Mondher said currently. At this point, the CD73 landscape, as all of you are aware, is quite crowded and continues to become more crowded.

So when we started the development for CD73, we asked ourselves, how can we set ourselves apart. I will hand this to -- hand over to Yannis who can speak a little bit to at least the scientific rationale around the HER2 that you have asked.

But we -- so when we started this, we said we will go ahead and differentiate ourselves. So we looked at how can we do this. And based on the science, we went into the HER2 space. Afterwards, as Mondher mentioned, the COAST data had come around. And now we're thinking to ourselves how can we optimize the development of our CD73 utilizing the clinical data that we have seen in COAST that -- and I think you'll see some also in the NeoCOAST study, which makes the CD73 landscape -- I mean, CD73 gives us another indication with proof in the clinical space.

So maybe I'll hand it over to Yannis who can speak a little bit about the science around the HER2.

Yes. Thank you, Joyson. Yes, like you said, we are actually differentiating our molecule first because of its increasing properties, our antibody as opposed to other CD73 inhibitors that are in development and especially the oleclumab.

Our antibody does not have the [book] effect, meaning that it continued to block the enzyme even at high dose, meaning that we are blocking the surface and sector, but we are also blocking the soluble molecule of CD73, which is very important for an enzyme.

And like said by Joyson, it was important also to differentiate the development of our assets going into combination that was not explored by others. Others were exploring mostly PD-1 combination. And based on preclinical data we have that the combination of CD73 is actually mediating -- CD73 is mediating resistance to the ADCT of HER2 targeting antibody. So that by combining the blockade of CD73 can increase the efficacy of trastuzumab in preclinical models.

Okay. Got it. That's really helpful. And then just one housekeeping question. Did Innate receive a milestone payment from AstraZeneca on the start of PACIFIC-9? And are there any other milestones tied to PACIFIC-9 that we should be aware of?

Yes. So again, maybe remind everyone that we are, of course, excited that PACIFIC-9 study has started. And of course, we still wait to their first patient being dosed.

We have not provided granularity on potentially mile stones. We have received so far EUR 400 million, the EUR 50 million on the first Phase III INTERLINK-1, which started in the fall of 2020. And interim analysis will also trigger a payment of EUR 50 million if the predefined (inaudible) activity is achieved.

In total, we could potentially receive another EUR 425 million in regulatory and developing milestones, and about EUR 400 million in commercial (inaudible) as well as a double-digit royalty part of the payment with AstraZeneca.

And our next question comes from Liisa Bayko of Evercore ISI.

First one, are you planning an interim analysis of INTERLINK for this year?

Liisa, thank you for joining the call and your questions. As you know, (inaudible) trial is being conducted by AstraZeneca and the plan was to -- is to have an interim analysis performed about 18 to 24 months after the first patient is (inaudible). The first patient was (inaudible) in November 2020, so the interim is expected for the second half of 2022.

Wonderful. Okay. Great. And then can you maybe discuss a little bit more specifically about your regulatory strategy for Sézary syndrome? Are you going to file just for this indication alone? I think there was some mention at JPMorgan that you might do some sort of combination with MF. Maybe you can just discuss.

Yes, absolutely. I think it's a good way to hand over to Joyson to recap our MF/Sezary syndrome registration strategy based on, again, the interaction we have with the FDA.

Joyson, can you please address this question?

Thanks, Mondher, and thank you for the question. So let me start off with at least our initial strategy. So our initial strategy for Sezary was, in fact, a fast-to-market strategy. And we do have the pivotal cohort that is ongoing that we are looking to present data about on -- later this year. So that cohort is still ongoing and does provide a potential registrational pathway.

To your question about what is another option, another possibility is that we take the approach of combining both SS and MF, which, as many of you know, the mogamulizumab label is both SS as well as MF. So there is precedent for combining both of these indications.

So we are looking at all possible options to be -- for a registrational pathway. But in addition, we're also having ongoing discussions with the FDA as well as the European health regulators to be able to make sure that they are also aligned with the options we have as well as the registrational path.

Okay. Any idea when you might have some more granularity on that? Or is it really data dependent? .

It is -- it will be data dependent. And as we mentioned, so we will be presenting data about Sezary syndrome as well as mycosis fungoides later this year.

And our next question comes from Keyur Parekh of Goldman Sachs.

Two, if I may, please. One, just as you kind of think about the opportunity across both Sezary syndrome and MF, just wondering if you can remind me how big you guys think these indications can be and how kind of -- how quickly do you think you might be able to get to the peak revenue sizes for this indication. That's kind of question number one.

And then separately for you, Mondher, as you think about kind of developing the tetra ANKET kind of products, you've been doing kind of oncology drug development longer than most people. Just help us think about what you think some of the challenges and the opportunities might be. We've all seen the bispecifics kind of struggle from a safety variability perspective.

So if you're kind of doing something that is targeting 5 different targets, just help us think through that and what it means from the perspective of the focus we should be having on the tolerability profile for these agents.

Thank you, Keyur. Great questions. I'll try to answer as clear and as precise as possible.

So first of all, maybe on the Sezary and MF, Sezary is -- we have (inaudible) data for U.S. and top 5 EU. So it's roughly, let's say, about 50% to 60% of the market. But nevertheless, I think it's quite significant to start having an idea.

There are about 100 to 200 new Sezary syndrome every year, okay, so it's really a niche indication. And this patient actually received multiple lines of therapy. They have a long PFS, and so they live longer and they get old.

And all in all, if you think about prevalence at one point in time, it's less than 1,000 patients. So it's really a small business. But we knew it from day 1. We all know Sezary is really a proof of concept on one side and a way to get to the market as quickly as possible, and that is a much bigger market opportunity.

And please keep in mind that MF is just one type of Sezary subtypes of cutaneous T cell lymphoma. About half of cutaneous T cell lymphoma are mycosis fungoides. And there are about 50% of cutaneous T cell lymphoma which are not mycosis fungoides.

It's very heterogenous. It's very sophisticated and actually difficult to classification. And it's quite challenging also to do some registration work on such heterogenous population. So that's why we elected to go after mycosis fungoides.

All in all, we are talking about maybe 3,000 to 4,000 new patients every year. And clearly, the cutaneous T cell lymphoma overall is not a very huge market opportunity, of course, when you compare it to peripheral T cell lymphoma, which is a much bigger one. We're talking about nearly 20,000 new patients every year, and half of them express the target.

So clearly, it's a much bigger indication. But again, we do not have data there. We just started last year. If I give you a number, it would be maybe, I'd say, too ambitious from my side because we are too early in our thinking about the commercial strategy. But we looked at the potential and a very good benchmark is mogamulizumab. And you may have followed the full year results of Kyowa, they sold about EUR 150 million of moga, which main indication is MF and Sezary.

So clearly, there is a business there in the cutaneous T cell lymphoma. And as you know, mogamulizumab is approved in the U.S. and in Europe, but it's not reimbursed everywhere in Europe. So we have a challenge, of course, in terms of market penetration. And the drug was just approved end of 2018 in the U.S. and in 2019 in Europe. So it's still quite new.

But nevertheless, I think it's a good indicator about the market opportunity when it comes to MF and Sezary. I hope I clarified this first question. I think your second question is really what we do every day actually and how trying to really figure out why we are progressing our proprietary ANKET product into IND-enabling studies and preparing for the clinic, thinking about how to develop this drug and how to position it actually as a new generation of multi-specific antibodies.

I think the main opportunity results actually into the safety of using an NK cell engager versus a T cell engager. And actually, we have a good reason to think that this could be one of the way to differentiate, but also could be an opportunity also for a combination strategy that we could afford.

And you have seen data already from others combining fresh cells, active cells with antibody engaging into (inaudible) the reserves pathway are quite amazing, especially in liquid tumors. Of course, it's small. And usually, you're talking about Phase I, II. But nevertheless, it provide some idea on the potential of this combination.

I think the opportunity resides in solid tumors as if we can do the same. And again, we are not the only ones working on the [screen] that is prepared to tackle the solid tumor space, engaging and to sense with antibodies that target solid tumors.

I believe there is a significant potential there that is impacted so far. And I think it's a great opportunity.

Last but not least, and this is one of the main challenge, but it's not the only one, is how to make sure that with our construct, it's pretty brand-new in terms of CMC and manufacturing. So there are challenges there that we have to overcome because it's the first time we develop (inaudible) complex antibody.

But on top of that, once we get into the clinic, remember, this is an antibody that included IMC (inaudible). Of course, we selected the IL2 variant for a purpose to expand the NK cells without the downside safety issue that you can encounter.

And of course, these are so far preclinical data. We need to make sure that this translates into the clinic with the same benefits and the same safety profile.

So these are the 2 main kind of short-term challenges that we have to go through, but the clinical data will tell whether what we have generated so far and what we presented at various meetings last year can translate in real clinical benefit for patients.

So sorry for the long answer, but I think it's a good opportunity maybe to put our ANKET platform development strategy into context and perspective.

(Operator Instructions) And our next question comes from Swayampakula Ramakanth from H.C. Wainwright.

Most of my questions have been asked, Mondher. However, on the 5201, the anti-CD39 antibody, in terms of what the next steps are, is it potentially AstraZeneca who has to make the decision? Or do you have any say in how the program will be developed from here onwards?

RK, good to have, and thank you for your question. CD39 license agreements with AstraZeneca look similar to the monalizumab agreement. So it's really a co-development, co-commercialization agreement where we are involved, and we are engaged also in the development of this policy. AstraZeneca did the first part of the escalation, single agent and then in combination. They oppose the development because we reached the, whatever you call it, milestone or objective of Phase I. And now we are in the planning phase and discussion with AstraZeneca on the next step, learning from, again, the COAST trial, which was, as I said, a proof-of-concept demonstration for the pathway, of course, tackling the CD73.

But nevertheless, I think it's an important milestone in the development of these antibody. So we're learning from that and discussing with AstraZeneca on how best to position and differentiate CD39 from the rest of the competition, and we're doing this in partnership, in collaboration.

We have no further questions. I'll hand the call back over to you, Mondher.

Thank you. Again, I think it's a great opportunity to present our full year results for 2021. And as you could appreciate, I hope we continue to execute against our strategic priority as we reported multiple readouts from both proprietary and partnered portfolio programs. These results are center stage for delivering both near-term and long-term value, while also highlighting the strength of -- and depth of our core R&D.

And just a reminder, looking ahead, we will continue to advance our lacutamab development program. We will continue to move our early-stage R&D activity toward the clinic, with our next generation NK platform. And for monalizumab, we look further clinical development in early lung cancer with the head and neck cancer well underway, which, of course, further enforce our strategy of building a sustainable business with our robust R&D engine.

With that said I wish you a wonderful day, and thank you for your participation to this call. Thank you. Bye-bye.

Ladies and gentlemen, this concludes today's call. Thank you all for joining. You may now disconnect your lines.