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spk08: Good afternoon, ladies and gentlemen, and welcome to the Innate Farmers full year 2021 results conference call. At this time, all participants are in a listen-only mode. As a reminder, this conference call is being recorded. I will now hand over to Mr Henry Wheeler, Head of Investor Relations of Innate Farmer to begin. Sir, please go ahead.
spk07: Thank you. Good morning, good afternoon and welcome everyone. This morning Enate issued a press release providing a business update to 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 milestones. The press release and today's presentation are both available on the IR section of the website. On slide two, 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 risk and uncertainties that may cause actual results to differ from those forecasted. On slide three, on today's call, we will be joined by Monde Batumi, our chief executive officer, who will then hand over to Dr. Joyston Caracanel, our EVP .
spk04: Thank you Henry. Do you hear me well? I can hear you well now. Perfect, thank you.
spk08: So let me first start by reminding you our strategy.
spk06: Please move to slide four. As you know, our strategy centers around three key priorities. We are willing to drive value from our early R&D efforts through data-based partnership, where it makes sense to do so. Firstly, we look to create near-term value driven by our lead proprietary product candidate, Lecutamab, 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 a primary focus on our multi-specific NK cell engager platform called NK. 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 via a partner agreement, we will consider that in our development plan for the product. This will further validate our science and offer capital that we 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 Enate, where we continued to deliver on our strategic objective, and we have demonstrated steady progress across all key strategic pillars, as can be seen on this busy slide. Starting with Lakuta 9 first, We presented exciting microdisponibility data earlier in the year at the ICMN meeting in Lugano and announced the advancement to the next stage of the phase two trial, TeleVac. We also initiated last year two trials in the larger indication of peripheral T-cell lymphoma. In the R&D pipeline, we were very pleased to see the lead trial-specific NCAT compound selected by Sanofi enter into the clinic. The data on the CB123 targeted agent in AML preclinical model were also presented at SITC last year. So we continue to progress our proprietary petra-specific NCAT towards IND-enabled studies with, here again, preclinical data presented throughout the year. On the iodine as in pathway front, we have initiated our phase one trial with our anti-CD73 APH5301 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 APH5201. Finally, as we turn to monolizumab, we were very pleased to see our partner AstraZeneca commence another Phase III registrational trial antidecrine in Phase III unresectable lung cancer, and also start a further randomized Phase II study called NEOCORS II in the neoadjuvant setting for receptable lung cancer patients. 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 fitting from the new COAST 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 monolizumab, turvalumab, and fitiximab in frontline head and neck cancer at the ESMO IOP. Let's move to the next slide. Before I hand over to Joyce, here is an overview of the pipeline, which shows how we have translated our science into a robust portfolio of proprietary and partner assets. It also illustrates how we are executing against our strategy with our lead proprietary assets like Udama, supported by partners and early stage products, in particular those from our NPSL engagement platform. We are also pleased to see the progress throughout the portfolio with multiple assets in the clinical stage now progressing from phase one through to registration phase three. And we look forward to a series 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 Joyce, who will review the progress made with our portfolio, starting with Lecithamab, our most advanced proprietary asset. Joyce, please. Thank you, Mandir. On slide seven, 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 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 lacudimab have shown promise demonstrating compelling single-agent activity and offering immense potential in T-cell lymphomas historically associated with a 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 telemax study for cesarean syndrome and mycosis fungoides. In mycosis fungoides, the Q3DL2 expressing cohort moved from stage one to stage two, clearing a predetermined threshold before 50% of the cohort was enrolled. The Cure3DL2 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 cohorts. As the number of responses to move to stage two was not reached as per the Simon two stage design and recruitment into this cohort was stopped. For the sensory 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 mycoses fungoides data in CURE3-DL2 expressors and cohort 3 nonexpressors. In the preliminary results of cohort 2, we showed an overall response rate of 35% in late-line patients with limited treatment options. 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 follow up, there have been six out of 17 confirmed responses. In the skin compartment, we have 11 out of 17 confirmed responses. Of the three 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 three non-expressors data. As I explained earlier, as anticipated in this non-expressing cohort, the three required events per the Simon two-stage design was not reached for the trial to progress from stage one to stage two. And due to this, recruitment was stopped. We are encouraged by the data and look forward to further proof points in 2022. On slide nine, let me summarize the progress we are making with Lacudamab. We are pursuing a fast-to-market strategy for lacudimab in T-cell lymphomas with a potentially pivotal trial underway in the niche setting of cesarean syndrome, where lacudimab was granted U.S. fast-track designation and EU prime designation last year. We have expanded past cesarean syndrome to mycosis fungoides, where we have seen encouraging preliminary data from our Phase II trials. For the cesarean 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 Cure3DL2 expressing cohort from stage one to stage two earlier than anticipated. And as expected, due to the number of events not having been reached, the non-expressing cohort three was closed 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 two clinical trials in the relapse setting. On slide 10, I would like to update you on our monolizumab efforts. To remind you, monolizumab is an anti-NKG2A, which acts upon the checkpoint pathway to potentiate NK cell activation that we have outlicensed to AstraZeneca. There are currently two ongoing phase three trials with monolizumab, one in combination with cetuximab in head and neck cancer, and one in combination with the anti-PD-L1 dervalumab in lung cancer. On this slide, I wanted to recap the results for the randomized phase two COAST study that AstraZeneca conducted in unresectable stage three 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 three arms evaluated the combinations of durvalumab plus monolizumab and durvalumab plus oleculumab, AstraZeneca's anti-CD73. For the results shown here, both arms performed well versus the standard of care on durvalumab. After a medium follow-up of 11.5 months, the results of an interim analysis showed a 10-month PFS rate of 72.7% for durvalumab plus monolizumab versus 39.2% with durvalumab alone. The results also showed an increase in the primary endpoint of confirmed overall response rate for dovalumab plus monolizumab over dovalumab alone of 36% versus 18% respectively. On the right side of the slide, cohort three evaluated the triple combination of monolizumab, dovalumab, and cetuximab in frontline head and neck cancer. The data demonstrated anti-tumor 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 48 trial. The approval is for pembrolizumab monotherapy in CPS greater than or equal to 1 and pembropus chemo in all chemo 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 monolizumab 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 monolizumab and olicumab plus Dervalumab 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 two clinical trial, neocost two in stages 2A to 3A non-small cell lung cancer that includes a treatment arm with monolizumab in combination with Dervalumab and chemotherapy. We look forward to seeing the data from phase two neocost at AACR as mentioned. On slide 12, moving to head and neck cancer, As mentioned, we presented data from cohort three of the phase two trial at ESMO-IO for the triplet of monolizumab plus dervalumab plus cetuximab in the first line head and neck cancer. Additionally, the phase three interlink one trial of monolizumab 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 new treatment. On slide 13, we are pleased to have presented our latest innovation to our proprietary multi-specific NK cell engager platform that we call MCAT, which Eric Vivier has presented at several meetings last year, including ESMO and CIS. NCAT stands for Antibody-Based NK Cell Engager Therapeutics. These multi-specific molecules are made up of various building blocks, as illustrated here. NCAT is a versatile, fit-for-purpose technology that is creating an entirely new class of tri- and tetra-specific molecules 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 NCAT platform is brought on because of the preclinical data we have to take. First, the NCAT 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 tetraspecific molecule and includes a specific tumor antigen. Overall, it demonstrates a better preclinical antitumor efficacy than we have seen preclinically with clinically approved antibiotics. On slide 14 is a summary of the data presented at CITSE 2021 on our lead tri-specific NCAT 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 trispecific NCAT demonstrated potent antitumor activity against all AML cell lines, including primary AML, which were resistant to ADCC by a competitor, anti-CD123 antibodies. On the right of the slide, we demonstrate that in non-human primates, 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 a recent generation of tetraspecific NCAT, which is made up of four 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 blue, a variant of the interleukin-2. On the left, we show you the contribution of the tetraspecific NCAT with the non-alpha IL-2 variant. The black graph on the far left is the vehicle. The green graph is the tetraspecific NCAT, and the red graph on the right is a trispecific NCAT with a systemic IL-2 variant. You can see the benefit with the green graph, including the tetraspecific NCAT with the IL-2 variant. On the right, you can see the benefit of the tetraspecific versus the vehicle, as well as abinituzumab in lung mouse models. On top, you have the vehicle. In the middle, tetraspecific NCAT. And on the bottom, the CD20 abinituzumab. Activity is seen with the tetraspecific model that is not seen with abinituzumab. We look forward to further updates on NCAT throughout the year as we progress toward IND-enabled studies. I will turn to Frederik for an update on the financials. Thank you, Jason, and good day, everyone. So moving to the finance slide 16, I will start with one of our pre-matrix, as usual, our cash position. Our cash and cash equivalents amounted to $259.7 million as of December 31st of 2021. This includes the state-guaranteed loan of $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 readouts to explore development pathways in different applications. We believe this approach ensures that we remain in position to strategically invest in our vision for INAID.
spk07: 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 more information. Note that, as compared to our previous filing, the LUMOKHETI activity has been classified as discontinued operations in the separate lines of the P&L for all relating
spk06: democracy income and expenses. I'll start with our revenue and other income, which amounted to 24.7 million euros this year. It mainly results from revenues from collaboration and licensing agreements and funding. The revenue line is characterized by the spreading of the funds and payments received from AstraZeneca for , which I 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. Operating expenses amounted to €72.5 million, showing an increase by 5% compared to 2020. R&D expenses were €47 million, decreasing by 5% compared to the last year.
spk07: The decrease was mainly due to the decrease in depreciation and amortization of intangible assets acquired by the company. mostly ETH 5201, fully amortized at the end of 2020, and ManelisMAP. Partly upset by an increase in direct research and development expenses, clinical and non-clinical.
spk06: Also, the company has paid €11.4 million to AstraZeneca related to the co-funding of the ManelisMAP programs in 2021, compared to €1.8 million in 2020. Turning to G&A expenses, there were $25.5 million for the year. The increase here was mainly due to an increase in restructuring costs relating to the evolving U.S.
spk07: business, excluding Lumoxity, and to an increase of non-scientific advisory fees.
spk06: G&A expenses related to Lumoxity discontinued operations amounted to $8.5 million in 2021 compared to $12.3 million in 2020, respectively. In 2021, these expenses are mainly composed of the settlement amount of 6.2 million USD, equivalent to 5.4 million euros, to be paid in a credit share to AstraZeneca as part of the pre-emission and transition agreement. As a reminder, the company has communicated in its 2020 consolidated financial statement on the contingent liability estimated to a maximum of 12.8 million euros related to the sharing of certain manufacturing costs. These are the last limoxity-related expenses we are expecting this year. Total G&A costs, including limoxity discount in operation, have increased actually by 9% year-on-year. To recap, we have a strong cash and credit equivalent position with €159.7 million at the end of 2021. We estimate that we have enough cash to fund planned operations to actually meet 2023. With that, I'm turning back to Mondaire. Thank you, Frederic. Please move to slide number 17. Frederic, if you can put yourself 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 two years. As you heard from Jason, Our Phase II KELOMAC study for LAPITANOT continues to progress. We continue to expect to report preliminary data from the potentially total trial in caesarean syndrome, as well as data in microcystic hunger deaths in the second half of this year. In addition, as you've heard, we are moving our terrestrial TCL lymphoma program into the clinic, with initial data expected next year. For Monolizumab, we look forward to further clinical development in early lung cancer with the head and neck cancer trials underway. We continue to advance the adenine pathway agent in the clinic, where we look forward to data from the entire CU39 APH5201 in 2023. In parallel, we continue to develop our NCATS technology platform, and we are very encouraged by the preclinical results from our next-generation NKCN engagers. 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 NCAT in the clinic with Canopy and look for dates on our proprietary NCAT for 2022. Let's move to the conclusion slide, number 18. As you can tell, we continue our exciting journey at Enate. We need to build our business to create value for patient and stakeholders. And in summary, we have positioned the company for the future with our strategy and made meaningful progress throughout 2021 across all three 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 €160 million as of 30th of December 2021, which provides us a runway into mid-2023. Collectively, we are driving value across our business and ultimately advancing our goal to deliver innovative machine to cancer patients. We look forward to keeping you updated on our progress throughout the year. That concludes our prepared remarks. We will now open the call to questions. Thank you.
spk08: If you would like to ask a question, please press star followed by the number one on your telephone keypads. If you choose to withdraw your question, please press star followed by the number two. When preparing to ask a question, please ensure your phone is unmuted locally. And our first question today comes from Dana Graybosh of SVB Lurie. Dana, please go ahead. Your line is open.
spk01: Hi. Thanks for taking my questions, guys. Maybe three for me, two on the Kudamab, one on monolizumab. On the Kudamab, can you confirm and help me understand the new all-comers cohort and mycosis fungoides in the context of not moving forward in the Ker-3 DL2 negative into the next stage? What's the purpose of the all-comers when you're not moving the other cohort forward? And then the second question on lacuna Mavis for mycosis fungoides, after this next stage of Telomax, Do you expect ultimately to be able to get a single-arm approval in MS, or would you expect to need to move into a randomized study for approval in MS? And then finally, on monolizumab, 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.
spk06: Thank you, Dana, for all three questions. When 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 2022. No change to the timeline. The date that you have seen on the slide presented by Gershon is for the final analysis that the interim is still scheduled toward the end of this year. Now, for your two questions on Equitamab, I'm going to ask Jason 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 continuous dialogue with the FDA, so we can give a little bit more color on our MF registration strategy. Jason, please. Thank you, Vandana. Thank you, Dana. So I'm going to kind of combine these questions into two. So please feel free to let me know if I cannot answer those questions. So just as a reminder for cohort two and cohort three, 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, you know, 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 TELEMAC study. And it comprises of patients that are similar to cohort two and cohort three. 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're planning for a phase three 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 three discussions with health authorities, and we hope to disclose more soon, especially as the data readouts come out. I hope that answers your question.
spk01: So just to confirm potentially, you know, 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.
spk06: Yes. So 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 here in comparison between both athletes.
spk01: That's very, very helpful. Thank you. Thank you, Ben.
spk06: Thank you, Dana. Thank you, Johnson. Operator, I think the second question from Igal.
spk08: Yep. Igal Nokomovich from City. Please go ahead.
spk02: Hi, this is Carly on Fregal. Thanks for taking our questions. 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 in 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 focus on the HER2 segments specifically. Thank you.
spk06: Thank you. Before I hand over to Jason 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 among the latest to get into the clinic. And that, of course, we used to learn from what other companies have delivered, and the COAST trial was extremely useful to help us actually better understand potential synergy with radiation therapy and the potential position in the early stage treatment of brain cancer. But in the same time, we have looked at the preclinical models and what we have in-house to try to differentiate our development, and we came up with this strategy, which is not in play for now because we started with the classic dose escalation. But I'm going to hand over to Joyce and Paul to give you a little bit more background of why we're going to have this indication and this combination is possible or not. Joyce? Thanks, Mandir, and thank you for the question. To begin, it goes back to what Mondaire 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 Yanis, who can speak a little bit to at least the scientific rationale around the HER2 that you have asked. 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 Manda 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 and i think you'll see some also in the neocost study which makes the cd73 landscape you know i mean a cd73 gives us another indication with proof in the clinical state so maybe i'll hand it over to janice who can speak to a little bit about that finds around the HER2. Yeah, thank you, Jason. Yeah, like you said, we are actually differentiating our molecule first Because of its intrinsic properties, our antibody, as opposed to other CD73 inhibitors that are in development, and especially the olecumab, our antibody does not have the hook effect, meaning that it continues to block the enzyme even at high dose, meaning that we are blocking the surface receptor, but we are also blocking the soluble molecule of CD73, which is very important for an enzyme. And like said by Jason, 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 resistance to the ADCC of R2 targeting antibody, so that by combining the blockade of CD73 can increase the efficacy of trastuzumab in preclinical models.
spk02: Okay, got it. That's really helpful. And then just one housekeeping question. Did a mate 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? Thanks again.
spk06: Yeah. So, again, maybe we remind everyone that we are, of course, excited that Pathetic 9 study has started. And, of course, we still wait to hear of the first patient being dosed. We have not provided the granularity on potential minor spots. We have received so far 400 million. with $50 million on the first phase three interlink one, which started in the fall of 2020. And an interim analysis will also trigger a payment of $50 million if the predefined official defectivity is reached. In total, we could potentially receive another $425 million in regulatory and developing milestones and about $400 million in commercial milestones, as well as a double-digit warranty part of the agreement with AstraZeneca. Thank you.
spk02: Okay, great. Thanks for taking the question.
spk08: Thank you. Thank you. And our next question comes from Lisa Baker of Evercore ISA. Lisa, please go ahead. Your line is open.
spk00: Hi there. Thanks for taking the questions. First one, are you planning an interim analysis of Interlink for this year?
spk06: Hi, Lisa. Thank you for joining the call and your question. As you know, this trial is being conducted by AstraZeneca, and the plan is to have an interim analysis performed about 18 to 24 months after the first patient is enrolled. The first patient was enrolled in November 2020, so the interim is expected for the second half of 2022.
spk00: Wonderful. Okay, great. And then... Can you maybe discuss a little bit more specifically about your regulatory strategy for cesarean syndrome? Are you going to file just for this indication alone? I think there was some mention at J.P. Morgan that you might do some sort of combination with MS, maybe you can just discuss things.
spk05: Yeah, absolutely.
spk06: I think it's a good way to hand over to Joyce to recap our MF slash cesarean syndrome registration strategy based on, again, the interaction we had with the FDA. Joyce, can you please answer this question? Thanks, Sanjay. Thanks, Sanjay. Thank you for the question. Let me start off with at least our initial strategy. So our initial strategy for CSRI 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 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 SF and MF, which as many of you know, the Mogamalizumab label is both SF as well as MF. So there is precedent for combining both of these indications. So we are looking at all possible options 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.
spk00: Okay. Any idea when you might have some more granularity on that? Or is it really data dependent?
spk06: It is. It will be data dependent. And as we mentioned, we will be presenting data about cesarean syndrome as well as mycosis fungal disease later this year.
spk00: Thanks a lot. Thank you.
spk08: Thank you. And our next question comes from Kaya Parekh of Goldman Sachs. Kaya, please go ahead. Your line is open.
spk03: Hi. Thank you for taking my questions too, if I may, please. One, just as you kind of think about the opportunity across both SARS syndrome and MS, just wondering if you could remind me how big you guys think these indications can be and how quickly do you think you might be able to get to the peak revenue sizes for these indications? That's kind of question number one. And then separately for you, Munder, as you think about kind of developing the DECRA and CAT kind of products, You've been doing 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 or remedy perspective. If you're kind of doing something that is targeting five 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 agencies. Thank you.
spk05: Thank you, Peter. Great questions. I'll try to answer as clear and as precise as possible. So first of all, maybe on the cesarean MF,
spk06: So that is, we have AP data for, you know, US and top five EU. So it's roughly, you know, 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 cesarean syndrome every year. So it's really a niche indication. And these patients actually receive 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 one. We are using Cesaria as really a proof of concept on one side and a way to get to the market as quickly as possible. NF is a much bigger market opportunity, and please keep in mind that NF is just one type of the various subtypes of cutaneous T-cell lymphoma. About half of cutaneous T-cell lymphoma are mycosis fungoridus, and there are about 50% of which are not mycosis fangregas. It's very heterogeneous, it's very sophisticated and actually difficult to classification. And it's quite challenging also to do some registration work on a such heterogeneous population. So that's why we elected to go after mycosis fangregas. All in all, we are talking about maybe 3 000 to 4 000 new patients every year and clearly the paternity cell lymphoma overall is not a very huge market opportunity of course when you compare to the peripheral descendant former which is a much bigger one with about nearly 20 000 new patients every year and half of them express the target so clearly uh it's a much bigger indication but again we do not have data there we just started last year if i give you Remember, it would be maybe 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 Mogamalizumab. And you may have followed the, you know, previous results of POR, but they're sold about, you know, 150 million for MOGA, which main indication is MFN2L. So clearly, there is a business there, and this, you know, could damage to cell lymphoma. And as you know, MOGA-Marizumab is approved in the U.S. and in Europe, but it's not reimbursed everywhere in Europe. So there is a challenge, of course, in terms of market penetration, and the drug was just approved at the end of 2018 in the US 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 NREP. clarify this first question. I think the second question is really what we do every day actually in-house trying to really figure out why we are progressing our proprietary product into, you know, IND neighboring studies and preparing for the clinic, thinking about how to develop this drug and how to position it actually as a new generation of multispecific antibodies. I think the main opportunity resides actually into the safety of using an NK cell engager versus a T cell engager. And actually we have good reason to think that this could be, you know, one of the way to differentiate, but also could be an opportunity also for combination strategy that we could afford. And you have seen data already from others combining, you know, fresh NK cells with with antibodies, engagement in cells, and the results are quite amazing, especially in heme, in liquid tumors. Of course, it's a small N, and usually we're talking about phase I, II, but nevertheless, it provides some idea on the potential of this combination. I think the opportunity resides in solid tumors. because if we can do the same, and again, we are not the only ones working on this field, others are preparing to tackle the solid-tunnel space, engaging NK cells 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 challenges, but it's not the only one, is how to make sure that our construct, It's pretty brand new in terms of CNC and manufacturing, so there are challenges there that we have to overcome, because it's the first time we developed such a complex antibody. But on top of that, once we get into the clinic, remember this is an antibody that included IM2 variants, Of course, we selected the IL-2 variant for purpose to expand the NK cells without, you know, the downside, you know, safety issue that you can encounter. And of course, these are so far preclinical data. We need to make sure that these translate into the clinic with the same, you know, benefits and the same safety profile. So these are the two main kind of short-term challenges that we have to uh go through but uh clinical data will tell whether what we have generated so far and what presented at various meetings last year uh can translate in really clinical benefits for patients so sorry for the long answer but i think it's a good opportunity maybe to put our and get a platform development strategy into context and perspective thank you monda that's very helpful for
spk03: You're welcome. Thank you.
spk06: Operator, next question.
spk03: Sorry.
spk08: Of course, just as another reminder, if you would like to ask a question today, please press star followed by the number one on your telephone keypads now. And our next question comes from Swayam Pakula Ramakant from HC Wainwright. Swayam Pakula, please go ahead. Your line is open.
spk06: Thank you. Most of my questions have been asked on there. 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? Hi, RK. Good to have you and thank you for your question. You know, the T-39 RISAS agreement with AstraZeneca looks similar to the Monolith Jamab agreement. So it's really a co-development, co-commercialization agreement where we are involved and we are engaged also in the development of these molecules. AstraZeneca did the first draft of the escalation, single agent, and then combination. They posed that development because we reached the, whatever you call it, milestone or objective on phase one, and now we are on the planning phase and discussion with AstraZeneca on the next step, learning from, again, the cost trial, which was, as I said, a proof-of-concept demonstration for the pathway, of course, tackling the CD39, but nevertheless, I think it's an important milestone in the development of these antibodies. So 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. Thank you, Mondaire. Thank you. Okay.
spk08: Thank you. We have no further questions. I'll hand the call back over to you, Mondaire.
spk06: Thank you. Again, I think it's a great opportunity to present our portfolio 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 partner portfolio programs. These results set the stage for delivering both near-term and long-term value, while also highlighting the strength and depth of our core R&D. And just a reminder, looking ahead, we will continue to advance our electrical network development program. We will continue to move our early-stage R&D activity toward the clinic with our next-generation NCAT platform. And for more reason not, we look forward to further clinical development in early lung cancer, with the head lung cancer well underway, which, of course, further enforces 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.
spk08: Thank you, ladies and gentlemen. This concludes today's call. Thank you all for joining. You may now disconnect your lines.
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